IP Library Granted Patent US 10,071,248
Granted Patent B2
US 10,071,248 · App. 15/344,723 · Granted Sep 11, 2018

Systems and methods for tuning closed-loop phasic burst stimulation based on a phase response curve

Inventors: Theoden Netoff (Minneapolis, MN); Dan Wilson (Santa Barbara, CA); Jeff Moehlis (Santa Barbara, CA); Abbey Holt Becker (Minneapolis, MN)
Assignees: Regents of the University of Minnesota; The Regents of the University of California
A61N1/36139A61N1/0534A61N1/36067A61N1/36178
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Quick Facts
Patent No.
US 10,071,248
App. No.
15/344,723
Granted
Sep 11, 2018
Kind
B2
Abstract

Systems and methods are provided for determining optimized settings for a closed-loop stimulation system based on analyzing a phase response curve measured from electrophysiological activity, such as electrical nerve activity or electrical muscle activity. The slope of the phase response curve is computed and used to determine a phase window during which phasic burst stimulation should be provided to achieve a desired effect on oscillations in the subject. When the slope of the phase response curve is positive, a phasic burst stimulation applied during the phase window will decrease synchrony of the oscillations. When the slope of the phase response curve is negative, a phasic burst stimulation applied during the phase window will increase synchrony of the oscillations.

Claims (44)

1. A method for controlling a closed-loop stimulation system having one or more electrodes configured to apply stimulating electrical signals and to receive electrophysiological signals, the method comprising:

a. measuring, with the one or more electrodes of the closed-loop stimulation system, electrophysiological signals from a subject;

b. estimating a phase response curve from the measured electrophysiological signals;

c. computing a slope of the phase response curve, wherein determining the electrical stimulation settings includes determining a phase window during which electrical stimulation is to be applied, wherein the phase window includes a range of phases during which the slope of the phase response curve has a positive slope;

d. determining electrical stimulation settings based on the computed slope of the phase response curve; and

e. controlling the closed-loop stimulation system to apply electrical stimulation based on the determined electrical stimulation settings.

2. The method of claim 1 , wherein the system is a closed-loop deep brain stimulation system, and the electrophysiological activity signals are neural activity signals.

3. The method of claim 2 , wherein controlling the stimulation system comprises applying an electrical stimulation to one or more neurons to suppress a pathological oscillation in the brain of the subject based on the slope of the phase response curve.

4. The method of claim 1 further including the step of applying a burst of electrical stimulation in the phase window.

5. The method of claim 1 , wherein controlling the closed-loop stimulation system includes applying an electrical pulse during each of a set of successive oscillations in the measured electrophysiological signals, wherein the electrical pulse is applied at a stimulus phase at which the phase response curve has its substantially steepest positive slope.

6. The method of claim 1 , wherein the phase response curve correlates phase of external stimulus delivery with phase of oscillation in the measured electrophysiological signals.

7. A method for controlling a closed-loop stimulation system having one or more electrodes configured to apply stimulating electrical signals and to receive electrophysiological signals, the method comprising:

a. measuring, with the one or more electrodes of the closed-loop stimulation system, electrophysiological signals from a subject;

b. estimating a phase response curve from the measured electrophysiological signals;

c. computing a slope of the phase response curve;

d. determining electrical stimulation settings based on the computed slope of the phase response curve;

e. controlling the closed-loop stimulation system based on the determined electrical stimulation settings; and

f. applying a burst of electrical stimulation when the slope of the phase response curve is positive to decrease synchrony of a pathological oscillation in the subject.

8. The method of claim 7 , wherein the system is a closed-loop deep brain stimulation system, and the electrophysiological activity signals are neural activity signals.

9. The method of claim 8 , wherein controlling the stimulation system comprises applying an electrical stimulation to one or more neurons to suppress a pathological oscillation in the brain of the subject based on the slope of the phase response curve.

10. The method of claim 7 , wherein controlling the closed-loop stimulation system includes applying an electrical pulse during each of a set of successive oscillations in the measured electrophysiological signals, wherein the electrical pulse is applied at a stimulus phase at which the phase response curve has its substantially steepest positive slope.

11. The method of claim 7 , wherein the phase response curve correlates phase of external stimulus delivery with phase of oscillation in the measured electrophysiological signals.

12. A closed-loop stimulation system having:

a. one or more electrodes configured to apply stimulating electrical signals in the brain of a subject, and to receive electrophysiological signals in the brain of the subject; and

b. a controller configured to:

i. measure electrophysiological signals received at the one or more electrodes;

ii. estimate a phase response curve from the measured electrophysiological signals;

iii. compute a slope of the phase response curve;

iv. determine electrical stimulation settings based on the computed slope of the phase response curve; and

v. apply electrical stimulation to one or more neurons to suppress a pathological oscillation in the brain of the subject based on the determined electrical stimulation settings using the one or more electrodes.

13. The system of claim 12 , wherein the controller is configured to, when determining electrical stimulation settings, determine a phase window during which to apply a phasic burst stimulation, wherein the phase window is a range of phases during which the slope of the phase response curve has a positive slope.

14. The system of claim 12 , wherein the controller is further configured to apply a phasic burst stimulation when the slope of the phase response curve is positive to decrease synchrony of oscillations in a subject.

15. The system of claim 12 , wherein the controller is further configured to:

a. determine a phase window during which electrical stimulation is to be applied when determining electrical stimulation settings, wherein the phase window is a range of phases during which the slope of the phase response curve has a positive slope; and

b. apply a burst of electrical stimulation in the phase window.

16. A method for deep brain stimulation using a closed-loop deep brain stimulation system having one or more electrodes configured to apply stimulating electrical signals and to receive neural signals, the method comprising:

a. measuring neural signals from the brain of a subject using the one or more electrodes;

b. estimating a phase response curve from the measured neural signals;

c. computing a slope of the phase response curve;

d. determining electrical stimulation settings based on the computed slope of the phase response curve, wherein determining the electrical stimulation settings comprises determining a range of phases during which the slope of the phase response curve is positive; and

e. applying electrical stimulation based on the determined electrical stimulation settings using the one or more electrodes to suppress a pathological oscillation in the brain of the subject.

17. The method of claim 16 wherein the method further comprises applying a burst of electrical stimulation over substantially all of the range of phases.

18. The method of claim 16 , further comprising decreasing synchrony of the pathological oscillation by applying a burst of electrical stimulation when the slope of the phase response curve is positive.

19. The method of claim 16 , wherein controlling the closed-loop stimulation system includes applying an electrical pulse during each of a set of successive oscillations, wherein the electrical pulse is applied at a stimulus phase at which the phase response curve has its substantially steepest positive slope.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 8, 2018
From: NETOFF, THEODEN
To: REGENTS OF THE UNIVERSITY OF MINNESOTA
Reel/Frame 046582/0723 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 8, 2018
From: MOEHLIS, JEFF; WILSON, DANIEL
To: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Reel/Frame 046582/0809 →
CONFIRMATORY LICENSE Recorded Dec 7, 2016
From: UNIVERSITY OF MINNESOTA
To: NATIONAL SCIENCE FOUNDATION
Reel/Frame 040837/0587 →
Continuity (2)
Provisional Application 62252192 · Nov 6, 2015
Related Publication 20170128729A1 · May 11, 2017