WO2023147401A1 - Electrical signal delivery device - Google Patents

Abstract

Methods and devices that include one or more electrodes configured to receive an electrical signal; and a holder configured to support the one or more electrodes, wherein the holder is configured to extend around at least a portion of a human's cranium. The electrodes beings specifically adapted for use in electrotherapy for anxiety using sinusoidal alternating current with a frequency between 1 and 10 Hz, and being positioned so as to target the amygdala and/or having a first electrode positioned on the prefrontal cortex, a second electrode positioned on the parietal cortex and a third electrode positioned on the temporal cortex.

Description

ELECTRICAL SIGNAL DELIVERY DEVICE

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No. 63/303,053, filed on January 26, 2022; the disclosure of which is herein incorporated by reference in its entirety.

BACKGROUND OF THE DISCLOSURE

[0002] Medical devices that deliver electrical signals to the brain have been approved by the Food and Drug Administration (FDA) for nearly 50 years. These devices, dating back to the first device in this class, the NeuroTone® 101, and have been referred to for many years as Cranial Electrical Stimulators (CES). These prior FDA approved and cleared CES medical devices deliver a variety of waveforms and frequencies (e.g., 1 - 1,500 Hz) to the brain, typically via intermittent pulses of about 2ms per pulse, initially for the treatment of anxiety/insomnia and depression.

[0003] Historically however, these devices were not very efficient or effective in their delivery of electrical signals to specific portions of the brain as a significant amount of their signal was lost to shunting around the scalp without penetrating the cranium. The 2^nd generation of these devices improved their efficacy and the target of these newer CES devices moved to the vagal nerve reportedly accessed from afferent fibers of this nerve ending on the outside of the ears. CES devices have not been developed to specifically target and manipulate specific regions or networks in the brain.

[0004] What is desired is a neuromodulation system including a non-invasive neuromodulation/CES device and methods to deliver, from a position exterior of a human’s cranium, electrical signals to specific regions and networks of the human brain. Embodiments of the present disclosure provide devices and methods that address the above needs.

SUMMARY OF THE DISCLOSURE

[0005] In accordance with one or more embodiments, methods of treatment and devices are provided.

[0006] The disclosure includes a device that comprises one or more electrodes configured to receive an electrical signal; and a holder such as a headband configured to support the one or more electrodes, wherein the holder is configured to extend around at least a portion of a human’s cranium.

[0007] The disclosure also includes a method of treating a condition, the method comprising: contacting a portion of a human’s cranium with one or more electrodes; and emitting an electrical current from the one or more electrodes supported by a holder, the holder configured to extend around at least a portion of the human’s cranium.

BRIEF DESCRIPTION OF THE DRAWINGS

[0008] The present disclosure will be better understood by reference to the following drawings, which are provided as illustrative of certain embodiments of the subject application, and not meant to limit the scope of the present disclosure.

[0009] The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.

[0010] FIGs. 1A and IB are illustrations of 10-20 international placement model of 19 EEG channels and their locations on a human’s cranium.

[0011] FIGs. 2 A and 2B are illustrations of a 10-20 and 10-10 international placement model of 64 EEG channels and their locations on a human’s cranium.

[0012] FIG. 3 is an illustration of example locations over the left cerebral hemisphere of 3 electrodes corresponding to the 10-20 placement map on a human’s cranium.

[0013] FIG. 4 is a heat map of local voltages in the right cerebral hemisphere of a human brain resulting from the 3 (tripod) channel model.

[0014] FIG. 5 is a heat map of local voltages in the right cerebral hemisphere of a human brain showing 2 of 4 channels from a 6 (hexagon) channel model.

[0015] FIG. 6 is a heat map of local voltages in the right cerebral hemisphere of a human brain showing a different configuration of the 2 of the 4 channels from a 6 (hexagon) channel model. [0016] FIG. 7 is a heat map of local voltages in the left cerebral hemisphere of a human brain showing 2 of the 4 channels from a 6 (hexagon) channel model. DETAILED DESCRIPTION OF THE DISCLOSURE

[0017] In the discussion and claims herein, the term “about” indicates that the value listed may be somewhat altered, as long as the alteration does not result in nonconformance of the process or device. For example, for some elements the term “about” can refer to a variation of ±0.1%, for other elements, the term “about” can refer to a variation of ±1% or ±10%, or any point therein.

