Disrupted Interhemispheric Synchrony in Default Mode Network Underlying the Impairment of Cognitive Flexibility in Late-Onset Depression

The intuitive association between cognitive impairment and aberrant functional activity in the brain network has prompted interest in exploring the role of functional connectivity in late-onset depression (LOD). The relationship of altered voxel-mirrored homotopic connectivity (VMHC) and cognitive dysfunction in LOD is not yet well understood. This study was designed to examine the implicit relationship between the disruption of interhemispheric functional coordination and cognitive impairment in LOD. LOD patients (N = 31) and matched healthy controls (HCs; N = 37) underwent neuropsychological tests and functional magnetic resonance imaging (fMRI) in this study. The intergroup difference of interhemispheric coordination was determined by calculating VMHC value in the whole brain. The neuro-behavioral relevancy approach was applied to explore the association between disrupted VMHC and cognitive measures. Receiver operating characteristic (ROC) curve analysis was used to determine the capability of disrupted regional VMHC to distinguish LOD. Compared to the HC group, significantly attenuated VMHC in the superior frontal gyrus (SFG), superior temporal gyrus (STG), posterior cerebellar lobe (CePL) and post- and precentral gyri were observed in the bilateral brain of LOD patients. The interhemispheric asynchrony in bilateral CePLs was positively correlated with the performance of trail making test B (TMT-B) in LOD patients (r = 0.367, P = 0.040). ROC analysis revealed that regions with abnormal VMHC could efficiently distinguish LOD from HCs (Area Under Curve [AUC] = 0.90, P < 0.001). Altered linkage patterns of intrinsic homotopic connectivity and impaired cognitive flexibility was first investigated in LOD, and it would provide a novel clue for revealing the neural substrates underlying cognitive impairment in LOD.