Granted Patent
B2
US 12,318,549 · App. 16/901,628 · Granted Jun 3, 2025
Methods and devices for providing a stimulus to a subject to induce gamma oscillations
Inventors:
Li-Huei Tsai (Cambridge, MA); Emery Brown (Brookline, MA); Hannah Iaccarino (Somerville, MA); Anthony James Martorell (Cambridge, MA); Chinnakkaruppan Adaikkan (Somerville, MA)
Assignee:
Massachusetts Institute of Technology
A61M21/00A61H23/00A61N5/062A61N5/0622A61M2021/0022A61M2021/0027A61M2021/0044A61N5/0618A61N2005/063A61N2005/0651A61N2005/0662
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Abstract
A method includes administering a non-invasive stimulus to a subject having a frequency of about 35 Hz to about 45 Hz to induce synchronized gamma oscillations in at least one brain region of the subject.
Claims (65)
1. A method comprising:
(a) stimulating a subject with a plurality of light pulses at a pulse frequency of about 35 pulses/s to about 45 pulses/s; and
(b) reducing tau phosphorylation in the visual cortex of the subject based, at least in part, on (a).
2. The method of claim 1 , further comprising inducing synchronized gamma oscillations in the visual cortex to reduce the tau phosphorylation.
3. The method of claim 1 , the reducing tau phosphorylation including reducing punctate localization of phosphorylated tau protein in the visual cortex of the subject.
4. The method of claim 1 , the reducing tau phosphorylation including reducing cell body localization of phosphorylated tau protein in the visual cortex of the subject.
5. The method of claim 1 , wherein the plurality of light pulses has the pulse frequency of about 40 pulses/s.
6. The method of claim 1 , wherein the subject is a human.
7. The method of claim 1 , wherein (a) comprises stimulating the subject with the plurality of light pulses at the pulse frequency of about 35 pulses/s to about 45 pulses/s for a duration of an exposure of the subject of at least one hour per day over a time period for repeating the exposure of at least seven days.
8. The method of claim 1 , the reducing tau phosphorylation including reducing tau phosphorylation associated with pTau(S202) and pTau(S400/T403/S404) in at least the visual cortex of the subject.
9. The method of claim 1 , further comprising:
(c) altering microglial cells in the visual cortex of the subject based at least in part on (a), wherein the altering includes at least one of:
(c1) increasing a number of the microglial cells;
(c2) inducing a morphological change in the microglial cells consistent with a neuroprotective state; or
(c3) increasing an activity of the microglial cells.
10. The method of claim 9 , comprising (c2), wherein (c2) comprises at least one of:
increasing a body diameter of the microglial cells; or
decreasing an average process length of the microglial cells.
11. The method of claim 9 , wherein (a) comprises stimulating the subject with the plurality of light pulses at the pulse frequency of about 35 pulses/s to about 45 pulses/s for a duration of an exposure of the subject of at least one hour per day over a time period for repeating the exposure of at least seven days.
12. A method, comprising:
(a) administering a non-invasive stimulus to a subject having a frequency of about 35 Hz to about 45 Hz; and
(b) reducing tau phosphorylation in at least one brain region of the subject based, at least in part, on (a).
13. The method of claim 12 , further comprising inducing synchronized gamma oscillations in the at least one brain region to reduce the tau phosphorylation.
14. The method of claim 12 , wherein the non-invasive stimulus has a frequency of about 40 Hz.
15. The method of claim 12 , wherein the subject is a human.
16. The method of claim 12 , wherein the non-invasive stimulus is a light stimulus.
17. The method of claim 12 , wherein the at least one brain region includes the visual cortex of the subject.
18. The method of claim 12 , wherein (a) comprises administering the non-invasive stimulus to the subject having the frequency of about 35 Hz to about 45 Hz for a duration of an exposure of the subject of at least one hour per day over a time period for repeating the exposure of at least seven days.
