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Multimodal Investigation of Excitatory/Inhibitory Imbalances and Network Dysfunction Related to Motor Control in OCD Youth: ÃÂ¹H fMRS and fMRI Applications

Award Number: R01MH059299
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/20/1999
PERIOD OF PERFORMANCE END DATE: 10/30/2026

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Multimodal Investigation of Excitatory/Inhibitory Imbalances and Network Dysfunction Related to Motor Control in OCD Youth: ÃÂ¹H fMRS and fMRI Applications - PROJECT SUMMARY/ABSTRACT This is a competitive renewal of grant award R01MH59299, enhanced by significant new in vivo multi-modal functional imaging directions (1H fMRS and fMRI). These innovations facilitate a never-before attempted understanding of specific aspects of dysfunctional neurobiology in youth with Obsessive Compulsive Disorder (OCD). OCD is a severe, prevalent, and chronically disabling disorder emerging during childhood/adolescence (80% of cases) with well-delineated clinical phenomenology/nosology. However, the relationship between the clinical phenomenology and modes of brain dysfunction is only generally understood. For example, our prior work using 1H MRS and fMRI has implicated general neurochemistry and function of the dorsal anterior cingulate cortex (dACC). However, dACC engages in contextually dependent excitatory or inhibitory modes of behavior/control that are likely to induce changes in the steady-state excitatory and inhibitory (E/I) synaptic drive of the dACC. However, which of these response modes (and the shift in the E/I balance they induce) is particularly relevant to OCD, and its sensitivity to OCD dimensions (Obsessions or Compulsions) and comorbid anxiety symptoms are completely unknown. Here, we aim to parse apart dysfunction in excitatory and/or inhibitory tone of the dACC in relation to OCD. In doing so, we provide a transformative extension of evidence supported under prior grant iterations demonstrating dysfunctional activation and connectivity of the dACC in OCD youth. Now, we use specifically designed motor paradigms with distinct excitatory or inhibitory response modes which induce complementary demands on dACC function. The tasks are administered during multi- modal functional imaging acquisition that includes ¹H fMRS and fMRI. 1H fMRS, which permits understanding of the functional biochemistry of the dACC, is uncoupled from hemodynamics and is ideally suited to investigate functional imbalances in the E/I synaptic drive of the dACC. In the same participants and using the same tasks, fMRI will be acquired in the service of understanding changes in task-induced whole brain network dynamics and connectomics. This unique project combines the clinical and multi-modal functional neuroimaging expertise at Wayne State University to achieve a transformative explication of the dysfunctional neurobiology of OCD. The combination of ¹H fMRS and fMRI will be acquired in 100 OCD youth and 100 matched healthy controls (12 - 19 years), allowing us to measure: a) brain function via glutamate modulation (¹H fMRS) and the BOLD signal (fMRI); b) brain plasticity related to shifts in the E/I synaptic drive (1H fMRS); and c) network dynamics and connectomics (fMRI). In addition to providing compelling and clinically relevant in vivo characterization of disordered excitatory vs. inhibitory signaling in the pathophysiology of OCD, the proposal provides a scientific blueprint for how multi-modal imaging can explicate in vivo brain function. The accumulated knowledge will promote better diagnostic and treatment approaches through a more detailed characterization of OCD pathophysiology.


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 = $0 )
2026	2025	WAYNE STATE UNIVERSITY	5700 CASS AVE STE 4900	DETROIT	MI	48202	WAYNE	USA	Mental Health Research Grants	000	24	12/9/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $600,800 )
2025	2025	WAYNE STATE UNIVERSITY	5700 CASS AVE STE 4900	DETROIT	MI	48202	WAYNE	USA	Mental Health Research Grants	000	24	12/6/2024	NON-COMPETING CONTINUATION	$600,800
														Subtotal = $600,800

