Theta-tACS modulates brain-heart interplay to enhance sleep in insomnia disorder.

Insomnia disorder (ID) is not merely a psychiatric condition but is also closely related to cardiovascular health. However, the role of brain-heart interplay (BHI) in the pathophysiology of ID, as well as the impact of transcranial current stimulation (tACS) on BHI, remains poorly understood. This study aimed to examine BHI alterations in ID and to investigate whether tACS can modulate these changes. Forty-four individuals with ID and 32 healthy controls (HCs) were enrolled. Patients with ID received theta-frequency tACS targeting the F3 electrode for 10 consecutive days. Synchronous electroencephalogram (EEG) and electrocardiogram (ECG) recordings were collected for the IDs before and after treatment. Bidirectional BHI metrics, derived from a synthetic data generation (SDG) model, as well as EEG power and heart rate variability (HRV), were compared between IDs and HCs at baseline, and pre-vs. post-tACS in IDs. Correlation and mediation analyses were conducted between BHI and behavioral outcomes. Our results revealed significantly increased BHI in both directions in IDs compared to HCs. Top-down BHI was associated with sleep quality (Pittsburgh Sleep Quality Index), while bottom-up BHI correlated with anxiety severity (Hamilton Anxiety Rating Scale). Notably, θ-tACS modulated the aberrant BHI in IDs. Furthermore, baseline top-down BHI at Fz predicted improvements in sleep quality and depressive symptoms, and mediated their recovery. These findings extend the hyperarousal theory of ID by highlighting the role of BHI, and suggest that BHI may serve as a promising predictor of clinical outcomes following θ-tACS intervention.