19. The method of claim 12 , the reducing tau phosphorylation including reducing tau phosphorylation associated with pTau(S202) and pTau(S400/T403/S404) in at least the visual cortex of the subject.
20. The method of claim 12 , further comprising:
(c) altering microglial cells in the at least one brain region of the subject based at least in part on (a), wherein the altering includes at least one of:
(c1) increasing a number of the microglial cells;
(c2) inducing a morphological change in the microglial cells consistent with a neuroprotective state; or
(c3) increasing an activity of the microglial cells.
21. The method of claim 20 , further comprising (c2), wherein (c2) comprises at least one of:
increasing a body diameter of the microglial cells; or
decreasing an average process length of the microglial cells.
22. The method of claim 20 , wherein (a) comprises administering the non-invasive stimulus to the subject having the frequency of about 35 Hz to about 45 Hz for a duration of an exposure of the subject of at least one hour per day over a time period for repeating the exposure of at least seven days.
23. A system comprising:
a signal generator to generate a signal having a fixed frequency in a range of approximately 35 Hz to approximately 45 Hz;
an emitter, coupled to the signal generator, to administer a stimulus non-invasively to a subject, based on the signal generated by the signal generator;
at least one processor communicatively coupled to at least one of the signal generator and the emitter to cause emission of the stimulus in response to execution of processor-executable instructions; and
memory, coupled to the at least one processor, storing:
the processor-executable instructions for the at least one processor;
stimulus parameters including a repetition frequency in the range from 35 Hz to 45 Hz; and
a stimulus-generation policy,
wherein the signal generator is configured to generate the signal in response to execution of the processor-executable instructions and based on the stimulus parameters and the stimulus-generation policy so that the stimulus reduces tau phosphorylation in at least one brain region of the subject in response to administering the stimulus to the subject.
24. The system of claim 23 , wherein the signal has the fixed frequency of about 40 Hz.
25. The system of claim 23 , wherein the emitter is a light emitter.
26. The system of claim 25 , wherein the light emitter is selected from the group consisting of a fiber-optic based emitter and a solid-state emitter.
27. The system of claim 26 , wherein the light emitter is a solid-state emitter and includes at least one light emitting diode (LED).
28. The system of claim 27 , further comprising eyewear, wherein the eyewear includes the at least one LED.
29. The system of claim 23 , wherein the emitter includes a display screen.
30. The system of claim 23 , wherein the emitter is a light emitter, further comprising a light occlusion device to reduce ambient light to at least one eye of the subject.
31. The system of claim 30 , further comprising eyewear, wherein the eyewear includes at least one of:
the light emitter; or
the light occlusion device.
32. The system of claim 23 , further comprising a scanner to monitor function in the at least one brain region of the subject before the administering, during the administering, or after the administering, or combinations thereof.
33. The system of claim 23 , wherein the at least one brain region is the visual cortex of the subject.
34. The system of claim 23 , wherein the signal generator is configured, based at least in part on the stimulus parameters and the stimulus-generation policy stored in the memory, to:
generate the signal for a duration of an exposure of the subject to the stimulus of at least one hour per day over a time period for repeating the exposure of at least seven days to reduce the tau phosphorylation in the at least one brain region of the subject.
35. The system of claim 23 , wherein the signal generator is configured, based at least in part on the stimulus parameters and the stimulus-generation policy stored in the memory, to generate the signal so that the stimulus reduces the tau phosphorylation and further causes a change in microglial cells in the at least one brain region of the subject, wherein the change in the microglial cells includes at least one of:
increasing a number of the microglial cells;
inducing a morphological change in the microglial cells consistent with a neuroprotective state; or
increasing an activity of the microglial cells.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 16, 2020
From: TSAI, LI-HUEI; BROWN, EMERY; IACCARINO, HANNAH; MARTORELL, ANTHONY JAMES; ADAIKKAN, CHINNAKKARUPPAN
To: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Reel/Frame 053224/0142 →
Continuity (4)
Provisional Application
62259187
· Nov 24, 2015
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