WO2022038112A1

WO2022038112A1 - Closed loop computer-brain interface device, physiologic signal transmitter and receiver device

Info

Publication number: WO2022038112A1
Application number: PCT/EP2021/072784
Authority: WO
Inventors: Saman HAGH GOOIE
Original assignee: CereGate GmbH
Priority date: 2020-08-21
Filing date: 2021-08-17
Publication date: 2022-02-24
Also published as: EP4200008A1

Abstract

The present application relates to a closed loop computer brain interface device for an individual comprising a receiver module configured to obtain at least one sensor signal indicative of a movement or action of the individual, a processing module operably connected to the receiver module and configured to determine at least one neuronal feedback signal based at least in part on the obtained sensor signal and a transmitter module operably connected to the processing module and configured to transmit the determined neuronal feedback signal to a neurostimulation device of the individual or a neurostimulation module operably connected to the processing module, wherein the neuronal feedback signal is configured to elicit a sensory percept in the cortex of the individual via stimulating afferent sensory axons of the central nervous system targeting sensory neurons of the cortex of the individual and wherein the elicited sensory percept indicates movement support information related to the obtained sensor signal to support the execution of the movement or action of the individual. The present application also relates to a physiologic signal transmitter device for an individual, comprising a receiver module configured to obtain one or more sensor signals monitoring one or more physiologic and / or mental states of the individual, a processing module operably connected to the receiver module and configured to determine one or more stimulation signals based at least in part on the obtained one or more sensor signals, and a stimulation module operably connected to the processing module and configured to apply the determined stimulation signals to a physiologic system or structure of the individual via a physiologic stimulation device of the individual, wherein the one or more stimulation signals are configured to elicit one or more artificial physiologic excitations propagating along the physiologic system or structure of the individual, and wherein the one or more artificial physiologic excitations encode information about the monitored one or more physiologic and / or mental states of the individual. For instance, artificially elicited neural or muscle excitations may be used to establish a physiologic communication channel between the transmitter and the receiver device.

Description

CLOSED LOOP COMPUTER-BRAIN INTERFACE DEVICE, PHYSIOLOGIC SIGNAL TRANSMITTER AND RECEIVER DEVICE

1. Technical field

The present application relates to closed loop computer brain interface devices, systems and computer programs that may be used for behavioral task training as well as patient recovery and rehabilitation.

The present application also relates to physiologic signal transmitter and receiver devices, physiologic signal transmission systems and computer programs that may be used for transmitting information relating to a physiologic or mental state of an individual via artificial physiologic excitations propagating within a physiologic system or structure of the body of the individual.

2. Technical Background

Movement disorders and unsafe, undesirable or unstable movements can originate from a range of medical conditions such as traumatic brain injury, stroke, cerebral palsy, Parkinson's disease (PD) and Parkinsonism, dystonia, Huntington's disease, ataxia, the many varieties of tremor, myoclonus, tics, Tourette's syndrome, restless leg syndrome, gait disorders, balance disorders, and the like.

For instance, in the United States, it is estimated that over 270,000 individuals are hospitalized each year for a traumatic brain injury and survive. While traumatic brain injury can result in a wide variety of cognitive impairments, motor disorders along with balance problems, are the most commonly reported symptoms. Apart from motor symptoms, many stroke survivors suffer from sensory impairments of their affected upper limbs which are characterized by reduced sense of touch, temperature, proprioception, and pain. These symptoms can affect the ability to use the upper limbs in everyday activities. There is consistent clinical evidence that somatosensory dysfunction negatively influences motor function. The impairments affect the ability to discriminate textures, weights, shapes, and sizes, to grasp and manipulate objects without vision, and to perform tasks using hands in everyday life. However very little attention is paid to sensory impairments in rehabilitation and recovery and behavioral task training.

For instance, conventional rehabilitation commonly involves a series of motor or cognitive tasks performed by a patient in context of physical therapy delivered by human therapists. More recently, robotic rehabilitation systems have been described that complement human therapists and enable novel rehabilitation exercises which may not be available from human therapists alone. For instance, a rehabilitation robot such as the BURT (cf. https://medical.barrett.com) can provide active visual, auditory, proprioceptive, and vibration feedback associated with a behavioral training task.

Futher, the publication Donati, A., Shokur, S., Morya, E. et al. “Long-Term Training with a Brain-Machine Interface-Based Gait Protocol Induces Partial Neurological Recovery in Paraplegic Patients” Sci Rep 6, 30383 (2016); https://d0i.0rg/10.1038/srep30383 suggests the importance of tactile feedback in long-term rehabilitation. The study demonstrates that long-term exposure to brain computer interface (BCI) -based protocols enriched with tactile feedback and combined with robotic gait training may induce cortical and subcortical plasticity capable of triggering partial neurological recovery even in patients originally diagnosed with a chronic complete spinal cord injury.

US 2010/0057161 Ai relates to treating medical conditions such as unilateral motor deficits, movement disorders, psychiatric disorders, epilepsy, speech or cognitive deficits associated with hemispheric lesions by neuromodulation. Further, US 2010/0057161 Al also discloses a method for enhancing memory, learning and/or cognitive capacity in a healthy individual by stimulating a target site of a cerebello- thalamo-cortical pathway and/ or a cortical-ponto-cerebellar pathway.

US 2015/0073492 relates to systems for treating motor deficits in stroke patients based on stimulating the vagus nerve of the patients during the performance of a selected therapeutic tasks, and thereby improving the patient's motor deficits.

US 9,974,478 relates to an adaptive movement recovery system for providing therapy and training to improve functional motor recovery and safety of movement of a subject suffering from an injury or from movement disorders. US 8,509,904 relates to a BCI apparatus for supporting the rehabilitation of stroke patients with motor impairments. The disclosed apparatus comprises an electrocorticography (EcoG) multi-electrode probe for recording neuronal activity signals, an evaluation unit for analysis of the activity signals, and an effector which is controlled by the evaluation unit in dependence of a detected motion. The effector can be an orthosis, or a display device or other effector means such as a stimulator for muscle or brain tissue, which gives the patient feedback about the degree of success of control.

EP 2486 897 Bi relates to an interface between a machine and a patient's brain, and more particularly to an interface between one or more types of neural signals originating in the brain of a patient. The neural signals are monitored and transmitted to a responsive mechanical device, which, in turn, relays sensory feedback to the patient. In this manner, one or more neural signals originating in a subject's brain are converted to motion in a mechanical device.

WO 2012/003451 A3 relates to a closed-loop electrical stimulation system comprising an electrode assembly adapted to electrically stimulate signal to the nervous system or muscles of a user, a sensor system adapted to detect a mechanical response to a muscle stimulation signal of a muscle associated with a muscle group stimulated by the nervous system and an electrical stimulation device operably coupled to the electrode assembly and the sensor system that includes a control system to receive feedback from the muscle and to adjust a parameter of the muscle stimulation signal as well as a programmed microprocessor for receiving input from the sensor system and controlling the electrical stimulation.

US 2014/0379046 Al relates to an implantable neurostimulator system for treating movement disorders that includes a sensor, a detection subsystem capable of identifying episodes of a movement disorder by analyzing a signal received from the sensor, and a therapy subsystem capable of supplying therapeutic electrical stimulation to treat the movement disorder. The system treats movement disorders by detecting physiological conditions characteristic of an episode of symptoms of the movement disorder and selectively initiating therapy when such conditions are detected.

Similarly, US 8,423,145 B2 relates to an implantable neurostimulator system adapted to provide therapy for various neurological disorders that is capable of varying therapy delivery strategies based on the context, physiological or otherwise, into which the therapy is to be delivered. Responsive and scheduled therapies can be varied depending on various sensor measurements, calculations, inferences, and device states to deliver an appropriate therapy.

Further information on the technical background of the present invention is provided by prior art documents US 8,290,596, US 8,475,172, US 9,357,938, EP 2552304, US 2015/0018724.

Concerning a further aspect of the present application, homeostasis of a living body refers to the state of steady internal, physical, and chemical conditions maintained by the body. Homeostasis ensures optimal functioning for the organism and includes many physiologic variables, such as body temperature, fluid balance, hormone and neurotransmitter levels etc. being kept within certain pre-set limits (homeostatic range). Other variables include the pH of extracellular fluid, the concentrations of sodium, potassium and calcium ions, as well as that of the blood sugar level, and these need to be regulated despite changes of the environment, diet, or level of activity of the living body. In healthy individuals each of these variables is controlled by one or more homeostatic mechanisms mainly evolved as physiologic feedback loops, which together maintain life.

Many homeostatic control mechanisms comprise interdependent components for the variable being regulated such as a physiologic receptor system or structure, a physiologic control system or structure and / or a physiologic effector system or structure. For instance, the receptor system or structure functions as a sensing component that monitors and responds to changes in the environment, either external or internal. Such receptor systems or structures include thermoreceptors, mechanoreceptors and chemoreceptors etc.

As an example, consider blood sugar concentration regulation in humans and mammals. In mammals the primary sensors for blood sugar levels are the beta cells of the pancreatic islets. The beta cells respond to a rise in the blood sugar level by secreting insulin into the blood, and simultaneously inhibiting their neighboring alpha cells from secreting glucagon into the blood. This combination (high blood insulin levels and low glucagon levels) act on effector organs and tissues, such as the liver, fat cells and muscle cells. The liver is inhibited from producing glucose, taking it up instead, and converting it to glycogen and triglycerides. Several medical conditions may interfere or even interrupt such homeostatic control mechanisms. For instance, insulin and / or glucagon production and / or transmission to the respective effector organ may be impaired. Further, physiologic sugar concentration chemoreceptors may also be impaired.

To treat such conditions, implantable drug delivery systems and implantable chemosensors have been developed.

The present invention is directed to novel signal transmission devices and systems that can be used together with such systems and sensors and significantly improve their performance. The present invention can also be used in conjunction with systems and devices for monitoring of neurological, psychological, or physiological states of an individual.

The following prior art systems may be relevant for characterizing the technological background of the present invention:

US 2017 / 0258370 relates to a system for provoking gait disorders usable for diagnosing and treatment. For instance, displays of situations calculated to cause freezing of gait are presented to a subject, optionally using virtual reality displays. Optionally incipit freezing of gait is identified using changes in gait parameters and used to guide attempts at causing freezing of gait. Based thereon a portable device can be configured to detect incipit freezing of gait events and generate a corrective signal to the subject.

US 9,008,762 relates to a system that computes a cardiac-based metric based upon characteristics of a subject's cardiac function. For instance, the end of a mechanical systole is identified for each of a plurality of cardiac cycles of a subject, based upon an acoustical vibration associated with closure of an aortic valve during the cardiac cycle. The end of an electrical systole of an ECG signal for each cardiac cycle is also identified. Based thereon an electronic device can be constructed that comprises an input circuit and a computer circuit configured for receiving an electrical signal representative of an ECG from a subject and to identify a plurality of cardiac cycles in the electrical signal. Such systems are implemented to address alterations that can impact cardiac function and arrhythmic risk indicative of the changes that occur at the cellular level, which vary with time, stress, and other stimuli. US 7,785,249 relates to an apparatus for relieving stress using biofeedback techniques used according to a specified regimen to enable a user to achieve a relaxed state. Such an apparatus may comprise a sensor wirelessly connected to a CPU, which processes signals from the sensor to produce a visual display and/ or auditory display that is representative of the relaxation state of the user.

US 8,983,591 relates to an apparatus for detecting seizures with motor manifestations may comprise one or more EMG electrodes capable of providing an EMG signal substantially representing seizure-related muscle activity and a processor configured to receive the EMG signal, process the EMG signal to determine whether a seizure may be occurring, and generate an alert if a seizure is determined to be occurring based on the EMG signal.

Similarly, US 10,543,359 relates to a medical system that implements a seizure detection algorithm to detect a seizure based on a first patient parameter. The medical system monitors a second patient parameter to adjust the seizure detection algorithm. For example, the medical system may determine a first patient parameter characteristic indicative of the target seizure detected based on the second patient parameter and store the first patient parameter characteristic as part of the seizure detection algorithm. In some examples, the first patient parameter is an electrical brain signal and the second patient parameter is patient activity. A similar system is also discussed in US 2010/0168603.

