US20150231396A1 - Neurostimulator - Google Patents
Neurostimulator Download PDFInfo
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- US20150231396A1 US20150231396A1 US14/604,625 US201514604625A US2015231396A1 US 20150231396 A1 US20150231396 A1 US 20150231396A1 US 201514604625 A US201514604625 A US 201514604625A US 2015231396 A1 US2015231396 A1 US 2015231396A1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
- A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
- A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
- A61N1/36103—Neuro-rehabilitation; Repair or reorganisation of neural tissue, e.g. after stroke
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- A61B5/103—Detecting, measuring or recording devices for testing the shape, pattern, colour, size or movement of the body or parts thereof, for diagnostic purposes
- A61B5/11—Measuring movement of the entire body or parts thereof, e.g. head or hand tremor, mobility of a limb
- A61B5/1104—Measuring movement of the entire body or parts thereof, e.g. head or hand tremor, mobility of a limb induced by stimuli or drugs
- A61B5/1106—Measuring movement of the entire body or parts thereof, e.g. head or hand tremor, mobility of a limb induced by stimuli or drugs to assess neuromuscular blockade, e.g. to estimate depth of anaesthesia
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- A61B5/279—Bioelectric electrodes therefor specially adapted for particular uses
- A61B5/296—Bioelectric electrodes therefor specially adapted for particular uses for electromyography [EMG]
Definitions
- the present disclosure is directed generally to the field of medical electro-medical therapy devices, and more particularly to implantable stimulators and stimulator systems used in neurological rehabilitation for the treatment of traumatic and non-traumatic injury or illness.
- Implantable neurostimulator and neuromodulator devices have been used to deliver therapy to patients to treat a variety of symptoms or conditions such as chronic pain, epilepsy, and tremor associated with and without Parkinson's disease.
- the implantable stimulators deliver stimulation therapy to targeted areas of the nervous system.
- the applied therapy is usually in the form of electrical pulse at a set frequency.
- the current is produced by a generator.
- the generator and an associated control module may be constructed from a variety of mechanical and electrical components.
- the generator is typically housed in a casing made of biocompatible material such as titanium, allowing for surgical placement subcutaneously within the abdomen or chest wall of a patient by someone with ordinary skill in the art of orthopedic spine and neurosurgery.
- the stimulator is attached via one or more leads to one or more electrodes that are placed in close proximity to one or more nerves, one or more parts of a nerve, one or more nerve roots, the spinal cord, the brain stem, or within the brain itself.
- the leads and electrode arrays may vary in length, and are also made of a biocompatible material.
- implantable stimulators and their attached electrodes positioned outside of the brain around the spinal cord, nerve roots, spinal nerves, and peripheral nerves have been used to manage and treat chronic pain; none to date have been commercially used or approved to restore function. Further, none have been aimed at permanent remodeling of the nervous system. Attempts to restore function in neurologically impaired subjects have been limited to adjunctive modalities, such as physical and occupational therapy with emphasis on adaptation to disability. Little progress has been achieved in actually restoring normal functional capacity to damaged nerve tissue, nerve structures and/or nerve components that make up the nervous system along with the organs and anatomical structures they innervate with the use of an implantable neurostimulator.
- the present application provides these and other advantages as will be apparent from the following detailed description and accompanying figures.
- Embodiments include neurostimulator devices and systems for use with a subject (e.g., a human patient or an animal).
- Neurostimulator devices may be for use with a plurality of groups of electrodes.
- the plurality of groups of electrodes may include more than four groups of electrodes.
- the electrodes are wired electrodes.
- the electrodes are wireless electrodes.
- the electrodes are a combination of wired and wireless electrodes.
- Neurostimulator devices may include a stimulation assembly connectable to the plurality of groups of electrodes.
- the electrodes can be electrical, chemical, mechanical, photonic, or a combination thereof.
- the stimulation assembly can be configured to deliver different stimulations to each of the plurality of groups of electrodes when the stimulation assembly is connected thereto. In some embodiments, the stimulation assembly can be configured to deliver different stimulations to an individual electrode within each group when the stimulation assembly is connected thereto.
- the neurostimulator device may also include at least one processor connected to the stimulation assembly. The at least one processor can be configured to direct the stimulation assembly to deliver different stimulation(s) to each of the plurality of groups of electrodes or individual electrodes within a group.
- the neurostimulator device may be configured for implantation in a subject (e.g., a human being or an animal).
- the stimulation delivered to at least one of the plurality of groups of electrodes or individual electrodes within a group may include one or more waveform shapes other than a square or rectangular wave shape.
- neurostimulator devices can be for use with a plurality of electrodes and one or more sensors.
- the neurostimulator device may include a stimulation assembly connectable to the plurality of electrodes.
- the stimulation assembly can be configured to deliver stimulation to selected electrodes within of the plurality of electrodes when the stimulation assembly is connected to the plurality of electrodes.
- Neurostimulator devices may also include a sensor interface connectable to the one or more sensors.
- the sensor interface can be configured to receive signals from the one or more sensors when the sensor interface is connected to the one or more sensors.
- the sensors can be wires sensors, wireless sensors implanted, external to the body, or a combination thereof. In some embodiments, some sensors are wired and some are wireless.
- the neurostimulator device may further include at least one processor connected to both the stimulation assembly and the sensor interface.
- the at least one processor can be configured to direct the stimulation assembly to deliver at least one complex stimulation pattern to selected electrodes within the plurality of electrodes and to receive the signals from the sensor interface.
- the at least one processor can be further configured to modify the at least one complex stimulation pattern delivered by the stimulation assembly based on the signals received from the sensor interface.
- the stimulation assembly, sensor interface, and at least one processor are housed inside a housing configured for implantation in the body of the subject.
- the at least one complex stimulation pattern may include a first stimulation pattern followed by a second stimulation pattern.
- the second stimulation pattern may be delivered to a second portion of selected electrodes within the plurality of electrodes less than about one microsecond after the first stimulation pattern is delivered to a first portion of selected electrodes within the plurality of electrodes.
- the first stimulation pattern may be delivered to a first portion of selected electrodes within the plurality of electrodes
- the second stimulation pattern is delivered to a second portion of selected electrodes within the plurality of electrodes, wherein the first portion is different from the second portion.
- Selected electrodes within the plurality of electrodes may include more than four groups of electrodes, and the at least one complex stimulation pattern may include different electrical stimulation for each of the groups of electrodes or an individual electrode of each group.
- the at least one processor may be configured to perform a machine learning method (based on the signals received from the sensor interface or recorded from the sensor interface) to determine a set of stimulation parameters. In such embodiments, the at least one processor may modify the at least one complex stimulation pattern based at least in part on the set of stimulation parameters.
- the at least one processor may be configured to receive and record electrical signals from the plurality of electrodes. The at least one processor may modify the at least one complex stimulation pattern based at least in part on the electrical signals received from the plurality of electrodes, the sensors, or a combination thereof.
- the at least one processor may include at least one of a microprocessor, a microcontroller, a field programmable gate array, and a digital signal processing engine.
- the neurostimulator device may be for use with, be at least partially controlled by, or send at least partial reports to a computing device.
- Computing devices may be any type of device including at least one processor and memory.
- Computing devices can include, but are not limited to hand held control units, cellular phones, smart phones (e.g., Apple, iPhone, Samsung Galaxy, etc.), tablets (e.g., Apple iPad), desktop computers, workstation computers, computer servers, laptop computers, ultrabook computers, netbook computers, gaming consoles, pagers, or the like.
- the at least one processor may be configured to transmit the recorded electrical signals to at least one computing device and to receive information therefrom.
- the at least one processor may be configured to modify the at least one complex stimulation pattern based at least in part on the information received from the computing device.
- the at least one processor may be configured to record the signals received from the sensor interface, transmit the recorded electrical signals to the computing device, and receive information from the computing device.
- the at least one processor may be configured to modify the at least one complex stimulation pattern based at least in part on the information received from the sensors and/or computing device.
- the plurality of sensors may include at least one of an electromyography sensor, an evoked potential sensor, a joint angle sensor, a flex sensor, an accelerometer, a gyroscope sensor, a flow sensor, a pressure sensor, a temperature sensor, a chemical sensor, a light sensor, a photonic sensor, a harmonic sensor, and a load sensor.
- the sensors may be located within the housing of the generator or electrode array. In other embodiments, the sensors may be remote to the housing wherein they are implanted elsewhere within the subject's body or reside external and superficial to the subject's body. In some embodiments, sensors may reside in combinations of inside the housing, implanted elsewhere, and reside external to the subject's body. In some embodiments, the sensors can be located in, on, or associated with one or more training devices. In some embodiments, the sensors can be wired or wireless.
- Embodiments of neurostimulator devices may be for use with a subject having a neurologically derived paralysis in a portion of his/her body.
- the subject can have a spinal cord with at least one selected spinal circuit that has a first stimulation threshold representing a minimum amount of stimulation required to activate the at least one selected spinal circuit, and a second stimulation threshold representing an amount of stimulation above which the at least one selected spinal circuit is fully activated.
- the at least one complex stimulation pattern When the at least one complex stimulation pattern is applied to a portion of a patient's spinal cord, the at least one complex stimulation pattern is below the second stimulation threshold such that the at least one selected spinal circuit is at least partially activatable by the addition of at least one of (a) neurological signals originating from the portion of the patient's body having the paralysis, and (b) supraspinal signals.
- the neurological signals originating from the portion of the patient's body having the paralysis may be neurological signals induced by physical training, mechanical manipulation, a physiological change, a response to light, an introduction of a pharmaceutical or active agent, or a chemical response.
- Induced neurological signals may include at least one of postural proprioceptive signals, locomotor proprioceptive signals, temperature signals or changes in temperature, vibratory signals, chemical signals, light signals, supraspinal signals, and combinations thereof.
- the at least one selected spinal circuit when at least partially activated, produces improved neurological function including at least one of voluntary movement of muscles involved in at least one of standing, stepping, reaching, grasping, voluntarily changing positions of one or both legs, voluntarily changing positions of one or both arms, voluntarily changing position of one's neck, voiding the subject's bladder, voiding the subject's bowel, breathing, coughing, chewing, swallowing, speaking, blinking, focusing visual fields, postural activity changing core (trunk) position, improve muscle tone postural activity, and improve locomotor activity.
- improved neurological function including at least one of voluntary movement of muscles involved in at least one of standing, stepping, reaching, grasping, voluntarily changing positions of one or both legs, voluntarily changing positions of one or both arms, voluntarily changing position of one's neck, voiding the subject's bladder, voiding the subject's bowel, breathing, coughing, chewing, swallowing, speaking, blinking, focusing visual fields, postural activity changing core (trunk) position, improve muscle tone
- the at least one selected spinal circuit when at least partially activated, produces improved neurological function including at least one of improved autonomic control of at least one of voiding the subject's bladder, voiding the subject's bowel, cardiovascular function, respiratory function, digestive function, body temperature, and metabolic processes. In some embodiments, when at least partially activated the at least one selected spinal circuit produces improved neurological function including at least one of an autonomic function, sexual function, motor function, vasomotor function, and cognitive function.
- the neurostimulator device may include at least one rechargeable battery configured to power various electronic components.
- the battery can be configured to power the at least one processor.
- the neurostimulator device can be plugged into a power source to charge the battery when needed. If the neurostimulator device requires frequent recharging and/or requires being plugged into a power source for recharging, multiple devices can be provided to a patient thereby allowing one to remain charged at all times.
- the neurostimulator device may include a wireless recharging assembly configured to receive power wirelessly and transmit at least a portion of the power received to the at least one rechargeable battery.
- the rechargeable battery system may be though transduction, ultrasonic, magnetic, or photonic.
- the neurostimulator device may be for use with a plurality of muscle electrodes.
- the neurostimulator device may include a muscle stimulation assembly connected to the at least one processor, and configured to deliver electrical stimulation to the plurality of muscle electrodes.
- the at least one processor may be configured to instruct the muscle stimulation assembly to deliver the electrical stimulation to the plurality of muscle electrodes.
- the neurostimulator device may be for use with a muscle stimulation device configured to deliver electrical stimulation to the plurality of muscle electrodes.
- the neurostimulator device may include an interface connected to the at least one processor, and configured to direct the muscle stimulation device to deliver electrical stimulation to the plurality of muscle electrodes.
- the neurostimulator device may be for use with at least one recording electrode.
- the at least one processor is connected to the at least one recording electrode, and configured to receive and record electrical signals received from the at least one recording electrode.
- recording electrodes may be located within the housing of the generator or an electrode array. In other embodiments, the recording electrodes may be remote to the housing wherein they are implanted elsewhere within the subject's body or reside external and superficial to the subject's body. In some embodiments, the recording electrodes may reside in combinations of inside the housing, implanted elsewhere, and reside external to the subject's body.
- the neurostimulator devices described above may be incorporated in one or more systems.
- An example of such a system may be for use with a subject having body tissue, and one or more sensors positioned to collect physiological data related to the subject.
- the system may include a plurality of electrodes, the neurostimulator device, and a computing device.
- the plurality of electrodes may be arranged in an electrode array implantable adjacent to the body tissue of the subject.
- the electrode array may be implantable adjacent to at least one of a portion of the spinal cord, one or more spinal nerves, one or more nerve roots, one or more peripheral nerves, the brain stem, the brain, and an end organ.
- the plurality of electrodes may include at least 16 electrodes, at least 32 electrodes, at least 64 electrodes, or at least 128 electrodes.
- the electrode array may be implantable along a portion of the dura of the spinal cord of the subject. In one embodiment, the electrode may be implanted along or adjacent to the dorsal root.
- the electrode array may be a high-density electrode array in which adjacent ones of the plurality of electrodes are positioned within 300 micrometers of each other.
- the neurostimulator device may be connected to the plurality of electrodes and configured to deliver complex stimulation patterns thereto.
- the computing device may be configured to transmit stimulation parameters to the neurostimulator device.
- the neurostimulator device may be configured to generate the complex stimulation patterns based at least in part on the stimulation parameters received from the computing device.
- the computing device may be further configured to determine the stimulation parameters based on at least in part on the physiological data collected by the one or more sensors or from one or more sensor associated with a training device.
- the stimulation parameters may identify a waveform shape, amplitude, frequency, and relative phasing of one or more electrical pulses delivered to one or more pairs of the plurality of electrodes.
- Each of the complex stimulation patterns may include a plurality of different electrical signals each delivered to a different pair of the plurality of electrodes.
- the computing device may be configured to perform a machine learning method operable to determine the stimulation parameters.
- the machine learning method may implement a Gaussian Process Optimization.
- the neurostimulator device may be configured to generate the complex stimulation patterns based at least in part on one or more stimulation parameters determined by the neurostimulator device.
- the neurostimulator device may be configured to perform a machine learning method operable to determine the one or more stimulation parameters.
- the machine learning method may implement a Gaussian Process Optimization.
- the neurostimulator device may be connected to the one or more sensors, and configured to transmit the physiological data collected by the one or more sensors to the computing device.
- the computing device may be connected to the one or more sensors, and configured to receive the physiological data from the one or more sensors.
- the one or more sensors may include at least one of a surface EMG electrode, a foot force plate sensor, an in-shoe sensor, an accelerator, and a gyroscope sensor attached to or positioned adjacent the body of the subject.
- the one or more sensors may include a motion capture system.
- the system may be for use with the subject having a body, a spinal cord, and a neurologically derived paralysis in a portion of the subject's body.
- the spinal cord has at least one selected spinal circuit that has a first stimulation threshold representing a minimum amount of stimulation required to activate the at least one selected spinal circuit, and a second stimulation threshold representing an amount of stimulation above which the at least one selected spinal circuit is fully activated.
- neurostimulator training systems can include a plurality of electrodes arranged in an electrode array implantable adjacent to body tissue; a neurostimulator device connected to the plurality of electrodes and configured to deliver complex stimulation patterns to the plurality of electrodes; at least one training device including one or more sensors; and a computing device configured to transmit stimulation parameters to the neurostimulator device, the neurostimulator device being configured to generate the complex stimulation patterns based at least in part on the stimulation parameters received from the computing device, the computing device being further configured to determine the stimulation parameters based on at least in part on data collected by the one or more sensors.
- the systems described may include a training device or system configured to physically train the subject and thereby induce neurological signals in the portion of the subject's body having paralysis.
- Training devices can use robotics, exoskeletons, treadmills, canes, walkers, crutches, body weight support systems, physical therapy, or a combination thereof to aid in training.
- Example training devices and systems can include, but are not limited to an EKSOTM Bionic Suit by EKSO BIONICS® (Ekso Bionics, Richmond, Calif.), the REWALKTM system by Argo Medical Technologies (Marlborough, Mass.), the RT300 system by Restorative Therapies, the RT200 system by Restorative Therapies, the RT600 system by Restorative Therapies, the THERASTRIDETM system by INNOVENTOR® (St. Louis, Mo.), or the LOCOMAT® or ARMEO® system by HOCOMA® (Hocoma AG cios anonyme (SA) SWITZERLAND).
- These training devices can also be used as standalone neurostimulation devices or used with an electrode, neurostimulator device, or neurostimulator system as described herein to form such a system.
- the induced neurological signals may be below the first stimulation threshold and insufficient to activate the at least one selected spinal circuit.
- the complex stimulation patterns may be below the second stimulation threshold such that the at least one selected spinal circuit is at least partially activatable by the addition of at least one of (a) a portion of the induced neurological signals, and (b) supraspinal signals.
- the system may include at least one recording electrode connected to the neurostimulator device.
- the neurostimulator device can be configured to receive and record electrical signals received from the at least one recording electrode.
- the at least one recording electrode may be positioned on the electrode array.
- the electrode array may be considered a first electrode array, and the system may include a second electrode array.
- the at least one recording electrode may be positioned on at least one of the first electrode array and the second electrode array.
- the system may include a plurality of muscle electrodes.
- the neurostimulator device may include a muscle stimulation assembly configured to deliver electrical stimulation to the plurality of muscle electrodes.
- the system may be for use with a plurality of muscle electrodes and a muscle stimulation device configured to deliver electrical stimulation to the plurality of muscle electrodes.
- the neurostimulator device may include an interface configured to direct the muscle stimulation device to deliver electrical stimulation to the plurality of muscle electrodes.
- the polarity of muscles electrodes maybe embedded in a garment suitable for wearing and/or carrying.
- FIG. 1 Another example of a system including at least one of the neurostimulator devices described above is for use with a network and a subject having body tissue, and one or more sensors positioned to collect physiological data related to the subject.
- the system includes a plurality of electrodes, the neurostimulator device, a first computing device, and a remote second computing device.
- the plurality of electrodes may be arranged in an electrode array implantable adjacent the body tissue of the subject.
- the neurostimulator device is connected to the plurality of electrodes and configured to deliver complex stimulation patterns thereto.
- the first computing device is connected to the network and configured to transmit stimulation parameters to the neurostimulator device.
- the neurostimulator device is configured to generate the complex stimulation patterns based at least in part on the stimulation parameters received from the first computing device.
- the remote second computing device is connected to the network.
- the first computing device is being configured to transmit the physiological data collected by the one or more sensors to the second computing device.
- the second computing device is configured to determine the stimulation parameters based at least in part on the physiological data collected by the one or more sensors, and transmit the stimulation parameters to the first computing device.
- the first computing device is configured to receive instructions from the second computing device and transmit them to the neurostimulator device.
- the first computing device may be configured to receive data from the neurostimulator device and communicate the data to the second computing device over the network.
- the second computing device may communicate directly with the neurostimulator device.
- neurostimulator systems can include a stimulation assembly connectable to a plurality of electrodes.
- the stimulation assembly can be configured to deliver stimulation to selected electrodes within the plurality of electrodes when the stimulation assembly is connected to the plurality of electrodes and wherein the stimulation assembly includes a pulse generating system.
- the systems can further include a sensor interface connectable to the one or more sensors, the sensor interface being configured to receive signals from the one or more sensors when the sensor interface is connected to the one or more sensors.
- the systems can further include at least one processor connected to the stimulation assembly, the pulse generating system, and the sensor interface, the at least one processor can be configured to direct the stimulation assembly and the pulse generating system to deliver at least one complex stimulation pattern to the selected electrodes, and to receive the signals from the sensor interface.
- the at least one processor can be further configured to modify the at least one complex stimulation pattern delivered by the stimulation assembly based on the signals received from the sensor interface and the pulse generating system.
- Neurostimulator devices can also be combined for use with a network and a subject having body tissue, and one or more pulse generators either implantable or external positioned to deliver an electrical, pulsed or other type of power generated stimulus which directly or indirectly brings about a physiological response.
- the combined systems can include a plurality of electrodes, a neurostimulator device, a first computing device, and a second stimulator device which may include a second computing device.
- Example second stimulator devices which may include a second computing device are MEDTRONIC®'s INTERSTIM® Therapy (Medtronic, Minneapolis, N. Mex.) for overactive bladder; ST. JUDE MEDICAL®'s ACCENTTM Pacemaker (St. Jude Medical, Maple Grove, Minn.), ST.
- the above listed stimulator devices can also be first stimulator devices.
- the plurality of electrodes may be arranged in an electrode array implantable adjacent the body tissue of the subject.
- at least one electrode or electrode array is transplanted adjacent to or touching the spinal cord.
- the at least one electrode or electrode array need to be adjacent to the spinal cord.
- stimulator devices such as MEDTRONIC®'s INTERSTIM® Therapy (Medtronic, Minneapolis, N. Mex.) for overactive bladder; ST. JUDE MEDICAL®'s ACCENTTM Pacemaker (St. Jude Medical, Maple Grove, Minn.), ST. JUDE MEDICAL®'s MICRONYTM Pacemaker, ST. JUDE MEDICAL®'s ZEPHYRTM Pacemanker; cardiac rhythm management devices such as ST.
- the above identified systems can be altered or otherwise modified to attain the herein described features and/or stimulation results.
- a neurostimulator device is connected to a plurality of electrodes and configured to deliver complex stimulation patterns thereto.
- the first computing device can be connected to the network and configured to transmit stimulation parameters to the neurostimulator device.
- the neurostimulator device can be configured to generate complex stimulation patterns based at least in part on the stimulation parameters received from the first computing device.
- the second stimulator device can also be connected to the network.
- the first computing device can be configured to transmit and receive data collected by the one or more sensors or electrodes from the second stimulator device and/or the second computing device.
- the second stimulator and/or computing device can be configured to determine the stimulation parameters based at least in part on the data collected by the one or more sensors or electrodes, and transmit these stimulation parameters to the targeted body tissue, organ or region to bring about a desired physiological response(s).
- the first computing device is configured to receive instructions from the second computing device and transmit them to the neurostimulator device.
- the first computing device may be configured to receive data from the neurostimulator device and communicate the data to the second computing device over the network.
- an implantable pulse generator is integrated into the herein described neurostimulator devices.
- an implantable pulse generator used for bladder spasticity can be integrated a neurostimulator device.
- FIG. 1 is an illustration of an implantable assembly.
- FIG. 2 is an illustration of a system incorporating the implantable assembly of FIG. 1 .
- FIG. 3A is an illustration of a first embodiment of an exemplary electrode array for use with the neurostimulator device of the implantable assembly of FIG. 1 .
- FIG. 3B is an illustration of a second embodiment of an exemplary electrode array for use with the neurostimulator device of the implantable assembly of FIG. 1 .
- FIG. 4A is an illustration of a waveform that may be generated by the neurostimulator device of the implantable assembly of FIG. 1 .
- FIG. 4B an illustration of another waveform that may be generated by the neurostimulator device of the implantable assembly of FIG. 1 .
- FIG. 5 is a block diagram of a first embodiment of an implantable assembly and an external system.
- FIG. 6A is a leftmost portion of a circuit diagram of a multiplexer sub-circuit of a neurostimulator device of the implantable assembly of FIG. 5 .
- FIG. 6B is a rightmost portion of the circuit diagram of the multiplexer sub-circuit of the neurostimulator device of the implantable assembly of FIG. 5 .
- FIG. 7 is a circuit diagram of a stimulator circuit of the neurostimulator device of the implantable assembly of FIG. 5 .
- FIG. 8 is a circuit diagram of a controller circuit of the neurostimulator device of the implantable assembly of FIG. 5 .
- FIG. 9 is a circuit diagram of a wireless power circuit of the neurostimulator device of the implantable assembly of FIG. 5 .
- FIG. 10 is a block diagram of a second embodiment of an implantable assembly.
- FIG. 11 is a block diagram of a third embodiment of an implantable assembly and the external system.
- FIG. 12A is a block diagram of stimulator circuitry and a wireless transceiver of a neurostimulator device of the implantable assembly of FIG. 11 .
- FIG. 12B is a block diagram of an alternate embodiment of the stimulator circuitry of FIG. 12A .
- FIG. 13 is an illustration of a multi-compartment physical model of electrical properties of a mammalian spinal cord, along with a 27 electrode implementation of the electrode array placed in an epidural position.
- FIG. 14 is a lateral cross-section through the model of the mammalian spinal cord depicted in FIG. 13 cutting through bipolarly activated electrodes showing isopotential contours of the stimulating electric field for the 2-electrode stimulation example.
- FIG. 15 shows instantaneous regret (a measure of machine learning error) vs. learning iteration (labeled as “query number”) for Gaussian Process Optimization of array stimulation parameters in the simulated spinal cord of FIGS. 13 and 14 .
- the “bursts” of poor performance corresponds to excursions of the learning algorithm to regions of parameter space that are previously unexplored, but which are found to have poor performance.
- FIG. 16 shows the average cumulative regret vs. learning iteration.
- the average cumulative regret is a smoothed version of the regret performance function which better shows the algorithm's overall progress in selecting optimal stimulation parameters.
- FIG. 17 is a diagram of a hardware environment and an operating environment in which the computing device of the system of FIG. 2 may be implemented.
- SCI spinal cord injury
- FIG. 1 illustrates an implantable electrode array assembly 100 . While the embodiment of the assembly 100 illustrated is configured for implantation in the human subject 102 (see FIG. 2 ), embodiments may be constructed for use in other subjects, such as other mammals, including rats, and such embodiments are within the scope of the present teachings.
- the subject 102 has a brain 108 , a spinal cord 110 with at least one selected spinal circuit (not shown), and a neurologically derived paralysis in a portion of the subject's body.
- the spinal cord 110 of the subject 102 has a lesion 112 .
- the selected spinal circuit when activated, may (a) enable voluntary movement of muscles involved in at least one of standing, stepping, reaching, grasping, voluntarily changing positions of one or both legs, voluntarily changing positions of one or both arms, voluntarily changing position of one's neck, voiding the subject's bladder, voiding the subject's bowel, breathing, coughing, chewing, swallowing, speaking, blinking, focusing visual fields, postural activity changing core (trunk) position, and locomotor activity, or improve muscle tone; (b) enable or improve autonomic control of at least one of cardiovascular function, body temperature, and metabolic processes; and/or (c) help facilitate recovery of at least one of an autonomic function, sexual function, vasomotor function, and cognitive function.
- improved neurological function The effects of activation of the selected spinal circuit will be referred to as “improved neurological function.”
- the selected spinal circuit has a first stimulation threshold representing a minimum amount of stimulation required to activate the selected spinal circuit, and a second stimulation threshold representing an amount of stimulation above which the selected spinal circuit is fully activated and adding the induced neurological signals has no additional effect on the at least one selected spinal circuit.
- the paralysis may be a motor complete paralysis or a motor incomplete paralysis.
- the paralysis may have been caused by a SCI classified as motor complete or motor incomplete.
- the paralysis may have been caused by an ischemic or traumatic brain injury.
- the paralysis may have been caused by an ischemic brain injury that resulted from a stroke or acute trauma.
- the paralysis may have been caused by a neurodegenerative brain injury.
- the neurodegenerative brain injury may be associated with at least one of Parkinson's disease, Huntington's disease, Dystonia, Alzheimer's, ischemia, stroke, amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), and cerebral palsy.
- Neurological signals may be induced in the paralyzed portion of the subject's body (e.g., by physical training). However, adding the induced neurological signals may have little or no additional effect on the selected spinal circuit, if the induced neurological signals are below the first stimulation threshold and insufficient to activate the at least one selected spinal circuit.
- the assembly 100 is configured to apply electrical stimulation to neurological tissue (e.g., a portion of the spinal cord 110 , one or more spinal nerves, one or more nerve roots, one or more peripheral nerves, the brain stem, and/or the brain 108 , and the like).
- neurological tissue e.g., a portion of the spinal cord 110 , one or more spinal nerves, one or more nerve roots, one or more peripheral nerves, the brain stem, and/or the brain 108 , and the like.
- the electrical stimulation may be applied to other types of tissue, including the tissue of one or more end organs (e.g., bladder, kidneys, heart, liver, and the like).
- the electrical stimulation will be described as being delivered to body tissue. While the stimulation may be delivered to body tissue that is not neurological tissue, the target of the stimulation is generally a component of the nervous system that is modified by the addition of the stimulation to the body tissue.
- the electrical stimulation delivered is configured to be below the second stimulation threshold such that the selected spinal circuit is at least partially activatable by the addition of (a) induced neurological signals and/or (b) supraspinal signals.
- Induced neurological signals can include neurological signals induced through physical training, mechanical manipulation, a temperature stimulation, a harmonic stimulation, a pressure stimulation, a physiological change, a response to light, an introduction of a pharmaceutical, or chemical response.
- the induced neurological signals may include at least one of postural proprioceptive signals, locomotor proprioceptive signals, temperature, vibratory, chemical or light signals, and/or supraspinal signals.
- the assembly 100 may be used to perform methods described in U.S.
- the selected spinal circuit may be at least partially activatable by the addition neurological signals other than those induced by physical training.
- the assembly 100 includes one or more electrode arrays 140 , one or more leads 130 , and a neurostimulator device 120 .
- the one or more electrode arrays 140 will be described as including a single electrode array.
- embodiments may be constructed that include two or more electrode arrays.
- embodiments may include two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, 13, 14, 15, 16, 17, 18, 19, 20, or more electrode arrays.
- the arrays can be wired or wireless.
- each electrode array can include one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 50, 100 or more electrodes per array.
- the sensors can be wired or wireless.
- the electrode can vary in shape such as paddle shape, oval, or tubular, and may be surgically implanted by means of open technique or percutaneously inserted.
- the neurostimulator device 120 generates electrical stimulation that is delivered to the electrode array 140 by the one or more leads 130 .
- the neurostimulator device 120 may be characterized as being a neuromodulator device.
- the electrode array 140 may be implemented using commercially available high-density electrode arrays designed and approved for implementation in human patients.
- a MEDTRONIC® Specify 5-6-5 multi-electrode array (incorporating 16 electrodes) may be used or BOSTON SCIENTIFIC®'s 32 lead electrode arrays such as the COVEREDGE® and the COVEREDGE®-X (Boston Scientific Neuromodulation Corporation, Valencia, Calif.).
- suitable electrode arrays include paddle-shaped electrodes (e.g., having a 5-6-5 electrode configuration) constructed from platinum wire and surface electrodes embedded in silicone.
- the electrode array 140 may be implemented using multiple electrode arrays (e.g., multiple 16-electrode arrays connected to the neurostimulator device 120 in a serial or parallel arrangement).
- FIG. 3A illustrates a conventional electrode array 148 having 16 electrodes “E- 1 ” to “E- 16 .”
- the electrode array 140 may be implemented using the electrode array 148 .
- Prior art stimulators allow a user (e.g., a clinician) to divide the electrodes “E- 1 ” to “E- 16 ” into up to four groups. Each group may include any number of electrodes. Stimulation having different frequency and pulse width may be delivered to the groups.
- the neurostimulator device 120 may divide the electrodes “E- 1 ” to “E- 16 ” into any number of groups. For example, each electrode may be assigned to its own group. By way of another example, one or more electrodes may belong to multiple groups. Table A below provides a few examples of groups that may be identified and stimulated independently. Which electrodes function as the anode and which function as a cathode are also specified for illustrative purposes.
- conventional stimulators are configured to deliver only rectangular waves to the electrodes “E- 1 ” to “E- 16 .”
- the neurostimulator device 120 is configured to deliver stimulation having waveform shapes beyond merely rectangular waves.
- the neurostimulator device 120 is configured to deliver stimulation to a single selected one of the electrodes 142 and/or use a single selected one of the electrodes 142 as a reference electrode.
- Prior art stimulators are not capable of this level of addressability.
- the electrode array 140 may be constructed using microfabrication technology to place numerous electrodes in an array configuration on a flexible substrate.
- One suitable epidural array fabrication method was first developed for retinal stimulating arrays (see, e.g., Maynard, Annu. Rev. Biomed. Eng., 3: 145-168 (2001); Weiland and Humayun, IEEE Eng. Med. Biol. Mag., 24(5): 14-21 (2005)), and U.S. Patent Publications 2006/0003090 and 2007/0142878 which are incorporated herein by reference for all purposes (e.g., the devices and fabrication methods disclosed therein).
- the stimulating arrays comprise one or more biocompatible metals (e.g., gold, platinum, chromium, titanium, iridium, tungsten, and/or oxides and/or alloys thereof) disposed on a flexible material (e.g., parylene A, parylene C, parylene AM, parylene F, parylene N, parylene D, or other flexible substrate materials).
- biocompatible metals e.g., gold, platinum, chromium, titanium, iridium, tungsten, and/or oxides and/or alloys thereof
- a flexible material e.g., parylene A, parylene C, parylene AM, parylene F, parylene N, parylene D, or other flexible substrate materials.
- Parylene has the lowest water permeability of available microfabrication polymers, is deposited in a uniquely conformal and uniform manner, has previously been classified by the FDA as a United States Pharmacopeia (USP) Class VI biocompatible material (enabling its use in chronic implants) (Wolgemuth, Medical Device and Diagnostic Industry, 22(8): 42-49 (2000)), and has flexibility characteristics (Young's modulus ⁇ 4 GPa (Rodger and Tai, IEEE Eng. Med. Biology, 24(5): 52-57 (2005))), lying in between those of PDMS (often considered too flexible) and most polyimides (often considered too stiff). Finally, the tear resistance and elongation at break of parylene are both large, minimizing damage to electrode arrays under surgical manipulation (Rodger et al., Sensors and Actuators B - Chemical, 117(1): 107-114 (2006)).
- the electrode array 140 may be characterized as being a microelectromechanical systems (“MEMS”) device. While the implementation of the electrode array 140 illustrated in FIG. 3B may be suited for use in animals, the basic geometry and fabrication technique can be scaled for use in humans.
- the electrode array 140 is configured for implantation along the spinal cord 110 (see FIG. 1 ) and to provide electrical stimulation thereto. For example, the electrode array 140 may provide epidural stimulation to the spinal cord 110 .
- the electrode array 140 allows for a high degree of freedom and specificity in selecting the site of stimulation compared to prior art wire-based implants, and triggers varied biological responses that can lead to an increased understanding of the spinal cord 110 and improved neurological function in the subject 102 .
- Electrode array 140 A non-limiting example of an electrode array that may be used to construct the electrode array 140 is described in co-pending U.S. patent application Ser. No. 13/356,499, filed on Jan. 23, 2012, and titled Parylene-Based Microelectrode Array Implant for Spinal Cord Stimulation, which is incorporated herein by reference in its entirety.
- the electrode array 140 includes a plurality of electrodes 142 (e.g., electrodes A 1 -A 9 , B 1 -B 9 , and C 1 -C 9 ), and a plurality of electrically conductive traces 144 .
- the electrodes 142 may vary in size, and be constructed using a biocompatible substantially electrically conductive material (such as platinum, Ag/AgCl, and the like), embedded in or positioned on a biocompatible substantially electrically non-conductive (or insulating) material (e.g., flexible parylene).
- a biocompatible substantially electrically conductive material such as platinum, Ag/AgCl, and the like
- a biocompatible substantially electrically non-conductive (or insulating) material e.g., flexible parylene
- Each of the electrodes 142 has one or more electrically conductive contacts (not shown) positionable alongside body tissue.
- the body tissue may include neurological tissue (e.g., the spinal cord 110 , one or more spinal nerves, one or more nerve roots, one or more peripheral nerves, the brain stem, and/or the brain 108 , and the like), other types of spinal tissue (e.g., the dura of the spinal cord 110 ), and the tissue of end organs.
- the electrode array 140 may be configured to be positionable alongside such body tissue.
- the electrode array 140 may be implanted using any of a number of methods (e.g., a laminectomy procedure, or percutaneously inserted) well known to those of skill in the art.
- the electrodes 142 may be implanted epidurally along the spinal cord 110 (see FIG. 1 ) or along side.
- the electrodes 142 may be positioned at one or more of a lumbosacral region, a cervical region, and a thoracic region of the spinal cord or along the brainstem 110 (see FIG. 1 ).
- electrodes 142 can be implanted at a combination of the above locations.
- the electrodes 142 are positioned distal to the lesion 112 (see FIG. 1 ) relative to the brain 108 (see FIG. 1 ). In other words, the electrodes 142 are positioned farther from the brain 108 than the lesion 112 .
- the one or more leads 130 include electrically conductive elements. In some embodiments, the one or more leads 130 include an electrically conductive element for each of the traces 144 of the electrode array 140 . By way of another non-limiting example, in some embodiments, the one or more leads 130 include an electrically conductive element for each of the electrodes 142 of the electrode array 140 .
- the one or more leads 130 of the assembly 100 connect the neurostimulator device 120 to the traces 144 of the electrode array 140 , which are each connected to one of the electrodes 142 .
- a signal generated by the neurostimulator device 120 is transmitted via the one or more leads 130 to selected ones of the traces 144 , which transmit the signal to selected ones of the electrodes 142 , which in turn deliver the stimulation to the body tissue in contact with the electrically conductive contacts (not shown) of the electrodes 142 .
- the one or more leads 130 may vary in length.
- the electrically conductive elements may be constructed using a biocompatible substantially electrically conductive material (such platinum, Ag/AgCl, and the like), embedded in or surrounded by a biocompatible substantially electrically non-conductive (or insulating) material (e.g., flexible parylene).
- the one or more leads 130 may include one or more connectors 132 and 134 . In the embodiment illustrated, the connector 132 is used to connect the one or more leads 130 to the electrode array 140 and the connector 134 is used to connect the one or more leads 130 to the neurostimulator device 220 .
- Epidural stimulating impulse generators can be combined with the neurostimulators described to produce a complex pattern of stimulating signals needed to produce improved neurological function (e.g., stepping, standing, arm movement, and the like after a severe SCI or/and occurrence of a neuromotor disorders).
- a complex pattern of stimulating signals needed to produce improved neurological function (e.g., stepping, standing, arm movement, and the like after a severe SCI or/and occurrence of a neuromotor disorders).
- an alternating spatiotemporal electric field having oscillations that peak over the right side of the spinal cord 110 (e.g., in the lumbosacral region) during a right leg swing phase, and oscillations that peak over the left side of the spinal cord 110 (e.g., in the lumbosacral region) during the left swing phase may be used.
- a rostral-caudal gradient in both electrode voltage and electrode stimulation frequency may be used. Rostral is nearer the brain 108 and caudal farther from the brain 108 . Prior art stimulators are simply not configured to deliver such complex stimulation patterns.
- Epidural stimulating impulse generators can have limitations that limit their ability to help patients recover functionality lost as a result of the neurologically derived paralysis. However, these limitations can be overcome when combined with the neurostimulators described herein.
- typical epidural stimulating impulse generators can deliver stimulation having the same amplitude to all active electrodes.
- Some epidural stimulating impulse generators can be configured to deliver stimulation having different amplitudes to four different groups of electrodes.
- typical epidural stimulating impulse generators can deliver stimulation having the same frequency to all channels (or electrodes).
- Some epidural stimulating impulse generators can be configured to deliver stimulation having different frequencies to four groups of channels (or electrodes).
