Altered cerebral functional activity and its associated genetic profiles underlying chronic insomnia disorder before and after treatment.

Objectives: The resting-state cerebral functional activity underlying chronic insomnia disorder (CID) remains inconsistent, and the effects of pharmacotherapy on such activity are unclear.

Methods: Imaging data and clinical variables were acquired from 82 patients with CID and 54 healthy controls (HCs). Patients were assigned to receive either modified Suanzaoren decoction (MSZRD) or estazolam treatment for six weeks. Spontaneous brain activity was evaluated by amplitude of low-frequency fluctuations (ALFF), Wavelet-ALFF, and fractional ALFF (fALFF). Machine-learning and cross-sample transcriptomic analysis were performed.

Results: Compared to HCs, patients with CID exhibited increased functional activity in the left precuneus/posterior cingulate cortex, left superior parietal gyrus, and bilateral angular gyrus; they also presented decreased activity in the right inferior parietal gyrus and bilateral middle frontal gyrus. After pharmacotherapy, patients in the MSZRD group showed increased activity in the left middle occipital gyrus compared to baseline. Receiver operating characteristic (ROC) curves based on these metrics were 0.98, 088, and 0.98; correlation coefficients between predicted and actual treatment responses ranged from 0.806 to 0.965.

Conclusion: Altered neural activity in regions of the default mode network, frontoparietal network and visual network might contribute to the neuropathological and therapeutic mechanisms of CID. (Clinical trial registration number: NCT06452953).