# Deep TMS Neuromodulation of Neural Circuits Associated with Stimulant Use Disorder

> **NIH NIH UG3** · STANFORD UNIVERSITY · 2024 · $1,491,755

## Abstract

ABSTRACT
Background: Converging lines of evidence suggest that neuromodulation of the neural circuits underlying
methamphetamine use disorder (MUD) and subsequent relapse may be an innovative next step in improving
treatment outcomes. Emerging research supports the salience network (SN) as a promising target to
accomplish these goals. Deep transcranial magnetic stimulation (dTMS) is one type of neuromodulation
technique that allows for deeper stimulation of cortical neurons, thus reaching core nodes of the SN like the
insula. Objective: The aim of this 2-phase proposal is to assess: 1) whether the H4 coil protocol is effective at
engaging the AIns core node of the SN, 2) does this coil and protocol engage the neural target better than a
sham condition, and 3) does stimulation of this core node have downstream effects on behavior (i.e., relapse
risk). Methods/Design: In the UG3 phase, we will enroll 30 treatment-seeking participants with MUD into a
mechanistic trial to determine whether this treatment site and protocol effectively modifies the desired neural
target and reduced relapse rates. Participants will receive 30 sessions of 10Hz dTMS to the insula and PFC
using the H4 coil. Participants will receive 3 dTMS treatments per day for 10 days totaling 30 treatment
sessions. Participants will complete neuroimaging assessments at baseline, after 50% of treatment sessions,
post-treatment and 1 month after treatment. In order to advance to the UH3 phase, we will require that dTMS
increases activation (of at least a medium effect size) to the respective neural target AND result in reduced
relapse rates relative to treatment as usual. If the UG3 milestone criteria are met, in the UH3 phase we will
enroll an additional 60 adults with MUD into a 2-arm randomized, double-blind, sham-controlled mechanistic
trial to confirm target engagement relative to sham, assess the impact of the protocol on methamphetamine
use behaviors, and determine moderators of treatment response. Specific Aims: For the UG3 (Study 1), we
aim to demonstrate feasibility, tolerability and target engagement (neural and behavioral improvements). If
milestone criteria are met, in the UH3 phase (Study 2), we aim to 1. Confirm target engagement in a 2-arm
randomized, double blind, sham-controlled trial. 2. Examine the relationship between target engagement to a
more refined measure of use behaviors (i.e., % days abstinent). 3. Determine predictors of treatment
outcomes. Impact: The proposed research will elucidate mechanisms of brain and behavior change,
accelerate the development of new, device-based, treatment options and will be the basis for developing a
large-scale, dose-varying, clinical trial to test new treatment strategies for MUD.

## Key facts

- **NIH application ID:** 11002135
- **Project number:** 1UG3DA061616-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Michelle RoseAnn Madore
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,491,755
- **Award type:** 1
- **Project period:** 2024-09-15 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11002135

## Citation

> US National Institutes of Health, RePORTER application 11002135, Deep TMS Neuromodulation of Neural Circuits Associated with Stimulant Use Disorder (1UG3DA061616-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11002135. Licensed CC0.

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