- typical epidural stimulating impulse generators can deliver stimulation having the same pulse width to all of the channels (or electrodes). Further, typical epidural stimulating impulse generators can lack the ability to generate non-pulse waveforms.
- Neurostimulator device systems can include a plurality of electrodes, a neurostimulator device such as neurostimulator devices 220 , 320 , and 420 , a first computing device, and a pulse generating system including a second stimulator device which may include a second computing device.
- Pulse generating systems combinable with the presently described neurostimulators to form neurostimulator device systems as described above can be SPINAL MODULATIONTM's AXIUMTM neurostimulator, MEDTRONIC®'s INTERSTIM® Therapy for overactive bladder; MEDTRONIC® ENTERRA®, ENTEROWAVE® GI Neuromodualtion System, ST. JUDE MEDICAL®'s ACCENTTM Pacemaker, ST.
- the plurality of electrodes may be arranged in an electrode array implantable adjacent the body tissue of the subject.
- stimulator devices such as SPINAL MODULATIONTM's AXIUMTM neurostimulator, MEDTRONIC®'s INTERSTIM® Therapy (Medtronic, Minneapolis, N. Mex.) for overactive bladder; MEDTRONIC® ENTERRA®, ENTEROWAVE® GI Neuromodualtion System, ST. JUDE MEDICAL®'s ACCENTTM Pacemaker (St. Jude Medical, Maple Grove, Minn.), ST. JUDE MEDICAL®'s MICRONYTM Pacemaker, ST. JUDE MEDICAL®'s ZEPHYRTM Pacemanker; cardiac rhythm management devices such as ST.
- stimulator devices such as SPINAL MODULATIONTM's AXIUMTM neurostimulator, MEDTRONIC®'s INTERSTIM® Therapy (Medtronic, Minneapolis, N. Mex.) for overactive bladder; MEDTRONIC® ENTERRA®, ENTEROWAVE® GI Neuromodualtion System, ST. JUDE MEDICAL®'s ACCENTTM
- JUDE MEDICAL®'s CURRENTTM Plus ICD and ELLIPSETM ICD CAMERON HEALTH®'s SQ-RXTM Pulse Generator (Cameron Health, San Clemente, Calif.); and MEDTRONIC®'s VIVATM XT, VIVATM S, PROTECTATM XT, and PROTECTATM S, BOSTON SCIENTIFIC®'s PRECISION SPECTRA® (Boston Scientific Neuromodulation Corporation, Valencia, Calif.); NEVRO®'s SENZA® system, STIMWAVE®'s Freedom SCS system; Axionics' Sacral Neuromodulation System can be used as a standalone stimulator device.
- a neurostimulator device system can include one or more electrodes and SPINAL MODULATIONTM's AXIUMTM neurostimulator.
- a neurostimulator device system can include one or more electrodes and MEDTRONIC® ENTERRA®.
- a neurostimulator device system can include one or more electrodes and ENTEROWAVE® GI Neuromodualtion System.
- a neurostimulator device system can include one or more electrodes and MEDTRONIC®'s INTERSTIM® Therapy for overactive bladder.
- a neurostimulator device system can include one or more electrodes and ST. JUDE MEDICAL®'s ACCENTTM Pacemaker.
- a neurostimulator device system can include one or more electrodes and ST. JUDE MEDICAL®'s MICRONYTM Pacemaker.
- a neurostimulator device system can include one or more electrodes and ST. JUDE MEDICAL®'s ZEPHYRTM Pacemanker.
- a neurostimulator device system can include one or more electrodes and ST. JUDE MEDICAL®'s CURRENTTM Plus ICD.
- a neurostimulator device system can include one or more electrodes and ST. JUDE MEDICAL®'s ELLIPSETM ICD.
- a neurostimulator device system can include one or more electrodes and CAMERON HEALTH®'s SQ-RX Pulse Generator.
- a neurostimulator device system can include one or more electrodes and MEDTRONIC®'s VIVATM XT.
- a neurostimulator device system can include one or more electrodes and MEDTRONIC®'s VIVATM S.
- a neurostimulator device system can include one or more electrodes and MEDTRONIC®'s PROTECTATM XT.
- a neurostimulator device system can include one or more electrodes and MEDTRONIC®'s PROTECTATM S.
- a neurostimulator device system can include one or more electrodes and BOSTON SCIENTIFIC®'s PRECISION SPECTRA.
- a neurostimulator device system can include one or more electrodes and NEVRO®'s SENZA® system.
- a neurostimulator device system can include one or more electrodes and STIMWAVE®'s Freedom SCS system.
- a neurostimulator device system can include one or more electrodes and Axionics' Sacral Neuromodulation System.
- neurostimulator device systems can include a neurostimulator device and SPINAL MODULATIONTM's AXIUMTM neurostimulator.
- neurostimulator device systems can include a neurostimulator device and MEDTRONIC®'s INTERSTIM® Therapy for overactive bladder.
- neurostimulator device systems can include a neurostimulator device and MEDTRONIC® ENTERRA®.
- neurostimulator device systems can include a neurostimulator device and ENTEROWAVE® GI Neuromodualtion System.
- neurostimulator device systems can include a neurostimulator device and ST. JUDE MEDICAL®'s ACCENTTM Pacemaker.
- neurostimulator device systems can include a neurostimulator device and ST. JUDE MEDICAL®'s MICRONYTM Pacemaker.
- neurostimulator device systems can include a neurostimulator device and ST. JUDE MEDICAL®'s ZEPHYRTM Pacemanker.
- neurostimulator device systems can include a neurostimulator device and ST. JUDE MEDICAL®'s CURRENTTM Plus ICD.
- neurostimulator device systems can include a neurostimulator device and ST. JUDE MEDICAL®'s ELLIPSETM ICD.
- neurostimulator device systems can include a neurostimulator device and CAMERON HEALTH®'s SQ-RX Pulse Generator.
- neurostimulator device systems can include a neurostimulator device and MEDTRONIC®'s VIVATM XT.
- neurostimulator device systems can include a neurostimulator device and MEDTRONIC®'s VIVATM S.
- neurostimulator device systems can include a neurostimulator device and MEDTRONIC®'s PROTECTATM XT.
- neurostimulator device systems can include a neurostimulator device and MEDTRONIC®'s PROTECTATM S.
- neurostimulator device systems can include a neurostimulator device and BOSTON SCIENTIFIC®'s PRECISION SPECTRA.
- neurostimulator device systems can include a neurostimulator device and NEVRO®'s SENZA® system.
- neurostimulator device systems can include a neurostimulator device and STIMWAVE®'s Freedom SCS system.
- neurostimulator device systems can include a neurostimulator device and Axionics' Sacral Neuromodulation System.
- a neurostimulator device can be SPINAL MODULATIONTM's AXIUMTM neurostimulator.
- a neurostimulator device can be MEDTRONIC®'s INTERSTIM® Therapy for overactive bladder.
- a neurostimulator device can be a MEDTRONIC® ENTERRA®.
- a neurostimulator device can be ENTEROWAVE® GI Neuromodualtion System.
- a neurostimulator device can be ST. JUDE MEDICAL®'s ACCENTTM Pacemaker.
- a neurostimulator device can be ST. JUDE MEDICAL®'s MICRONYTM Pacemaker.
- a neurostimulator device can be ST. JUDE MEDICAL®'s ZEPHYRTM Pacemanker.
- a neurostimulator device can be ST. JUDE MEDICAL®'s CURRENTTM Plus ICD.
- a neurostimulator device can be ST. JUDE MEDICAL®'s ELLIPSETM ICD.
- a neurostimulator device can be CAMERON HEALTH®'s SQ-RX Pulse Generator.
- a neurostimulator device can be MEDTRONIC®'s VIVATM XT.
- a neurostimulator device can be MEDTRONIC®'s VIVATM S.
- a neurostimulator device can be MEDTRONIC®'s PROTECTATM XT.
- a neurostimulator device can be MEDTRONIC®'s PROTECTATM S.
- a neurostimulator device can be BOSTON SCIENTIFIC®'s PRECISION SPECTRA.
- a neurostimulator device can be NEVRO®'s SENZA® system.
- a neurostimulator device can be STIMWAVE®'s Freedom SCS system.
- a neurostimulator device can be Axionics' Sacral Neuromodulation System.
- a more complex waveform than the type generated by conventional stimulators must be delivered to one or more target locations.
- non-rectangular waveforms e.g., waveform 160 illustrated in FIG. 4A
- small “prepulses” e.g., prepulse 162 illustrated in FIG. 4B
- main “driving” pulse e.g., driving pulse 164 illustrated in FIG. 4B
- the timing of the onset of electrical stimulation must be carefully controlled.
- the spatio-temporal characteristics of the stimulating voltage fields needed for stepping require the ability to specify and control the phase shift (the exact timing of the onset of the stimulating waveform) between the electrodes 142 , across the entire electrode array 140 .
- Conventional stimulators can lack this ability.
- conventional systems can be modified to include the features of the described neurostimulator devices and bring about improved neurological function.
- Modifiable conventional stimulators can include, but are not limited to MEDTRONIC®'s RESTORESENSOR®, MEDTRONIC®'s RESTOREULTRA®, MEDTRONIC®'s RESTOREADVANCED®, MEDTRONIC®'s RESTOREPRIME®, MEDTRONIC®'s PRIMEADVANCED®, BOSTON SCIENTIFIC®'s PRECISION PLUSTM SCS System (Boston Scientific, Maple Grove, Minn.), SPINAL MODULATIONTM's AXIUMTM neurostimulator, ST. JUDE MEDICAL®'s EON MINITM, ST. JUDE MEDICAL®'s EON CTM, ST. JUDE MEDICAL®'s EONTM, ST.
- JUDE MEDICAL® EON Rechargeable IPG. NEVRO®'s SENZA® High Frequency Neuromodualtion System, MAIN STAY MEDICAL REACTIV8, and NEVRO® MATRI SOLEVE.
- combinations of the above conventional sensors can be utilized.
- these conventional stimulator systems can be transplanted adjacent to or touching the spinal cord. In other embodiments, these conventional stimulator systems need to be transplanted adjacent to the spinal cord.
- modifiable conventional stimulators such as MEDTRONIC®'s RESTORESENSOR®, MEDTRONIC®'s RESTOREULTRA®, MEDTRONIC®'s RESTOREADVANCED®, MEDTRONIC®'s RESTOREPRIME®, MEDTRONIC®'s PRIMEADVANCED®, BOSTON SCIENTIFIC®'s PRECISION PLUSTM SCS System (Boston Scientific, Maple Grove, Minn.), SPINAL MODULATIONTM's AXIUMTM neurostimulator, ST. JUDE MEDICAL®'s EON MINITM, ST. JUDE MEDICAL®'s EON CTM, ST. JUDE MEDICAL®'s EONTM, ST.
- JUDE MEDICAL® EON Rechargeable IPG. NEVRO®'s SENZA® Neuromodualtion System, MAIN STAY MEDICAL REACTIV8, NEVRO®'s MATRI SOLEVE, NEVRO®'s SENZA® BOSTON SCIENTIFIC®'s PRECISION SPECTRA, STIMWAVE®'s Freedom SCS system, Axionics' Sacral Neuromodulation System can be used as to block pain.
- the above identified modifiable conventional stimulators can be altered or otherwise tweaked go attain the herein described features and/or stimulation results.
- neurostimulator device systems can include a neurostimulator device and MEDTRONIC®'s RESTORESENSOR®.
- neurostimulator device systems can include a neurostimulator device and MEDTRONIC®'s RESTOREULTRA®.
- neurostimulator device systems can include a neurostimulator device and MEDTRONIC®'s RESTOREADVANCED®.
- neurostimulator device systems can include a neurostimulator device and MEDTRONIC®'s RESTOREPRIME®.
- neurostimulator device systems can include a neurostimulator device and MEDTRONIC®'s PRIMEADVANCED®.
- neurostimulator device systems can include a neurostimulator device and BOSTON SCIENTIFIC®'s PRECISION PLUSTM SCS System.
- neurostimulator device systems can include a neurostimulator device and SPINAL MODULATIONTM's AXIUMTM neurostimulator.
- neurostimulator device systems can include a neurostimulator device and ST. JUDE MEDICAL®'s EON MINITM.
- neurostimulator device systems can include a neurostimulator device and ST. JUDE MEDICAL®'s EON CTM system.
- neurostimulator device systems can include a neurostimulator device and ST. JUDE MEDICAL®'s EONTM system.
- neurostimulator device systems can include a neurostimulator device and ST. JUDE MEDICAL®'s EON Rechargeable IPG system.
- neurostimulator device systems can include a neurostimulator device and NEVRO® SENZA® High Frequency Neuromodualtion System.
- neurostimulator device systems can include a neurostimulator device and MAIN STAY MEDICAL's REACTIV8 system.
- neurostimulator device systems can include a neurostimulator device and a NEVRO®'s MATRI SOLEVE system.
- neurostimulator device systems can include a neurostimulator device and a NEVRO®'s SENZA®.
- neurostimulator device systems can include a neurostimulator device and a BOSTON SCIENTIFIC®'s PRECISION SPECTRA.
- neurostimulator device systems can include a neurostimulator device and a STIMWAVE®'s Freedom SCS system.
- neurostimulator device systems can include a neurostimulator device and a Axionics' Sacral Neuromodulation System.
- a neurostimulator device can be MEDTRONIC®'s RESTORESENSOR®.
- a neurostimulator device can be MEDTRONIC®'s RESTOREULTRA®.
- a neurostimulator device can be MEDTRONIC®'s RESTOREADVANCED®.
- a neurostimulator device can be MEDTRONIC®'s RESTOREPRIME®.
- a neurostimulator device can be MEDTRONIC®'s PRIMEADVANCED®.
- a neurostimulator device can be BOSTON SCIENTIFIC®'s PRECISION PLUSTM SCS System.
- a neurostimulator device can be SPINAL MODULATIONTM's AXIUMTM neurostimulator.
- a neurostimulator device can be ST. JUDE MEDICAL®'s EON MINITM.
- a neurostimulator device can be ST. JUDE MEDICAL®'s EON CTM system.
- a neurostimulator device can be ST. JUDE MEDICAL®'s EONTM system.
- a neurostimulator device can be ST. JUDE MEDICAL®'s EON Rechargeable IPG system.
- a neurostimulator device can be NEVRO® SENZA® High Frequency Neuromodualtion System.
- a neurostimulator device can be MAIN STAY MEDICAL's REACTIV8 system.
- a neurostimulator device can be NEVRO®'s MATRI SOLEVE system.
- a neurostimulator device can be NEVRO®'s SENZA®.
- a neurostimulator device can be BOSTON SCIENTIFIC®'s PRECISION SPECTRA.
- a neurostimulator device can be STIMWAVE®'s Freedom SCS system.
- a neurostimulator device can be Axionics' Sacral Neuromodulation System.
- the neurostimulator device 120 can be configured to generate complex types and patterns of electrical stimulation that achieve improved neurological function.
- the neurostimulator device 120 is configured to generate (and deliver to the electrode array 140 ) one or more “complex stimulation patterns.”
- a complex stimulation pattern has at least the following properties:
- a type of stimulation to apply to each of the electrodes 142 (which may include the application of no stimulation to one or more selected electrodes 142 , if appropriate), the type of stimulation is defined by stimulation type parameters that include waveform shape, amplitude, waveform period, waveform frequency, and the like, the electrodes 142 being individually addressable;
- stimulation timing that indicates when stimulation is to be applied to each of the electrodes 142 (which defines a sequence for applying stimulation to the electrodes 142 ), stimulation timing is defined by timing parameters that include an onset of stimulation, relative delay between waveform onset on different electrodes, a duration during which stimulation is delivered, a duration during which no stimulation is delivered, and the like;
- transition parameters that define how one waveform may be smoothly adapted over time to change (or morph) into a different waveform. Such smooth changes between waveform patterns may be helpful for enabling complex motor function, such as the transition from sitting to standing.
- the neurostimulator device 120 delivers the complex stimulation pattern to the electrode array 140 .
- the electrode array 140 is configured such that which of the electrodes 142 will receive stimulation may be selected.
- the electrodes 142 are individually addressable by the neurostimulator device 120 .
- the neurostimulator device 120 may also be configured such that the frequency, waveform width (or period), and/or amplitude of the stimulation delivered to each of the selected ones of the electrodes 142 may also be adjustable.
- the complex stimulation pattern may remain constant, repeat, or change over time.
- the configurability of the complex stimulation patterns delivered by the neurostimulator device 120 (by changing the stimulation parameters) enables the identification of effective complex stimulation patterns and the adjustment of the complex stimulation patterns to correct for migration and/or initial surgical misalignment.
- the neurostimulator device 120 may be configured to deliver a plurality of different complex stimulation patterns to the electrodes 142 .
- the neurostimulator device 120 can be programmable (e.g., by the subject 102 or a physician).
- the neurostimulator device 120 may be programmed with stimulation parameters and/or control parameters configured to deliver a complex stimulation pattern that is safe, efficacious, and/or selected to target specific body tissue. Further, stimulation parameters and/or control parameters may be customized for each patient (e.g., based on response to pre-surgical (implant) evaluation and testing).
- the neurostimulator device 120 may have a variable activation control for providing a complex stimulation pattern either intermittently or continuously, and allowing for adjustments to frequency, waveform width, amplitude, and duration.
- the neurostimulator device 120 may be used to (a) generate or maintain efficacious and/or optimal complex stimulation patterns, and/or (b) adjust the location of the application of stimulation (relative to the neural tissue) when the assembly 100 migrates and/or was misaligned during implantation.
- the neurostimulator device 120 may be configured to store, send, and receive data.
- the data sent and received may be transmitted wirelessly (e.g., using current technology, such as Bluetooth, ZigBee, WiFi, Z-wave, FCC-approved MICS medical transmission frequency bands, and the like) via a wireless connection 155 (see FIG. 2 ).
- the neurostimulator device 120 may be configured to be regulated automatically (e.g., configured for open loop and/or closed loop functionality). Further, the neurostimulator device 120 may be configured to record field potentials detected by the electrodes 142 , such as somatosensory evoked potentials (SSEPs) generated by the dorsum of the spinal cord 110 .
- the neurostimulator device 120 may be configured to be rechargeable.
- the neurostimulator device 120 may be configured with one or more of the following properties or features:
- the neurostimulator device 120 may be connected to one or more sensors 188 via connections 194 (e.g., wires, wireless connections, and the like).
- Sensors can be any type of sensor that can provide the data required by a neurostimulator device.
- sensors can include, but are not limited to electromyography (“EMG”) sensors 190 , joint angle (or flex) sensors 191 , evoked potential sensors, accelerometers 192 , gyroscopic sensors, pressure sensors, temperature sensors, flow sensors, load sensors, chemical sensors, light sensors, harmonic sensors, and the like.
- the connections (e.g., the connections 194 ) and sensors 188 may be implemented using external components and/or implanted components.
- the neurostimulator device 120 may be configured to modify or adjust the complex stimulation pattern based on information received from the sensors 188 via the connections 194 .
- the connections 194 may be implemented using wired or wireless connections.
- the neurostimulator device 120 may be connected to reference wires 196 . In FIG. 2 , one of the reference wires 196 is positioned near the shoulder, the other of the reference wires 196 is positioned in the lower back. However, this is not a requirement.
- a neurostimulator system can include at least one training device including one or more sensors that can provide data to a processor.
- a neurostimulator device can be configured to generate complex stimulation patterns based at least in part on the stimulation parameters received from the computing device, the computing device being further configured to determine the stimulation parameters based on at least in part on data collected by the one or more sensors associated with one or more training devices.
- Training devices can be standalone products or can be integrated into a neurostimular device or system. Further, a training device can include external adjunctive devices to aid a subject in using the training device. External adjunctive devices can include, training devices or systems configured to physically train subjects and thereby induce neurological signals in the paralyzed portion of the subject's body. Such training devices can use robotics, exoskeletons, treadmills, canes, walkers, crutches, body weight support systems, physical therapy, or a combination thereof to aid in training.
- Example training devices and systems can include, but are not limited to an EKSOTM Bionic Suit by EKSO BIONICS®, the REWALKTM system by Argo Medical Technologies, the THERASTRIDETM system by INNOVENTOR®, the RT300 system by Restorative Therapies, the RT200 system by Restorative Therapies, the RT600 system by Restorative Therapies, or the LOCOMAT system by HOCOMA®.
- the connections 194 may include one or more connectors 136 and 138 .
- the connector 136 is used to connect the connections 194 to the sensors 188 and the connector 138 is used to connect the connections 194 to the neurostimulator device 220 .
- the neurostimulator device 120 may be approximately 20 mm to approximately 25 mm wide, approximately 45 mm to approximately 55 mm long, and approximately 4 mm to approximately 6 mm thick.
- the neurostimulator device 120 may be approximately 3 mm to approximately 4 mm wide, approximately 20 mm to approximately 30 mm long, and approximately 2 mm to approximately 3 mm thick.
- the electrodes 142 are positioned on or near a target area (e.g., distal the lesion 112 illustrated in FIG. 1 ). If the subject 102 (see FIG. 2 ) has a SCI, the electrode array 140 may be positioned along the spinal cord 110 in a target area that is just distal to a margin of the lesion 112 . Thus, if the paralysis was caused by SCI at a first location along the spinal cord 110 (see FIG. 1 ), the electrodes 142 may be implanted (e.g., epidurally) at a second location below the first location along the spinal cord relative to the subject's brain 108 . The electrodes 142 may be placed in or on the spinal cord 110 (see FIG. 1 ), one or more spinal nerves, one or more nerve roots, one or more peripheral nerves, the brain stem, and/or the brain 108 (see FIG. 1 ).
- the complex stimulation pattern may include at least one of tonic stimulation and intermittent stimulation.
- the stimulation applied may be pulsed.
- the electrical stimulation may include simultaneous or sequential stimulation of different regions of the spinal cord 110 , one or more spinal nerves, one or more nerve roots, one or more peripheral nerves, the brain stem, and/or the brain 108 (see FIG. 1 ).
- the complex stimulation pattern applied by the assembly 100 may be below the second stimulation threshold such that the at least one selected spinal circuit is at least partially activatable by the addition of neurological signals (e.g., neurological signals induced by physical training or neurological signals originating from the brain 108 ) generated by the subject 102 (see FIG. 2 ).
- neurological signals e.g., neurological signals induced by physical training or neurological signals originating from the brain 108
- neurological signals generated by the subject 102 may be induced by subjecting the subject to physical activity or training (such as stepping on a treadmill 170 while suspended in a harness 172 or other support structure).
- the neurological signals generated by the subject 102 may be induced in a paralyzed portion of the subject 102 .
- the neurological signals generated by the subject 102 may include supraspinal signals (or neurological signals originating from the brain 108 ).
- the embodiment of the assembly 100 illustrated in FIG. 1 is configured for implantation in the subject 102 (see FIG. 2 ).
- embodiments may be constructed for use with other subjects, such as other mammals, including rats.
- the assembly 100 may be configured for chronic implantation and use.
- the assembly 100 may be used to stimulate one or more nerve roots, one or more nerves, the spinal cord 110 (see FIG. 1 ), the brain stem, and/or the brain over time.
- the dorsal root can be stimulated.
- the implantable assembly 100 may be used with an external system 180 illustrated in FIG. 2 .
- the external system 180 includes an external control unit 150 that may be used program, gather data, and/or charge the neurostimulator device 120 (e.g., via a wireless connection 155 ).
- the external control unit 150 is configured to be handheld.
- the external system 180 includes a computing device 152 described in detail below.
- the external control unit 150 may be connected via a connection 154 (e.g., a USB connection, wireless connection, and the like) to an external computing device 152 .
- the computing device 152 may be connected to a network 156 (e.g., the Internet) and configured to send and receive information across the network to one or more remote computing devices (e.g., a remote computing device 157 ).
- a network 156 e.g., the Internet
- remote computing devices e.g., a remote computing device 157
- the external control unit 150 may be omitted and the computing device 152 may communicate instructions directly to the neurostimulator device 120 via the wireless connection 155 .
- the computing device 152 may be implemented as a cellular telephone, tablet computing device, and the like having a conventional wireless communication interface.
- the computing device 152 may communicate instructions to the neurostimulator device 120 using a wireless communication protocol, such as Bluetooth.
- the computing device 152 may receive data from the neurostimulator device 120 via the wireless connection 155 . Instructions and data may be communicate to and received from the remote computing device 157 over the network 156 .
- the remote computing device 157 may be used to remotely program the neurostimulator device 120 (via the computing device 152 ) over the network 156 .
- One or more external sensors 158 may be connected to the computing device 152 via (wired and/or wireless) connections 159 . Further, a motion capture system 166 may be connected to the computing device 152 . The external sensors 158 and/or motion capture system 166 may be used to gather data about the subject 102 for analysis by the computing device 152 and/or the neurostimulator device 120 .
- the external sensors 158 may include at least one of the following: foot pressure sensors, a foot force plate, in-shoe sensors, accelerometers, surface EMG sensors, gyroscopic sensors, and the like.
- the external sensors 158 may be attached to or positioned near the body of the subject 102 .
- the motion capture system 166 may include any conventional motion capture system (e.g. a video-based motion capture system) and the present teachings are not limited to use with any particular motion capture system.
- FIG. 5 is a block diagram of a first embodiment of a system 200 .
- the system 200 includes an implantable assembly 202 substantially similar to the assembly 100 described above, and an external system 204 substantially similar to the external system 180 described above. Therefore, only components of the assembly 202 that differ from those of the assembly 100 , and components of the external system 204 that differ from those of the external system 180 will be described in detail. For ease of illustration, like reference numerals have been used to identify like components in FIGS. 1-3 and 5 .
- the assembly 202 includes a neurostimulator device 220 , the one or more leads 130 , and the electrode array 140 , and the connections 194 .
- the assembly 202 may also include the reference wires 196 (see FIG. 2 ).
- the assembly 202 may include the two reference wires illustrated in FIG. 2 .
- the connections 194 include sixteen wires, each connected to a different one of the sensors 188 (e.g., the EMG sensors 190 ).
- this is not a requirement and embodiments may be constructed using a different number of connections (e.g., wires), a different number of sensors, and/or different types of sensors without departing from the scope of the present teachings.
- the electrode array 140 includes the 27 electrodes A 1 -A 9 , B 1 -B 9 , and C 1 -C 9 .
- Particular embodiments include at least 16 electrodes.
- the neurostimulator device 220 is configured to send a stimulating signal (e.g., a “pulse”) to any of the electrodes 142 in the electrode array 140 .
- the neurostimulator device 220 is also configured to switch between different electrodes very rapidly.
- the neurostimulator device 220 can effectively send a predefined pattern of pulses to selected ones of the electrodes 142 in the electrode array 140 .
- the neurostimulator device 220 is configured to generate a wide variety of waveforms such that virtually any pulsed waveform can be generated.
- the electrodes 142 may be arranged in more than four groups, each group including one or more of the electrodes. Further, an electrode may be included in more than one group. In groups including more than one electrode, the electrodes may be stimulated simultaneously.
- the wireless connection 155 may be two components, a communication connection 155 A and a power transfer connection 155 B.
- the neurostimulator device 220 may be configured to deliver stimulation having the following properties:
- a maximum voltage (e.g., a constant voltage mode) of about ⁇ 12 V;
- a maximum stimulating current (e.g., a constant current mode) of about ⁇ 5 mA;
- DAC Digital to Analog converter
- any pair of the electrodes 142 may be addressed with multiple groups (e.g., more than four groups) of electrodes being addressable (e.g., stimulated or recorded from) simultaneously);
- any of the electrodes 142 if not used for applying stimulation, can be selected as a differential pair of electrodes and used for recording;
- the neurostimulator device 220 includes a multiplexer sub-circuit 230 , a stimulator circuit 240 , a controller 250 (connected to a controller circuit 252 illustrated in FIG. 8 ), and an optional wireless power circuit 260 .
- the controller 250 sends three control signals Clock, Data, and EN to the multiplexer sub-circuit 230 , and receives data A 1 ′-A 4 ′ from the multiplexer sub-circuit 230 .
- the stimulator circuit 240 provides a first stimulation signal STIM+ and a second stimulation signal STIM ⁇ to the multiplexer sub-circuit 230 .
- the controller 250 sends control signals PWM and MODE to the stimulator circuit 240 .
- the control signal MODE sent by the controller 250 to the stimulator circuit 240 instructs the stimulator circuit 240 to operate in either constant voltage mode or constant current mode.
- the control signal PWM sent by the controller 250 to the stimulator circuit 240 uses pulse-width modulation to control power sent by the stimulator circuit 240 to the multiplexer sub-circuit 230 as the first and second stimulation signals STIM+ and STIM ⁇ .
- the control signal PWM configures at least a portion of the complex stimulation pattern.
- the multiplexer sub-circuit 230 determines which of the electrodes 142 and/or connections 194 receives the stimulation. Therefore, the multiplexer sub-circuit 230 configures at least a portion of the complex stimulation pattern.
- both the stimulator circuit 240 and the multiplexer sub-circuit 230 configure the complex stimulation pattern based on instructions received from the controller 250 .
- the controller 250 is connected wirelessly to the external programming unit 150 via the communication connection 155 A.
- the communication connection 155 A may be configured to provide bi-directional wireless communication over which the controller 250 may receive system control commands and data from the external programming unit 150 , as well as transmit status information and data to the external programming unit 150 .
- the communication connection 155 A may include one or more analog communication channels, one or more digital communication channels, or a combination thereof.
- the controller 250 receives power (e.g., 3V) from the wireless power circuit 260 and a power monitoring signal PWRMON from the wireless power circuit 260 .
- the wireless power circuit 260 provides power (e.g., 12V and 3V) to the multiplexer sub-circuit 230 .
- the wireless power circuit 260 also provides power (e.g., 12V and 3V) to the stimulator circuit 240 .
- the wireless power circuit 260 receives power wirelessly from the external programming unit 150 via the power transfer connection 155 B.
- FIGS. 6A and 6B are a circuit diagram of an exemplary implementation of the multiplexer sub-circuit 230 .
- FIG. 6A is a leftmost portion of the circuit diagram of the multiplexer sub-circuit 230
- FIG. 6B is a rightmost portion of the circuit diagram of the multiplexer sub-circuit 230 .
- the circuit diagram of FIGS. 6A and 6B includes amplifiers AMP 1 -AMP 4 , shift registers SR 1 -SR 4 (e.g., implemented using NXP Semiconductors 74HC164), and analog multiplexer chips M 0 -M 9 .
- the amplifiers AMP 1 -AMP 4 output the data A 1 ′-A 4 ′, respectively.
- the amplifiers AMP 1 -AMP 4 (e.g., Analog Devices AD8224) may be implemented as differential amplifiers with a gain set to 200. However, as is apparent to those of ordinary skill in the art, other gain values may be used. Further, the gains of the amplifiers AMP 1 -AMP 4 may be readily changed by modifications to the components known to those of ordinary skill in the art.
- the multiplexer sub-circuit 230 routes the first and second stimulation signals Stim+ and Stim ⁇ to the selected ones of the electrodes 142 and/or connections 194 .
- the multiplexer sub-circuit 230 also routes signals received from selected ones of the electrodes 142 and/or connections 194 to the amplifiers AMP 1 -AMP 4 .
- the multiplexer sub-circuit 230 is configured to route signals between the stimulator circuit 240 , the amplifiers AMP 1 -AMP 4 , the electrodes 142 , and the connections 194 .
- the controller 250 sends a 30-bit serial data stream through the control signals Clock and Data to the multiplexer sub-circuit 230 , which is fed into the shift registers SR 1 -SR 4 .
- the shift registers SR 1 -SR 4 in turn control the analog multiplexer chips M 0 -M 9 , which are enabled by the control signal EN.
- the multiplexer chip M 0 has inputs “Da” and “Db” for receiving the first and second stimulation signals STIM+ and STIM ⁇ , respectively, from the controller 250 .
- the multiplexer chip M 0 is used to disconnect one or more of the electrodes 142 and/or one or more of the sensors 188 (e.g., the EMG sensors 190 ) during recording of signals detected by the disconnect component(s).
- the multiplexer chip M 0 is also used to select a polarity (or tristate) for each of the electrodes 142 when stimulation is applied.
- the multiplexer chip M 0 may be implemented as a 2 ⁇ (4:1) multiplexer (e.g., Analog Devices ADG1209).
- the multiplexer chips M 1 -M 9 are interconnected to connect almost any pair of the electrodes 142 or connections 194 to the amplifier AMP 1 and the inputs “Da” and “Db” (which receive the first and second stimulation signals STIM+ and STIM ⁇ , respectively) of multiplexer chip M 0 .
- the multiplexer chips M 1 -M 9 may each be implemented using an 8:1 multiplexer (e.g., Analog Devices ADG1208).
- a label in each rectangular tag in the circuit diagram identifies a connection to one of the electrodes 142 or connections 194 .
- Each label in a rectangular tag starting with the letter “E” identifies a connection to one of the connections 194 connected to one of the sensors 188 (e.g., one of the EMG sensors 190 ).
- the label “E 1 +” adjacent multiplexer chip M 1 identifies a connection to a first wire
- the label “E 1 ⁇ ” adjacent multiplexer chip M 2 identifies a connection to a second wire.
- the labels “E 1 +” and “E 1 ⁇ ” identify connections to a first pair of the connections 194 .
- the labels “G 1 ” and “G 2 ” adjacent multiplexer chip M 9 identify connections to the reference wires 196 (see FIG. 2 ).
- Each label in a rectangular tag starting with a letter other than the letter “E” or the letter “G” identifies a connection to one of the electrodes 142 .
- the label “A 3 ” refers to a connection to the electrode A 3 (see FIG. 3B ) in column A and row 3 (where column A is leftmost, column B is in the middle, column C is rightmost, row 1 is rostral, and row 9 is caudal).
- some key electrodes may have more than one connection to the multiplexer sub-circuit 230 .
- the electrodes A 1 , B 1 , C 1 , A 9 , B 9 , and C 9 are each identified by more than one label.
- the multiplexer sub-circuit 230 is designed to operate in four modes. In a first mode, the multiplexer sub-circuit 230 is configured to select an individual electrode to which to apply a monopolar stimulating pulse. In a second mode, the multiplexer sub-circuit 230 is configured to select a pair of the electrodes 142 to stimulate in a bipolar fashion. In a third mode, the multiplexer sub-circuit 230 is configured to select a single electrode from which to record, with the recorded waveform referenced to a ground signal. In a fourth mode, the multiplexer sub-circuit 230 is configured to select a pair of the electrodes 142 from which to record in a differential fashion.
- the neurostimulator device 220 can provide selective stimulation to any of the electrodes 142 .
- the multiplexer sub-circuit 230 is configured to route stimulation between almost any pair of the electrodes 142 or the connections 194 .
- the electrode A 1 may be the anode and the electrode B 6 the cathode.
- the multiplexer sub-circuit 230 is configured route signals received from the connections 194 to the amplifiers AMP 1 -AMP 4 and to the controller 250 (in data A 1 ′-A 4 ′) for recording thereby. Similarly, the multiplexer sub-circuit 230 is configured route signals received from the electrodes 142 to the amplifiers AMP 1 -AMP 4 and to the controller 250 (in data A 1 ′-A 4 ′) for recording thereby. By way of a non-limiting example, the multiplexer sub-circuit 230 may be configured route signals received from four electrodes positioned in the same column (e.g.
- Electrodes A 1 , A 3 , A 5 , and A 7 and signals received from a fifth electrode (e.g., electrode A 9 ) positioned in the same column to the controller 250 (in data A 1 ′-A 4 ′ output by the amplifiers AMP 1 -AMP 4 ) so that a differential signal received from the first four relative to the fifth may be recorded by the controller 250 for each pair of electrodes (e.g., a first pair including electrodes A 1 and A 9 , a second pair including electrodes A 3 and A 9 , a third pair including electrodes A 5 and A 9 , and a fourth pair including electrodes A 7 and A 9 ).
- a fifth electrode e.g., electrode A 9
- the multiplexer sub-circuit 230 receives power (e.g., 12V and 3V) from the wireless power circuit 260 .
- power lines providing this power to the multiplexer sub-circuit 230 have been omitted.
- the power lines may be implemented using one line having a voltage of about +12V, one line having a voltage of about +2V to about +6V (e.g., +3V), and one ground line.
- the multiplexer sub-circuit 230 may be configured to change configurations in less than one microsecond in embodiments in which the control signals Clock and Data are fast enough. This allows the first and second stimulation signals Stim+ and Stim ⁇ (received from the stimulator circuit 240 ) to be delivered in short pulses to selected ones of the electrodes 142 in about one millisecond and also allows the amplifiers AMP 1 -AMP 4 to rapidly switch input signals so the controller 250 may effectively record from 8 or 16 signals (instead of only four) within as little as about 20 microseconds. In some embodiments, the controller 250 may effectively record from 8 or 16 signals (instead of only four) within as little as 5 microseconds.
- FIG. 7 is a circuit diagram of an exemplary implementation of the stimulator circuit 240 .
- the stimulator circuit 240 is configured to selectively operate in two modes: constant voltage mode and constant current mode.
- labels “Mode 1 ” and “Mode 2 ” identify connections to pins “P 1 _ 0 ” and “P 1 _ 1 ,” respectively, of the controller 250 (see FIG. 8 ).
- pin “P 1 _ 0 ” (connected to the connection labeled “Mode 1 ”) is set to ground and pin “P 1 _ 1 ” (connected to the connection labeled “Mode 2 ”) is high impedance
- the stimulator circuit 240 is in constant voltage mode.
- the stimulator circuit 240 When pin “P 1 _ 1 ” (connected to the connection labeled “Mode 2 ”) is set to ground and pin “P 1 _ 0 ” (connected to the connection labeled “Mode 1 ”) is high impedance, the stimulator circuit 240 is in constant current mode.
- FIG. 8 is a circuit diagram of an exemplary implementation of a controller circuit 252 that includes the controller 250 and its surrounding circuitry.
- the controller 250 controls the multiplexer sub-circuit 230 , records amplified signals received (in the data A 1 ′-A 4 ′) from the multiplexer sub-circuit 230 , and monitors wireless power (using the power monitoring signal PWRMON received from the wireless power circuit 260 ).
- the controller 250 also communicates with an external controller 270 .
- the controller 250 has been implemented using a Texas Instruments CC1110.
- controller 250 is implemented using a different microcontroller, a microprocessor, a Field Programmable Gate Array (“FPGA”), a Digital Signal Processing (“DSP”) engine, a combination thereof, and the like.
- FPGA Field Programmable Gate Array
- DSP Digital Signal Processing
- the controller circuit 252 is configured to record voltages and currents received from the electrode array 140 when it is not stimulated. In such embodiments, the controller circuit 252 is also configured to transmit the recorded data over the communication connection 155 A (e.g., in “real time”) to the external programming unit 150 . In the embodiment illustrated, the controller circuit 252 includes an antenna 272 configured to communicate with the external controller 270 . The controller circuit 252 may be configured to coordinate stimulating (signal sending) and reading (signal receiving) cycles with respect to the electrode array 140 .
- signals e.g., Motor Evoked Potentials (MEPs)
- MEPs Motor Evoked Potentials
- the controller circuit 252 may be configured to measure (and/or control) the exact timing of the onset of stimulation.
- the controller circuit 252 may be configured to reset or stop stimulation at a desired time.
- the controller circuit 252 may be configured to transition smoothly between successive stimulation (e.g., pulses) and successive stimulation patterns.
- the controller circuit 252 may be configured to monitor electrode impedance, and impedance at the electrode/tissue interface. Of particular concern is impedance at relatively low frequencies (e.g., 10-1000 Hz).
- the controller circuit 252 may be configured to limit current and voltage. Further, the controller circuit 252 may be configured to trigger an alarm (or send an alarm message to the computing device 152 ) when voltage or current limits are exceeded.
