Effective connectivity analysis of resting-state mentalizing brain networks in spinocerebellar ataxia type 2: A dynamic causal modeling study

Neuroimaging studies on healthy subjects described the causal effective connectivity of cerebellar-cerebral social mentalizing networks, revealing the presence of closed-loops. These studies estimated effective connectivity by applying Dynamic Causal Modeling on task-related fMRI data of healthy subjects performing mentalizing tasks. Thus far, few studies have applied Dynamic Causal Modeling to resting-state fMRI (rsfMRI) data to test the effective connectivity within the cerebellar-cerebral mentalizing network in the absence of experimental manipulations, and no study applied Dynamic Causal Modeling on fMRI data of patients with cerebellar disorders typically showing social cognition deficits. Thus, in this research we applied spectral Dynamic Causal Modeling, to rsfMRI data of 13 patients affected by spinocerebellar ataxia type 2 (SCA2) and of 23 matched healthy subjects. Specifically, effective connectivity was tested between acknowledged mentalizing regions of interest: bilateral cerebellar Crus II, dorsal and ventral medial prefrontal cortex, bilateral temporo-parietal junctions and precuneus. SCA2 and healthy subjects shared some similarities in cerebellar-cerebral mentalizing effective connectivity at rest, confirming the presence of closed-loops between cerebellar and cerebral mentalizing regions in both groups. However, relative to healthy subjects, SCA2 patients showed effective connectivity variations mostly in cerebellar-cerebral closed loops, namely weakened inhibitory connectivity from the cerebellum to the cerebral cortex, but stronger inhibitory connectivity from the cerebral cortex to the cerebellum. The present study demonstrated that effective connectivity changes affect a function-specific mentalizing network in SCA2 patients, allowing to deepen the direction and strength of the causal effective connectivity mechanisms driven by the cerebellar damage associated with SCA2.