Timing dysfunction and cerebellar resting state functional connectivity abnormalities in youth at clinical high-risk for psychosis

Background Consistent with pathophysiological models of psychosis, temporal disturbances in schizophrenia spectrum populations may reflect abnormal cortical (e.g. prefrontal cortex) and subcortical (e.g. striatum) cerebellar connectivity. However, few studies have examined associations between cerebellar connectivity and timing dysfunction in psychosis populations, and none have been conducted in youth at clinical high-risk (CHR) for psychosis. Thus, it is currently unknown if impairments in temporal processes are present in CHR youth or how they may be associated with cerebellar connectivity and worsening of symptoms. Methods A total of 108 (56 CHR/52 controls) youth were administered an auditory temporal bisection task along with a resting state imaging scan to examine cerebellar resting state connectivity. Positive and negative symptoms at baseline and 12 months later were also quantified. Results Controlling for alcohol and cannabis use, CHR youth exhibited poorer temporal accuracy compared to controls, and temporal accuracy deficits were associated with abnormal connectivity between the bilateral anterior cerebellum and a right caudate/nucleus accumbens striatal cluster. Poor temporal accuracy accounted for 11% of the variance in worsening of negative symptoms over 12 months. Conclusions Behavioral findings suggest CHR youth perceive durations of auditory tones as shortened compared to objective time, which may indicate a slower internal clock. Poorer temporal accuracy in CHR youth was associated with abnormalities in brain regions involved in an important cerebellar network implicated in prominent pathophysiological models of psychosis. Lastly, temporal accuracy was associated with worsening of negative symptoms across 12 months, suggesting temporal dysfunction may be sensitive to illness progression.