- the neurostimulator device 220 may shut down or power down if an unsafe condition is detected.
- the external controller 270 may be used to program the controller 250 .
- the external controller 270 may be a component of the external control unit 150 (see FIG. 2 ).
- the external controller 270 may be implemented using a Texas Instruments CC1111.
- the external controller 270 may relay information to and from the computing device 152 through the connection 154 (e.g., a USB connection, and/or a wireless connection).
- the computing device 152 may be configured to control data streams to be sent to the neurostimulator device 220 .
- the computing device 152 may interpret data streams received from the neurostimulator device 220 .
- the computing device 152 is configured to provide a graphical user interface for communicating with the neurostimulator device 220 .
- the user interface may be used to program the neurostimulator device 220 to deliver particular stimulation. For example, the user interface may be used to queue up a particular sequence of stimuli.
- the computing device 152 may execute a method (e.g., a machine learning method described below) configured to determine stimulation parameters.
- the user interface may be used to configure the method performed by the computing device 152 .
- the user interface may be used to transfer information recorded by the neurostimulator device 220 to the computing device 152 for storage and/or analysis thereby.
- the user interface may be used to display information indicating an internal system state (such the current selection of stimulation parameters values) and/or mode of operation (e.g., constant voltage mode, constant current mode, and the like).
- FIG. 9 is a circuit diagram of an exemplary implementation of the optional wireless power circuit 260 .
- the wireless power circuit 260 is configured to receive power wirelessly from an external wireless power circuit 280 .
- the wireless power circuit 260 may supply both about 3V DC (output VCC) and about 12V DC (output VDD).
- the output VCC is connected to the multiplexer sub-circuit 230 , the stimulator circuit 240 , and the controller 250
- the output VDD is connected to the multiplexer sub-circuit 230 and the stimulator circuit 240 .
- the external wireless power circuit 280 may be a component of the external control unit 150 (see FIG. 2 ).
- the external wireless power circuit 280 may be implemented using a Class E amplifier and configured to provide variable output.
- the external wireless power circuit 280 provides power to the wireless power circuit 260 via inductive coupling over the power transfer connection 155 B.
- the wireless power circuit 260 may include a radio frequency (“RF”) charging coil 264 and the external wireless power circuit 280 includes an RF charging coil 284 configured to transfer power (e.g., inductively) to the RF charging coil 264 .
- RF radio frequency
- communication channels may be multiplexed on the wireless transmission.
- the wireless power circuit 260 may be connected to one or more rechargeable batteries (not shown) that are chargeable using power received from the external wireless power circuit 280 .
- the batteries may be implemented using rechargeable multi-cell Lithium Ion Polymer batteries.
- FIG. 10 is a block diagram of an implantable assembly 300 .
- the assembly 300 may be configured to communicate with the external controller 270 via the communication connection 155 A.
- the assembly 300 may receive power wirelessly from the external wireless power circuit 280 via inductive coupling over the power transfer connection 155 B.
- the assembly 300 is configured to also provide electrical stimulation directly to muscles (not shown) that will cause the muscle to move (e.g., contract) to thereby augment the improved neurological function provided by the complex stimulation patterns alone.
- the assembly 300 is configured to provide one or more complex stimulation patterns to 16 or more individually addressable electrodes for purposes of providing improved neurological function (e.g., improved mobility recovery after SCI).
- the assembly 300 includes a neurostimulator device 320 , the one or more leads 130 , and the electrode array 140 , the connections 194 (connected to the sensors 188 ), and connections 310 (e.g., wires, wireless connections, and the like) to (implanted and/or external) muscle electrodes 312 .
- the assembly 300 may also include the reference wires 196 (see FIG. 2 ).
- the assembly 300 may include the two reference wires illustrated in FIG. 2 .
- the connections 194 include sixteen wires, each connected to a different one of the sensors 188 (e.g., the EMG sensors 190 ).
- the neurostimulator device 320 includes a controller 322 , a recording subsystem 330 , a monitor and control subsystem 332 , a stimulating subsystem 334 , a muscle stimulator drive 336 , a sensor interface 338 , a wireless communication interface 340 , an RF power interface 342 , and at least one power source 344 (e.g., a rechargeable battery).
- the controller 322 has been implemented using a microcontroller (e.g., a Texas Instruments CC1110).
- a microcontroller e.g., a Texas Instruments CC1110
- embodiments may be constructed in which the controller 250 is implemented using a microprocessor, FPGA, DSP engine, a combination thereof, and the like.
- the rechargeable battery can include a charging system such as through transduction, ultrasonics, magnetism, or photonics.
- the battery may not be rechargeable, but rather disposable and user replaceable.
- the recording subsystem 330 is configured to record electrical signals received from one or more of the electrodes 142 in the electrode array 140 .
- the electrodes used to record may be the same electrodes used to provide the complex stimulation pattern, or different electrodes specialized for recording.
- the recording subsystem 330 may be connected (directly or otherwise) to one or more of the leads 130 . In the embodiment illustrated, the recording subsystem 330 is connected to the leads 130 via the monitor and control subsystem 332 .
- the recording subsystem 330 includes one or more amplifiers 346 .
- the amplifiers 346 are implemented as low noise amplifiers (“LNAs”) with programmable gain.
- LNAs low noise amplifiers
- the monitor and control subsystem 332 illustrated includes a blanking circuit 350 that is connected directly to the leads 130 .
- the blanking circuit 350 is configured to disconnect the recording subsystem 330 (which is connected thereto) from the leads 130 when the complex stimulation pattern is applied to the electrodes 142 to avoid damaging the amplifiers 346 .
- Bidirectional control and status lines (not shown) extending between the blanking circuit 350 and the controller 340 control the behavior of the blanking circuit 350 .
- the monitor and control subsystem 332 monitors the overall activity of the neurostimulator device 320 , as well as the functionality (e.g., operability) of the electrode array 140 .
- the monitor and control subsystem 332 is connected to the CPU by bidirectional digital and analog signal and control lines 352 .
- the monitor and control subsystem 332 includes a circuit 354 configured to monitor electrode impedance.
- a multiplexer (not shown) may be connected to the leads 130 , allowing the monitor and control subsystem 332 to selectively interrogate the signal received from each electrode.
- the output of the multiplexer (not shown) is connected to an A/D circuit (not shown), so that a signal received from a selected one of the electrodes 142 can be digitized, and transmitted to the controller 322 to assess the functionality of the stimulating circuitry.
- the monitor and control subsystem 332 may include circuitry 356 configured to assess the functionality (e.g., operability) of the power source 344 .
- the amplifiers 346 receive signals from the leads 130 when the blanking circuit 350 is in the off state. In some embodiments, a different one of the amplifiers 346 is connected to each different one of the leads 130 . In other embodiments, the blanking circuit 350 includes or is/may be connected to a multiplexing circuit having an input is connected to the leads 130 and the output of the blanking system 350 . In such embodiments, the multiplexing circuit routes an electrode signal (selected by the controller 322 ) to a single one of the amplifiers 346 . The amplifiers 346 are connected to the controller 322 via bidirectional control and status lines (not shown) that allow the controller 322 to control the gain and behavior of the amplifiers 346 .
- the recording subsystem 330 includes an analog-to-digital (“A/D”) circuit 347 that digitizes the output(s) received from the amplifiers 346 .
- A/D analog-to-digital
- a separate A/D circuit is dedicated to the output of each amplifier 346 .
- a multiplexing circuit (not shown) routes the output of a selected one of the amplifiers 346 to a single A/D circuit.
- the output of the A/D circuit 347 is connected via a serial or parallel digital bus 348 to the controller 322 .
- the recording subsystem 330 includes a parallel to serial circuit 349 that serializes the output received from the A/D circuit 347 for transmission on the bus 348 .
- Control and status lines (not shown) connect the A/D circuit 347 to the controller 322 , allowing the controller 322 to control the timing and behavior of the A/D circuit 347 .
- the stimulating subsystem 334 will be described as delivering complex stimulation patterns over channels. Each channel corresponds to one of the electrodes 142 . Stimulation delivered over a channel is applied to the corresponding one of the electrodes 142 . Similarly, stimulation received from one of the electrodes 142 may be received over the corresponding channel. However, in some embodiments, two or more electrodes may be physically connected to the same channel so their operation is governed by a single channel.
- the stimulating subsystem 334 is configured to generate complex stimulation patterns, which as explained above include complex waveforms (either in voltage or current mode), and deliver the stimulation on each of one or more of the channels.
- the stimulating subsystem 334 is connected to the controller 322 by multiple bidirectional lines 360 over which the stimulating subsystem 334 receives commands and stimulating waveform information.
- the stimulating subsystem 334 may transmit circuit status information to the controller 322 over the lines 360 .
- Each output is connected to one of the leads 130 , thereby stimulating a single one of the electrodes 142 in the electrode array 140 .
- the stimulating subsystem 334 includes a digital-to-analog amplifier 362 that receives stimulating waveform shape information from the controller 322 .
- the amplifier 362 turn drives (voltage or current) amplifiers 364 .
- the outputs of the amplifiers 364 are monitored and potentially limited by over-voltage or over-current protection circuitry 366 ).
- the muscle stimulator drive 336 is configured to drive one or more of the muscle electrodes 312 .
- the muscle stimulator drive 336 may provide an interface to a separate drive system (not shown).
- the muscle stimulator drive 336 is connected by bidirectional control lines 368 to the controller 322 to control the operation of the muscle stimulator drive 336 .
- the sensor interface 338 interfaces with one or more of the sensors 188 (the EMG sensors 190 , joint angle sensors 191 , accelerometers 192 , and the like). Depending upon the implementation details, the sensor interface 338 may include digital signal inputs (not shown), low noise amplifiers (not shown) configured for analog signal line inputs, and analog inputs (not shown) connected to A/D circuits (not shown).
- the controller 322 may be connected wirelessly to the external programming unit 150 via the communication connection 155 A.
- the communication connection 155 A may be configured to provide bi-directional wireless communication over which the controller 322 may receive system control commands and data from the external programming unit 150 , as well as transmit status information and data to the external programming unit 150 .
- the communication connection 155 A may include one or more analog communication channels, one or more digital communication channels, or a combination thereof.
- the RF power interface 342 may receive power wirelessly from the external programming unit 150 via the power transfer connection 155 B.
- the RF power interface 342 may include a radio frequency (“RF”) charging coil 372 .
- the RF charging coil 284 of the external wireless power circuit 280 may be configured to transfer power (e.g., inductively) to the RF charging coil 272 .
- communication channels may be multiplexed on the wireless transmission.
- the power source 344 may be implemented using one or more rechargeable multi-cell Lithium Ion Polymer batteries.
- FIG. 11 is a block diagram of a first embodiment of a system 400 .
- the system 400 includes an implantable assembly 402 substantially similar to the assembly 100 described above, and an external system 404 substantially similar to the external system 180 described above. Therefore, only components of the assembly 402 that differ from those of the assembly 100 , and components of the external system 404 that differ from those of the external system 180 will be described in detail. For ease of illustration, like reference numerals have been used to identify like components in FIGS. 1-3 , 5 , and 10 - 12 B.
- the assembly 402 includes a neurostimulator device 420 , the electrode array 140 , and the one or more traces 130 .
- the neurostimulator device 420 is connected by a controller interface bus 437 to an implantable muscle stimulator package 438 , and an EMG module 446 .
- the neurostimulator device 420 is configured to interface with and control both the implantable muscle stimulator package 438 and the EMG module 446 .
- suitable implantable muscle stimulator packages for use with the system may include a Networked Stimulation system developed at Case Western University.
- the neurostimulator device 420 includes a transceiver 430 , stimulator circuitry 436 , a wireless power circuit 440 , a power source 448 (e.g., a battery), and a controller 444 for the EMG module 446 and the power source 448 .
- the neurostimulator device 420 illustrated is configured interface with and control the separate EMG module 446 .
- EMG recording and management capabilities may be incorporated into the neurostimulator device 420 , as they are in the neurostimulator device 320 (see FIG. 10 ).
- the EMG module 446 includes an analog to digital converter (“ADC”) 445 . Digital data output by the EMG module 446 and received by the controller 444 is sent to the stimulator circuitry 436 via the controller interface bus 437 .
- ADC analog to digital converter
- the transceiver 430 is configured to communicate with a corresponding transceiver 432 of the external programming unit 150 connected to the external controller 270 over the communication connection 155 A.
- the transceivers 430 and 432 may each be implemented as Medical Implant Communication Service (“MICS”) band transceivers.
- MIMS Medical Implant Communication Service
- the transceiver 432 may be implemented using ZL70102 MICS band transceiver connected to a 2.45 GHz transmitter.
- the transmitter may be configured to “wake up” the transceiver 430 .
- the transceiver 430 may be implemented using a ZL70102 MICS band transceiver.
- FIG. 12A is a block diagram illustrating the transceiver 430 and the components of the stimulator circuitry 436 .
- connections labeled “SPI” have been implemented for illustrative purposes using Serial Peripheral Interface Buses.
- the stimulator circuitry 436 includes a central processing unit (“CPU”) or controller 422 , one or more data storage devices 460 and 462 , a digital to analog converter 464 , an analog switch 466 , and an optional complex programmable logic device (“CPLD”) 468 .
- the controller 422 has been implemented using a field-programmable gate array (“FPGA”). Digital data output by the EMG module 446 and received by the controller 444 is sent to the controller 422 via the controller interface bus 437 .
- FPGA field-programmable gate array
- the storage device 460 is connected to the controller 422 and configured to store instructions for the controller 422 .
- the storage device 460 may be implemented as FPGA configured memory (e.g., PROM or non-flash memory).
- the optional CPLD 468 is connected between the transceiver 430 and the storage device 460 .
- the optional CPLD 468 may be configured to provide robust access to the storage device 460 that may be useful for storing updates to the instructions stored on the storage device 460 .
- the storage device 462 is connected to the controller 422 and configured to store recorded waveform data.
- the storage device 462 may include 8 MB or more of memory.
- the digital to analog converter 464 is connected to the controller 422 and configured to convert digital signals received therefrom into analog signals to be delivered to the electrode array 140 .
- the digital to analog converter 464 may be implemented using an AD5360 digital to analog converter.
- the analog switch 466 is positioned between the digital to analog converter 464 and the leads 130 .
- the analog switch 466 is configured to modulate (e.g., selectively switch on and off) the analog signals received from the digital to analog converter 464 based on instructions received from the controller 422 .
- the analog switch 466 may include a plurality of analog switches (e.g., a separate analog switch for each channel).
- the analog switch 466 may have a high-impedance mode.
- the analog switch 466 may be configured to operate in the high-impedance mode (in response to instructions from the controller 422 instructing the analog switch 466 to operate in the high-impedance mode) when the neurostimulator device is not delivering stimulation to the electrodes 142 .
- the analog switch 466 may receive instructions from the controller 422 over one or more control lines 467 .
- the ability to directly stimulate muscles is not integrated into the neurostimulator device 420 as it is in the neurostimulator device 320 described above and illustrated in FIG. 10 .
- the controller 422 communicates with the separate implantable muscle stimulator package 438 via the controller interface bus 437 .
- a monitor and control subsystem (like the monitor and control subsystem 332 of the neurostimulator device 320 ) may be omitted from the neurostimulator device 420 .
- the neurostimulator device 420 is configured to deliver stimulation to each of a plurality of channels independently. As explained above, each channel corresponds to one of the electrodes 142 . Stimulation delivered over a channel is applied to the corresponding one of the electrodes 142 . In the embodiment illustrated, the plurality of channels includes 16 channels. However, this is not a requirement. To deliver stimulation, the neurostimulator device 420 uses one positive channel and one negative channel.
- signals detected or received by one or more of the electrodes 142 may be received by the neurostimulator device 420 over the corresponding channels.
- the neurostimulator device 420 may be configured to control the polarity (positive or negative) or tristate (positive, negative, or high Z) of each of the channels.
- the neurostimulator device 420 may be configured to deliver stimulation having a frequency within a range of about 0.1 Hz to about 100 Hz.
- the stimulation delivered may have an amplitude of about ⁇ 10 Vdc to about +10 Vdc with an increment of about 0.1 Vdc.
- the neurostimulator device 420 is configured to generate stimulation having a standard waveform shape (e.g., sine, triangle, square, and the like) and/or a custom defined waveform shape.
- the duty cycle of the neurostimulator device 420 may be configured (for example, for square waveform shapes).
- the neurostimulator device 420 may provide phase shift in specified increments (e.g., in 25 microsecond increments).
- the neurostimulator device 420 may be configured to satisfy timing requirements. For example, the neurostimulator device 420 may be configured to deliver a minimum pulse width of about 50 ⁇ s and to update all positive channels within a minimum pulse width. In such embodiments, a maximum number of positive channels may be determined (e.g., 15 channels). The neurostimulator device 420 may be configured to accommodate a minimum amount of phase shift (e.g., 25 ⁇ s phase shift). Further, the neurostimulator device 420 may be configured to update some channels during a first time period (e.g., 25 ⁇ s) and to rest during a second time period (e.g., 25 ⁇ s). The neurostimulator device 420 may be configured to simultaneously update the output channels.
- a first time period e.g., 25 ⁇ s
- a second time period e.g., 25 ⁇ s
- the neurostimulator device 420 may be configured to simultaneously update the output channels.
- the neurostimulator device 420 may be configured to satisfy particular control requirements. For example, it may be useful to configure the neurostimulator device 420 so that channel output configuration can be configured on the fly. Similarly, in some embodiments, practical limitations (e.g., a limit of a few seconds) may be placed on update time. Further, in some embodiments, the neurostimulator device 420 is configured to operate with adjustable custom waveform definitions. It may also be desirable to configure the neurostimulator device 420 such that output stimulation does not stop (or drop-out) during output reconfiguration.
- recording via the EMG module 446 (see FIG. 11 ) and delivering stimulation to the electrodes 142 may be performed completely separately (or independently). Further, in some embodiments, commands or instructions may be sent to the implantable muscle stimulator package 438 (or an integrated muscle stimulator system) independently or separately. Thus, this embodiment may operate in a full duplex mode.
- the neurostimulator device 420 may be connected to the EMG sensors 190 or recording electrodes (not shown) that are independent of the electrodes 142 used to deliver stimulation.
- Such recording electrodes can be implanted within a subject's body or external to the subject's body.
- a pre-amp (not shown) and ADC (not shown) may be included in the stimulator circuitry 436 and used to send digital EMG or nerve recording signals directly to the controller 422 .
- Such embodiments provide two completely separate, continuous time channels between recording and stimulation and therefore, may be characterized as being operable in a full duplex mode.
- the recording electrodes may be incorporated in the electrode array 140 and/or a separate electrode array (not shown).
- the analog switch 466 may be used to switch between a stimulate mode and a record mode.
- the analog switch 466 may receive instructions from the controller 422 (via the control lines 467 ) instructing the analog switch 466 in which mode to operate.
- This implementation may help reduce the number of electrodes by using the same electrodes or a subset thereof to record and stimulate.
- This exemplary embodiment may be characterized as being operable in a half-duplex mode.
- the stimulator circuitry 436 is configured to operate in a constant voltage mode.
- the output of the DAC 446 (and the analog switch 466 ) is a plurality (e.g., 16 ) of constant voltage signals (or sources).
- the stimulator circuitry 436 is configured to switch between the constant voltage mode and a constant current mode.
- the analog switch 466 includes a separate analog switch (e.g., a single pull, double throw switch) for each channel and a 2-1 multiplexer (“MUX”).
- MUX 2-1 multiplexer
- This embodiment also includes an analog switch 470 and a circuit block 472 .
- the analog switch 470 may include a separate analog switch (e.g., a single pull, double throw switch) for each channel and a 1-2 demultiplexer (“DEMUX”).
- the output of the analog switch 470 is a plurality (e.g., 16 ) of constant voltage signals selectively delivered to either the analog switch 466 or the circuit block 472 .
- the analog switches 470 and 466 may be configured to allow either a constant current signal or constant voltage signal to be applied to the electrode array 140 .
- the circuit block 472 includes voltage to current converter circuitry and constant current source circuitry.
- the circuit block 472 receives the plurality (e.g., 16 ) of constant voltage signals from the analog switch 470 and outputs a plurality (e.g., 16 ) of constant current signals (or sources).
- the neurostimulator device 420 may be configured to provide feedback (received from the sensor 188 , recording electrodes, and/or the electrodes 142 ) to the controller 422 , which the controller may use to modify or adjust the stimulation pattern or waveform.
- the controller 422 may be configured to modify the complex stimulation patterns delivered to the subject 102 in near realtime. Further, the controller 422 may be used to customize the complex stimulation pattern(s) for different subjects.
- the wireless power circuit 440 illustrated include a RF charging coil 449 configured to receive power via the power transfer connection 155 B. The power received may be used to charge the power source 448 (e.g., a battery).
- the power source 448 e.g., a battery
- a learning system e.g., the computing device 152 and/or one of the neurostimulator devices 220 , 320 , and 420 ) may be programmed to “learn” a personalized (or custom) stimuli pattern for the subject 102 , and continually adapt this stimuli pattern over time.
- the learning system receives input from one or more of the sensors 188 and/or external adjunctive devices, which may be implanted along with the neurostimulator device 220 , 320 , or 420 and/or temporarily applied to the subject 102 (e.g., in a clinical setting).
- sensors include the EMG sensors 190 , joint angle sensors 191 , accelerometers 192 , and the like.
- the external adjunctive devices may include support platforms, support stands, external bracing systems (e.g., exo-skeletal systems), in shoe sensor systems, and/or therapy machines. Information received from the electrodes 142 , the connections 194 , and/or the external adjunctive devices may be used to tune and/or adjust the complex stimulation pattern delivered by the neurostimulator devices 220 , 320 , and 420 .
- External adjunctive devices can include, training devices or systems configured to physically train subjects and thereby induce neurological signals in the paralyzed portion of the subject's body.
- Such training devices can use robotics, exoskeletons, treadmills, canes, walkers, crutches, body weight support systems, physical therapy, or a combination thereof to aid in training.
- Example training devices and systems can include, but are not limited to an EKSOTM Bionic Suit by EKSO BIONICS®, the REWALKTM system by Argo Medical Technologies, the THERASTRIDETM system by INNOVENTOR®, the RT300 system by Restorative Therapies, the RT200 system by Restorative Therapies, the RT600 system by Restorative Therapies, or the LOCOMAT system by HOCOMA®.
- a training device can be an EKSOTM Bionic Suit by EKSO BIONICS®.
- a training device can be a REWALK system by Argo Medical Technologies.
- a training device can be a THERASTRIDETM system by INNOVENTOR®.
- a training device can be a LOCOMAT system by HOCOMA®.
- a training device can be an RT300 system by Restorative Therapies.
- a training device can be an RT200 system by Restorative Therapies.
- a training device can be an RT600 system by Restorative Therapies.
- a neurostimulator can include an EKSOTM Bionic Suit by EKSO BIONICS®.
- a neurostimulator can include a REWALK system by Argo Medical Technologies.
- a neurostimulator can include a THERASTRIDETM system by INNOVENTOR®.
- a neurostimulator can include a LOCOMAT system by HOCOMA®.
- a neurostimulator can include an RT300 system by Restorative Therapies.
- a neurostimulator can include an RT200 system by Restorative Therapies.
- a neurostimulator can include an RT600 system by Restorative Therapies.
- the learning system may perform a machine learning method (described below) that determines suitable or optimal stimulation parameters based on information received from the sensors 188 . It is believed that it may be more efficient to perform larger adjustments to the stimulation in a clinical setting (e.g., using the computing device 152 and external programming unit 150 ), and smaller adjustments (fine tuning) on an ongoing basis (e.g., using one of the neurostimulator devices 220 , 320 , and 420 ).
- EMG sensors 190 In the clinical setting, numerous and sensitive EMG sensors 190 , as well as foot pressure sensors (not shown), accelerometers 192 , and motion tracking systems (not shown) can be used to gather extensive data on the performance of the subject 102 in response to specific stimuli. These assessments of performance can be used by the learning system to determine suitable and/or optimal stimulation parameters. Soon after the subject 102 is implanted with one of the neurostimulator devices 220 , 320 , and 420 , the subject 102 will begin physical training in a clinical setting (e.g., walking on the treadmill 170 ), which will continue for a few months during which the learning system can tune the stimulation parameters. Thereafter, the subject 102 may return to the clinic occasionally (e.g., on a regular basis (e.g., every 3 months)) for more major “tune ups.”
- a clinical setting e.g., walking on the treadmill 170
- the subject 102 may return to the clinic occasionally (e.g., on a regular basis (e.
- the neurostimulator devices 220 , 320 , and 420 receive signals from on-board, implanted, and external sensing systems (e.g., the electrodes 142 , the sensors 188 , and the like). This information may be used by the one of the neurostimulator devices 220 , 320 , and 420 to tune the stimulation parameters.
- on-board, implanted, and external sensing systems e.g., the electrodes 142 , the sensors 188 , and the like. This information may be used by the one of the neurostimulator devices 220 , 320 , and 420 to tune the stimulation parameters.
- systems and neurostimulator devices 220 , 320 , and 420 may each be configured to provide patient-customized stimuli, compensate for errors in surgical placement of the electrode array 140 , and adapt the stimuli over time to spinal plasticity (changes in spinal cord function and connectivity).
- suitable stimulation parameters e.g., a pattern of electrode array stimulating voltage amplitudes, stimulating currents, stimulating frequencies, and stimulating waveform shapes
- a machine learning method is employed to more efficiently search for effective parameter combinations. Over time, the machine learning method may be used to adapt (e.g., occasionally, periodically, continually, randomly, as needed, etc.) the operating parameters used to configure the stimulation.
- the machine learning method (which seeks to optimize the stimuli parameters) alternates between an exploration phase (in which the parameter space is searched and a regression model built that relates stimulus and motor response) and an exploitation phase (in which the stimuli patterns are optimized based on the regression model).
- an exploration phase in which the parameter space is searched and a regression model built that relates stimulus and motor response
- an exploitation phase in which the stimuli patterns are optimized based on the regression model.
- GPO Gaussian Process Optimization
- GPO is an active learning method with an update rule that explores and exploits the space of possible stimulus parameters while constructing an online regression model of the underlying mapping from stimuli to motor performance (e.g., stepping, standing, arm reaching, and the like).
- GPR Gaussian Process Regression
- GPR the regression modeling technique at the core of GPO, is well suited to online use because it requires fairly minimal computation to incorporate each new data point, rather than the extensive re-computation of many other machine learning regression techniques.
- GPR is also non-parametric; predictions from GPO are based on an ensemble of an infinite number of models lying within a restricted set, rather than from a single model, allowing it to avoid the over-fitting difficulties inherent in many parametric regression and machine learning methods.
- GPR is formulated around a kernel function, k(•,•), which can incorporate prior knowledge about the local shape of the performance function (obtained from experience and data derived in previous epidural stimulation studies), to extend inference from previously explored stimulus patterns to new untested stimuli.
- k(•,•) a kernel function that measures performance
- GPO is based on two key formulae and the selection of an appropriate kernel function.
- ⁇ t ( x *) k ( x*,X )[ K t ( X,X )+ ⁇ n 2
- ⁇ t 2 ( x *) k ( x*,x *) ⁇ k ( x*,X )[ K t ( X,X )+ ⁇ n 2
- K t is the noiseless covariance matrix of past data
- ⁇ n 2 is the estimated noise covariance of the data that is used in the performance evaluation.
- x t+1 argmax x ⁇ X* [ ⁇ t ( x )+ ⁇ t ⁇ t ( x )].
- GPO converges with high probability to the optimal action, given sufficient time.
- the method described above is a sequential updating method that works in a simple cycle.
- a single known stimulus is applied to the electrode array, and the patient's response to the stimulus is measured using either implanted sensors (such as EMG sensors 190 connected to the connections 194 ), and/or using external sensors (such as surface EMG electrodes, foot plate forces, and motion capture data gathered from a video monitoring system).
- implanted sensors such as EMG sensors 190 connected to the connections 194
- external sensors such as surface EMG electrodes, foot plate forces, and motion capture data gathered from a video monitoring system.
- the mean and covariance of the Gaussian Process system are immediately updated based on the single stimulus, and the upper confidence procedure of Equation (1) selects the next stimuli pattern to evaluate. This process continues until a termination criteria, such as a minimal increase in performance, is reached.
- x t+1 argmax x ⁇ X* [ ⁇ t ⁇ B ( x )+ ⁇ t ⁇ t ( x )].
- Equation (2) is evaluated B times to produce a batch of B proposed stimuli to evaluate, but the mean function ⁇ (x) is only updated at the end of the last batch of experiments, and the variance ⁇ t (x) is updated for each item in the proposed batch.
- a performance function that characterizes human motor behavior may depend upon at least two factors: (1) what kinds of motor performance data is available (e.g., video-based motion capture data, foot pressure distributions, accelerometers, EMG measurements, etc.); and (2) the ability to quantify motor performance. While more sensory data is preferable, a machine learning approach to parameter optimization can employ various types of sensory data related to motor performance. It should be noted that even experts have great difficulty determining stepping or standing quality from such data without also looking at video or the actual subject 102 as he/she undertakes a motor task.
- FIG. 13 depicts a multi-compartment physical model of the electrical properties of a mammalian spinal cord 500 , along with a 27 electrode implementation of the electrode array 140 placed in an epidural position.
- first and second electrodes 502 and 504 have been activated (i.e., are delivering stimulation to the spinal cord 500 ).
- One of the activated electrodes is the cathode and the other the anode.
- Electrode 506 has not been activated and is considered to be neutral.
- FIG. 14 the electrodes 502 and 504 have been activated.
- FIG. 14 shows the isopotential contours 508 (in slice through the center of the bipolarly activated electrodes) of the stimulating electric field for the 2-electrode stimulation example.
- the mammalian spinal cord 500 includes a dura 510 , white matter 512 , gray matter 514 , and epidural fat 516 .
- FIG. 15 shows the instantaneous regret (a measure of the error in the machine learning methods search for optimal stimuli parameters) when the Gaussian Process Optimization method summarized above is used to optimize the array stimulus pattern that excites neurons in the dorsal roots between segments L 2 and S 2 in the simulated spinal cord 500 .
- the instantaneous regret performance shows that the machine learning method rapidly finds better stimulating parameters, but also continually explores the stimulation space (the “bursts” in the graph of instantaneous regret correspond to excursions of the machine learning method to regions of stimulus parameter space which were previously unknown, but which have are found to have poor performance).
- FIG. 16 shows the average cumulative regret vs. learning iteration.
- the average cumulative regret is a smoothed version of the regret performance function that better shows the machine learning method's overall progress in selecting optimal stimulation parameters.
- the machine learning method may be performed by the computing device 152 , one of the neurostimulator devices 220 , 320 , and 420 , and/or a second stimulator device which may include a second computing device.
- instructions for performing the method may be stored in a non-transitory memory storage hardware device of at least one of the computing device 152 , the neurostimulator device 220 , the neurostimulator device 320 , the neurostimulator device 420 , and a second stimulator device which may include a second computing device. Further, these devices may interact during the performance of the method or distribute portions of its execution.
- the computing device 152 , the neurostimulator device 220 , the neurostimulator device 320 , the neurostimulator device 420 , and/or the second stimulator device which may include a second computing device may determine the stimulation parameters (e.g., the waveform shape, amplitude, frequency, and relative phasing) of the complex stimulation pattern applied to the electrodes 142 .
- the machine learning method may implement a Sequential or Batch Gaussian Process Optimization (“GPO”) method using an Upper Confidence Bound procedure to select and optimize the stimulation parameters.
- GPO Sequential or Batch Gaussian Process Optimization
- FIG. 17 is a diagram of hardware and an operating environment in conjunction with which implementations of the computing device 152 and/or the remote computing device 157 may be practiced.
- the description of FIG. 17 is intended to provide a brief, general description of suitable computer hardware and a suitable computing environment in which implementations may be practiced.
- implementations are described in the general context of computer-executable instructions, such as program modules, being executed by a computer, such as a personal computer.
- program modules include routines, programs, objects, components, data structures, etc., that perform particular tasks or implement particular abstract data types.
- implementations may be practiced with other computer system configurations, including hand-held devices, multiprocessor systems, microprocessor-based or programmable consumer electronics, network PCs, minicomputers, workstations, mainframe computers, cellular phones, smart phones (e.g., Apple iphone, Samsung Galaxy, etc.), tablet computers (e.g., Apple iPad, Barnes and Noble Nook, Amazon Kindle Fire, Microsoft Surface, etc.), laptop computer, ultrabook computer, netbook computer, pager, gaming console (e.g., Microsoft Xbox 360 or Xbox One, Sony Playstation 3 or 4, Nintendo Wii or WiiU, etc.), and the like. Implementations may also be practiced in distributed computing environments where tasks are performed by remote processing devices that are linked through a communications network. In a distributed computing environment, program modules may be located in both local and remote memory storage devices.
- the exemplary hardware and operating environment of FIG. 17 includes a general-purpose computing device in the form of a computing device 12 .
- the computing device 152 and/or the remote computing device 157 may be substantially identical to the computing device 12 .
- the computing device 12 includes a system memory 22 , the processing unit 21 , and a system bus 23 that operatively couples various system components, including the system memory 22 , to the processing unit 21 .
- the processing units may be heterogeneous.
- such a heterogeneous processing environment may include a conventional CPU, a conventional graphics processing unit (“GPU”), a floating-point unit (“FPU”), combinations thereof, and the like.
- the computing device 12 may be a conventional computer, a distributed computer, any other type of computer, any type of wired computing device, or any type of wireless computing device.
- the system bus 23 may be any of several types of bus structures including a memory bus or memory controller, a peripheral bus, and a local bus using any of a variety of bus architectures.
- the system memory 22 may also be referred to as simply the memory, and includes read only memory (ROM) 24 and random access memory (RAM) 25 .
- ROM read only memory
- RAM random access memory
- a basic input/output system (BIOS) 26 containing the basic routines that help to transfer information between elements within the computing device 12 , such as during start-up, is stored in ROM 24 .
- the computing device 12 further includes a hard disk drive 27 for reading from and writing to a hard disk, not shown, a magnetic disk drive 28 for reading from or writing to a removable magnetic disk 29 , and an optical disk drive 30 for reading from or writing to a removable optical disk 31 such as a CD ROM, DVD, or other optical media.
- a hard disk drive 27 for reading from and writing to a hard disk, not shown
- a magnetic disk drive 28 for reading from or writing to a removable magnetic disk 29
- an optical disk drive 30 for reading from or writing to a removable optical disk 31 such as a CD ROM, DVD, or other optical media.
- the hard disk drive 27 , magnetic disk drive 28 , and optical disk drive 30 are connected to the system bus 23 by a hard disk drive interface 32 , a magnetic disk drive interface 33 , and an optical disk drive interface 34 , respectively.
- the drives and their associated computer-readable media provide nonvolatile storage of computer-readable instructions, data structures, program modules, and other data for the computing device 12 . It should be appreciated by those skilled in the art that any type of computer-readable media which can store data that is accessible by a computer, such as magnetic cassettes, flash memory cards, solid state memory devices (“SSD”), USB drives, digital video disks, Bernoulli cartridges, random access memories (RAMs), read only memories (ROMs), and the like, may be used in the exemplary operating environment.
- SSD solid state memory devices
- RAMs random access memories
- ROMs read only memories
- the hard disk drive 27 and other forms of computer-readable media e.g., the removable magnetic disk 29 , the removable optical disk 31 , flash memory cards, SSD, USB drives, and the like
- the processing unit 21 may be considered components of the system memory 22 .
- a number of program modules may be stored on the hard disk drive 27 , magnetic disk 29 , optical disk 31 , ROM 24 , or RAM 25 , including an operating system 35 , one or more application programs 36 , other program modules 37 , and program data 38 .
- a user may enter commands and information into the computing device 12 through input devices such as a keyboard 40 and pointing device 42 .
- Other input devices may include a microphone, joystick, game pad, satellite dish, scanner, touch sensitive devices (e.g., a stylus or touch pad), video camera, depth camera, or the like.
- serial port interface 46 that is coupled to the system bus 23 , but may be connected by other interfaces, such as a parallel port, game port, a universal serial bus (USB), or a wireless interface (e.g., a Bluetooth interface).
- a monitor 47 or other type of display device is also connected to the system bus 23 via an interface, such as a video adapter 48 .
- computers typically include other peripheral output devices (not shown), such as speakers, printers, and haptic devices that provide tactile and/or other types of physical feedback (e.g., a force feed back game controller).
- the input devices described above are operable to receive user input and selections. Together the input and display devices may be described as providing a user interface.
- the computing device 12 may operate in a networked environment using logical connections to one or more remote computers, such as remote computer 49 . These logical connections are achieved by a communication device coupled to or a part of the computing device 12 (as the local computer). Implementations are not limited to a particular type of communications device.
- the remote computer 49 may be another computer, a server, a router, a network PC, a client, a memory storage device, a peer device or other common network node, and typically includes many or all of the elements described above relative to the computing device 12 .
- the remote computer 49 may be connected to a memory storage device 50 .
- the logical connections depicted in FIG. 17 include a local-area network (LAN) 51 and a wide-area network (WAN) 52 . Such networking environments are commonplace in offices, enterprise-wide computer networks, intranets and the Internet.
- a LAN may be connected to a WAN via a modem using a carrier signal over a telephone network, cable network, cellular network, or power lines.
- a modem may be connected to the computing device 12 by a network interface (e.g., a serial or other type of port).
- a network interface e.g., a serial or other type of port.
- many laptop computers may connect to a network via a cellular data modem.
- the computing device 12 When used in a LAN-networking environment, the computing device 12 is connected to the local area network 51 through a network interface or adapter 53 , which is one type of communications device. When used in a WAN-networking environment, the computing device 12 typically includes a modem 54 , a type of communications device, or any other type of communications device for establishing communications over the wide area network 52 , such as the Internet.
- the modem 54 which may be internal or external, is connected to the system bus 23 via the serial port interface 46 .
- program modules depicted relative to the personal computing device 12 may be stored in the remote computer 49 and/or the remote memory storage device 50 . It is appreciated that the network connections shown are exemplary and other means of and communications devices for establishing a communications link between the computers may be used.
- the computing device 12 and related components have been presented herein by way of particular example and also by abstraction in order to facilitate a high-level view of the concepts disclosed.
- the actual technical design and implementation may vary based on particular implementation while maintaining the overall nature of the concepts disclosed.
- system memory 22 stores computer executable instructions that when executed by one or more processors cause the one or more processors to perform all or portions of the machine learning method described above.
- Such instructions may be stored on one or more non-transitory computer-readable media (e.g., the storage device 460 illustrated in FIG. 12A ).
- any two components herein combined to achieve a particular functionality can be seen as “associated with” each other such that the desired functionality is achieved, irrespective of architectures or intermedial components.
- any two components so associated can also be viewed as being “operably connected,” or “operably coupled,” to each other to achieve the desired functionality.
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Abstract
Description
- This application is a continuation-in-part of U.S. patent application Ser. No. 14/007,262 filed on Feb. 17, 2014, which is a national stage entry of PCT/US2012/030624 filed on Mar. 26, 2012, which claims the benefit of U.S. provisional patent application No. 61/467,107 filed Mar. 24, 2011, the entire disclosures each of which are incorporated herein by reference.
- This application claims the benefit of U.S. provisional patent application No. 61/931,430 filed Jan. 24, 2014, the entire disclosure of which is incorporated herein by reference.
- The present disclosure is directed generally to the field of medical electro-medical therapy devices, and more particularly to implantable stimulators and stimulator systems used in neurological rehabilitation for the treatment of traumatic and non-traumatic injury or illness.
