# The effect of right dlPFC cTBS on acute measures of anxiety, functional connectivity, and TMS-evoked BOLD responses

> **NIH MH R01** · UNIVERSITY OF PENNSYLVANIA · 2026 · $762,440

## Abstract

The right dorsolateral prefrontal cortex (dlPFC) is increasingly being targeted with transcranial magnetic
stimulation (TMS) to reduce anxiety expression in anxiety disorders, depression, and posttraumatic stress
disorder (PTSD). There seems to be clear mechanistic evidence that right dlPFC downregulation of amygdala
activity should reduce fear and anxiety. Despite this mechanistic evidence, the primary approaches to treat
anxiety with neuromodulation involve right dlPFC inhibition. Accordingly, there is a critical need to understand
the mechanisms of action underlying neuromodulatory right dlPFC TMS protocols, yet there is not a
standardized protocol to yield such evidence. Concurrent TMS/fMRI offers a unique translational perspective
for understanding psychopathology. By experimentally stimulating a region of the brain and then directly
measuring the activity evoked by this stimulation, it is possible to causally determine the downstream targets of
this region, facilitating the development of novel TMS treatments for disorders like PTSD and anxiety. The
objective of the current project is to develop a protocol using interleaved TMS/fMRI that can assess the effect
of neuromodulatory (potentially therapeutic) TMS protocols on neural and behavioral measures related to
anxiety expression. As a proof of concept, we will determine the effect of continuous theta burst stimulation
(cTBS) to the right dlPFC on TMS-evoked fMRI responses in anxious subjects. Our central hypothesis is that
cTBS of the right dlPFC will drive down activity throughout its downstream targets, resulting in reduced anxiety
and greater TMS-evoked deactivations in these downstream circuits. Accordingly, our approach will be to
measure anxious arousal and TMS-evoked BOLD responses before and immediately after 1800 pulses of
cTBS, or sham stimulation in 140 high anxious individuals using a within-subjects crossover design. Our
primary outcome will be TMS-evoked BOLD responses in a network of downstream

## Key facts

- **NIH application ID:** 11222995
- **Project number:** 1R01MH138375-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Lily A Brown; nicholas LEE balderston
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** MH
- **Fiscal year:** 2026
- **Award amount:** $762,440
- **Award type:** 1
- **Project period:** 2026-04-01T00:00:00 → 2031-01-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11222995

## Citation

> US National Institutes of Health, RePORTER application 11222995, The effect of right dlPFC cTBS on acute measures of anxiety, functional connectivity, and TMS-evoked BOLD responses (1R01MH138375-01A1). Retrieved via AI Analytics 2026-06-26 from https://api.ai-analytics.org/grant/nih/11222995. Licensed CC0.

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