# Leveraging Ultra-High Field MRI to Elucidate Glutamatergic Mechanisms of rTMS in Depression

> **NIH NIH F30** · UNIVERSITY OF PENNSYLVANIA · 2024 · $53,974

## Abstract

PROJECT SUMMARY
Major depressive disorder (MDD) is a leading cause of disability in the United States and worldwide, yet current
pharmacologic treatment options are insufficient for many patients. Repetitive transcranial magnetic stimulation
(rTMS) is a non-invasive, FDA-approved treatment that utilizes electromagnetic pulses to modulate brain activity,
but clinical efficacy is inconsistent, and the mechanism of action is still being determined. Understanding how
rTMS alters glutamate (Glu) signaling and functional connectivity (FC) in the Salience Network (SN), a functional
brain network that regulates attentional and emotional processing, could pave the way for improving or
personalizing this promising intervention. Previous studies using magnetic resonance spectroscopy or resting-
state functional magnetic resonance imaging (rsfMRI) at 3T have reported that rTMS increases Glu and FC in
the SN. However, methodological limitations contribute to extensive heterogeneity in this literature. This proposal
aims to overcome these limitations by applying robust, cutting-edge, ultra-high field (UHF; 7T) neuroimaging
techniques, including Glutamate Chemical Exchange Saturation Transfer (GluCEST) and rsfMRI, that confer
unprecedented spatial resolution and sensitivity. We aim to elucidate the manner in which rTMS alters Glu (Aim
1) and FC (Aim 2) in the SN, and how this associates with clinical improvement, as measured by our
comprehensive psychological assessment. The overarching hypothesis is that the antidepressant effect of rTMS
stems from increased glutamatergic activity and FC in key SN regions that regulate activity across functional
networks. Our high spatial resolution, multimodal imaging approach will provide unprecedented mechanistic
insights into the effects of rTMS and the role of Glu in the pathophysiology of MDD. To further investigate
individual differences in treatment response, we will employ an exploratory multivariate model incorporating Glu,
FC, and proximity of the stimulation site to the SN (Aim 2.3, exploratory). This project would both advance our
ability to predict outcomes for individuals receiving rTMS therapy and build the applicant’s skills in human
neuroimaging, neuromodulation, interventional psychiatry, and scientific communication in an environment with
clear expertise in these areas. A world-class mentoring team – Dr. David Roalf, Dr. Desmond Oathes, Dr.
Theodore Satterthwaite, and Dr. Kristin Linn – will provide complementary advising and resources in research
and clinical arenas as the candidate gains independence over the course of the project. With a detailed training
plan aligned with innovative scientific aims, this NRSA is the ideal opportunity for the candidate to develop key
skills to undertake not only strong experimental and computational work, but also care for patients with mood
disorders while effectively tailoring her research to the needs of this patient population as an interventional
psychiatrist-scient...

## Key facts

- **NIH application ID:** 10995521
- **Project number:** 1F30MH136690-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Margaret Kasey Pecsok
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $53,974
- **Award type:** 1
- **Project period:** 2024-07-16 → 2028-07-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10995521

## Citation

> US National Institutes of Health, RePORTER application 10995521, Leveraging Ultra-High Field MRI to Elucidate Glutamatergic Mechanisms of rTMS in Depression (1F30MH136690-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10995521. Licensed CC0.

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