The objective of the study is to investigate the relationship between altered resting-state cortico-cerebellar functional connectivity (FC) and depression as well as cognitive impairment in late-onset depression (LOD). A total of 32 LOD and 39 well-matched normal controls (NCs) were recruited and underwent resting-state functional MRI (R-fMRI) scans. Seed-based correlation analysis was performed to explore the cortico-cerebellar FC. Hamilton Depression Rating Scale (HAMD) and mini-mental state examination (MMSE) were used to evaluate the depressive severity and cognitive impairment, respectively. A set of neuropsychological measurements was also applied to evaluate the detailed cognitions. Spearman correlations were applied to examine the depressive and cognitive association of these altered cortico-cerebellar networks. Compared with the NCs, LOD patients showed increased FC between the cerebellum and the right ventromedial frontal cortex (vmPFC), supplementary motor area (SMA), middle temporal gyrus (MTG), bilateral supramarginal gyrus (SMG), and anterior cingulated cortex (ACC). However, reduced cerebellar FC was observed in bilateral cerebellum, posterior cingulated cortex (PCC) and left dorsolateral prefrontal cortex (dlPFC). Moreover, the cerebellar FC with the vmPFC and ACC was positively correlated with HAMD score, whereas the cerebellar FC with the dlPFC and PCC was positively correlated with MMSE score in LOD patients. The cortico-cerebellar disconnections might underlie the pathogenesis of LOD. While depression mainly relates to the excessive cerebellar FC with the vmPFC and ACC, cognitive decline is primarily associated with the uncoupling of the cerebellar FC with the dlPFC and PCC.