[0018] As used herein, the term “substantially”, or “substantial”, is a broad term and is used in its ordinary sense, including, without limitation, being largely but not necessarily wholly that which is specified, which is equally applicable when used in a negative connotation to refer to the complete or near complete lack of an action, characteristic, property, state, structure, item, or result. For example, a surface that is “substantially” flat would mean either completely flat, or so nearly flat that the effect would be the same as if it were completely flat.

[0019] As used herein terms such as “a”, “an” and “the” are not intended to refer to only a singular entity, but include the general class of which a specific example may be used for illustration.

[0020] As used herein, terms defined in the singular are intended to include those terms defined in the plural and vice versa.

[0021] References in the specification to “one embodiment”, “certain embodiments”, some embodiments” or “an embodiment”, indicate that the embodiment(s) described may include a particular feature or characteristic, but every embodiment may not necessarily include the particular feature, structure, or characteristic. Moreover, such phrases are not necessarily referring to the same embodiment. Further, when a particular feature, structure, or characteristic is described in connection with an embodiment, it is submitted that it is within the knowledge of one skilled in the art to affect such feature, structure, or characteristic in connection with other embodiments whether or not explicitly described.

[0022] For purposes of the description hereinafter, the terms “upper”, “lower”, “right”, “left”, "vertical", "horizontal", "top", "bottom", and derivatives thereof shall relate to the invention, as it is oriented in the drawing figures. The terms “overlying”, “atop”, “positioned on” or “positioned atop” means that a first element, is present on a second element, wherein intervening elements interface between the first element and the second element. The term “direct contact” or “attached to” means that a first element and a second element are connected without any intermediary element at the interface of the two elements.

[0023] Reference herein to any numerical range expressly includes each numerical value (including fractional numbers and whole numbers) encompassed by that range. To illustrate, reference herein to a range of “at least 50” or “at least about 50” includes whole numbers of 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, etc., and fractional numbers 50.1, 50.2 50.3, 50.4, 50.5, 50.6, 50.7, 50.8, 50.9, etc. In a further illustration, reference herein to a range of “less than 50” or “less than about 50” includes whole numbers 49, 48, 47, 46, 45, 44, 43, 42, 41, 40, etc., and fractional numbers 49.9, 49.8, 49.7, 49.6, 49.5, 49.4, 49.3, 49.2, 49.1, 49.0, etc.

[0024] As used herein, the term “contact” and grammatical variations thereof, when referring to the one or more electrodes and a human’s body refers to actual physical contact between the one or more electrodes an a portion of the human’s body (e.g. scalp) or may include being within a threshold distance from the skin of the human’s body such that the one or more electrodes can still emit sufficient electrical signals and sufficient electrical signals pass through a portion of the human’s body. Within the threshold distance can include barriers below a thickness threshold (e.g. hair follicles, gels (such as conductive gels)) that do not impact electrical signal transmission, or substantially do not impact electrical signal transmission, or can be accounted and adjusted for. The threshold distance from the portion of the human’s body may be a range, for example about 0 mm to about 1 cm, or about 0 mm to about 5.0 millimeters, or about 0 mm to about 3.0 millimeters, or about 0 mm to about 2.0 millimeters, or about 0 mm to about 1.0 millimeters. The skin contact sensor may be configured to measure the distance from the measuring device to the skin of the user, or an aspect that facilitates determining the distance from the skin.

[0025] As used herein, the terms “treatment” and “treating” refer to all processes, wherein there may be a slowing, interrupting, arresting, controlling, or stopping of the progression of the disorders described herein, but does not necessarily indicate a total elimination of all disorder symptoms, as well as the prophylactic therapy of the mentioned conditions, particularly in a patient who is predisposed to such disease or disorder.

