Arousal state modulation with electrical stimulation

• US 8,565,886 B2
• Filed: 11/03/2011
• Issued: 10/22/2013
• Est. Priority Date: 11/10/2010
• Status: Active Grant

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Nelson, Dwight E., Wu, Jianping, Giftakis, Jonathon E., Rise, Mark T.
• Primary Examiner(s): Layno, Carl H
• Assistant Examiner(s): Stice, Paula J
• Application Number:
  US13/288,797
• Publication Number:
  US 20120116475A1
• Time in Patent Office: 719 Days
• Field of Search: 607/45
• US Class Current: 607/45
• CPC Class Codes: A61N 1/00 Electrotherapy; Circuits therefor A61N2/00 takes precedence; irradiation apparatus A61N5/00
• CPC Class Codes: A61N 1/0534 Electrodes for deep brain stimulation
• CPC Class Codes: A61N 1/36082 Cognitive or psychiatric applications, e.g. dementia or Alzheimer's disease
• CPC Class Codes: A61N 1/36139 with automatic adjustment
• CPC Class Codes: A61N 1/37247 User interfaces, e.g. input or presentation means
• CPC Class Codes: A61N 1/37264 Changing the program; Upgrading firmware
• CPC Class Codes: A61N 1/37282 characterised by communication with experts in remote locations using a network

Abstract

In some examples, an arousal network of a brain of a patient can be activated to modify the arousal state of the patient, which may be useful in treating a cognitive disorder of the patient. In some examples, a bioelectrical brain signal indicative of electrical activity in a first portion of the brain is monitored to determine whether the patient is in a first arousal state, and, in response to determining the patient is in the first arousal state, electrical stimulation is delivered to a second portion of the brain to activate an arousal neural network in the first portion of the brain to induce a second arousal state to treat the cognitive disorder, where the second arousal state is different than the first arousal state.

Claims

1. A method comprising:

receiving, from a sensing module, a bioelectrical brain signal indicative of electrical activity in a first portion of a brain of a patient;

determining, with a processor, that the brain of the patient is in a first arousal state based on the bioelectrical brain signal, wherein determining that the brain of the patient is in the first arousal state comprises detecting a biomarker indicative of the first arousal state based on the bioelectrical brain signal; and

controlling, with the processor, a stimulation module to deliver electrical stimulation to a second portion of the brain of the patient that is different than the first portion in response to determining that the first portion of the brain of the patient is in the first arousal state, wherein the electrical stimulation is configured to activate an arousal neural network in the first portion of the brain of the patient to induce a second arousal state in the brain of the patient, wherein the first portion of the brain of the patient exhibits a higher amount of electrical activity in the second arousal state than in the first arousal state, and wherein the electrical stimulation is configured to treat a cognitive disorder of the patient.

2. The method of claim 1, further comprising determining, with the processor, that the brain of the patient is in the second arousal state based on the bioelectrical brain signal.

3. The method of claim 2, wherein determining that the brain of the patient is in the second arousal state based on the bioelectrical brain signal comprises determining whether the bioelectrical brain signal exhibits a high frequency relative to a first threshold value and a low amplitude relative to a second threshold value, wherein the high frequency and the low amplitude are indicative of desynchronization within the first portion of the brain of the patient.

4. The method of claim 1, wherein the bioelectrical brain signal comprises at least one of an electroencephalogram (EEG) signal, an electrocorticogram (ECoG) signal, a local field potential (LFP) signal, or an action potential from a single cell within the patient'"'"'s brain.

5. The method of claim 1, further comprising:

receiving a signal indicative of a physiological parameter of the patient; and

determining, with the processor, the brain of the patient is in the second arousal state based on the signal.

6. The method of claim 5, wherein the at least one physiological parameter comprises at least one of a galvanic skin response of the patient, a heart rate of the patient, a respiratory rate of the patient, a body temperature of the patient, or muscle activity of the patient.

7. The method of claim 1, wherein the bioelectrical brain signal comprises a first bioelectrical brain signal, the method further comprising:

receiving a second bioelectrical brain signal sensed via a plurality of external electrodes;

detecting, with the processor, widespread activation of the arousal neural network based on the second bioelectrical brain signal; and

determining, with the processor, that the brain of the patient is in the second arousal state based on detecting the widespread activation.

