Apparatus and method for closed-loop intracranial stimulation for optimal control of neurological disease

• US 7,209,787 B2
• Filed: 11/20/2003
• Issued: 04/24/2007
• Est. Priority Date: 08/05/1998
• Status: Expired due to Term

• Current Assignee: Cyberonics, Inc, DiLorenzo Biomedical, LLC
• Original Assignee: Bioneuronics Corporation
• Inventors: DiLorenzo, Daniel John
• Primary Examiner(s): Getzow; Scott M.
• Application Number:
  US10/718,248
• Publication Number:
  US 20050021103A1
• Time in Patent Office: 1,251 Days
• Field of Search: 607/45, 607/72, 607/73, 607/74, 607/48
• US Class Current: 607/45
• CPC Class Codes: A61N 1/0529 Electrodes for brain stimulation
• CPC Class Codes: A61N 1/0531 Brain cortex electrodes
• CPC Class Codes: A61N 1/0534 Electrodes for deep brain stimulation
• CPC Class Codes: A61N 1/0539 Anchoring of brain electrode systems, e.g. within burr hole
• CPC Class Codes: A61N 1/3605 Implantable neurostimulators for stimulating central or peripheral nerve system
• CPC Class Codes: A61N 1/36064 Epilepsy
• CPC Class Codes: A61N 1/36067 Movement disorders, e.g. tremor or Parkinson disease stimulating motor muscle A61N1/36003
• CPC Class Codes: A61N 1/36082 Cognitive or psychiatric applications, e.g. dementia or Alzheimer's disease
• CPC Class Codes: A61N 1/372 Arrangements in connection with the implantation of stimulators
• CPC Class Codes: A61N 1/3787 from an external energy source

Abstract

A neurological control system for modulating activity of any component or structure comprising the entirety or portion of the nervous system, or any structure interfaced thereto, generally referred to herein as a “nervous system component.” The neurological control system generates neural modulation signals delivered to a nervous system component through one or more intracranial (IC) stimulating electrodes in accordance with treatment parameters. Such treatment parameters may be derived from a neural response to previously delivered neural modulation signals sensed by one or more sensors, each configured to sense a particular characteristic indicative of a neurological or psychiatric condition.

Claims

1. A neurological control system for modulating the activity of at least one nervous system component, the neurological control system comprising:

at least one intracranial stimulating electrode, each constructed and arranged to deliver a neural modulation signal to at least one nervous system component;

at least one sensor, each constructed and arranged to sense at least one parameter that comprises at least one of physiologic values and neural signals, which is indicative or predictive of a seizure; and

a stimulating and recording unit constructed and arranged to generate said neural modulation signal based upon a neural response sensed by said at least one sensor in response to a previously delivered neural modulation signal.

2. The system of claim 1, wherein said stimulating and recording unit generates said neural modulation signal in accordance with predetermined treatment parameters to treat the seizure.

3. The system of claim 1, wherein said stimulating and recording unit comprises:

a signal processor constructed and arranged to process said neural response to determine a neural system state; and

a control module for adjusting said neural modulation signal based upon said neural system state.

4. The system of claim 3, wherein each of said at least one sensor generates one or more neural response signals, and wherein said stimulating and recording unit further comprises:

a signal conditioner, interposed between said at least one sensor and said signal processor, constructed and arranged to modify said one or more neural response signals appropriately for said signal processor.

5. The system of claim 4, wherein said signal conditioner comprises:

at least one amplifier, each constructed and arranged to amplify said one or more neural response signals generated by an associated one of said at least one sensor; and

at least one signal filter, each constructed and arranged to filter said one or more amplified neural response signals generated by an associated one of said at least one amplifier.

6. The system of claim 5, wherein said at least one signal filter performs at least one of lowpass filtering, highpass filtering, bandpass filtering and notch filtering of said one or more amplified neural response signals.

7. An apparatus for modulating the activity of at least one nervous system component, said system comprising:

means for monitoring parameters that are indicative or predictive of a seizure;

means for delivering neural modulation signals to said nervous system component when the means for monitoring indicate or predict the onset of the seizure;

means for sensing a neural response to said neural modulation signals; and

controller means for modulating parameters of a subsequent neural modulation signal based on the sensed neural response to a previously delivered neural modulation signal.

8. The apparatus of claim 7, wherein said delivery means comprises means for generating said neural modulation signals, said generating means comprises:

signal conditioning means for conditioning said sensed neural response signals, said conditioning including but not limited to at least one of amplification, lowpass filtering, highpass filtering, bandpass filtering, notch filtering, root-mean square calculation, envelope determination, and rectification; and

wherein said sensing means comprises signal processing means for processing said conditioned sensed neural response signals to determine neural system states.