Further, US 7,269,455 relates to a system for the detection and prevention of epileptic seizures utilizing bioelectric signals to assess a seizure profile and an adaptive control system for neurofeedback therapy. The system provides the detection of changes in the non-linear dynamics of brain electrical activities to characterize and differentiate individual susceptibility to seizure onset, predict the occurrence of a seizure episode, and initiate neurofeedback training to prevent the attack.

In this context, the earlier patent applications DE 10 2019 202666 and US 2020/0269049 by the applicant are also relevant for specifying the technological background of the present invention.

Moreover, the article “Electroceuticals” by Geoffrey Ling and Corinna E. Lathan published in Scientific American on Sep 14, 2018 (accessible at https://www.scie.ntificamerican.com/article/electroceiiticals/') discusses a electroceutical communication system employing natural orthodromic nerve conduction properties of neural fibers within the body for closed-loop control.

Further, US 2010/ 0305437 relates to a system for generating a mechanical signal in a mammal, the mechanical signal having a frequency no more than 50,000 Hz, and for transmitting the mechanical signal through the musculoskeletal system in the mammal, and sensing the mechanical signal from the musculoskeletal system. Such system can for instance be used for drug delivery by generating a mechanical signal internal or external to a mammal, transmitting the signal through the musculoskeletal system of the mammal, detecting the mechanical signal, and delivering the drug in response to the mechanical signal.

Similarly, US 6,754,472 relates to an apparatus for distributing power and data to devices coupled to the human body. The human body is used as a conductive medium, e.g., a bus, over which power and/or data is distributed.

EP 2 208458 relates to a network that has two different network nodes connected with a body of a patient. The two network nodes have a medical function such as diagnostic function and medication function. The network nodes are designed to directly communicate with one another via the body of the patient and exchange data and/or instructions. The network nodes include a temperature sensor, blood pressure sensor, sensor for detecting glucose, lactate, carbon dioxide, boric acid and metaboric acid and another sensor for detecting bodily functions i.e. kidney function.

Further, related prior art is provided by US 9,812,788 and US 2006/0243288.

The review article “A Review on Human Body Communication: Signal Propagation Model, Communication Performance, and Experimental Issues” published in Hindawi Wireless Communications and Mobile Computing, Volume 2017, Article ID 5842310 provides a recent overview on human body communication systems.

The prior art systems and devices discussed above exhibit various deficiencies.

For instance, several of the discussed prior art systems require implantation of dedicated interface devices such as dedicated cortex stimulation electrodes via invasive surgical procedures that may not be safe and / or not yet fully approved for widespread clinical use. Moreover, the available systems for aiding patients during rehabilitation from neurological diseases or injury rely on unspecific or indirect feedback resulting in an unsatisfactory therapy success. In addition, many of the prior art systems cannot be calibrated for individual patients and thus lack the capability to perform patient specific therapy optimization.

Moreover, some of the prior art systems such as the brain-machine interface disclosed in EP 2486897 Bi use sensory feedback to improve control of a mechanical device via the brain-machine interface. However, such systems are fundamentally limited to sensory feedback mimicking the bioelectric signals normally generated from physiological sensory organs (e.g. visual feedback signals obtained from a retina implant, auditory feedback signals obtained from a cochlea implant etc.). Naturally, such plain sensory feedback is thus limited to physiological sensory modalities.

It is thus a problem underlying the one aspect of the present application to overcome such deficiencies of previous technologies by providing novel neuronal stimulation equipment that may be used for treating or rehabilitating cognitive and/or motor deficits due to neurological disorders or injury. One aspect of the present application is further directed to provide novel behavioral training paradigms and devices that are based on neurostimulation techniques.

Moreover, the available systems for monitoring or detecting a deteriorating physiologic or mental state of an individual cannot be calibrated for individual patients and thus lack the capability to perform patient specific device functioning optimization. Moreover, the way how monitoring is executed and / or how the individual may be informed about the result of the monitoring may be inefficient, inconvenient and / or unreliable.

Moreover, several of the prior art systems use bulk body tissue such as bones, fat tissue and / or bulk muscle tissue to transmit non-physiologic signals in an undirected way through the body of an individual. This approach maybe harmful to the individual, easily affected by external interference and / or require substantial transmit power due to signal dampening within the respective body tissue.

Accordingly, treating deteriorating homeostatic mechanisms and similar medial conditions with prior art devices and systems may not always lead to satisfying results.

It is thus a problem underlying the present invention to overcome such and similar deficiencies of previous technologies. 3. Summary of the invention

Some of the above-mentioned problems are at least partially solved by a closed loop CBI (CLCBI) device as specified in independent claim i and by the computer program of independent claim 17. Exemplary embodiments of the present invention are specified in the dependent claims.

Generally, the present invention allows to implement a novel closed-loop approach to patient rehabilitation and recoveiy as well as sensory enhancement and behavioral task training. This approach is based on direct neurostimulation of afferent sensory axons (e.g. thalamoctical axons and / or afferent sensoiy axons of the spinal cord) targeting directly or indirectly (i.e. via multi-synaptic afferent pathways of the central nervous system) specific sensory neurons in the cortex to support an individual with executing a behavioral task while taking into account task performance and / or a behavioral or movement state of the patient via a feedback loop, for purposes including enhanced motor, sensory and cognitive learning and/or memoiy formation. For instance, the present invention is well suited to reinforce active daily living tasks (ADL) in patients recovering from post-stroke symptom. A simple instance of such a behavioral task may include a reach and grasp task where selective neurostimulation provided at pitch moments during the task can provide sensory cues associated with task training indications to the individual in the same manner as a human therapist assisting the individual to better learn the task.

More specifically, the present invention provides a CLCBI device for an individual comprising a receiver module configured to obtain at least one sensor signal indicative of a movement or action of the individual, a processing module operably connected to the receiver module and configured to determine at least one neuronal feedback signal based at least in part on the obtained sensor signal and a transmitter module operably connected to the processing module and configured to transmit the determined neuronal feedback signal to a neurostimulation device of the individual or a neurostimulation module operably connected to the processing module, wherein the neuronal feedback signal is configured to elicit a sensory percept in the cortex of the individual via stimulating afferent sensoiy axons of the central nervous system targeting sensoiy neurons of the cortex, and wherein the elicited sensoiy percept indicates movement support information related to the obtained sensor signal to support the execution of the movement or action of the individual. The various modules of the devices and systems disclosed herein can for instance be implemented in hardware, software or a combination thereof. For instance, the various modules of the devices and systems disclosed herein may be implemented via application specific hardware components such as application specific integrated circuits, ASICs, and / or field programmable gate arrays, FPGAs, and / or similar components and / or application specific software modules being executed on multipurpose data and signal processing equipment such as CPUs, DSPs and / or systems on a chip (SOCs) or similar components or any combination thereof.

For instance the various modules of the CLCBI device discussed above may be implemented on a multi-purpose data and signal processing device configured for executing application specific software modules and for communicating with various sensor devices and / or neurostimulation devices via conventional wireless communication interfaces such as a NFC, a WIFI and / or a Bluetooth interface.

Alternatively, the various modules of the CLCBI device discussed above may also be part of an integrated neurostimulation apparatus, further comprising specialized electronic circuitry (e.g. neurostimulation signal generators, amplifiers etc.) for generating and applying the determined neuronal feedback signals to a neurostimulation interface of the individual (e.g. a multi-contact deep brain stimulation (DBS) electrode, a spinal cord stimulation electrode, etc.).

The neuronal feedback signals generated by the CLCBI device described above may for instance also be transmitted to a neuronal stimulation device comprising a signal amplifier driving a multi-contact DBS electrode that may already be implanted into a patient’s brain for a purpose different than providing the neuronal feedback signals or to a spinal cord stimulation interface. Alternatively, dedicated DBS-like electrodes or spinal cord stimulation electrodes may be implanted for the purpose of applying the neuronal feedback signals generated by the CLCBI device via established and approved surgical procedures that were developed for implantation of conventional DBS electrodes or spinal cord stimulation electrodes. Further, as mentioned above the CLCBI device described above may also be integrated together with a neuronal stimulation device into a single device.

Further, it is important to note that the movement support information that is indicated by the sensory percept elicited by the neuronal feedback signal differs from mere sensory feedback. As will be explained in detail below (see for example Fig. 6 and Fig. na /b) any kind of abstract information that can support the execution of the movement or action (e.g. a geographic position indication, a distance indication, a movement trajectory indication etc.) can be transmitted to the individual with a CLCBI device according to the present invention. For instance, different neuronal feedback signals may be configured to elicit sensory percepts related to a specific sensation (e.g. a tough sensation in the left hand) having different characteristics (e.g. different intensities or frequencies). The CLCBI device provided by the present invention may then be calibrated such that the different characteristics of the elicited sensory percept indicate different movement support information such as different distances to an object that is to be manipulated by the individual or a degree of deviation from a desired movement trajectoiy that is to be executed by the individual.

For instance, the action or movement executed by the individual and supported by the CLCBI device maybe associated with a training task and the movement support information may support the individual with performing the training task.

In particular, the movement support information provided by the neuronal feedback signal may be configured to provide one or more of the following to the individual: a distance indication relating to an object to be manipulated by the individual, an orientation indication for the individual or a body part of the individual, a success or failure indication for a training task executed by the individual, an indication, preferably continuous, of a desired or unwanted trajectory of a movement or action to be executed by the individual, an indication quantifying a degree of deviation from a desired trajectory of a movement or action to be executed by the individual, an indication designating a desired or unwanted object to be manipulated by the individual, an indication to start of stop the execution of the movement or action and an indication configured to provide the individual with a non-verbal instruction related to the execution of a task.

The present invention also provides a computer program comprising instructions for carrying out the following steps when being executed by the signal processing and transceiver modules of a signal and data processing device, a neuronal stimulation device or system: obtain at least one sensor signal indicative of a movement or action of an individual, determine a neuronal feedback signal based at least in part on the obtained sensor signal, and transmit the neuronal feedback signal to a neurostimulation device or module of the individual, wherein the neuronal feedback signal is configured to elicit a sensory percept in the cortex of the individual via stimulating afferent sensory axons of the central nervous system targeting sensory neurons of the cortex, and wherein the elicited sensory percept indicates artificial movement support information related to the obtained sensor signal to support the execution of the movement or action of the individual.

Further, the at least one sensor signal that is obtained by the CLCBI device maybe indicative of at least one of the following: a position, distance, and / or orientation of a body part of the individual with respect to a fixed reference frame and / or another body part of the individual, and / or an object to be manipulated by the individual; a muscle tension, contraction and / or relaxation state of the at least one body part of the individual; a flexion, extension, supination, pronation and / or rotation angle of a joint of the at least one body part of the individual; a movement speed or acceleration associated with the at least one body part; a contact pressure between a portion of the at least one body part and an object to be manipulated by the individual.

In this way the CLCBI device is enabled to obtain and take into account detailed information about the state of the body of the individual that is operating the CLCBI device (e.g. while performing a behavioral learning / training task or a rehabilitation and recovery procedure) and thus is enabled to determine and transmit highly specific neuronal feedback signals that facilitate faster and more task specific learning success. As mentioned above the neuronal feedback signal may be determined based on processed input data from multiple signal sources such as video cameras and force, acceleration and / or position sensors, or biopotential transducers. The processed feedback information may be utilized to trigger neurostimulation by activating appropriate perceptual / sensory communication channels. In this manner, the present invention allows the use accurately timed message blocks that provide effective and automatic sensory feedback cues to the individual to enhance and fine-tune performance on behavioral tasks.

For instance, the obtained sensor signals maybe received from at least one of the following sensor devices: a computer vision tracking device; a kinematic sensor device; a touch sensor; a force, angle, position, tension and / or acceleration sensor device; an electroencephalography device; an electromyography device; a skin conductance, respiratory rate, electrocardiogram, and temperature sensor device, a deep brain local field potential recording device; and an electrocorticography device.