Issue Date FY: 2024 ( Subtotal = $706,825 )
2024	2024	WAYNE STATE UNIVERSITY	5700 CASS AVE STE 4900	DETROIT	MI	48202	WAYNE	USA	Mental Health Research Grants	000	23	10/26/2023	NON-COMPETING CONTINUATION	$636,143
2024	2024	WAYNE STATE UNIVERSITY	5700 CASS AVE STE 4900	DETROIT	MI	48202	WAYNE	USA	Mental Health Research Grants	001	23	6/27/2024	NON-COMPETING CONTINUATION	$70,682
														Subtotal = $706,825

Issue Date FY: 2023 ( Subtotal = $636,143 )
2023	2023	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Mental Health Research Grants	001	22	2/2/2023	NON-COMPETING CONTINUATION	$63,614
2023	2023	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Mental Health Research Grants	000	22	11/2/2022	NON-COMPETING CONTINUATION	$572,529
														Subtotal = $636,143

Issue Date FY: 2022 ( Subtotal = $671,483 )
2022	2022	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Mental Health Research Grants	003	21	5/11/2022	NON-COMPETING CONTINUATION	$67,149
2022	2022	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Mental Health Research Grants	001	21	2/18/2022	NON-COMPETING CONTINUATION	$604,334
2022	2021	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Mental Health Research Grants	002	20	2/21/2022	COMPETING CONTINUATION	$0
2022	2019	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Mental Health Research Grants	000	19	1/10/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $671,483

Issue Date FY: 2021 ( Subtotal = $746,088 )
2021	2021	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Mental Health Research Grants	001	20	1/12/2021	COMPETING CONTINUATION	$671,479
2021	2021	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Mental Health Research Grants	002	20	5/7/2021	COMPETING CONTINUATION	$74,609
2021	2019	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Mental Health Research Grants	000	19	1/12/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $746,088

Issue Date FY: 2019 ( Subtotal = $236,576 )
2019	2019	WAYNE STATE UNIVERSITY	5057 WOODWARD 13 FLOOR	DETROIT	MI	48202	WAYNE	USA	Mental Health Research Grants	000	19	4/19/2019	NON-COMPETING CONTINUATION	$236,576
														Subtotal = $236,576

Issue Date FY: 2018 ( Subtotal = $413,852 )
2018	2018	WAYNE STATE UNIVERSITY	5057 WOODWARD 13 FLOOR	DETROIT	MI	48202	WAYNE	USA	Mental Health Research Grants	000	18	5/1/2018	NON-COMPETING CONTINUATION	$413,852
														Subtotal = $413,852

Issue Date FY: 2017 ( Subtotal = $418,010 )
2017	2017	WAYNE STATE UNIVERSITY	5057 WOODWARD 13 FLOOR	DETROIT	MI	48202	WAYNE	USA	Mental Health Research Grants	001	17	8/11/2017	NON-COMPETING CONTINUATION	$41,801
2017	2017	WAYNE STATE UNIVERSITY	5057 WOODWARD 13 FLOOR	DETROIT	MI	48202	WAYNE	USA	Mental Health Research Grants	000	17	4/18/2017	NON-COMPETING CONTINUATION	$376,209
														Subtotal = $418,010

Issue Date FY: 2016 ( Subtotal = $416,879 )
2016	2016	WAYNE STATE UNIVERSITY	5700 CASS SUITE 4602	DETROIT	MI	48202	WAYNE	USA	Mental Health Research Grants	000	16	4/21/2016	NON-COMPETING CONTINUATION	$416,879
														Subtotal = $416,879

Issue Date FY: 2015 ( Subtotal = $475,873 )
2015	2015	WAYNE STATE UNIVERSITY	5700 CASS SUITE 4602	DETROIT	MI	48202	WAYNE	USA	Mental Health Research Grants	000	15	6/25/2015	COMPETING CONTINUATION	$475,873
														Subtotal = $475,873

Issue Date FY: 2013 ( Subtotal = $501,934 )
2013	2013	WAYNE STATE UNIVERSITY	5700 CASS SUITE 4602	DETROIT	MI	48202	WAYNE	USA	Mental Health Research Grants	001	14	7/12/2013	NON-COMPETING CONTINUATION	$31,372
2013	2013	WAYNE STATE UNIVERSITY	5700 CASS SUITE 4602	DETROIT	MI	48202	WAYNE	USA	Mental Health Research Grants	000	14	4/3/2013	NON-COMPETING CONTINUATION	$470,562
														Subtotal = $501,934

