Altered directional brain–heart interactions across resting states and frequency bands in schizophrenia

Schizophrenia is associated with abnormalities in cortical activity and autonomic regulation, but directional brain-heart interaction (BHI) across resting states and frequency bands remains unclear. Resting-state electroencephalography (EEG) and electrocardiography (ECG) were recorded simultaneously in 33 medicated men with schizophrenia and 29 healthy men during eyes-open and eyes-closed conditions. Directional BHI was assessed across two coupling directions, two cardiac frequency components, and five EEG frequency bands. Global-average and spatial cluster-based permutation analyses were performed, with family-wise error rate correction across all 40 predefined BHI features. Compared with healthy controls, patients with schizophrenia showed higher theta, alpha, and beta EEG power during eyes-open rest and higher theta and alpha EEG power during eyes-closed rest after false discovery rate correction. Cardiac low-frequency (LF) and high-frequency (HF) spectral power did not differ significantly between groups. During eyes-open rest, patients showed lower global-average brain-to-heart high-frequency (BtH-HF) coupling across all five EEG bands (global family-wise error rate-corrected p = 0.0151-0.0349; Hedges' g = -0.911 to -0.841). This finding was supported by spatial cluster analysis and multitaper sensitivity analysis. No eyes-closed BtH-HF effects survived global correction. Although four eyes-open heart-to-brain (HtB) clusters were initially significant under the fixed-order model, none survived the Bayesian information criterion-based order sensitivity analysis. No significant Condition × Group interaction was detected across the five BtH-HF features. Schizophrenia was associated with reduced eyes-open BtH-HF coupling across EEG bands, indicating altered statistical brain-heart coupling.