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Neurobiology and Cognitive Role of Slow Brain Network Fluctuations

Award Number: P50MH109429
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/15/2017
PERIOD OF PERFORMANCE END DATE: 03/31/2028

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Neurobiology and Cognitive Role of Slow Brain Network Fluctuations - CENTER ABSTRACT: Patterns of ongoing thought vary over time, and experiences like “mind-wandering” show that cognition is often decoupled from an ongoing task. A traditional assumption is that states of off-task cognition reflects a cognitive error. An emerging alternative view is that switching between “off-task” and on- task states is a fundamental feature of human cognition, facilitating long term goals and mental health. Experimental findings over the past several decades show that off-task cognition is accompanied by slow, correlated fluctuations in neural/autonomic signals and behavior, and that these are strongly linked to slow quasiperiodic shifts in large scale brain network activations. This Conte Center explores the cost/benefits of off- task cognition while testing the overarching hypothesis that related slow fluctuations of neural activity extending below 1 Hz, down to at least 0.01 Hz (timescales of seconds to 10’s of seconds) are critical determinants of affect, cognition and behavior. We pose a set of linking hypotheses (Overview, b.2.a.), two of which relate to features of slow neural fluctuations may represent organizing principles for brain operation. First, local slow neural fluctuations link to larger scale slow brain network fluctuations (SBNFs) that significantly impact cognitive processes like attention, behavioral indices like reaction times and autonomic measures like cardiac variability and pupil diameter. Second, there is causal hierarchical coupling of neural activity across frequencies extending from infraslow up to action potential frequency ranges; i.e., the phase of lower frequency controls the amplitude of activity in higher frequencies. This “phase-amplitude coupling” (PAC) provides a likely mechanism for network orchestration of excitability states in distributed ensembles of neurons, that by definition, integrates across time scales. On one hand, the SBNF may be a tool the brain can use to deploy and shift/re-deploy PAC and other resources according to momentary needs or task demands. On the other hand, when endogenously-triggered SBNFs may provide the brain with a means of avoiding entrapment of its resources by the demands of an immediate task or context. Despite our increasingly nuanced understanding of individual brain network states and their transitions, the precise cognitive/behavioral functions and the underlying physiological mechanisms of SBNFs remain largely open questions. We address these two broad questions with an integrative program of research combining: 1) fMRI/EEG and intracranial (i)EEG in humans, with fMRI/EEG and field potential/unit recordings in nonhuman primates (NHPs), and with autonomic measures in all cases, 2) local cell circuit and network biophysical modeling, 3) experimental conditions ranging from structured tasks to completely unscripted sessions and 4) approaches aimed at identifying causal elements in network dynamics. The Center’s discoveries will contribute to the integrated mechanistic understanding of the brain and to improved treatment of neuropsychiatric disorders.


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: 2025 ( Subtotal = $3,140,199 )
2025	2025	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	140 OLD ORANGEBURG RD BLDG 35	ORANGEBURG	NY	10962	ROCKLAND	USA	Mental Health Research Grants	000	8	6/10/2025	NON-COMPETING CONTINUATION	$3,140,199
														Subtotal = $3,140,199

Issue Date FY: 2024 ( Subtotal = $3,166,995 )
2024	2024	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	140 OLD ORANGEBURG RD BLDG 35	ORANGEBURG	NY	10962	ROCKLAND	USA	Mental Health Research Grants	000	7	7/1/2024	NON-COMPETING CONTINUATION	$3,166,995
2024	2023	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	140 OLD ORANGEBURG RD BLDG 35	ORANGEBURG	NY	10962	ROCKLAND	USA	Mental Health Research Grants	002	6	8/9/2024	COMPETING CONTINUATION	$233,647
2024	2021	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	001	5	8/9/2024	NON-COMPETING CONTINUATION	-$233,647
														Subtotal = $3,166,995

Issue Date FY: 2023 ( Subtotal = $3,427,178 )
2023	2023	RESEARCH FOUNDATION FOR MENTAL HYGIENE INC	140 OLD ORANGEBURG RD	ORANGEBURG	NY	10962	ROCKLAND	USA	Mental Health Research Grants	000	6	4/30/2023	COMPETING CONTINUATION	$3,427,178
														Subtotal = $3,427,178

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2021	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	5	3/7/2022	NON-COMPETING CONTINUATION	$0
2022	2021	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	002	5	6/17/2022	NON-COMPETING CONTINUATION	$0
2022	2021	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	001	5	5/13/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $1,773,524 )
2021	2021	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	002	5	9/9/2021	NON-COMPETING CONTINUATION	$0
2021	2021	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	001	5	6/25/2021	NON-COMPETING CONTINUATION	$1,773,524
2021	2020	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	4	11/24/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,773,524

Issue Date FY: 2020 ( Subtotal = $1,786,921 )
2020	2020	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	4	5/29/2020	NON-COMPETING CONTINUATION	$1,786,921
														Subtotal = $1,786,921

Issue Date FY: 2019 ( Subtotal = $1,892,182 )
2019	2019	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	3	6/1/2019	NON-COMPETING CONTINUATION	$1,892,182
2019	2019	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	001	3	9/24/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,892,182

Issue Date FY: 2018 ( Subtotal = $1,910,210 )
2018	2018	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	2	6/8/2018	NON-COMPETING CONTINUATION	$1,910,210
														Subtotal = $1,910,210

Issue Date FY: 2017 ( Subtotal = $1,912,097 )
2017	2017	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	1	4/13/2017	NEW	$1,912,097
														Subtotal = $1,912,097

Grand Total All Awards = $19,009,306

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Neurobiology and Cognitive Role of Slow Brain Network Fluctuations

Award Number: P50MH109429

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/15/2017

PERIOD OF PERFORMANCE END DATE: 03/31/2028

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