- Implantable neurostimulator and neuromodulator devices have been used to deliver therapy to patients to treat a variety of symptoms or conditions such as chronic pain, epilepsy, and tremor associated with and without Parkinson's disease. The implantable stimulators deliver stimulation therapy to targeted areas of the nervous system. The applied therapy is usually in the form of electrical pulse at a set frequency. The current is produced by a generator. The generator and an associated control module may be constructed from a variety of mechanical and electrical components. The generator is typically housed in a casing made of biocompatible material such as titanium, allowing for surgical placement subcutaneously within the abdomen or chest wall of a patient by someone with ordinary skill in the art of orthopedic spine and neurosurgery.
- The stimulator is attached via one or more leads to one or more electrodes that are placed in close proximity to one or more nerves, one or more parts of a nerve, one or more nerve roots, the spinal cord, the brain stem, or within the brain itself. The leads and electrode arrays may vary in length, and are also made of a biocompatible material.
- Historically, implantable stimulators and their attached electrodes positioned outside of the brain around the spinal cord, nerve roots, spinal nerves, and peripheral nerves have been used to manage and treat chronic pain; none to date have been commercially used or approved to restore function. Further, none have been aimed at permanent remodeling of the nervous system. Attempts to restore function in neurologically impaired subjects have been limited to adjunctive modalities, such as physical and occupational therapy with emphasis on adaptation to disability. Little progress has been achieved in actually restoring normal functional capacity to damaged nerve tissue, nerve structures and/or nerve components that make up the nervous system along with the organs and anatomical structures they innervate with the use of an implantable neurostimulator.
- Therefore, a need exists for a neurostimulator device configured to deliver stimulation through an electrode array that will help a patient regain voluntary movements, and/or recover autonomic, sexual, vasomotor, and/or improved cognitive function after a motor incomplete SCI or motor complete SCI. The present application provides these and other advantages as will be apparent from the following detailed description and accompanying figures.
- Embodiments include neurostimulator devices and systems for use with a subject (e.g., a human patient or an animal). Neurostimulator devices may be for use with a plurality of groups of electrodes. In particular implementations, the plurality of groups of electrodes may include more than four groups of electrodes. In some embodiments, the electrodes are wired electrodes. In other embodiments, the electrodes are wireless electrodes. In still other embodiments, the electrodes are a combination of wired and wireless electrodes. Neurostimulator devices may include a stimulation assembly connectable to the plurality of groups of electrodes. In some embodiments, the electrodes can be electrical, chemical, mechanical, photonic, or a combination thereof. The stimulation assembly can be configured to deliver different stimulations to each of the plurality of groups of electrodes when the stimulation assembly is connected thereto. In some embodiments, the stimulation assembly can be configured to deliver different stimulations to an individual electrode within each group when the stimulation assembly is connected thereto. The neurostimulator device may also include at least one processor connected to the stimulation assembly. The at least one processor can be configured to direct the stimulation assembly to deliver different stimulation(s) to each of the plurality of groups of electrodes or individual electrodes within a group. The neurostimulator device may be configured for implantation in a subject (e.g., a human being or an animal). The stimulation delivered to at least one of the plurality of groups of electrodes or individual electrodes within a group may include one or more waveform shapes other than a square or rectangular wave shape.
- In other embodiments, neurostimulator devices can be for use with a plurality of electrodes and one or more sensors. In such embodiments, the neurostimulator device may include a stimulation assembly connectable to the plurality of electrodes. The stimulation assembly can be configured to deliver stimulation to selected electrodes within of the plurality of electrodes when the stimulation assembly is connected to the plurality of electrodes. Neurostimulator devices may also include a sensor interface connectable to the one or more sensors. The sensor interface can be configured to receive signals from the one or more sensors when the sensor interface is connected to the one or more sensors. The sensors can be wires sensors, wireless sensors implanted, external to the body, or a combination thereof. In some embodiments, some sensors are wired and some are wireless. In other embodiments, some sensors are implanted and some are external to the body. In still other embodiments, all the sensors are wired and implanted, wired and external to the body, wireless and implanted, or wireless and external to the body. Various combinations thereof are also possible. The neurostimulator device may further include at least one processor connected to both the stimulation assembly and the sensor interface. The at least one processor can be configured to direct the stimulation assembly to deliver at least one complex stimulation pattern to selected electrodes within the plurality of electrodes and to receive the signals from the sensor interface. The at least one processor can be further configured to modify the at least one complex stimulation pattern delivered by the stimulation assembly based on the signals received from the sensor interface. In some embodiments, the stimulation assembly, sensor interface, and at least one processor are housed inside a housing configured for implantation in the body of the subject.
- The at least one complex stimulation pattern may include a first stimulation pattern followed by a second stimulation pattern. In such embodiments, the second stimulation pattern may be delivered to a second portion of selected electrodes within the plurality of electrodes less than about one microsecond after the first stimulation pattern is delivered to a first portion of selected electrodes within the plurality of electrodes. Optionally, the first stimulation pattern may be delivered to a first portion of selected electrodes within the plurality of electrodes, and the second stimulation pattern is delivered to a second portion of selected electrodes within the plurality of electrodes, wherein the first portion is different from the second portion. Selected electrodes within the plurality of electrodes may include more than four groups of electrodes, and the at least one complex stimulation pattern may include different electrical stimulation for each of the groups of electrodes or an individual electrode of each group.
- The at least one processor may be configured to perform a machine learning method (based on the signals received from the sensor interface or recorded from the sensor interface) to determine a set of stimulation parameters. In such embodiments, the at least one processor may modify the at least one complex stimulation pattern based at least in part on the set of stimulation parameters. Optionally, the at least one processor may be configured to receive and record electrical signals from the plurality of electrodes. The at least one processor may modify the at least one complex stimulation pattern based at least in part on the electrical signals received from the plurality of electrodes, the sensors, or a combination thereof.
- The at least one processor may include at least one of a microprocessor, a microcontroller, a field programmable gate array, and a digital signal processing engine.
- The neurostimulator device may be for use with, be at least partially controlled by, or send at least partial reports to a computing device. Computing devices may be any type of device including at least one processor and memory. Computing devices can include, but are not limited to hand held control units, cellular phones, smart phones (e.g., Apple, iPhone, Samsung Galaxy, etc.), tablets (e.g., Apple iPad), desktop computers, workstation computers, computer servers, laptop computers, ultrabook computers, netbook computers, gaming consoles, pagers, or the like.
- In such embodiments, the at least one processor may be configured to transmit the recorded electrical signals to at least one computing device and to receive information therefrom. The at least one processor may be configured to modify the at least one complex stimulation pattern based at least in part on the information received from the computing device. Optionally, the at least one processor may be configured to record the signals received from the sensor interface, transmit the recorded electrical signals to the computing device, and receive information from the computing device. The at least one processor may be configured to modify the at least one complex stimulation pattern based at least in part on the information received from the sensors and/or computing device.
- The plurality of sensors may include at least one of an electromyography sensor, an evoked potential sensor, a joint angle sensor, a flex sensor, an accelerometer, a gyroscope sensor, a flow sensor, a pressure sensor, a temperature sensor, a chemical sensor, a light sensor, a photonic sensor, a harmonic sensor, and a load sensor. In some embodiments, the sensors may be located within the housing of the generator or electrode array. In other embodiments, the sensors may be remote to the housing wherein they are implanted elsewhere within the subject's body or reside external and superficial to the subject's body. In some embodiments, sensors may reside in combinations of inside the housing, implanted elsewhere, and reside external to the subject's body. In some embodiments, the sensors can be located in, on, or associated with one or more training devices. In some embodiments, the sensors can be wired or wireless.
- Embodiments of neurostimulator devices may be for use with a subject having a neurologically derived paralysis in a portion of his/her body. The subject can have a spinal cord with at least one selected spinal circuit that has a first stimulation threshold representing a minimum amount of stimulation required to activate the at least one selected spinal circuit, and a second stimulation threshold representing an amount of stimulation above which the at least one selected spinal circuit is fully activated. When the at least one complex stimulation pattern is applied to a portion of a patient's spinal cord, the at least one complex stimulation pattern is below the second stimulation threshold such that the at least one selected spinal circuit is at least partially activatable by the addition of at least one of (a) neurological signals originating from the portion of the patient's body having the paralysis, and (b) supraspinal signals. The neurological signals originating from the portion of the patient's body having the paralysis may be neurological signals induced by physical training, mechanical manipulation, a physiological change, a response to light, an introduction of a pharmaceutical or active agent, or a chemical response. Induced neurological signals may include at least one of postural proprioceptive signals, locomotor proprioceptive signals, temperature signals or changes in temperature, vibratory signals, chemical signals, light signals, supraspinal signals, and combinations thereof.
- In some embodiments, when at least partially activated, the at least one selected spinal circuit produces improved neurological function including at least one of voluntary movement of muscles involved in at least one of standing, stepping, reaching, grasping, voluntarily changing positions of one or both legs, voluntarily changing positions of one or both arms, voluntarily changing position of one's neck, voiding the subject's bladder, voiding the subject's bowel, breathing, coughing, chewing, swallowing, speaking, blinking, focusing visual fields, postural activity changing core (trunk) position, improve muscle tone postural activity, and improve locomotor activity. In some embodiments, when at least partially activated, the at least one selected spinal circuit produces improved neurological function including at least one of improved autonomic control of at least one of voiding the subject's bladder, voiding the subject's bowel, cardiovascular function, respiratory function, digestive function, body temperature, and metabolic processes. In some embodiments, when at least partially activated the at least one selected spinal circuit produces improved neurological function including at least one of an autonomic function, sexual function, motor function, vasomotor function, and cognitive function.
- Optionally, the neurostimulator device may include at least one rechargeable battery configured to power various electronic components. In one embodiment, the battery can be configured to power the at least one processor. In one embodiment, the neurostimulator device can be plugged into a power source to charge the battery when needed. If the neurostimulator device requires frequent recharging and/or requires being plugged into a power source for recharging, multiple devices can be provided to a patient thereby allowing one to remain charged at all times. In other embodiments, the neurostimulator device may include a wireless recharging assembly configured to receive power wirelessly and transmit at least a portion of the power received to the at least one rechargeable battery. In other embodiments, the rechargeable battery system may be though transduction, ultrasonic, magnetic, or photonic.
- The neurostimulator device may be for use with a plurality of muscle electrodes. In such embodiments, the neurostimulator device may include a muscle stimulation assembly connected to the at least one processor, and configured to deliver electrical stimulation to the plurality of muscle electrodes. In such embodiments, the at least one processor may be configured to instruct the muscle stimulation assembly to deliver the electrical stimulation to the plurality of muscle electrodes. In alternate embodiments, the neurostimulator device may be for use with a muscle stimulation device configured to deliver electrical stimulation to the plurality of muscle electrodes. In such embodiments, the neurostimulator device may include an interface connected to the at least one processor, and configured to direct the muscle stimulation device to deliver electrical stimulation to the plurality of muscle electrodes.
- Optionally, the neurostimulator device may be for use with at least one recording electrode. In such embodiments, the at least one processor is connected to the at least one recording electrode, and configured to receive and record electrical signals received from the at least one recording electrode. In some embodiments, recording electrodes may be located within the housing of the generator or an electrode array. In other embodiments, the recording electrodes may be remote to the housing wherein they are implanted elsewhere within the subject's body or reside external and superficial to the subject's body. In some embodiments, the recording electrodes may reside in combinations of inside the housing, implanted elsewhere, and reside external to the subject's body.
- The neurostimulator devices described above may be incorporated in one or more systems. An example of such a system may be for use with a subject having body tissue, and one or more sensors positioned to collect physiological data related to the subject. The system may include a plurality of electrodes, the neurostimulator device, and a computing device. The plurality of electrodes may be arranged in an electrode array implantable adjacent to the body tissue of the subject. The electrode array may be implantable adjacent to at least one of a portion of the spinal cord, one or more spinal nerves, one or more nerve roots, one or more peripheral nerves, the brain stem, the brain, and an end organ. The plurality of electrodes may include at least 16 electrodes, at least 32 electrodes, at least 64 electrodes, or at least 128 electrodes. The electrode array may be implantable along a portion of the dura of the spinal cord of the subject. In one embodiment, the electrode may be implanted along or adjacent to the dorsal root. The electrode array may be a high-density electrode array in which adjacent ones of the plurality of electrodes are positioned within 300 micrometers of each other.
- The neurostimulator device may be connected to the plurality of electrodes and configured to deliver complex stimulation patterns thereto. The computing device may be configured to transmit stimulation parameters to the neurostimulator device. The neurostimulator device may be configured to generate the complex stimulation patterns based at least in part on the stimulation parameters received from the computing device. The computing device may be further configured to determine the stimulation parameters based on at least in part on the physiological data collected by the one or more sensors or from one or more sensor associated with a training device. The stimulation parameters may identify a waveform shape, amplitude, frequency, and relative phasing of one or more electrical pulses delivered to one or more pairs of the plurality of electrodes. Each of the complex stimulation patterns may include a plurality of different electrical signals each delivered to a different pair of the plurality of electrodes.
- The computing device may be configured to perform a machine learning method operable to determine the stimulation parameters. The machine learning method may implement a Gaussian Process Optimization.
- The neurostimulator device may be configured to generate the complex stimulation patterns based at least in part on one or more stimulation parameters determined by the neurostimulator device. In such embodiments, the neurostimulator device may be configured to perform a machine learning method operable to determine the one or more stimulation parameters. The machine learning method may implement a Gaussian Process Optimization.
- The neurostimulator device may be connected to the one or more sensors, and configured to transmit the physiological data collected by the one or more sensors to the computing device. The computing device may be connected to the one or more sensors, and configured to receive the physiological data from the one or more sensors.
- The one or more sensors may include at least one of a surface EMG electrode, a foot force plate sensor, an in-shoe sensor, an accelerator, and a gyroscope sensor attached to or positioned adjacent the body of the subject. The one or more sensors may include a motion capture system.
- The system may be for use with the subject having a body, a spinal cord, and a neurologically derived paralysis in a portion of the subject's body. The spinal cord has at least one selected spinal circuit that has a first stimulation threshold representing a minimum amount of stimulation required to activate the at least one selected spinal circuit, and a second stimulation threshold representing an amount of stimulation above which the at least one selected spinal circuit is fully activated.
- In some embodiments, neurostimulator training systems are described and can include a plurality of electrodes arranged in an electrode array implantable adjacent to body tissue; a neurostimulator device connected to the plurality of electrodes and configured to deliver complex stimulation patterns to the plurality of electrodes; at least one training device including one or more sensors; and a computing device configured to transmit stimulation parameters to the neurostimulator device, the neurostimulator device being configured to generate the complex stimulation patterns based at least in part on the stimulation parameters received from the computing device, the computing device being further configured to determine the stimulation parameters based on at least in part on data collected by the one or more sensors.
- The systems described may include a training device or system configured to physically train the subject and thereby induce neurological signals in the portion of the subject's body having paralysis. Training devices can use robotics, exoskeletons, treadmills, canes, walkers, crutches, body weight support systems, physical therapy, or a combination thereof to aid in training. Example training devices and systems can include, but are not limited to an EKSO™ Bionic Suit by EKSO BIONICS® (Ekso Bionics, Richmond, Calif.), the REWALK™ system by Argo Medical Technologies (Marlborough, Mass.), the RT300 system by Restorative Therapies, the RT200 system by Restorative Therapies, the RT600 system by Restorative Therapies, the THERASTRIDE™ system by INNOVENTOR® (St. Louis, Mo.), or the LOCOMAT® or ARMEO® system by HOCOMA® (Hocoma AG Société anonyme (SA) SWITZERLAND). These training devices can also be used as standalone neurostimulation devices or used with an electrode, neurostimulator device, or neurostimulator system as described herein to form such a system.
- The induced neurological signals may be below the first stimulation threshold and insufficient to activate the at least one selected spinal circuit. The complex stimulation patterns may be below the second stimulation threshold such that the at least one selected spinal circuit is at least partially activatable by the addition of at least one of (a) a portion of the induced neurological signals, and (b) supraspinal signals.
- Optionally, the system may include at least one recording electrode connected to the neurostimulator device. In such embodiments, the neurostimulator device can be configured to receive and record electrical signals received from the at least one recording electrode. The at least one recording electrode may be positioned on the electrode array. The electrode array may be considered a first electrode array, and the system may include a second electrode array. The at least one recording electrode may be positioned on at least one of the first electrode array and the second electrode array.
- Optionally, the system may include a plurality of muscle electrodes. In such embodiment, the neurostimulator device may include a muscle stimulation assembly configured to deliver electrical stimulation to the plurality of muscle electrodes. Alternatively, the system may be for use with a plurality of muscle electrodes and a muscle stimulation device configured to deliver electrical stimulation to the plurality of muscle electrodes. In such embodiments, the neurostimulator device may include an interface configured to direct the muscle stimulation device to deliver electrical stimulation to the plurality of muscle electrodes. In such embodiments, the polarity of muscles electrodes maybe embedded in a garment suitable for wearing and/or carrying.
- Another example of a system including at least one of the neurostimulator devices described above is for use with a network and a subject having body tissue, and one or more sensors positioned to collect physiological data related to the subject. The system includes a plurality of electrodes, the neurostimulator device, a first computing device, and a remote second computing device. The plurality of electrodes may be arranged in an electrode array implantable adjacent the body tissue of the subject. The neurostimulator device is connected to the plurality of electrodes and configured to deliver complex stimulation patterns thereto. The first computing device is connected to the network and configured to transmit stimulation parameters to the neurostimulator device. The neurostimulator device is configured to generate the complex stimulation patterns based at least in part on the stimulation parameters received from the first computing device. The remote second computing device is connected to the network. The first computing device is being configured to transmit the physiological data collected by the one or more sensors to the second computing device. The second computing device is configured to determine the stimulation parameters based at least in part on the physiological data collected by the one or more sensors, and transmit the stimulation parameters to the first computing device. In some embodiments, the first computing device is configured to receive instructions from the second computing device and transmit them to the neurostimulator device. The first computing device may be configured to receive data from the neurostimulator device and communicate the data to the second computing device over the network. In some embodiments, the second computing device may communicate directly with the neurostimulator device.
- In some embodiments, neurostimulator systems can include a stimulation assembly connectable to a plurality of electrodes. The stimulation assembly can be configured to deliver stimulation to selected electrodes within the plurality of electrodes when the stimulation assembly is connected to the plurality of electrodes and wherein the stimulation assembly includes a pulse generating system. The systems can further include a sensor interface connectable to the one or more sensors, the sensor interface being configured to receive signals from the one or more sensors when the sensor interface is connected to the one or more sensors. The systems can further include at least one processor connected to the stimulation assembly, the pulse generating system, and the sensor interface, the at least one processor can be configured to direct the stimulation assembly and the pulse generating system to deliver at least one complex stimulation pattern to the selected electrodes, and to receive the signals from the sensor interface. The at least one processor can be further configured to modify the at least one complex stimulation pattern delivered by the stimulation assembly based on the signals received from the sensor interface and the pulse generating system.
- Neurostimulator devices can also be combined for use with a network and a subject having body tissue, and one or more pulse generators either implantable or external positioned to deliver an electrical, pulsed or other type of power generated stimulus which directly or indirectly brings about a physiological response. The combined systems can include a plurality of electrodes, a neurostimulator device, a first computing device, and a second stimulator device which may include a second computing device. Example second stimulator devices which may include a second computing device are MEDTRONIC®'s INTERSTIM® Therapy (Medtronic, Minneapolis, N. Mex.) for overactive bladder; ST. JUDE MEDICAL®'s ACCENT™ Pacemaker (St. Jude Medical, Maple Grove, Minn.), ST. JUDE MEDICAL®'s MICRONY™ Pacemaker, ST. JUDE MEDICAL®'s ZEPHYR™ Pacemanker; cardiac rhythm management devices such as ST. JUDE MEDICAL®'s CURRENT™ Plus ICD and ELLIPSE™ ICD; CAMERON HEALTH®'s SQ-RX™ Pulse Generator (Cameron Health, San Clemente, Calif.); and MEDTRONIC®'s VIVA™ XT, VIVA™ S, PROTECTA™ XT, PROTECTA™ S, MEDTRONIC®'s RESTORESENSOR®, MEDTRONIC
® ITREL® 4, BOSTON SCIENTIFIC® PRECISION SPECTRA™ SCS SYSTEM, BOSTON SCIENTIFIC® PRECISION SPECTRA™ SCS SYSTEM, MEDTRONIC®'s RESTOREULTRA®, MEDTRONIC®'s RESTOREADVANCED®, MEDTRONIC®'s RESTOREPRIME®, MEDTRONIC®'s PRIMEADVANCED®, BOSTON SCIENTIFIC®'s PRECISION PLUS™ SCS System (Boston Scientific, Maple Grove, Minn.), SPINAL MODULATION™'s AXIUM™ neurostimulator, ST. JUDE MEDICAL®'s EON MINI™, ST. JUDE MEDICAL®'s EON C™, and ST. JUDE MEDICAL®'s EON™, NEVRO®'s SENZA® system (Nevro Corp., Menlo Park, Calif.), STIMWAVE®'s Freedom SCS system (Stimwave Technologies, Inc., Scottsdale, Ariz.)); Axionics Sacral Neuromodulation (Lake Forest, Calif.). In some embodiments, the above listed stimulator devices can also be first stimulator devices. The plurality of electrodes may be arranged in an electrode array implantable adjacent the body tissue of the subject. In some embodiments, at least one electrode or electrode array is transplanted adjacent to or touching the spinal cord. In other embodiments, the at least one electrode or electrode array need to be adjacent to the spinal cord. - In other embodiments, stimulator devices such as MEDTRONIC®'s INTERSTIM® Therapy (Medtronic, Minneapolis, N. Mex.) for overactive bladder; ST. JUDE MEDICAL®'s ACCENT™ Pacemaker (St. Jude Medical, Maple Grove, Minn.), ST. JUDE MEDICAL®'s MICRONY™ Pacemaker, ST. JUDE MEDICAL®'s ZEPHYR™ Pacemanker; cardiac rhythm management devices such as ST. JUDE MEDICAL®'s CURRENT™ Plus ICD and ELLIPSE™ ICD; CAMERON HEALTH®'s SQ-RX™ Pulse Generator (Cameron Health, San Clemente, Calif.); and MEDTRONIC
® ITREL® 4, BOSTON SCIENTIFIC® PRECISION SPECTRA™ SCS SYSTEM, BOSTON SCIENTIFIC® PRECISION SPECTRA™ SCS SYSTEM, MEDTRONIC®'s VIVA™ XT, VIVA™ S, PROTECTA™ XT, PROTECTA™ S, MEDTRONIC®'s RESTORESENSOR®, MEDTRONIC®'s RESTOREULTRA®, MEDTRONIC®'s RESTOREADVANCED®, MEDTRONIC®'s RESTOREPRIME®, MEDTRONIC®'s PRIMEADVANCED®, BOSTON SCIENTIFIC®'s PRECISION PLUS™ SCS System (Boston Scientific, Maple Grove, Minn.), SPINAL MODULATION™'s AXIUM™ neurostimulator, ST. JUDE MEDICAL®'s EON MINI™, ST. JUDE MEDICAL®'s EON C™, ST. JUDE MEDICAL®'s EON™, ST. JUDE MEDICAL® EON Rechargeable IPG., NERVO®'s SENZA® Neuromodualtion System, MAIN STAY MEDICAL REACTIV8, NERVO®'s MATRI SOLEVE, STIMWAVE®'s Freedom SCS system, and Axionics Sacral Neuromodulation (Lake Forest, Calif.) can be used as a standalone stimulator device. - Whether used as a standalone stimulator system or used with another stimulator system described herein, the above identified systems can be altered or otherwise modified to attain the herein described features and/or stimulation results.
- In one system described herein, a neurostimulator device is connected to a plurality of electrodes and configured to deliver complex stimulation patterns thereto. The first computing device can be connected to the network and configured to transmit stimulation parameters to the neurostimulator device. The neurostimulator device can be configured to generate complex stimulation patterns based at least in part on the stimulation parameters received from the first computing device. The second stimulator device can also be connected to the network. The first computing device can be configured to transmit and receive data collected by the one or more sensors or electrodes from the second stimulator device and/or the second computing device. The second stimulator and/or computing device can be configured to determine the stimulation parameters based at least in part on the data collected by the one or more sensors or electrodes, and transmit these stimulation parameters to the targeted body tissue, organ or region to bring about a desired physiological response(s). In some embodiments, the first computing device is configured to receive instructions from the second computing device and transmit them to the neurostimulator device. The first computing device may be configured to receive data from the neurostimulator device and communicate the data to the second computing device over the network.
- In one embodiment, a system is described wherein an implantable pulse generator is integrated into the herein described neurostimulator devices. For example, in one embodiment, an implantable pulse generator used for bladder spasticity can be integrated a neurostimulator device.
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FIG. 1 is an illustration of an implantable assembly. -
FIG. 2 is an illustration of a system incorporating the implantable assembly ofFIG. 1 . -
FIG. 3A is an illustration of a first embodiment of an exemplary electrode array for use with the neurostimulator device of the implantable assembly ofFIG. 1 . -
FIG. 3B is an illustration of a second embodiment of an exemplary electrode array for use with the neurostimulator device of the implantable assembly ofFIG. 1 . -
FIG. 4A is an illustration of a waveform that may be generated by the neurostimulator device of the implantable assembly ofFIG. 1 .FIG. 4B an illustration of another waveform that may be generated by the neurostimulator device of the implantable assembly ofFIG. 1 . -
FIG. 5 is a block diagram of a first embodiment of an implantable assembly and an external system. -
FIG. 6A is a leftmost portion of a circuit diagram of a multiplexer sub-circuit of a neurostimulator device of the implantable assembly ofFIG. 5 . -
FIG. 6B is a rightmost portion of the circuit diagram of the multiplexer sub-circuit of the neurostimulator device of the implantable assembly ofFIG. 5 . -
FIG. 7 is a circuit diagram of a stimulator circuit of the neurostimulator device of the implantable assembly ofFIG. 5 . -
FIG. 8 is a circuit diagram of a controller circuit of the neurostimulator device of the implantable assembly ofFIG. 5 . -
FIG. 9 is a circuit diagram of a wireless power circuit of the neurostimulator device of the implantable assembly ofFIG. 5 . -
FIG. 10 is a block diagram of a second embodiment of an implantable assembly. -
FIG. 11 is a block diagram of a third embodiment of an implantable assembly and the external system. -
FIG. 12A is a block diagram of stimulator circuitry and a wireless transceiver of a neurostimulator device of the implantable assembly ofFIG. 11 . -
FIG. 12B is a block diagram of an alternate embodiment of the stimulator circuitry ofFIG. 12A . -
FIG. 13 is an illustration of a multi-compartment physical model of electrical properties of a mammalian spinal cord, along with a 27 electrode implementation of the electrode array placed in an epidural position. -
FIG. 14 is a lateral cross-section through the model of the mammalian spinal cord depicted inFIG. 13 cutting through bipolarly activated electrodes showing isopotential contours of the stimulating electric field for the 2-electrode stimulation example. -
FIG. 15 shows instantaneous regret (a measure of machine learning error) vs. learning iteration (labeled as “query number”) for Gaussian Process Optimization of array stimulation parameters in the simulated spinal cord ofFIGS. 13 and 14 . The “bursts” of poor performance corresponds to excursions of the learning algorithm to regions of parameter space that are previously unexplored, but which are found to have poor performance. -
FIG. 16 shows the average cumulative regret vs. learning iteration. The average cumulative regret is a smoothed version of the regret performance function which better shows the algorithm's overall progress in selecting optimal stimulation parameters. -
FIG. 17 is a diagram of a hardware environment and an operating environment in which the computing device of the system ofFIG. 2 may be implemented. - All publications (including published patent applications and issued patents) cited herein are incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated as being incorporated by reference. The following description includes information that may be useful in understanding the technology. The description is not an admission that any of the information provided herein is prior art, or that any publication specifically or implicitly referenced is prior art.
- This application incorporates the entire disclosures of U.S. patent application Ser. No. 14/007,262, filed Sep. 24, 2013, International Patent Application PCT/US2012/030624 filed on Mar. 26, 2012, and U.S. Provisional Application No. 61/467,107, filed Mar. 24, 2011.
- Research has shown that the most effective method for improving function after a spinal cord injury (“SCI”) is to combine different strategies, as neurological deficits (such as those caused by SCI) are complex, and there is wide variability in the deficit profiles among patients. These strategies include physical therapy, along with electrical stimulation (e.g., high-density epidural stimulation), and optionally one or more serotonergic agents, dopaminergic agents, noradregeneric agents, GABAergic agents, and and/or glycinergic agents. It is believed such combination strategies facilitate modulation of electrophysiological properties of spinal circuits in a subject so they are activated by proprioceptive input and indirectly use voluntary control of spinal cord circuits not normally available to connect the brain to the spinal cord. In other words, these strategies exploit the spinal circuitry and its ability to interpret proprioceptive information, and respond to that proprioceptive information in a functional way.
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FIG. 1 illustrates an implantableelectrode array assembly 100. While the embodiment of theassembly 100 illustrated is configured for implantation in the human subject 102 (seeFIG. 2 ), embodiments may be constructed for use in other subjects, such as other mammals, including rats, and such embodiments are within the scope of the present teachings. The subject 102 has abrain 108, aspinal cord 110 with at least one selected spinal circuit (not shown), and a neurologically derived paralysis in a portion of the subject's body. In the example discussed herein, thespinal cord 110 of the subject 102 has alesion 112. - By way of non-limiting examples, when activated, the selected spinal circuit may (a) enable voluntary movement of muscles involved in at least one of standing, stepping, reaching, grasping, voluntarily changing positions of one or both legs, voluntarily changing positions of one or both arms, voluntarily changing position of one's neck, voiding the subject's bladder, voiding the subject's bowel, breathing, coughing, chewing, swallowing, speaking, blinking, focusing visual fields, postural activity changing core (trunk) position, and locomotor activity, or improve muscle tone; (b) enable or improve autonomic control of at least one of cardiovascular function, body temperature, and metabolic processes; and/or (c) help facilitate recovery of at least one of an autonomic function, sexual function, vasomotor function, and cognitive function. The effects of activation of the selected spinal circuit will be referred to as “improved neurological function.”
- Without being limited by theory, it is believed that the selected spinal circuit has a first stimulation threshold representing a minimum amount of stimulation required to activate the selected spinal circuit, and a second stimulation threshold representing an amount of stimulation above which the selected spinal circuit is fully activated and adding the induced neurological signals has no additional effect on the at least one selected spinal circuit.
- The paralysis may be a motor complete paralysis or a motor incomplete paralysis. The paralysis may have been caused by a SCI classified as motor complete or motor incomplete. The paralysis may have been caused by an ischemic or traumatic brain injury. The paralysis may have been caused by an ischemic brain injury that resulted from a stroke or acute trauma. By way of another example, the paralysis may have been caused by a neurodegenerative brain injury. The neurodegenerative brain injury may be associated with at least one of Parkinson's disease, Huntington's disease, Dystonia, Alzheimer's, ischemia, stroke, amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), and cerebral palsy.
- Neurological signals may be induced in the paralyzed portion of the subject's body (e.g., by physical training). However, adding the induced neurological signals may have little or no additional effect on the selected spinal circuit, if the induced neurological signals are below the first stimulation threshold and insufficient to activate the at least one selected spinal circuit.
- The
assembly 100 is configured to apply electrical stimulation to neurological tissue (e.g., a portion of thespinal cord 110, one or more spinal nerves, one or more nerve roots, one or more peripheral nerves, the brain stem, and/or thebrain 108, and the like). Further, the electrical stimulation may be applied to other types of tissue, including the tissue of one or more end organs (e.g., bladder, kidneys, heart, liver, and the like). For ease of illustration, the electrical stimulation will be described as being delivered to body tissue. While the stimulation may be delivered to body tissue that is not neurological tissue, the target of the stimulation is generally a component of the nervous system that is modified by the addition of the stimulation to the body tissue. - The electrical stimulation delivered is configured to be below the second stimulation threshold such that the selected spinal circuit is at least partially activatable by the addition of (a) induced neurological signals and/or (b) supraspinal signals. Induced neurological signals can include neurological signals induced through physical training, mechanical manipulation, a temperature stimulation, a harmonic stimulation, a pressure stimulation, a physiological change, a response to light, an introduction of a pharmaceutical, or chemical response. The induced neurological signals may include at least one of postural proprioceptive signals, locomotor proprioceptive signals, temperature, vibratory, chemical or light signals, and/or supraspinal signals. By way of a non-limiting example, the
assembly 100 may be used to perform methods described in U.S. patent application Ser. No. 13/342,903, filed Jan. 3, 2012, and titled High Density Epidural Stimulation for Facilitation of Locomotion, Posture, Voluntary Movement, and Recovery of Autonomic, Sexual, Vasomotor and Cognitive Function after Neurological Injury, which is incorporated herein by reference in its entirety. However, the selected spinal circuit may be at least partially activatable by the addition neurological signals other than those induced by physical training. - The
assembly 100 includes one ormore electrode arrays 140, one or more leads 130, and aneurostimulator device 120. For ease of illustration, the one ormore electrode arrays 140 will be described as including a single electrode array. However, through application of ordinary skill to the present teachings, embodiments may be constructed that include two or more electrode arrays. For example, embodiments may include two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, 13, 14, 15, 16, 17, 18, 19, 20, or more electrode arrays. In some embodiments, the arrays can be wired or wireless. Further, each electrode array can include one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 50, 100 or more electrodes per array. In some embodiments, the sensors can be wired or wireless. Furthermore, by way of non-limiting example, the electrode can vary in shape such as paddle shape, oval, or tubular, and may be surgically implanted by means of open technique or percutaneously inserted. - Therefore, such embodiments are within the scope of the present teachings. The
neurostimulator device 120 generates electrical stimulation that is delivered to theelectrode array 140 by the one or more leads 130. Depending upon the implementation details, theneurostimulator device 120 may be characterized as being a neuromodulator device. - The
electrode array 140 may be implemented using commercially available high-density electrode arrays designed and approved for implementation in human patients. By way of a non-limiting example, a MEDTRONIC® Specify 5-6-5 multi-electrode array (incorporating 16 electrodes) may be used or BOSTON SCIENTIFIC®'s 32 lead electrode arrays such as the COVEREDGE® and the COVEREDGE®-X (Boston Scientific Neuromodulation Corporation, Valencia, Calif.). Examples of suitable electrode arrays include paddle-shaped electrodes (e.g., having a 5-6-5 electrode configuration) constructed from platinum wire and surface electrodes embedded in silicone. Further, theelectrode array 140 may be implemented using multiple electrode arrays (e.g., multiple 16-electrode arrays connected to theneurostimulator device 120 in a serial or parallel arrangement). -
FIG. 3A illustrates aconventional electrode array 148 having 16 electrodes “E-1” to “E-16.” Theelectrode array 140 may be implemented using theelectrode array 148. Prior art stimulators allow a user (e.g., a clinician) to divide the electrodes “E-1” to “E-16” into up to four groups. Each group may include any number of electrodes. Stimulation having different frequency and pulse width may be delivered to the groups. In contrast, theneurostimulator device 120 may divide the electrodes “E-1” to “E-16” into any number of groups. For example, each electrode may be assigned to its own group. By way of another example, one or more electrodes may belong to multiple groups. Table A below provides a few examples of groups that may be identified and stimulated independently. Which electrodes function as the anode and which function as a cathode are also specified for illustrative purposes. -
TABLE A Group Number Anode electrodes Cathode electrodes 1 1 3 2 1 and 2 3, 4, 5, and 6 3 1, 2, and 3 13, 16, and 15 4 1, 2, and 3 6, 7, 8, and 9 - Further, conventional stimulators are configured to deliver only rectangular waves to the electrodes “E-1” to “E-16.” In contrast and as will be described in detail below, the
neurostimulator device 120 is configured to deliver stimulation having waveform shapes beyond merely rectangular waves. - In particular embodiments, the
neurostimulator device 120 is configured to deliver stimulation to a single selected one of theelectrodes 142 and/or use a single selected one of theelectrodes 142 as a reference electrode. Prior art stimulators are not capable of this level of addressability. - In some embodiments, the
electrode array 140 may be constructed using microfabrication technology to place numerous electrodes in an array configuration on a flexible substrate. One suitable epidural array fabrication method was first developed for retinal stimulating arrays (see, e.g., Maynard, Annu. Rev. Biomed. Eng., 3: 145-168 (2001); Weiland and Humayun, IEEE Eng. Med. Biol. Mag., 24(5): 14-21 (2005)), and U.S. Patent Publications 2006/0003090 and 2007/0142878 which are incorporated herein by reference for all purposes (e.g., the devices and fabrication methods disclosed therein). In various embodiments the stimulating arrays comprise one or more biocompatible metals (e.g., gold, platinum, chromium, titanium, iridium, tungsten, and/or oxides and/or alloys thereof) disposed on a flexible material (e.g., parylene A, parylene C, parylene AM, parylene F, parylene N, parylene D, or other flexible substrate materials). Parylene has the lowest water permeability of available microfabrication polymers, is deposited in a uniquely conformal and uniform manner, has previously been classified by the FDA as a United States Pharmacopeia (USP) Class VI biocompatible material (enabling its use in chronic implants) (Wolgemuth, Medical Device and Diagnostic Industry, 22(8): 42-49 (2000)), and has flexibility characteristics (Young's modulus ˜4 GPa (Rodger and Tai, IEEE Eng. Med. Biology, 24(5): 52-57 (2005))), lying in between those of PDMS (often considered too flexible) and most polyimides (often considered too stiff). Finally, the tear resistance and elongation at break of parylene are both large, minimizing damage to electrode arrays under surgical manipulation (Rodger et al., Sensors and Actuators B-Chemical, 117(1): 107-114 (2006)). - In the embodiment illustrated in
FIG. 3B , theelectrode array 140 may be characterized as being a microelectromechanical systems (“MEMS”) device. While the implementation of theelectrode array 140 illustrated inFIG. 3B may be suited for use in animals, the basic geometry and fabrication technique can be scaled for use in humans. Theelectrode array 140 is configured for implantation along the spinal cord 110 (seeFIG. 1 ) and to provide electrical stimulation thereto. For example, theelectrode array 140 may provide epidural stimulation to thespinal cord 110. Theelectrode array 140 allows for a high degree of freedom and specificity in selecting the site of stimulation compared to prior art wire-based implants, and triggers varied biological responses that can lead to an increased understanding of thespinal cord 110 and improved neurological function in the subject 102. A non-limiting example of an electrode array that may be used to construct theelectrode array 140 is described in co-pending U.S. patent application Ser. No. 13/356,499, filed on Jan. 23, 2012, and titled Parylene-Based Microelectrode Array Implant for Spinal Cord Stimulation, which is incorporated herein by reference in its entirety. - Turning to
FIG. 3B , theelectrode array 140 includes a plurality of electrodes 142 (e.g., electrodes A1-A9, B1-B9, and C1-C9), and a plurality of electrically conductive traces 144. Theelectrodes 142 may vary in size, and be constructed using a biocompatible substantially electrically conductive material (such as platinum, Ag/AgCl, and the like), embedded in or positioned on a biocompatible substantially electrically non-conductive (or insulating) material (e.g., flexible parylene). One or more of thetraces 144 is connected to each of theelectrodes 142. Connecting more than one of thetraces 144 to each of theelectrodes 142 may help ensure signals reach and are received from each of theelectrodes 142. In other words, redundancy may be used to improve reliability. Each of theelectrodes 142 has one or more electrically conductive contacts (not shown) positionable alongside body tissue. The body tissue may include neurological tissue (e.g., thespinal cord 110, one or more spinal nerves, one or more nerve roots, one or more peripheral nerves, the brain stem, and/or thebrain 108, and the like), other types of spinal tissue (e.g., the dura of the spinal cord 110), and the tissue of end organs. Further, theelectrode array 140 may be configured to be positionable alongside such body tissue. - The
electrode array 140 may be implanted using any of a number of methods (e.g., a laminectomy procedure, or percutaneously inserted) well known to those of skill in the art. By way of a non-limiting example, theelectrodes 142 may be implanted epidurally along the spinal cord 110 (seeFIG. 1 ) or along side. Theelectrodes 142 may be positioned at one or more of a lumbosacral region, a cervical region, and a thoracic region of the spinal cord or along the brainstem 110 (seeFIG. 1 ). In some embodiments,electrodes 142 can be implanted at a combination of the above locations. In the embodiment illustrated, theelectrodes 142 are positioned distal to the lesion 112 (seeFIG. 1 ) relative to the brain 108 (seeFIG. 1 ). In other words, theelectrodes 142 are positioned farther from thebrain 108 than thelesion 112. - The one or more leads 130 include electrically conductive elements. In some embodiments, the one or more leads 130 include an electrically conductive element for each of the
traces 144 of theelectrode array 140. By way of another non-limiting example, in some embodiments, the one or more leads 130 include an electrically conductive element for each of theelectrodes 142 of theelectrode array 140. The one or more leads 130 of theassembly 100 connect theneurostimulator device 120 to thetraces 144 of theelectrode array 140, which are each connected to one of theelectrodes 142. Thus, a signal generated by theneurostimulator device 120 is transmitted via the one or more leads 130 to selected ones of thetraces 144, which transmit the signal to selected ones of theelectrodes 142, which in turn deliver the stimulation to the body tissue in contact with the electrically conductive contacts (not shown) of theelectrodes 142. The one or more leads 130 may vary in length. The electrically conductive elements may be constructed using a biocompatible substantially electrically conductive material (such platinum, Ag/AgCl, and the like), embedded in or surrounded by a biocompatible substantially electrically non-conductive (or insulating) material (e.g., flexible parylene). Optionally, the one or more leads 130 may include one ormore connectors connector 132 is used to connect the one or more leads 130 to theelectrode array 140 and theconnector 134 is used to connect the one or more leads 130 to theneurostimulator device 220. - Epidural stimulating impulse generators (e.g., of the type designed for applications like back pain relief) can be combined with the neurostimulators described to produce a complex pattern of stimulating signals needed to produce improved neurological function (e.g., stepping, standing, arm movement, and the like after a severe SCI or/and occurrence of a neuromotor disorders). For example, to recover stepping, an alternating spatiotemporal electric field having oscillations that peak over the right side of the spinal cord 110 (e.g., in the lumbosacral region) during a right leg swing phase, and oscillations that peak over the left side of the spinal cord 110 (e.g., in the lumbosacral region) during the left swing phase may be used. By way of another example, to recover independent standing, a rostral-caudal gradient in both electrode voltage and electrode stimulation frequency may be used. Rostral is nearer the
brain 108 and caudal farther from thebrain 108. Prior art stimulators are simply not configured to deliver such complex stimulation patterns. - Epidural stimulating impulse generators can have limitations that limit their ability to help patients recover functionality lost as a result of the neurologically derived paralysis. However, these limitations can be overcome when combined with the neurostimulators described herein. For example, typical epidural stimulating impulse generators can deliver stimulation having the same amplitude to all active electrodes. Some epidural stimulating impulse generators can be configured to deliver stimulation having different amplitudes to four different groups of electrodes. Further, typical epidural stimulating impulse generators can deliver stimulation having the same frequency to all channels (or electrodes). Some epidural stimulating impulse generators can be configured to deliver stimulation having different frequencies to four groups of channels (or electrodes). Additionally, typical epidural stimulating impulse generators can deliver stimulation having the same pulse width to all of the channels (or electrodes). Further, typical epidural stimulating impulse generators can lack the ability to generate non-pulse waveforms.