9. The apparatus of claim 8, wherein said means for generating a neural modulation signal employs a control law using as input signals derived from at least one of accelerometers, electromyography electrodes, acoustic sensors, intracranial electrodes, electroencephalography electrodes, and peripheral nerve electrodes.

10. The apparatus of claim 8, wherein said means for generating a neural modulation signal employs a control law using as input a weighted aggregate of professed signals derived from at least one of accelerometers, electromyography electrodes, acoustic sensors, intracranial electrodes, electroencephalography electrodes, and peripheral nerve electrodes.

11. The apparatus of claim 7, wherein said means for delivering neural modulation signals to said nervous system component includes electrodes implemented into at least one of the globus pallidus internus (GPi), including globus pallidus intemus internal segment (GPi,i) and globus pallidus internus external segment (GPi,e), globus pallidus externus (GPe), ventral medial (Vim) thalamic nucleus, other portion of the thalamus, subthalamic nucleus (STN), caudate, putamen, other basal ganglia components, cingulate gyrus, other subcortical nuclei, nucleus locus ceruleus, pedunculopontine nuclei of the reticular formation, red nucleus, substantia nigra, other brainstem structure, cerebellum, internal capsule, external capsule, corticospinal tract, pyramidal tract, ansa lenticularis, white matter tracts, motor cortex, premotor cortex, supplementary motor cortex, other motor cortical regions, somatosensory cortex, other sensory cortical regions, Brocats area, Wernicke'"'"'s area, other cortical regions, other central nervous system structure, other peripheral nervous system structure, other neural structure, sensory organs, muscle tissue, or other non-neural structure.

12. The apparatus of claim 7, wherein said means for sensing a neural response includes at least one of accelerometers, electromyography electrodes, acoustic sensors, intracranial electrodes, electroencephalography electrodes, and peripheral nerve electrodes.

13. The apparatus of claim 7, wherein said means for sensing a neural response includes a weighted aggregate of processed signals derived from at least one of accelerometers, electromyography electrodes, acoustic sensors, intracranial electrodes, electroencephalography electrodes, and peripheral nerve electrodes.

14. A system for neural modulation in the treatment of disease, comprising:

a system enclosure, in mechanical communication with a calvarium;

a control circuit positioned within said system enclosure and in electronic communication with a signal processor;

an output stage circuit in electronic communication with said control circuit;

a stimulating electrode array, in electronic communication with said output circuit;

an intracranial catheter that is attached to said stimulating electrode array; and

a microelectrode attached to a microelectrode shaft which is positioned along a longitudinal axis of said intracranial catheter.

15. A system as in claim 14, wherein said intracranial catheter includes at least one microelectrode tunnel for receiving said microelectrode shaft.

16. A system as in claim 14, said system enclosure comprising at least one intracranial catheter port.

17. A system as in claim 16, said intracranial catheter port positioned at the center of said system enclosure.

18. A system as in claim 17, said intracranial catheter port positioned at the periphery of said system enclosure.

19. A system as in claim 14, said system enclosure including a catheter recess.

20. A system as in claim 19, said catheter recess comprising means for establishing contact between said system enclosure and said intracranial catheter.

21. A system as in claim 14, further comprising catheter stabilization means.

22. A system as in claim 21, wherein said catheter stabilization means comprises a catheter mount ball.

23. A system as in claim 22, wherein said catheter mount ball comprises a catheter ball channel.

24. A system as in claim 21, wherein said catheter stabilization means comprises a catheter insertion mount.

25. A system as in claim 24, wherein said catheter insertion mount comprises a catheter mount system enclosure attachment means.

26. A system as in claim 24, wherein said system enclosure comprises a system enclosure catheter mount attachment means.

27. A system as in claim 21, wherein said catheter stabilization means comprises a catheter locking mechanism.

28. A system as in claim 27, wherein said catheter locking mechanism comprises a compressible material.

29. A system as in claim 28, wherein said compressible material is compressed against said intracranial catheter.

30. A system as in claim 27, wherein said catheter locking mechanism comprises a catheter mount ball locking screw.

31. A system as in claim 30, wherein said catheter mount ball locking screw provides force to compress said catheter locking mechanism.

32. A system as in claim 14, further comprising at least one electrode contact.

33. A system as in claim 32, wherein said electrode contact is in mechanical connection to said system enclosure.

34. A system as in claim 32, wherein said electrode contact is contained within a catheter recess.

35. A system as in claim 14, wherein said system comprises a multiplicity of intracranial catheters.

36. A system as in claim 14, further comprising a multiplicity of intracranial catheters, wherein elements of said stimulating electrode array are mechanically attached to at least one of said intracranial catheters.

