Differential Cerebellar-cerebral Dynamic Functional Connectivity Between Depressive And Remitted Bipolar Disorder:A Resting-state FMRI Study

Objective: Bipolar disorder(BD)is a common severe mental disease.Recent neuroimaging studies have demonstrated structural and functional abnormalities of the cerebellum in BD patients,but the role of the cerebellum in the pathophysiological mechanism of BD is unclear.Dynamic functional connectivity(d FC)analysis is better to reveal changes in the brain’s intrinsic information than conventional static functional connectivity(s FC)analysis.The present study aims to investigate the d FC between the cerebellum and cerebrum,especially cerebellum-the central executive network(CEN)and-the default-mode network(DMN)of bipolar II disorder(BD II)in different mood states,in order to seek possible imaging biomarkers of BD.Methods: 44 patients with unmedicated BD II depression,37 patients with remitted BD II and 50 healthy controls(HCs)underwent resting-state functional magnetic resonance imaging(rs-f MRI)at 3.0T magnetic resonance.We chose four cerebellar seeds,including bilateral Crus Ia reported to be involved in the CEN and bilateral Crus Ib involved in the DMN,then we performed a sliding-window correlational analysis and seed-based connectivity analysis to calculate the d FC value of the cerebellar-CEN and-DMN among the three groups.One-way ANOVA was used to compare the differences of d FC values among the three groups,and post-hoc t-tests,restricted to the voxels showing significant differences by ANOVA analyses,were performed to identify differences between each pair of group.Correction method based on Gaussian random field(GRF)theory was used to analyze the inter-group difference threshold(z>2.3,cluster threshold <0.05),p<0.05 were considered statistically significant.Then partial correlation analyses were used to analyze the correlation between d FC values of brain regions showing significant differences and clinical variables in the patient group(p<0.05).Results: In the CEN,the three groups showed significant d FC differences in the right Crus Ia-left cerebellar Crus II.Compared with HCs,depressive BD patients showed no significant difference,while remitted BD patients appeared increased d FC in the right Crus Ia-left Crus II.Relative to depressive BD,remitted BD patients also showed increased d FC in the right Crus Ia-left Crus II(p<0.05,GRF corrected).In the DMN,the three groups revealed significant d FC differences in the right Crus Ib-left medial prefrontal cortex,-left angular gyrus and-right precuneus.Compared with HCs,depressive BD displayed reduced d FC in the right Crus Ib-left medial prefrontal cortex,and-right precuneus,while remitted BD patients showed increased d FC in the right Crus Ib-left angular gyrus,and reduced d FC in the right Crus Ib-right precuneus;Relative to depressive BD patients,remitted BD patients appeared increased d FC in the right Crus Ib-left medial prefrontal cortex and-left angular gyrus,but reduced d FC in Crus Ib-right precuneus(p<0.05,GRF corrected).No altered d FC between the left Crus Ia or Crus Ib and the cerebral regions was observed.No significant correlation between the d FC value and the clinical variables in BD was found.Conclusions: Both depressive and remitted BD patients showed different degrees of abnormal fluctuation of functional connectivity between the cerebellum and the CEN(mainly in the Crus II)and DMN(mainly in the medial prefrontal cortex,angular gyrus,and precuneus),suggesting that it might be involved in the pathophysiological mechanism of BD.Moreover,the abnormalities of d FC in the cerebellum-precuneus appeared in both depressive and remitted BD patients,speculating that it might be the potential neurogenetic marker of BD.