Sex differences in the neural correlates of autonomic arousal: a pilot PET study

Electrophysiology, behavioral, and neuroimaging studies have revealed sex-related differences in autonomic cardiac control, as reflected in measurements of heart rate variability (HRV). Imaging studies indicate that the neurobiological correlates of autonomic nervous system (ANS) function can be investigated by measuring indices of HRV during the performance of mildly strenuous motor tasks or mildly stressful cognitive tasks. In this preliminary study, fifteen male and seven female healthy subjects underwent H(2)(15)O-positron emission tomography (PET) and electrocardiograph (ECG) recording while performing a handgrip motor task and an n-back task. Indices of HRV were calculated and correlated with regional cerebral blood flow (rCBF). We hypothesized that sex differences would be evident in brain regions known to participate in autonomic regulation: the anterior insula, the anterior cingulate cortex, the orbitofrontal cortex, and the amygdala. Our study found that associations between rCBF and parasympathetic indices differed significantly between female and male subjects in the amygdala. Females showed a positive correlation between rCBF and parasympathetic indices while males exhibited negative correlations. This differential correlation of amygdala rCBF and parasympathetic activity between males and females may reflect differences in parasympathetic/sympathetic balance between sexes, consistent with known sexual dimorphism in the amygdala and closely related structures such as the hypothalamus. These preliminary imaging results are consistent with earlier reports of significant correlation between brain activity and HRV, and extend these findings by demonstrating prominent sex differences in the neural control of the ANS. While the generalizability of our results was limited by the small size of the study samples, the relatively robust effect size of the differences found between groups encourages further work in larger samples to characterize sex differences in the neural correlates of autonomic arousal.