Temporal regularity of intrinsic cerebral activity in patients with chronic primary insomnia: a brain entropy study using resting-state fMRI

Introduction: Several neuroimaging studies have suggested that patients with chronic primary insomnia (CPI) exhibit anatomical and functional alterations of the brain, but the temporal regularity in spontaneous neuronal activity remains unknown. Here, brain entropy (BEN), a data-driven method used to measure the signal regularity of a time series, was applied for the first time to investigate changes in the entire brain at the voxel level. Methods: Resting-state functional MRI data were used to investigate insomnia-related BEN alterations and the resting-state functional connectivity (rsFC) pattern in seed regions with altered BEN in 29 patients with identified and untreated CPI and 29 matched healthy controls. Subsequently, within the CPI group, correlation analysis was conducted to evaluate the relationship between the clinical variables and the BEN and rsFC of the abnormal regions. Results: Chronic primary insomnia patients showed significant increase in BEN in the central part of the default-mode network (DMN), the anterior regions of the task-positive network (TPN), the hippocampus (Hipp), and basal ganglia (BG), and decreases in BEN in the right postcentral gyrus (PoCG) and right temporal-occipital junction (TOJ). We also demonstrated that three altered resting-state functional connectivity (rsFC) patterns were associated with abnormal BEN regions in CPI patients. Correlation analysis identified an association between the altered rsFC and clinical variables, such as the Pittsburgh Sleep Quality Index (PSQI), in CPI patients. Conclusions: Together, these findings suggest that abnormal BEN-related intrinsic functional plasticity in CPI patients corresponds to poor sleep quality during chronic insomnia. Alterations in both BEN and its affected connectivity may improve our understanding of treatment-naive CPI patients and promote the future development of new therapeutic strategies.