Electronic Thesis and Dissertation Repository


Doctor of Philosophy




Kevin Shoemaker


Dysregulation of autonomic control often develops with advancing age, favoring a chronic state of heightened sympathetic outflow with parasympathetic withdrawal. However, the mechanisms of this age-related autonomic impairment are not known and may relate to alterations in brain structure (e.g. cortical atrophy) and/or altered neural function, particularly in regions related to the cortical autonomic network, namely, the medial prefrontal cortex (MPFC), insula cortex (IC), and hippocampus (HC). Exercise exerts beneficial effects on brain structure and, in the case of cognition, neurologic function; however, how exercise affects regions of the brain related to autonomic function are not known. This thesis tested the hypothesis that changes in autonomic outflow across the adult age-span are related to cerebral cortex atrophy and function, and are sensitive to the effects of physical fitness. Study 1 demonstrated that advancing age impairs the heart rate (HR) response and modifies the cortical patterns associated with cardiovascular control during isometric handgrip (IHG), and is further exacerbated with coronary artery disease. The utility of aerobic exercise to prevent these age-related changes is not known. Study 2 revealed that lifelong, sustained aerobic training builds cortical reserve early in life, and sustains this benefit over the 40-70 year age span, but did not alter the rate of age-related cortical or subcortical decline. Study 3 demonstrated that cardiorespiratory fitness correlated strongly with whole-brain cortical thickness, while markers of autonomic outflow were specifically associated with cortical mass at the MPFC. Importantly, the strength of the relationship between autonomic variables and cortical thickness was determined by age, and was not altered following adjustments for cardiorespiratory fitness. Study 4 revealed a positive effect of high fitness on MPFC activation, yet did not affect absolute HR responses to IHG in this age range. Therefore, this series of studies implicates cortical atrophy in the frontal lobe as a contributor to the dysregulation of autonomic outflow associated with advancing age, and suggests that high cardiorespiratory fitness delays the age-related decline in cortical circuitry associated with cardiovascular control.