Altered Effective Connectivity of Precuneus Subregions and Associated Gene Profiles in Chronic Insomnia Disorder Patients Before and After Treatment

BACKGROUND: Previous studies have highlighted the crucial role of the precuneus in the hyperarousal state of insomnia. However, the causal effects between its subregions and other regions remain unclear. Both traditional Chinese medicines (TCMs) and benzodiazepines are effective in insomnia treatment, but limited studies have compared the therapeutic mechanisms of these two treatments. METHODS: This study included 82 chronic insomnia disorder (CID) patients and 80 healthy controls (HCs). CID patients were assigned to receive either modified suanzaoren decoction, a TCM for treating insomnia, or estazolam treatment for 6 weeks. Granger causality analysis seeded on the precuneus subregions was employed to detect effective connectivity (EC) alterations at pre- and post-treatment. Moreover, a neuroimaging-transcription association analysis was conducted. RESULTS: Compared to HCs, CID patients showed increased EC from the precuneus to the right postcentral/precentral gyrus (PoCG/PrCG) and left lingual gyrus. Meanwhile, decreased ECs from the bilateral PoCG/PrCG, right cerebellum crus VIIB, and right calcarine cortex to the precuneus were observed. After 6 weeks of treatment, significant group-by-time interactions on ECs from the bilateral midcingulate cortex to precuneus, as well as from the bilateral midcingulate cortex, left PrCG, and right supramarginal gyrus to precuneus were observed. Genes associated with these ECs were identified. CONCLUSIONS: The bidirectional ECs between the precuneus and regions in the sensory-motor and visual networks in CID may reflect both hyperarousal states and compensatory responses to counteract abnormal hyperarousal. TCM tended to alleviate the hyperarousal state in CID while benzodiazepines induced an adaptive regulation due to their rapid sedative effects. TRIAL REGISTRATION: Clinical trial registration number: NCT06452953.