Method and system for modulating neural activity

• US 10,092,692 B2
• Filed: 10/13/2017
• Issued: 10/09/2018
• Est. Priority Date: 12/05/2007
• Status: Active Grant

• Current Assignee: Soovu Labs, Inc.
• Original Assignee: Gearbox LLC (Intellectual Ventures LLC)
• Inventors: Dacey, Jr., Ralph G., Della Rocca, Gregory J., Derdeyn, Colin P., Dowling, Joshua L., Goodall, Eleanor V., Hyde, Roderick A., Ishikawa, Muriel Y., Kare, Jordin T., Leuthardt, Eric C., Myhrvold, Nathan P., Smith, Michael A., Wood, Jr., Lowell L., Wood, Victoria Y. H., Zipfel, Gregory J.
• Primary Examiner(s): Gedeon, Brian T
• Application Number:
  US15/783,963
• Publication Number:
  US 20180104407A1
• Time in Patent Office: 361 Days
• Field of Search: None
• CPC Class Codes: A61B 5/0205 Simultaneously evaluating both cardiovascular conditions and different types of body conditions, e.g. heart and respiratory condition
• CPC Class Codes: A61B 5/021 Measuring pressure in heart or blood vessels A61B5/0205 takes precedence
• CPC Class Codes: A61B 5/024 Detecting, measuring or recording pulse rate or heart rate A61B5/0205, A61B5/021 take precedence
• CPC Class Codes: A61B 5/1118 Determining activity level
• CPC Class Codes: A61B 5/14539 for measuring pH
• CPC Class Codes: A61B 5/318 Heart-related electrical modalities, e.g. electrocardiography [ECG]
• CPC Class Codes: A61B 5/369 Electroencephalography [EEG] devices for psychotechnics A61B5/16
• CPC Class Codes: A61B 5/389 Electromyography [EMG]
• CPC Class Codes: A61B 5/4035 Evaluating the autonomic nervous system
• CPC Class Codes: A61B 5/4041 Evaluating nerves condition
• CPC Class Codes: A61B 5/411 Detecting or monitoring allergy or intolerance reactions to an allergenic agent or substance
• CPC Class Codes: A61B 5/441 Skin evaluation, e.g. for skin disorder diagnosis
• CPC Class Codes: A61B 5/4821 Determining level or depth of anaesthesia A61B5/1106 takes precedence
• CPC Class Codes: A61B 5/4839 combined with drug delivery
• CPC Class Codes: A61F 2007/0075 using a Peltier element, e.g. near the spot to be heated or cooled
• CPC Class Codes: A61F 7/00 Heating or cooling appliances for medical or therapeutic treatment of the human body heating or cooling means in connection with bedsteads or mattresses A47C21/00 ; massage, therapeutic baths A61H; hyperthermia using electric or magnetic fields or ultrasound A61N; electric heating elements H05B
• CPC Class Codes: A61F 7/0085 Devices for generating hot or cold treatment fluids
• CPC Class Codes: A61M 2005/14208 with a programmable infusion control system, characterised by the infusion program
• CPC Class Codes: A61M 2005/1726 the body parameters being measured at, or proximate to, the infusion site
• CPC Class Codes: A61M 2037/0007 having means for enhancing the permeation of substances through the epidermis, e.g. using suction or depression, electric or magnetic fields, sound waves or chemical agents
• CPC Class Codes: A61M 2205/0244 : Micromachined materials, e.g. made from silicon wafers, microelectromechanical systems [MEMS] or comprising nanotechnology
• CPC Class Codes: A61M 2210/1003 : Spinal column
• CPC Class Codes: A61M 35/10 : Wearable devices, e.g. garments, glasses or masks
• CPC Class Codes: A61M 37/00 : Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04
• CPC Class Codes: A61M 37/0015 : by using microneedles
• CPC Class Codes: A61M 37/0092 : using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis
• CPC Class Codes: A61M 5/14244 : adapted to be carried by the patient, e.g. portable on the body
• CPC Class Codes: A61M 5/14248 : of the skin patch type
• CPC Class Codes: A61M 5/14276 : specially adapted for implantation
• CPC Class Codes: A61M 5/16827 : controlling delivery of multiple fluids, e.g. sequencing, mixing or via separate flow-paths infusion of multiple fluids without using a controller A61M5/1407
• CPC Class Codes: A61M 5/1723 : using feedback of body parameters, e.g. blood-sugar, pressure measurement of body parameters A61B5/00
• CPC Class Codes: A61N 1/0412 : Specially adapted for transcutaneous electroporation, e.g. including drug reservoirs
• CPC Class Codes: A61N 1/0428 : Specially adapted for iontophoresis, e.g. AC, DC or including drug reservoirs
• CPC Class Codes: A61N 1/30 : Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
• CPC Class Codes: A61N 1/303 : Constructional details electrodes for external use A61N1/0428
• CPC Class Codes: A61N 1/306 : Arrangements where at least part of the apparatus is introduced into the body
• CPC Class Codes: A61N 1/325 : for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body electrodes for external use A61N1/0428
• CPC Class Codes: A61N 1/327 : for enhancing the absorption properties of tissue, e.g. by electroporation
• CPC Class Codes: A61N 1/36103 : Neuro-rehabilitation; Repair or reorganisation of neural tissue, e.g. after stroke
• CPC Class Codes: A61N 1/36135 : using physiological parameters
• CPC Class Codes: A61N 1/37252 : Details of algorithms or data aspects of communication system, e.g. handshaking, transmitting specific data or segmenting data
• CPC Class Codes: A61N 2/002 : in combination with another treatment
• CPC Class Codes: A61N 2/006 : for magnetic stimulation of nerve tissue
• CPC Class Codes: A61N 2007/0026 : Stimulation of nerve tissue
• CPC Class Codes: A61N 7/00 : Ultrasound therapy lithotripsy A61B17/22, A61B17/225; massage using supersonic vibration A61H23/00 ; using ultrasound for introducing media into the body A61M37/0092