37. A system as in claim 14, said stimulating electrode array comprising a conducting film mechanically attached to said intracranial catheter.

38. A system as in claim 14, said stimulating electrode array comprising a conducting layer deposited on said intracranial catheter.

39. An intracranial catheter for use in the treatment of disease, comprising at least one stimulating electrode and at least one microelectrode,

wherein said microelectrode is attached to a microelectrode shaft which is positioned along the longitudinal axis of said intracranial catheter.

40. An intracranial catheter as in claim 39, wherein said microelectrode is attached to said microelectrode shaft which is parallel to the longitudinal axis of said intracranial catheter.

41. An intracranial catheter as in claim 39, wherein said microelectrode is removable.

42. An intracranial catheter for use in the treatment of disease, the intracranial catheter comprising at least one stimulating electrode and at least one microelectrode, wherein said microelectrode is attached to a microelectrode shaft which is parallel to a longitudinal axis of said intracranial catheter.

43. The intracranial catheter as in claim 42, wherein said microelectrode is removably coupled to said at least one stimulating electrode.

44. The intracranial catheter as in claim 42, wherein said at least one stimulating electrode is disposed around an outer surface of said intracranial catheter.

45. The intracranial catheter as in claim 42, wherein said at least one stimulating electrode comprises a plurality of stimulating electrodes, the plurality of stimulating electrodes disposed around an outer surface of said intracranial catheter and spaced longitudinally along a length of the intracranial catheter.

46. The intracranial catheter as in claim 42, wherein said intracranial catheter comprises a microelectrode channel for receiving the microelectrode shaft.

47. The intracranial catheter as in claim 42, wherein a distal tip of said microelectrode is configured to be positionable distal of a distal tip of the intracranial catheter.

48. The intracranial catheter as in claim 42, wherein said microelectrode is configured to record single cell activity during advancement of said intracranial catheter through a patient'"'"'s brain.

49. A method of managing a neurological or psychiatric disease state, the method comprising:

measuring one or more signals from a patient'"'"'s brain;

extracting at least one parameter from the one or more signals that are predictive of future symptomatology of a neurological or psychiatric disease;

delivering a neural modulation signal to the patient when the one or more signals predict an onset of the symptomatology;

monitoring a patient'"'"'s response to the neural modulation signal;

processing the patient'"'"'s response to the neural modulation signal to derive at least one parameter of a subsequent neural modulation signal; and

delivering the subsequent neural modulation signal to the patient if the response to the neural modulation signal indicates that the subsequent neural modulation signal is needed.

50. The method of claim 49, further comprising storing data in a memory that is reflective of the at least one extracted parameters, wherein the memory is implanted in the patient'"'"'s body.

51. The method of claim 50, comprising transcutaneously transmitting the stored data from the memory that is implanted in the patient'"'"'s body to a communication module that is external to the patient'"'"'s body.

52. The method of claim 49, wherein the one or more signals comprise brain activity signals and wherein the patient'"'"'s response comprises a brain activity response.

53. The method of claim 52, wherein monitoring the patient'"'"'s response comprises extracting the at least one parameter that is predictive of the future symptomatology from the brain activity response and comparing the extracted at least one brain activity response parameter to at least one clinician programmed reference parameter.

54. The method of claim 53, wherein extracting the at least one parameter and comparing the at least one brain activity response parameter to the at least one clinician programmed reference parameter are performed in a unit that is implanted in the patient'"'"'s body.

55. The method of claim 54, wherein the unit is implanted intracranially in the patient'"'"'s body.

56. The method of claim 49, wherein the at least one extracted parameter comprises parameters of an EEG signal.

57. The method of claim 56, wherein the at least one extracted parameter comprises at least one of a peak-to-valley times, valley-to-peak times, positive phase amplitudes, and negative phase amplitudes of the EEG signal.

58. The method of claim 56, wherein the at least one extracted parameter comprises a peak-to-valley times, a valley-to-peak times, a positive phase amplitudes, and a negative phase amplitudes of the EEG signal.

59. The method of claim 49, wherein monitoring the patient'"'"'s response to the neural modulation signal comprises determining if undesirable brain activity is present.

60. The method of claim 49, wherein the subsequent neural modulation signal is needed if a desired change in brain activity is not achieved with the neural modulation signal.

61. The method of claim 49, wherein at least one of the neural modulation signal and subsequent neural modulation signals comprise a pulse train of waveforms.

62. The method of claim 61, wherein the pulse train of waveforms comprise one or more bursts of waveforms.

63. The method of claim 62, wherein the one or more bursts each comprise one or more charge-balanced biphasic stimulus pulses.

64. The method of claim 62, wherein the pulse train of waveforms comprise a plurality of bursts of charge-balanced biphasic stimulus pulses.