The receiver module of the CLCBI device may further be configured to obtain training data indicative of a training task associated with the movement or action of the individual.

For instance, the movement support information may indicate to the CLCBI device that a desired behavioral task was completed successfully or partially successfully or that the task has failed. Other movement support information might provide information about a desired movement trajectory to be executed during training. In response, the CLCBI device may generate a neuronal feedback signal that is transmitted to a neuronal stimulation device of the individual (e.g. a neurostimulation signal generator and amplifier driving one or more contacts of a DBS electrode or a spinal cord stimulation electrode), wherein the neuronal feedback signal is configured such that a sensory percept is elicited in the cortex of the individual corresponding to the desired movement support information, e.g. providing the desired training indication as discussed above.

Further, the CLCBI device described above maybe further configured to access a data storage device storing a plurality of relations, specific for the individual, associating a plurality of neuronal feedback signals with a plurality of corresponding movement support information. In some embodiments, the CLCBI device may also include the data storage device storing the plurality of relations, specific for the individual, associating the plurality of neuronal feedback signals with the plurality of corresponding movement support information.

For instance, the data storage device may contain a personalized communication library for the individual, the library storing the relations between a plurality of movement support information and a plurality of corresponding neuronal feedback signals. Such a stimulation / feedback signal library can be calibrated for each individual through neuroimaging and / or individualized testing of the individual. Neuroimaging may first be used to identify theoretically possible ranges of activation for an individual stimulation electrode while individualized testing determines which points in the parameter space of feedback signal parameters can be perceived and decoded by the cortex of the individual. It should be emphasized that conscious individualized testing of an individual is merely one specific example of how to generate the individualized relations stored in the memory. In other embodiments such relations may also be obtained from unconscious patients, e.g. through the non- invasive observation of corresponding functional MRI responses on the somatosensory cortex or EEG recordings.

Further, once the communication library is established or while it is being established for an individual a specific training procedure can be executed that links a specific sensory percept to the corresponding movement support information. As long as the cortex of the individual responds to classical conditioning, pair learning can be executed. In the context of the present invention, such a pair consists of a given sensory percept corresponding to a given neuronal feedback signal and the corresponding movement support information (e.g., an indication related to execution of a behavioral training task / procedure as discussed above) to be associated with said given sensory percept and the corresponding neuronal feedback signal.

Importantly, the type of information to be conveyed via the CLCBI device described above whether it is a movement support information or similar information can be chosen more or less freely. Any information or message which can be broken down into message blocks (i.e. pieces of conceptual information that can be decoded by the cortex of an individual) can be transmitted. This includes continuous neuronal feedback signals such as a (quasi-) continuous indication of a desired movement trajectory or other information that may be relevant for executing the desired movement or action (e.g. a start or stop indication, an indication of objects to be avoided or manipulated, etc.).

In particular, the specific relations may be based at least in part on one or more of the following: conceptual or perceptual learning data for the individual, neuro-imaging data for the individual, electrophysiological measurement data for the individual, neuronal connectivity information for the individual, electric field simulation data for the neurostimulation device of the individual and neuronal excitability model data for the individual. In this way, even complex movement support information such as a continuous movement trajectory indication can be associated with corresponding sensory percepts that are specific for each individual. For instance, the individual may participate in a conceptual learning procedure in order to establish a perceptual communication channel (PC) for communicating artificial sensory input signals provided from a motion tracking camera system or similar sensor equipment.

Further, the neuronal feedback signal may be characterized by a plurality of signal parameters such as a signal waveform, a signal frequency, a signal polarity, a signal pulse shape, a signal amplitude and / or a signal pulse width and wherein different combinations of signal parameters correspond to different movement support information.

Moreover, the neuronal feedback signal may be adapted to elicit a sensory percept in a portion of the cortex of the individual that is associated with a specific sensory modality and wherein the portion of the cortex is one or more of the following: a somatosensory cortex area; an auditory cortex area; a visual cortex area; an olfactory cortex area; an entorhinal cortex area or components of the circuit of Papez.

In particular, the neuronal feedback signal may be configured to stimulate thalamocortical axons projecting from the thalamus to the sensory neurons of the cortex. For instance, if the neuronal feedback signal is to be applied via a conventional DBS electrode the signal parameters of the neuronal feedback signal may be adjusted such that action potentials are elicited in specific sub-populations of such thalamocortical axons, e.g. in a set of axons projecting to specific somatosensory neurons in the cortex. Alternatively or additionally, the neuronal feedback signal may also be configured to stimulate afferent sensoiy axons of the spinal cord projecting directly (i.e. via a monosynaptic pathway) or indirectly (i.e. via a multi-synaptic pathway) to the thalamus or the cortex.

In general, the sensational modality, location, type, and intensity of the sensory percept that is elicited in the cortex in response to these afferent action potentials can be controlled via precise electrode location and selection of neurostimulation parameters. The present invention uses such artificial sensations to transmit information directly to the brain in form of discrete or continuous message blocks by forming the desired PCs. As discussed above the PCs may be established via a single or via multiple electrical contacts of a DBS electrode or a spinal cord stimulation electrode which are electrically activated with calibrated neurostimulation parameters to deliver specific sensory messages to the individual. The sensation modality of the mentioned PCs may include tactile, proprioceptive, visual, or auditory sensations based on the application or location and orientation of the implanted stimulation electrode.

Furthermore, various biological signals, including kinematic data (accelerometer) and those obtained using electromyography (EMG), EEG, ECoG, and local field potentials, (LFPs), could also be considered as sensor input signals that may be used by the CLCBI device to determine corresponding neuronal feedback signals. Each of these feedback modalities varies with respect to invasiveness, resolution, signal content, and clinical relevance. For instance, data from accelerometers can detect onset of the movement or alternatively detect symptoms such as tremor. Surface EMG (sEMG) from symptomatic limbs or muscle groups can provide useful information as a biomarker for example to initiate stimulation in a movement-triggered fashion.

In a further embodiment, the present invention provides a recovery and rehabilitation system comprising the above discussed CLCBI device. For instance, such a recovery and rehabilitation system may in addition to the CLCBI device also comprise at least one of the above described sensor devices and / or the above described data storage device and / or a neuronal stimulation device and / or a corresponding neurostimulation electrode. Several or all of these system components may also be integrated in a single integrated multi-purpose neuronal stimulation device.

Further, the above discussed CLCBI device may also be used in a prosthetic system for an individual comprising - in addition to the CLCBI device - an electromechanic prosthetic device for the individual and a control interface, device configured to control the electromechanic prosthetic device, wherein the movement support information transmitted by the CLCBI device is configured to support the control of the electromechanic prosthetic device via the control interface.

Such a prosthetic system may further comprise at least one of the sensor devices and / or the data storage device described in detail above.

Moreover, the control interface device of such a prosthetic system may comprise a brain computer interface device, BCI, configured to monitor neural activity of the individual related to the control of the electromechanic prosthetic device. In this way, one aspect of the present invention even facilitates the design of novel closed loop artificial body parts.

Embodiments directed to physiologic signal transmission

Further, some of the above-mentioned problems are at least partially solved by a physiologic signal transmitter device of claim 20 and a physiologic signal receiver device of claim 37 as well as by a corresponding computer program.

Specifically, the present invention provides a physiologic signal transmitter device for an individual, comprising a receiver module configured to obtain one or more sensor signals monitoring one or more physiologic and / or mental states of the individual, a processing module operably connected to the receiver module and configured to determine one or more stimulation signals based at least in part on the obtained one or more sensor signals and a stimulation module operably connected to the processing module and configured to apply the determined stimulation signals to a physiologic system or structure of the individual via a physiologic stimulation device of the individual. The one or more stimulation signals are configured to elicit one or more artificial physiologic excitations propagating along the physiologic system or structure of the individual and the one or more artificial physiologic excitations encode information about the monitored one or more physiologic and / or mental states of the individual.

In this context and for the remaining part of this application the term “physiologic and / or mental state” is to be understood such that it does not cover a behavioral state (e.g. a movement) of the individual. Thus, the above-mentioned sensor signals do not monitor movement states or behavioral states of the individual.

In essence, the present invention allows to implement a novel physiologic signal transmission system based on artificial physiologic excitations of a natural physiologic system or structure of an individual. In contrast to several of the prior art systems this approach is thus not based on transmitting non-physiologic signals via bulk body tissue such as ultrasound signals or non-physiologic electrical signals. For instance, the physiologic system or structure used by the physiologic signal transmission system may comprise one or more of the following: a muscle fiber of the individual, a nerve fiber or neuron of the individual, a blood vessel of the individual.

Further, the artificial physiologic excitation may comprise one or more of the following: on or more action potentials, sub-threshold electrical activity of muscle fibers of the individual, sub-threshold electric potentials of nerve fibers or neurons of the individual and / or an artificial modulation of a natural physiologic excitation of the physiologic system or structure, such as an amplitude modulated, shape modulated and / or frequency modulated heartbeat of the individual.

By not transmitting non-physiological signals through bulk body tissues unwanted side effects and / or the otherwise inevitable damping of signal strength can substantially be reduced. In essence, the present invention greatly increases the versatility, biocompatibility, directivity and power efficiency as compared to prior art systems.

In some embodiments of the present invention the natural physiologic structure or system may project to a target organ and / or a target position within the body of the individual associated with an external or surgically implanted device of the individual.

In this way, the high degree of directivity and spatial resolution of natural physiologic structures capable of propagating natural and artificial physiologic excitations can be used to interface the physiologic signal transmission device with one or more receiver devices or to communicate information about the monitored physiologic or mental states to the cortex, as explained in more detail below.

Further, a binaiy code maybe used to encode the transmitted information. Alternatively, or additionally part of the transmitted information may also be encoded in analog form. In this way, common modulation and coding techniques know from electrical signal transmission systems may readily be applied to the physiologic signal transmission devices and systems provided by the present invention.

In some embodiments, the one or more physiologic excitations are generated by the physiologic signal transmission device such that the normal function of the physiologic system or structure and / or of the target organ or target position is not substantially affected by the one or more physiologic excitations.

In this way, the provided physiologic signal transmission device can reliably exchange information with one or more receiver devices without affecting the normal functioning of the body of the individual and even without being sensed or perceived by the individual.

In some embodiments, the stimulation module of the physiologic signal transmission device may be configured to apply the determined stimulation signals to a neurostimulation electrode of the individual. In this case, the one or more stimulation signals may be configured to elicit one or more electrophysiologic excitations propagating in one or more nerve fibers or neurons (e.g. within the vagus nerve and / or efferent motor neurons), projecting to a target organ or target position of the individual and wherein the one or more stimulation signals may then elicit one or more electrophysiologic excitations that encode information related to the obtained one or more sensor signals.

Due to their excellent signal transmission properties, nerve fibers and in particular myelinated axons allow for highly efficient signal transmission with low power consumption and high bandwidth.

For instance, if a binary code and / or analog encoding is used for physiologic signal transmission encoding the transmitted information may be based on one or more of the following, an interspike interval, an excitation amplitude, a spike count within a burst, a spike frequency within a bust, an excitation duty cycle and / or an excitation waveform or pulse shape.

Further, the one or more electrophysiologic excitations may be generated such that the normal function of the one or more nerve fibers or neurons and / or of the target organ or target position is not substantially affected by the one or more electrophysiologic excitations. For instance, the one or more electrophysiologic excitations may be generated such that they lie outside a natural frequency range, amplitude range and / or excitation signal shape range of the one or more nerve fibers or neurons projecting to the target organ or position of the individual.

Alternatively, or additionally, the one or more electrophysiologic excitations may correspond to a non-natural spiking patter within the one or more nerve fibers or neurons projecting to the target organ or target position of the individual.

More specifically, the frequency and / or the amplitude and / or the signal shape of the one or more stimulation signals may be chosen such that no action potentials are elicited in the one or more nerve fibers or neurons.

Alternatively, the frequency and / or the amplitude and / or the signal shape of the one or more stimulation signals may be chosen such that action potentials that are elicited in the one or more nerve fibers or neurons do not activate synapses of the one or more nerve fiber or neurons that affect the function of the target organ or target position.