Abstract

Methods and related systems for modulating neural activity by repetitively blocking conduction in peripheral neural structures with chemical blocking agents are disclosed. Methods and systems for reversing effects of chemical blocking agents and/or for producing substantially permanent conduction block are also disclosed.

Claims

1. A neural modulation system comprising:

an activity signal input structure adapted to receive an activity signal indicative of an activity state of at least a portion of a body of the subject innervated by the peripheral neural structure from a sensor operatively connected to the activity signal input structure; and

a signal processing portion including

circuitry for distinguishing a first activity state of the at least a portion of the body of the subject innervated by the peripheral neural structure from a second activity state of the at least a portion of the body of the subject innervated by the peripheral neural structure from the activity signal received at the activity signal input structure;

circuitry for generating an ultrasonic stimulus control signal for driving production of an ultrasonic stimulus by an ultrasonic stimulus source, the ultrasonic stimulus configured to reversibly modulate neural activity in at least a portion of a peripheral neural structure of the subject during at least a portion of the first activity state, wherein the circuitry for generating the ultrasonic stimulus control signal is configured to generate the ultrasonic stimulus control signal based at least in part upon the activity signal; and

circuitry for generating a secondary stimulus control signal for driving production of a secondary stimulus adapted to modulate neural activity by a secondary stimulus source.

2. The neural modulation system of claim 1, wherein the circuitry for generating the secondary stimulus control signal includes circuitry for generating a control signal for driving production of at least one of an electrical stimulus, a magnetic stimulus, an ultrasonic stimulus, an optical stimulus, a thermal stimulus, or a chemical stimulus by a secondary stimulus source.

3. The neural modulation system of claim 1, including the ultrasonic stimulus source and the secondary stimulus source.

4. The neural modulation system of claim 3, wherein the secondary stimulus source includes at least one of an electrical stimulus source, a magnetic stimulus source, an ultrasonic stimulus source, an optical stimulus source, a thermal stimulus source, or a chemical stimulus source.

5. The neural modulation system of claim 3, wherein the secondary stimulus source includes a second ultrasonic stimulus source.

6. The neural modulation system of claim 3, wherein the secondary stimulus source is configured to operate in combination with the ultrasonic stimulus source to reversibly modulate neural activity in the at least a portion of the peripheral neural structure of the subject.

7. The neural modulation system of claim 6, wherein the secondary stimulus source includes a chemical stimulus source, an electrical stimulus source, or a magnetic stimulus source.

8. The neural modulation system of claim 3, wherein the secondary stimulus source is configured to oppose or reverse the reversible modulation of neural activity by the ultrasonic stimulus source.

9. The neural modulation system of claim 1, wherein the activity signal input structure is adapted to receive the activity signal via a wireless connection.

10. The neural modulation system of claim 1, wherein the circuitry for generating the ultrasonic stimulus control signal includes circuitry for generating a blocking stimulus control signal for driving production of a blocking stimulus by the ultrasonic stimulus source.

11. The neural modulation system of claim 1, wherein the circuitry for generating the ultrasonic stimulus control signal includes circuitry for generating the stimulus control signal for driving production of the ultrasonic stimulus by an ultrasonic stimulus source positioned on or substantially adjacent the body of the subject.

12. The neural modulation system of claim 1, including

a user signal input structure adapted to receive a user input signal indicative of an instruction from a user regarding operation of the neural modulation system, the user input signal transmitted from a user input device adapted to receive a user input indicative of the instruction from the user;

and

circuitry for modifying operation of the neural modulation system responsive to receipt of the user input signal.