Issue Date FY: 2012 ( Subtotal = $522,847 )
2012	2012	WAYNE STATE UNIVERSITY	5700 CASS SUITE 4602	DETROIT	MI	48202	WAYNE	USA	Mental Health Research Grants	000	13	3/15/2012	NON-COMPETING CONTINUATION	$522,847
														Subtotal = $522,847

Issue Date FY: 2011 ( Subtotal = $516,852 )
2011	2011	WAYNE STATE UNIVERSITY	5700 CASS SUITE 4602	DETROIT	MI	48202	WAYNE	USA	Mental Health Research Grants	000	12	6/3/2011	NON-COMPETING CONTINUATION	$516,852
														Subtotal = $516,852

Issue Date FY: 2010 ( Subtotal = $460,983 )
2010	2010	WAYNE STATE UNIVERSITY	5700 CASS SUITE 4602	DETROIT	MI	48202	WAYNE	USA	Mental Health Research Grants	000	11	5/24/2010	NON-COMPETING CONTINUATION	$460,983
														Subtotal = $460,983

Issue Date FY: 2009 ( Subtotal = $542,246 )
2009	2009	WAYNE STATE UNIVERSITY	5700 CASS SUITE 4602	DETROIT	MI	48202	WAYNE	USA	Mental Health Research Grants	000	10	9/9/2009	COMPETING CONTINUATION	$542,246
														Subtotal = $542,246

Issue Date FY: 2007 ( Subtotal = $489,479 )
2007	2007	WAYNE STATE UNIVERSITY	5700 CASS SUITE 4602	DETROIT	MI	48202	WAYNE	USA	Mental Health Research Grants	000	9	5/15/2007	NON-COMPETING CONTINUATION	$489,479
														Subtotal = $489,479

Issue Date FY: 2006 ( Subtotal = $489,417 )
2006	2006	WAYNE STATE UNIVERSITY	5700 CASS SUITE 4602	DETROIT	MI	48202	WAYNE	USA	Mental Health Research Grants	000	8	5/16/2006	NON-COMPETING CONTINUATION	$489,417
														Subtotal = $489,417

Issue Date FY: 2005 ( Subtotal = $486,598 )
2005	2005	WAYNE STATE UNIVERSITY	5700 CASS SUITE 4602	DETROIT	MI	48202	WAYNE	USA	Mental Health Research Grants	000	7	6/3/2005	NON-COMPETING CONTINUATION	$486,598
														Subtotal = $486,598

Issue Date FY: 2004 ( Subtotal = $472,425 )
2004	2004	WAYNE STATE UNIVERSITY	5700 CASS SUITE 4602	DETROIT	MI	48202	WAYNE	USA	Mental Health Research Grants	000	6	7/30/2004	NON-COMPETING CONTINUATION	$472,425
														Subtotal = $472,425

Issue Date FY: 2003 ( Subtotal = $461,384 ) (Continued on the next page)
Grand Total All Awards = $11,401,609

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Multimodal Investigation of Excitatory/Inhibitory Imbalances and Network Dysfunction Related to Motor Control in OCD Youth: ÃÂ¹H fMRS and fMRI Applications

Award Number: R01MH059299

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/20/1999

PERIOD OF PERFORMANCE END DATE: 10/30/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer

Award Information

Multimodal Investigation of Excitatory/Inhibitory Imbalances and Network Dysfunction Related to Motor Control in OCD Youth: ÃÂ¹H fMRS and fMRI Applications

Award Number: R01MH059299

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/20/1999

PERIOD OF PERFORMANCE END DATE: 10/30/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer

Multimodal Investigation of Excitatory/Inhibitory Imbalances and Network Dysfunction Related to Motor Control in OCD Youth: ÃÂ¹H fMRS and fMRI Applications