For example, a pulse frequency of the stimulation signals maybe chosen larger or equal to io kHz, and / or a pulse duration of the one or more stimulation signals may be chosen smaller or equal to a i ps and / or the pulse frequency of the stimulation signals may be chosen substantially larger than the inverse of a refractory period of the one or more nerve fibers or neurons.

In this manner, any kind of information about the one or more monitored physiologic or mental states of the individual can safely and reliably transmitted via the nervous system of the individual to any kind of receiver device or reception organ without interfering with the normal function of the nervous system.

Importantly, the encoding of the monitored states is implemented as physiologic signals which are then transmitted along the body’s own natural neural communication pathways, namely the peripheral and/or central nervous system. For instance, a blood composition sensor in the carotid artery could (instead of transmitting the sensor data outside of the body or along an implanted wire) stimulate the vagus nerve in downstream direction with a signal train that does not change the nerve function itself but can be successfully decoded by a downstream implanted second device (the recipient; see below) to react in a pre-programmed manner, forming a within-body closed-loop system using the natural nervous system as the information signaling pathway. In some application of the present invention differentiate signals transmitted via the nerve fibers do not themselves alter the target organ’s (where that nerve terminates) function, but rather regulates or instruct an effector device which in turn may alter that target organ’s function.

In another embodiment of the present invention the stimulation module may be configured to apply the determined one or more stimulation signals to a neurostimulation electrode of the individual, wherein the one or more stimulation signals are configured to elicit one or more electrophysiologic excitations in one or more nerve fibers or neurons of the central nervous system projecting to the sensoiy cortex of the individual, wherein the one or more electrophysiologic excitations are configured to elicit a sensoiy percept in the sensory cortex of the individual, and wherein the elicited sensory percept provides information to the individual about the one or more monitored physiologic and / or mental states of the individual.

In other words, the electrophysiologic excitations generated by the physiologic signal transmitting device may not only be transmitted to electronic receiver devices but also to the sensory cortex of the individual. Naturally, the encoding of the information must be performed such, that the sensory cortex can decode it.

For such embodiments of the present invention the processing module may further be configured to derive, based on the obtained sensor signals, a continuous or categorical metric characterizing the one or more physiologic and / or mental states of the individual, and the determined one or more stimulation signals may be configured to elicit a sensoiy percept in the cortex of the individual indicating a current value of the derived metric to the individual (see for example Fig. 6 below). For instance, the one or more sensor signals may monitor a mental state of the individual related to a recurring neurological condition and the derived metric may indicate to the individual a likelihood for the neurological condition to recur.

Further, the processing module may be configured such that the determining of the one or more neural stimulation signals comprises determining one or more signal parameters of the one or more neural stimulation signals based at least in part on a determination function that maps the current value of the metric to one or more values of the one or more signal parameters.

For example, the one or more signal parameters may comprise one or more of the following: one or more activated stimulation channels, a signal amplitude, a signal frequency, a signal duty cycle, a signal pulse width, a signal polarity, a signal burst frequency, a signal burst spike count and / or the determination function may comprise an activation function such as a sigmoid function, a gaussian function, a rectified linear function, a logistic function, a hyperbolic function.

In this manner the physiologic transmitter device is enabled to derive metrics about complex physiologic or mental states of the individual, such as psychologic stress levels, arousal states, depression states, and the like.

In some embodiments, the processing module may further be configured to derive, based on the obtained one or more sensor signals, a continuous or categorical metric characterizing the one or more physiological and / or mental states of the individual, to compare a current value of the metric to a reference value for the metric and, in response to determining that the current value of the metric has exceeded the reference value determine a stimulation signal that is configured to elicit a sensory percept indicating to the individual that the reference value was exceeded.

In this way, the physiologic signal transmitter device may be enabled to provide the individual with warning signals that the monitored physiologic or mental state is about to deteriorate and that countermeasures (e.g. drug or food intake, autogenic procedures, resting periods, etc.) are recommended. The one or more stimulation signals may even be configured to elicit a multi-modal sensory percept in the cortex of the individual, e.g. an essentially synchronous visual and touch sensation. In this manner, the amount of different types of information that can be transmitted about the monitored physiologic or mental states can substantially be increased.

In another embodiment, the present invention provides a corresponding physiologic signal receiver device for an individual, comprising a receiver module configured to obtain one or more physiologic measurement signals obtained from a physiologic measuring device or sensor monitoring the physiologic activity of one or more physiologic systems or structures projecting to a target organ or target position of the individual, a processing module operably connected to the receiver module and configured to extract transmitted information encoded in a subset of the obtained physiologic measurement signals, wherein the extracted transmitted information is related to one or more sensor signals monitoring one or more physiologic and / or mental states of the individual.

Such a physiologic signal receiver device may also comprise (or communicate with) one or more effector modules (or devices) configured to affect or modulate the function of the target organ or target position of the individual and / or a memory module storing predefined signal characteristics that are used for extracting the transmitted information from the obtained physiologic measurement signals and / or a stimulation module configured for applying a blocking stimulation to the one or more natural physiologic structures blocking or canceling the propagation of an artificial physiologic excitation encoding the extracted information downstream of the physiologic signal receiver device.

For instance, the effector modules (or devices) may comprise one or more of the following: an electrostimulation module, a drug administration module, a heating and / or cooling module, a light emission module, an artificial synapse and / or a vibration or ultrasonic effector module.

Based on the specifications provided above, the present invention also provides a physiologic signal transmission system for an individual, comprising one or more of the above discussed physiologic transmitter devices and one or more of the physiologic signal receiver devices discussed above, wherein at least a subset of the physiologic systems or structures stimulated by the one or more physiologic signal transmitter devices are monitored, at least indirectly, by the one or more physiologic signal receiver devices.

In this manner, various types of present or future electroceuticals (implanted or external) can easily communicate with each in a reliable, biocompatible and highly directive and thus power efficient manner.

For instance, also integrated physiologic monitoring systems can be designed that comprise such a physiologic signal transmission system and one of the above physiologic signal transmitter devices that provide information about the monitored physiologic or mental states of the individual to the sensory cortex of the individual.

The one or more sensor signals may relate to a blood pressure, a blood composition, a drug or body substance level of the individual, a stress level, and / or a neural activity level or pattern of the individual.

For instance, such sensor signals maybe received from at least one of the following sensor devices: a touch sensor; an electroencephalography device; an electromyography device; a sensor device for measuring a skin conductance, a respiratory rate, an electrocardiogram, and / or a temperature; a deep brain local field potential recording device; a chemo-sensor device for measuring the concentration of a substance in a body fluid of the individual; and an electrocorticography device.

In essence, the present invention thus allows to establish a physiologic communication channel between implanted or external transmitter and receiver devices based on artificially elicited physiologic excitations (e.g., neural or muscle excitations). 4. Short Description of the Figures

Various aspects of the present invention are described in more detail in the following by reference to the accompanying figures. These figures show:

Fig. 1 a diagram illustrating an individual taking part in a behavioral training task such as a recovery and rehabilitation procedure using a CLCBI device according to an embodiment of the present invention;

Fig. 2 a diagram illustrating a movement or action of an individual that may be supported by movement support information generated by a CLCBI device according to an embodiment of the present invention;

Fig. 3 a diagram illustrating a force sensor generating a sensor signal that may be used as input to a CLCBI device according to an embodiment of the present;

Fig. 4 a diagram illustrating the design of a closed loop balance rehabilitation system using an array of accelerometers in conjunction with a CLCBI device according to an embodiment of the present invention;

Fig. 5 a diagram illustrating the design of a closed-loop balance rehabilitation system using accelerometers and gyroscopes integrated with a CLCBI device according to an embodiment of the present invention;

Fig. 6 a diagram illustrating the design of a (quasi-)continuous closed-loop motion correction system based on a CLCBI device according to an embodiment of the present invention;

Fig. 7 diagram illustrating a neuronal stimulation electrode for stimulating afferent axons targeting the sensory cortex of an individual. The neuronal stimulation electrode can be interfaced with a CLCBI device according to an embodiment of the present invention; Fig. 8 a diagram illustrating a therapeutic multi-contact neuromodulation electrode. The electrode can be used for stimulating afferent axons of the central nervous system targeting the sensory cortex of an individual via a CLCBI device according to an embodiment of the present invention.

Fig. 9 a functional block circuit diagram illustrating a CLCBI device according to an embodiment of the present invention;

Fig. io a functional block circuit diagram illustrating a CLCBI device according to another embodiment of the present invention;

Fig. na a diagram illustrating an individual taking part in a behavioral training task using a CLCBI device according to an embodiment of the present invention; the subject is non-verbally informed to stop approaching an undesired target utilizing a specific PC established via sensory percepts associated with the arm region.

Fig. lib a diagram illustrating an individual taking part in a behavioral training task using a CLCBI device according to an embodiment of the present invention; the subject is non-verbally informed to approach towards a desired target utilizing a specific PC established via sensoiy percepts associated with the hand area.

Fig. 12 a diagram illustrating an individual operating a stress level monitoring system using an implanted blood pressure / heart rate sensor as well as wearable external sensor;

Fig. 13 a diagram illustrating signal transmission via a nerve to send encoded information in spikes / action potentials to a receiver implanted next to the target organ;

Fig. 14 a diagram illustrating another example of signal transmission via muscle fibers to control bladder function; Fig. 15 a functional block diagram of a physiologic signal transmitter device according to an embodiment of the present invention;

Fig. 16 a functional block diagram of a physiologic signal receiver device according to an embodiment of the present invention;

Fig. 17 illustrates how an artificial electrophysiologic stimulation signal can be used to elicit a sensory percept in the cortex of an individual encoding a metric characterizing the stress level of an individual.

5. Detailed Description of some exemplary embodiments

In the following, some exemplary embodiments of the present invention are described in more detail, with reference to a CLCBI device that can be interfaced with neuronal stimulation electrodes such as DBS electrodes and / or spinal cord stimulation electrodes, e.g. via an intermediate neuronal stimulation device. However, the present invention can also be used with any other neuronal stimulation interface that is capable of stimulating afferent sensory axons of the central nervous system targeting the sensory cortex of an individual.

While specific feature combinations are described in the following with respect to the exemplary embodiments of the present invention, it is to be understood that not all features of the discussed embodiments have to be present for realizing the invention, which is defined by the subject matter of the claims. The disclosed embodiments may be modified by combining certain features of one embodiment with one or more features of another embodiment. Specifically, the skilled person will understand that features, components and / or functional elements of one embodiment can be combined with technically compatible features, components and / or functional elements of any other embodiment of the present invention.

Figure 1 depicts an individual too, e.g. a stroke patient, that takes part in a behavioral training task such as a rehabilitation and recovery procedure. The individual too has been implanted with a neuronal stimulation electrode 101 such as a DBS electrode or spinal cord stimulation electrode that may have multiple independently controllable electric contacts (see also Fig. 8). For instance, the neuronal stimulation electrode 101 may be already implanted into the brain of the individual too for the purpose of providing a neuromodulation therapy, e.g. for treating PD symptoms. The neuronal stimulation electrode 101 may also be implanted for other purposes such as for the purpose of neuronal communication and /or treatment of other movement impairments and neurological diseases such as Alzheimer’s disease, epilepsy, depression, etc. Alternatively, the electrode 101 may also be implanted as a dedicated neurostimulation interface for the CLCBI devices provided by the present invention.

The individual too may be further equipped with a neurostimulation device 102, that may be an implantable and programmable pulse generator (IPG) implanted under the skin if the individual. Alternatively, the neurostimulation device 102 maybe arranged on the head of the individual too or somewhere else on or in the vicinity of the body of the individual too. The neurostimulation device 102 may be in wireless communication (e.g. via a Bluetooth, WI-FI, NFC or a similar wireless interface technology) with a control device / pocket processor 103, that may be implemented by a dedicated signal and data processing device such as a smartphone or a similar electronic information processing device. Depending on implementation details, the CLCBI devices provided by the present invention may be implemented via application specific hardware and / or software modules comprising circuitry and / or software instructions to implement the devices and systems according to the present invention.