13. The neural modulation system of claim 12, wherein the user signal input structure is configured to receive the user input signal from at least one of a cell phone, a remote controller, or a computer.

14. The neural modulation system of claim 12, wherein the circuitry for generating the ultrasonic stimulus control signal is configured to generate the ultrasonic stimulus control signal based at least in part upon the user input signal.

15. The neural modulation system of claim 12, wherein the user signal input structure is adapted to receive the user input signal via a wireless connection.

16. The neural modulation system of claim 12, wherein the user signal input structure is adapted to receive an instruction from the user to override delivery of the ultrasonic stimulus, and wherein the circuitry for modifying operation of the neural modulation system responsive to receipt of the user input signal is configured to discontinue generation of the ultrasonic stimulus control signal for driving production of the ultrasonic stimulus by the ultrasonic stimulus source.

17. The neural modulation system of claim 12, wherein the user signal input structure is adapted to receive an instruction from the user to modify a pattern of delivery of the ultrasonic stimulus, and wherein the circuitry for modifying operation of the neural modulation system responsive to receipt of the user input signal includes circuitry for modifying generation of the ultrasonic stimulus control signal.

18. The neural modulation system of claim 12, wherein the user signal input structure is adapted to receive an instruction from the user to modify a definition of at least one of the first activity state and the second activity state, and wherein the circuitry for modifying operation of the neural modulation system is adapted to modify the definition of the at least one of the first activity state and the second activity state based upon the instruction from the user.

19. A neural modulation method comprising:

receiving at an activity signal input structure of a neural modulation system an activity signal indicative of an activity state of at least a portion of a body of the subject innervated by a peripheral neural structure from a sensor operatively connected to the activity signal input structure; and

distinguishing, with signal processing circuitry of the neural modulation system, a first activity state of the at least a portion of the body of the subject innervated by the peripheral neural structure from a second activity state of the at least a portion of the body of the subject innervated by the peripheral neural structure from the activity signal received at the activity signal input structure; and

generating, with the signal processing portion of the neural modulation system, an ultrasonic stimulus control signal for driving production of an ultrasonic stimulus by an ultrasonic stimulus source, the ultrasonic stimulus configured to reversibly modulate neural activity in at least a portion of a peripheral neural structure of the subject during at least a portion of the first activity state; and

generating, with the signal processing portion of the neural modulation system, a secondary stimulus control signal for driving production by a secondary stimulus source of a secondary stimulus adapted to modulate neural activity.

20. The neural modulation method of claim 19, wherein generating the secondary stimulus control signal includes generating a control signal for driving production of at least one of an electrical stimulus, a magnetic stimulus, an ultrasonic stimulus, an optical stimulus, a thermal stimulus, or a chemical stimulus by the secondary stimulus source.

21. The neural modulation method of claim 19, including delivering the ultrasonic stimulus with the ultrasonic stimulus source responsive to the ultrasonic stimulus control signal;

and

delivering the secondary stimulus with the secondary stimulus source responsive to the secondary stimulus control signal.

22. The neural modulation method of claim 21, wherein delivering the secondary stimulus includes delivering at least one of an electrical stimulus, a magnetic stimulus, an ultrasonic stimulus, an optical stimulus, a thermal stimulus, or a chemical stimulus.

23. The neural modulation method of claim 21, wherein the ultrasonic stimulus source is a primary ultrasonic stimulus source, and wherein delivering the secondary stimulus includes delivering an ultrasonic stimulus with a secondary ultrasonic stimulus source aimed and focussed to produce constructive interference with the ultrasonic stimulus from the primary ultrasonic stimulus source.

24. The neural modulation method of claim 21, wherein the ultrasonic stimulus and the secondary stimulus operate in combination to reversibly modulate neural activity in the at least a portion of the peripheral neural structure of the subject.

25. The neural modulation method of claim 21, wherein the secondary stimulus opposes or reverses the reversible modulation of neural activity by the ultrasonic stimulus.

26. The neural modulation method of claim 19, wherein delivering the ultrasonic stimulus includes delivering a blocking stimulus.

27. The neural modulation method of claim 19, wherein delivering the ultrasonic stimulus includes delivering the ultrasonic stimulus with an ultrasonic stimulus source positioned on or substantially adjacent the body of the subject.

28. The neural modulation method of claim 21, wherein delivering the ultrasonic stimulus includes delivering the ultrasonic stimulus to at least one of a peripheral nerve, a cranial nerve, a spinal nerve, a nerve plexus, a spinal ganglia, an autonomic ganglia, a motor nerve, a sensory nerve, a sensory-motor nerve, or an autonomic nerve.

