Abstract
Insomnia disorder (ID) is not merely a psychiatric disorder but is also closely related to heart health. The role of brain-heart interplay (BHI) in the mechanism of ID and the effect of noninvasive brain stimulation on BHI remains unclear. To explore the BHI in the mechanism of ID and investigate whether tACS affects BHI. Forty-four IDs and 32 healthy controls (HCs) were enrolled. The IDs received θ-tACS targeting F3 for 10 consecutive days. Synchronous electroencephalogram (EEG) and electrocardiogram (ECG) were collected for the IDs before and after treatment. Comparisons of bidirectional BHI indexes based on a synthetic data generation (SDG) model, EEG power, and heart rate variability (HRV), were conducted between IDs and HCs at baseline, as well as changes in these measures before and after tACS. Correlations and mediation analyses between BHI and behavioral assessments were also investigated. IDs exhibited significantly higher BHI in both directions. Correlation results indicated that the Pittsburgh Sleep Quality Index (PSQI) was associated with top-down BHI, while the Hamilton Anxiety Rating Scale (HAMA) was correlated with bottom-up BHI. Additionally, θ-tACS modulated abnormal BHI. Notably, baseline top-down BHI at Fz could predict improvements in sleep quality and depression and mediated the recovery of sleep quality and depression. We extended the hyperarousal theory of ID from a new perspective of BHI. Furthermore, BHI was identified as a potential predictor of clinical outcomes following θ-tACS intervention.