The control device / pocket processor 103 may provide the individual too with a user interface to adjust the neuronal feedback signals and /or a neuromodulation therapy applied via the neurostimulation device 102 and the neuronal stimulation electrode 101. The control device 103 may also provide connectivity to a packet based wireless large area network such as an LTE or 5G network. For instance, the individual too may use the control device 103 to adjust signal parameters such as a signal frequency, a pulse width, a pulse shape and /or a signal amplitude of the neuronal feedback signals as well as for retrieving data from the internet.

The various modules of the CLCBI device provided by the present invention may be implemented by the control device 103, the neuronal stimulation device 102 or by a combination thereof (for examples see Figs. 9 and 10). The CLCBI device provided by the present invention can for instance assist patients that are rehabilitating from sensory-motor deficits due to acute or chronic neurological disease such as stroke via performing repetitive goal-directed sensory-motor tasks, as depicted in Fig. 1. During the rehabilitation procedure, the patient is instructed to perform a therapeutic task such as reaching and grasping for an object 108. The reaching motion could be defined in such a way that it incorporates specific muscle groups that require rehabilitation.

The communication channels established by the CLCBI device may be utilized in different ways including but not limited to cueing the patient at an exact moment in time to provide artificial sensory feedback cues to the patient. The cueing information may include physical requirements of correct task performance such as ideal hand position joint angles, adequate force to hold an object, or information about shape or texture of objects.

Information such as sEMG muscle activity 105, accelerometer or gyroscope data 106, as well as the outputs of a motion tracking system 107 may be input into the pocket processor / control device 103. The pocket processor / control device 103 may be responsible for performing preprocessing on raw input information to remove noise and artifacts. Afterwards, the input data may be further analyzed by the pocket processor / control device 103 in order to determine at which point in time what type of stimulation program needs to be activated by the IPG 102. Each message block may therefore include a series of stimulation programs which may be preloaded in the IPG during a calibration phase. Once data processing is finalized on the pocket processor 103, it may transmit trigger information along with a list of programs to the IPG via a wireless link 104.

In order to establish a PC, individuals may take part in an initial calibration and learning procedure where the individual too learns the interpretation of each movement support information through an initial training period. For example, activation of the first PC with medium intensity could be felt in the arm of the individual and then be assigned to a trial success indicator. Other PCs could be utilized to inform the individual too about a joint angle of the hand of the individual in a graded way such that low intensities resemble a relaxed joint and higher stimulation intensities represent a constricted or fully closed hand.

Further, the individual’s limb position may continuously be tracked during task performance via a video tracking system 107 and / or via wearable accelerometers 106. The tracking data may be compared with an expected trajectory model by the pocket processor / control device 103. In case the actual limb motion is in accordance with the expected or desired trajectory, a success feedback signal is sent to the individual via the CLBIS device. This may be used to help the individual 100 to reinforce the correct movement and facilitate the learning and neuronal reorganization process by the brain.

Further, the movement support information could also be triggered via or based on monitoring of sEMG signals. More precisely, the individual’s mobility may be restricted due to limited intensity of efferent motor signals from the brain. While these subthreshold motor signals could not lead to limb movement, the existence of residual EMG activity can be detected and after each detection, a success message can be transmitted to the individual as neuronal feedback signal.

A PC with specific intensity level can also be used to translate timing cues to the individual. As illustrated in Fig. 2 another embodiment could involve generating timing cues to instruct the individual to open the hand as in 201 or close it again once the hand is in the correct position 202.

In another embodiment, as depicted in Fig. 3, the target object could be equipped with at least one force or touch sensor 303 providing a sensor signal corresponding to the strength of a grasping force the individual exerts of the target object when grasping it 301, 302. The force sensor 303 may also be linked to the pocket processor / control device 103 and the IPG 102 can modulate the stimulation intensity or other signal parameters of a PC based on the amount of pressure being exerted to the object.

This may be beneficial when training individuals who have lost sense of touch due to brain injuries or diseases. The CLCBI device could assist an individual performing joint angle anticipation tasks in which the individual must guess the correct joint angle in the affected limb using no visual information. The correct joint angles could be extracted in real-time mode using a computer vision system then translated into continuous stimulation patterns after being assigned to a PC. In this way, the individual can get real-time and continuous training by perceiving the joint angle via a substitute sensory modality.

The CLCBI devices provided by the present invention can be further applied to virtual reality, augmented reality, and sensory enrichment paradigms with the aim of creating a sensory-rich environment for the individual. In such applications, the individual wears goggles equipped with built-in displays then performs different tasks via interacting with objects in the virtual world using wireless joysticks. Each object may have specific properties such as texture, shape, size, or rigidity. The position of the hand-held joysticks are continuously rendered via built-in accelerometers and infra-red tracking equipment. This approach may be used to provide movement support information to the individual in order to re-educate motor skills, for example, teach the individual how to reach for a target object and grasp it correctly. After the individual has accomplished the reaching task a series of separate movement support information (using other PCs) could artificially substitute a sense of touch to teach an individual to maintain a constant pressure required for holding the virtual target.

Another embodiment of the present invention includes assisting individuals, e.g. poststroke patients, with a compromised sense of balance. For instance, the system depicted in Fig. 4 may allow an individual to maintain a correct posture and prevent falls. An array of accelerometers 403 could for instance be incorporated in a training jacket. The sensors 403 may be linked with a pocket processor / control device 405 which is in wireless communication 404 with an implanted IPG / neurostimulation device 402. The IPG 402 may be linked with at least one or ideally two (or more) implanted stimulation electrodes 401. The pocket processor / control device 405 continuously analyses the sensor signals provided from all accelerometers 403 and may be configured to detect if the body is losing balance by swaying in one direction. The pocket processor / control device 405 may then wirelessly send necessary triggers to the IPG 402 to generate movement support information for the individual to counter the body sway. The perceived intensity of these balance cues may be proportional to the level of the body sway. Small body tilts are perceived by the subject as weak sensations while large tilts with risk of a fall are felt with larger perceived intensities.

Using bilateral DBS electrodes or bilateral spinal cord stimulation electrodes may enable the individual to experience a more naturalistic sensation with regards to the direction of the body sway such that location of the artificial perception is ipsilateral to the direction of body sway.

As shown in Fig. 5, the acceleration sensors and / or gyroscopes 503 could also be integrated inside the IPG 502 to alleviate the need for an external wearable array of accelerometers as well as wireless communication thus reducing electric power consumption while using similar implanted stimulation electrodes 501 as discussed for Fig. 4-

The CLCBI devices and system disclosed herein could also be embodied in a fashion to assist individuals to learn or master certain repetitive actions or skills by improving the safety and efficiency of their movements. For instance, the system could benefit from integrated inertia sensors to detect a state of the individual such as walking, running, or cycling. Each of the mentioned activities involve certain muscle groups which must become active sequentially at certain phases during the activity cycle. In a walking scenario, two PCs may be employed such that the individual can receive two sets of bilateral cues with different perceived intensities. Channel intensities may correspond with four different phases in the gait cycle including heel strike, early flatfoot, late flatfoot, and toe off. The same cycle may then be repeated for the other foot.

In another embodiment, the CLCBI device could be employed as a closed-loop motion corrective device as shown in Fig. 6. An example of a reach and grasp task is depicted where an individual must reach to a target 602 then after following a specific trajectory 603 place the target 602 inside a bucket. The trajectory of the hand 605 maybe determined using a wearable accelerometer 601 placed on the wrist of the individual. The accelerometer sensor 601 could also be equipped with infra-red reflective markers to enable hand motion tracking using a video camera as described above. The angle 604 of at least one joint may be calculated using the positional data with reference to the horizontal plane. For instance, the joint angle 604 calculation maybe done by a wearable pocket processor / control device 607. The initial and final shoulder joint angles in the sagittal plane are also marked by the pocket processor / control device 607. Corrective movement support information could be triggered by the pocket processor / control device 607 which is in wireless communication 608 with an IPG / neurostimulation device 606 that is configured to apply neuronal feedback signals to afferent sensory axons of the central nervous system targeting the sensory cortex of the individual as explained in detail above. Various movement support information maybe provided at specific points in time where the actual hand position 609 sways outside of the defined trajectory 603 (indicated by the lightning symbols in Fig 6). The stimulation could also get triggered to correct arm position provided that the joint angle falls outside of defined range 604.

Figure 7 depicts a neuronal stimulation electrode 702 for stimulating afferent axons 730 targeting sensory neurons in the cortex of a human brain. The afferent axons 730 that may target different sensory areas 710, 720 of the cortex that may be related to different sensory modalities (e.g. touch, temperature sense, vision, hearing, etc.) and / or different body regions (e.g. cochlea, retina, hand, tongue, foot etc.) from which the respective sensory modality is perceived by the respective area of the cortex. For instance, the cortical area 710 may be a somatosensory area of the right foot and the cortical area 720 may be a somatosensory area of the left hand.

The afferent sensory axons 730 are connected via synapses (not shown) with their respective target neurons in the respective sensory area 710, 720. For instance, the axons 730 may be thalamocortical axons relaying sensory information from the thalamus to the cerebral cortex. The neuronal stimulation electrode 720 may comprise a plurality of independently controllable electric contacts (see Fig. 8 below) that may be arranged in the vicinity of a bundle of afferent sensory axons 730 targeting the sensory areas 720 and 710 of the cerebral cortex.

In the illustrated example, the neuronal stimulation electrode 702 is connected to a neuronal stimulation device 701, which is adapted to apply neuronal stimulation signals to brain areas associated with certain neurophysiological symptoms and / or to the afferent sensory axons 730, e.g. via independently controllable electric contacts of the neuronal stimulation electrode 702. The neuronal stimulation device 701 may comprise the CLCBI device provided by the present invention or may communicate (e.g wirelessly) with the CLCBI device. In addition, the neuronal stimulation device 701 may further comprise a wireless interface for interfacing the neuronal stimulation device 701 with other devices such as the sensor devices described above or further devices that may be adapted to obtain and / or determine the waveform and / or signal parameters (e.g. pulse width, pulse shape, frequency, amplitude, number of pulses etc.) of the neuronal feedback signal that is applied by the neuronal stimulation device 701 to the afferent sensory axons 730 via the stimulation electrode 702.

For instance, the CLCBI device provided by the present invention may determine the waveform and / or signal parameters of the neuronal stimulation signal such that a desired sensory percept is elicited in a desired area of the sensory cortex of the individual. In some embodiments of the present invention, the cortex of the individual which is receiving the neuronal stimulation signal (i.e. via afferent action potentials of the stimulated afferent axons 730) may associate the corresponding sensory percept with several types of movement support information. For example, similar to learning how to understand Morse code, the individual may have previously participated in a learning procedure establishing an associative link between a given sensory percept elicited by a given neuronal stimulation signal and a corresponding movement support information that is to be communicated to the individual via the neuronal stimulation electrode 702.

In this approach no nuclei or neuron-rich grey matter are preferably targeted by the neuronal stimulation electrode 702 but preferably the axon-rich white matter of the brain or the spinal cord, which contains the information transmitting pathways the brain uses for natural neural communication of sensory information. In this manner, the present invention provides a white-matter computer-brain-interface, i.e. a device that generates and provides electrical signals the brain can interpret as meaningful sensory input, e.g. as a balance cue for countering loss of balance in recovering stroke patients.

As mentioned above the present invention is not limited to stimulating afferent sensory axons arranged within the brain. Another option, for example, is to stimulate afferent sensory axons in the spinal cord of the individual, e.g. via applying the neuronal feedback signals generated by the CLCBI device via a single or multi-contact spinal cord stimulation electrode. As long as the neuronal feedback signal is configured to elicit information carrying sensory percepts in the cortex of the individual, stimulation may be performed at various locations of the afferent sensory pathways of the central nervous system.