- Neurostimulator device systems can include a plurality of electrodes, a neurostimulator device such as
neurostimulator devices - In other embodiments, stimulator devices such as SPINAL MODULATION™'s AXIUM™ neurostimulator, MEDTRONIC®'s INTERSTIM® Therapy (Medtronic, Minneapolis, N. Mex.) for overactive bladder; MEDTRONIC® ENTERRA®, ENTEROWAVE® GI Neuromodualtion System, ST. JUDE MEDICAL®'s ACCENT™ Pacemaker (St. Jude Medical, Maple Grove, Minn.), ST. JUDE MEDICAL®'s MICRONY™ Pacemaker, ST. JUDE MEDICAL®'s ZEPHYR™ Pacemanker; cardiac rhythm management devices such as ST. JUDE MEDICAL®'s CURRENT™ Plus ICD and ELLIPSE™ ICD; CAMERON HEALTH®'s SQ-RX™ Pulse Generator (Cameron Health, San Clemente, Calif.); and MEDTRONIC®'s VIVA™ XT, VIVA™ S, PROTECTA™ XT, and PROTECTA™ S, BOSTON SCIENTIFIC®'s PRECISION SPECTRA® (Boston Scientific Neuromodulation Corporation, Valencia, Calif.); NEVRO®'s SENZA® system, STIMWAVE®'s Freedom SCS system; Axionics' Sacral Neuromodulation System can be used as a standalone stimulator device.
- In one embodiment, a neurostimulator device system can include one or more electrodes and SPINAL MODULATION™'s AXIUM™ neurostimulator.
- In one embodiment, a neurostimulator device system can include one or more electrodes and MEDTRONIC® ENTERRA®.
- In one embodiment, a neurostimulator device system can include one or more electrodes and ENTEROWAVE® GI Neuromodualtion System.
- In one embodiment, a neurostimulator device system can include one or more electrodes and MEDTRONIC®'s INTERSTIM® Therapy for overactive bladder.
- In one embodiment, a neurostimulator device system can include one or more electrodes and ST. JUDE MEDICAL®'s ACCENT™ Pacemaker.
- In one embodiment, a neurostimulator device system can include one or more electrodes and ST. JUDE MEDICAL®'s MICRONY™ Pacemaker.
- In one embodiment, a neurostimulator device system can include one or more electrodes and ST. JUDE MEDICAL®'s ZEPHYR™ Pacemanker.
- In one embodiment, a neurostimulator device system can include one or more electrodes and ST. JUDE MEDICAL®'s CURRENT™ Plus ICD.
- In one embodiment, a neurostimulator device system can include one or more electrodes and ST. JUDE MEDICAL®'s ELLIPSE™ ICD.
- In one embodiment, a neurostimulator device system can include one or more electrodes and CAMERON HEALTH®'s SQ-RX Pulse Generator.
- In one embodiment, a neurostimulator device system can include one or more electrodes and MEDTRONIC®'s VIVA™ XT.
- In one embodiment, a neurostimulator device system can include one or more electrodes and MEDTRONIC®'s VIVA™ S.
- In one embodiment, a neurostimulator device system can include one or more electrodes and MEDTRONIC®'s PROTECTA™ XT.
- In one embodiment, a neurostimulator device system can include one or more electrodes and MEDTRONIC®'s PROTECTA™ S.
- In one embodiment, a neurostimulator device system can include one or more electrodes and BOSTON SCIENTIFIC®'s PRECISION SPECTRA.
- In one embodiment, a neurostimulator device system can include one or more electrodes and NEVRO®'s SENZA® system.
- In one embodiment, a neurostimulator device system can include one or more electrodes and STIMWAVE®'s Freedom SCS system.
- In one embodiment, a neurostimulator device system can include one or more electrodes and Axionics' Sacral Neuromodulation System.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and SPINAL MODULATION™'s AXIUM™ neurostimulator.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and MEDTRONIC®'s INTERSTIM® Therapy for overactive bladder.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and MEDTRONIC® ENTERRA®.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and ENTEROWAVE® GI Neuromodualtion System.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and ST. JUDE MEDICAL®'s ACCENT™ Pacemaker.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and ST. JUDE MEDICAL®'s MICRONY™ Pacemaker.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and ST. JUDE MEDICAL®'s ZEPHYR™ Pacemanker.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and ST. JUDE MEDICAL®'s CURRENT™ Plus ICD.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and ST. JUDE MEDICAL®'s ELLIPSE™ ICD.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and CAMERON HEALTH®'s SQ-RX Pulse Generator.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and MEDTRONIC®'s VIVA™ XT.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and MEDTRONIC®'s VIVA™ S.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and MEDTRONIC®'s PROTECTA™ XT.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and MEDTRONIC®'s PROTECTA™ S.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and BOSTON SCIENTIFIC®'s PRECISION SPECTRA.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and NEVRO®'s SENZA® system.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and STIMWAVE®'s Freedom SCS system.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and Axionics' Sacral Neuromodulation System.
- In one embodiment, a neurostimulator device can be SPINAL MODULATION™'s AXIUM™ neurostimulator.
- In one embodiment, a neurostimulator device can be MEDTRONIC®'s INTERSTIM® Therapy for overactive bladder.
- In one embodiment, a neurostimulator device can be a MEDTRONIC® ENTERRA®.
- In one embodiment, a neurostimulator device can be ENTEROWAVE® GI Neuromodualtion System.
- In one embodiment, a neurostimulator device can be ST. JUDE MEDICAL®'s ACCENT™ Pacemaker.
- In one embodiment, a neurostimulator device can be ST. JUDE MEDICAL®'s MICRONY™ Pacemaker.
- In one embodiment, a neurostimulator device can be ST. JUDE MEDICAL®'s ZEPHYR™ Pacemanker.
- In one embodiment, a neurostimulator device can be ST. JUDE MEDICAL®'s CURRENT™ Plus ICD.
- In one embodiment, a neurostimulator device can be ST. JUDE MEDICAL®'s ELLIPSE™ ICD.
- In one embodiment, a neurostimulator device can be CAMERON HEALTH®'s SQ-RX Pulse Generator.
- In one embodiment, a neurostimulator device can be MEDTRONIC®'s VIVA™ XT.
- In one embodiment, a neurostimulator device can be MEDTRONIC®'s VIVA™ S.
- In one embodiment, a neurostimulator device can be MEDTRONIC®'s PROTECTA™ XT.
- In one embodiment, a neurostimulator device can be MEDTRONIC®'s PROTECTA™ S.
- In one embodiment, a neurostimulator device can be BOSTON SCIENTIFIC®'s PRECISION SPECTRA.
- In one embodiment, a neurostimulator device can be NEVRO®'s SENZA® system.
- In one embodiment, a neurostimulator device can be STIMWAVE®'s Freedom SCS system.
- In one embodiment, a neurostimulator device can be Axionics' Sacral Neuromodulation System.
- In some embodiments, to achieve improved neurological function (e.g., stepping, standing, arm movement, and the like), a more complex waveform than the type generated by conventional stimulators must be delivered to one or more target locations. For example, it is known that non-rectangular waveforms (e.g.,
waveform 160 illustrated inFIG. 4A ) and small “prepulses” (e.g., prepulse 162 illustrated inFIG. 4B ) having a different amplitude and pulse width than the main “driving” pulse (e.g., drivingpulse 164 illustrated inFIG. 4B ) may be used to selectively recruit neurons with different fiber diameters and different electrical properties. Z.-P. Fang and J. T. Mortimer, “Selective Activation of Small Motor Axons by Quasitrapezoidal Current Pulses,” IEEE Trans. Biomedical Engineering, 38(2):168-174, February 1991; and W. M. Grill and J. T. Mortimer, “Inversion of the Current-Distance Relationship by Transient Depolarization,” IEEE Trans. Biomedical Engineering, 44(1):1-9, January 1997. Thus, these waveforms may be used to selectively recruit different parts of one or more sensory/motor circuits (e.g., activate different spinal circuits) as needed to achieve different therapeutic goals. - To achieve improved neurological function (e.g., stepping, pulse generating system is, arm movement, and the like), the timing of the onset of electrical stimulation must be carefully controlled. For example, the spatio-temporal characteristics of the stimulating voltage fields needed for stepping require the ability to specify and control the phase shift (the exact timing of the onset of the stimulating waveform) between the
electrodes 142, across theentire electrode array 140. Conventional stimulators can lack this ability. However, conventional systems can be modified to include the features of the described neurostimulator devices and bring about improved neurological function. Modifiable conventional stimulators can include, but are not limited to MEDTRONIC®'s RESTORESENSOR®, MEDTRONIC®'s RESTOREULTRA®, MEDTRONIC®'s RESTOREADVANCED®, MEDTRONIC®'s RESTOREPRIME®, MEDTRONIC®'s PRIMEADVANCED®, BOSTON SCIENTIFIC®'s PRECISION PLUS™ SCS System (Boston Scientific, Maple Grove, Minn.), SPINAL MODULATION™'s AXIUM™ neurostimulator, ST. JUDE MEDICAL®'s EON MINI™, ST. JUDE MEDICAL®'s EON C™, ST. JUDE MEDICAL®'s EON™, ST. JUDE MEDICAL® EON Rechargeable IPG., NEVRO®'s SENZA® High Frequency Neuromodualtion System, MAIN STAY MEDICAL REACTIV8, and NEVRO® MATRI SOLEVE. In some embodiments, combinations of the above conventional sensors can be utilized. - In some embodiments, these conventional stimulator systems can be transplanted adjacent to or touching the spinal cord. In other embodiments, these conventional stimulator systems need to be transplanted adjacent to the spinal cord.
- In other embodiments, modifiable conventional stimulators such as MEDTRONIC®'s RESTORESENSOR®, MEDTRONIC®'s RESTOREULTRA®, MEDTRONIC®'s RESTOREADVANCED®, MEDTRONIC®'s RESTOREPRIME®, MEDTRONIC®'s PRIMEADVANCED®, BOSTON SCIENTIFIC®'s PRECISION PLUS™ SCS System (Boston Scientific, Maple Grove, Minn.), SPINAL MODULATION™'s AXIUM™ neurostimulator, ST. JUDE MEDICAL®'s EON MINI™, ST. JUDE MEDICAL®'s EON C™, ST. JUDE MEDICAL®'s EON™, ST. JUDE MEDICAL® EON Rechargeable IPG., NEVRO®'s SENZA® Neuromodualtion System, MAIN STAY MEDICAL REACTIV8, NEVRO®'s MATRI SOLEVE, NEVRO®'s SENZA® BOSTON SCIENTIFIC®'s PRECISION SPECTRA, STIMWAVE®'s Freedom SCS system, Axionics' Sacral Neuromodulation System can be used as to block pain.
- Whether used as a standalone stimulator system or used with another stimulator system described herein, the above identified modifiable conventional stimulators can be altered or otherwise tweaked go attain the herein described features and/or stimulation results.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and MEDTRONIC®'s RESTORESENSOR®.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and MEDTRONIC®'s RESTOREULTRA®.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and MEDTRONIC®'s RESTOREADVANCED®.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and MEDTRONIC®'s RESTOREPRIME®.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and MEDTRONIC®'s PRIMEADVANCED®.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and BOSTON SCIENTIFIC®'s PRECISION PLUS™ SCS System.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and SPINAL MODULATION™'s AXIUM™ neurostimulator.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and ST. JUDE MEDICAL®'s EON MINI™.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and ST. JUDE MEDICAL®'s EON C™ system.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and ST. JUDE MEDICAL®'s EON™ system.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and ST. JUDE MEDICAL®'s EON Rechargeable IPG system.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and NEVRO® SENZA® High Frequency Neuromodualtion System.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and MAIN STAY MEDICAL's REACTIV8 system.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and a NEVRO®'s MATRI SOLEVE system.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and a NEVRO®'s SENZA®.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and a BOSTON SCIENTIFIC®'s PRECISION SPECTRA.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and a STIMWAVE®'s Freedom SCS system.
- In one embodiment, neurostimulator device systems can include a neurostimulator device and a Axionics' Sacral Neuromodulation System.
- In one embodiment, a neurostimulator device can be MEDTRONIC®'s RESTORESENSOR®.
- In one embodiment, a neurostimulator device can be MEDTRONIC®'s RESTOREULTRA®.
- In one embodiment, a neurostimulator device can be MEDTRONIC®'s RESTOREADVANCED®.
- In one embodiment, a neurostimulator device can be MEDTRONIC®'s RESTOREPRIME®.
- In one embodiment, a neurostimulator device can be MEDTRONIC®'s PRIMEADVANCED®.
- In one embodiment, a neurostimulator device can be BOSTON SCIENTIFIC®'s PRECISION PLUS™ SCS System.
- In one embodiment, a neurostimulator device can be SPINAL MODULATION™'s AXIUM™ neurostimulator.
- In one embodiment, a neurostimulator device can be ST. JUDE MEDICAL®'s EON MINI™.
- In one embodiment, a neurostimulator device can be ST. JUDE MEDICAL®'s EON C™ system.
- In one embodiment, a neurostimulator device can be ST. JUDE MEDICAL®'s EON™ system.
- In one embodiment, a neurostimulator device can be ST. JUDE MEDICAL®'s EON Rechargeable IPG system.
- In one embodiment, a neurostimulator device can be NEVRO® SENZA® High Frequency Neuromodualtion System.
- In one embodiment, a neurostimulator device can be MAIN STAY MEDICAL's REACTIV8 system.
- In one embodiment, a neurostimulator device can be NEVRO®'s MATRI SOLEVE system.
- In one embodiment, a neurostimulator device can be NEVRO®'s SENZA®.
- In one embodiment, a neurostimulator device can be BOSTON SCIENTIFIC®'s PRECISION SPECTRA.
- In one embodiment, a neurostimulator device can be STIMWAVE®'s Freedom SCS system.
- In one embodiment, a neurostimulator device can be Axionics' Sacral Neuromodulation System.
- The
neurostimulator device 120 can be configured to generate complex types and patterns of electrical stimulation that achieve improved neurological function. In other words, theneurostimulator device 120 is configured to generate (and deliver to the electrode array 140) one or more “complex stimulation patterns.” A complex stimulation pattern has at least the following properties: - 1. a type of stimulation to apply to each of the electrodes 142 (which may include the application of no stimulation to one or more selected
electrodes 142, if appropriate), the type of stimulation is defined by stimulation type parameters that include waveform shape, amplitude, waveform period, waveform frequency, and the like, theelectrodes 142 being individually addressable; - 2. stimulation timing that indicates when stimulation is to be applied to each of the electrodes 142 (which defines a sequence for applying stimulation to the electrodes 142), stimulation timing is defined by timing parameters that include an onset of stimulation, relative delay between waveform onset on different electrodes, a duration during which stimulation is delivered, a duration during which no stimulation is delivered, and the like;
- 3. transition parameters that define how one waveform may be smoothly adapted over time to change (or morph) into a different waveform. Such smooth changes between waveform patterns may be helpful for enabling complex motor function, such as the transition from sitting to standing.
- Together the stimulation type parameters, timing parameters, and transition parameters are “stimulation parameters” that define the complex stimulation pattern. The
neurostimulator device 120 delivers the complex stimulation pattern to theelectrode array 140. Thus, theelectrode array 140 is configured such that which of theelectrodes 142 will receive stimulation may be selected. In particular embodiments, theelectrodes 142 are individually addressable by theneurostimulator device 120. Further, theneurostimulator device 120 may also be configured such that the frequency, waveform width (or period), and/or amplitude of the stimulation delivered to each of the selected ones of theelectrodes 142 may also be adjustable. The complex stimulation pattern may remain constant, repeat, or change over time. - The configurability of the complex stimulation patterns delivered by the neurostimulator device 120 (by changing the stimulation parameters) enables the identification of effective complex stimulation patterns and the adjustment of the complex stimulation patterns to correct for migration and/or initial surgical misalignment. The
neurostimulator device 120 may be configured to deliver a plurality of different complex stimulation patterns to theelectrodes 142. - The
neurostimulator device 120 can be programmable (e.g., by the subject 102 or a physician). Theneurostimulator device 120 may be programmed with stimulation parameters and/or control parameters configured to deliver a complex stimulation pattern that is safe, efficacious, and/or selected to target specific body tissue. Further, stimulation parameters and/or control parameters may be customized for each patient (e.g., based on response to pre-surgical (implant) evaluation and testing). Theneurostimulator device 120 may have a variable activation control for providing a complex stimulation pattern either intermittently or continuously, and allowing for adjustments to frequency, waveform width, amplitude, and duration. By generating such customizable stimulation, theneurostimulator device 120 may be used to (a) generate or maintain efficacious and/or optimal complex stimulation patterns, and/or (b) adjust the location of the application of stimulation (relative to the neural tissue) when theassembly 100 migrates and/or was misaligned during implantation. - The
neurostimulator device 120 may be configured to store, send, and receive data. The data sent and received may be transmitted wirelessly (e.g., using current technology, such as Bluetooth, ZigBee, WiFi, Z-wave, FCC-approved MICS medical transmission frequency bands, and the like) via a wireless connection 155 (seeFIG. 2 ). Theneurostimulator device 120 may be configured to be regulated automatically (e.g., configured for open loop and/or closed loop functionality). Further, theneurostimulator device 120 may be configured to record field potentials detected by theelectrodes 142, such as somatosensory evoked potentials (SSEPs) generated by the dorsum of thespinal cord 110. Theneurostimulator device 120 may be configured to be rechargeable. - Depending upon the implementation details, the
neurostimulator device 120 may be configured with one or more of the following properties or features: - 1. a form factor enabling the
neurostimulator device 120 to implanted via a surgical procedure; - 2. a power generator with rechargeable battery;
- 3. a secondary back up battery;
- 4. electronic and/or mechanical components encapsulated in a hermetic package made from one or more biocompatible materials;
- 5. programmable and autoregulatory;
- 6. ability to record field potentials;
- 7. ability to operate independently, or in a coordinated manner with other implanted or external devices; and/or
- 8. ability to send, store, and receive data via wireless technology.
- Optionally, the
neurostimulator device 120 may be connected to one ormore sensors 188 via connections 194 (e.g., wires, wireless connections, and the like). Sensors can be any type of sensor that can provide the data required by a neurostimulator device. Such sensors can include, but are not limited to electromyography (“EMG”)sensors 190, joint angle (or flex)sensors 191, evoked potential sensors,accelerometers 192, gyroscopic sensors, pressure sensors, temperature sensors, flow sensors, load sensors, chemical sensors, light sensors, harmonic sensors, and the like. The connections (e.g., the connections 194) andsensors 188 may be implemented using external components and/or implanted components. In embodiments including thesensors 188, theneurostimulator device 120 may be configured to modify or adjust the complex stimulation pattern based on information received from thesensors 188 via theconnections 194. Theconnections 194 may be implemented using wired or wireless connections. Optionally, theneurostimulator device 120 may be connected toreference wires 196. InFIG. 2 , one of thereference wires 196 is positioned near the shoulder, the other of thereference wires 196 is positioned in the lower back. However, this is not a requirement. - In some embodiments, a neurostimulator system can include at least one training device including one or more sensors that can provide data to a processor. In other embodiments, a neurostimulator device can be configured to generate complex stimulation patterns based at least in part on the stimulation parameters received from the computing device, the computing device being further configured to determine the stimulation parameters based on at least in part on data collected by the one or more sensors associated with one or more training devices.
- Training devices can be standalone products or can be integrated into a neurostimular device or system. Further, a training device can include external adjunctive devices to aid a subject in using the training device. External adjunctive devices can include, training devices or systems configured to physically train subjects and thereby induce neurological signals in the paralyzed portion of the subject's body. Such training devices can use robotics, exoskeletons, treadmills, canes, walkers, crutches, body weight support systems, physical therapy, or a combination thereof to aid in training.
- Example training devices and systems can include, but are not limited to an EKSO™ Bionic Suit by EKSO BIONICS®, the REWALK™ system by Argo Medical Technologies, the THERASTRIDE™ system by INNOVENTOR®, the RT300 system by Restorative Therapies, the RT200 system by Restorative Therapies, the RT600 system by Restorative Therapies, or the LOCOMAT system by HOCOMA®.
- In embodiments in which the
connections 194 are implemented using wires, optionally, theconnections 194 may include one ormore connectors 136 and 138. In the embodiment illustrated, the connector 136 is used to connect theconnections 194 to thesensors 188 and theconnector 138 is used to connect theconnections 194 to theneurostimulator device 220. - By way of a non-limiting example for use with relatively large subjects (e.g., humans), the
neurostimulator device 120 may be approximately 20 mm to approximately 25 mm wide, approximately 45 mm to approximately 55 mm long, and approximately 4 mm to approximately 6 mm thick. By way of another non-limiting example for use with relatively small subjects (e.g., rats), theneurostimulator device 120 may be approximately 3 mm to approximately 4 mm wide, approximately 20 mm to approximately 30 mm long, and approximately 2 mm to approximately 3 mm thick. - As previously mentioned, placement of the
assembly 100 is subcutaneous. Theelectrodes 142 are positioned on or near a target area (e.g., distal thelesion 112 illustrated inFIG. 1 ). If the subject 102 (seeFIG. 2 ) has a SCI, theelectrode array 140 may be positioned along thespinal cord 110 in a target area that is just distal to a margin of thelesion 112. Thus, if the paralysis was caused by SCI at a first location along the spinal cord 110 (seeFIG. 1 ), theelectrodes 142 may be implanted (e.g., epidurally) at a second location below the first location along the spinal cord relative to the subject'sbrain 108. Theelectrodes 142 may be placed in or on the spinal cord 110 (seeFIG. 1 ), one or more spinal nerves, one or more nerve roots, one or more peripheral nerves, the brain stem, and/or the brain 108 (seeFIG. 1 ). - The complex stimulation pattern may include at least one of tonic stimulation and intermittent stimulation. The stimulation applied may be pulsed. The electrical stimulation may include simultaneous or sequential stimulation of different regions of the
spinal cord 110, one or more spinal nerves, one or more nerve roots, one or more peripheral nerves, the brain stem, and/or the brain 108 (seeFIG. 1 ). The complex stimulation pattern applied by theassembly 100 may be below the second stimulation threshold such that the at least one selected spinal circuit is at least partially activatable by the addition of neurological signals (e.g., neurological signals induced by physical training or neurological signals originating from the brain 108) generated by the subject 102 (seeFIG. 2 ). By way of a non-limiting example, neurological signals generated by the subject 102 may be induced by subjecting the subject to physical activity or training (such as stepping on atreadmill 170 while suspended in aharness 172 or other support structure). The neurological signals generated by the subject 102 may be induced in a paralyzed portion of the subject 102. By way of another non-limiting example, the neurological signals generated by the subject 102 may include supraspinal signals (or neurological signals originating from the brain 108). - As mentioned above, the embodiment of the
assembly 100 illustrated inFIG. 1 is configured for implantation in the subject 102 (seeFIG. 2 ). However, through application of ordinary skill in the art to the present teachings, embodiments may be constructed for use with other subjects, such as other mammals, including rats. Theassembly 100 may be configured for chronic implantation and use. For example, theassembly 100 may be used to stimulate one or more nerve roots, one or more nerves, the spinal cord 110 (seeFIG. 1 ), the brain stem, and/or the brain over time. In one embodiment, the dorsal root can be stimulated. - The implantable assembly 100 (see
FIG. 1 ) may be used with anexternal system 180 illustrated inFIG. 2 . Turning toFIG. 2 , theexternal system 180 includes anexternal control unit 150 that may be used program, gather data, and/or charge the neurostimulator device 120 (e.g., via a wireless connection 155). In the embodiment illustrated inFIG. 2 , theexternal control unit 150 is configured to be handheld. Optionally, theexternal system 180 includes acomputing device 152 described in detail below. Theexternal control unit 150 may be connected via a connection 154 (e.g., a USB connection, wireless connection, and the like) to anexternal computing device 152. - The
computing device 152 may be connected to a network 156 (e.g., the Internet) and configured to send and receive information across the network to one or more remote computing devices (e.g., a remote computing device 157). - In embodiments in which the
computing device 152 is implemented with a wireless communication interface, theexternal control unit 150 may be omitted and thecomputing device 152 may communicate instructions directly to theneurostimulator device 120 via thewireless connection 155. For example, thecomputing device 152 may be implemented as a cellular telephone, tablet computing device, and the like having a conventional wireless communication interface. In such embodiments, thecomputing device 152 may communicate instructions to theneurostimulator device 120 using a wireless communication protocol, such as Bluetooth. Further, thecomputing device 152 may receive data from theneurostimulator device 120 via thewireless connection 155. Instructions and data may be communicate to and received from theremote computing device 157 over thenetwork 156. Thus, theremote computing device 157 may be used to remotely program the neurostimulator device 120 (via the computing device 152) over thenetwork 156. - One or more
external sensors 158 may be connected to thecomputing device 152 via (wired and/or wireless)connections 159. Further, amotion capture system 166 may be connected to thecomputing device 152. Theexternal sensors 158 and/ormotion capture system 166 may be used to gather data about the subject 102 for analysis by thecomputing device 152 and/or theneurostimulator device 120. - The
external sensors 158 may include at least one of the following: foot pressure sensors, a foot force plate, in-shoe sensors, accelerometers, surface EMG sensors, gyroscopic sensors, and the like. Theexternal sensors 158 may be attached to or positioned near the body of the subject 102. - The
motion capture system 166 may include any conventional motion capture system (e.g. a video-based motion capture system) and the present teachings are not limited to use with any particular motion capture system. -
FIG. 5 is a block diagram of a first embodiment of asystem 200. Thesystem 200 includes animplantable assembly 202 substantially similar to theassembly 100 described above, and anexternal system 204 substantially similar to theexternal system 180 described above. Therefore, only components of theassembly 202 that differ from those of theassembly 100, and components of theexternal system 204 that differ from those of theexternal system 180 will be described in detail. For ease of illustration, like reference numerals have been used to identify like components inFIGS. 1-3 and 5. - The
assembly 202 includes aneurostimulator device 220, the one or more leads 130, and theelectrode array 140, and theconnections 194. Theassembly 202 may also include the reference wires 196 (seeFIG. 2 ). By way of a non-limiting example, theassembly 202 may include the two reference wires illustrated inFIG. 2 . In the embodiment illustrated, theconnections 194 include sixteen wires, each connected to a different one of the sensors 188 (e.g., the EMG sensors 190). However, this is not a requirement and embodiments may be constructed using a different number of connections (e.g., wires), a different number of sensors, and/or different types of sensors without departing from the scope of the present teachings. - In the embodiment illustrated, the
electrode array 140 includes the 27 electrodes A1-A9, B1-B9, and C1-C9. However, this is not a requirement and embodiments including different numbers of electrodes (e.g., 16 electrodes, 32 electrodes, 64 electrodes, 256 electrodes, etc.) are within the scope of the present teachings. Particular embodiments include at least 16 electrodes. - The
neurostimulator device 220 is configured to send a stimulating signal (e.g., a “pulse”) to any of theelectrodes 142 in theelectrode array 140. Theneurostimulator device 220 is also configured to switch between different electrodes very rapidly. Thus, theneurostimulator device 220 can effectively send a predefined pattern of pulses to selected ones of theelectrodes 142 in theelectrode array 140. In some embodiments, theneurostimulator device 220 is configured to generate a wide variety of waveforms such that virtually any pulsed waveform can be generated. As mentioned above, theelectrodes 142 may be arranged in more than four groups, each group including one or more of the electrodes. Further, an electrode may be included in more than one group. In groups including more than one electrode, the electrodes may be stimulated simultaneously. - The
wireless connection 155 may be two components, acommunication connection 155A and apower transfer connection 155B. - Depending upon the implementation details, the
neurostimulator device 220 may be configured to deliver stimulation having the following properties: - 1. A maximum voltage (e.g., a constant voltage mode) of about ±12 V;
- 2. A maximum stimulating current (e.g., a constant current mode) of about ±5 mA;
- 3. A maximum stimulation frequency of about 100 kHz;
- 4. A minimum pulse width of about 0.1 ms having a frequency as high as about 50 kHz;
- 5. A maximum recording bandwidth of about 60 kHz (−3 dB);
- 6. Digital to Analog converter (“DAC”) resolution of about 7 bits to about 12 bits;
- 7. Configuration switch time of about 3 μs;
- 8. Ability to configure stimulation and deliver stimulation (e.g., a pulse) about 100 times per millisecond;
- 9. Simultaneously addressable electrodes (e.g., any pair of the
electrodes 142 may be addressed with multiple groups (e.g., more than four groups) of electrodes being addressable (e.g., stimulated or recorded from) simultaneously); - 10. Any of the
electrodes 142, if not used for applying stimulation, can be selected as a differential pair of electrodes and used for recording; - 11. A wireless data transfer rate of about 250 kBps (ISM band 915 MHz) across the
communication connection 155A to send and/or receive data; and - 12. A maximum power consumption of about 100 mW.
- In the embodiment illustrated, the
neurostimulator device 220 includes amultiplexer sub-circuit 230, astimulator circuit 240, a controller 250 (connected to acontroller circuit 252 illustrated inFIG. 8 ), and an optionalwireless power circuit 260. Thecontroller 250 sends three control signals Clock, Data, and EN to themultiplexer sub-circuit 230, and receives data A1′-A4′ from themultiplexer sub-circuit 230. Thestimulator circuit 240 provides a first stimulation signal STIM+ and a second stimulation signal STIM− to themultiplexer sub-circuit 230. Thecontroller 250 sends control signals PWM and MODE to thestimulator circuit 240. The control signal MODE sent by thecontroller 250 to thestimulator circuit 240 instructs thestimulator circuit 240 to operate in either constant voltage mode or constant current mode. The control signal PWM sent by thecontroller 250 to thestimulator circuit 240 uses pulse-width modulation to control power sent by thestimulator circuit 240 to themultiplexer sub-circuit 230 as the first and second stimulation signals STIM+ and STIM−. Thus, the control signal PWM configures at least a portion of the complex stimulation pattern. However, themultiplexer sub-circuit 230 determines which of theelectrodes 142 and/orconnections 194 receives the stimulation. Therefore, themultiplexer sub-circuit 230 configures at least a portion of the complex stimulation pattern. However, both thestimulator circuit 240 and themultiplexer sub-circuit 230 configure the complex stimulation pattern based on instructions received from thecontroller 250. - The
controller 250 is connected wirelessly to theexternal programming unit 150 via thecommunication connection 155A. Thecommunication connection 155A may be configured to provide bi-directional wireless communication over which thecontroller 250 may receive system control commands and data from theexternal programming unit 150, as well as transmit status information and data to theexternal programming unit 150. In some embodiments, thecommunication connection 155A may include one or more analog communication channels, one or more digital communication channels, or a combination thereof. - The
controller 250 receives power (e.g., 3V) from thewireless power circuit 260 and a power monitoring signal PWRMON from thewireless power circuit 260. Thewireless power circuit 260 provides power (e.g., 12V and 3V) to themultiplexer sub-circuit 230. Thewireless power circuit 260 also provides power (e.g., 12V and 3V) to thestimulator circuit 240. Thewireless power circuit 260 receives power wirelessly from theexternal programming unit 150 via thepower transfer connection 155B. -
FIGS. 6A and 6B are a circuit diagram of an exemplary implementation of themultiplexer sub-circuit 230.FIG. 6A is a leftmost portion of the circuit diagram of themultiplexer sub-circuit 230, andFIG. 6B is a rightmost portion of the circuit diagram of themultiplexer sub-circuit 230. The circuit diagram ofFIGS. 6A and 6B includes amplifiers AMP1-AMP4, shift registers SR1-SR4 (e.g., implemented using NXP Semiconductors 74HC164), and analog multiplexer chips M0-M9. - The amplifiers AMP1-AMP4 output the data A1′-A4′, respectively. The amplifiers AMP1-AMP4 (e.g., Analog Devices AD8224) may be implemented as differential amplifiers with a gain set to 200. However, as is apparent to those of ordinary skill in the art, other gain values may be used. Further, the gains of the amplifiers AMP1-AMP4 may be readily changed by modifications to the components known to those of ordinary skill in the art.
