# Network-Targeted Neuromodulation for Nicotine Dependence in Schizophrenia

> **NIH NIH K23** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $185,544

## Abstract

PROJECT SUMMARY
Tobacco use is the top preventable cause of early mortality in schizophrenia, leading to a 20-year decreased life
expectancy compared to the general population. Current smoking cessation treatments are derived from people
without psychosis and are significantly less effective for people with schizophrenia. We used a data-driven,
agnostic approach to identify a schizophrenia-specific circuit of nicotine dependence (the Default Mode Network,
DMN) then tested pharmacologic and neuromodulation interventions on this circuit. We observed craving was
bidirectionally mediated by DMN connectivity: 1) nicotine administration (which reduces craving) decreased DMN
connectivity in schizophrenia, while 2) a single session of intermittent theta burst stimulation (iTBS), which
increases connectivity, applied to a DMN node acutely increased craving in schizophrenia. This provides
evidence that 1) nicotine craving is mediated by this network and 2) this target can be engaged bidirectionally
via multiple interventions. This K23 mentored patient-oriented career development award proposes to test if
multiple repetitive transcranial magnetic stimulation (rTMS) sessions lead to enduring circuit change and reduce
nicotine craving. Our central hypothesis is that the brain circuit most effective to reduce nicotine craving in
schizophrenia is distinct from the pathway identified in a non-schizophrenia population. To test this hypothesis,
we will compare 1) DMN-targeted continuous theta burst stimulation (cTBS) to 2) iTBS targeted to the left
dorsolateral prefrontal cortex (L DLPFC), which reduces cigarette consumption and craving in smokers without
psychosis. cTBS has been shown to decrease network connectivity. By applying cTBS to the DMN, we aim to
decrease connectivity, thereby decreasing craving. We will determine if rTMS manipulates functional connectivity
and craving and if craving change correlates with connectivity change for each rTMS target. To optimize rTMS
response, we will also test if variability in rTMS response is explained by individual differences in network
controllability. The applicant is a psychiatrist with fellowship-level training in neuroimaging and rTMS for
substance use disorders in schizophrenia. Her long-term career goal is to build an independent research
program using neuroimaging to identify brain networks linked to substance use in psychotic disorders then test
neuroscience-based, network-targeted rTMS interventions in clinical trials for co-occurring substance use
disorders in schizophrenia. To accomplish these goals, the applicant requires additional training in: 1) design
and conduct of personalized network-targeted rTMS interventions, 2) individualized neuroimaging to optimize
rTMS response, and 3) clinical trials and biostatistics. Training will include formal coursework, didactics, and on-
site trainings, guided under a mentorship team of experts in network-targeted rTMS interventions in psychotic
disorders, computatio...

## Key facts

- **NIH application ID:** 10783927
- **Project number:** 1K23DA059690-01
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Heather Burrell Ward
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $185,544
- **Award type:** 1
- **Project period:** 2024-02-01 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10783927

## Citation

> US National Institutes of Health, RePORTER application 10783927, Network-Targeted Neuromodulation for Nicotine Dependence in Schizophrenia (1K23DA059690-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10783927. Licensed CC0.

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