# Personalized circuit-based neuromodulation targets for depression

> **NIH NIH K23** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $195,660

## Abstract

PROJECT SUMMARY/ABSTRACT
This proposal requests support for a five-year program of training and research to better understand how
distinct brain circuits can be mapped and selectively stimulated with transcranial magnetic stimulation (TMS) to
treat different symptoms of major depression.
In the proposed training plan, I will build upon my previous psychiatric and computational experience to
perform a multidisciplinary project at Beth Israel Deaconess Medical Center. My career development plan
includes training in brain circuit mapping, neuromodulation, biostatistics/data science, psychiatric phenotyping,
clinical trials, and general translational research.
TMS is an effective treatment for major depression which is capable of modulating specific brain circuits.
However, efficacy varies greatly across patients and the mechanisms are not well-understood. Recent work
from our lab shows that the efficacy of TMS can be improved by stimulating specific targets based on their
connectivity profile. Additionally, different TMS targets can modulate different brain networks which may be
involved in different symptoms of depression. The brain circuit connected to each stimulation site can be
mapped by using functional connectivity MRI (fcMRI), either at the group level or the individual level. A general
estimated map of stimulation site connectivity can be generated from the human connectome, a normative
wiring diagram of the human brain based on fcMRI of a thousand healthy controls. A more precise map of
connectivity can be generated based on subject-specific fcMRI data.
This proposal aims to personalize TMS targets based on symptoms, emotional task performance, and
brain connectivity. In my preliminary data, this approach yielded distinct circuits responsible for improvement
in “dysphoric” versus “anxiosomatic” symptom clusters. However, these results are limited by retrospective
nature, reliance on subjective symptom scales, and reliance on group-based connectivity. In this proposal, I will
address these limitations by confirming our results in a prospective randomized trial, incorporating task-based
behavioral metrics, and incorporating subject-specific connectivity.
More broadly, this research aims to develop a model for mapping specific circuits associated with distinct
symptom clusters that can be modulated with therapeutic brain stimulation. This will lay the foundation for
personalized approaches to transdiagnostic neuromodulation in clinical psychiatry.

## Key facts

- **NIH application ID:** 10487590
- **Project number:** 5K23MH121657-03
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Shan Siddiqi
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $195,660
- **Award type:** 5
- **Project period:** 2020-09-04 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10487590

## Citation

> US National Institutes of Health, RePORTER application 10487590, Personalized circuit-based neuromodulation targets for depression (5K23MH121657-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10487590. Licensed CC0.

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