# Suicide Circuit Therapeutics: Engaging Novel Targets with Rapid and Individualized MRI-Guided Accelerated TMS

> **NIH NIH R61** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $947,267

## Abstract

PROJECT SUMMARY AND ABSTRACT
 Suicide is a leading cause of death worldwide, with tragic consequences for individuals and their families.
Despite the increased access to mental health services and use of psychiatric treatments, suicide rates have
remained unchanged over the last century. Worse, from 1999 to 2019 suicide rates increased 33% in the U.S.
Rapid, safe and effective antisuicidal therapies are critically needed.
 Our group has characterized a circuit biomarker that may predict and explain the antisuicidal effects of
ECT. Before ECT, excessively anticorrelated functional connectivity (FC) between the anterior cingulate cortex
(ACC) and the right inferior parietal lobule (IPL) predicts greater post-ECT antisuicidal response (predictor
biomarker), and greater reduction of ACC-IPL anticorrelated FC during ECT is associated with greater
antisucidal efficacy (response biomarker or treatment target). This finding led us to hypothesize a novel
biomarker-informed treatment strategy aiming to engage this treatment target: TMS over the right IPL could be
used to focally reduce ACC-IPL anticorrelated FC and hence reduce suicidal thoughts and behaviors (STB).
 Recent innovations in TMS have established that intermittent Theta Burst Stimulation (iTBS), an efficient
TMS protocol that lasts less than 3 minutes, is as effective an antidepressant when applied over the
dorsolateral prefrontal cortex (DLPFC) as the traditional 38 minutes 10Hz TMS protocol: DLPFC iTBS was
cleared by the FDA in 2018. Given the brevity of iTBS, accelerated protocols (aiTBS) have been established to
deliver the equivalent number of pulses of an FDA-cleared 6-week course of iTBS in a single day, and to
repeat this for 5 consecutive days. When applied to the DLPFC, aiTBS seems safe and rapidly effective for
depression. Our preliminary evidence shows that individualized MRI-guided aiTBS over the right IPL of suicidal
patients is feasible, safe, leads to rapid reduction of STB and reduces ACC-IPL anticorrelation as predicted.
 The current proposal aims to develop rapid antisuicidal therapies for patients in their most vulnerable
periods: during hospitalization and post-discharge. The R61 phase will randomize patients in a depressive
episode with moderate to severe STB to receive 1 day (10 sessions) of active or sham aiTBS to the right IPL.
We will measure changes in FC, clinical reduction of STB and safety/tolerability. If we meet our a priori go
criteria, the following R33 phase will randomize patients hospitalized in a psychiatric unit with acute STB to
receive a full course of 5 days (50 sessions) of aiTBS, and we will measure FC, reduction of STB acutely and
during 1 month post-discharge and safety/tolerability of this intensive protocol. If successful, this project will
contribute to the development of highly individualized and biomarker-informed rapid treatments for suicidal
patients using noninvasive device neuromodulation, and establish the biological and clinical evidence...

## Key facts

- **NIH application ID:** 10832102
- **Project number:** 5R61MH132869-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Joan A Camprodon
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $947,267
- **Award type:** 5
- **Project period:** 2023-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10832102

## Citation

> US National Institutes of Health, RePORTER application 10832102, Suicide Circuit Therapeutics: Engaging Novel Targets with Rapid and Individualized MRI-Guided Accelerated TMS (5R61MH132869-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10832102. Licensed CC0.

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