Evaluating the abnormal neural variability in schizophrenia: A TMS-EEG study.

BACKGROUND

The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) (TMS-EEG) has become a pivotal tool for investigating neurophysiological mechanisms in schizophrenia (SZ), a disorder marked by pronounced clinical and neurobiological heterogeneity. However, conventional analyses of TMS-EEG data frequently neglect trial-to-trial neural variability, a critical dimension of dynamic brain responses that may reflect core pathophysiological features of SZ.

METHODS

The TMS-EEG data and MCCB were collected from 45 SZ patients and 45 healthy controls (HC). Trial-by-trial variability (TTV) was quantified through the maximum eigenvalue extracted from singular value decomposition of TMS-evoked trials data. Correlation analyses were conducted between TTV and scores.

RESULTS

TMS pulse significantly reduced the TTV of neural activity in both groups. Compared to HC, SZ patients demonstrated increased beta TTV but decreased theta TTV. Notably, elevated beta TTV correlated with reasoning and problem solving, working memory and verbal learning while diminished theta TTV was associated with speed of processing and social cognition.

CONCLUSIONS

This pioneering study establishes altered trial-wise neural variability as a novel electrophysiological signature of SZ. The frequency-specific TTV abnormalities and their cognitive correlations suggest that dysregulated neural dynamics may underlie core symptomatology, providing quantifiable biomarkers for clinical stratification and therapeutic development.