Cerebellum-Cerebrum Dynamics During Gaze Processing in Schizophrenia: Evidence for Social-Cognitive Modulation and Associations With Social Functioning Across Independent Samples.

BACKGROUND

Individuals with schizophrenia have prominent impairments in social cognition that contribute to poor functional outcomes. Gaze processing, the social-cognitive ability to accurately perceive human eye gaze direction, is similarly abnormal in schizophrenia and associated with social functioning. Although gaze processing has known neural underpinnings in cerebral social-processing brain regions, emerging data suggest that the posterior cerebellum (PCb) plays a key but often neglected role in social-cognitive function. Elucidating the bidirectional PCb-cerebrum dynamics underlying social cognition is critical to identifying a novel treatment target.

METHODS

Thirty-nine individuals with schizophrenia or schizoaffective disorder (SZ) and 33 nonclinical control (NCC) participants completed an eye-contact detection task during functional magnetic resonance imaging. Dynamic causal modeling was used to delineate the dynamics between the PCb (crus II) and 3 cerebral social processing (inferior parietal lobule, anterior insula, and fusiform gyrus) nodes and to quantify abnormal effective connectivity in SZ. A sensitivity analysis using an independent sample (SZ = 27, NCC = 22) was conducted to confirm the results.

RESULTS

Relative to NCC participants, participants with SZ showed less upregulation of cerebellar outputs during gaze processing (t68 = 2.853, p = .006), and this decreased upregulation was associated with social dysfunction (ρ = -0.251, p = .034). Convergent evidence of these results was observed in the independent sample.

CONCLUSIONS

With convergent evidence across 2 independent samples, the current study showed that people with schizophrenia have altered PCb-cerebrum dynamics during gaze processing that is linked to social functioning. Given the greater accessibility of the PCb from the scalp for noninvasive brain stimulation relative to many cerebral social-cognitive regions, our findings have critical implications for translational interventions.