# Multimodal Investigation of Excitatory/Inhibitory Imbalances and Network Dysfunction Related to Motor Control in OCD Youth: ¹H fMRS and fMRI Applications

> **NIH NIH R01** · WAYNE STATE UNIVERSITY · 2021 · $746,088

## Abstract

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 br...

## Key facts

- **NIH application ID:** 10130102
- **Project number:** 2R01MH059299-20A1
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** Vaibhav A. Diwadkar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $746,088
- **Award type:** 2
- **Project period:** 1999-08-20 → 2025-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10130102

## Citation

> US National Institutes of Health, RePORTER application 10130102, Multimodal Investigation of Excitatory/Inhibitory Imbalances and Network Dysfunction Related to Motor Control in OCD Youth: ¹H fMRS and fMRI Applications (2R01MH059299-20A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10130102. Licensed CC0.

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