Studies of resting-state functional connectivity (FC), measured by functional magnetic resonance imaging (rsfMRI), have revealed extensive functional connections between the cerebellum and association regions in the brain, ...
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Studies of resting-state functional connectivity (FC), measured by functional magnetic resonance imaging (rsfMRI), have revealed extensive functional connections between the cerebellum and association regions in the brain, supporting an important role for the cerebellum in cognition. These findings have been based on static FC measures averaged across entire scans spanning a few minutes. However, this is a narrow view that has been recently challenged, with findings pointing to the presence of an ongoing, behaviorally relevant dynamics in resting-state FC occurring at short timescales of a few seconds, which, given the dynamic nature of the brain, is a more natural view that may encode information about complex cognitive functions. So far, however, the cerebellum has been overlooked in most, if not all, studies of dynamic FC, despite its well-recognized role in coordinating complex cognitive functions. In this thesis, we hypothesized that the dynamics of cerebro-cerebellar FC, during rest, may be behaviorally relevant, capturing aspects of cognition and behavior not accounted for by static FC and exhibiting alterations in brain disorders commonly associated with cerebro-cerebellar dysfunction, such as alcohol use disorder (AUD). We tested these hypotheses in two separate studies focusing on the dynamics of cerebro-cerebellar FC in relation to complex traits and disorders, such as impulsivity (first study) and AUD (second study). The first study has been motivated by a recent hypothesis for a role of the cerebellum in impulsivity; a complex personality trait defined as the tendency to act without foresight. We hypothesized that individual differences in normal impulsivity traits could be associated with the (static) strength and (dynamic) temporal variability of cerebro-cerebellar resting-state FC. We tested this hypothesis using rsfMRI data and self-report questionnaires of impulsivity (UPPS-P and BIS/BAS) collected from a group of healthy individuals. In particular, we employed data-driven techniques to identify cerebral and cerebellar resting-state networks, compute summary measures of static and dynamic FC, and test for associations with self-reported impulsivity. We observed evidence linking multiple forms of impulsivity to the strength and temporal variability of resting-state FC between the cerebellum and a set of highly dynamic and integrative brain networks that support top-down cognitive control and bottom-up reward/saliency processes, supporting our hypothesis that cerebro-cerebellar FC dynamics are behaviorally relevant. In the second study, we hypothesized that the dynamics of cerebro-cerebellar FC at short timescales would differ between AUD and controls, especially in the frontocerebellar circuits. To test this hypothesis, we explored the differences in the dynamic cerebro-cerebellar FC between an AUD group (N=18) and a group of unaffected controls (N=18) by comparing groups on different dynamic connectivity measures. Results revealed altered cerebro-cerebellar FC dynamics in the AUD group characterized by hypervariability of FC within fronto-parieto-cerebellar networks, reduced cerebellar flexibility, and increased cerebellar integration, compared with controls. These results suggest a possible role for the dynamics of fronto-parieto-cerebellar networks in the pathophysiology of this disorder. Taken together, the findings from this thesis highlight the utility of complementing static FC approaches with dynamic FC analysis in furthering our understanding of the functional repertoire of cerebro-cerebellar networks and the neurobiological architecture of complex behaviors and brain disorders.
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