Methods and systems for treating neurological movement disorders

• US 9,295,838 B2
• Filed: 10/31/2013
• Issued: 03/29/2016
• Est. Priority Date: 10/31/2012
• Status: Active Grant

• Current Assignee: US Department of Veterans Affairs (Government of the United States of America), Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Starr, Philip A., de Hemptinne, Coralie, Ostrem, Jill, Swann, Nicole
• Primary Examiner(s): EVANISKO, GEORGE ROBERT
• Application Number:
  US14/069,170
• Publication Number:
  US 20140163627A1
• Time in Patent Office: 880 Days
• US Class Current: 1/1
• 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 1/0531 Brain cortex electrodes
• CPC Class Codes: A61N 1/0534 Electrodes for deep brain stimulation
• CPC Class Codes: A61N 1/36067 Movement disorders, e.g. tremor or Parkinson disease stimulating motor muscle A61N1/36003
• CPC Class Codes: A61N 1/36139 with automatic adjustment

Abstract

The present disclosure provides methods for reducing the clinical presentations of a neurological movement disorder in a subject. Aspects of the methods include measuring cortical local field potentials (LFPs) from the subject'"'"'s brain, calculating a modulation index related to brain synchronization from the LFPs, and administering deep brain stimulation to the subject if the calculated modulation index is outside of a threshold range. Also provided are devices, systems, and kits that may be used in practicing the subject methods.

Claims

1. A method for reducing clinical presentations of a neurological movement disorder in a subject, the method comprising:

(i) administering a first deep brain stimulus train to the subject;

(ii) measuring cortical local field potentials (LFPs) from a surface of the subject'"'"'s primary motor cortex using at least one electrode, wherein the at least one electrode is located at a position corresponding to an arm area of primary motor cortex M1;

(iii) calculating, with a processor, a modulation index for synchronization of brain rhythms in the LFPs, wherein the synchronization of brain rhythms in the LFPs comprises synchronization of phase of beta rhythm and amplitude of gamma activity; and

(iv) administering a second deep brain stimulus train to the subject when the calculated modulation index is outside of a predefined threshold range;

wherein steps (i)-(iv) are continued in a manner effective to reduce the clinical presentations of the neurological movement disorder.

2. The method according to claim 1, wherein at least one parameter of the second deep brain stimulus train is different relative to the first deep brain stimulus train.

3. The method according to claim 2, wherein the at least one parameter is selected from the group consisting of contact choice, amplitude, and frequency.

4. The method according to claim 1, further comprising changing, with the processor, at least one parameter of the first deep brain stimulus train prior to administering the second deep brain stimulus train if the calculated modulation index is outside of the predefined threshold range.

5. The method according to claim 1, wherein administering the first or second deep brain stimulus train to the subject comprises stimulating one or more structures in the subject'"'"'s thalamus, basal ganglia, or both.

6. The method according to claim 5, wherein administering the first or second deep brain stimulus train to the subject comprises stimulating the subject'"'"'s subthalamic nucleus (STN) or globus pallidus.

7. The method according to claim 5, wherein the stimulation is administered using a stimulation electrode array.

8. The method according to claim 1, further comprising placing a stimulation electrode array in the subject'"'"'s brain to administer deep brain stimulation.

9. The method according to claim 8, further comprising placing the stimulation electrode array in one or more structures in the subject'"'"'s thalamus, basal ganglia, or both.

10. The method according to claim 9, further comprising placing the stimulation electrode array in the subject'"'"'s subthalamic nucleus (STN) or globus pallidus.

11. The method according to claim 1, wherein the predefined threshold range is tailored for the subject.

12. The method according to claim 1, further comprising placing the at least one electrode on the surface of the subject'"'"'s brain, wherein the at least one electrode is placed at a position corresponding to an arm area of primary motor cortex M1.

13. The method according to claim 12, wherein the electrode is a non-brain-penetrating electrode.

14. The method according to claim 1, further comprising digitizing the LFPs at a sampling rate of about 400 to 2000 samples per second prior to calculating the modulation index.

15. The method according to claim 1, further comprising digitizing the LFPs at a sampling rate of about 400 to 800 samples per second prior to calculating the modulation index.

16. The method according to claim 1, further comprising filtering out the LFPs that are not in a frequency range of about 15 Hz to about 30 Hz, thereby generating a set of LFPs that comprise a frequency range of about 15 Hz to about 30 Hz prior to calculating the modulation index.

17. The method according to claim 1, further comprising filtering out the LFPs that are not in an amplitude range of about 50 Hz to about 200 Hz, thereby generating a set of LFPs that comprise an amplitude range of about 50 Hz to about 200 Hz prior to calculating the modulation index.

18. The method according to claim 1, wherein calculating the modulation index comprises calculating a Kullback-Liebler-based modulation index.

19. The method according to claim 1, wherein calculating the modulation index comprises calculating a mean vector length modulation index.

20. The method according to claim 1, wherein calculating the modulation index comprises applying a phase-amplitude coupling palette method.

21. The method according to claim 1, wherein calculating the modulation index comprises applying a linear regression.

22. The method according to claim 1, further comprising administering an effective amount of a pharmacological agent to the subject.

23. The method according to claim 22, wherein the pharmacological agent is selected from the group consisting of levodopa, carbidopa, catechol O-methyltransferase inhibitors, monoamine oxidase inhibitors, dopamine agonists, anticholinergics, catecholamines, baclofen, benzodiazepines, tetrabenezine, diazepam, clonazepam, and lorazepam.

24. The method according to claim 22, wherein the administering comprises infusion.

25. The method according to claims 22, wherein the pharmacological agent is administered to the subject if the calculated modulation index is outside of the predefined threshold range, and wherein administration of the pharmacological agent is controlled by the processor.

26. The method according to claim 25, wherein the processor changes at least one parameter of the administration of the pharmacological agent if the calculated modulation index is outside of the predefined threshold range.

27. The method according to claim 1, wherein the neurological movement disorder comprises Parkinson'"'"'s disease.

28. The method according to claim 27, wherein the subject has been diagnosed with Parkinson'"'"'s disease.

29. The method according to claim 1, wherein the neurological movement disorder comprises dystonia.

30. The method according to claim 29, wherein the subject has been diagnosed with dystonia.

31. The method according to claim 1, wherein the subject is human.

32. The method according to claim 1, wherein the measuring cortical LFPs is by electrocorticography (ECoG).

33. The method according to claim 1, wherein the measuring cortical LFPs is by electroencephalography (EEG).

34. The method according to claim 1, wherein the cortical LFPs are measured during movement preparation.

35. The method according to claim 1, wherein the cortical LFPs are measured during movement execution.

36. The method according to claim 1, wherein the cortical LFPs are measured during rest.