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

• US 20050021104A1
• Filed: 04/05/2004
• Published: 01/27/2005
• Est. Priority Date: 08/05/1998
• Status: Active Grant

• Current Assignee: Cyberonics, Inc, DiLorenzo Biomedical, LLC
• Original Assignee: NeuroVista Corporation
• Inventors: DiLorenzo, Daniel John
• Granted Patent: US 7,277,758 B2
• Time in Patent Office: Days
• 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 1/0539 Anchoring of brain electrode systems, e.g. within burr hole
• CPC Class Codes: A61N 1/36082 Cognitive or psychiatric applications, e.g. dementia or Alzheimer's disease

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 system for modulating the activity of at least one nervous system component, the system comprising:

A. at least one neuromodulator, each constructed and arranged to deliver a neural modulation signal to at least one nervous system component or non-neural structure;

B. at least one sensor, each constructed ands arranged to sense at least one parameter, including but not limited to physiologic values and neural signals, which is indicative of at least one of disease state, magnitude of symptoms, and response to therapy; and

C. 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. A system as recited in claim 1 wherein said non-neural structure comprises the skin.

3. A system as recited in claim 2 wherein said skin comprises at least one of the face and scalp.

4. A system as recited in claim 1 wherein said wherein said neural structure comprises a cranial nerve

5. A system as recited in claim 1 wherein said wherein said neuromodulator is located at least one of overlying or adjacent to the skin.

6. A system as recited in claim 1 wherein said sensor is located at least one of overlying or adjacent to the skin.

7. A system as recited in claim 1 wherein entirety of said system is located external to the skin.

8. A system as recited in claim 1 wherein said neural structure comprises at least one of hippocampus, ventral medial Vim thalamic nucleus, other portion of the thalamus, entirety 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, limbic circuit of Papez, the fronto-basal ganglionic-thalamocortical system, white matter tracts, motor cortex, premotor cortex, supplementary motor cortex, other motor cortical regions, somatosensory cortex, other sensory cortical regions, Broca'"'"'s area, Wernickie'"'"'s area, other cortical regions, ventricular region, paraventricular region, other central nervous system structure, other peripheral nervous system structure, other neural structure, sensory organs, and other structure.

9. A system as recited in claim 1 wherein said neural structure comprises at least one of trigeminal nerve, cervical nerve C2, cervical nerve C3, other cervical nerve, facial nerve, and olfactory nerve.

10. A system as recited in claim 1 wherein said neural structure comprises at least one of subcutaneous nerve, dura, frontal lobe, temporal lobe, parietal lobe, occipital lobe, cerebellum, dorsal column, spinothalamic tract, raphe nucleus, solitary nucleus,

11. A system as recited in claim 1 wherein said neural structure comprises the anterior nucleus of the thalamus.

12. A system as recited in claim 1 wherein said neural structure comprises the ventral medial Vim nucleus of the thalamus.

13. A system as recited in claim 1 wherein said neural structure comprises the hippocampus.

14. A system as recited in claim 1 wherein said neural modulation signal is used for the treatment of at least one of seizure disorder, epilepsy, narcolepsy, schizophrenia, psychosis, bipolar disorder, depression, mania, headaches, migraine headaches, cluster headaches, other headaches, other neurological disease, other psychiatric disease, hypertension, hypotension, diabetes, and arrhythmias.

17. A system, as in claim 1, wherein said control circuit generates output signal that is a function of a neurological state.

20. A system, as in claim 1, wherein said control circuit generates output signal that is a function of the probability of a predicted neurological state.

23. A system, as in claim 1, wherein said control circuit generates output signal that is a function of likelihood of a current neurological state.

28. A system as in claim 1, wherein said neural modulation signal is selected to modulate neural chaos.

29. A system as in claim 28, wherein said neural modulation signal is selected to increase neural chaos.

30. A system as in claim 29, wherein said neural modulation signal comprises at least one energy pulse.

31. A system as in claim 30, wherein said energy pulse comprises at least one of electrical energy, optical energy, electromagnetic energy, radiofrequency energy, ultrasonic energy, thermal energy, vibration energy, vibrotactile energy, chemical energy, and electrostatic energy.

32. A system as in claim 30, wherein said neural modulation signal is in the form of at least one of a thermal energy source, thermal energy sink, heat source, or cold source.