65. The method of claim 49 wherein delivering the neural modulation signal and delivering the subsequent neural modulation signal comprise delivering the signal to a peripheral nerve.

66. The method of claim 49 wherein measuring one or more signals from a patient'"'"'s brain comprises using at least one intracranial electrode.

67. The method of claim 49 wherein the neurological or psychiatric disease is epilepsy and the future symptomatology is a seizure.

68. A method, comprising:

delivering electrical stimulation to a vagus nerve of a patient;

monitoring a brain activity response to the electrical stimulation to the vagus nerve; and

delivering a subsequent electrical stimulation to the patient if brain activity response indicates that the subsequent electrical stimulation is needed,

wherein monitoring the brain activity response comprises identifying action potentials in individual neurons in the patient'"'"'s brain.

69. The method of claim 68, further comprising:

coupling at least one electrode to the vagus nerve of the patient, wherein the electrical stimulation is delivered to the electrode coupled to the vagus nerve of the patient; and

intracranially implanting one or more electrodes, wherein the one or more electrodes are used to monitor the brain activity response to the electrical stimulation to the vagus nerve.

70. The method of claim 68, wherein identifying action potentials in individual neurons in the patient'"'"'s brain is performed using one or more microelectrodes.

71. The method of claim 68, wherein monitoring the brain activity response comprises monitoring aggregate activity from groups of neurons.

72. The method of claim 71, wherein monitoring the brain activity response comprises extracting parameters from one or more signals that are indicative of electrical activity of groups of neurons in the patient'"'"'s brain.

73. The method of claim 71, further comprising, prior to delivering electrical stimulation to the vagus nerve of a patient,:

measuring one or more signals from the patient'"'"'s brain;

extracting one or more parameters from the one or more signals that are predictive of future symptomatology,

wherein the electrical stimulation is delivered to the vagus nerve of the patient only when the future symptomatology is predicted.

74. The method of claim 71, further comprising storing the patient'"'"'s response to the electrical stimulation signal in a memory device.

75. A method, comprising:

delivering electrical stimulation to a vagus nerve of a patient;

monitoring a brain activity response to the electrical stimulation to the vagus nerve;

deriving parameters of a subsequent electrical stimulation signal from the brain activity response to the electrical stimulation signal; and

delivering the subsequent electrical stimulation to the patient if brain activity response indicates that the subsequent electrical stimulation is needed.

76. A method of managing epilepsy, comprising:

monitoring parameters of a patient'"'"'s brain activity to predict an onset of a seizure;

delivering a first neural modulation signal to the patient when the monitored parameters of a patient'"'"'s brain activity indicate undesirable brain activity that is predictive of the onset of a seizure;

monitoring a patient'"'"'s brain activity response after delivering the first neural modulation signal; and

delivering a second neural modulation signal to the patient if the monitored brain activity response indicates that said patient'"'"'s brain activity is undesirable,

wherein monitoring the patient'"'"'s brain activity response comprises identifying action potentials in individual neurons in the patient'"'"'s brain.

77. The method of claim 76, wherein at least one of the first and second neural modulation signal comprises one or more electrical stimulation waveforms.

78. The method of claim 77, wherein the one or more electrical stimulation waveform comprises one or more charge-balanced biphasic waveforms.

79. The method of claim 76, wherein at least one of the first and second neural modulation signals is delivered to a peripheral nerve.

80. The method of claim 76, wherein identifying action potentials in individual neurons in the patient'"'"'s brain is performed using one or more microelectrodes.

81. The method of claim 76, wherein monitoring the patient'"'"'s brain activity response comprises monitoring aggregate activity from a population of neurons.

82. The method of claim 76, wherein monitoring parameters of the patient'"'"'s brain activity response comprises:

monitoring one or more signals from a nervous system component; and

extracting parameters from the one or more signals that are indicative of electrical activity of groups of neurons in the patient'"'"'s brain.

83. The method of claim 76, further comprising storing the patient'"'"'s response to the first neural modulation signal in a memory device.

84. A method of managing epilepsy, comprising:

monitoring parameters of a patient'"'"'s brain activity to predict an onset of a seizure;

delivering a first neural modulation signal to the patient when the monitored parameters of a patient'"'"'s brain activity indicate undesirable brain activity that is predictive of the onset of a seizure;

monitoring a patient'"'"'s brain activity response after delivering the first neural modulation signal;

deriving parameters of a second neural modulation signal from the patient'"'"'s brain activity response to the first neural modulation signal,

delivering the second neural modulation signal to the patient if the monitored brain activity response indicates that said patient'"'"'s brain activity is undesirable.

85. The method of claim 84, wherein at least one of the first and second neural modulation signals comprises medication.