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CRCNS: Optimization of closed-loop control of gamma oscillations

Award Number: R01MH122023
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/26/2019
PERIOD OF PERFORMANCE END DATE: 05/31/2026

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CRCNS: Optimization of closed-loop control of gamma oscillations - Throughout the brain, specialized systems carry out different but complementary functions, sometimes independently but often in cooperation. However, we do not understand how their activity is dynamically coordinated, and dysregulation of this is associated with many mental health conditions. Neuronal oscillations, which are detectable in local field potentials (LFPs) at various frequencies, are a promising target for this coordination. Gamma oscillations (40-100 Hz) in particular have been singled out since they enhance stimulus responses, facilitate interactions between brain regions, and are expressed ubiquitously across cortical and subcortical regions. Indeed, gamma oscillations occur in the basolateral nucleus of the amygdala (BL), an important regulator of emotional behaviors. BL gamma oscillations are enhanced during periods of heightened vigilance during a foraging task, following emotionally salient experiences, and upon presentation of socially-relevant stimuli. The variety of circumstances that engage it make it a promising target for interventions affecting emotional behaviors in general. However, technical challenges abound because gamma manifests as brief intermittent oscillatory bursts, layered atop numerous ongoing activities in other frequency bands. This precludes manipulating gamma exclusively with traditional pharmacological, optogenetic, or chemogenetic approaches, since these have substantial effects on ongoing non-gamma activities, and are delivered irrespective of whether gamma bursts are present or absent. To overcome this, a closed-loop algorithm was developed that monitors the LFP in real-time for gamma oscillations and delivers precisely timed optogenetic stimulation capable of enhancing or suppressing gamma strength on a cycle-by-cycle basis. While this improves upon the status quo,, further refinement is needed. Aim 1 of this proposal seeks to clarify how the gamma modulation technique operates via biophysically detailed modeling of the local circuits in the BL that generate gamma, the effects of optogenetic stimulation, and the closed-loop algorithm. Aim 2 designs better signal processing routines for detecting and parameterizing gamma in real-time. Aim 3 develops an approach to create customized biophysical models that reproduce the properties of gamma observed in individual subjects, which when combined with the results of Aims 1 and 2 should allow for optimized control over gamma oscillations in individual subjects. RELEVANCE (See instructions): Gamma oscillations occur in the basolateral amygdala, a brain region implicated in emotional regulation. By developing improved methods to manipulate these oscillations, we hope to better understand their function and improve our ability to control emotional states and behaviors.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2027 ( Subtotal = $0 )
2027	2023	UNIVERSITY OF MISSOURI SYSTEM	121 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Mental Health Research Grants	000	5	10/14/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2023	UNIVERSITY OF MISSOURI SYSTEM	121 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Mental Health Research Grants	000	5	7/9/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $284,005 )
2023	2023	UNIVERSITY OF MISSOURI SYSTEM	121 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Mental Health Research Grants	000	5	6/2/2023	NON-COMPETING CONTINUATION	$284,005
														Subtotal = $284,005

Issue Date FY: 2022 ( Subtotal = $284,005 )
2022	2022	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Mental Health Research Grants	000	4	6/4/2022	NON-COMPETING CONTINUATION	$284,005
														Subtotal = $284,005

Issue Date FY: 2021 ( Subtotal = $284,005 )
2021	2021	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Mental Health Research Grants	000	3	6/4/2021	NON-COMPETING CONTINUATION	$284,005
														Subtotal = $284,005

Issue Date FY: 2020 ( Subtotal = $284,005 )
2020	2020	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Mental Health Research Grants	000	2	6/30/2020	NON-COMPETING CONTINUATION	$284,005
														Subtotal = $284,005

Issue Date FY: 2019 ( Subtotal = $297,755 )
2019	2019	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Mental Health Research Grants	000	1	8/26/2019	NEW	$297,755
														Subtotal = $297,755

Grand Total All Awards = $1,433,775

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CRCNS: Optimization of closed-loop control of gamma oscillations

Award Number: R01MH122023

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/26/2019

PERIOD OF PERFORMANCE END DATE: 05/31/2026

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