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

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.

Rethinking Time Series Domain Generalization via Structure-Stratified Calibration

For time series arising from latent dynamical systems, existing cross-domain generalization methods commonly assume that samples are comparably meaningful within a shared representation space. In real-world settings, however, different datasets often originate from structurally heterogeneous families of dynamical systems, leading to fundamentally distinct feature distributions. Under such circumstances, performing global alignment while neglecting structural differences is highly prone to establishing spurious correspondences and inducing negative transfer. From the new perspective of cross-domain structural correspondence failure, we revisit this problem and propose a structurally stratified calibration framework. This approach explicitly distinguishes structurally consistent samples and performs amplitude calibration exclusively within structurally compatible sample clusters, thereby effectively alleviating generalization failures caused by structural incompatibility. Notably, the proposed framework achieves substantial performance improvements through a concise and computationally efficient calibration strategy. Evaluations on 19 public datasets (100.3k samples) demonstrate that SSCF significantly outperforms strong baselines under the zero-shot setting. These results confirm that establishing structural consistency prior to alignment constitutes a more reliable and effective pathway for improving cross-domain generalization of time series governed by latent dynamical systems.