# CRCNS US-France Research Proposal: Probing the Dorsolateral Prefrontal Cortex and Central Executive Network for Improving Neuromodulation in Depression

> **NIH NIH R01** · STANFORD UNIVERSITY · 2022 · $208,088

## Abstract

The overarching goal of this work is to improve treatments of medication-resistant neuropsychiatric diseases with
repetitive transcranial stimulation (rTMS) by tailoring the target to an individual's brain networks. We are indeed in
critical need of these individualized treatments for mental health disorders, which affect nearly 50% of Americans
during our lifetimes, and brain stimulation treatments, including rTMS represent innovative approaches for these
patients. To alleviate depression, rTMS attempts to target a region of the prefrontal cortex generally located within
the central executive network (CEN), which drives decision making, cognitive control, and is critically impaired in
depression. However, rTMS is delivered without targeting an individual's CEN, and as such may inadvertently
deliver stimulation outside the CEN. This application is motivated by recent developments in the field, including a
large-scale whole-brain connectivity database derived from invasive recordings and the demonstration that rTMS
in depressed patients induces brain changes that predict clinical improvement. In this proposal, we combine non-
invasive TMS studies in healthy subjects and depressed patients with invasive direct stimulation studies from
surgical patients. We test the hypothesis that the CEN connectivity is weakened in depression and can be
maximally modulated by individualizing localization. The project consists of three aims: (1) investigate the
excitability, connectivity, and neuronal properties within the CEN using direct brain recordings in surgical patients
with epilepsy; (2) derive accurate TMS tools to measure CEN connectivity non-invasively in healthy and depressed
populations; and (3) in a depressed population characterize inter-individual variability within the CEN and
prospectively test if localization with TMS at the individual level more effectively modulates this brain network. This
approach, which can be generalized to any brain region and disorder, utilizes a large database of direct brain
recordings to map a brain network at an unparalleled level of detail, develops a link to direct brain recordings in
order to yield validated non-invasive brain measures, and applies these insights to individually localize the network
and improve targeted brain stimulation. Scientific outcomes include: (1) the first causal, functional map of the
human CEN from direct brain recordings; (2) novel non-invasive brain measures of connectivity grounded in
electrophysiology; (3) causal brain signatures of depression in the CEN; (4) a methodology to target an individual's
CEN in the clinic; and (5) improved modulation of the CEN using this methodology. In summary, a successful
outcome of the proposed work would yield an algorithm and guidelines for personalized TMS targeting based on
fully validated brain signatures in depression.
RELEVANCE (See instructions):
Brain stimulation for depression targets the central executive network (CEN), involved in decision ...

## Key facts

- **NIH application ID:** 10561527
- **Project number:** 7R01MH129018-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Corey J Keller
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $208,088
- **Award type:** 7
- **Project period:** 2022-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10561527

## Citation

> US National Institutes of Health, RePORTER application 10561527, CRCNS US-France Research Proposal: Probing the Dorsolateral Prefrontal Cortex and Central Executive Network for Improving Neuromodulation in Depression (7R01MH129018-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10561527. Licensed CC0.

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