Aberrant cerebello-cerebral connectivity in remitted bipolar patients 1 and 2: new insight into understanding the cerebellar role in mania and hypomania

Objectives. Bipolar Disorder (BD) is a major mental illness characterized by periods of (hypo) mania and depression with inter-episode remission periods. Functional studies in BD have consistently implicated a set of linked cortical and subcortical limbic regions in the pathophysiology of the disorder, also including the cerebellum. However, the cerebellar role in the neurobiology of BD still needs to be clarified. Methods. Seventeen euthymic patients with BD type1 (BD1) (mean age/SD: 38.64/13.48; M/F:9/8) and 13 euthymic patients with BD type 2 (BD2) (mean age/SD: 41.42/14.38; M/F:6/7) were compared with 37 sex- and age-matched healthy subjects (HS) (mean age/SD: 45.65/14.15; M/F:15/22). T1 weighted and resting-state functional connectivity (FC) scans were acquired. The left and right dentate nucleus were used as seed regions for the seed based analysis. FC between each seed and the rest of the brain was compared between patients and HS. Correlations between altered cerebello-cerebral connectivity and clinical scores were then investigated. Results. Different patterns of altered dentate-cerebral connectivity were found in BD1 and BD2. Overall, impaired dentate-cerebral connectivity involved regions of the anterior limbic network specifically related to the (hypo)manic states of BD Conclusion. Cerebello-cerebral connectivity is altered in BD1 and BD2. Interestingly, the fact that these altered FC patterns persist during euthymia, supports the hypothesis that cerebello-cerebral FC changes reflect the neural correlate of subthreshold symptoms, as trait-based pathophysiology and/or compensatory mechanism to maintain a state of euthymia.