[0026] As used herein a “condition” can refer to any disease, condition, psychiatric condition or disorder including anxiety disorders and related disorders as described in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) (1994, American Psychiatric Association, Washington, D.C.). An “anxiety disorder” as used herein refers to any disorder characterized by increased anxiety, including insomnia. Anxiety disorders include but are not limited to generalized anxiety, social anxiety, insomnia secondary to anxiety, anxiety secondary to Post traumatic stress disorder (PTSD), social phobia, PTSD, panic disorder, panic attacks, and obsessive-compulsive disorder. Anxiety disorders can be associated with a variety of physical systems, including a faster heart rate, skipped heartbeats, rapid breathing, sweating, trembling, dizziness, dry mouth, and weight loss. PTSD as used herein refers to disorder that occurs after exposure to a traumatic event and results in the subject feeling scared, confused, and/or angry to the extent that daily activities are difficult to perform. Traumatic events include but are not limited to combat or military exposure, child sexual or physical abuse, terrorist attacks, sexual or physical assault, serious accidents, and natural disasters (such as a fire, tornado, hurricane, flood, or earthquake).

[0027] The device of the present disclosure is non-invasive and remains exterior of a human’s cranium. The device of the present disclosure uses one or more electrodes to deliver an electrical signal to a cranium of a human to treat a condition. The device of the present disclosure is configured to deliver signal(s) that are substantially targeted to the human’s amygdala, but the device can be configured to deliver an electrical signal to any other portion of the brain.

[0028] The one or more electrodes can be any suitable electrode, including a gel encapsulated electrode (GEE) having any suitable size and shape. The suitable diameter can be any suitable distance, including, about 25 mm or more, about 5 mm to about 20 mm, about 8 mm to about 16 mm, about 10 mm to about 14 mm, about 11 mm to about 13 mm, or about 12 mm.

[0029] The one or more suitable electrodes are configured to create transcranial, alternating, sinusoidal current stimulation at about 5 Hz to deliver various voltages as part of an electrical signal to various anatomical targets within the brain, such as the amygdala. However, in other embodiments, different transcranial currents can be emitted, such as different waveforms and/or intermittent pulses. Also, in other embodiments, different frequencies can be used, such as about 1 Hz to about 10 Hz, about 2 Hz to about 9 Hz, about 3 Hz to about 8 Hz, about 4 Hz to about 7 Hz, or about 4 Hz to about 6 Hz. If two or more electrodes are included in the disclosed device, each of the two or more electrodes can deliver the same voltage, or each of the two or more electrodes can deliver different voltages as compared to other electrodes. [0030] The waveform output of the one or more electrodes of the disclosed device can be any suitable amount, and can be limited to a total output of about 4 mA (total of all primary stimulating electrodes with zero phase shift) and can be set to automatically titrate up about 2 mA. In other embodiments the total output can be about 4 mA, about 5mA or more, and the automatic titration can be about 3 mA, about 4 mA or more. Additionally, the total output, instant output and titration level may all be adjusted by a user through input received by the controller, noted below.

[0031] A controller in communication with the disclosed device can adjust the output current of the one or more electrodes in any suitable range, such as about 0 mA to about 2mA/electrode, or more. This controller, or circuit, as used herein can be incorporated in any suitable processing device, such as a printed circuit board. In other embodiments, the circuitry and/or software of the present application may refer to, be part of, or include an Application Specific Integrated Circuit (ASIC), an electronic circuit, a processor (shared, dedicated, or group), and/or memory (shared, dedicated, or group) that execute one or more software or firmware programs, a combinational logic circuit, and/or other suitable hardware components that provide the described functionality. In some embodiments, the circuitry may be implemented in, or functions associated with the circuitry may be implemented by, one or more software or firmware modules. In some embodiments, circuitry may include logic, at least partially operable in hardware.

