DMN-Targeted TMS Reduces Neural Cue-Reactivity in Individuals with Schizophrenia who Use Nicotine
- 1Vanderbilt University Medical Center
Abstract
BackgroundNicotine dependence is a major contributor to early mortality in individuals with schizophrenia, yet effective treatments remain limited. Drug cue-reactivity is a key contributor to nicotine use. Although transcranial magnetic stimulation (TMS) can reduce nicotine use and cue-reactivity, conventional left dorsolateral parietal (DLPFC)-targeted TMS is less effective in those with schizophrenia, highlighting the need for alternative, circuit-based targets. Because default node network (DMN) function is implicated in schizophrenia, cue-reactivity, and nicotine use, we investigated whether DMN-targeted TMS modulates cue-elicited brain activity in nicotine-using individuals with schizophrenia.
Study Design63 nicotine-using individuals (schizophrenia: n=31, non-psychosis control: n=32) participated in a randomized, crossover study comparing DMN-targeted and DLPFC-targeted TMS with pre/post-TMS neuroimaging and craving assessment. A nicotine cue-reactivity task was used concurrently with neuroimaging. Mixed-effect models were used to determine effects of TMS target and diagnosis, and model relationship between baseline craving and cue-reactivity change.
Study ResultsAt baseline, we found a Cue Reactive Network composed of regions overlapping with the DMN, including clusters in the posterior cingulate cortex, medial prefrontal cortex, and bilateral lateral occipital cortex (voxel-wise p<0.005, cluster p<0.05). Baseline cue-reactivity in schizophrenia did not differ from controls. DMN-targeted TMS decreased cue-reactivity in schizophrenia across Cue Reactive Network (estimate=-0.180, p=0.009). DLPFC-targeted TMS did not impact cue-reactivity. We did not observe an effect of either TMS target in controls. Higher baseline unprovoked craving predicted larger decrease in cue-reactivity across the Cue Reactive Network (estimate=-0.034, p=0.004).
ConclusionDMN-targeted TMS is a promising intervention that modulates nicotine cue-elicited brain activity in schizophrenia.
Related
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BibTeX
@misc{bai2026dmntargeted,
title = {{DMN-Targeted TMS Reduces Neural Cue-Reactivity in Individuals with Schizophrenia who Use Nicotine}},
author = {Y. Bai and A. Huang and J. Connolly and S. H. Blyth and S. Vandekar and B. P. Rogers and L. Tunison and C. Chang and H. Tindle and S. Heckers and R. O. Brady and A. Janes and H. B. Ward},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.15.26363162},
url = {https://www.medrxiv.org/content/10.64898/2026.09.15.26363162v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - DMN-Targeted TMS Reduces Neural Cue-Reactivity in Individuals with Schizophrenia who Use Nicotine
AU - Y. Bai
AU - A. Huang
AU - J. Connolly
AU - S. H. Blyth
AU - S. Vandekar
AU - B. P. Rogers
AU - L. Tunison
AU - C. Chang
AU - H. Tindle
AU - S. Heckers
AU - R. O. Brady
AU - A. Janes
AU - H. B. Ward
PY - 2026
DA - 2026/09/15
PB - medRxiv
DO - 10.64898/2026.09.15.26363162
UR - https://www.medrxiv.org/content/10.64898/2026.09.15.26363162v1
AB - BackgroundNicotine dependence is a major contributor to early mortality in individuals with schizophrenia, yet effective treatments remain limited. Drug cue-reactivity is a key contributor to nicotine use. Although transcranial magnetic stimulation (TMS) can reduce nicotine use and cue-reactivity, conventional left dorsolateral parietal (DLPFC)-targeted TMS is less effective in those with schizophrenia, highlighting the need for alternative, circuit-based targets. Because default node network (DMN) function is implicated in schizophrenia, cue-reactivity, and nicotine use, we investigated whether DMN-targeted TMS modulates cue-elicited brain activity in nicotine-using individuals with schizophrenia. Study Design63 nicotine-using individuals (schizophrenia: n=31, non-psychosis control: n=32) participated in a randomized, crossover study comparing DMN-targeted and DLPFC-targeted TMS with pre/post-TMS neuroimaging and craving assessment. A nicotine cue-reactivity task was used concurrently with neuroimaging. Mixed-effect models were used to determine effects of TMS target and diagnosis, and model relationship between baseline craving and cue-reactivity change. Study ResultsAt baseline, we found a Cue Reactive Network composed of regions overlapping with the DMN, including clusters in the posterior cingulate cortex, medial prefrontal cortex, and bilateral lateral occipital cortex (voxel-wise p<0.005, cluster p<0.05). Baseline cue-reactivity in schizophrenia did not differ from controls. DMN-targeted TMS decreased cue-reactivity in schizophrenia across Cue Reactive Network (estimate=-0.180, p=0.009). DLPFC-targeted TMS did not impact cue-reactivity. We did not observe an effect of either TMS target in controls. Higher baseline unprovoked craving predicted larger decrease in cue-reactivity across the Cue Reactive Network (estimate=-0.034, p=0.004). ConclusionDMN-targeted TMS is a promising intervention that modulates nicotine cue-elicited brain activity in schizophrenia.
ER -