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

;

A. a sensor array in electronic communication with a signal conditioning circuit;

B. a control circuit in electronic communication with said signal conditioning circuit;

C. an output stage circuit in electronic communication with said control circuit; and

D. a neuromodulator array, in electronic communication with said output stage circuit.

19. A system, as in claim 15, wherein said control circuit generates output signal that is a function of the likelihood of a predicted neurological state.

21. A system, as in claim 15 wherein said control circuit generates output signal that is a function of predicted time to onset of a neurological state.

33. A system as in claim 15, wherein said neuromodulator array comprises at least one of single stimulating electrode, plurality of stimulating electrodes, drug delivery catheter, light source, electromagnetic coil, electromagnetic transducer, radiofrequency transducer, ultrasonic transducer, thermal energy source, thermal energy sink, piezoelectric transducer, vibrotactile transducer, chemical source, electrostatic field source.

34. A system as in claim 33, wherein said neuromodulator array modulates neural chaos.

35. A system as in claim 33, wherein said neuromodulator array increases neural chaos.

36. A system as in claim 33, wherein said neuromodulator array delivers at least one signal patterned in time.

37. A system as in claim 33, wherein said neuromodulator array delivers at least one signal patterned in space.

38. A system as in claim 37, wherein said neuromodulator array delivers a multiplicity of signals that are at least one of asynchronous, uncorrelated, non-identical, and unrelated by a multiplicative factor, unrelated by an additive factor, unrelated by any other function.

39. A system as in claim 37, wherein said neuromodulator array delivers a multiplicity of signals that are at least one of synchronous, correlated, identical, and related by a multiplicative factor, related by an additive factor, related by other function.

40. A system as in claim 33, wherein said neuromodulator array delivers at least one signal that is at least one of random, pseudorandom, non-repeating, non-patterned, pink noise, and white noise.

41. A system as in claim 33, wherein said neuromodulator array delivers at least one signal, the frequency of which varies over time.

42. A system as in claim 33, wherein said neuromodulator array delivers at least two signals.

43. A system as in claim 42, wherein said two signals differ in at least one of frequency, amplitude, voltage, current, intensity, burst count, burst frequency, and anatomical location.

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

;

A. a sensor array in electronic communication with a control circuit;

B. an output stage circuit in electronic communication with said control circuit; and

C. a neuromodulator array, in electronic communication with said output stage circuit.

18. A system, as in claim 16, wherein said control circuit generates output signal that is a function of a predicted neurological state.

22. A system, as in claim 16, wherein said control circuit generates output signal that is a function of likelihood of a future neurological state.

24. A system, as in claim 16, wherein said predicted neurological state is the occurrence of a seizure.

25. A system, as in claim 16, wherein said predicted neurological state is the occurrence of a headache.

26. A system, as in claim 16, wherein said predicted neurological state is the occurrence of sleep.

27. A system, as in claim 16, wherein said predicted neurological state is the occurrence of a narcoleptic event.

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

(A) a signal conditioning circuit;

(B) a sensor array in electronic communication with said signal conditioning circuit, wherein said sensor array senses a particular characteristic indicative of a neurological or psychiatric condition;

(C) a signal processor in electronic communication with said signal conditioning circuit;

(D) a control circuit in electronic communication with said signal processor; and

(E) an output stage circuit in electronic communication with said control circuit.

45. A system, as in claim 44, further comprising an array of neuromodulators

46. A system as in claim 44, wherein said signal processor calculates a value representative of chaos in the nervous system

47. A system as in claim 44, wherein said signal processor calculates a value representative of correlation between signals in the nervous system

48. A system as in claim 44, wherein said signal processor generates a seizure warning based on the plurality of signals detected by said plurality of signals detected by said sensor array, said signal processor comprising:

A. means for receiving the plurality of signals detected by sensor array;

B. means [signal conditioner] for preprocessing said plurality of signals detected by said sensors so as to produce a digital equivalent for each of said signals;

C. means for generating a spatio-temporal response for each of a corresponding one of the plurality of digital signals;

D. means for generating a chaoticity profile, comprising a sequence of chaoticity values, from each spatiotemporal response,

E. means for determining whether a level of entrainment between chaoticity profiles associated with a critical pair of signals is statistically significant;

F. means for generating a seizure warning if it is determined that the level of entrainment associated with the critical signal pair is statistically significant

49. A system as in claim 48, further comprising a means for delivering a warning to at least one of patient, observer, control circuit, physician, and other person.