- The multiplexer sub-circuit 230 routes the first and second stimulation signals Stim+ and Stim− to the selected ones of the
electrodes 142 and/orconnections 194. The multiplexer sub-circuit 230 also routes signals received from selected ones of theelectrodes 142 and/orconnections 194 to the amplifiers AMP1-AMP4. Thus, themultiplexer sub-circuit 230 is configured to route signals between thestimulator circuit 240, the amplifiers AMP1-AMP4, theelectrodes 142, and theconnections 194. - The
controller 250 sends a 30-bit serial data stream through the control signals Clock and Data to themultiplexer sub-circuit 230, which is fed into the shift registers SR1-SR4. The shift registers SR1-SR4 in turn control the analog multiplexer chips M0-M9, which are enabled by the control signal EN. - The multiplexer chip M0 has inputs “Da” and “Db” for receiving the first and second stimulation signals STIM+ and STIM−, respectively, from the
controller 250. The multiplexer chip M0 is used to disconnect one or more of theelectrodes 142 and/or one or more of the sensors 188 (e.g., the EMG sensors 190) during recording of signals detected by the disconnect component(s). The multiplexer chip M0 is also used to select a polarity (or tristate) for each of theelectrodes 142 when stimulation is applied. The multiplexer chip M0 may be implemented as a 2×(4:1) multiplexer (e.g., Analog Devices ADG1209). - The multiplexer chips M1-M9 are interconnected to connect almost any pair of the
electrodes 142 orconnections 194 to the amplifier AMP1 and the inputs “Da” and “Db” (which receive the first and second stimulation signals STIM+ and STIM−, respectively) of multiplexer chip M0. The multiplexer chips M1-M9 may each be implemented using an 8:1 multiplexer (e.g., Analog Devices ADG1208). - With respect to the multiplexer chips M1-M9, a label in each rectangular tag in the circuit diagram identifies a connection to one of the
electrodes 142 orconnections 194. Each label in a rectangular tag starting with the letter “E” identifies a connection to one of theconnections 194 connected to one of the sensors 188 (e.g., one of the EMG sensors 190). For example, the label “E1+” adjacent multiplexer chip M1 identifies a connection to a first wire, and the label “E1−” adjacent multiplexer chip M2 identifies a connection to a second wire. Together, the labels “E1+” and “E1−” identify connections to a first pair of theconnections 194. - The labels “G1” and “G2” adjacent multiplexer chip M9 identify connections to the reference wires 196 (see
FIG. 2 ). - Each label in a rectangular tag starting with a letter other than the letter “E” or the letter “G” identifies a connection to one of the
electrodes 142. For example, the label “A3” refers to a connection to the electrode A3 (seeFIG. 3B ) in column A and row 3 (where column A is leftmost, column B is in the middle, column C is rightmost,row 1 is rostral, androw 9 is caudal). - Optionally, some key electrodes may have more than one connection to the
multiplexer sub-circuit 230. For example, the electrodes A1, B1, C1, A9, B9, and C9 are each identified by more than one label. - The
multiplexer sub-circuit 230 is designed to operate in four modes. In a first mode, themultiplexer sub-circuit 230 is configured to select an individual electrode to which to apply a monopolar stimulating pulse. In a second mode, themultiplexer sub-circuit 230 is configured to select a pair of theelectrodes 142 to stimulate in a bipolar fashion. In a third mode, themultiplexer sub-circuit 230 is configured to select a single electrode from which to record, with the recorded waveform referenced to a ground signal. In a fourth mode, themultiplexer sub-circuit 230 is configured to select a pair of theelectrodes 142 from which to record in a differential fashion. - As mentioned above, the
neurostimulator device 220 can provide selective stimulation to any of theelectrodes 142. Themultiplexer sub-circuit 230 is configured to route stimulation between almost any pair of theelectrodes 142 or theconnections 194. For example, the electrode A1 may be the anode and the electrode B6 the cathode. - The
multiplexer sub-circuit 230 is configured route signals received from theconnections 194 to the amplifiers AMP1-AMP4 and to the controller 250 (in data A1′-A4′) for recording thereby. Similarly, themultiplexer sub-circuit 230 is configured route signals received from theelectrodes 142 to the amplifiers AMP1-AMP4 and to the controller 250 (in data A1′-A4′) for recording thereby. By way of a non-limiting example, themultiplexer sub-circuit 230 may be configured route signals received from four electrodes positioned in the same column (e.g. electrodes A1, A3, A5, and A7) and signals received from a fifth electrode (e.g., electrode A9) positioned in the same column to the controller 250 (in data A1′-A4′ output by the amplifiers AMP1-AMP4) so that a differential signal received from the first four relative to the fifth may be recorded by thecontroller 250 for each pair of electrodes (e.g., a first pair including electrodes A1 and A9, a second pair including electrodes A3 and A9, a third pair including electrodes A5 and A9, and a fourth pair including electrodes A7 and A9). - As mentioned above, the
multiplexer sub-circuit 230 receives power (e.g., 12V and 3V) from thewireless power circuit 260. For ease of illustration, power lines providing this power to themultiplexer sub-circuit 230 have been omitted. The power lines may be implemented using one line having a voltage of about +12V, one line having a voltage of about +2V to about +6V (e.g., +3V), and one ground line. - The
multiplexer sub-circuit 230 may be configured to change configurations in less than one microsecond in embodiments in which the control signals Clock and Data are fast enough. This allows the first and second stimulation signals Stim+ and Stim− (received from the stimulator circuit 240) to be delivered in short pulses to selected ones of theelectrodes 142 in about one millisecond and also allows the amplifiers AMP1-AMP4 to rapidly switch input signals so thecontroller 250 may effectively record from 8 or 16 signals (instead of only four) within as little as about 20 microseconds. In some embodiments, thecontroller 250 may effectively record from 8 or 16 signals (instead of only four) within as little as 5 microseconds. -
FIG. 7 is a circuit diagram of an exemplary implementation of thestimulator circuit 240. As mentioned above, thestimulator circuit 240 is configured to selectively operate in two modes: constant voltage mode and constant current mode. InFIG. 7 , labels “Mode1” and “Mode2” identify connections to pins “P1_0” and “P1_1,” respectively, of the controller 250 (seeFIG. 8 ). When pin “P1_0” (connected to the connection labeled “Mode1”) is set to ground and pin “P1_1” (connected to the connection labeled “Mode2”) is high impedance, thestimulator circuit 240 is in constant voltage mode. When pin “P1_1” (connected to the connection labeled “Mode2”) is set to ground and pin “P1_0” (connected to the connection labeled “Mode1”) is high impedance, thestimulator circuit 240 is in constant current mode. -
FIG. 8 is a circuit diagram of an exemplary implementation of acontroller circuit 252 that includes thecontroller 250 and its surrounding circuitry. Thecontroller 250 controls themultiplexer sub-circuit 230, records amplified signals received (in the data A1′-A4′) from themultiplexer sub-circuit 230, and monitors wireless power (using the power monitoring signal PWRMON received from the wireless power circuit 260). Thecontroller 250 also communicates with anexternal controller 270. In the embodiment illustrated, thecontroller 250 has been implemented using a Texas Instruments CC1110. However, through application of ordinary skill to the present teachings, embodiments may be constructed in which thecontroller 250 is implemented using a different microcontroller, a microprocessor, a Field Programmable Gate Array (“FPGA”), a Digital Signal Processing (“DSP”) engine, a combination thereof, and the like. - It may be desirable to record signals (e.g., Motor Evoked Potentials (MEPs)) received from the
electrode array 140. For example, recorded MEPs can help assess the health and state of thespinal cord 110, and may be used to monitor the rate and type of recovery of spinal cord function under long-term epidural stimulation. Therefore, in some embodiments, thecontroller circuit 252 is configured to record voltages and currents received from theelectrode array 140 when it is not stimulated. In such embodiments, thecontroller circuit 252 is also configured to transmit the recorded data over thecommunication connection 155A (e.g., in “real time”) to theexternal programming unit 150. In the embodiment illustrated, thecontroller circuit 252 includes anantenna 272 configured to communicate with theexternal controller 270. Thecontroller circuit 252 may be configured to coordinate stimulating (signal sending) and reading (signal receiving) cycles with respect to theelectrode array 140. - With respect to controlling the state of the implanted
neurostimulator device 220, thecontroller circuit 252 may be configured to measure (and/or control) the exact timing of the onset of stimulation. Thecontroller circuit 252 may be configured to reset or stop stimulation at a desired time. Thecontroller circuit 252 may be configured to transition smoothly between successive stimulation (e.g., pulses) and successive stimulation patterns. - With respect to patient monitoring and safety, the
controller circuit 252 may be configured to monitor electrode impedance, and impedance at the electrode/tissue interface. Of particular concern is impedance at relatively low frequencies (e.g., 10-1000 Hz). Thecontroller circuit 252 may be configured to limit current and voltage. Further, thecontroller circuit 252 may be configured to trigger an alarm (or send an alarm message to the computing device 152) when voltage or current limits are exceeded. Optionally, theneurostimulator device 220 may shut down or power down if an unsafe condition is detected. - The
external controller 270 may be used to program thecontroller 250. Theexternal controller 270 may be a component of the external control unit 150 (seeFIG. 2 ). Theexternal controller 270 may be implemented using a Texas Instruments CC1111. Theexternal controller 270 may relay information to and from thecomputing device 152 through the connection 154 (e.g., a USB connection, and/or a wireless connection). - The
computing device 152 may be configured to control data streams to be sent to theneurostimulator device 220. Thecomputing device 152 may interpret data streams received from theneurostimulator device 220. In some implementations, thecomputing device 152 is configured to provide a graphical user interface for communicating with theneurostimulator device 220. The user interface may be used to program theneurostimulator device 220 to deliver particular stimulation. For example, the user interface may be used to queue up a particular sequence of stimuli. Alternatively, thecomputing device 152 may execute a method (e.g., a machine learning method described below) configured to determine stimulation parameters. In some embodiments, the user interface may be used to configure the method performed by thecomputing device 152. The user interface may be used to transfer information recorded by theneurostimulator device 220 to thecomputing device 152 for storage and/or analysis thereby. The user interface may be used to display information indicating an internal system state (such the current selection of stimulation parameters values) and/or mode of operation (e.g., constant voltage mode, constant current mode, and the like). -
FIG. 9 is a circuit diagram of an exemplary implementation of the optionalwireless power circuit 260. Thewireless power circuit 260 is configured to receive power wirelessly from an externalwireless power circuit 280. Thewireless power circuit 260 may supply both about 3V DC (output VCC) and about 12V DC (output VDD). As mentioned above, the output VCC is connected to themultiplexer sub-circuit 230, thestimulator circuit 240, and thecontroller 250, and the output VDD is connected to themultiplexer sub-circuit 230 and thestimulator circuit 240. - The external
wireless power circuit 280 may be a component of the external control unit 150 (seeFIG. 2 ). The externalwireless power circuit 280 may be implemented using a Class E amplifier and configured to provide variable output. In the embodiment illustrated, the externalwireless power circuit 280 provides power to thewireless power circuit 260 via inductive coupling over thepower transfer connection 155B. Thewireless power circuit 260 may include a radio frequency (“RF”) chargingcoil 264 and the externalwireless power circuit 280 includes anRF charging coil 284 configured to transfer power (e.g., inductively) to theRF charging coil 264. Optionally, communication channels may be multiplexed on the wireless transmission. - The
wireless power circuit 260 may be connected to one or more rechargeable batteries (not shown) that are chargeable using power received from the externalwireless power circuit 280. The batteries may be implemented using rechargeable multi-cell Lithium Ion Polymer batteries. -
FIG. 10 is a block diagram of animplantable assembly 300. For ease of illustration, like reference numerals have been used to identify like components inFIGS. 1-3 , 5, and 10. Theassembly 300 may be configured to communicate with theexternal controller 270 via thecommunication connection 155A. Optionally, theassembly 300 may receive power wirelessly from the externalwireless power circuit 280 via inductive coupling over thepower transfer connection 155B. - In addition to providing complex stimulation patterns to body tissue (e.g., neurological tissue), the
assembly 300 is configured to also provide electrical stimulation directly to muscles (not shown) that will cause the muscle to move (e.g., contract) to thereby augment the improved neurological function provided by the complex stimulation patterns alone. Theassembly 300 is configured to provide one or more complex stimulation patterns to 16 or more individually addressable electrodes for purposes of providing improved neurological function (e.g., improved mobility recovery after SCI). - The
assembly 300 includes aneurostimulator device 320, the one or more leads 130, and theelectrode array 140, the connections 194 (connected to the sensors 188), and connections 310 (e.g., wires, wireless connections, and the like) to (implanted and/or external) muscle electrodes 312. Theassembly 300 may also include the reference wires 196 (seeFIG. 2 ). By way of a non-limiting example, theassembly 300 may include the two reference wires illustrated inFIG. 2 . In the embodiment illustrated, theconnections 194 include sixteen wires, each connected to a different one of the sensors 188 (e.g., the EMG sensors 190). However, this is not a requirement and embodiments may be constructed using a different number of wires, a different number of EMG sensors, and/or different types of sensors without departing from the scope of the present teachings. - The
neurostimulator device 320 includes acontroller 322, arecording subsystem 330, a monitor andcontrol subsystem 332, a stimulatingsubsystem 334, amuscle stimulator drive 336, asensor interface 338, awireless communication interface 340, anRF power interface 342, and at least one power source 344 (e.g., a rechargeable battery). In the embodiment illustrated, thecontroller 322 has been implemented using a microcontroller (e.g., a Texas Instruments CC1110). However, through application of ordinary skill to the present teachings, embodiments may be constructed in which thecontroller 250 is implemented using a microprocessor, FPGA, DSP engine, a combination thereof, and the like. - If a rechargeable battery is used in any embodiment described herein as a source of power, the rechargeable battery can include a charging system such as through transduction, ultrasonics, magnetism, or photonics. In other embodiments, as battery technology evolves, the battery may not be rechargeable, but rather disposable and user replaceable.
- The
recording subsystem 330 is configured to record electrical signals received from one or more of theelectrodes 142 in theelectrode array 140. The electrodes used to record may be the same electrodes used to provide the complex stimulation pattern, or different electrodes specialized for recording. Therecording subsystem 330 may be connected (directly or otherwise) to one or more of theleads 130. In the embodiment illustrated, therecording subsystem 330 is connected to theleads 130 via the monitor andcontrol subsystem 332. - The
recording subsystem 330 includes one ormore amplifiers 346. In the embodiment illustrated, theamplifiers 346 are implemented as low noise amplifiers (“LNAs”) with programmable gain. - The monitor and
control subsystem 332 illustrated includes ablanking circuit 350 that is connected directly to theleads 130. The blankingcircuit 350 is configured to disconnect the recording subsystem 330 (which is connected thereto) from theleads 130 when the complex stimulation pattern is applied to theelectrodes 142 to avoid damaging theamplifiers 346. Bidirectional control and status lines (not shown) extending between the blankingcircuit 350 and thecontroller 340 control the behavior of the blankingcircuit 350. - The monitor and
control subsystem 332 monitors the overall activity of theneurostimulator device 320, as well as the functionality (e.g., operability) of theelectrode array 140. The monitor andcontrol subsystem 332 is connected to the CPU by bidirectional digital and analog signal andcontrol lines 352. In some embodiments, the monitor andcontrol subsystem 332 includes acircuit 354 configured to monitor electrode impedance. Optionally, a multiplexer (not shown) may be connected to theleads 130, allowing the monitor andcontrol subsystem 332 to selectively interrogate the signal received from each electrode. The output of the multiplexer (not shown) is connected to an A/D circuit (not shown), so that a signal received from a selected one of theelectrodes 142 can be digitized, and transmitted to thecontroller 322 to assess the functionality of the stimulating circuitry. The monitor andcontrol subsystem 332 may includecircuitry 356 configured to assess the functionality (e.g., operability) of thepower source 344. - The
amplifiers 346 receive signals from theleads 130 when the blankingcircuit 350 is in the off state. In some embodiments, a different one of theamplifiers 346 is connected to each different one of theleads 130. In other embodiments, the blankingcircuit 350 includes or is/may be connected to a multiplexing circuit having an input is connected to theleads 130 and the output of theblanking system 350. In such embodiments, the multiplexing circuit routes an electrode signal (selected by the controller 322) to a single one of theamplifiers 346. Theamplifiers 346 are connected to thecontroller 322 via bidirectional control and status lines (not shown) that allow thecontroller 322 to control the gain and behavior of theamplifiers 346. - The
recording subsystem 330 includes an analog-to-digital (“A/D”)circuit 347 that digitizes the output(s) received from theamplifiers 346. In some embodiments, a separate A/D circuit is dedicated to the output of eachamplifier 346. In other embodiments, a multiplexing circuit (not shown) routes the output of a selected one of theamplifiers 346 to a single A/D circuit. The output of the A/D circuit 347 is connected via a serial or paralleldigital bus 348 to thecontroller 322. In the embodiment illustrated, therecording subsystem 330 includes a parallel toserial circuit 349 that serializes the output received from the A/D circuit 347 for transmission on thebus 348. Control and status lines (not shown) connect the A/D circuit 347 to thecontroller 322, allowing thecontroller 322 to control the timing and behavior of the A/D circuit 347. - The stimulating
subsystem 334 will be described as delivering complex stimulation patterns over channels. Each channel corresponds to one of theelectrodes 142. Stimulation delivered over a channel is applied to the corresponding one of theelectrodes 142. Similarly, stimulation received from one of theelectrodes 142 may be received over the corresponding channel. However, in some embodiments, two or more electrodes may be physically connected to the same channel so their operation is governed by a single channel. - The stimulating
subsystem 334 is configured to generate complex stimulation patterns, which as explained above include complex waveforms (either in voltage or current mode), and deliver the stimulation on each of one or more of the channels. The stimulatingsubsystem 334 is connected to thecontroller 322 by multiplebidirectional lines 360 over which the stimulatingsubsystem 334 receives commands and stimulating waveform information. The stimulatingsubsystem 334 may transmit circuit status information to thecontroller 322 over thelines 360. Each output is connected to one of theleads 130, thereby stimulating a single one of theelectrodes 142 in theelectrode array 140. - In the embodiment illustrated, the stimulating
subsystem 334 includes a digital-to-analog amplifier 362 that receives stimulating waveform shape information from thecontroller 322. Theamplifier 362 turn drives (voltage or current)amplifiers 364. The outputs of theamplifiers 364 are monitored and potentially limited by over-voltage or over-current protection circuitry 366). - The
muscle stimulator drive 336 is configured to drive one or more of the muscle electrodes 312. Alternatively, themuscle stimulator drive 336 may provide an interface to a separate drive system (not shown). Themuscle stimulator drive 336 is connected bybidirectional control lines 368 to thecontroller 322 to control the operation of themuscle stimulator drive 336. - The
sensor interface 338 interfaces with one or more of the sensors 188 (theEMG sensors 190,joint angle sensors 191,accelerometers 192, and the like). Depending upon the implementation details, thesensor interface 338 may include digital signal inputs (not shown), low noise amplifiers (not shown) configured for analog signal line inputs, and analog inputs (not shown) connected to A/D circuits (not shown). - The
controller 322 may be connected wirelessly to theexternal programming unit 150 via thecommunication connection 155A. Thecommunication connection 155A may be configured to provide bi-directional wireless communication over which thecontroller 322 may receive system control commands and data from theexternal programming unit 150, as well as transmit status information and data to theexternal programming unit 150. In some embodiments, thecommunication connection 155A may include one or more analog communication channels, one or more digital communication channels, or a combination thereof. - The
RF power interface 342 may receive power wirelessly from theexternal programming unit 150 via thepower transfer connection 155B. TheRF power interface 342 may include a radio frequency (“RF”) chargingcoil 372. In such embodiments, theRF charging coil 284 of the externalwireless power circuit 280 may be configured to transfer power (e.g., inductively) to theRF charging coil 272. Optionally, communication channels may be multiplexed on the wireless transmission. - The
power source 344 may be implemented using one or more rechargeable multi-cell Lithium Ion Polymer batteries. -
FIG. 11 is a block diagram of a first embodiment of asystem 400. Thesystem 400 includes animplantable assembly 402 substantially similar to theassembly 100 described above, and anexternal system 404 substantially similar to theexternal system 180 described above. Therefore, only components of theassembly 402 that differ from those of theassembly 100, and components of theexternal system 404 that differ from those of theexternal system 180 will be described in detail. For ease of illustration, like reference numerals have been used to identify like components inFIGS. 1-3 , 5, and 10-12B. - The
assembly 402 includes aneurostimulator device 420, theelectrode array 140, and the one or more traces 130. Theneurostimulator device 420 is connected by acontroller interface bus 437 to an implantablemuscle stimulator package 438, and anEMG module 446. Theneurostimulator device 420 is configured to interface with and control both the implantablemuscle stimulator package 438 and theEMG module 446. By way of a non-limiting example, suitable implantable muscle stimulator packages for use with the system may include a Networked Stimulation system developed at Case Western University. - The
neurostimulator device 420 includes atransceiver 430,stimulator circuitry 436, awireless power circuit 440, a power source 448 (e.g., a battery), and acontroller 444 for theEMG module 446 and thepower source 448. Theneurostimulator device 420 illustrated is configured interface with and control theseparate EMG module 446. However, in alternate embodiments, EMG recording and management capabilities may be incorporated into theneurostimulator device 420, as they are in the neurostimulator device 320 (seeFIG. 10 ). In the embodiment illustrated, theEMG module 446 includes an analog to digital converter (“ADC”) 445. Digital data output by theEMG module 446 and received by thecontroller 444 is sent to thestimulator circuitry 436 via thecontroller interface bus 437. - The
transceiver 430 is configured to communicate with acorresponding transceiver 432 of theexternal programming unit 150 connected to theexternal controller 270 over thecommunication connection 155A. Thetransceivers transceiver 432 may be implemented using ZL70102 MICS band transceiver connected to a 2.45 GHz transmitter. The transmitter may be configured to “wake up” thetransceiver 430. By way of a non-limiting example, thetransceiver 430 may be implemented using a ZL70102 MICS band transceiver. -
FIG. 12A is a block diagram illustrating thetransceiver 430 and the components of thestimulator circuitry 436. InFIG. 12A , connections labeled “SPI” have been implemented for illustrative purposes using Serial Peripheral Interface Buses. - Referring to
FIG. 12A , thestimulator circuitry 436 includes a central processing unit (“CPU”) orcontroller 422, one or moredata storage devices analog converter 464, ananalog switch 466, and an optional complex programmable logic device (“CPLD”) 468. In the embodiment illustrated, thecontroller 422 has been implemented using a field-programmable gate array (“FPGA”). Digital data output by theEMG module 446 and received by thecontroller 444 is sent to thecontroller 422 via thecontroller interface bus 437. - The
storage device 460 is connected to thecontroller 422 and configured to store instructions for thecontroller 422. By way of a non-limiting example, thestorage device 460 may be implemented as FPGA configured memory (e.g., PROM or non-flash memory). Theoptional CPLD 468 is connected between thetransceiver 430 and thestorage device 460. Theoptional CPLD 468 may be configured to provide robust access to thestorage device 460 that may be useful for storing updates to the instructions stored on thestorage device 460. - The
storage device 462 is connected to thecontroller 422 and configured to store recorded waveform data. By way of a non-limiting example, thestorage device 462 may include 8 MB or more of memory. - The digital to
analog converter 464 is connected to thecontroller 422 and configured to convert digital signals received therefrom into analog signals to be delivered to theelectrode array 140. The digital toanalog converter 464 may be implemented using an AD5360 digital to analog converter. - The
analog switch 466 is positioned between the digital toanalog converter 464 and theleads 130. Theanalog switch 466 is configured to modulate (e.g., selectively switch on and off) the analog signals received from the digital toanalog converter 464 based on instructions received from thecontroller 422. Theanalog switch 466 may include a plurality of analog switches (e.g., a separate analog switch for each channel). Optionally, theanalog switch 466 may have a high-impedance mode. Theanalog switch 466 may be configured to operate in the high-impedance mode (in response to instructions from thecontroller 422 instructing theanalog switch 466 to operate in the high-impedance mode) when the neurostimulator device is not delivering stimulation to theelectrodes 142. Theanalog switch 466 may receive instructions from thecontroller 422 over one ormore control lines 467. - In the embodiment illustrated, the ability to directly stimulate muscles (as an adjunct to the neurological stimulation) is not integrated into the
neurostimulator device 420 as it is in theneurostimulator device 320 described above and illustrated inFIG. 10 . Instead, thecontroller 422 communicates with the separate implantablemuscle stimulator package 438 via thecontroller interface bus 437. Optionally, a monitor and control subsystem (like the monitor andcontrol subsystem 332 of the neurostimulator device 320) may be omitted from theneurostimulator device 420. However, this is not a requirement. - The
neurostimulator device 420 is configured to deliver stimulation to each of a plurality of channels independently. As explained above, each channel corresponds to one of theelectrodes 142. Stimulation delivered over a channel is applied to the corresponding one of theelectrodes 142. In the embodiment illustrated, the plurality of channels includes 16 channels. However, this is not a requirement. To deliver stimulation, theneurostimulator device 420 uses one positive channel and one negative channel. - In some embodiments, signals detected or received by one or more of the
electrodes 142 may be received by theneurostimulator device 420 over the corresponding channels. - The
neurostimulator device 420 may be configured to control the polarity (positive or negative) or tristate (positive, negative, or high Z) of each of the channels. Theneurostimulator device 420 may be configured to deliver stimulation having a frequency within a range of about 0.1 Hz to about 100 Hz. The stimulation delivered may have an amplitude of about −10 Vdc to about +10 Vdc with an increment of about 0.1 Vdc. Theneurostimulator device 420 is configured to generate stimulation having a standard waveform shape (e.g., sine, triangle, square, and the like) and/or a custom defined waveform shape. The duty cycle of theneurostimulator device 420 may be configured (for example, for square waveform shapes). Theneurostimulator device 420 may provide phase shift in specified increments (e.g., in 25 microsecond increments). - The
neurostimulator device 420 may be configured to satisfy timing requirements. For example, theneurostimulator device 420 may be configured to deliver a minimum pulse width of about 50 μs and to update all positive channels within a minimum pulse width. In such embodiments, a maximum number of positive channels may be determined (e.g., 15 channels). Theneurostimulator device 420 may be configured to accommodate a minimum amount of phase shift (e.g., 25 μs phase shift). Further, theneurostimulator device 420 may be configured to update some channels during a first time period (e.g., 25 μs) and to rest during a second time period (e.g., 25 μs). Theneurostimulator device 420 may be configured to simultaneously update the output channels. - The
neurostimulator device 420 may be configured to satisfy particular control requirements. For example, it may be useful to configure theneurostimulator device 420 so that channel output configuration can be configured on the fly. Similarly, in some embodiments, practical limitations (e.g., a limit of a few seconds) may be placed on update time. Further, in some embodiments, theneurostimulator device 420 is configured to operate with adjustable custom waveform definitions. It may also be desirable to configure theneurostimulator device 420 such that output stimulation does not stop (or drop-out) during output reconfiguration. - In the embodiment illustrated in
FIG. 12A , recording via the EMG module 446 (seeFIG. 11 ) and delivering stimulation to theelectrodes 142 may be performed completely separately (or independently). Further, in some embodiments, commands or instructions may be sent to the implantable muscle stimulator package 438 (or an integrated muscle stimulator system) independently or separately. Thus, this embodiment may operate in a full duplex mode. - In an alternate embodiment, the
neurostimulator device 420 may be connected to theEMG sensors 190 or recording electrodes (not shown) that are independent of theelectrodes 142 used to deliver stimulation. Such recording electrodes can be implanted within a subject's body or external to the subject's body. A pre-amp (not shown) and ADC (not shown) may be included in thestimulator circuitry 436 and used to send digital EMG or nerve recording signals directly to thecontroller 422. Such embodiments provide two completely separate, continuous time channels between recording and stimulation and therefore, may be characterized as being operable in a full duplex mode. Optionally, the recording electrodes may be incorporated in theelectrode array 140 and/or a separate electrode array (not shown). - In another alternate embodiment, the
analog switch 466 may be used to switch between a stimulate mode and a record mode. Theanalog switch 466 may receive instructions from the controller 422 (via the control lines 467) instructing theanalog switch 466 in which mode to operate. This implementation may help reduce the number of electrodes by using the same electrodes or a subset thereof to record and stimulate. This exemplary embodiment may be characterized as being operable in a half-duplex mode. - The embodiment illustrated in
FIG. 12A thestimulator circuitry 436 is configured to operate in a constant voltage mode. Thus, the output of the DAC 446 (and the analog switch 466) is a plurality (e.g., 16) of constant voltage signals (or sources). However, referring toFIG. 12B , in alternate embodiments, thestimulator circuitry 436 is configured to switch between the constant voltage mode and a constant current mode. In this embodiment, theanalog switch 466 includes a separate analog switch (e.g., a single pull, double throw switch) for each channel and a 2-1 multiplexer (“MUX”). This embodiment also includes ananalog switch 470 and acircuit block 472. Theanalog switch 470 may include a separate analog switch (e.g., a single pull, double throw switch) for each channel and a 1-2 demultiplexer (“DEMUX”). The output of theanalog switch 470 is a plurality (e.g., 16) of constant voltage signals selectively delivered to either theanalog switch 466 or thecircuit block 472. Essentially, the analog switches 470 and 466 may be configured to allow either a constant current signal or constant voltage signal to be applied to theelectrode array 140. - The
circuit block 472 includes voltage to current converter circuitry and constant current source circuitry. Thecircuit block 472 receives the plurality (e.g., 16) of constant voltage signals from theanalog switch 470 and outputs a plurality (e.g., 16) of constant current signals (or sources). - The
neurostimulator device 420 may be configured to provide feedback (received from thesensor 188, recording electrodes, and/or the electrodes 142) to thecontroller 422, which the controller may use to modify or adjust the stimulation pattern or waveform. In embodiments in which thecontroller 422 is implemented using a FPGA, the FPGA may be configured to modify the complex stimulation patterns delivered to the subject 102 in near realtime. Further, thecontroller 422 may be used to customize the complex stimulation pattern(s) for different subjects. - The
wireless power circuit 440 illustrated include aRF charging coil 449 configured to receive power via thepower transfer connection 155B. The power received may be used to charge the power source 448 (e.g., a battery). - Since each patient's injury or illness is different, it is believed the best pattern of stimulation will vary significantly across patients. Furthermore, it is believed optimal stimuli will change over time due to the plasticity of the
spinal cord 110. For this purpose, a learning system (e.g., thecomputing device 152 and/or one of theneurostimulator devices - The learning system receives input from one or more of the
sensors 188 and/or external adjunctive devices, which may be implanted along with theneurostimulator device EMG sensors 190,joint angle sensors 191,accelerometers 192, and the like. The external adjunctive devices may include support platforms, support stands, external bracing systems (e.g., exo-skeletal systems), in shoe sensor systems, and/or therapy machines. Information received from theelectrodes 142, theconnections 194, and/or the external adjunctive devices may be used to tune and/or adjust the complex stimulation pattern delivered by theneurostimulator devices - External adjunctive devices can include, training devices or systems configured to physically train subjects and thereby induce neurological signals in the paralyzed portion of the subject's body. Such training devices can use robotics, exoskeletons, treadmills, canes, walkers, crutches, body weight support systems, physical therapy, or a combination thereof to aid in training. Example training devices and systems can include, but are not limited to an EKSO™ Bionic Suit by EKSO BIONICS®, the REWALK™ system by Argo Medical Technologies, the THERASTRIDE™ system by INNOVENTOR®, the RT300 system by Restorative Therapies, the RT200 system by Restorative Therapies, the RT600 system by Restorative Therapies, or the LOCOMAT system by HOCOMA®.
- In one embodiment, a training device can be an EKSO™ Bionic Suit by EKSO BIONICS®.
- In one embodiment, a training device can be a REWALK system by Argo Medical Technologies.
- In one embodiment, a training device can be a THERASTRIDE™ system by INNOVENTOR®.
- In one embodiment, a training device can be a LOCOMAT system by HOCOMA®.
- In one embodiment, a training device can be an RT300 system by Restorative Therapies.
- In one embodiment, a training device can be an RT200 system by Restorative Therapies.
- In one embodiment, a training device can be an RT600 system by Restorative Therapies.
- These training devices can also be used as standalone neurostimulation systems including at least one electrode as described herein. For example, in one embodiment, a neurostimulator can include an EKSO™ Bionic Suit by EKSO BIONICS®.
- In another embodiment, a neurostimulator can include a REWALK system by Argo Medical Technologies.
- In another embodiment, a neurostimulator can include a THERASTRIDE™ system by INNOVENTOR®.
- In another embodiment, a neurostimulator can include a LOCOMAT system by HOCOMA®.
- In another embodiment, a neurostimulator can include an RT300 system by Restorative Therapies.
- In another embodiment, a neurostimulator can include an RT200 system by Restorative Therapies.
- In another embodiment, a neurostimulator can include an RT600 system by Restorative Therapies.
- The learning system may perform a machine learning method (described below) that determines suitable or optimal stimulation parameters based on information received from the
sensors 188. It is believed that it may be more efficient to perform larger adjustments to the stimulation in a clinical setting (e.g., using thecomputing device 152 and external programming unit 150), and smaller adjustments (fine tuning) on an ongoing basis (e.g., using one of theneurostimulator devices - In the clinical setting, numerous and
sensitive EMG sensors 190, as well as foot pressure sensors (not shown),accelerometers 192, and motion tracking systems (not shown) can be used to gather extensive data on the performance of the subject 102 in response to specific stimuli. These assessments of performance can be used by the learning system to determine suitable and/or optimal stimulation parameters. Soon after the subject 102 is implanted with one of theneurostimulator devices - As mentioned above, outside the clinic, the
neurostimulator devices electrodes 142, thesensors 188, and the like). This information may be used by the one of theneurostimulator devices - As mentioned above, systems and
neurostimulator devices electrode array 140, and adapt the stimuli over time to spinal plasticity (changes in spinal cord function and connectivity). However, with this flexibility comes the burden of finding suitable stimulation parameters (e.g., a pattern of electrode array stimulating voltage amplitudes, stimulating currents, stimulating frequencies, and stimulating waveform shapes) within the vast space of possible patterns and parameters. It is impractical to test all possible parameters within this space to find suitable and/or optimal parameter combinations. Such a process would consume a large amount of clinical resources, and may also frustrate the subject 102. Therefore, a machine learning method is employed to more efficiently search for effective parameter combinations. Over time, the machine learning method may be used to adapt (e.g., occasionally, periodically, continually, randomly, as needed, etc.) the operating parameters used to configure the stimulation. - The machine learning method (which seeks to optimize the stimuli parameters) alternates between an exploration phase (in which the parameter space is searched and a regression model built that relates stimulus and motor response) and an exploitation phase (in which the stimuli patterns are optimized based on the regression model). As is apparent to those of ordinary skill in the art, many machine learning methods incorporate exploration and exploitation phases and such methods may be adapted to determine suitable or optimal stimulation parameters through application of ordinary skill in the art to the present teachings.
- By way of a non-limiting example, a Gaussian Process Optimization (“GPO”) may be used to determine the stimulation parameters. C. E. Rasmussen, Gaussian Processes for Machine Learning, MIT Press, 2006. GPO is an active learning method with an update rule that explores and exploits the space of possible stimulus parameters while constructing an online regression model of the underlying mapping from stimuli to motor performance (e.g., stepping, standing, arm reaching, and the like). Gaussian Process Regression (“GPR”), the regression modeling technique at the core of GPO, is well suited to online use because it requires fairly minimal computation to incorporate each new data point, rather than the extensive re-computation of many other machine learning regression techniques. GPR is also non-parametric; predictions from GPO are based on an ensemble of an infinite number of models lying within a restricted set, rather than from a single model, allowing it to avoid the over-fitting difficulties inherent in many parametric regression and machine learning methods.
- GPR is formulated around a kernel function, k(•,•), which can incorporate prior knowledge about the local shape of the performance function (obtained from experience and data derived in previous epidural stimulation studies), to extend inference from previously explored stimulus patterns to new untested stimuli. Given a function that measures performance (e.g., stepping, standing, or reaching), GPO is based on two key formulae and the selection of an appropriate kernel function. The core GPO equation describes the predicted mean μt(x*) and variance σt 2(x*) of the performance function (over the space of possible stimuli), at candidate stimuli x*, on the basis of past measurements (tests of stimuli values X={x1,x2, . . . } that returned noisy performance values Yt={y1,y2, . . . })
-
μt(x*)=k(x*,X)[K t(X,X)+σn 2|]−1 Y t; -
σt 2(x*)=k(x*,x*)−k(x*,X)[K t(X,X)+σn 2|]−1 k(X,x*) - where Kt is the noiseless covariance matrix of past data, and σn 2 is the estimated noise covariance of the data that is used in the performance evaluation. To balance exploration of regions of the stimuli space where little is known about expected performance with exploitation of regions where we expect good performance, GPO uses an upper confidence bound update rule (N. Srinivas, A. Krause, et. al., “Guassian Process Optimization in the bandit setting: No Regret and Experimental Design,” Proc. Conf. on Machine Learning, Haifa Israel, 2010.):
-
x t+1=argmaxxεX*[μt(x)+βtσt(x)]. (1) - When the parameter βt increase with time, and if the performance function is a Gaussian process or has a low Reproducing Kernel Hilbert Space norm relative to a Gaussian process, GPO converges with high probability to the optimal action, given sufficient time.
- The method described above is a sequential updating method that works in a simple cycle. A single known stimulus is applied to the electrode array, and the patient's response to the stimulus is measured using either implanted sensors (such as
EMG sensors 190 connected to the connections 194), and/or using external sensors (such as surface EMG electrodes, foot plate forces, and motion capture data gathered from a video monitoring system). The mean and covariance of the Gaussian Process system are immediately updated based on the single stimulus, and the upper confidence procedure of Equation (1) selects the next stimuli pattern to evaluate. This process continues until a termination criteria, such as a minimal increase in performance, is reached. - Alternatively, it may be desirable to propose a batch of stimuli to apply in one clinical therapy session and then evaluate the batch of results, updating the regression model using the entire batch of stimulus-response pairs, and then proposing a new batch of stimulus patterns to be evaluated during the next clinical session. The upper confidence bound method described above can be readily extended to this case. T. Desautels, J. Burdick, and A. Krause, “Parallelizing Exploration-Exploitation Tradeoffs with Gaussian Process Bandit Optimization,” (submitted) International Conference on Machine Learning, Edinburgh, Scotland, Jun. 26-Jul. 1, 2012. The stimulus update rule for the batch process can take the following form:
-
x t+1=argmaxxεX*[μt−B(x)+βtσt(x)]. (2) - where now the Equation (2) is evaluated B times to produce a batch of B proposed stimuli to evaluate, but the mean function μ(x) is only updated at the end of the last batch of experiments, and the variance σt(x) is updated for each item in the proposed batch.
- The definition of a performance function that characterizes human motor behavior (e.g. standing or stepping behavior) may depend upon at least two factors: (1) what kinds of motor performance data is available (e.g., video-based motion capture data, foot pressure distributions, accelerometers, EMG measurements, etc.); and (2) the ability to quantify motor performance. While more sensory data is preferable, a machine learning approach to parameter optimization can employ various types of sensory data related to motor performance. It should be noted that even experts have great difficulty determining stepping or standing quality from such data without also looking at video or the
actual subject 102 as he/she undertakes a motor task. However, given a sufficient number of training examples from past experiments and human grading of the standing or stepping in those experiments, a set of features that characterize performance (with respect to the given set of available sensors) can be learned and then used to construct a reasonable performance model that captures expert knowledge and uses the available measurement data. -
FIG. 13 depicts a multi-compartment physical model of the electrical properties of a mammalianspinal cord 500, along with a 27 electrode implementation of theelectrode array 140 placed in an epidural position. InFIG. 13 , first andsecond electrodes Electrode 506 has not been activated and is considered to be neutral. InFIG. 14 , theelectrodes FIG. 14 shows the isopotential contours 508 (in slice through the center of the bipolarly activated electrodes) of the stimulating electric field for the 2-electrode stimulation example. The mammalianspinal cord 500 includes adura 510,white matter 512,gray matter 514, andepidural fat 516. -
FIG. 15 shows the instantaneous regret (a measure of the error in the machine learning methods search for optimal stimuli parameters) when the Gaussian Process Optimization method summarized above is used to optimize the array stimulus pattern that excites neurons in the dorsal roots between segments L2 and S2 in the simulatedspinal cord 500. The instantaneous regret performance shows that the machine learning method rapidly finds better stimulating parameters, but also continually explores the stimulation space (the “bursts” in the graph of instantaneous regret correspond to excursions of the machine learning method to regions of stimulus parameter space which were previously unknown, but which have are found to have poor performance). -
FIG. 16 shows the average cumulative regret vs. learning iteration. The average cumulative regret is a smoothed version of the regret performance function that better shows the machine learning method's overall progress in selecting optimal stimulation parameters. - The machine learning method may be performed by the
computing device 152, one of theneurostimulator devices computing device 152, theneurostimulator device 220, theneurostimulator device 320, theneurostimulator device 420, and a second stimulator device which may include a second computing device. Further, these devices may interact during the performance of the method or distribute portions of its execution. By performing the method, thecomputing device 152, theneurostimulator device 220, theneurostimulator device 320, theneurostimulator device 420, and/or the second stimulator device which may include a second computing device may determine the stimulation parameters (e.g., the waveform shape, amplitude, frequency, and relative phasing) of the complex stimulation pattern applied to theelectrodes 142. As discussed above, the machine learning method may implement a Sequential or Batch Gaussian Process Optimization (“GPO”) method using an Upper Confidence Bound procedure to select and optimize the stimulation parameters. -
FIG. 17 is a diagram of hardware and an operating environment in conjunction with which implementations of thecomputing device 152 and/or theremote computing device 157 may be practiced. The description ofFIG. 17 is intended to provide a brief, general description of suitable computer hardware and a suitable computing environment in which implementations may be practiced. Although not required, implementations are described in the general context of computer-executable instructions, such as program modules, being executed by a computer, such as a personal computer. Generally, program modules include routines, programs, objects, components, data structures, etc., that perform particular tasks or implement particular abstract data types. - Moreover, those skilled in the art will appreciate that implementations may be practiced with other computer system configurations, including hand-held devices, multiprocessor systems, microprocessor-based or programmable consumer electronics, network PCs, minicomputers, workstations, mainframe computers, cellular phones, smart phones (e.g., Apple iphone, Samsung Galaxy, etc.), tablet computers (e.g., Apple iPad, Barnes and Noble Nook, Amazon Kindle Fire, Microsoft Surface, etc.), laptop computer, ultrabook computer, netbook computer, pager, gaming console (e.g.,
Microsoft Xbox 360 or Xbox One,Sony Playstation - The exemplary hardware and operating environment of
FIG. 17 includes a general-purpose computing device in the form of acomputing device 12. Thecomputing device 152 and/or theremote computing device 157 may be substantially identical to thecomputing device 12. Thecomputing device 12 includes asystem memory 22, theprocessing unit 21, and asystem bus 23 that operatively couples various system components, including thesystem memory 22, to theprocessing unit 21. There may be only one or there may be more than oneprocessing unit 21, such that the processor ofcomputing device 12 includes a single central-processing unit (“CPU”), or a plurality of processing units, commonly referred to as a parallel processing environment. When multiple processing units are used, the processing units may be heterogeneous. By way of a non-limiting example, such a heterogeneous processing environment may include a conventional CPU, a conventional graphics processing unit (“GPU”), a floating-point unit (“FPU”), combinations thereof, and the like. - The
computing device 12 may be a conventional computer, a distributed computer, any other type of computer, any type of wired computing device, or any type of wireless computing device. - The
system bus 23 may be any of several types of bus structures including a memory bus or memory controller, a peripheral bus, and a local bus using any of a variety of bus architectures. Thesystem memory 22 may also be referred to as simply the memory, and includes read only memory (ROM) 24 and random access memory (RAM) 25. A basic input/output system (BIOS) 26, containing the basic routines that help to transfer information between elements within thecomputing device 12, such as during start-up, is stored inROM 24. Thecomputing device 12 further includes ahard disk drive 27 for reading from and writing to a hard disk, not shown, amagnetic disk drive 28 for reading from or writing to a removablemagnetic disk 29, and anoptical disk drive 30 for reading from or writing to a removableoptical disk 31 such as a CD ROM, DVD, or other optical media. - The
hard disk drive 27,magnetic disk drive 28, andoptical disk drive 30 are connected to thesystem bus 23 by a harddisk drive interface 32, a magneticdisk drive interface 33, and an opticaldisk drive interface 34, respectively. The drives and their associated computer-readable media provide nonvolatile storage of computer-readable instructions, data structures, program modules, and other data for thecomputing device 12. It should be appreciated by those skilled in the art that any type of computer-readable media which can store data that is accessible by a computer, such as magnetic cassettes, flash memory cards, solid state memory devices (“SSD”), USB drives, digital video disks, Bernoulli cartridges, random access memories (RAMs), read only memories (ROMs), and the like, may be used in the exemplary operating environment. As is apparent to those of ordinary skill in the art, thehard disk drive 27 and other forms of computer-readable media (e.g., the removablemagnetic disk 29, the removableoptical disk 31, flash memory cards, SSD, USB drives, and the like) accessible by theprocessing unit 21 may be considered components of thesystem memory 22. - A number of program modules may be stored on the
hard disk drive 27,magnetic disk 29,optical disk 31,ROM 24, orRAM 25, including anoperating system 35, one ormore application programs 36,other program modules 37, andprogram data 38. A user may enter commands and information into thecomputing device 12 through input devices such as akeyboard 40 andpointing device 42. Other input devices (not shown) may include a microphone, joystick, game pad, satellite dish, scanner, touch sensitive devices (e.g., a stylus or touch pad), video camera, depth camera, or the like. These and other input devices are often connected to theprocessing unit 21 through aserial port interface 46 that is coupled to thesystem bus 23, but may be connected by other interfaces, such as a parallel port, game port, a universal serial bus (USB), or a wireless interface (e.g., a Bluetooth interface). Amonitor 47 or other type of display device is also connected to thesystem bus 23 via an interface, such as avideo adapter 48. In addition to the monitor, computers typically include other peripheral output devices (not shown), such as speakers, printers, and haptic devices that provide tactile and/or other types of physical feedback (e.g., a force feed back game controller). - The input devices described above are operable to receive user input and selections. Together the input and display devices may be described as providing a user interface.