Figure 8 depicts a multi-contact neuromodulation electrode 802 e.g., adapted for neuromodulation of the sub-thalamic nucleus 820 via electric contacts 830. The electrode 802 can also be used for stimulating afferent sensory axons 842, 844 projecting from the thalamus 810 to the sensory cortex of an individual via a CLCBI device according to the present invention. For example, neuronal feedback signals may be provided by unused contacts 840, 850 of the neuromodulation electrode 802 that was implanted for a therapeutic purpose (e.g. neuromodulation of the subthalamic nucleus 820 via the therapeutic electric contacts 830) different from providing the neuronal stimulation signal to the afferent sensory axons 844, 842. For instance, the contacts that are not used for neuromodulation of the sub-thalamic nucleus 820 may be used to provide different kinds of movement support information to the cortex of the individual, e.g., for supporting the individual performing a behavioral training task such as a recovery and rehabilitation procedure. For example, such movement support information may be signaled via a sensory percept elicited by a neuronal feedback signal that is applied to the axons 844 targeting a cortex area related to a touch sensation for instance in the left foot or the right hand.

In many cases, an electrode 802 that is used as a neuromodulator, e.g., for treatment of symptoms of PD etc., is not always active and / or may comprise independently controllable contacts that are not required for achieving the therapeutic purpose. Thus, the neuromodulation electrode can also be used for applying neuronal stimulation signals provided by a CLCBI device according to the present invention. For instance, if implantation in e.g. the subthalamic nucleus 820 is conducted for the tip contacts 830 to control, for example, the primary PD symptoms more distal contacts 840, 850 could be used in combination with the above disclosed invention to communicate movement support information and directly into the brain of the patient. Fig. 9 illustrates an exemplary CLCBI device 900 according to an embodiment of the present invention. In this embodiment the CLCBI device 900 comprises an integrated neurostimulation module 910 (e.g., comprising a neuronal signal generator and an output amplifier) that is connected to a plurality of output signal leads 915 that may be interfaced with a neurostimulation interface of the individual (e.g. a DBS electrode or a spinal cord stimulation electrode). The CLCBI device 900 further comprises a communication antenna 920 operably connected to a transceiver module 930, configured for wireless communication (e.g., via NFC, Bluetooth or a similar wireless communication technology).

The transceiver module 930 is configured, for example, to receive one or more sensor signals from one or more sensors (as discussed above), indicative of an action or movement of an individual (e.g., a distance measurement obtained from a motion tracking sensor device, acceleration signals obtained form an accelerometer etc.). The transceiver module 930 is operably connected to a data / signal processing module 940 configured to generate one or more neuronal feedback signals and /or signal parameters (e.g., waveform, pulse shape, amplitude, frequency, burst count, burst duration etc.) for generating the one or more neuronal feedback signals. For instance, the processing module 940 may access a data storage module 950 configured to store a plurality of relations, specific for the individual, associating a plurality of neuronal feedback signals (or parameters used for generating a plurality of neuronal feedback signals) with a plurality of corresponding movement support information.

The generated neuronal feedback signal and / or the signal parameters are input into the integrated neurostimulation module 910 that may be configured to process (e.g., modulate, switch, amplify, covert, rectify, multiplex, phase shift, etc.) the one or more neuronal feedback signals generated by the processing module 940 or to generate the one or more neuronal feedback signals based on the signal parameters provided by the processing module 940.

The generated and processed neuronal feedback signals are then output by the neurostimulation module 910 and can be applied to one or more electric contacts of a neurostimulation electrode (e.g., a DBS electrode or spinal cord stimulation electrode; not shown) via output leads 915. The CLCBI device 900 may also comprise a rechargeable power source 960 that, for instance may be wirelessly charged via a wireless charging interface 970.

Fig. 10 illustrates a further exemplary CLCBI device 1000 according to an embodiment of the present invention. In this embodiment, the CLCBI device 1000 does not comprises an integrated neurostimulation module (see Fig. 9 above). Instead, the data / signal processing module 1040 is connected to a wireless transmitter module 1010 that is connected to a wireless transmit antenna 1070. The processing module 1040 maybe configured for generating one or more neuronal feedback signals and /or signal parameters (e.g., waveform, pulse shape, amplitude, frequency, burst count, burst duration etc.) for generating the one or more neuronal feedback signals. For instance, the processing module 1040 may access a data storage module 1050 configured to store a plurality of relations, specific for the individual, associating a plurality of neuronal feedback signals (or parameters used for generating a plurality of neuronal feedback signals) with a plurality of corresponding movement support information.

The transmitter module 1010 is configured for wireless communication (e.g., via NFC, Bluetooth, WIFI or a similar wireless communication technology) with a neurostimulation device of the individual (not shown; see Figs. 1, 4, 11a and 11b.). The transmitter module 1010 maybe configured to transmit the generated neuronal feedback signal and / or the generated feedback signal parameters to the neurostimulation device of the individual that maybe configured to process (e.g. modulate, switch, amplify, covert, rectify, multiplex, phase shift, etc.) the one or more neuronal feedback signals received from the transmitter module 1010 or to generate the one or more neuronal feedback signals based on the signal parameters received from the transmitter module 1010.

The CLCBI device 1000 further comprises a wired receiver module 1030 that is configured to receive / obtain one or more sensor signals from one or more sensors (as discussed above), indicative of an action or movement of an individual (e.g., a distance measurement obtained from a motion tracking sensor device, acceleration data obtained from an accelerometer etc.). In the embodiment of Fig. 10 the sensor signals are not received wirelessly but are obtained via sensor signal leads 1020. The neurostimulation device of the individual is configured to output and apply the generated and processed neuronal feedback signals to one or more electric contacts of a neurostimulation electrode (e.g., a DBS electrode or spinal cord stimulation electrode; not shown) to elicit the desired sensory percept.

The CLCBI device 1010 may also comprise a power source 1060 that, for instance may be a removable battery.

Similar to Fig. i discussed above, Fig. na and Fig. nb illustrate an individual, e.g. a stroke patient, taking part in a behavioral training task such as a rehabilitation and recovery procedure. The individual has been implanted with a neuronal stimulation electrode not / 1201 such as a DBS electrode or a spinal cord stimulation electrode that may have multiple independently controllable electric contacts.

The individual may be further equipped with a neuronal stimulation device 1105 / 1205, that may be an IGB implanted under the skin if the individual. The neuronal stimulation device 1105 / 1205 maybe in wireless communication 1104/1204 (e.g., via a Bluetooth, WI-FI, NFC, etc.) with a control device / pocket processor 1103/1203, that maybe implemented by a dedicated signal and data processing device, a smartphone or a similar electronic information processing device. Depending on implementation details the devices provided by the present invention may be implemented via application specific hardware and / or software modules comprising circuitry and / or software instructions to implement the devices and systems according to the present invention.

As discussed above with reference to Figs. 9 and 10 the various modules of the CLCBI device provided by the present invention may be implemented by the control device 1103 / 1203 or the neuronal stimulation device 1105 / 1205 or by a combination thereof.

Similar to the behavioral training task discussed in detail above with reference to Fig. 1 the CLCBI device may be configured to receive sensor signals from a motion tracking camera 1107 / 1207 and a wearable accelerometer 1106 / 1206. For instance, the individual’s limb position may continuously be tracked during task performance. The tracking data maybe used to determine whether the hand of the individual is moved into the vicinity of an object 1102 / 1202. Depending on the behavioral learning task, the individual may receive movement support information via the CLCBI device that may indicate whether the object 1102 / 1202 should be avoided (see Fig. 11a) or be manipulated (e.g., grasped, see Fig. 11b) by the individual. For instance, a neuronal feedback signal provided by the CLCBI device may have been associated with a specific sensory modality and location such as a tough sensation of increasing intensity on the upper arm of the individual (see 1108 in Fig. 11a) to indicate the degree of proximity to objects that should be avoided. In this manner, the CLCBI device is enabled to inform the individual when it comes close to a hot or dangerous object.

Another neuronal feedback signal provided by the CLCBI device may have been associated with a tough sensation of increasing intensity in the palm of the hand of the individual (see region 1208 in Fig. 11b), in order to indicate the degree of proximity to an object that is to be manipulated by the individual (e.g., to help a stroke patient to train drinking from a cup again)

Naturally, this approach may also be combined with further sensor signals such as a touch sensor on the surface of the cup or any of the sensor signals described in detail above.

Embodiments directed to physiologic signal transmission

In the following, some exemplary embodiments of the present invention are described in more detail, with reference to a physiologic signal transmitter and receiver device that can be interfaced with stimulation electrodes for muscle or nerve fibers. However, the present invention can also be used with any other stimulation device capable of stimulating physiologic systems or structures of an individual that can propagate artificially elicited physiologic excitations carrying information to be transmitted.

While specific feature combinations are described in the following with respect to the exemplary embodiments of the present invention, it is to be understood that not all features of the discussed embodiments have to be present for realizing the invention, which is defined by the subject matter of the claims. The disclosed embodiments may be modified by combining certain features of one embodiment with one or more features of another embodiment. Specifically, the skilled person will understand that features, components and / or functional elements of one embodiment can be combined with technically compatible features, components and / or functional elements of any other embodiment of the present invention given that the resulting combination falls within the definition of the invention provided by the claims.

Figure 12 depicts an individual, e.g., patient suffering from a recurring neurological condition that maybe triggered by an increased stress level. The individual has been implanted with a neuronal stimulation electrode IOIX such as a spinal cord stimulation electrode or a DBS electrode that may have multiple independently controllable electric contacts. The individual may also use an implanted or external pulse generator & processor device 102X that may implement a physiologic signal transmission device according to an embodiment of the present invention.

For instance, pulse generator & processor device i02x may comprise a receiver module configured for receiving one or more sensor signals received from one or more sensor devices such as the implanted bio sensor 103X measuring the heart rate and / or blood pressure of the individual and / or a wearable bio sensor 104X e.g., measuring skin temperature, skin conductance, skin pressure variations, etc.

The sensor devices 103X and 104X may wirelessly transmit 105 their respective sensor signals to the pulse generator & processor device / neurostimulation device i02x.

As explained in detail in section 3. “Summary of the Invention” above and with reference to Fig. 15 below, the pulse generator & processor device i02x may also comprise a processing module and a neurostimulation module for stimulating afferent sensory pathways of the central nervous system eliciting artificial sensations in the cortex of the individual as explained in detail in the applicant’s earlier patent applications DE 102019202666 and US 2020/0269049 (which are both incorporated by reference in their entirety). For example, the processing module may determine the applied stimulation signals based on stored specific relations based at least in part on conceptual learning data for the individual, wherein the conceptual learning data associate a plurality of information about the monitored one or more physiologic or mental states of the individual with a plurality of corresponding stimulation signals.

In the illustrated embodiment, the processing module of the pulse generator & processor device i02x may for instance be configured to derive a continuous or categorical metric for a stress level experienced by the individual based on the one or more sensor signals received from the one or more implanted or wearable sensor devices 103X and 104X. In some embodiments, the determined value of the metric may directly be transmitted to the individual by selecting appropriately calibrated stimulation signals (see Fig. 17 below). Alternatively, the current value off the derived metric may also be compared to a reference or threshold value and a specifically chosen stimulation signal may be determined and transmitted by the pulse generator & processor device i02x to indicate to the individual that the reference value or threshold value was crossed by the metric. In response the individual may take actions to reduce his stress level.

Figure 13 depicts an individual, e.g., patient suffering from an impairment of a homeostatic feedback loop regulating the concentration of a body substance within the body of the organism. The individual has been implanted with a physiologic signal transmission system according to an embodiment of the present invention. The system comprises a physiologic signal transmitter with integrated bio sensor 20ix. The bio sensor may also be separated from and connected (e.g., wirelessly) to the transmitter device 20ix.

For instance, the sensor may be arranged in the carotid artery and may be a chemosensor monitoring the blood composition of the individual, a thermosensor, blood pressure sensor, etc. Based on the received sensor signals the physiologic signal transmitter device 20ix may apply electrophysiologic stimulation signals to a nerve fiber or neuron of the individual, e.g., to the vagus nerve, in downstream direction (i.e., towards the body) via a stimulation electrode (not shown) that also may be integrated or separated from the physiologic signal transmitter device 2iox. For instance, the nerve fiber or neuron may be stimulated with a signal train 202 that does not change the nerve function itself but can be successfully decoded by a downstream implanted second device (the recipient) to react in a pre-programmed manner, forming a within-body closed-loop system using the natural nervous system of the individual as the information transmission pathway 203X. The nerve fiber may be stimulated such that artificially elicited action potentials / spikes 202x are generated. Alternatively, the stimulation parameters may also be chosen such that sub-threshold excitations propagate in downstream direction along the nerve to the receiver device. For instance, the stimulation frequency may substantially be larger than the inverse refractory period of the targeted nerve fiber or neuron.

