Altered dorsal striatal subregional connectivity associated with distinct executive function deficits in first-episode, drug-naïve major depressive disorder: Evidence from functional connectivity and granger causality analysis.

Executive dysfunction is a common cognitive impairment in Major Depressive Disorder (MDD). The dorsal striatum (DS) has been implicated in executive function, yet its role in early-stage MDD and the neural mechanisms underlying executive deficits remain unclear. Seventy-four first-episode, drug-naïve MDD patients and 78 healthy controls (HCs) underwent rs-fMRI and neuropsychological tests assessing executive function. Seed-based functional connectivity (FC) and Granger causality analysis (GCA) were performed with three bilateral DS subregions as seeds. MDD patients showed poorer executive performance than HCs. Altered FC was found between DS subregions and several brain regions. The left dorsal caudal putamen (DCP) showed enhanced FC with dorsolateral prefrontal cortex and reduced FC with cerebellum, the right dorsal caudate (DC) showed reduced FC with precuneus, and the left dorsal rostral putamen (DRP) showed enhanced FC with inferior parietal lobule (IPL). GCA revealed increased causal outflow from the orbitofrontal cortex (OFC) and cerebellum to DC, and from DC to anterior cingulate cortex. Exploratory correlation analyses showed that FC between left DCP and cerebellum was positively correlated with task-switching abilities, while FC between left DRP and IPL was positively associated with inhibitory control in MDD patients. These findings suggested that distinct subregions of the dorsal striatum may be differentially involved in executive dysfunction, providing preliminary evidence for the neural basis of cognitive impairment in early-stage major depressive disorder.