8. The method of claim 1, wherein detecting the biomarker indicative of the first arousal state based on the bioelectrical brain signal comprises determining that the bioelectrical brain signal exhibits a high amplitude relative to a first threshold value and a low frequency relative to a second threshold value, wherein the high amplitude and the low frequency are indicative of synchronization.

9. The method of claim 1, wherein the first portion of the brain of the patient comprises a thalamus.

10. The method of claim 1, wherein the first portion of the brain of the patient comprises a cortex.

11. The method of claim 1, wherein the second portion of the brain of the patient comprises at least one of the anterior thalamic nucleus, the internal capsule, the cingulate cortex, the formix, the mammillary bodies, the mammillothalamic tract, the hippocampus, the Basal Nucleus of Meynert, the medial septal nucleus, the thalamic reticular nucleus, the orbitofrontal cortex, the locus coeruleus, the raphe nucleus, the substantia nigra, the amygdala, the interior thalamus, the hypothalamus, and the thalamus.

12. The method of claim 1, further comprising, with the processor, adjusting the electrical stimulation delivered by the stimulation module based on determining that the brain of the patient is in the second arousal state.

13. The method of claim 1, wherein the first arousal state is characterized by slowing of the bioelectrical brain signal relative to the second arousal state.

14. The method of claim 1, wherein the cognitive disorder is Alzheimer'"'"'s disease, and wherein detecting the biomarker indicative of the first arousal state based on the bioelectrical brain signal comprises detecting at least one of lack of normal, high frequency oscillations in the bioelectrical brain signal, disrupted frequency matching of oscillations in the bioelectrical brain signal between at least two regions of the brain of the patient, reduced phase locking of oscillations in the bioelectrical brain signal, or pathological synchronization in the bioelectrical brain signal between at least two regions of the brain of the patient.

15. The method of claim 1, wherein detecting a biomarker indicative of the first arousal state based on the bioelectrical brain signal comprises comparing the bioelectrical brain signal to a template and detecting a particular frequency domain characteristic indicative of the first arousal state based on the comparison.

16. The method of claim 1, wherein the first portion of the brain of the patient is a thalamus and the second portion of the brain of the patient is a medullary reticular formation.

17. The method of claim 1, wherein the first portion of the brain of the patient is a cortex and the second portion of the brain of the patient is at least one of a Basal Nucleus of Meynert or a hypothalamus.

18. A system comprising:

a sensing module configured to sense a bioelectrical brain signal indicative of electrical activity in a first portion of a brain of a patient;

a processor configured to determine that the brain of the patient is in a first arousal state based on the bioelectrical brain signal, wherein the processor is configured to determine that the brain of the patient is in the first arousal state by at least detecting a biomarker indicative of the first arousal state based on the bioelectrical brain signal; and

a stimulation generator configured to generate and deliver electrical stimulation to a second portion of the brain of the patient that is different than the first portion,

wherein the processor is configured to control the stimulation generator to deliver electrical stimulation to the second portion of the brain of the patient in response to determining that the first portion of the brain of the patient is in the first arousal state, wherein the electrical stimulation is configured to activate an arousal neural network in the first portion of the brain of the patient to induce a second arousal state in the brain of the patient, wherein the first portion of the brain of the patient exhibits a higher amount of electrical activity in the second arousal state than in the first arousal state, and wherein the electrical stimulation is configured to treat a cognitive disorder of the patient.

19. The system of claim 18, wherein the processor is configured to determine that the brain of the patient is in the second arousal state based on the bioelectrical brain signal.

20. The system of claim 19, wherein the processor is configured to determine that the brain of the patient is in the second arousal state by at least determining the bio electrical brain signal exhibits a high frequency relative to a first threshold value and a low amplitude relative to a second threshold value, wherein the high frequency and the low amplitude are indicative of desynchronization within the first portion of the brain of the patient.

21. The system of claim 18, further comprising an external sensor configured to generate a signal indicative of a physiological parameter of the patient, wherein the processor is configured to determine the brain of the patient is in the second arousal state based on the signal.

22. The system of claim 21, wherein the at least one physiological parameter comprises at least one of a galvanic skin response of the patient, a heart rate of the patient, a respiratory rate of the patient, a body temperature of the patient, or muscle activity of the patient.

