# Examining the mechanisms of anxiety regulation using a novel, sham-controlled, fMRI-guided rTMS protocol and a translational laboratory model of anxiety.

> **NIH NIH K01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $180,846

## Abstract

Although extensive research has explored the involvement of subcortical structures in arousal, arousal
symptoms are only one facet of the symptom profile shared across anxiety disorders. Much less is known
about the cognitive symptoms (i.e. difficulty concentrating) experienced by anxiety patients. Accordingly, there
is a critical need for mechanistic research into the CNS mechanisms that mediate the cognitive symptoms
experienced by anxiety patients. Without such research, treatment development for these disorders will
continue to make slow progress. The objective of this application is to determine the key neural mechanisms
that mediate the cognitive symptoms of anxiety. My central hypothesis is that the right dorsolateral prefrontal
cortex (dlPFC) regulates emotion through top-down inhibition of emotion-related regions. My approach will be
to use repetitive transcranial magnetic stimulation (rTMS) to study the effect of right dlPFC activity on objective
and subjective measures of induced anxiety, anxiety-related working memory deficits (WM), and TMS-evoked
blood oxygenation-level dependent (BOLD) responses during simultaneous TMS/fMRI (i.e. target
engagement). My rationale for this approach is that by experimentally manipulating right dlPFC activity using
rTMS, I will be able to causally demonstrate involvement of this region in anxiety regulation, which could
translate to future targeted rTMS treatments for anxiety. My first aim will be to determine the effect of a 1-week
course of rTMS treatment (1 Hz vs. 10 Hz; right dlPFC target) on anxiety using the threat of unpredictable
shock paradigm. My second aim will be to determine the effect of a 1-week course of rTMS treatment (1 Hz vs.
10 Hz; right dlPFC target) on anxiety-related WM-deficits using the Sternberg WM paradigm during threat of
shock. My third aim will be to demonstrate target engagement by measuring BOLD responses evoked by TMS
pulses to the right dlPFC during threat of shock. The work is innovative because it will combine advanced
neuromodulatory techniques (fMRI guidance, electric-field modelling, neuronavigation, active-sham control)
with a translational threat of shock paradigm.

## Key facts

- **NIH application ID:** 10207409
- **Project number:** 5K01MH121777-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** nicholas LEE balderston
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $180,846
- **Award type:** 5
- **Project period:** 2019-09-17 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10207409

## Citation

> US National Institutes of Health, RePORTER application 10207409, Examining the mechanisms of anxiety regulation using a novel, sham-controlled, fMRI-guided rTMS protocol and a translational laboratory model of anxiety. (5K01MH121777-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10207409. Licensed CC0.

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