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 in identifying negative (vs. neutral) images represents a behavioral marker of individual anxiety 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 vs neutral) and evaluated the results at a corrected threshold. Women but not men showed a significant correlation between individual anxiety and RT (negative vs neutral), with a slope test confirming the sex difference. In women alone the cerebellar vermis showed activity in positive correlation with RT (negative vs 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 in significant correlation with both STAI State score and RT (negative vs 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.

The authors have declared no competing interest.

The current study was supported by NIH grants R21AG067024 (Li) and R01AG072893 (Li).

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Human Investigation Committee at Yale School of Medicine

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