[0032] This controller controls the amount of electrical signal that is transmitted to each of the one or more sensors. The electrical signal transmitted to each of the one or more sensors can be received from any suitable electrical source that is capable of providing the electrical energy needed for the electrodes disclosed herein to emit the signals described herein. Some examples of this suitable electrical source are any suitable one or more batteries and a suitable electrical power source such as a receptacle or battery, with or without one or more transformers. The one or more sensors can receive the electrical signal from the suitable electrical source in any suitable way, such as through wired connections and/or wireless transmission.

[0033] The disclosed device can deliver signals for any suitable length of time per session, such as about 1 second, about 30 seconds, about 1 minute, about 3 minutes, about 5 minutes, about 10 minutes, about 15 minutes, about 20 minutes, about 25 minutes, about 30 minutes, about 45 minutes, or more. Additionally, each session can be once per day, or can be repeated two times per day, three times per day, or more. The sessions can occur daily, or on a non-every day schedule and can continue for 1 day, 2 days, 4 days, 1 week, 2 weeks, 1 month, 2 months, 6 months, or more.

[0034] The one or more electrodes of the disclosure can be contained in and/or on a suitable holder, such as a headband and/or cap, or any other suitable structure that can extend around a human’s cranium and hold/support the one or more electrodes.

[0035] Target Optimization (TO) as used herein can refer to identifying and localizing the electrical signals emitted from the one or more sensors on one or more anatomical features of a human’s brain. As one example, TO can refer to identifying and localizing the right anterior amygdala.

[0036] The placement of the electrodes on the patient’s cranium is based on this Target Optimization (TO) procedure described herein and is categorized by the patient that the disclosed device will be used on. Specifically, either or both of the patient’s own brain MRI images, or if their own MRI images are not available, available age-match brain MRI template images from other patient(s) can be used to create a tetrahedral mesh segmented according to validated probabilistic tissue maps.

[0037] The conductivity properties of each tissue type were mapped onto the individual nodes of the tetrahedral mesh, so that the electric field created by the one or more electrodes could be simulated and refined for TO using the finite element model of the Laplace equation.

[0038] A finite element model (FEM), consisting of a stiffness matrix and a boundary condition vector is assembled and solved N times (with N = to the number of electrodes), with each solution applying a test current at the boundary of electrode i (with z representing the electrode for the given FEM being computed), and an opposite current at a designated reference electrode). Once the FEM has been solved for each electrode, the solution vectors containing the electric fields are horizontally concatenated and used as input for simulating an optimization equation compliant with the following constraints represented in a vector:

[0039] 1.) Maximize the electric field at the target node (defined by talairach or MNI coordinates for the target node, e.g. amygdala; 2.) Minimize the electric field at any anti-targets (defined by talairach or MNI coordinates); 3.) The magnitude of the electric field is set to about 0.6V per square meter to ensure safety of the current intensity being applied; and 4.) The total sum of all current delivered at any point during the montage cannot exceed the safety limit set in the disclosed device.

[0040] Using this TO as part of the disclosed device montage enhances the safety and efficacy of the treatment by increasing the likelihood that only the region of interest (RO I) (e.g., amygdala) and its associated network is modulated in the intended direction.

[0041] The result of the TO process is a determination of the suitable signal to be emitted from each of the one or more electrodes, as well as the placement on the cranium of the one or more electrodes. Although there are an infinite number of locations on a human’s cranium, FIGs. 1 A and IB, as well as FIGs. 2A and 2B illustrate several examples, reference locations, any one or more of which can be where the one or more electrodes are to be located for treatment of the condition. Thus, any method or use of any device in the present disclosure can include placement on one or more of the several reference locations, and/or any portion in between the reference locations.

Example 1

[0042] In this example, a simulation was performed. In this simulation, three electrodes were used. In this simulation, one electrode was over the right prefrontal cortex, a second electrode was over the right parietal cortex and a third electrode was over the right temporal cortex, as shown in FIG. 3 which depicts a left-sided view.

[0043] For each of the electrodes, five cycles (periods) of electrical waves were emitted in about one second. As one example of this cycle, the duration of one period is about 200ms, about the first 100ms of that period is positive current, and about the second 100ms is negative current.

