# Prefrontal circuit mechanisms of repetitive transcranial magnetic stimulation

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $234,000

## Abstract

PROJECT SUMMARY
Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation method FDA-approved to
treat major depression and obsessive compulsive disorder, and also used off-label for treating numerous
neurological and psychiatric disorders. Clinical high frequency (HF) rTMS is typically targeted to the prefrontal
cortex (PFC) and is thought to enhance cortical excitability. However, effects on activity and clinical efficacy are
highly variable and the detailed mechanisms of action are not known. The primary obstacle limiting investigation
of cell-type and circuit-specific mechanisms is lack of established animal models with strong face validity. Our
lab has acquired the first rodent TMS coil capable of generating focal, suprathreshold stimulation of a cortical
subregion. We will use this coil to address the cell-type specific mechanisms by which HF-rTMS modifies
excitatory and inhibitory prefrontal subnetworks in vivo. By combining rTMS with cutting edge neuroscience tools,
we will test the hypothesis that HF-rTMS enhances prefrontal excitability by rapidly suppressing activity in
inhibitory neurons leading to subsequent enhancement of principal neuron activity. In Aim 1, we will use fiber
photometry to record calcium signals arising from excitatory (Emx1+) and inhibitory (PV+) prefrontal networks
before, during and after delivery of clinical HF-rTMS. In Aim 2, we will combine these cell-type specific recordings
of neural activity with optogenetic stimulation of long-range cortical inputs to determine how HF-rTMS modifies
synaptically-evoked activity in excitatory vs. inhibitory cortical networks. This proposal addresses a pressing
need to understand the cell-type and circuit specific mechanisms that mediate the effects of rTMS on cortical
function. Our research can inform the rational design of more effective rTMS treatments that precisely target
specific deficits underlying the pathophysiology of psychiatric disorders. These foundational studies will support
future projects aimed at determining how chronic rTMS can reverse pathological circuit changes in rodent stress
models.

## Key facts

- **NIH application ID:** 10649292
- **Project number:** 1R21MH133212-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Scott Allen Wilke
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $234,000
- **Award type:** 1
- **Project period:** 2023-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10649292

## Citation

> US National Institutes of Health, RePORTER application 10649292, Prefrontal circuit mechanisms of repetitive transcranial magnetic stimulation (1R21MH133212-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10649292. Licensed CC0.

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