Date of Award

2006

Degree Type

Thesis

Degree Name

Doctor of Philosophy

Program

Kinesiology

Supervisor

Dr. J. Kevin Shoemaker

Abstract

he maintenance of arterial blood pressure during an orthostatic challenge requires baroreflex-mediated increases in heart rate (HR) and sympathetic nerve activity (SNA). Although stimulation of the human cerebral cortex has been shown to elicit cardiovascular responses, the cortical regions involved specifically with the baroreflex

are not well defined. Based on these experiments, the overall hypothesis was that the insular cortex (IC), anterior cingulate cortex (ACC), ventral medial prefrontal cortex (vMPFC) and amygdala are involved with the physiologie responses produced by progressive reductions in central blood volume ( baroreceptor unloading). The main objective was to determine the cortical regions associated with baroreflex-mediated HR and SNA responses to a simulated orthostatic stress produced using lower body negative pressure (LBNP). Cortical activity was estimated using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI). The initial study (Chapter 1) identified reproducible cortical BOLD signal responses, in men, that correlated with changes in LBNP and HR. This included greater activation of the right posterior superior IC and deactivation of the left IC, ventral ACC, vMPFC, amygdala and medial dorsal thalamus (MD). The purpose of the subsequent studies was to use gender (Chapter 2) and post-exercise hypotension (PEH, Chapter 3) models, both associated with altered baroreflex function, to examine whether this cortical network was involved with differential autonomie cardiovascular control. Compared with women, 35 mmHg LBNP elicited augmented HR and SNA reactions in men (P < 0.05). The larger HR response was matched by greater activation of the dorsal ACC and deactivation of the ventral ACC and the amygdala, whereas the augmented SNA response corresponded with greater

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activation of the right posterior superior IC and deactivation of the left IC and vMPFC in men versus women (all, P < 0.005). During PEH, 35 mmHg LBNP produced larger increases in HR and SNA compared with the no-exercise condition (P < 0.05). These post-exercise responses were associated with greater activation of the right posterior

superior IC and dorsal ACC and deactivation of the vMPFC and MD (all, P < 0.005). Taken together these studies suggest that the amygdala and ventral ACC are associated with the control of cardiac function, the left insula and vMPFC with the regulation of peripheral vasoconstrictor nerve activity, whereas the right insula and dorsal ACC may

influencebothoftheseresponsesduringasimulatedorthostaticchallenge. Inconclusion, these studies provide the first known evidence highlighting the cortical network involved with the regulation of autonomie and cardiovascular responses to baroreceptor unloading

in conscious humans.

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