Impaired Effective Connectivity During a Cerebellar-Mediated Sensorimotor Synchronization Task in Schizophrenia

Abstract

Prominent conceptual models characterize schizophrenia as a dysconnectivity syndrome, with recent research focusing on the contributions of the cerebellum in this framework. The present study examined the role of the cerebellum and its effective connectivity to the cerebrum during sensorimotor synchronization in schizophrenia. Specifically, the role of the cerebellum in temporally coordinating cerebral motor activity was examined through path analysis. Thirty-one individuals diagnosed with schizophrenia and 40 healthy controls completed a finger-tapping fMRI task including tone-paced synchronization and self-paced continuation tapping at a 500 ms intertap interval (ITI). Behavioral data revealed shorter and more variable ITIs during self-paced continuation, greater clock (vs motor) variance, and greater force of tapping in the schizophrenia group. In a whole-brain analysis, groups showed robust activation of the cerebellum during self-paced continuation but not during tone-paced synchronization. However, effective connectivity analysis revealed decreased connectivity in individuals with schizophrenia between the cerebellum and primary motor cortex but increased connectivity between cerebellum and thalamus during self-paced continuation compared with healthy controls. These findings in schizophrenia indicate diminished temporal coordination of cerebral motor activity by cerebellum during the continuation tapping portion of sensorimotor synchronization. Taken together with the behavioral finding of greater temporal variability in schizophrenia, these effective connectivity results are consistent with structural and temporal models of dysconnectivity in the disorder.

Cerebellar–cortical dysconnectivity in resting‐state associated with sensorimotor tasks in schizophrenia

“…Also, the sway path and area for individuals with schizophrenia were significantly greater than for control groups ( p < .05 for all conditions). Findings of finger‐tapping and postural sway measures were consistent with our previous studies (Apthorp et al, 2019; Moussa‐Tooks et al, 2019).…”

“…In our previous study, we demonstrated that self‐paced tapping, in which the cerebellum is highly involved in the temporal coordination of motor activities, is impaired in schizophrenia, and showed a dyscoordination of the cortico‐cerebellar‐thalamo‐cortical circuit during this task (Moussa‐Tooks et al, 2019). The current study demonstrated that resting‐state connectivity from Crus I and II (cognitive‐related) was disproportionally associated with cerebellar‐mediated sensorimotor performance in patients with schizophrenia during the self‐paced portion of the task.…”

“…Details about the acquisition and processing of finger‐tapping data were described in our previous study (Moussa‐Tooks et al, 2019). Briefly, participants completed three 6‐min, consecutive sessions of a sensorimotor synchronization finger‐tapping task.…”

“…(b) “Which functional networks in the cerebrum are predominant in the lobular dysconnectivity of schizophrenia?” In addition to abnormal connectivity in the motor network, typically identified in functional abnormalities in schizophrenia, we also anticipated abnormal connectivity in higher‐level association networks in the cerebrum—for example, ventral attention network as seen in Shinn, Baker, Lewandowski, Ongur, and Cohen (2015) and Guo et al (2018). Finally, (c) “Is the lobular connectivity associated with motor task behaviors related to cerebellar functioning?” In our previous study, we found that schizophrenia‐spectrum disorders showed abnormal motor‐related effective connectivity during sensorimotor synchronization (Moussa‐Tooks et al, 2019). Therefore, based on the broad overlap between task and resting‐state fMRI abnormalities in schizophrenia (Mwansisya et al, 2017) and the shared cognitive abnormalities in the cortico‐cerebellar circuit in schizophrenia (Sheffield & Barch, 2016), resting‐state cerebellar–cortical functional connectivity was also predicted to be weakly associated with finger‐tapping behavior in individuals with schizophrenia compared to controls.…”

“…Anatomical findings include gray matter deficits (Wolfers et al, 2018), reduced white matter integrity (Mamah, Ji, Rutlin, & Shimony, 2019), disrupted connectivity (Klauser et al, 2017) and modularity (D. J. Kim et al, 2014) in the cerebellum in schizophrenia. Such structural abnormalities contribute to impairments in cognitive processes (Andreasen et al, 1996; Andreasen & Pierson, 2008; Ridler et al, 2006) and contribute to sensorimotor dysfunction—for example, postural sway (Apthorp, Bolbecker, Bartolomeo, O'Donnell, & Hetrick, 2019), sensorimotor synchronization (Moussa‐Tooks et al, 2019), and prediction (Shergill et al, 2014) mediated by the cerebellum. Resting‐state functional connectivity disturbances have also been detected.…”