[0044] The delivery of the electrical signal from three placement of these three electrodes and the distribution of current based on age-matched brain MRI templates is referred to as “Montage 1”, which is a unilateral 2mA - 2.5mA tripod model.

[0045] As can be seen in FIG. 4, a first electrode is located at “T8” (as shown in FIGs. 2A and 2B) and delivered 5Hz, at +/-2000 microamps (“+/-“ refers herein to a range from positive current to negative current, e.g., the range of positive current about +2,000 mA to negative current -2,000 mA), with varying titrations schedules of varying amounts, such as about 1,000 microamps and about 1,500 microamps. As can be seen in FIG. 4, a second electrode is located at “F4” (as shown in FIGs. 2A and 2B) and delivered 5Hz, at +/-1615 microamps, with varying titrations schedules of varying amounts, such as about 808 microamps and about 1,211 microamps. As can be seen in FIG. 4, a third electrode is located at “P4” (as shown in FIGs. 2A and 2B) and delivered 5Hz, at +/-385 microamps, with varying titrations schedules of varying amounts, such as about 192 microamps and about 289 microamps.

[0046] The result of this Montage 1 is shown in FIG. 4. FIG. 4 is a simulated heat map of voltage values at varying parts of a human’s brain upon delivery of the electrical signals of Montage 1. In Montage 1 the current disruption of the returns is a variable that changes based on the age categorization of the patient and/or the patient’s own MRI images.

[0047] As can be seen in FIG. 4 a higher voltage value is near the “T8” location, which is near a human’s amygdala. This higher voltage is substantially concentrated about the targeted amygdala such that voltage values are about 0.3 mV higher than (i) voltage values nearer the other electrode locations and (ii) other portions of the cranium away from the amygdala location.

Example 2

[0048] In this example, another simulation was performed. In this simulation, six electrodes were placed on a human’s cranium. In this simulation, the electrodes were placed as shown in FIGs. 5-7.

[0049] For each of the electrodes, five cycles (periods) of electrical waves were emitted in about one second. As one example of this cycle, the duration of one period is about 200ms, about the first 100ms of that period is positive current, and about the second 100ms is negative current.

[0050] The delivery of the electrical signal from four out the six electrodes is referred to as “Montage 2”:

Channel 1 : tACS 5 hz at F8 at full dosage at +/- 2000 microamps (titration schedule: session 1 at 1,000 and session 2 at 1500) and/or

Channel 2: tACS 5 hz at FT8 at full dosage at +/- 2000 microamps (titration schedule: session 1 at 1,000 and session 2 at 1500) and/or

Channel 3: tACS 5 hz at T8 at full dosages at +/- 2000 microamps (titration schedule: session 1 at 1,000 and session 2 at 1500)

Channel 4: tACS 5 hz at F7 Return at full dosage at +/-2000 microamps (titration schedule: session 1 at 1000, and session 2 at 1500) and/or Channel 5: tACS 5 hz at FT7 Return at full dosages at +/-2000 microamps (titration schedule: session 1 at 1000 and session 2 at 1500) and/or

Channel 6: tACS 5 hz at T7 Return at full dosage at +/- 2000 microamps (titration schedule: session 1 at 1000, and session 2 at 1500).

[0051] The determination of which 4 channels is selected is based on the patient’s age-matched brain MRI templates. Up to a total of a unilateral 4mA across 4-channels is part of this six-pod model montage. In this Montage 2, two of the “Group A” electrodes can operate at the same time, while two of the “Group B” electrodes can operate at the same time.

[0052] An example of a 4-channel montage can be seen in FIGs. 5 and 6; whereas FIG 5 depicts an example when F8-T8 is selected based on the patient’s age and another example in FIG. 6 when T8-FT8 is selected. The corresponding channels on the opposite side are determine by the selection of age-matched channels on the right side of the scalp. The current distributions do not fluctuate in Montage 2 and titrate up to +/- 2000 microamps.

[0053] The result of this example of Montage 2 is shown in FIGs. 5-7. FIGs. 5-7 are simulated heat maps of voltage values at varying parts of a human’s brain upon delivery of the electrical signals of Montage 2. In Montage 2 the current disruption of the returns is a variable that changes based on the age categorization of the patient and/or the patient’s own MRI images.