- The
computing device 12 may operate in a networked environment using logical connections to one or more remote computers, such asremote computer 49. These logical connections are achieved by a communication device coupled to or a part of the computing device 12 (as the local computer). Implementations are not limited to a particular type of communications device. Theremote computer 49 may be another computer, a server, a router, a network PC, a client, a memory storage device, a peer device or other common network node, and typically includes many or all of the elements described above relative to thecomputing device 12. Theremote computer 49 may be connected to amemory storage device 50. The logical connections depicted inFIG. 17 include a local-area network (LAN) 51 and a wide-area network (WAN) 52. Such networking environments are commonplace in offices, enterprise-wide computer networks, intranets and the Internet. - Those of ordinary skill in the art will appreciate that a LAN may be connected to a WAN via a modem using a carrier signal over a telephone network, cable network, cellular network, or power lines. Such a modem may be connected to the
computing device 12 by a network interface (e.g., a serial or other type of port). Further, many laptop computers may connect to a network via a cellular data modem. - When used in a LAN-networking environment, the
computing device 12 is connected to thelocal area network 51 through a network interface oradapter 53, which is one type of communications device. When used in a WAN-networking environment, thecomputing device 12 typically includes amodem 54, a type of communications device, or any other type of communications device for establishing communications over thewide area network 52, such as the Internet. Themodem 54, which may be internal or external, is connected to thesystem bus 23 via theserial port interface 46. In a networked environment, program modules depicted relative to thepersonal computing device 12, or portions thereof, may be stored in theremote computer 49 and/or the remotememory storage device 50. It is appreciated that the network connections shown are exemplary and other means of and communications devices for establishing a communications link between the computers may be used. - The
computing device 12 and related components have been presented herein by way of particular example and also by abstraction in order to facilitate a high-level view of the concepts disclosed. The actual technical design and implementation may vary based on particular implementation while maintaining the overall nature of the concepts disclosed. - In some embodiments, the
system memory 22 stores computer executable instructions that when executed by one or more processors cause the one or more processors to perform all or portions of the machine learning method described above. Such instructions may be stored on one or more non-transitory computer-readable media (e.g., thestorage device 460 illustrated inFIG. 12A ). - The foregoing described embodiments depict different components contained within, or connected with, different other components. It is to be understood that such depicted architectures are merely exemplary, and that in fact many other architectures can be implemented which achieve the same functionality. In a conceptual sense, any arrangement of components to achieve the same functionality is effectively “associated” such that the desired functionality is achieved. Hence, any two components herein combined to achieve a particular functionality can be seen as “associated with” each other such that the desired functionality is achieved, irrespective of architectures or intermedial components. Likewise, any two components so associated can also be viewed as being “operably connected,” or “operably coupled,” to each other to achieve the desired functionality.
- While particular embodiments of the present invention have been shown and described, it will be obvious to those skilled in the art that, based upon the teachings herein, changes and modifications may be made without departing from this invention and its broader aspects and, therefore, the appended claims are to encompass within their scope all such changes and modifications as are within the true spirit and scope of this invention. Furthermore, it is to be understood that the invention is solely defined by the appended claims. It will be understood by those within the art that, in general, terms used herein, and especially in the appended claims (e.g., bodies of the appended claims) are generally intended as “open” terms (e.g., the term “including” should be interpreted as “including but not limited to,” the term “having” should be interpreted as “having at least,” the term “includes” should be interpreted as “includes but is not limited to,” etc.). It will be further understood by those within the art that if a specific number of an introduced claim recitation is intended, such an intent will be explicitly recited in the claim, and in the absence of such recitation no such intent is present. For example, as an aid to understanding, the following appended claims may contain usage of the introductory phrases “at least one” and “one or more” to introduce claim recitations. However, the use of such phrases should not be construed to imply that the introduction of a claim recitation by the indefinite articles “a” or “an” limits any particular claim containing such introduced claim recitation to inventions containing only one such recitation, even when the same claim includes the introductory phrases “one or more” or “at least one” and indefinite articles such as “a” or “an” (e.g., “a” and/or “an” should typically be interpreted to mean “at least one” or “one or more”); the same holds true for the use of definite articles used to introduce claim recitations. In addition, even if a specific number of an introduced claim recitation is explicitly recited, those skilled in the art will recognize that such recitation should typically be interpreted to mean at least the recited number (e.g., the bare recitation of “two recitations,” without other modifiers, typically means at least two recitations, or two or more recitations).
- Accordingly, the invention is not limited except as by the appended claims.
Claims (20)
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Cited By (38)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20160030737A1 (en) * | 2013-03-15 | 2016-02-04 | The Regents Of The University Of California | Multi-site transcutaneous electrical stimulation of the spinal cord for facilitation of locomotion |
US9409011B2 (en) | 2011-01-21 | 2016-08-09 | California Institute Of Technology | Method of constructing an implantable microelectrode array |
US20160250470A1 (en) * | 2015-02-26 | 2016-09-01 | Stryker Corporation | Rehabilitation Monitor And Pain Treatment Assembly |
WO2017035140A1 (en) * | 2015-08-26 | 2017-03-02 | Boston Scientific Neuromodulation Corporation | Machine learning to optimize spinal cord stimulation |
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WO2018026974A1 (en) * | 2016-08-02 | 2018-02-08 | Motometrix Inc. | System and method for identification of brain injury |
US9907958B2 (en) | 2011-01-03 | 2018-03-06 | The Regents Of The University Of California | High density epidural stimulation for facilitation of locomotion, posture, voluntary movement, and recovery of autonomic, sexual, vasomotor, and cognitive function after neurological injury |
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US10016600B2 (en) | 2013-05-30 | 2018-07-10 | Neurostim Solutions, Llc | Topical neurological stimulation |
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US10092750B2 (en) | 2011-11-11 | 2018-10-09 | Neuroenabling Technologies, Inc. | Transcutaneous neuromodulation system and methods of using same |
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US10124166B2 (en) | 2011-11-11 | 2018-11-13 | Neuroenabling Technologies, Inc. | Non invasive neuromodulation device for enabling recovery of motor, sensory, autonomic, sexual, vasomotor and cognitive function |
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US10773074B2 (en) | 2014-08-27 | 2020-09-15 | The Regents Of The University Of California | Multi-electrode array for spinal cord epidural stimulation |
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US10953225B2 (en) | 2017-11-07 | 2021-03-23 | Neurostim Oab, Inc. | Non-invasive nerve activator with adaptive circuit |
US11077301B2 (en) | 2015-02-21 | 2021-08-03 | NeurostimOAB, Inc. | Topical nerve stimulator and sensor for bladder control |
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US11229789B2 (en) | 2013-05-30 | 2022-01-25 | Neurostim Oab, Inc. | Neuro activator with controller |
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Families Citing this family (142)
Publication number | Priority date | Publication date | Assignee | Title |
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US6907884B2 (en) | 2002-09-30 | 2005-06-21 | Depay Acromed, Inc. | Method of straddling an intraosseous nerve |
US8972017B2 (en) | 2005-11-16 | 2015-03-03 | Bioness Neuromodulation Ltd. | Gait modulation system and method |
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US10588691B2 (en) | 2012-09-12 | 2020-03-17 | Relievant Medsystems, Inc. | Radiofrequency ablation of tissue within a vertebral body |
EP2914186B1 (en) | 2012-11-05 | 2019-03-13 | Relievant Medsystems, Inc. | Systems for creating curved paths through bone and modulating nerves within the bone |
US9440070B2 (en) | 2012-11-26 | 2016-09-13 | Thyne Global, Inc. | Wearable transdermal electrical stimulation devices and methods of using them |
US10537703B2 (en) | 2012-11-26 | 2020-01-21 | Thync Global, Inc. | Systems and methods for transdermal electrical stimulation to improve sleep |
US11033731B2 (en) | 2015-05-29 | 2021-06-15 | Thync Global, Inc. | Methods and apparatuses for transdermal electrical stimulation |
US10814131B2 (en) | 2012-11-26 | 2020-10-27 | Thync Global, Inc. | Apparatuses and methods for neuromodulation |
US9421366B2 (en) | 2012-12-14 | 2016-08-23 | Case Western Reserve University | Methods of treating medical conditions by population based encoding of neural information |
WO2014111882A1 (en) * | 2013-01-16 | 2014-07-24 | Egzotech Spółka Z O.O. | Rehabilitation device |
JP2016515026A (en) * | 2013-03-13 | 2016-05-26 | デューク ユニバーシティ | System and method for optimizing spinal cord stimulation by applying electrical stimulation |
KR101648463B1 (en) * | 2013-05-29 | 2016-08-16 | 주식회사 아이엠바이오 | Bionic Implant Device |
US10293161B2 (en) | 2013-06-29 | 2019-05-21 | Thync Global, Inc. | Apparatuses and methods for transdermal electrical stimulation of nerves to modify or induce a cognitive state |
WO2014210595A1 (en) | 2013-06-29 | 2014-12-31 | Thync, Inc. | Transdermal electrical stimulation devices and methods for modifying or inducing cognitive state |
JP2016525390A (en) * | 2013-07-11 | 2016-08-25 | アナリティカ リミテッド | Stimulus and electromyogram detection |
US9724151B2 (en) | 2013-08-08 | 2017-08-08 | Relievant Medsystems, Inc. | Modulating nerves within bone using bone fasteners |
US9265943B2 (en) | 2013-09-13 | 2016-02-23 | Ybrain Inc. | Method for stimulating living body more accurately and apparatus using the same |
CN103480086B (en) * | 2013-09-27 | 2015-10-14 | 江苏德长医疗科技有限公司 | Networking rehabilitation system |
EP3082946B1 (en) * | 2013-12-16 | 2021-08-11 | Case Western Reserve University | Patterned stimulation intensity for neural stimulation |
US9707391B2 (en) | 2013-12-22 | 2017-07-18 | The Research Foundation Of The City University Of New York | Method for modulation of effector organs |
US9707390B2 (en) | 2013-12-22 | 2017-07-18 | The Research Foundation Of The City University Of New York | Apparatus for modulation of effector organs |
DK3082947T3 (en) * | 2013-12-22 | 2019-06-17 | Univ City New York Res Found | Transspinal DC modulation systems |
CN106573138A (en) | 2014-02-27 | 2017-04-19 | 赛威医疗公司 | Methods and apparatuses for user control of neurostimulation |
US9867985B2 (en) | 2014-03-24 | 2018-01-16 | Bioness Inc. | Systems and apparatus for gait modulation and methods of use |
JP6701096B2 (en) | 2014-05-17 | 2020-05-27 | ハイイン エクイティ インベストメント ファンド エル.ピー. | Method and apparatus for ensemble waveform application using transcutaneous nerve stimulation |
EP3903875A1 (en) | 2014-05-20 | 2021-11-03 | Nevro Corporation | Implanted pulse generators with reduced power consumption via signal strength/duration characteristics, and associated systems and methods |
KR20170063440A (en) | 2014-05-25 | 2017-06-08 | 하이인 에쿼티 인베스트먼트 펀드 엘.피. | Wearable transdermal neurostimulators |
US9333334B2 (en) | 2014-05-25 | 2016-05-10 | Thync, Inc. | Methods for attaching and wearing a neurostimulator |
WO2016004152A2 (en) | 2014-07-03 | 2016-01-07 | Duke University | Systems and methods for model-based optimization of spinal cord stimulation electrodes and devices |
US10398369B2 (en) | 2014-08-08 | 2019-09-03 | Medtronic Xomed, Inc. | Wireless stimulation probe device for wireless nerve integrity monitoring systems |
CN107205641A (en) * | 2014-08-29 | 2017-09-26 | 因赛飞公司 | Method and apparatus for strengthening nervous function |
EP3197539A4 (en) * | 2014-09-26 | 2018-03-14 | Duke University | Systems and methods for spinal cord stimulation |
WO2016057396A1 (en) * | 2014-10-06 | 2016-04-14 | The Trustees Of Princeton University | Adaptive cognitive prosthetic and applications thereof |
US9498628B2 (en) * | 2014-11-21 | 2016-11-22 | Medtronic, Inc. | Electrode selection for electrical stimulation therapy |
WO2016109851A1 (en) | 2015-01-04 | 2016-07-07 | Thync, Inc. | Methods and apparatuses for transdermal stimulation of the outer ear |
US11534608B2 (en) | 2015-01-04 | 2022-12-27 | Ist, Llc | Methods and apparatuses for transdermal stimulation of the outer ear |
CN104587599B (en) * | 2015-01-16 | 2016-10-12 | 江苏科技大学 | The injection nerve stimulator that a kind of micro cell is powered |
US10130813B2 (en) | 2015-02-10 | 2018-11-20 | Neuropace, Inc. | Seizure onset classification and stimulation parameter selection |
US11980465B2 (en) | 2015-04-03 | 2024-05-14 | Medtronic Xomed, Inc. | System and method for omni-directional bipolar stimulation of nerve tissue of a patient via a bipolar stimulation probe |
US10039915B2 (en) | 2015-04-03 | 2018-08-07 | Medtronic Xomed, Inc. | System and method for omni-directional bipolar stimulation of nerve tissue of a patient via a surgical tool |
AU2016249420A1 (en) * | 2015-04-17 | 2017-11-09 | Micron Devices Llc | Flexible circuit for an implantable device |
JP6541776B2 (en) * | 2015-05-01 | 2019-07-10 | Cyberdyne株式会社 | Functional improvement evaluation device for model animals and neural cell culture device |
KR20160133306A (en) | 2015-05-12 | 2016-11-22 | 삼성전자주식회사 | wearable device and method for providing feedback |
CN107847744A (en) | 2015-06-01 | 2018-03-27 | 赛威医疗公司 | Apparatus and method for nerve modulation |
DE102015108861A1 (en) * | 2015-06-03 | 2016-12-08 | Cortec Gmbh | Method and apparatus for neurostimulation |
CN107735020A (en) * | 2015-06-04 | 2018-02-23 | 因维克塔医药公司 | Method and apparatus for disposing ekbom syndrome |
US10076667B2 (en) | 2015-06-09 | 2018-09-18 | Nuvectra Corporation | System and method of performing computer assisted stimulation programming (CASP) with a non-zero starting value customized to a patient |
US9669227B2 (en) | 2015-06-09 | 2017-06-06 | Nuvectra Corporation | Systems, methods, and devices for generating arbitrary stimulation waveforms |
US10052490B2 (en) | 2015-06-09 | 2018-08-21 | Nuvectra Corporation | Systems, methods, and devices for performing electronically controlled test stimulation |
US9872988B2 (en) | 2015-06-09 | 2018-01-23 | Nuvectra Corporation | Systems, methods, and devices for evaluating lead placement based on patient physiological responses |
US9750946B2 (en) | 2015-06-09 | 2017-09-05 | Nuvectra Corporation | Systems, methods, and devices for evaluating lead placement based on generated visual representations of sacrum and lead |
JP6796089B2 (en) * | 2015-06-22 | 2020-12-02 | リサーチ ファウンデーション オブ ザ シティー ユニバーシティ オブ ニューヨークResearch Foundation Of The City University Of New York | Methods and devices for adjusting effectors |
EP3319683A4 (en) | 2015-07-10 | 2018-12-26 | Axonics Modulation Technologies, Inc. | Implantable nerve stimulator having internal electronics without asic and methods of use |
WO2017027703A1 (en) * | 2015-08-11 | 2017-02-16 | Rhode Island Hospital | Methods for detecting neuronal oscillation in the spinal cord associated with pain and diseases or disorders of the nervous system |
CN108135519B (en) * | 2015-08-18 | 2022-08-09 | 路易斯维尔大学研究基金会公司 | Synchronous pulse detector |
CN108136182B (en) * | 2015-08-18 | 2022-03-18 | 路易斯维尔大学研究基金会公司 | Method of applying epidural electrical stimulation |
GB201518205D0 (en) | 2015-10-14 | 2015-11-25 | Univ Newcastle | Probe response signals |
US11458308B2 (en) * | 2015-12-10 | 2022-10-04 | Carlo Menon | Electrical stimulation device for improving fluidity of motion |
US10300277B1 (en) | 2015-12-14 | 2019-05-28 | Nevro Corp. | Variable amplitude signals for neurological therapy, and associated systems and methods |
WO2017106411A1 (en) | 2015-12-15 | 2017-06-22 | Cerevast Medical, Inc. | Electrodes having surface exclusions |
US9956405B2 (en) | 2015-12-18 | 2018-05-01 | Thyne Global, Inc. | Transdermal electrical stimulation at the neck to induce neuromodulation |
WO2017106878A1 (en) | 2015-12-18 | 2017-06-22 | Thync Global, Inc. | Apparatuses and methods for transdermal electrical stimulation of nerves to modify or induce a cognitive state |
RU2627359C2 (en) | 2015-12-29 | 2017-08-07 | Общество с ограниченной ответственностью "Косима" (ООО "Косима") | Device for noninvasive electric stimulation of the spinal cord |
US10183167B2 (en) * | 2015-12-30 | 2019-01-22 | Boston Scientific Neuromodulation Corporation | Method and apparatus for composing spatio-temporal patterns of neurostimulation for cumulative effects |
WO2017117434A1 (en) | 2015-12-30 | 2017-07-06 | Boston Scientific Neuromodulation Corporation | System for guided optimization of neurostimulation patterns |
AU2017206723B2 (en) | 2016-01-11 | 2021-11-25 | Bioness Inc. | Systems and apparatus for gait modulation and methods of use |
WO2017132566A1 (en) | 2016-01-27 | 2017-08-03 | The Regents Of The University Of California | Wireless implant for motor function recovery after spinal cord injury |
JP6334588B2 (en) * | 2016-03-10 | 2018-05-30 | H2L株式会社 | Electrical stimulation system |
US10646708B2 (en) | 2016-05-20 | 2020-05-12 | Thync Global, Inc. | Transdermal electrical stimulation at the neck |
CN109310329A (en) * | 2016-05-31 | 2019-02-05 | 加利福尼亚大学董事会 | System and method for reducing noise caused by the stimulation artifact in the nerve signal received as neuromodulation device |
US11103708B2 (en) * | 2016-06-01 | 2021-08-31 | Duke University | Systems and methods for determining optimal temporal patterns of neural stimulation |
CN105978110B (en) * | 2016-07-15 | 2019-08-20 | 上海力声特医学科技有限公司 | A kind of wireless charging device and its sacral nerve stimulation system |
KR101838150B1 (en) * | 2016-08-31 | 2018-03-15 | 가천대학교 산학협력단 | Photodiode array based sub-retinal prosthetic device and method thereby |
US10849517B2 (en) | 2016-09-19 | 2020-12-01 | Medtronic Xomed, Inc. | Remote control module for instruments |
CA3043007A1 (en) | 2016-11-07 | 2018-05-11 | Micro-Leads, Inc. | Multi-electrode array with unitary body |
US11285321B2 (en) | 2016-11-15 | 2022-03-29 | The Regents Of The University Of California | Methods and apparatuses for improving peripheral nerve function |
EP3323466B1 (en) * | 2016-11-16 | 2024-04-03 | ONWARD Medical N.V. | An active closed-loop medical system |
EP3544495A4 (en) * | 2016-11-25 | 2020-08-19 | Kinaptic, LLC | Haptic human machine interface and wearable electronics methods and apparatus |
CN106730337A (en) * | 2016-12-22 | 2017-05-31 | 北京品驰医疗设备有限公司 | A kind of vagus nerve stimulator electronic prescription configuration system of quickly-chargeable |
US11027122B2 (en) | 2017-01-19 | 2021-06-08 | Micro-Leads, Inc. | Spinal cord stimulation method to treat lateral neural tissues |
US10523258B2 (en) | 2017-03-06 | 2019-12-31 | Samsung Electronics Co., Ltd. | Communication device to perform wireless communication and wireless power transfer, and electrode device to transmit and receive electrical signal from target |
US11116980B2 (en) * | 2017-04-07 | 2021-09-14 | Medtronic, Inc. | Complex variation of electrical stimulation therapy parameters |
US20180344171A1 (en) * | 2017-06-06 | 2018-12-06 | Myant Inc. | Sensor band for multimodal sensing of biometric data |
US11728018B2 (en) | 2017-07-02 | 2023-08-15 | Oberon Sciences Ilan Ltd | Subject-specific system and method for prevention of body adaptation for chronic treatment of disease |
US11257259B2 (en) * | 2017-08-15 | 2022-02-22 | Siemens Healthcare Gmbh | Topogram prediction from surface data in medical imaging |
KR102062252B1 (en) * | 2017-08-30 | 2020-01-03 | 부산대학교 산학협력단 | Intraoperative Neuromonitoring System Using Bio-pressure Sensor |
US10821286B2 (en) * | 2017-09-08 | 2020-11-03 | Medtronic, Inc. | Electrical stimulator configuration with initial high-density stimulation |
WO2019070406A1 (en) * | 2017-10-04 | 2019-04-11 | Boston Scientific Neuromodulation Corporation | Adjustment of stimulation in a stimulator using detected evoked compound action potentials |
WO2019087196A1 (en) * | 2017-11-05 | 2019-05-09 | Oberon Sciences Ilan Ltd. | A subject-tailored continuously developing randomization based method for improving organ function |
CR20200357A (en) | 2018-01-30 | 2021-03-29 | Nevro Corp | Efficient use of an implantable pulse generator battery, and associated systems and methods |
US11992686B2 (en) | 2018-03-16 | 2024-05-28 | The Regents Of The University Of California | Flexible spinal cord stimulators for pain and trauma management through neuromodulation |
US11278724B2 (en) | 2018-04-24 | 2022-03-22 | Thync Global, Inc. | Streamlined and pre-set neuromodulators |
JP2021522934A (en) * | 2018-05-10 | 2021-09-02 | コーニンクレッカ フィリップス エヌ ヴェKoninklijke Philips N.V. | Systems and methods for enhancing sensory stimuli delivered to users using neural networks |
EP3793673B1 (en) * | 2018-05-17 | 2023-07-26 | Boston Scientific Scimed Inc. | System for controlling blood pressure |
CN109173047A (en) * | 2018-08-10 | 2019-01-11 | 复旦大学 | A kind of non-intrusion type closed loop transcranial electrical stimulation device |
KR102118713B1 (en) * | 2018-08-14 | 2020-06-04 | 광운대학교 산학협력단 | Wireless transmission medical device with a plurality of brainwave collection sensors of multichannel ECoG electrodes using F-TFTA for brain disease treatment |
CN112867533A (en) * | 2018-08-14 | 2021-05-28 | 神经触发有限公司 | Method and apparatus for percutaneous facial nerve stimulation and application thereof |
RU187884U1 (en) * | 2018-08-15 | 2019-03-21 | Андрей Владимирович Цимбалов | Neurostimulation apparatus |
US11058875B1 (en) | 2018-09-19 | 2021-07-13 | Nevro Corp. | Motor function in spinal cord injury patients via electrical stimulation, and associated systems and methods |
US11602633B2 (en) * | 2018-10-22 | 2023-03-14 | Pathmaker Neurosystems Inc. | Method and apparatus for controlling multi-site neurostimulation |
DE18205814T1 (en) * | 2018-11-13 | 2020-12-24 | Gtx Medical B.V. | MOTION RECONSTRUCTION CONTROL SYSTEM |
KR20240010560A (en) | 2018-11-20 | 2024-01-23 | 뉴에너치 인크 | Electrical stimulation device for applying frequency and peak voltage having inverse relationship |
KR102238067B1 (en) * | 2018-12-12 | 2021-04-08 | 광운대학교 산학협력단 | EEG detection and nerve stimulation system including a wearable EEG headset communicated with 3D headup display and method thereof |
US11395924B2 (en) | 2019-01-07 | 2022-07-26 | Micro-Leads, Inc. | Implantable devices with welded multi-contact electrodes and continuous conductive elements |
US11590352B2 (en) | 2019-01-29 | 2023-02-28 | Nevro Corp. | Ramped therapeutic signals for modulating inhibitory interneurons, and associated systems and methods |
US11481578B2 (en) | 2019-02-22 | 2022-10-25 | Neuropace, Inc. | Systems and methods for labeling large datasets of physiological records based on unsupervised machine learning |
US11612750B2 (en) | 2019-03-19 | 2023-03-28 | Neuropace, Inc. | Methods and systems for optimizing therapy using stimulation mimicking natural seizures |
CN111013012A (en) * | 2019-03-26 | 2020-04-17 | 中国人民解放军军事科学院军事医学研究院 | Remote monitoring system of implantable instrument |
US11813446B2 (en) | 2019-04-05 | 2023-11-14 | University Of Louisville Research Foundation, Inc. | Methods of for improvement of lower urinary tract function |
US20220193415A1 (en) * | 2019-04-05 | 2022-06-23 | University Of Louisville Research Foundation, Inc. | Closed loop control system |
US11458303B2 (en) * | 2019-04-15 | 2022-10-04 | Medtronic, Inc. | Implantable medical leads having fewer conductors than distal electrodes |
WO2020242900A1 (en) | 2019-05-24 | 2020-12-03 | Axonics Modulation Technologies, Inc. | Trainer device for a neurostimulator programmer and associated methods of use with a neurostimulation system |
ES2798182B2 (en) * | 2019-06-06 | 2021-04-22 | Univ Pablo De Olavide | System for neurostimulation |
US11065461B2 (en) | 2019-07-08 | 2021-07-20 | Bioness Inc. | Implantable power adapter |
WO2021021886A1 (en) * | 2019-07-29 | 2021-02-04 | Mayo Foundation For Medical Education And Research | Epidural stimulation and spinal structure locating techniques |
AU2020346827A1 (en) | 2019-09-12 | 2022-03-31 | Relievant Medsystems, Inc. | Systems and methods for tissue modulation |
KR102334427B1 (en) * | 2019-10-29 | 2021-12-03 | 주식회사 뉴아인 | Multi mode system for stimulating facial nerves |
KR102387763B1 (en) * | 2020-02-18 | 2022-04-18 | 서울대학교산학협력단 | Totally implantable visual prosthetic system and operating method thereof |
EP3875142A1 (en) * | 2020-03-04 | 2021-09-08 | ONWARD Medical B.V. | A neuromodulation system |
CN111408044A (en) * | 2020-03-31 | 2020-07-14 | 北京百科康讯科技有限公司 | Controller, voice recognition method thereof and spinal cord epidural stimulation system |
JP7462213B2 (en) | 2020-04-03 | 2024-04-05 | 国立大学法人千葉大学 | Electrical Therapy Device |
RU206363U1 (en) * | 2020-05-15 | 2021-09-07 | федеральное государственное бюджетное образовательное учреждение высшего образования "Санкт-Петербургский государственный университет" | NEURAL IMPLANT |
US11752326B2 (en) * | 2020-06-06 | 2023-09-12 | Battelle Memorial Institute | Portable and wearable hand-grasp neuro-orthosis |
CN111905258B (en) * | 2020-08-04 | 2023-07-25 | 太原理工大学 | Force and electricity stimulation physiotherapy instrument capable of being used at multiple positions and parameter setting method |
US11897134B2 (en) | 2020-08-12 | 2024-02-13 | General Electric Company | Configuring a simulator for robotic machine learning |
US11654566B2 (en) | 2020-08-12 | 2023-05-23 | General Electric Company | Robotic activity decomposition |
WO2022258212A1 (en) * | 2021-06-11 | 2022-12-15 | INBRAIN Neuroelectronics S.L. | Neurostimulation system for deep brain stimulation |
WO2022271777A1 (en) * | 2021-06-23 | 2022-12-29 | Brown University | Systems and method for modulating the spinal cord based on spinal field potentials |
KR102567821B1 (en) * | 2021-07-05 | 2023-08-18 | (재)예수병원유지재단 | Sympathetic nerve stimulation apparatus |
CN113546307A (en) * | 2021-07-15 | 2021-10-26 | 清华大学 | Motion adjustment device and method, electronic apparatus, and storage medium |
WO2023177690A1 (en) * | 2022-03-14 | 2023-09-21 | Canary Medical Switzerland Ag | Implantable medical device with sensing and communication functionality utilizing a substrate antenna |
CN114870250B (en) * | 2022-04-20 | 2022-11-25 | 浙江帝诺医疗科技有限公司 | Nerve regulation system and nerve regulation stimulator based on same |
WO2023225099A1 (en) * | 2022-05-19 | 2023-11-23 | University Of Washington | Methods and systems to reduce symptoms of cerebral palsy in children |
CN117045966B (en) * | 2023-09-11 | 2024-04-30 | 北京领创医谷科技发展有限责任公司 | Combined mode adjusting method and device of nerve stimulator |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090112281A1 (en) * | 2007-10-26 | 2009-04-30 | Medtronic, Inc. | Medical device configuration based on sensed brain signals |
US20100185253A1 (en) * | 2009-01-19 | 2010-07-22 | Dimarco Anthony F | Respiratory muscle activation by spinal cord stimulation |
US20130123568A1 (en) * | 2010-07-01 | 2013-05-16 | Stimdesigns Llc | Universal closed-loop electrical stimulation system |
Family Cites Families (252)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3543761A (en) | 1967-10-05 | 1970-12-01 | Univ Minnesota | Bladder stimulating method |
US3662758A (en) | 1969-06-30 | 1972-05-16 | Mentor Corp | Stimulator apparatus for muscular organs with external transmitter and implantable receiver |
US3724467A (en) | 1971-04-23 | 1973-04-03 | Avery Labor Inc | Electrode implant for the neuro-stimulation of the spinal cord |
US4044774A (en) | 1976-02-23 | 1977-08-30 | Medtronic, Inc. | Percutaneously inserted spinal cord stimulation lead |
US4102344A (en) | 1976-11-15 | 1978-07-25 | Mentor Corporation | Stimulator apparatus for internal body organ |
US4141365A (en) | 1977-02-24 | 1979-02-27 | The Johns Hopkins University | Epidural lead electrode and insertion needle |
US4285347A (en) | 1979-07-25 | 1981-08-25 | Cordis Corporation | Stabilized directional neural electrode lead |
US4340063A (en) | 1980-01-02 | 1982-07-20 | Empi, Inc. | Stimulation device |
US4379462A (en) | 1980-10-29 | 1983-04-12 | Neuromed, Inc. | Multi-electrode catheter assembly for spinal cord stimulation |
US4414986A (en) | 1982-01-29 | 1983-11-15 | Medtronic, Inc. | Biomedical stimulation lead |
US4538624A (en) | 1982-12-08 | 1985-09-03 | Cordis Corporation | Method for lead introduction and fixation |
US4549556A (en) | 1982-12-08 | 1985-10-29 | Cordis Corporation | Implantable lead |
US4800898A (en) | 1983-10-07 | 1989-01-31 | Cordis Corporation | Neural stimulator electrode element and lead |
US4934368A (en) | 1988-01-21 | 1990-06-19 | Myo/Kinetics Systems, Inc. | Multi-electrode neurological stimulation apparatus |
US5081989A (en) | 1989-04-07 | 1992-01-21 | Sigmedics, Inc. | Microprocessor-controlled enhanced multiplexed functional electrical stimulator for surface stimulation in paralyzed patients |
US5002053A (en) | 1989-04-21 | 1991-03-26 | University Of Arkansas | Method of and device for inducing locomotion by electrical stimulation of the spinal cord |
US5031618A (en) | 1990-03-07 | 1991-07-16 | Medtronic, Inc. | Position-responsive neuro stimulator |
US5121754A (en) | 1990-08-21 | 1992-06-16 | Medtronic, Inc. | Lateral displacement percutaneously inserted epidural lead |
EP0532143A1 (en) | 1991-09-12 | 1993-03-17 | BIOTRONIK Mess- und Therapiegeräte GmbH & Co Ingenieurbüro Berlin | Neurostimulator |
EP0580928A1 (en) | 1992-07-31 | 1994-02-02 | ARIES S.r.l. | A spinal electrode catheter |
US5344439A (en) | 1992-10-30 | 1994-09-06 | Medtronic, Inc. | Catheter with retractable anchor mechanism |
US5417719A (en) | 1993-08-25 | 1995-05-23 | Medtronic, Inc. | Method of using a spinal cord stimulation lead |
US5501703A (en) | 1994-01-24 | 1996-03-26 | Medtronic, Inc. | Multichannel apparatus for epidural spinal cord stimulator |
US5562718A (en) | 1994-06-03 | 1996-10-08 | Palermo; Francis X. | Electronic neuromuscular stimulation device |
US5733322A (en) | 1995-05-23 | 1998-03-31 | Medtronic, Inc. | Positive fixation percutaneous epidural neurostimulation lead |
US6066163A (en) * | 1996-02-02 | 2000-05-23 | John; Michael Sasha | Adaptive brain stimulation method and system |
CA2171067A1 (en) | 1996-03-05 | 1997-09-06 | Brian J. Andrews | Neural prosthesis |
US6505078B1 (en) | 1996-04-04 | 2003-01-07 | Medtronic, Inc. | Technique for adjusting the locus of excitation of electrically excitable tissue |
US6609031B1 (en) | 1996-06-07 | 2003-08-19 | Advanced Neuromodulation Systems, Inc. | Multiprogrammable tissue stimulator and method |
ES2222515T3 (en) | 1996-06-13 | 2005-02-01 | The Victoria University Of Manchester | STIMULATION OF MUSCLES. |
US5983141A (en) | 1996-06-27 | 1999-11-09 | Radionics, Inc. | Method and apparatus for altering neural tissue function |
RU2130326C1 (en) | 1996-08-20 | 1999-05-20 | Шапков Юрий Тимофеевич | Method for treating patients having injured spinal cord |
RU2141851C1 (en) | 1997-03-31 | 1999-11-27 | Российский научный центр реабилитации и физиотерапии | Method of treatment of children's displastic scoliosis |
US5948007A (en) | 1997-04-30 | 1999-09-07 | Medtronic, Inc. | Dual channel implantation neurostimulation techniques |
US6319241B1 (en) | 1998-04-30 | 2001-11-20 | Medtronic, Inc. | Techniques for positioning therapy delivery elements within a spinal cord or a brain |
WO1999056818A1 (en) | 1998-04-30 | 1999-11-11 | Medtronic, Inc. | Multiple electrode lead body for spinal cord stimulation |
US7209787B2 (en) | 1998-08-05 | 2007-04-24 | Bioneuronics Corporation | Apparatus and method for closed-loop intracranial stimulation for optimal control of neurological disease |
US6366813B1 (en) | 1998-08-05 | 2002-04-02 | Dilorenzo Daniel J. | Apparatus and method for closed-loop intracranical stimulation for optimal control of neurological disease |
US6104957A (en) | 1998-08-21 | 2000-08-15 | Alo; Kenneth M. | Epidural nerve root stimulation with lead placement method |
US6470213B1 (en) | 1999-03-30 | 2002-10-22 | Kenneth A. Alley | Implantable medical device |
RU2178319C2 (en) | 1999-05-11 | 2002-01-20 | Российский научно-исследовательский нейрохирургический институт им. проф. А.Л. Поленова | Electric stimulator |
US6516227B1 (en) | 1999-07-27 | 2003-02-04 | Advanced Bionics Corporation | Rechargeable spinal cord stimulator system |
AU7064200A (en) | 1999-08-20 | 2001-03-19 | Regents Of The University Of California, The | Method, apparatus and system for automation of body weight support training (bwst) of biped locomotion over a treadmill using a programmable stepper device (psd) operating like an exoskeleton drive system from a fixed base |
US6308103B1 (en) | 1999-09-13 | 2001-10-23 | Medtronic Inc. | Self-centering epidural spinal cord lead and method |
RU2160127C1 (en) | 1999-09-16 | 2000-12-10 | Вязников Александр Леонидович | Method for treating diseases and applying local impulse electric stimulation |
US7949395B2 (en) | 1999-10-01 | 2011-05-24 | Boston Scientific Neuromodulation Corporation | Implantable microdevice with extended lead and remote electrode |
RU2192897C2 (en) | 1999-11-17 | 2002-11-20 | Красноярская государственная медицинская академия | Method for treating cases of postinsult pareses |
AU5439801A (en) | 1999-12-17 | 2001-06-25 | Advanced Bionics Corporation | Magnitude programming for implantable electrical stimulator |
US6885888B2 (en) * | 2000-01-20 | 2005-04-26 | The Cleveland Clinic Foundation | Electrical stimulation of the sympathetic nerve chain |
US7096070B1 (en) | 2000-02-09 | 2006-08-22 | Transneuronix, Inc. | Medical implant device for electrostimulation using discrete micro-electrodes |
US7305268B2 (en) * | 2000-07-13 | 2007-12-04 | Northstar Neurscience, Inc. | Systems and methods for automatically optimizing stimulus parameters and electrode configurations for neuro-stimulators |
US7831305B2 (en) | 2001-10-15 | 2010-11-09 | Advanced Neuromodulation Systems, Inc. | Neural stimulation system and method responsive to collateral neural activity |
US7024247B2 (en) | 2001-10-15 | 2006-04-04 | Northstar Neuroscience, Inc. | Systems and methods for reducing the likelihood of inducing collateral neural activity during neural stimulation threshold test procedures |
US6895283B2 (en) | 2000-08-10 | 2005-05-17 | Advanced Neuromodulation Systems, Inc. | Stimulation/sensing lead adapted for percutaneous insertion |
