Sex differences in insular gyri responses to the cold pressor challenge

Introduction Sex differences in autonomic control may contribute to physiological sex differences in cardiovascular disease, thermoregulation, and the experience of pain. We previously showed sex differences in functional mapping of autonomic responses across the insula, a central autonomic control region. Anterior insula response patterns to sympathetic activation (Valsalva) and parasympathetic withdrawal (handgrip) differed between men and women. We here assessed sex differences in autonomic insula gyrus responses to a cold pressor challenge, which involves temperature and pain regulation. Methods Functional MRI (fMRI) involved a 1-minute right-foot cold pressor challenge in 22 women (age; mean±std: 50±4 yrs), and 39 men (45±3 yrs). Regions of interest (ROI) comprised left and right anterior short gyrus (ASG), middle short gyrus (MSG), posterior short gyrus (PSG), anterior long gyrus (ALG), and posterior long gyrus (PLG). Two-second time intervals of fMRI signal responses per ROI and concurrently recorded heart rate and blood oxygen saturation (SaO 2 ) were tested for within- and between-group effects over time (repeated measures ANOVA P ≤0.05). We tested sex differences in 1) each ROI; 2) lateralization effects; and 3) posterior-to-anterior gradients in responses. Results No sex differences emerged in heart rate or SaO 2 . Women showed larger signal changes in several gyri than men after cold pressor onset and offset. Most consistently, women showed a greater right-over-left hemisphere dominance in cold pressor response compared to men in the MSG, PSG and ALG. Greater right-over-left hemisphere anterior-to-posterior dominance was more pronounced in men. Conclusions The findings confirm anterior and right-hemispheric dominance of insular responses during sympathetic activation that includes pain and cold. Although distinct transient male-female differences in fMRI responses appeared during the cold pressor, unlike the Valsalva and handgrip, no sex differences in ASG lateralization emerged, suggesting that the previously found sex differences may not solely relate to regulating blood pressure responses.