Regional homogeneity and interhemispheric connectivity alterations in major depressive disorder

Frontotemporal neural synchronization and hemispheric lateralization imbalances are core features of major depressive disorder (MDD), but objective Functional near-infrared spectroscopy (fNIRS) - derived biomarkers capturing these abnormalities remain underdeveloped.

We recruited 236 MDD patients and 124 healthy controls (HCs) who completed a verbal fluency task (VFT) during 52-channel fNIRS scanning. Regional Homogeneity (ReHo) and hemispheric Laterality Index (LI) were computed to assess local neural synchronization and interhemispheric balance across four VFT phases (pre-task, task-period, post-task, whole-process). Interhemispheric functional connectivity (Spearman partial correlation) and a random forest classifier (5-fold stratified cross-validation) were further analyzed, with false discovery rate (FDR) correction for multiple comparisons.

Compared to HCs, MDD patients showed reduced ReHo in left inferior frontal gyrus (LIFG) and left temporal lobe (LT) across all phases (FDR-corrected p < 0.05), a pathological rightward shift in LI (most pronounced during task-period: LI_T = 0.006, LI_IFG = 0.015, LI_F = 0.015), and impaired interhemispheric connectivity in LIFG-RIFG (task-period z = 2.39, p = 0.017). The random forest model integrating ReHo features achieved robust diagnostic performance, with the highest area under the curve (AUC) of 0.831 in the whole-process phase.

MDD is characterized by left-lateralized frontotemporal synchronization deficits, pathological rightward lateralization, and disrupted interhemispheric coordination during cognitive processing. fNIRS-derived ReHo features hold promise as non-invasive biomarkers for MDD diagnosis, advancing objective psychiatric assessment.