Cortical regions associated with autonomic cardiovascular regulation during lower body negative pressure in humans

The purpose of the present study was to determine the cortical structures involved with integrated baroreceptor-mediated modulation of autonomic cardiovascular function in conscious humans independent of changes in arterial blood pressure. We assessed the brain regions associated with lower body negative pressure (LBNP)-induced baroreflex control using functional magnetic resonance imaging with blood oxygen level-dependent (BOLD) contrast in eight healthy male volunteer subjects. The levels of LBNP administered were 5, 15 and 35 mmHg. Heart rate (HR; representing the cardiovascular response) and LBNP (representing the baroreceptor activation level) were simultaneously monitored during the scanning period. In addition, estimated central venous pressure (CVP), arterial blood pressure (ABP) and muscle sympathetic nerve activity were recorded on a separate session. Random effects analyses (SPM2) were used to evaluate significant (P < 0.05) BOLD signal changes that correlated separately with both LBNP and HR (15- and 35-mmHg versus 5-mmHg LBNP). Compared to baseline, steady-state LBNP at 15 and 35 mmHg decreased CVP (from 7 +/- 1 to 5 +/- 1 and 4 +/- 1 mmHg, respectively) and increased MSNA (from 12 +/- 1 to 23 +/- 3 and 36 +/- 4 bursts min(-1), respectively, both P < 0.05 versus baseline). Furthermore, steady-state LBNP elevated HR from 54 +/- 2 beats min(-1) at baseline to 64 +/- 2 beats min(-1) at 35-mmHg suction. Both mean arterial and pulse pressure were not different between rest and any level of LBNP. Cortical regions demonstrating increased activity that correlated with higher HR and greater LBNP included the right superior posterior insula, frontoparietal cortex and the left cerebellum. Conversely, using the identical statistical paradigm, bilateral anterior insular cortices, the right anterior cingulate, orbitofrontal cortex, amygdala, midbrain and mediodorsal nucleus of the thalamus showed decreased neural activation. These data corroborate previous investigations highlighting the involved roles of the insula, anterior cingulate cortex and amygdala in central autonomic cardiovascular control. In addition, we have provided the first evidence for the identification of the cortical network involved specifically with baroreflex-mediated autonomic cardiovascular function in conscious humans.