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Subcortical influence on the respiratory coordination of cortical neurodynamics related to cognition

Award Number: R21MH125242
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2022
PERIOD OF PERFORMANCE END DATE: 02/29/2024

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Subcortical influence on the respiratory coordination of cortical neurodynamics related to cognition - Slow cortical oscillations, such as theta (5-9Hz) band activity, may provide 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. The role of theta/GBO coupling (TG coupling) in cognitive processing is well established. However, more recent studies have observed that nasal respiration can also temporally coordinate dynamic neural activity in the brain, reflected as respiratory-entrained oscillations (REO), which 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 attention-related performance. Aim 1: RG coupling in the frontoparietal attentional network correlates with performance in an attention-demanding operant task. We will measure respiration and REO in local field potentials in select brain regions to evaluate RG coupling during an operant signal detection task used to measure sustained 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 BF parvalbumin neurons (BF-PV) will impair/improve attention-related performance in the rPVT. Our preliminary findings show that closed-loop gamma frequency stimulation (CLS) of BF-PV in relation to respiratory inhalation, but not exhalation, promotes RG coupling. Therefore, we will utilize this CLS paradigm to determine how modulation of RG coupling impacts attention-related performance. Across a range of select neuropsychiatric illnesses, the pathological processes behind cognitive deficits involve abnormal neural temporal dynamics. Thus, these studies will help to inform the development of translational therapies to restore/enhance cognitive function.


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: 2024 ( Subtotal = -$1,263 )
2024	2022	BOSTON VA RESEARCH INSTITUTE, INC.	2 AVENUE DE LAFAYETTE	BOSTON	MA	02111	SUFFOLK	USA	Mental Health Research Grants	000	2	7/11/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$1,263
														Subtotal = -$1,263

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	BOSTON VA RESEARCH INSTITUTE, INC.	150 S HUNTINGTON AVE	BOSTON	MA	02130	SUFFOLK	USA	Mental Health Research Grants	001	2	3/8/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$36,292
2023	2021	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Mental Health Research Grants	000	1	3/8/2023	NEW	-$36,292
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $196,168 )
2022	2022	BOSTON VA RESEARCH INSTITUTE, INC.	150 S HUNTINGTON AVE # 151B	BOSTON	MA	02130	SUFFOLK	USA	Mental Health Research Grants	001	2	8/29/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$196,168
2022	2021	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Mental Health Research Grants	000	1	8/27/2022	NEW	$0
														Subtotal = $196,168

Issue Date FY: 2021 ( Subtotal = $166,731 )
2021	2021	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Mental Health Research Grants	000	1	9/8/2021	NEW	$166,731
														Subtotal = $166,731

Grand Total All Awards = $361,636

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Subcortical influence on the respiratory coordination of cortical neurodynamics related to cognition

Award Number: R21MH125242

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2022

PERIOD OF PERFORMANCE END DATE: 02/29/2024

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