In contrast to the embodiment of Fig. 12, in Fig. 13, conscious or even cerebral decoding and / or perception of the signal is not required. However, an encoding step of state-data to encoded nerve-travelling signal 202x still needs to occur (followed by a decoding at the recipient point(s)). It is important to differentiate that the state-data encoding signals transmitted downstream (or upstream) of the nerve do not themselves alter the target organ (where that nerve terminates, e.g., the liver) function, but rather regulates or instructs a second device which in turn may then alter that target organ function.

For instance, the recipient device maybe an implanted receiver and/or spike filter device 204X modulating the function of the target organ 205X (e.g., the liver, the pancreatic gland and / or the adrenal gland). Such physiologic signal receiver devices may comprise or communicate with an effector module or device that affects or modulates the function of the target organ 205X.

The receiver device 20 lx may also comprise a receiver module for receiving electrophysiologic measuring signals monitoring the bioelectric activity of the nerve fiber or neurons stimulated by the transmitter device 20ix. A memory module may store predefined signal characteristics that may be used for extracting the transmitted information from the obtained physiologic measurement signals and a stimulation module may then apply a blocking stimulation to the nerve fiber or neurons for blocking or canceling the propagation of the artificial stimulation electrophysiologic signal, e.g., the spikes travelling downstream the nerve fiber. In this manner, the natural function of the nerve fiber downstream the receiver device is not affected by the information transmission between transmitter 20ix and receiver 204X.

Examples of effector modules or devices (not shown) comprise electrostimulation modules, drug administration modules, temperature modification modules, light emission modules (e.g., for interacting with optogenetically modified organ tissues or with light sensitive drugs such as light sensitive ion channel blockers), artificial synapses, vibration or ultrasonic effector modules, etc.

In another possible embodiment, for instance, a wearable device may be receiving encoded state-data travelling downstream the ulnar and medial nerves into the hand, with a high-resolution receiver device sitting on the skin and picking up the within- body data to be processed outside the body.

Figure 14 illustrates a further embodiment of the present invention, wherein information is transmitted vie artificial excitations of muscle fibers of the individual. More specifically, a physiologic signal transmission system provided by the present invention is used to implement a bladder function prosthesis. For instance, the urinary bladder has two important physiologic functions: storage of urine and emptying. Storage of urine occurs at low pressure; bladder muscles relax during the filling phase. Emptying happens at high pressures, requires a coordinated contraction of the bladder and relaxation of the urethra muscles 306X.

An implanted urinary pressure bio sensor and transmitter device 30ix maybe attached to the body of the bladder monitoring the pressure state of the bladder. The transmitter device transmits artificial EMG evoked potentials encoding control information to an implanted muscle controller 304X modulating contraction function of the bladder muscles and to an implanted muscle controller 305X modulating the contraction and relaxation function of the urethra muscles 306X. The control information may for instance be encoded in subthreshold muscle activity propagating through bladder body muscles. During the bladder filling stage, the pressure sensor, for instance, detects a relatively low pressure and in response the transmitter device 30ix transmits control information instructing the implanted muscle controller 304X to keep the bladder body muscles in a relaxed state and the urethra muscles 306X in a contracted state to ensure proper filling of the bladder without urine flowing out unintentionally. When the pressure sensor detects that the balder is full, the transmitter device 301X may inform the individual (e.g., electronically or via a mild vibration stimulation or via an electrophysiologic sensoiy excitation travelling to the sensory cortex as explained above) that the bladder should be emptied. In response, the individual may instruct the transmitter device 30ix to execute bladder contraction and urethra muscle relaxation.

Figure 15 depicts a block diagram of an exemplary physiologic signal transmitter device according to an embodiment of the present invention. In this embodiment the physiologic signal transmitter device comprises an integrated neurostimulation module 43OX (e.g., comprising a neuronal signal generator and an output amplifier) that is connected to a plurality of output signal leads 480X that may be interfaced with a neurostimulation interface of the individual (e.g., a DBS electrode or a spinal cord stimulation electrode; not shown). The physiologic signal transmitter device further comprises a communication antenna 460X operably connected to a receiver module 4iox, configured for wireless communication (e.g., via NFC, Bluetooth or a similar wireless communication technology).

The receiver module 410X may be configured, for example, to receive one or more sensor signals from one or more sensors (as discussed above), indicative of one or more physiologic or mental states of an individual (e.g., a blood composition and / or blood pressure measurement obtained from implanted or wearable chemo or pressure sensors etc.). The receiver module 410X may be operably connected to a data / signal processing module 420X configured to generate one or more stimulation signals and /or signal parameters (e.g., waveform, pulse shape, amplitude, frequency, burst count, burst duration etc.) for generating the one or more stimulation signals. For instance, the processing module 420X may access a data storage module 44OX configured to store a plurality of relations, specific for the individual, associating a plurality of stimulation signals (or parameters used for generating a plurality of stimulation signals) with a plurality of corresponding sensory percepts associated with a plurality of information about the monitored physiologic or mental states of the individual to be transmitted to the sensory cortex of the individual.

The generated stimulation signals and / or the signal parameters are input into the integrated neurostimulation module 43OX that may be configured to process (e.g., modulate, switch, amplify, covert, rectify, multiplex, phase shift, etc.) the one or more stimulation signals generated by the processing module 420X or to generate the one or more stimulation signals based on the signal parameters provided by the processing module 420X. The generated and processed stimulation signals are then output by the neurostimulation module 43OX and can for instance be applied to one or more electric contacts of a neurostimulation electrode (e.g., a DBS electrode or spinal cord stimulation electrode; not shown) via output leads 480X.

The illustrated physiologic signal transmitter device may also comprise a rechargeable power source 460X that, for instance may be wirelessly charged via a wireless charging interface 47OX.

Figure 16 depicts a block diagram of an exemplary physiologic signal receiver device according to an embodiment of the present invention. In this embodiment the physiologic signal receiver device comprises an integrated effector module 53OX such as a drug administration module, an electrostimulation module, etc. The physiologic signal receiver device further comprises a receiver module 510X.

The receiver module 510X maybe configured, for example, to receive one or more sensor signals from one or more sensors monitoring the (electro-)physiologic activity of one or more physiologic systems or structures of the individual, such as nerve or muscle fibers (see Fig. 13 and Fig. 14 above). The receiver module 510X may be operably connected to a data / signal processing module 520X configured to extract transmitted information (e.g., transmitted by the signal transmitter device of Fig. 15) that maybe encoded in a subset of the obtained physiologic measurement signals. For instance, the extracted transmitted information may be related to one or more sensor signals monitoring one or more physiologic and / or mental states of the individual as described above. The processing module 520X may access a data storage module 54OX configured to store predefined signal characteristics that can be used for extracting the transmitted information from the obtained physiologic measurement signals. For instance, the predefined signal characteristics may be used to extract non-natural spiking patterns from extracellular recordings of myelinated axons of the central or peripheral nervous system.

The processing module 52OX may generate instructions for the integrated effector module 53OX such as instructions to begin or cease administration of a drug or electrostimulation. The effector module 53OX may also be configured to apply a blocking stimulation to the monitored physiologic structure or systems via output wire 570x.

The illustrated physiologic signal receiver device may also comprise a power source 55OX such as an exchangeable battery.

Figure 17 illustrates how an artificial electrophysiologic stimulation signal can be used to elicit a sensory percept in the cortex of an individual encoding a metric characterizing the stress level of an individual, e.g., derived by the processing module 420X of the physiologic signal transmitter device of Fig. 15 based on the one or more received sensor signals.

For instance, the measurement signals of the implanted and wearable sensors discussed above with reference to Fig. 12 maybe used to derive a metric quantifying the stress level experienced by an individual. The processing module may further determine a stimulation signal that is to be applied to nerve fibers or neurons of the central nervous system (e.g., the spinal cord) targeting the sensory cortex of the individual. The determined (neuro-) stimulation signal may correspond to the current value of the derived metric that is to be communicated to the individual.

As shown in Fig. 17, such a stress level metric maybe encoded by a combination of stimulation signal parameters such as a pulse width, a pulse amplitude, a pulse frequency, etc. of a pulse train signal evoking specific and distinguishable sensoiy percepts in the sensory cortex of the individual such as different and distinguishable artificial tough sensations in the left hand of the individual. In the example shown in Fig. 17, the signal parameter A may for instance corresponds to pulse width and the signal parameter B to a stimulation frequency. In this case, the elicited sensory percept corresponding to a low frequency pulse train having a short pulse width (A) may indicate a low stress level (A) whereas a high frequency pulse train having a long pulse width (C) may evoke a different sensory percept that indicates a critical stress level (C) that may require intervention by the individual.

Claims

48

Claims Closed loop computer brain interface, CLCBI, device (900, 1000) for an individual (100) comprising: a receiver module (930, 1030) configured to obtain at least one sensor signal indicative of a movement or action of the individual; a processing module (940, 1040) operably connected to the receiver module and configured to determine at least one neuronal feedback signal based at least in part on the obtained sensor signal; and a transmitter module (910, 1010) operably connected to the processing module and configured to transmit the determined neuronal feedback signal to a neurostimulation device (102) of the individual or a neurostimulation module (910) operably connected to the processing module; wherein the neuronal feedback signal is configured to elicit a sensoiy percept in the cortex of the individual via stimulating afferent sensory axons of the central nervous system targeting sensory neurons (730) of the cortex of the individual; and wherein the elicited sensoiy percept indicates movement support information related to the obtained sensor signal to support the execution of the movement or action of the individual. CLCBI device of claim 1, wherein the action or movement executed by the individual is associated with a training task and the movement support information supports the individual with performing the training task. CLCBI device of claims 1 or 2 wherein the movement support information is configured to provide one or more of the following to the individual: a distance indication relating to an object to be manipulated by the individual; 49 an orientation indication for the individual or a body part of the individual; an indication of a geographic position of the individual; a success or failure indication for a training task executed by the individual; an indication, preferably continuous, of a desired or unwanted trajectory of a movement or action to be executed by the individual; an indication quantifying a degree of deviation from a desired trajectory of a movement or action to be executed by the individual; an indication designating a desired or unwanted object to be manipulated by the individual; an indication to start of stop the execution of the movement or action; and an indication to provide the individual with a non-verbal instruction related to the execution of a task.

4. CLCBI device of any of the preceding claims, wherein the at least one sensor signal is indicative of at least one of the following: a position, distance, and / or orientation of a body part of the individual with respect to a fixed reference frame and / or another body part of the individual, and / or an object to be manipulated by the individual; a muscle tension, contraction and / or relaxation state of the at least one body part of the individual; a flexion, extension, supination, pronation and / or rotation angle of a joint of the at least one body part of the individual; a movement speed associated with the at least one body part; a contact pressure between a portion of the at least one body part and an object to be manipulated by the individual.

5. CLCBI device of any of the preceding claims 2 - 4, wherein the receiver module is further configured to obtain training data indicative of a training task associated with the movement or action of the individual. 50

6. CLCBI device according to any of the preceding claims, wherein the obtained sensor signal is received from at least one of the following sensor devices: a computer vision tracking device; a kinematic sensor device; a touch sensor; a force, angle, position, tension and / or acceleration sensor device; an electroencephalography device; an electromyography device; a skin conductance, respiratory rate, electrocardiogram, and temperature sensor device; a deep brain local field potential recording device; a GPS device, and an electrocorticography device.

7. CLCBI device of any of the preceding claims, further configured to access a data storage device or a data storage module (950, 1050) storing a plurality of relations, specific for the individual, associating a plurality of neuronal feedback signals with a plurality of corresponding movement support information.