29. The neural modulation method of claim 19, including receiving the activity signal input at the activity signal input structure via a wireless connection.

30. The neural modulation method of claim 19, including

receiving via a user signal input structure a user input signal indicative of an instruction from a user regarding operation of the neural modulation method, the user input signal transmitted from a user input device adapted to receive a user input indicative of the instruction from the user;

and

modifying operation of the neural modulation system responsive to receipt of the user input signal.

31. The neural modulation method of claim 30, wherein receiving the user input signal includes receiving the user input signal from a cell phone, a remote controller, or a computer.

32. The neural modulation method of claim 30, wherein modifying operation of the neural modulation system responsive to receipt of the user input signal includes generating the stimulus control signal based at least in part upon the user input signal.

33. The neural modulation method of claim 30, including receiving the user input signal at the user signal input structure via a wireless connection.

34. The neural modulation method of claim 30, wherein receiving the user input signal includes receiving an instruction from the user to override delivery of the ultrasonic stimulus, and wherein modifying operation of the neural modulation system responsive to receipt of the user input signal includes discontinuing generation of the ultrasonic stimulus control signal for driving production of the ultrasonic stimulus by the ultrasonic stimulus source.

35. The neural modulation method of claim 30, wherein receiving the user input signal includes receiving an instruction from the user to modify a pattern of delivery of the ultrasonic stimulus, and wherein modifying operation of the neural modulation system responsive to receipt of the user input signal includes modifying generation of the ultrasonic stimulus control signal.

36. The neural modulation method of claim 30, wherein receiving the user input signal includes receiving an instruction from the user to modify a definition of at least one of the first activity state and the second activity state, and modifying operation of the neural modulation system includes modifying the definition of the at least one of the first activity state and the second activity state based upon the instruction from the user.

37. A neural modulation system, comprising:

a package configured to be secured to a portion of a body of a subject adjacent a skin surface in the vicinity of a peripheral neural structure;

a signal input structure configured to receive a signal indicative of an activity state of the subject;

a first stimulus source adapted to produce a first stimulus sufficient to reversibly modulate neural activity in at least a portion of the peripheral neural structure;

a second stimulus source adapted to produce a second stimulus sufficient to reversibly modulate neural activity in the at least a portion of the peripheral neural structure; and

a signal processing portion within the package, the signal processing portion including circuitry configured to;

distinguish a first activity state of the subject from a second activity state of the subject based on the signal received at the signal input structure;

generate a first stimulus control signal for driving production of the first stimulus by the first stimulus source in a cyclical application pattern in response to at least one of the first activity state and the second activity state; and

generate a second stimulus control signal for driving production of the second stimulus by the second stimulus source in a cyclical application pattern in response to at least one of the second activity state and the second activity state;

wherein at least one of the first stimulus source and the second stimulus source includes an ultrasonic stimulus source, and

wherein at least one of a first stimulus control signal and the second stimulus control signal is configured to drive production of a blocking signal for blocking conduction in the at least a portion of the peripheral neural structure.

38. The neural modulation system of claim 37, including at least one of a wrap adapted to be positioned around the at least a portion of the body of the subject, a bandage or patch configured to be adhered or secured to at least a portion of skin of the subject, or a bracelet, an anklet, an armband, a cuff, a fitted garment, or an item of clothing configured to be worn by the subject.

39. The neural modulation system of claim 37, wherein the cyclical application pattern includes

a blocking period during which the first stimulus is applied at least intermittently, the blocking period coinciding at least in part with the first activity state in the subject;

and

a release period during which no stimulus is applied, the release period coinciding at least in part with the second activity state in the subject.

40. The neural modulation system of claim 37, wherein the signal input structure is configured to receive the signal indicative of the activity state of the subject from at least one of a sensor adapted to sense a parameter indicative of an activity state of the subject and a user input device.

41. The neural modulation system of claim 37, wherein the signal input structure is configured to receive the signal indicative of the activity state of the subject from at least one of a sensor adapted to sense a parameter indicative of an activity state of the subject, wherein the sensor includes at least one of a sensor associated with the package, a pressure sensor, a force sensor, a chemical sensor, a temperature sensor, an electrical sensor, a magnetic sensor, an optical sensor, a motion sensor, an accelerometer, a gyro, a mercury switch, a piezoelectric device, a switch, a physiological sensor, a body temperature sensor, a heart activity sensor, a peripheral neural activity sensor, or a muscle activity sensor.

42. The neural modulation system of claim 37, wherein the signal input structure is configured to receive the signal indicative of the activity state of the subject from a user input device, wherein the user input device includes at least one of a voice or sound activated input, a switch, a knob, a keyboard, a mouse, a touch screen, a remote controller, a cell phone, or a remote computer operated by the user.