[0054] As can be seen in FIGs. 5-7 a higher voltage value is near the “T8” location, which is near a human’s amygdala. This higher voltage is substantially concentrated about the targeted amygdala such that voltage values are about 0.45 mV higher than (i) voltage values nearer the other electrode locations and (ii) other portions of the cranium away from the amygdala location.

[0055] The described embodiments and examples of the present disclosure are intended to be illustrative rather than restrictive, and are not intended to represent every embodiment or example of the present disclosure. While the fundamental novel features of the disclosure as applied to various specific embodiments thereof have been shown, described and pointed out, it will also be understood that various omissions, substitutions and changes in the form and details of the devices illustrated and, in their operation, may be made by those skilled in the art without departing from the spirit of the disclosure. For example, it is expressly intended that all combinations of those elements and/or method steps which perform substantially the same function in substantially the same way to achieve the same results are within the scope of the disclosure. Moreover, it should be recognized that structures and/or elements and/or method steps shown and/or described in connection with any disclosed form or embodiment of the disclosure may be incorporated in any other disclosed or described or suggested form or embodiment as a general matter of design choice. Further, various modifications and variations can be made without departing from the spirit or scope of the disclosure as set forth in the following claims both literally and in equivalents recognized in law.

Claims

Claims:

1. A device comprising: one or more electrodes configured to receive an electrical signal; and a holder configured to support the one or more electrodes, wherein the holder is configured to extend around at least a portion of a human’s cranium.

2. The device of claim 1, wherein the one or more electrodes are gel encapsulated electrodes (GEE), and each of the one or more electrodes is of a diameter between about 5 mm and about 20 mm.

3. The device of claim 1 , wherein the one or more electrodes are configured to emit transcranial, alternating, sinusoidal current stimulation at about 1 Hz to about 10Hz.

4. The device of claim 1, wherein the one or more electrodes are configured to emit transcranial, alternating, sinusoidal current stimulation at about 3 Hz to about 8 Hz.

5. The device of claim 1, wherein the one or more electrodes are configured to emit transcranial, alternating, sinusoidal current stimulation at about 5 Hz.

6. The device of claim 1, further comprising a controller, the controller comprising a processor and an input, wherein the processor is configured to control the electrical signal received by the one or more electrodes.

7. The device of claim 1, wherein the holder is configured to: support a first electrode of the one or more electrodes over a right prefrontal cortex of the human’s cranium; support a second electrode of the one or more electrodes over a right parietal cortex; and support a third electrode of the one or more electrodes over a right temporal cortex.

8. The device of claim 1, wherein the holder is configured to support the one or more electrodes in locations configured to target an amygdala of the human.

9. The device of claim 1, wherein the one or more electrodes are configured to emit transcranial, alternating, sinusoidal current stimulation up to about +/- 2000 microamps.

10. A method of treating a condition, the method comprising: contacting a portion of a human’s cranium with one or more electrodes; and emitting an electrical current from the one or more electrodes supported by a holder, the holder configured to extend around at least a portion of the human’ s cranium.

11. The method of claim 10, wherein the condition is selected from the group consisting of generalized anxiety, social anxiety, insomnia secondary to anxiety, anxiety secondary to Post traumatic stress disorder (PTSD), social phobia, PTSD, panic disorder, panic attacks, and obsessive-compulsive disorder.

12. The method of claim 10, wherein the condition is selected from the group consisting of generalized anxiety, social anxiety, and insomnia secondary to anxiety.

13. The method of claim 10, wherein the condition is selected from the group consisting of generalized anxiety, and social anxiety.

14. The method of claim 10, wherein the one or more electrodes are gel encapsulated electrodes (GEE), and each of the one or more electrodes is of a diameter between about 5 mm and about 20 mm.

15. The method of claim 10, wherein the one or more electrodes are configured to emit transcranial, alternating, sinusoidal current stimulation at about 1 Hz to about