50. A system as in claim 49, wherein said means for delivering a warning comprises at least one of electrical connector, vibrotactile transducer, light source, sound source, pressure source, heat source, heat sink, piezoelectric transducer, other transducer, means for chemical release, and means for drug release.

51. A system as in claim 49, wherein said warning is at least one of an electrical voltage, electrical current, electrical signal, optical signal, audible signal, vibrational signal, vibrotactile signal, pressure signal, thermal signal, radiofrequency signal, neural signal, chemical signal, benzodiazepine, muscimol, phenytoin, tegratol, valproic acid, anticonvulsant, muscimol, GABA antagonist, pharmacological signal, or other signal.

52. A system as in claim 48, further comprising an array of at least one neuromodulator.

53. A system as in claim 52, wherein said neuromodulator modulates neural activity to control [or influence/change/modulate] at least one of said spatio-temporal response, said chaoticity profile, said chaoticity values, and said level of entrainment.

54. A system as in claim 52, wherein said neuromodulator modulates activity in at least one of hippocampus, ventral medial Vim thalamic nucleus, other portion of the thalamus, entirety 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, limbic circuit of Papez, the fronto-basal ganglionic-thalamocortical system, white matter tracts, motor cortex, premotor cortex, supplementary motor cortex, other motor cortical regions, somatosensory cortex, other sensory cortical regions, Broca'"'"'s area, Wernickie'"'"'s area, other cortical regions, ventricular region, paraventricular region, other central nervous system structure, other peripheral nervous system structure, other neural structure, sensory organs, and other structure.

55. A system as in claim 52, wherein said neuromodulator comprises an electrode catheter with at least one electrode.

56. A system as in claim 55, wherein said neuromodulator delivers electrical signal to at least one of the hippocampus, anterior nucleus of the thalamus, ventral medial (Vim) nucleus of the thalamus, other neural structure, and other non-neural structure.

57. A system as in claim 55, wherein said electrode delivers electrical waveform with a frequency below or equal to 100 Hz.

58. A system as in claim 55, wherein said electrode delivers electrical waveform with a frequency above or equal to 100 Hz.

59. A system as in claim 52, wherein control circuit generates output to maintain at least one of said chaoticity profile, said chaoticity values, and said level of entrainment above a threshold.

60. A system as in claim 59, wherein at least one of said chaoticity profile, said chaoticity values, and said level of entrainment is measured using a T-index.

61. A method for modulating signals for use in treating disease, comprising:

(A) sensing a biological signal in a biological body;

(B) conditioning said sensed biological signal;

(C) processing said conditioned biological signal; and

(D) generating a neuromodulating signal for communication in said biological body.

62. A method as in claim 61, wherein said neuromodulatory signal is at least one of electrical, chemical, pharmacological, electromagnetic, radiofrequency, optical, vibrational, ultrasonic, heat source, heat sink, and thermal

63. A method as in claim 61, wherein said processing comprises

A. generation, for each channel, of a spatio-temporal response based upon the corresponding time series signal;

B. quantifying a sequence of chaoticity values for each channel based on the corresponding spatio-temporal response, wherein each sequence of chaoticity values constitutes a chaoticity profile;

C. comparing, over time, the chaoticity profiles associated with each of a number of channel pairs;

D. evaluating, over time, levels of entrainment between the chaoticity profiles associated with each of the channel pairs

E. determining whether the levels of entrainment associated with one or more of the channel pairs are statistically significant; and

64. A method as in claim 63, further comprising:

generating a seizure warning if it is determined that the levels of entrainment associated with one or more of the channel pairs are statistically significant.

65. A method as in claim 63, wherein said neuromodulating signal is generated by a control law which is a function of said levels of entrainment.

66. A method as in claim 63, wherein said neuromodulating signal is generated by a control law which is a function of said chaoticity profiles.

67. A method as in claim 63, wherein said neuromodulating signal is generated by a control law which is a function of level of chaos.

68. A method as in claim 63, wherein said neuromodulating signal is generated by a control law which is a function of a T-index.