# A mechanistic trial of the neurobiology of extinction learning and intraparietal sulcus stimulation

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $811,653

## Abstract

Project Summary
Posttraumatic stress disorder (PTSD) is associated with alterations in arousal that do not respond well to
evidence-based practices. Patients with PTSD tend to fall into one of two groups in extinction training (and in
exposure therapy): 1) over-engagers, where arousal is too high; and 2) under-engagers, where patients are so
worried about becoming upset that they distract themselves from the task (which prevents learning). In this
mechanistic clinical trial, we will evaluate a strategy to augment extinction training with neuromodulation to
reduce arousal and improve extinction retention. Augmenting extinction training with continuous theta burst
stimulation (cTBS, a type of transcranial magnetic stimulation) delivered to the intraparietal sulcus (IPS) may
lead to targeted reductions in arousal. Our team has shown that the IPS is a “connectivity hub” for arousal and
that stimulating this region with TMS can reduce excessive arousal in healthy people. The goal for this R01 is to
evaluate the main effects of IPS cTBS (versus sham cTBS, a between-subject comparison) and its interaction
with extinction training (vs. neutral training) on arousal among patients with PTSD. We hypothesize that reducing
parietal hyperexcitability will help patients with PTSD to modulate arousal during extinction training—enough
arousal to ensure that they can benefit, but not too much arousal which prevents learning. These results could
translate into future opportunities for novel therapeutic targets among patients with PTSD. The specific aims are
as follows: Aim 1: To evaluate the optimal dose of IPS cTBS. H1: Attenuation of startle for IPS cTBS vs. sham
cTBS will plateau at 1200 pulses, the anticipated optimal cumulative dose. Aim 2: To compare the main effect
of IPS cTBS and its interaction with extinction training on arousal (measured by startle response). Using
a two (between group: sham vs. IPS cTBS) x 2 (within group: extinction training vs. control/neutral training)
randomized controlled design among patients with PTSD (N = 120), we will examine the potential benefit of
cTBS and extinction training on reduction in arousal. H2a: IPS cTBS will result in greater reduction in arousal
compared to sham cTBS. H2b: Participants who receive IPS cTBS will have a significantly lower difference in
retention of extinction learning vs. control/neutral training (indicative of greater retention of extinction learning)
compared to participants who receive sham cTBS. Secondary: We will test analogous hypotheses on subjective
outcomes and on cognitive outcomes and we hypothesize similar directions of effects. Aim 3: To evaluate
neural mechanisms of action of IPS cTBS + extinction training. Participants will complete a resting state
fMRI scan on tests of retention of learning experimental visits to evaluate neural changes from training. H3: We
will observe attenuated activation (relative to pre-test) of the IPS for participants who received IPS cTBS
compared to those...

## Key facts

- **NIH application ID:** 10802597
- **Project number:** 1R01MH132740-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Lily A Brown
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $811,653
- **Award type:** 1
- **Project period:** 2024-01-15 → 2028-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10802597

## Citation

> US National Institutes of Health, RePORTER application 10802597, A mechanistic trial of the neurobiology of extinction learning and intraparietal sulcus stimulation (1R01MH132740-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10802597. Licensed CC0.

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