# Subcortical influence on the respiratory coordination of cortical neurodynamicsrelated to cognition

> **NIH NIH R21** · HARVARD MEDICAL SCHOOL · 2021 · $166,731

## Abstract

Slow cortical oscillations, such as theta band activity (5-9Hz), may be critical for coherence of activity over
large distances, providing a mechanism for interregional communication involved in neural processing. Faster
gamma band oscillations (GBO; 30-200 Hz) are thought to play a major role in higher-level cognitive
processing including attention. While the role of Theta/GBO coupling in select aspects of cognitive processing
has been a topic of intense interest, recent findings suggest that nasal respiration can also temporally
coordinate dynamic neural activity in the brain. These respiratory-entrained oscillations also exhibit high phase-
amplitude coupling to GBO (RG coupling) during select behaviors. Presently it is unknown if RG coupling has
a role in cognition. Our overarching hypothesis posits that the strength of RG coupling in the attention-
related frontoparietal network (prelimbic and posterior parietal cortices) will correlate with vigilant attention-
dependent performance.
 Aim 1: RG coupling in the frontoparietal attentional network correlates with performance in an
attention-demanding operant task. We will measure respiration and respiratory-entrained oscillations in local
field potentials in select brain regions to evaluate RG coupling during an operant signal detection task used to
measure vigilant attention, the rodent psychomotor vigilance task (rPVT). In the rPVT, mice maintain attention
to a stimulus location, and respond to detection of a brief and unpredictable cue with a short-latency operant
response to receive food reward. Prior to correct trials, we predict that RG coupling will be strong in the
frontoparietal attention network, and that fast reaction times will correlate with robust RG coupling. In contrast,
prior to omission trials (attention failures), we predict that RG coupling will be diminished.
 Aim 2: Attenuation/promotion of RG coupling by means of optogenetic manipulation of basal
forebrain parvalbumin neurons will impair/improve performance in the rPVT. Our preliminary findings
show that closed-loop gamma frequency stimulation of basal forebrain parvalbumin neurons in relation to
respiratory inhalation, but not exhalation, promotes RG coupling. Therefore, we will utilize this stimulation
paradigm to determine how modulation of RG coupling impacts performance in the rPVT.
 Across a range of select neuropsychiatric illnesses, the pathological processes behind cognitive deficits
involve abnormal neural temporal dynamics. Thus, these basic research studies will help to inform the
development of translational therapies to restore/enhance cognitive function.

## Key facts

- **NIH application ID:** 10302446
- **Project number:** 1R21MH125242-01A1
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** JAMES M MCNALLY
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $166,731
- **Award type:** 1
- **Project period:** 2021-09-10 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10302446

## Citation

> US National Institutes of Health, RePORTER application 10302446, Subcortical influence on the respiratory coordination of cortical neurodynamicsrelated to cognition (1R21MH125242-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10302446. Licensed CC0.

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