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Prefrontal Anatomic Pathways in Executive Control

Award Number: R01MH117785
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/1987
PERIOD OF PERFORMANCE END DATE: 01/31/2025

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Prefrontal Anatomic Pathways in Executive Control - Goal-directed behavior requires selection of signals from the external and internal emotional environments based on memory and prior experience for action. Processes that rely on emotions and memory engage the network of medial frontal area 25 and medial temporal lobe (MTL) cortices, which are affected in psychiatric diseases. The goal of the proposed studies is to investigate specific circuits of the medial frontal (subgenual area 25) and MTL regions in rhesus monkeys. Pathways will be studied in the context of the excitatory and inhibitory neuronal composition in both monkeys and humans, which critically affects function and disruption in brain diseases. Our overarching hypothesis is that the Structural Model, which predicts the patterns and strength of cortical connections studied in non-human primates, apply for study of the human brain and can be applied to understand the circuit basis of the involvement of subgenual area 25 and MTL in depression. The goal of the proposed studies is to use high resolution connections in monkeys to investigate the circuit mechanisms between medial prefrontal A25 and MTL areas through study of: (1) The synaptic targets of frontal area 25 to MTL area 28 in monkeys, and the excitatory-inhibitory neuronal composition of the respective areas in both monkeys and humans; (2) Laminar connections within MTL in monkeys and their relationship to the local architecture; (3) The normal excitatory and inhibitory neuronal and glial make-up of frontal area 25 in monkeys and humans, based on evidence that hyperactivity in area 25 perturbs function in depression; and (4) The density of axons below area 25 in human control brains, which give rise to bidirectional pathways that link it with nearby prefrontal and distant cortices. Hypotheses about pathway relationships are based on the theoretical and data based Structural Model, in the context of principles of excitatory and inhibitory control in primates. Pathways in rhesus monkeys will be labeled with distinct neural tracers, combined with multiple labeling for inhibitory neurons and receptors. Quantitative data will be obtained using correlated light, confocal and electron microscopy and analyzed using advanced statistical methods and synthesized through modeling. Findings will establish the still unknown circuit interactions of medial prefrontal areas and MTL, and their likely involvement in depression, which perturbs the excitation-inhibition balance and the processes of interoception, emotion and memory.


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 = $627,604 )
2024	2024	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	001	35	8/14/2024	NON-COMPETING CONTINUATION	$62,761
2024	2024	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	000	35	1/19/2024	NON-COMPETING CONTINUATION	$564,843
														Subtotal = $627,604

Issue Date FY: 2023 ( Subtotal = $641,523 )
2023	2023	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	000	34	2/21/2023	NON-COMPETING CONTINUATION	$641,523
														Subtotal = $641,523

Issue Date FY: 2022 ( Subtotal = $739,427 )
2022	2022	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	001	33	2/22/2022	NON-COMPETING CONTINUATION	$589,534
2022	2022	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	002	33	5/16/2022	NON-COMPETING CONTINUATION	$65,504
2022	2021	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	000	32	1/5/2022	NON-COMPETING CONTINUATION	$84,389
														Subtotal = $739,427

Issue Date FY: 2021 ( Subtotal = $583,774 )
2021	2021	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	002	32	4/26/2021	NON-COMPETING CONTINUATION	$583,774
2021	2020	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	001	31	2/2/2021	COMPETING CONTINUATION	$235,690
2021	2019	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	30	1/27/2021	NON-COMPETING CONTINUATION	-$235,690
														Subtotal = $583,774

Issue Date FY: 2020 ( Subtotal = $755,692 )
2020	2020	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	001	31	3/27/2020	COMPETING CONTINUATION	$755,692
2020	2019	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	30	3/12/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $755,692

Issue Date FY: 2019 ( Subtotal = $605,202 )
2019	2019	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	30	2/11/2019	NON-COMPETING CONTINUATION	$605,202
														Subtotal = $605,202

Issue Date FY: 2018 ( Subtotal = $598,493 )
2018	2018	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	29	3/1/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$538,643
2018	2018	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	29	6/15/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$59,850
														Subtotal = $598,493

Grand Total All Awards = $4,551,715

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Prefrontal Anatomic Pathways in Executive Control

Award Number: R01MH117785

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/1987

PERIOD OF PERFORMANCE END DATE: 01/31/2025

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