Forebrain neural patterns associated with sex differences in autonomic and cardiovascular function during baroreceptor unloading

Generally, women demonstrate smaller autonomic and cardiovascular reactions to stress, compared with men. The mechanism of this sex-dependent difference is unknown, although reduced baroreflex sensitivity may be involved. Recently, we identified a cortical network associated with autonomic cardiovascular responses to baroreceptor unloading in men. The current investigation examined whether differences in the neural activity patterns within this network were related to sex-related physiological responses to lower body negative pressure (LBNP, 5, 15, and 35 mmHg). Forebrain activity in healthy men and women (n = 8 each) was measured using functional magnetic resonance imaging with blood oxygen level-dependent (BOLD) contrast. Stroke volume (SV), heart rate (HR), and muscle sympathetic nerve activity (MSNA) were collected on a separate day. Men had larger decreases in SV than women (P < 0.01) during 35 mmHg LBNP only. At 35 mmHg LBNP, HR increased more in males then females (9 +/- 1 beats/min vs. 4 +/- 1 beats/min, P < 0.05). Compared with women, increases in total MSNA were similar at 15 mmHg LBNP but greater during 35 mmHg LBNP in men [1,067 +/- 123 vs. 658 +/- 103 arbitrary units (au), P < 0.05]. BOLD signal changes (P < 0.005, uncorrected) were identified within discrete forebrain regions associated with these sex-specific HR and MSNA responses. Men had larger increases in BOLD signal within the right insula and dorsal anterior cingulate cortex than women. Furthermore, men demonstrated greater BOLD signal reductions in the right amygdala, left insula, ventral anterior cingulate, and ventral medial prefrontal cortex vs. women. The greater changes in forebrain activity in men vs. women may have contributed to the elevated HR and sympathetic responses observed in men during 35 mmHg LBNP.