23. The system of claim 18, wherein the bioelectrical brain signal comprises a first bioelectrical brain signal, wherein the system further comprises a plurality of external electrodes configured to sense a second bioelectrical brain signal, and wherein the processor is configured to detect widespread activation of the arousal neural network based on at least the second bioelectrical brain signal and determine that the brain of the patient is in the second arousal state based on detecting the widespread activation.

24. The system of claim 18, wherein the processor is configured to detect the biomarker indicative of the first arousal state based on the bioelectrical brain signal by at least determining that the bioelectrical brain signal exhibits a high amplitude relative to a first threshold value and a low frequency relative to a second threshold value, wherein the high amplitude and the low frequency are indicative of synchronization in the first portion of the brain of the patient.

25. The system of claim 18, wherein the first portion of the brain of the patient comprises at least one of one of a thalamus or a cortex.

26. The system of claim 18, wherein the second portion of the brain of the patient comprises at least one of the anterior thalamic nucleus, the internal capsule, the cingulate cortex, the formix, the mammillary bodies, the mammillothalamic tract, the hippocampus, the Basal Nucleus of Meynert, the medial septal nucleus, the thalamic reticular nucleus, the orbitofrontal cortex, the locus coeruleus, the raphe nucleus, the substantia nigra, the amygdala, the interior thalamus, the hypothalamus, and the thalamus.

27. The system of claim 18, wherein the processor is configured to adjust the electrical stimulation based on determining that the brain of the patient is in the second arousal state.

28. The system of claim 18, wherein the cognitive disorder is Alzheimer'"'"'s disease, and wherein the processor is configured to detect the biomarker indicative of the first arousal state based on the bioelectrical brain signal by detecting at least one of lack of normal, high frequency oscillations in the bioelectrical brain signal, disrupted frequency matching of oscillations in the bioelectrical brain signal between at least two regions of the brain of the patient, reduced phase locking of oscillations in the bioelectrical brain signal, or pathological synchronization in the bioelectrical brain signal between at least two regions of the brain of the patient.

29. A non-transitory computer-readable medium comprising instructions that cause a programmable processor to:

receive, from a sensing module, a bioelectrical brain signal indicative of electrical activity in a first portion of a brain of a patient;

determine that the brain of the patient is in a first arousal state based on the bioelectrical brain signal by at least detecting a biomarker indicative of the first arousal state based on the bioelectrical brain signal; and

control a stimulation generator to deliver electrical stimulation to a second portion of the brain of the patient in response to determining that the first portion of the brain of the patient is in the first arousal state, wherein the electrical stimulation is configured to activate an arousal neural network in the first portion of the brain of the patient to induce a second arousal state in the brain of the patient, wherein the first portion of the brain of the patient exhibits a higher amount of electrical activity in the second arousal state than in the first arousal state, and wherein the electrical stimulation is configured to treat a cognitive disorder of the patient.

30. The non-transitory computer-readable medium of claim 29, further comprising instructions that cause the processor to determine that the brain of the patient is in the second arousal state based on the bioelectrical brain signal.

31. The non-transitory computer-readable medium of claim 29, further comprising instructions that cause the processor to:

receive a signal indicative of a physiological parameter of the patient; and

determine the brain of the patient is in the second arousal state based on the signal.

32. A system comprising:

means for receiving a bioelectrical brain signal indicative of electrical activity in a first portion of a brain of a patient;

means for determining that the brain of the patient is in a first arousal state based on the bioelectrical brain signal, wherein the means for determining that the brain of the patient is in a first arousal state based on the bioelectrical brain signal comprises means for detecting a biomarker indicative of the first arousal state based on the bioelectrical brain signal; and

means for controlling delivery of electrical stimulation to a second portion of the brain of the patient that is different than the first portion in response to determining that the first portion of the brain of the patient is in the first arousal state, wherein the electrical stimulation is configured to activate an arousal neural network in the first portion of the brain of the patient to induce a second arousal state in the brain of the patient, wherein the first portion of the brain of the patient exhibits a higher amount of electrical activity in the second arousal state than in the first arousal state, and wherein the electrical stimulation is configured to treat a cognitive disorder of the patient.

33. The system of claim 32, further comprising means for determining that the brain of the patient is in the second arousal state based on the bioelectrical brain signal.

34. The system of claim 32, further comprising:

means for receiving a signal indicative of a physiological parameter of the patient; and

means for determining that the brain of the patient is in the second arousal state based on the signal indicative of the physiological parameter of the patient.