Effects of CBT-I in modulating neuroplasticity in brain regions associated with insomnia disorder and serum 27-OHC levels.

Insomnia disorder (ID) is often accompanied by cognitive deficits and disturbances in brain networks and metabolism. As a potential marker of central metabolism and oxidative stress, the role of 27-hydroxycholesterol (27-OHC) in ID pathophysiology and dCBT-I-induced neuroplasticity remains unclear. This study investigated the relationships among alterations in brain function, 27-OHC levels, and the therapeutic effects of dCBT-I. We collected resting-state fMRI data and serum samples from 32 ID patients (at baseline and after six weeks of dCBT-I) and 32 healthy controls. We compared group differences in spontaneous anterior cingulate cortex (ACC) activity and resting-state functional connectivity (rsFC), and assessed whether changes in brain function and 27-OHC levels were associated with dCBT-I effects. Results showed that ID patients exhibited decreased spontaneous activity in the right ACC and enhanced rsFC within the sensorimotor network. Serum 27-OHC concentrations were significantly elevated and positively correlated with rsFC strength of the supplementary motor area. After dCBT-I, 27-OHC levels significantly decreased, and the treatment reversed aberrant activity in several brain regions. Post-treatment changes in dysfunctional beliefs about sleep were closely associated with normalized activity in the left putamen and left middle temporal gyrus. In summary, elevated serum 27-OHC and its aberrant coupling with the sensorimotor network jointly constitute an important biological basis for hyperarousal in ID. dCBT-I not only alleviates peripheral metabolic stress but also reshapes patients' cognition by inducing neuroplasticity within the striatum (especially the putamen and caudate).