8. CLCBI device of the preceding claim, comprising the data storage device storing the plurality of relations, specific for the individual, associating the plurality of neuronal feedback signals with the plurality of corresponding movement support information.

9. CLCBI device of any of the preceding claims 7 or 8, wherein the specific relations are based at least in part on one or more of the following: conceptual or perceptive learning data for the individual; neuro-imaging data for the individual; electrophysiological measurement data for the individual; neuronal connectivity information for the individual; electric field simulation data for the neurostimulation device of the individual; and neuronal excitability model data for the individual.

10. CLCBI device of any of the preceding claims, wherein the neuronal feedback signal is characterized by a plurality of signal parameters such as a signal waveform, a signal frequency, a signal polarity, a signal pulse shape, a signal amplitude, a signal pulse width, a burst frequency, a burst pulse count and / or a burst duration; and wherein different combinations of signal parameters correspond to different movement support information. 51

11. CLCBI device of any of the preceding claims, wherein the neuronal feedback signal is adapted to elicit a sensory percept in a portion of the cortex of the individual associated with a specific sensory modality; and wherein the portion of the cortex is one or more of the following: a somatosensory cortex area; an auditory cortex area; a visual cortex area; an olfactory cortex area; an entorhinal cortex area or components of the circuit of Papez.

12. CLCBI device of any of the preceding claims, wherein the neuronal feedback signal is configured to stimulate thalamocortical axons projecting from the thalamus to the sensory neurons of the cortex and / or wherein the neuronal feedback signal is configured to stimulate afferent sensory axons of the spinal cord projecting, via mono-synaptic or multi-synaptic pathways, to the thalamus or the cortex of the individual.

13. Recovery and rehabilitation system comprising the CLCBI device according to any of the preceding claims 1 - 12.

14. Recovery and rehabilitation system of the preceding claim 13 further comprising at least one of the sensor devices of the preceding claim 6 and / or the data storage device of claim 7.

15. Prosthetic system for an individual comprising: the CLCBI device of any of the preceding claims 1 - 12; an electromechanic prosthetic device for the individual; and a control interface device configured to control the electromechanic prosthetic device, wherein the movement support information transmitted by the CLCBI device is configured to support the control of the electromechanic prosthetic device via the control interface.

16. Prosthetic system of the preceding claim, further comprising at least one of the sensor devices of the preceding claim 6 and / or the data storage device of claim 7. Prosthetic system of the preceding claim 15 or 16, wherein the control interface device comprises a brain computer interface, BCI, device, configured to monitor neural activity of the individual related to the control of the electromechanic prosthetic device. Computer program comprising instructions for carrying out the following steps when being executed by the signal processing and transceiver modules of a signal and data processing device, a neuronal stimulation device or system: obtain at least one sensor signal indicative of a movement or action of an individual; determine a neuronal feedback signal based at least in part on the obtained sensor signal; and transmit the neuronal feedback signal to a neurostimulation device or module of the individual; wherein the neuronal feedback signal is configured to elicit a sensory percept in the cortex of the individual via stimulating afferent sensory axons of the central nervous system targeting sensory neurons of the cortex; and wherein the elicited sensory percept indicates movement support information related to the obtained sensor signal to support the execution of the movement or action of the individual. Computer program of claim 18, comprising further instructions for implementing the CLCBI device of the preceding claims 2 - 12, when being executed by the signal processing and transceiver modules of a signal and data processing device, a neuronal stimulation device or system. Physiologic signal transmitter device (102X, 20ix, 3Oix) for an individual, comprising: a receiver module (4iox) configured to obtain one or more sensor signals monitoring one or more physiologic and / or mental states of the individual; a processing module (420X) operably connected to the receiver module and configured to determine one or more stimulation signals based at least in part on the obtained one or more sensor signals; and a stimulation module (430x) operably connected to the processing module and configured to apply the determined stimulation signals to a physiologic system or structure of the individual via a physiologic stimulation device of the individual, wherein the one or more stimulation signals are configured to elicit one or more artificial physiologic excitations propagating along the physiologic system or structure of the individual; and wherein the one or more artificial physiologic excitations encode information about the monitored one or more physiologic and / or mental states of the individual. Physiologic signal transmitter device of claim 20, wherein the physiologic system or structure comprises one or more of the following: a muscle fiber of the individual; a nerve fiber or neuron of the individual; a blood vessel of the individual; and / or wherein the artificial physiologic excitation comprises one or more of the following: on or more action potentials; sub-threshold electrical activity of muscle fibers of the individual; sub-threshold electric potentials of nerve fibers or neurons of the individual; an artificial modulation of a natural physiologic excitation of the physiologic system or structure, such as an amplitude modulated, shape modulated and / or frequency modulated heartbeat of the individual. Physiologic signal transmitter device of claim 20 or claim 21, wherein the physiologic structure or system projects to a target organ and / or a target position within the body of the individual associated with an external or surgically implanted device of the individual. Physiologic signal transmitter device of any of the preceding claims 20 - 22, wherein a binaiy code is used to encode the transmitted information; and / or 54 wherein the transmitted information is encoded in analog form. Physiologic signal transmitter device of any of the preceding claims 20 - 23, wherein the one or more physiologic excitations are generated such that the normal function of the physiologic system or structure and / or of the target organ or target position is not substantially affected by the one or more physiologic excitations. Physiologic signal transmitter device of any of the preceding claims 20 - 22, wherein the stimulation module is configured to apply the determined stimulation signals to a neurostimulation electrode of the individual, wherein the one or more stimulation signals are configured to elicit one or more electrophysiologic excitations propagating in one or more nerve fibers or neurons projecting to a target organ or position of the individual; and wherein the one or more stimulation signals elicit one or more electrophysiologic excitations that encode information about the monitored one or more physiologic and / or mental states of the individual. Physiologic signal transmitter device according to claim 23 and 25, wherein the binary code and / or the analog encoding is based on one or more of the following: an interspike interval; an excitation amplitude; a spike count within a burst; a spike frequency within a bust; an excitation duty cycle; an excitation waveform or pulse shape. Physiologic signal transmitter device of any of the preceding claims 25 - 26, wherein the one or more electrophysiologic excitations are generated such that the normal function of the one or more nerve fibers or neurons and / or of the target organ or target position is not substantially affected by the one or more electrophysiologic excitations. 55

28. Physiologic signal transmitter device according to claim 27, wherein the one or more electrophysiologic excitations are generated such that they lie outside a natural frequency range, amplitude range and / or excitation signal shape range of the one or more nerve fibers or neurons projecting to the target organ or position of the individual and / or wherein the one or more electrophysiologic excitations correspond to a non-natural spiking patter within the one or more nerve fibers or neurons projecting to the target organ or target position of the individual.

29. Physiologic signal transmitter device according to claim 27 or claim 28, wherein the frequency and / or the amplitude and / or the signal shape of the one or more stimulation signals is chosen such that no action potentials are elicited in the one or more nerve fibers or neurons; or wherein the frequency and / or the amplitude and / or the signal shape of the one or more stimulation signals is chosen such that action potentials that are elicited in the one or more nerve fibers or neurons do not activate synapses of the one or more nerve fiber or neurons that affect the function of the target organ or target position.

30. Physiologic signal transmitter device according to any of the claims 27 - 29, wherein a pulse frequency of the stimulation signals is larger or equal to 10 kHz; and / or wherein a pulse duration of the one or more stimulation signals is smaller or equal to a 1 ps; and / or wherein a pulse frequency of the stimulation signals is substantially larger than the inverse of a refractory period of the one or more nerve fibers or neurons.

31. Physiologic signal transmitter device of claim 20, wherein the stimulation module is configured to apply the determined one or more stimulation signals to a neurostimulation electrode of the individual, 56 wherein the one or more stimulation signals are configured to elicit one or more electrophysiologic excitations in one or more nerve fibers or neurons of the central nervous system projecting to the sensory cortex of the individual; wherein the one or more electrophysiologic excitations are configured to elicit a sensory percept in the sensory cortex of the individual; and wherein the elicited sensory percept provides information to the individual about the one or more monitored physiologic and / or mental states of the individual.

32. Physiologic signal transmitter device of claim 31, wherein the processing module is further configured to derive, based on the obtained sensor signals, a continuous or categorical metric characterizing the one or more physiologic and / or mental states of the individual, and wherein the determined one or more stimulation signals are configured to elicit a sensory percept indicating a current value of the derived metric to the individual.

33. Physiologic signal transmitter device of claim 32, wherein the processing module is configured such that the determining of the one or more neural stimulation signals comprises: determining one or more signal parameters of the one or more neural stimulation signals based at least in part on a determination function that maps the current value of the metric to one or more values of the one or more signal parameters.

34. Physiologic signal transmitter device of claim 33, wherein the one or more signal parameters comprise one or more of the following: one or more activated stimulation channels, a signal amplitude, a signal frequency, a signal duty cycle, a signal pulse width, a signal polarity, a signal burst frequency, a signal burst spike count and / or wherein the determination function comprises an activation function such as a sigmoid function, a gaussian function, a rectified linear function, a logistic function, a hyperbolic function. 57

35. Physiologic signal transmitter device of any of the preceding claims 31 - 34, wherein the processing module is further configured to derive, based on the obtained one or more sensor signals, a continuous or categorical metric characterizing the one or more physiological and / or mental states of the individual; compare a current value of the metric to a reference value for the metric; and, in response to determining that the current value of the metric has exceeded the reference value: determine a stimulation signal that is configured to elicit a sensory percept indicating to the individual that the reference value was exceeded.

36. Physiologic signal transmitter device of any of the preceding claims 31 - 35, wherein the one or more stimulation signals are configured to elicit a multi-modal sensory percept in the cortex of the individual.

37. Physiologic signal receiver device (204X, 304X, 305X) for an individual, comprising: a receiver module (5iox) configured to obtain one or more physiologic measurement signals obtained from a physiologic measuring device monitoring the physiologic activity of a physiologic system or structure of the individual projecting to a target organ or position of the individual; a processing module (520X) operably connected to the receiver module (5iox) and configured to extract transmitted information encoded in a subset of the obtained physiologic measurement signals; wherein the extracted transmitted information is related to one or more sensor signals monitoring one or more physiologic and / or mental states of the individual.

38. Physiologic signal receiver device of claim 37, further comprising one or more effector modules (53OX) configured to affect or modulate the function of the target organ or position; and / or a memory module (540x) storing predefined signal characteristics that are used for extracting the transmitted information from the obtained physiologic measurement signals; and / or 58 a stimulation module (530x) configured for applying a blocking stimulation to the physiologic structure blocking or canceling the propagation of an artificial physiologic excitation encoding the extracted information downstream of the physiologic signal receiver device.

39. Physiologic signal receiver device of claim 38, wherein the one or more effector modules comprise one or more of the following: an electrostimulation module; a drug administration module; a heating and / or cooling module; a light emission module; an artificial synapse; a vibration or ultrasonic effector module.

40. Physiologic signal transmission system for an individual, comprising one or more physiologic transmitter devices according to any of the claims 20 - 30; and one or more physiologic signal receiver devices according to any of the claims 37 - 39; wherein at a subset of the physiologic systems or structures stimulated by the one or more physiologic signal transmitter devices are monitored, at least indirectly, by the one or more physiologic signal receiver devices.

41. Integrated physiologic monitoring system, comprising; the physiologic signal transmission system of claim 40; and a physiologic signal transmitter device of any of the claims 31 - 36.

42. Physiologic signal device or system of any of the preceding claims, wherein the one or more sensor signals relate to a blood pressure, a blood composition, a drug or body substance level, a stress level, and / or a neural activity pattern of the individual. 59 Physiologic signal device or system of any of the preceding claims, wherein one or more sensor signals are received from at least one of the following sensor devices: a touch sensor; an electroencephalography device; an electromyography device; a sensor device for measuring a skin conductance, a respiratory rate, an electrocardiogram, and / or a temperature; a deep brain local field potential recording device; a chemo-sensor device for measuring the concentration of a substance in a body fluid of the individual; and an electrocorticography device. Computer program, comprising instructions for implementing the physiologic signal transceiver devices and systems of any of the preceding claims 20 - 43.