Fronto-parietal and fronto-temporal EEG coherence as predictive neuromarkers of transcutaneous auricular vagus nerve stimulation response in treatment-resistant schizophrenia: A machine learning study

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Main Authors: Cui, Yapeng, Yun, Ruoxi, Zhang, Shumin, Gong, Yi, Li, Zhiqin, Chen, Ying, Su, Mingbing, Wu, Dongniya, Wu, Jingxia, Wang, Qian, Wang, Jianan, Tian, Qianqian, Yuan, Yangyang, Mei, Shuhao, Wu, Lei, Li, Xinghua, Zhang, Bingkui, Guo, Taipin, Sun, Jinbo
Format: Preprint
Published: 2026
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author Cui, Yapeng
Yun, Ruoxi
Zhang, Shumin
Gong, Yi
Li, Zhiqin
Chen, Ying
Su, Mingbing
Wu, Dongniya
Wu, Jingxia
Wang, Qian
Wang, Jianan
Tian, Qianqian
Yuan, Yangyang
Mei, Shuhao
Wu, Lei
Li, Xinghua
Zhang, Bingkui
Guo, Taipin
Sun, Jinbo
author_facet Cui, Yapeng
Yun, Ruoxi
Zhang, Shumin
Gong, Yi
Li, Zhiqin
Chen, Ying
Su, Mingbing
Wu, Dongniya
Wu, Jingxia
Wang, Qian
Wang, Jianan
Tian, Qianqian
Yuan, Yangyang
Mei, Shuhao
Wu, Lei
Li, Xinghua
Zhang, Bingkui
Guo, Taipin
Sun, Jinbo
contents Response variability limits the clinical utility of transcutaneous auricular vagus nerve stimulation (taVNS) for negative symptoms in treatment-resistant schizophrenia (TRS). This study aimed to develop an electroencephalography (EEG)-based machine learning (ML) model to predict individual response and explore associated neurophysiological mechanisms. We used ML to develop and validate predictive models based on pre-treatment EEG data features (power, coherence, and dynamic functional connectivity) from 50 TRS patients enrolled in the taVNS trial, within a nested cross-validation framework. Participants received 20 sessions of active or sham taVNS (n = 25 each) over two weeks, followed by a two-week follow-up. The prediction target was the percentage change in the positive and negative syndrome scale-factor score for negative symptoms (PANSS-FSNS) from baseline to post-treatment, with further evaluation of model specificity and neurophysiological relevance.The optimal model accurately predicted taVNS response in the active group, with predicted PANSS-FSNS changes strongly correlated with observed changes (r = 0.87, p < .001); permutation testing confirmed performance above chance (p < .001). Nine consistently retained features were identified, predominantly fronto-parietal and fronto-temporal coherence features. Negligible predictive performance in the sham group and failure to predict positive symptom change support the predictive specificity of this oscillatory signature for taVNS-related negative symptom improvement. Two coherence features within fronto-parietal-temporal networks showed post-taVNS changes significantly associated with symptom improvement, suggesting dual roles as predictors and potential therapeutic targets. EEG oscillatory neuromarkers enable accurate prediction of individual taVNS response in TRS, supporting mechanism-informed precision neuromodulation strategies.
format Preprint
id arxiv_https___arxiv_org_abs_2603_13850
institution arXiv
publishDate 2026
record_format arxiv
spellingShingle Fronto-parietal and fronto-temporal EEG coherence as predictive neuromarkers of transcutaneous auricular vagus nerve stimulation response in treatment-resistant schizophrenia: A machine learning study
Cui, Yapeng
Yun, Ruoxi
Zhang, Shumin
Gong, Yi
Li, Zhiqin
Chen, Ying
Su, Mingbing
Wu, Dongniya
Wu, Jingxia
Wang, Qian
Wang, Jianan
Tian, Qianqian
Yuan, Yangyang
Mei, Shuhao
Wu, Lei
Li, Xinghua
Zhang, Bingkui
Guo, Taipin
Sun, Jinbo
Machine Learning
Response variability limits the clinical utility of transcutaneous auricular vagus nerve stimulation (taVNS) for negative symptoms in treatment-resistant schizophrenia (TRS). This study aimed to develop an electroencephalography (EEG)-based machine learning (ML) model to predict individual response and explore associated neurophysiological mechanisms. We used ML to develop and validate predictive models based on pre-treatment EEG data features (power, coherence, and dynamic functional connectivity) from 50 TRS patients enrolled in the taVNS trial, within a nested cross-validation framework. Participants received 20 sessions of active or sham taVNS (n = 25 each) over two weeks, followed by a two-week follow-up. The prediction target was the percentage change in the positive and negative syndrome scale-factor score for negative symptoms (PANSS-FSNS) from baseline to post-treatment, with further evaluation of model specificity and neurophysiological relevance.The optimal model accurately predicted taVNS response in the active group, with predicted PANSS-FSNS changes strongly correlated with observed changes (r = 0.87, p < .001); permutation testing confirmed performance above chance (p < .001). Nine consistently retained features were identified, predominantly fronto-parietal and fronto-temporal coherence features. Negligible predictive performance in the sham group and failure to predict positive symptom change support the predictive specificity of this oscillatory signature for taVNS-related negative symptom improvement. Two coherence features within fronto-parietal-temporal networks showed post-taVNS changes significantly associated with symptom improvement, suggesting dual roles as predictors and potential therapeutic targets. EEG oscillatory neuromarkers enable accurate prediction of individual taVNS response in TRS, supporting mechanism-informed precision neuromodulation strategies.
title Fronto-parietal and fronto-temporal EEG coherence as predictive neuromarkers of transcutaneous auricular vagus nerve stimulation response in treatment-resistant schizophrenia: A machine learning study
topic Machine Learning
url https://arxiv.org/abs/2603.13850