# The Role for in vivo Glutamate Modulation in Maintaining Cognitive Control in Trauma-Exposed Adolescents

> **NIH NIH F31** · WAYNE STATE UNIVERSITY · 2024 · $47,884

## Abstract

Abstract
 Childhood trauma is highly prevalent in the United States, and can greatly increase the risk for developing
anxiety disorders in youth. Experiences of trauma promote heightened emotional responses to potential threats,
which in turn may impact cognitive ability. The imbalance between emotional and cognitive processes may
contribute to hallmark symptoms of anxiety disorders, such as excessive fear and impaired functioning. It is
critical to investigate the biochemical mechanisms underlying cognitive neural engagement to identify novel
therapeutic targets and develop better targeted pharmacotherapies aimed at maintaining cognitive control ability
in vulnerable populations like trauma-exposed youth.
 Functional MRI studies demonstrate that the dorsal anterior cingulate cortex (dACC) is a critical
component of maintaining cognitive control, and that visual cues of negative affect may interfere with these
functions. However, the key barrier to advancing this mechanistic understanding is that the vast majority of
current investigations utilize functional MRI, which relies on the hemodynamic response function, and is an
imprecise indicator of neural engagement. A more precise measure of neural engagement can be obtained using
in vivo ¹H functional MR spectroscopy (¹H fMRS), which is a novel tool sensitive to temporal changes in glutamate
under contrasting task-conditions.
 The objective in this proposal is to investigate the impact of childhood trauma on dACC neural
engagement related to cognitive control with and without negative affect, and its association with pediatric anxiety
symptoms. We will enroll 60 adolescents (ages 11-15, 50% female) from an urban setting with high rates of
trauma exposure (30 trauma-exposed, 30 control). Participants undergo ¹H fMRS scanning while completing a
cognitive control task specifically designed to allow direct characterization of the dACC neural engagement
during cognitive control following negative affect interference. The task includes two modes that target different
components of cognition: sustained attention and response inhibition. Both modes will be tested in the context
of threatening faces (negative affect condition), as well as neutral shapes (no affect condition). This proposal
hypothesizes that childhood trauma will potentiate negative affect interference with dACC neural engagement
necessary for cognitive control functioning – demonstrated by reduced dACC glutamate modulation during the
negative affect conditions of the task.
 This innovative approach will facilitate investigation into the neural processes which maintain cognitive
control in the presence of threat in trauma-exposed adolescents. This training project will provide PI France with
training in conceptual (neurobiology of trauma and anxiety) and methodological approaches (¹H fMRS and
psychological assessments). It will also prepare the PI for a successful F32 submission and future academic
research career.

## Key facts

- **NIH application ID:** 10871700
- **Project number:** 5F31MH132307-02
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** John McClellan France
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $47,884
- **Award type:** 5
- **Project period:** 2023-08-17 → 2025-08-16

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10871700

## Citation

> US National Institutes of Health, RePORTER application 10871700, The Role for in vivo Glutamate Modulation in Maintaining Cognitive Control in Trauma-Exposed Adolescents (5F31MH132307-02). Retrieved via AI Analytics 2026-06-24 from https://api.ai-analytics.org/grant/nih/10871700. Licensed CC0.

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