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Neurocircuitry of OCD: Effects of Modulation

Award Number: P50MH106435
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2015
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Neurocircuitry of OCD: Effects of Modulation - ABSTRACT. The goal of Project 3 (P3) is to characterize, in OCD, white matter (WM) bundle and functional neural abnormalities among regions in a putative OCD neural network that are associated with persistent avoidance, a characteristic feature of OCD. Our overarching Center renewal hypothesis, building on our present findings, is that persistent avoidance in OCD is a manifestation of dysfunctional connections among specific hubs, i.e., subregions that integrate and distribute information from multiple regions, in the ventrolateral prefrontal cortex (vlPFC) and rostral anterior cingulate cortex (rACC), and other regions in the OCD network, including the insula, dorsal ACC (dACC), orbitofrontal cortex (OFC) and rostral striatum. These dysfunctional connections lead to impaired behavioral flexibility in response to changing contextual cues, specifically in situations with uncertain aversive outcomes. In P3, we will recruit and examine 50 unmedicated/ serotonin reuptake inhibitor/clomipramine medicated participants with OCD, and 50 healthy participants (18-35 yrs; to minimize effects of long illness history and medication on neural measures). We will use state-of-the-art diffusion imaging (dMRI), using tractography, segmentation and tract profiling - tractometry - to examine WM bundles in the network. We will use functional Magnetic Resonance Imaging (fMRI) to examine activity, functional and effective connectivity (FC, EC) among network regions during a novel probabilistic approach avoidance task (PAAT) that we developed to examine the influence of uncertain rewarding and aversive outcomes on choice behavior, and neural activity, FC and EC during evaluation and anticipation of these outcomes. We will examine relationships among WM, activity, FC and EC abnormalities in the OCD network in OCD participants and the severity of OCD symptom dimensions associated with persistent avoidance, e.g., harm avoidance. Biological sex will be a covariate in analyses. Aim (A)1 will compare the microstructure of WM bundles that connect vlPFC, rACC, insula, dACC, OFC and rostral striatum in OCD vs. healthy participants, using a novel combination of tractography, segmentation and tractometry. A2 will compare activity within and FC and EC among these OCD network regions in OCD vs. healthy participants during the PAAT, to determine relationships among PAAT performance and fMRI abnormalities in OCD vs. healthy participants. A3 will examine relationships among OCD symptom dimensions that are relevant to persistent avoidance: e.g., harm avoidance, contamination/ washing, responsibility for harm/checking symptoms, and: WM and fMRI abnormalities in A1-2. P3 will benefit from expertise in: NHP neuroanatomy and physiology in P1, 2 (A2); dMRI data analysis in P1, Core B (A1); clinical assessment and treatment of OCD in P4, 5 (A3); the study of individual differences in neuroanatomy in Core C (A2-3); and integration of analyses across projects in Core D. In close collaboration with other projects and cores, P3 will be the first study to elucidate the specific WM bundle, and functional, OCD network abnormalities that are associated with persistent avoidance, to inform interventions for disorders characterized by this behavior.


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: 2026 ( Subtotal = $3,036,516 )
2026	2026	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Mental Health Research Grants	000	10	1/26/2026	NON-COMPETING CONTINUATION	$3,036,516
														Subtotal = $3,036,516

Issue Date FY: 2025 ( Subtotal = $3,069,435 )
2025	2025	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Mental Health Research Grants	000	9	1/28/2025	NON-COMPETING CONTINUATION	$3,069,435
														Subtotal = $3,069,435

Issue Date FY: 2024 ( Subtotal = $3,082,457 )
2024	2024	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Mental Health Research Grants	000	8	1/19/2024	NON-COMPETING CONTINUATION	$2,774,210
2024	2024	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Mental Health Research Grants	001	8	5/8/2024	NON-COMPETING CONTINUATION	$308,247
														Subtotal = $3,082,457

Issue Date FY: 2023 ( Subtotal = $3,067,776 )
2023	2023	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Mental Health Research Grants	003	7	2/6/2023	NON-COMPETING CONTINUATION	$3,067,776
2023	2023	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Mental Health Research Grants	004	7	6/1/2023	NON-COMPETING CONTINUATION	$0
2023	2022	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Mental Health Research Grants	002	6	12/6/2022	COMPETING CONTINUATION	$532,374
2023	2019	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Mental Health Research Grants	001	5	12/6/2022	SUPPLEMENT FOR EXPANSION	-$379,071
2023	2019	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Mental Health Research Grants	000	5	12/6/2022	NON-COMPETING CONTINUATION	-$153,303
														Subtotal = $3,067,776

Issue Date FY: 2022 ( Subtotal = $3,180,058 )
2022	2022	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Mental Health Research Grants	001	6	3/17/2022	COMPETING CONTINUATION	$3,180,058
2022	2019	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Mental Health Research Grants	000	5	3/11/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $3,180,058

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Mental Health Research Grants	000	5	6/26/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2019	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Mental Health Research Grants	000	5	1/15/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $2,379,071 )
2019	2019	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Mental Health Research Grants	001	5	5/31/2019	SUPPLEMENT FOR EXPANSION	$379,071
2019	2019	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Mental Health Research Grants	000	5	5/24/2019	NON-COMPETING CONTINUATION	$2,000,000
2019	2019	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Mental Health Research Grants	002	5	6/4/2019	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $2,379,071

Issue Date FY: 2018 ( Subtotal = $2,000,000 )
2018	2018	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Mental Health Research Grants	000	4	6/12/2018	NON-COMPETING CONTINUATION	$2,000,000
														Subtotal = $2,000,000

Issue Date FY: 2017 ( Subtotal = $2,000,000 )
2017	2017	UNIVERSITY OF ROCHESTER	601 ELMWOOD AVE	ROCHESTER	NY	14642	MONROE	USA	Mental Health Research Grants	000	3	6/1/2017	NON-COMPETING CONTINUATION	$2,000,000
														Subtotal = $2,000,000

Issue Date FY: 2016 ( Subtotal = $2,000,000 )
2016	2016	UNIVERSITY OF ROCHESTER	1325 MOUNT HOPE AVE, SUITE 260	ROCHESTER	NY	14642	MONROE	USA	Mental Health Research Grants	000	2	6/1/2016	NON-COMPETING CONTINUATION	$2,000,000
														Subtotal = $2,000,000

Issue Date FY: 2015 ( Subtotal = $2,000,000 )
2015	2015	UNIVERSITY OF ROCHESTER	1325 MOUNT HOPE AVE, SUITE 260	ROCHESTER	NY	14642	MONROE	USA	Mental Health Research Grants	000	1	5/15/2015	NEW	$2,000,000
														Subtotal = $2,000,000

Grand Total All Awards = $25,815,313

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Neurocircuitry of OCD: Effects of Modulation

Award Number: P50MH106435

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/01/2015

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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