Introduction

Bipolar type I disorder is a major psychiatric disorder which significantly impacts the lives of approximately 1.0% of the population. The neural underpinnings of this disease are still unknown, but work to date has identified the emotional control network as being involved in the large mood swings that occur in this disorder. In addition, there is growing evidence that the cerebellum is also abnormal in the disorder. This has included observations of abnormal structure, function, and metabolism. Given these observations, we were interested in better understanding connectivity of the cerebellum with the cerebrum in bipolar disorder and if this connectivity changed with mood.

Methods

This study enrolled 128 participants with bipolar type I disorder and 83 control comparison participants who completed an imaging session at 3T (Fig 1), which included anatomical imaging as well as ten minutes of resting state BOLD imaging. Data was analyzed using standard analysis pipelines and then a whole brain atlas was assembled by existing brain atlases for the cerebral cortex, subcortical structures, and cerebellum. Functional connectivity of the cerebellar vermis to all other brain regions was assessed to determine if there were differences between the participants with bipolar disorder and comparison control subjects. In addition, in the subjects with bipolar disorder we examined if there were relationships between functional connectivity and mood. We also explored if medication had an impact on the functional connectivity observed.

Results

Functional connectivity of the cerebellar vermis in bipolar disorder was found to be significantly different (Fig 2) between the following regions as compared to controls: Vermis V to Left Pars Opercularis, Vermis V to Right Posterior Cingulate Gyrus (Schafer parcel X), Vermis V to Left Postcentral Gyrus, Vermis VIIIB to Left Postcentral Gyrus, Vermis VIIIB to Right Pre/Postcentral Gyrus, and Vermis X to Left Lateral Amygdala. All of the connections observed to be different between groups exhibited stronger connectivity in the participants with bipolar disorder with the exception of Vermis V to Left Pars Opercularis. In the participants with bipolar disorder, total scores from the MADRS scale was significantly associated with functional connectivity between the following regions (Fig 3): vermis IX to Left Ventroposterior Thalamus, vermis IX to Right Anterior Parahippocampal Gyrus, and Vermis X to Left Ventroposterior Thalamus. In the evaluation of YMRS scores to functional connectivity (Fig 3), a significant relationship between vermis X and left middle frontal gyrus was found. All of the associations with mood were negative meaning that increased mood ratings was associated lower functional connectivity between these regions. Associations with medication were found for the antidepressants and lithium with increased connectivity being associated with being on a particular class of medication.

Conclusion

This study revealed significant differences in vermal connectivity in bipolar disorder to brain regions associated with emotion, language production, and motor function. The association between functional connectivity and mood in the participants with bipolar disorder all showed a decrease in connectivity associated with increased mood symptoms. The cerebellar vermis could be a key node in the emotional control network and future studies should consider expanding this network to include the cerebellum.

References

No reference found.