Cingulate and frontopolar cortical projections to the cerebellar vermis support prolonged reaction time in identifying negative emotional scenes in women

Abstract

We previously observed sex differences in the association of individual anxiety and reaction time (RT) during identification of negative emotional scenes in a Hariri task. Prolonged RT, an attention marker, in identifying negative (vs. neutral) images correlated with anxiety level in women but not in men. However, the neural circuit that supports this behavioral observation remains unclear. Here, with a larger sample (64 men and 62 women), we employed whole-brain regression on individual differences in RT during matching negative vs. neutral images or RT (negative – neutral) and evaluated the results at a corrected threshold. Women but not men showed a significant correlation between individual anxiety and RT (negative – neutral), with a slope test confirming the sex difference. In women alone the cerebellar vermis showed activity in positive correlation with RT (negative – neutral). Further, Granger causality mapping (GCM) showed multiple brain regions, including the anterior cingulate cortex/frontopolar cortex (ACC/FPC), that provide inputs to the cerebellar vermis in women. Amongst these regions, only the ACC/FPC cluster showed activity (β) in significant correlation with both STAI State score and RT (negative – neutral) in women. GCM also identified a small cluster in the pons, suggesting that the cortical pontine cerebellar circuit may support prolonged RT during identification of negative emotions. Path analyses further characterized the inter-relationships amongst the neural markers, RT, and anxiety. These findings highlight a behavioral and circuit marker of anxiety state in neurotypical women. Studies with different behavioral paradigms are needed to characterize the behavioral and neural mechanisms of male anxiety.