# Deriving TMS Targets for Mood Valence and Mood Stabilization in Bipolar Disorder

> **NIH NIH K23** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $195,500

## Abstract

Project Summary
 New treatments are needed for bipolar disorder (BD). Transcranial magnetic stimulation (TMS) shows
promise for BD, but the optimal treatment targets for mania, depression, and mood stabilization are unknown.
Studying brain lesions that cause BD symptoms provides causal insights into neuroanatomy. These causal
insights are critically important for target identification. Lesion network mapping (LNM) leverages the human
connectome to map brain lesions onto brain networks rather than single brain regions, enhancing lesion
localization and target identification. Pioneered by the Fox lab (Mentor), LNM shows promise for optimizing TMS
targets for unipolar depression. Two recent Fox lab studies used LNM to examine the brain circuitry causally
implicated in mania (n=56, two datasets) and depression (n=461, five datasets). However, there are two critical
limitations of this prior work. First, mania and depression were analyzed as independent states rather than
opposing poles of a valence spectrum in BD. This limitation will be addressed with a single model analysis of
mania, depression, and control lesions. Second, these studies did not validate targets in patients with BD. This
limitation will be addressed by validating lesion-derived targets in patients with BD using functional neuroimaging
and behavioral testing. Aim 1 is to derive and validate TMS targets for mood valence. These valence-specific
targets will be derived with LNM contrasts of mania vs. depression (and vice versa) in an a priori prefrontal cortex
mask, and the results will be validated by correlating their whole-brain connectivity to task-based measures of
valence bias in patients with BD. Aim 2 is to derive and validate a TMS target for mood stabilization. This
valence-nonspecific target will be derived with LNM contrasts of mania plus depression vs. controls in an a priori
ventrolateral prefrontal cortex mask, and the resulting target will be validated by correlating its whole-brain
connectivity to a task-based measure of emotion regulation in patients with BD.
 This study aligns with the NIMH 2020 Strategic Plan objective of developing novel tools with which to
characterize brain networks causally implicated in affective processes. A follow-up R01 or R61/33 grant
examining whether TMS alters behavioral metrics, functional connectivity, and clinical outcomes in patients with
BD aligns with NIMH’s experimental therapeutics approach. This grant was designed to provide the stepwise
scientific training necessary to fulfill this plan, from LNM and biostatistics to translational research involving
phenotyping and imaging of patients with BD. It also fits well with the long-term goal of becoming an
independently funded physician-scientist who leads an Interventional Psychiatry research program primarily
focused on deriving, validating, and testing circuit-based TMS targets. With this goal in focus, there is no better
place to train than Brigham and Women’s Hospital, a Harvard ...

## Key facts

- **NIH application ID:** 10590940
- **Project number:** 1K23MH129829-01A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Joseph Jeffrey Taylor
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $195,500
- **Award type:** 1
- **Project period:** 2022-09-19 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10590940

## Citation

> US National Institutes of Health, RePORTER application 10590940, Deriving TMS Targets for Mood Valence and Mood Stabilization in Bipolar Disorder (1K23MH129829-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10590940. Licensed CC0.

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