Validating the neurobiological model of obsessive-compulsive disorder: a brain entropy study using resting-state fMRI.

BACKGROUND AND HYPOTHESIS: Obsessive-compulsive disorder (OCD) has been consistently associated with dysfunction within the cortico-striato-thalamo-cortical (CSTC) circuits. Brain entropy (BEN) is a nonlinear measure of the complexity and irregularity of neural signals, including blood oxygen level-dependent (BOLD) time series. Although OCD has been extensively studied using conventional resting-state fMRI (rs-fMRI) metrics, alterations in intrinsic temporal complexity remain unclear. We investigated BEN alterations in OCD and their associations with OCD symptoms. STUDY DESIGN: Sixty-seven patients with OCD and 60 healthy controls underwent rs-fMRI. BEN maps were computed using sample entropy and compared between groups. Associations between regional BEN and OCD-related clinical measures were examined using correlation analyses. STUDY RESULTS: Patients with OCD showed increased BEN in CSTC regions, including the orbitofrontal cortex, caudate, and thalamus, and in extra-CSTC regions, including the superior temporal gyrus (STG) and middle cingulate cortex (FDR-corrected p < .05). Within the OCD group, higher BEN was associated with DOCS total scores in the right thalamus (r = 0.380), contamination symptoms in the left caudate (r = 0.382), unacceptable thoughts in the right thalamus (r = 0.429), and importance/control of thoughts scores in the right STG (r = 0.384; all FDR-adjusted p = .023). CONCLUSIONS: BEN revealed OCD-related alterations across both CSTC and extra-CSTC regions, with regional BEN associated with specific symptom dimensions and obsessive beliefs. BEN appeared to capture alterations particularly in subcortical and midline structures, providing complementary information beyond conventional rs-fMRI measures and offering a new perspective on the neural mechanisms underlying OCD.