# Utilizing changes in human brain connectivity to establish a dose-response relationship involved in the therapeutic actions of prefrontal brain stimulation on depression symptoms

> **NIH NIH R01** · STANFORD UNIVERSITY · 2021 · $555,754

## Abstract

ABSTRACT
Major depressive disorder (MDD) is prevalent and debilitating, and development of improved treatments is limited
in part by insufficient understanding of the mechanism of disease remission. In turn, efforts to elucidate
mechanisms have been challenging due to disease heterogeneity and limited effectiveness of treatments, which
require weeks-to-months to induce remission. In this application, we propose to focus on applying a novel
neurostimulation strategy to participants with TRD. We recently developed a form of repetitive transcranial
magnetic stimulation that induces remission in 90% of individuals with severe, treatment resistant MDD in 1-5
days which we called Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT). This methodology
provides a new tool to begin exploring the network-level mechanisms of MDD remission. Following SAINT, fc
significantly decreases default mode network (DMN)-subgenual cingulate cortex (sgACC) which is correlated
with change in clinical scales. In this application, we propose to target the L-DLPFC-sgACC target with active
(n=50) versus sham (n=50) SAINT and determine if active SAINT (Aim 1) attenuates sgACC-DMN connectivity
and (Aim 2) significantly reduces symptoms of depression. Decreases in fc may underlie reductions in
depression; thus, we will relate reductions in these potential moderators to identify the best symptom targets.
Completion of this proposal will further establish a safe, effective, and non-invasive device-based treatment for
TRD along with the iterative neural circuitry changes at each daily dose of stimulation that summate to produce
the clinical effect.

## Key facts

- **NIH application ID:** 10131265
- **Project number:** 5R01MH122754-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Nolan R. Williams
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $555,754
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10131265

## Citation

> US National Institutes of Health, RePORTER application 10131265, Utilizing changes in human brain connectivity to establish a dose-response relationship involved in the therapeutic actions of prefrontal brain stimulation on depression symptoms (5R01MH122754-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10131265. Licensed CC0.

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