US6662053B2 (en) | 2000-08-17 | 2003-12-09 | William N. Borkan | Multichannel stimulator electronics and methods |
US6871099B1 (en) * | 2000-08-18 | 2005-03-22 | Advanced Bionics Corporation | Fully implantable microstimulator for spinal cord stimulation as a therapy for chronic pain |
JP2002200178A (en) | 2000-12-28 | 2002-07-16 | Japan Science & Technology Corp | Pelvis surface stimulation electrode instrument and undergarment for wearing the electrode instrument |
US7065408B2 (en) | 2001-01-11 | 2006-06-20 | Herman Richard M | Method for restoring gait in individuals with chronic spinal cord injury |
US7299096B2 (en) | 2001-03-08 | 2007-11-20 | Northstar Neuroscience, Inc. | System and method for treating Parkinson's Disease and other movement disorders |
US6892098B2 (en) | 2001-04-26 | 2005-05-10 | Biocontrol Medical Ltd. | Nerve stimulation for treating spasticity, tremor, muscle weakness, and other motor disorders |
US6839594B2 (en) | 2001-04-26 | 2005-01-04 | Biocontrol Medical Ltd | Actuation and control of limbs through motor nerve stimulation |
JP4156933B2 (en) | 2001-05-16 | 2008-09-24 | フォンダシオン スイス プール レ シベルテーゼ | Device for retraining and / or training of human lower limbs |
US6685729B2 (en) | 2001-06-29 | 2004-02-03 | George Gonzalez | Process for testing and treating aberrant sensory afferents and motors efferents |
AU2002318466A1 (en) | 2001-07-03 | 2003-01-21 | The Trustees Of The University Of Pennsylvania | Device and method for electrically inducing osteogenesis in the spine |
US7263402B2 (en) | 2001-08-13 | 2007-08-28 | Advanced Bionics Corporation | System and method of rapid, comfortable parameter switching in spinal cord stimulation |
AU2002334749A1 (en) | 2001-09-28 | 2003-04-07 | Northstar Neuroscience, Inc. | Methods and implantable apparatus for electrical therapy |
CA2461934A1 (en) | 2001-09-28 | 2003-04-03 | Meagan Medical, Inc. | Method and apparatus for controlling percutaneous electrical signals |
US7127296B2 (en) | 2001-11-02 | 2006-10-24 | Advanced Bionics Corporation | Method for increasing the therapeutic ratio/usage range in a neurostimulator |
US6975907B2 (en) | 2001-11-13 | 2005-12-13 | Dynamed Systems, Llc | Apparatus and method for repair of spinal cord injury |
US6829510B2 (en) * | 2001-12-18 | 2004-12-07 | Ness Neuromuscular Electrical Stimulation Systems Ltd. | Surface neuroprosthetic device having an internal cushion interface system |
US7110820B2 (en) | 2002-02-05 | 2006-09-19 | Tcheng Thomas K | Responsive electrical stimulation for movement disorders |
AUPS042802A0 (en) | 2002-02-11 | 2002-03-07 | Neopraxis Pty Ltd | Distributed functional electrical stimulation system |
US7239920B1 (en) | 2002-02-12 | 2007-07-03 | Advanced Bionics Corporation | Neural stimulation system providing auto adjustment of stimulus output as a function of sensed pressure changes |
US7697995B2 (en) | 2002-04-25 | 2010-04-13 | Medtronic, Inc. | Surgical lead paddle |
US6937891B2 (en) | 2002-04-26 | 2005-08-30 | Medtronic, Inc. | Independent therapy programs in an implantable medical device |
US6950706B2 (en) | 2002-04-26 | 2005-09-27 | Medtronic, Inc. | Wave shaping for an implantable medical device |
US7349739B2 (en) | 2002-05-03 | 2008-03-25 | Afferent Corporation | Method and apparatus for neurophysiologic performance |
US8147421B2 (en) * | 2003-01-15 | 2012-04-03 | Nuvasive, Inc. | System and methods for determining nerve direction to a surgical instrument |
WO2003101533A1 (en) | 2002-05-29 | 2003-12-11 | Oklahoma Foundation For Digestive Research | Spinal cord stimulation as treatment for functional bowel disorders |
US7228179B2 (en) | 2002-07-26 | 2007-06-05 | Advanced Neuromodulation Systems, Inc. | Method and apparatus for providing complex tissue stimulation patterns |
US7047079B2 (en) | 2002-07-26 | 2006-05-16 | Advanced Neuromodulation Systems, Inc. | Method and system for energy conservation in implantable stimulation devices |
US7027860B2 (en) | 2002-08-29 | 2006-04-11 | Department Of Veterans Affairs | Microstimulator neural prosthesis |
WO2004036370A2 (en) | 2002-10-15 | 2004-04-29 | Medtronic Inc. | Channel-selective blanking for a medical device system |
AU2003285888A1 (en) | 2002-10-15 | 2004-05-04 | Medtronic Inc. | Medical device system with relaying module for treatment of nervous system disorders |
US7797057B2 (en) | 2002-10-23 | 2010-09-14 | Medtronic, Inc. | Medical paddle lead and method for spinal cord stimulation |
RU2226114C1 (en) | 2002-11-05 | 2004-03-27 | Беленький Виктор Евгеньевич | Electrotherapy method |
US7020521B1 (en) * | 2002-11-08 | 2006-03-28 | Pacesetter, Inc. | Methods and apparatus for detecting and/or monitoring heart failure |
US7035690B2 (en) | 2002-11-15 | 2006-04-25 | Medtronic, Inc. | Human-implantable-neurostimulator user interface having multiple levels of abstraction |
US7047084B2 (en) | 2002-11-20 | 2006-05-16 | Advanced Neuromodulation Systems, Inc. | Apparatus for directionally stimulating nerve tissue |
TR200202651A2 (en) | 2002-12-12 | 2004-07-21 | Met�N�Tulgar | the vücutádışındanádirekátedaviásinyaliátransferliáábeyinápil |
AR043467A1 (en) | 2003-03-05 | 2005-07-27 | Osmotica Argentina S A | DRUG COMBINATION FOR MOTOR DYSFUNCTION IN PARKINSON'S DISEASE |
IL154801A0 (en) | 2003-03-06 | 2003-10-31 | Karotix Internat Ltd | Multi-channel and multi-dimensional system and method |
US7103417B1 (en) * | 2003-04-18 | 2006-09-05 | Advanced Bionics Corporation | Adaptive place-pitch ranking procedure for optimizing performance of a multi-channel neural stimulator |
US7463928B2 (en) | 2003-04-25 | 2008-12-09 | Medtronic, Inc. | Identifying combinations of electrodes for neurostimulation therapy |
US20070083240A1 (en) | 2003-05-08 | 2007-04-12 | Peterson David K L | Methods and systems for applying stimulation and sensing one or more indicators of cardiac activity with an implantable stimulator |
US6999820B2 (en) | 2003-05-29 | 2006-02-14 | Advanced Neuromodulation Systems, Inc. | Winged electrode body for spinal cord stimulation |
US20050004622A1 (en) | 2003-07-03 | 2005-01-06 | Advanced Neuromodulation Systems | System and method for implantable pulse generator with multiple treatment protocols |
RU2258496C2 (en) | 2003-07-15 | 2005-08-20 | Саратовский научно-исследовательский институт травматологии и ортопедии (СарНИИТО) Министерства здравоохранения РФ | Method for treating patients with traumatic and degenerative lesions of vertebral column and spinal cord |
US7340298B1 (en) | 2003-09-03 | 2008-03-04 | Coaxia, Inc. | Enhancement of cerebral blood flow by electrical nerve stimulation |
US7252090B2 (en) | 2003-09-15 | 2007-08-07 | Medtronic, Inc. | Selection of neurostimulator parameter configurations using neural network |
US7184837B2 (en) | 2003-09-15 | 2007-02-27 | Medtronic, Inc. | Selection of neurostimulator parameter configurations using bayesian networks |
US7200443B2 (en) | 2003-10-07 | 2007-04-03 | John Faul | Transcutaneous electrical nerve stimulator for appetite control |
US8260436B2 (en) | 2003-10-31 | 2012-09-04 | Medtronic, Inc. | Implantable stimulation lead with fixation mechanism |
EP1694403A2 (en) | 2003-11-20 | 2006-08-30 | Advanced Neuromodulation Systems, Inc. | Electrical stimulation system, lead, and method providing reduced neuroplasticity effects |
US20080015659A1 (en) * | 2003-12-24 | 2008-01-17 | Yi Zhang | Neurostimulation systems and methods for cardiac conditions |
EP1706178B1 (en) | 2004-01-22 | 2013-04-24 | Rehabtronics Inc. | System for routing electrical current to bodily tissues via implanted passive conductors |
US9238137B2 (en) | 2004-02-05 | 2016-01-19 | Motorika Limited | Neuromuscular stimulation |
US8165695B2 (en) | 2004-02-11 | 2012-04-24 | Ethicon, Inc. | System and method for selectively stimulating different body parts |
US7590454B2 (en) | 2004-03-12 | 2009-09-15 | Boston Scientific Neuromodulation Corporation | Modular stimulation lead network |
US7330760B2 (en) | 2004-03-16 | 2008-02-12 | Medtronic, Inc. | Collecting posture information to evaluate therapy |
US20050231186A1 (en) | 2004-03-23 | 2005-10-20 | Saavedra Barrera Rafael H | High throughput electrophysiology system |
US7313440B2 (en) | 2004-04-14 | 2007-12-25 | Medtronic, Inc. | Collecting posture and activity information to evaluate therapy |
US20050246004A1 (en) | 2004-04-28 | 2005-11-03 | Advanced Neuromodulation Systems, Inc. | Combination lead for electrical stimulation and sensing |
US8195304B2 (en) | 2004-06-10 | 2012-06-05 | Medtronic Urinary Solutions, Inc. | Implantable systems and methods for acquisition and processing of electrical signals |
US9308382B2 (en) | 2004-06-10 | 2016-04-12 | Medtronic Urinary Solutions, Inc. | Implantable pulse generator systems and methods for providing functional and/or therapeutic stimulation of muscles and/or nerves and/or central nervous system tissue |
US7398255B2 (en) * | 2004-07-14 | 2008-07-08 | Shriners Hospitals For Children | Neural prosthesis with fuzzy logic control system |
US20060041295A1 (en) | 2004-08-17 | 2006-02-23 | Osypka Thomas P | Positive fixation percutaneous epidural neurostimulation lead |
US7463927B1 (en) * | 2004-09-02 | 2008-12-09 | Intelligent Neurostimulation Microsystems, Llc | Self-adaptive system for the automatic detection of discomfort and the automatic generation of SCS therapies for chronic pain control |
US7502651B2 (en) | 2004-09-08 | 2009-03-10 | Spinal Modulation, Inc. | Methods for stimulating a dorsal root ganglion |
US20060089696A1 (en) | 2004-10-21 | 2006-04-27 | Medtronic, Inc. | Implantable medical lead with reinforced outer jacket |
US9050455B2 (en) | 2004-10-21 | 2015-06-09 | Medtronic, Inc. | Transverse tripole neurostimulation methods, kits and systems |
US7613520B2 (en) | 2004-10-21 | 2009-11-03 | Advanced Neuromodulation Systems, Inc. | Spinal cord stimulation to treat auditory dysfunction |
US7377006B2 (en) | 2004-10-29 | 2008-05-27 | Imig Inc. | Vacuum cleaner with magnetic pick-up mechanism |
US8095209B2 (en) | 2005-01-06 | 2012-01-10 | Braingate Co., Llc | Biological interface system with gated control signal |
US20080009927A1 (en) * | 2005-01-11 | 2008-01-10 | Vilims Bradley D | Combination Electrical Stimulating and Infusion Medical Device and Method |
US8788044B2 (en) | 2005-01-21 | 2014-07-22 | Michael Sasha John | Systems and methods for tissue stimulation in medical treatment |
US8744585B2 (en) | 2005-02-23 | 2014-06-03 | Medtronics, Inc. | Implantable medical device providing adaptive neurostimulation therapy for incontinence |
US20070060954A1 (en) | 2005-02-25 | 2007-03-15 | Tracy Cameron | Method of using spinal cord stimulation to treat neurological disorders or conditions |
GB0505940D0 (en) * | 2005-03-23 | 2005-04-27 | Bmr Res & Dev Ltd | Muscle stimulation apparatus and method |
WO2006113397A2 (en) | 2005-04-13 | 2006-10-26 | Nagi Hatoum | System and method for providing a waveform for stimulating biological tissue |
US7603178B2 (en) | 2005-04-14 | 2009-10-13 | Advanced Neuromodulation Systems, Inc. | Electrical stimulation lead, system, and method |
US7813803B2 (en) | 2005-06-09 | 2010-10-12 | Medtronic, Inc. | Regional therapies for treatment of pain |
CA2608397A1 (en) | 2005-06-28 | 2007-01-04 | Bioness Development, Llc | Improvements to an implant, system and method using implanted passive conductors for routing electrical current |
WO2007003019A2 (en) | 2005-07-01 | 2007-01-11 | K.U. Leuven Research & Development | Means for functional restoration of a damaged nervous system |
US7415309B2 (en) | 2005-07-11 | 2008-08-19 | Boston Scientific Scimed, Inc. | Percutaneous access for neuromodulation procedures |
US7499752B2 (en) * | 2005-07-29 | 2009-03-03 | Cyberonics, Inc. | Selective nerve stimulation for the treatment of eating disorders |
US20070049814A1 (en) | 2005-08-24 | 2007-03-01 | Muccio Philip E | System and device for neuromuscular stimulation |
US7856264B2 (en) | 2005-10-19 | 2010-12-21 | Advanced Neuromodulation Systems, Inc. | Systems and methods for patient interactive neural stimulation and/or chemical substance delivery |
US8589316B2 (en) * | 2009-08-27 | 2013-11-19 | The Cleveland Clinic Foundation | System and method to estimate region of tissue activation |
US7660636B2 (en) | 2006-01-04 | 2010-02-09 | Accelerated Care Plus Corp. | Electrical stimulation device and method for the treatment of dysphagia |
WO2007089738A2 (en) | 2006-01-26 | 2007-08-09 | The Regents Of The University Of Michigan | Microelectrode with laterally extending platform for reduction of tissue encapsulation |
US7979131B2 (en) | 2006-01-26 | 2011-07-12 | Advanced Neuromodulation Systems, Inc. | Method of neurostimulation of distinct neural structures using single paddle lead to treat multiple pain locations and multi-column, multi-row paddle lead for such neurostimulation |
US7801601B2 (en) | 2006-01-27 | 2010-09-21 | Cyberonics, Inc. | Controlling neuromodulation using stimulus modalities |
US7467016B2 (en) | 2006-01-27 | 2008-12-16 | Cyberonics, Inc. | Multipolar stimulation electrode with mating structures for gripping targeted tissue |
ATE428468T1 (en) | 2006-02-10 | 2009-05-15 | Advanced Neuromodulation Sys | SELF-FOLDING PADDLE-SHAPED PIPE AND METHOD FOR PRODUCING A PADDLE-SHAPED PIPE |
EP1984066B1 (en) | 2006-02-16 | 2020-05-06 | Imthera Medical, Inc. | An rfid based system for therapeutic treatment of a patient |
US7729781B2 (en) | 2006-03-16 | 2010-06-01 | Greatbatch Ltd. | High efficiency neurostimulation lead |
ITMO20060087A1 (en) | 2006-03-17 | 2007-09-18 | Lorenz Biotech Spa | APPARATUS AND ELECTROSTIMULATION METHOD |
US20120109251A1 (en) | 2006-03-23 | 2012-05-03 | Valery Pavlovich Lebedev | Transcranial electrostimulation device |
JP5188494B2 (en) * | 2006-04-07 | 2013-04-24 | ボストン サイエンティフィック ニューロモデュレイション コーポレイション | System and method using multiple timing channels for electrode adjustment during implant stimulator setup |
US8099172B2 (en) | 2006-04-28 | 2012-01-17 | Advanced Neuromodulation Systems, Inc. | Spinal cord stimulation paddle lead and method of making the same |
US8005543B2 (en) * | 2006-05-08 | 2011-08-23 | Cardiac Pacemakers, Inc. | Heart failure management system |
US7613522B2 (en) | 2006-06-09 | 2009-11-03 | Cardiac Pacemakers, Inc. | Multi-antenna for an implantable medical device |
US20100152811A1 (en) | 2006-06-30 | 2010-06-17 | Flaherty Christopher J | Nerve regeneration system and lead devices associated therewith |
US7765011B2 (en) | 2006-08-21 | 2010-07-27 | Medtronic, Inc. | Assembly methods for medical electrical leads |
US8532778B2 (en) | 2006-08-28 | 2013-09-10 | The United States Of America As Represented By The Department Of Veterans Affairs | Restoring cough using microstimulators |
US8170638B2 (en) | 2006-09-11 | 2012-05-01 | University Of Florida Research Foundation, Inc. | MEMS flexible substrate neural probe and method of fabricating same |
JP4839163B2 (en) | 2006-09-14 | 2011-12-21 | テルモ株式会社 | Leg exercise device by electrical stimulation |
US9643004B2 (en) | 2006-10-31 | 2017-05-09 | Medtronic, Inc. | Implantable medical elongated member with adhesive elements |
US7831307B1 (en) | 2006-11-07 | 2010-11-09 | Boston Scientific Neuromodulation Corporation | System and method for computationally determining migration of neurostimulation leads |
WO2008070809A2 (en) | 2006-12-06 | 2008-06-12 | Spinal Modulation, Inc. | Implantable flexible circuit leads and methods of use |
WO2008070807A2 (en) | 2006-12-06 | 2008-06-12 | Spinal Modulation, Inc. | Delivery devices, systems and methods for stimulating nerve tissue on multiple spinal levels |
US7734351B2 (en) | 2006-12-15 | 2010-06-08 | Medtronic Xomed, Inc. | Method and apparatus for assisting deglutition |
RU2461397C2 (en) | 2006-12-21 | 2012-09-20 | Сапиенс Стиринг Брейн Стимьюлейшн Б.В. | Biomimetic neurostimulation apparatus |
US20080234791A1 (en) * | 2007-01-17 | 2008-09-25 | Jeffrey Edward Arle | Spinal cord implant systems and methods |
US8554337B2 (en) | 2007-01-25 | 2013-10-08 | Giancarlo Barolat | Electrode paddle for neurostimulation |
US7949403B2 (en) | 2007-02-27 | 2011-05-24 | Accelerated Care Plus Corp. | Electrical stimulation device and method for the treatment of neurological disorders |
WO2008109862A2 (en) | 2007-03-08 | 2008-09-12 | Second Sight Medical Products, Inc. | Flexible circuit electrode array |
ES2896950T3 (en) | 2007-03-09 | 2022-02-28 | Mainstay Medical Ltd | muscle stimulator |
WO2008115754A1 (en) | 2007-03-16 | 2008-09-25 | Advanced Neuromodulation Systems, Inc. | Paddle lead comprising opposing diagonal arrangements of electrodes |
US8180445B1 (en) | 2007-03-30 | 2012-05-15 | Boston Scientific Neuromodulation Corporation | Use of interphase to incrementally adjust the volume of activated tissue |
US8364273B2 (en) | 2007-04-24 | 2013-01-29 | Dirk De Ridder | Combination of tonic and burst stimulations to treat neurological disorders |
GB0709834D0 (en) * | 2007-05-22 | 2007-07-04 | Gillbe Ivor S | Array stimulator |
US7742810B2 (en) | 2007-05-23 | 2010-06-22 | Boston Scientific Neuromodulation Corporation | Short duration pre-pulsing to reduce stimulation-evoked side-effects |
US7769463B2 (en) | 2007-06-19 | 2010-08-03 | Kalaco Scientific, Inc. | Multi-channel electrostimulation apparatus and method |
RU2361631C2 (en) | 2007-07-04 | 2009-07-20 | Федеральное государственное учреждение здравоохранения Центральная клиническая больница восстановительного лечения Федерального медико-биологического агентства (ФГУЗ ЦКБВЛ ФМБА России) | Way of treatment of patients with traumatic disease of spinal cord |
EP2195084A4 (en) | 2007-09-26 | 2010-10-20 | Univ Duke | Method of treating parkinson's disease and other movement disorders |
DE102007051848B4 (en) | 2007-10-30 | 2014-01-02 | Forschungszentrum Jülich GmbH | Device for stimulating neuronal associations |
US20090204173A1 (en) | 2007-11-05 | 2009-08-13 | Zi-Ping Fang | Multi-Frequency Neural Treatments and Associated Systems and Methods |
US8170659B2 (en) | 2007-12-05 | 2012-05-01 | The Invention Science Fund I, Llc | Method for thermal modulation of neural activity |
US8195298B2 (en) * | 2008-02-15 | 2012-06-05 | Andres M Lozano | Method for treating neurological/psychiatric disorders with stimulation to the subcaudate area of the brain |
AU2009220057A1 (en) | 2008-03-06 | 2009-09-11 | Stryker Corporation | Foldable, implantable electrode array assembly and tool for implanting same |
US9259568B2 (en) | 2008-04-29 | 2016-02-16 | Cardiac Pacemakers, Inc. | Systems and methods for delivering electric current for spinal cord stimulation |
US7890182B2 (en) | 2008-05-15 | 2011-02-15 | Boston Scientific Neuromodulation Corporation | Current steering for an implantable stimulator device involving fractionalized stimulation pulses |
RU2368401C1 (en) | 2008-05-26 | 2009-09-27 | Андрей Александрович Олейников | Treatment method of hernias of lumbar intervertebral discs |
US8108052B2 (en) | 2008-05-29 | 2012-01-31 | Nervo Corporation | Percutaneous leads with laterally displaceable portions, and associated systems and methods |
US20090306491A1 (en) | 2008-05-30 | 2009-12-10 | Marcus Haggers | Implantable neural prosthetic device and methods of use |
WO2009155084A1 (en) | 2008-05-30 | 2009-12-23 | Stryker Corporation | Method of assembling an electrode array that includes a plastically deformable carrier |
CA3075063A1 (en) * | 2008-07-02 | 2010-01-07 | Sage Products, Llc | Systems and methods for automated muscle stimulation |
RU2396995C2 (en) | 2008-07-14 | 2010-08-20 | Государственное образовательное учреждение высшего профессионального образования "Санкт-Петербургская государственная медицинская академия им. И.И. Мечникова Федерального агентства по здравоохранению и социальному развитию" | Method of treating patients suffering lumbar osteochondrosis with radicular syndrome |
WO2010011721A1 (en) | 2008-07-24 | 2010-01-28 | Boston Scientific Neuromodulation Corporation | System and method for maintaining a distribution of currents in an electrode array using independent voltage sources |
US8155750B2 (en) | 2008-07-24 | 2012-04-10 | Boston Scientific Neuromodulation Corporation | System and method for avoiding, reversing, and managing neurological accommodation to electrical stimulation |
US20100023103A1 (en) | 2008-07-28 | 2010-01-28 | Boston Scientific Neuromodulation Corporation | Systems and Methods for Treating Essential Tremor or Restless Leg Syndrome Using Spinal Cord Stimulation |
US7987000B2 (en) * | 2008-09-04 | 2011-07-26 | Boston Scientific Neuromodulation Corporation | Multiple tunable central cathodes on a paddle for increased medial-lateral and rostral-caudal flexibility via current steering |
US8442655B2 (en) | 2008-09-04 | 2013-05-14 | Boston Scientific Neuromodulation Corporation | Multiple tunable central cathodes on a paddle for increased medial-lateral and rostral-caudal flexibility via current steering |
US8050773B2 (en) | 2008-09-28 | 2011-11-01 | Jie Zhu | Expandable neuromodular stimulation lead |
EP3202457B1 (en) * | 2008-10-27 | 2020-05-27 | Spinal Modulation Inc. | Selective stimulation systems and signal parameters for medical conditions |
US8311639B2 (en) | 2009-07-08 | 2012-11-13 | Nevro Corporation | Systems and methods for adjusting electrical therapy based on impedance changes |
US7974705B2 (en) | 2008-11-13 | 2011-07-05 | Proteus Biomedical, Inc. | Multiplexed multi-electrode neurostimulation devices |
US8504160B2 (en) | 2008-11-14 | 2013-08-06 | Boston Scientific Neuromodulation Corporation | System and method for modulating action potential propagation during spinal cord stimulation |
RU2387467C1 (en) | 2008-11-18 | 2010-04-27 | Инна Игоревна Русинова | Method for correction of muscular imbalance in children with fault in posture and scoliosis 1 and 2 degree |
RU2397788C2 (en) | 2008-11-21 | 2010-08-27 | Государственное учреждение Московский областной научно-исследовательский клинический институт им. М.Ф. Владимирского (МОНИКИ им. М.Ф. Владимирского) | Method of restoring microcirculation in affected tissues |
EP2393551A4 (en) | 2009-02-09 | 2013-04-17 | Proteus Digital Health Inc | Multiplexed multi-electrode neurostimulation devices with integrated circuit having integrated electrodes |
AU2010213807B2 (en) | 2009-02-10 | 2015-08-06 | Nevro Corporation | Systems and methods for delivering neural therapy correlated with patient status |
WO2010114998A1 (en) | 2009-04-03 | 2010-10-07 | Stryker Corporation | Delivery assembly for percutaneously delivering and deploying an electrode array at a target location, the assembly capable of steering the electrode array to the target location |
EP2421600B1 (en) | 2009-04-22 | 2014-03-05 | Nevro Corporation | Spinal cord modulation systems for inducing paresthetic and anesthetic effects |
CN101596338A (en) * | 2009-04-29 | 2009-12-09 | 天津大学 | Functional electric stimulation precision control method based on BP neural network tuned proportion integration differentiation PID |
CN105844087A (en) * | 2009-04-30 | 2016-08-10 | 麦德托尼克公司 | Patient state detection based on support vector machine based algorithm |
TWI397789B (en) * | 2009-05-12 | 2013-06-01 | Univ Nat Chiao Tung | Parameter adjusting device and method thereof |
US8046077B2 (en) | 2009-06-05 | 2011-10-25 | Intelect Medical, Inc. | Selective neuromodulation using energy-efficient waveforms |
US9737703B2 (en) * | 2009-07-10 | 2017-08-22 | Boston Scientific Neuromodulation Corporation | Method to enhance afferent and efferent transmission using noise resonance |
US8498710B2 (en) * | 2009-07-28 | 2013-07-30 | Nevro Corporation | Linked area parameter adjustment for spinal cord stimulation and associated systems and methods |
US8781600B2 (en) | 2009-08-05 | 2014-07-15 | Stryker Corporation | Implantable electrode array assembly including a carrier in which control modules for regulating the operation of the electrodes are disposed and electrodes that are disposed on top of the carrier |
JP2011055912A (en) * | 2009-09-07 | 2011-03-24 | Terumo Corp | Electric stimulator |
US8543200B2 (en) | 2009-08-28 | 2013-09-24 | Boston Scientific Neuromodulation Corporation | Methods to avoid frequency locking in a multi-channel neurostimulation system using pulse placement |
US9724513B2 (en) | 2009-08-28 | 2017-08-08 | Boston Scientific Neuromodulation Corporation | Methods to avoid frequency locking in a multi-channel neurostimulation system using pulse shifting |
US9061134B2 (en) | 2009-09-23 | 2015-06-23 | Ripple Llc | Systems and methods for flexible electrodes |
AU2010303588B2 (en) | 2009-10-05 | 2015-07-30 | Neurosigma, Inc. | Extracranial implantable devices, systems and methods for the treatment of neurological disorders |
US8412345B2 (en) | 2009-11-03 | 2013-04-02 | Boston Scientific Neuromodulation Corporation | System and method for mapping arbitrary electric fields to pre-existing lead electrodes |
TW201117849A (en) | 2009-11-30 | 2011-06-01 | Unimed Invest Inc | Implantable pulsed-radiofrequency micro-stimulation system |
WO2011067297A1 (en) | 2009-12-01 | 2011-06-09 | ECOLE POLYTECHNIQUE FéDéRALE DE LAUSANNE | Microfabricated neurostimulation device and methods of making and using the same |
WO2011082071A1 (en) | 2009-12-30 | 2011-07-07 | Boston Scientific Neuromodulation Corporation | System for independently operating multiple neurostimulation channels |
CN101773701A (en) * | 2010-01-11 | 2010-07-14 | 杭州诺尔康神经电子科技有限公司 | Nerve stimulator |
US8626295B2 (en) | 2010-03-04 | 2014-01-07 | Cardiac Pacemakers, Inc. | Ultrasonic transducer for bi-directional wireless communication |
WO2011112773A2 (en) | 2010-03-11 | 2011-09-15 | Mainstay Medical, Inc. | Modular stimulator for treatment of back pain, implantable rf ablation system and methods of use |
CN105477782B (en) | 2010-03-22 | 2019-01-04 | 纽约城市大学研究基金会 | Charge enhances stimulation system |
SG184395A1 (en) | 2010-04-01 | 2012-11-29 | Ecole Polytech | Device for interacting with neurological tissue and methods of making and using the same |
CN101816822B (en) * | 2010-05-27 | 2012-11-28 | 天津大学 | Setting method of functional electrical stimulation PID (Proportion Integration Differentiation) parameter double source characteristic fusion particle swarm |
AU2011258026A1 (en) | 2010-05-27 | 2012-12-20 | Ndi Medical, Llc | Waveform shapes for treating neurological disorders optimized for energy efficiency |
US8452410B2 (en) | 2010-09-07 | 2013-05-28 | Aalborg Universitet | Method and device for reflex-based functional gait training |
AU2011302521B2 (en) | 2010-09-15 | 2014-07-10 | Cardiac Pacemakers, Inc. | Automatic selection of lead configuration for a neural stimulation lead |
US9155891B2 (en) | 2010-09-20 | 2015-10-13 | Neuropace, Inc. | Current management system for a stimulation output stage of an implantable neurostimulation system |
US8239038B2 (en) | 2010-10-14 | 2012-08-07 | Wolf Ii Erich W | Apparatus and method using near infrared reflectometry to reduce the effect of positional changes during spinal cord stimulation |
WO2012064968A1 (en) | 2010-11-11 | 2012-05-18 | IINN, Inc. | Motor nerve root stimulation |
RU2445990C1 (en) | 2010-11-12 | 2012-03-27 | Государственное учреждение Московский областной научно-исследовательский клинический институт им. М.Ф. Владимирского (ГУ МОНИКИ им. М.Ф. Владимирского) | Method of treating paresis and paralysis |
WO2012075198A2 (en) | 2010-11-30 | 2012-06-07 | Nevro Corporation | Extended pain relief via high frequency spinal cord modulation, and associated systems and methods |
WO2012094346A2 (en) | 2011-01-03 | 2012-07-12 | The Regents Of The University Of California | High density epidural stimulation for facilitation of locomotion, posture, voluntary movement, and recovery of autonomic, sexual, vasomotor, and cognitive function after neurological injury |
CN103608067A (en) | 2011-01-21 | 2014-02-26 | 加利福尼亚理工学院 | A parylene-based microelectrode array implant for spinal cord stimulation |
US20120232615A1 (en) | 2011-03-07 | 2012-09-13 | Giancarlo Barolat | Modular Limb Peripheral Nerve Stimulation System and Method of Use |
RU2471518C2 (en) | 2011-03-23 | 2013-01-10 | Учреждение Российской Академии Наук Институт физиологии им. И.П. Павлова ИФ РАН | Method for electric stimulation of spinal cord |
JP6060146B2 (en) | 2011-03-24 | 2017-01-11 | カリフォルニア インスティテュート オブ テクノロジー | Nerve stimulator |
RU2475283C2 (en) | 2011-05-10 | 2013-02-20 | Федеральное государственное бюджетное учреждение "Санкт-Петербургский научно-исследовательский институт фтизиопульмонологии" Министерства здравоохранения и социального развития Российской Федерации | Method of restoring arm movements in patients with upper paralyses and pareses |
US8688233B2 (en) | 2011-06-23 | 2014-04-01 | Boston Scientific Neuromodulation Corporation | System and method for spinal cord stimulation to treat motor disorders |
US9314629B2 (en) | 2011-10-13 | 2016-04-19 | Marc Possover | Method for recovering body functions |
US10092750B2 (en) | 2011-11-11 | 2018-10-09 | Neuroenabling Technologies, Inc. | Transcutaneous neuromodulation system and methods of using same |
ES2728143T3 (en) | 2011-11-11 | 2019-10-22 | Univ California | Transcutaneous spinal cord stimulation: non-invasive tool for locomotor circuit activation |
KR20140098780A (en) | 2011-11-11 | 2014-08-08 | 뉴로이네이블링 테크놀로지스, 인크. | Non invasive neuromodulation device for enabling recovery of motor, sensory, autonomic, sexual, vasomotor and cognitive function |
US9622671B2 (en) | 2012-03-20 | 2017-04-18 | University of Pittsburgh—of the Commonwealth System of Higher Education | Monitoring and regulating physiological states and functions via sensory neural inputs to the spinal cord |
US8918185B2 (en) | 2012-03-23 | 2014-12-23 | Boston Scientific Neuromodulation Corporation | Heuristic safety net for transitioning configurations in a neural stimulation system |
US9993642B2 (en) | 2013-03-15 | 2018-06-12 | The Regents Of The University Of California | Multi-site transcutaneous electrical stimulation of the spinal cord for facilitation of locomotion |
US20150217120A1 (en) | 2014-01-13 | 2015-08-06 | Mandheerej Nandra | Neuromodulation systems and methods of using same |
US20160175586A1 (en) | 2014-10-10 | 2016-06-23 | Neurorecovery Technologies, Inc. | Epidural stimulation for facilitation of locomotion, posture, voluntary movement, and recovery of autonomic, sexual, vasomotor, and cognitive function after neurological injury |
-
2012
- 2012-03-26 JP JP2014501307A patent/JP6060146B2/en active Active
- 2012-03-26 BR BR112013024491A patent/BR112013024491A2/en not_active Application Discontinuation
- 2012-03-26 CN CN201280011915.1A patent/CN103608069B/en active Active
- 2012-03-26 AU AU2012230699A patent/AU2012230699A1/en not_active Abandoned
- 2012-03-26 EP EP12760696.0A patent/EP2688642B1/en active Active
- 2012-03-26 WO PCT/US2012/030624 patent/WO2012129574A2/en active Application Filing
- 2012-03-26 KR KR1020137027989A patent/KR20140013043A/en not_active Application Discontinuation
- 2012-03-26 US US14/007,262 patent/US9409023B2/en active Active
- 2012-03-26 CA CA2825550A patent/CA2825550C/en active Active
- 2012-03-26 CN CN201710196342.9A patent/CN107361741B/en active Active
- 2012-03-26 MX MX2013010998A patent/MX344095B/en active IP Right Grant
-
2015
- 2015-01-23 US US14/604,625 patent/US20150231396A1/en not_active Abandoned
-
2016
- 2016-03-09 AU AU2016201541A patent/AU2016201541B2/en not_active Ceased
- 2016-06-30 US US15/199,580 patent/US9931508B2/en active Active
- 2016-08-12 JP JP2016158448A patent/JP6268240B2/en active Active
-
2017
- 2017-05-11 AU AU2017203132A patent/AU2017203132B2/en not_active Ceased
- 2017-09-01 AU AU2017221868A patent/AU2017221868B2/en active Active
-
2018
- 2018-03-29 US US15/940,473 patent/US10737095B2/en active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090112281A1 (en) * | 2007-10-26 | 2009-04-30 | Medtronic, Inc. | Medical device configuration based on sensed brain signals |
US20100185253A1 (en) * | 2009-01-19 | 2010-07-22 | Dimarco Anthony F | Respiratory muscle activation by spinal cord stimulation |
US20130123568A1 (en) * | 2010-07-01 | 2013-05-16 | Stimdesigns Llc | Universal closed-loop electrical stimulation system |
Non-Patent Citations (2)
Title |
---|
Claims from US Application 14/007262 as of 3/31/2016 * |
Claims from US Application 14/007262 filed 6/23/2015 * |
Cited By (63)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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US9907958B2 (en) | 2011-01-03 | 2018-03-06 | The Regents Of The University Of California | High density epidural stimulation for facilitation of locomotion, posture, voluntary movement, and recovery of autonomic, sexual, vasomotor, and cognitive function after neurological injury |
US11957910B2 (en) | 2011-01-03 | 2024-04-16 | California Institute Of Technology | High density epidural stimulation for facilitation of locomotion, posture, voluntary movement, and recovery of autonomic, sexual, vasomotor, and cognitive function after neurological injury |
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US10124166B2 (en) | 2011-11-11 | 2018-11-13 | Neuroenabling Technologies, Inc. | Non invasive neuromodulation device for enabling recovery of motor, sensory, autonomic, sexual, vasomotor and cognitive function |
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US11229789B2 (en) | 2013-05-30 | 2022-01-25 | Neurostim Oab, Inc. | Neuro activator with controller |
US11123312B2 (en) | 2013-09-27 | 2021-09-21 | The Regents Of The University Of California | Engaging the cervical spinal cord circuitry to re-enable volitional control of hand function in tetraplegic subjects |
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US10786673B2 (en) | 2014-01-13 | 2020-09-29 | California Institute Of Technology | Neuromodulation systems and methods of using same |
US10751533B2 (en) | 2014-08-21 | 2020-08-25 | The Regents Of The University Of California | Regulation of autonomic control of bladder voiding after a complete spinal cord injury |
US10773074B2 (en) | 2014-08-27 | 2020-09-15 | The Regents Of The University Of California | Multi-electrode array for spinal cord epidural stimulation |
US11077301B2 (en) | 2015-02-21 | 2021-08-03 | NeurostimOAB, Inc. | Topical nerve stimulator and sensor for bladder control |
US20160250470A1 (en) * | 2015-02-26 | 2016-09-01 | Stryker Corporation | Rehabilitation Monitor And Pain Treatment Assembly |
US10668281B2 (en) | 2015-03-13 | 2020-06-02 | Tokai University Educational System | Spinal cord stimulation device for gait training |
US11666761B2 (en) | 2015-08-26 | 2023-06-06 | Boston Scientific Neuromodulation Corporation | Machine learning to optimize spinal cord stimulation |
US10842997B2 (en) | 2015-08-26 | 2020-11-24 | Boston Scientific Neuromodulation Corporation | Machine learning to optimize spinal cord stimulation |
WO2017035140A1 (en) * | 2015-08-26 | 2017-03-02 | Boston Scientific Neuromodulation Corporation | Machine learning to optimize spinal cord stimulation |
US11298533B2 (en) | 2015-08-26 | 2022-04-12 | The Regents Of The University Of California | Concerted use of noninvasive neuromodulation device with exoskeleton to enable voluntary movement and greater muscle activation when stepping in a chronically paralyzed subject |
US11565114B2 (en) * | 2015-09-21 | 2023-01-31 | Boston Scientific Neuromodulation Corporation | Automated program optimization |
US11097122B2 (en) | 2015-11-04 | 2021-08-24 | The Regents Of The University Of California | Magnetic stimulation of the spinal cord to restore control of bladder and/or bowel |
CN106902458A (en) * | 2015-12-22 | 2017-06-30 | 洛桑联邦理工学院 | The system that selective space-time stimulates spinal cord |
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US11399770B2 (en) | 2016-08-01 | 2022-08-02 | Med-El Elektromedizinische Geraete Gmbh | Respiratory triggered parasternal electromyographic recording in neurostimulators |
WO2018026974A1 (en) * | 2016-08-02 | 2018-02-08 | Motometrix Inc. | System and method for identification of brain injury |
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