# CRCNS: Optimization of closed-loop control of gamma oscillations

> **NIH NIH R01** · UNIVERSITY OF MISSOURI-COLUMBIA · 2021 · $284,005

## Abstract

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.

## Key facts

- **NIH application ID:** 10207403
- **Project number:** 5R01MH122023-03
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** Satish S Nair
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $284,005
- **Award type:** 5
- **Project period:** 2019-08-26 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10207403

## Citation

> US National Institutes of Health, RePORTER application 10207403, CRCNS: Optimization of closed-loop control of gamma oscillations (5R01MH122023-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10207403. Licensed CC0.

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