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

TL;DR

This study developed an EEG-based machine learning model that accurately predicts individual response to transcutaneous auricular vagus nerve stimulation in treatment-resistant schizophrenia, highlighting specific neurophysiological markers linked to symptom improvement.

Contribution

The paper introduces a novel EEG coherence-based machine learning approach for predicting taVNS response in TRS, emphasizing neurophysiological features as both predictors and therapeutic targets.

Findings

Model predicted treatment response with high accuracy (r = 0.87)

Fronto-parietal and fronto-temporal coherence features are key predictors

EEG markers are specific to active taVNS and linked to negative symptom improvement

Abstract

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.