Cognition in healthy aging and Parkinson's disease : structural and functional integrity of neural circuits

Abstract

This dissertation documents how healthy aging and Parkinson's disease (PD) affect brain anatomy and physiology and how these neural changes relate to measures of cognition and perception. While healthy aging and PD are both accompanied by a wide-range of cognitive impairments, the neural underpinnings of cognitive decline in each is likely mediated by deterioration of different systems. The four chapters of this dissertation address specific aspects of how healthy aging and PD affect the neural circuits that support sensory processes and high-level cognition. The experiments in Chapters 2 and 3 examine the effects of healthy aging on the integrity of neural circuits that modulate cognitive control processes. In Chapter 2, we test the hypothesis that the patterns of age-related change differ between white matter and gray matter regions, and that changes in the integrity of anterior regions correlate most strongly with performance on cognitive control tasks. In Chapter 3, we build upon the structural findings by examining the hypothesis that age-related changes in white matter integrity are associated with disrupted oscillatory dynamics observed during a visual search task. Chapter 4 investigates healthy age-related changes in somatosensory mu rhythms and evoked responses and uses a computational model of primary somatosensory cortex to predict the underlying cellular and neurophysiolgical bases of these alterations. In contrast to the widespread cortical changes seen in healthy OA, the cardinal motor symptoms of PD are largely explained by degeneration of the dopaminergic substantia nigra, pars compacta (SNc). Cognitive sequelae of PD, however, likely result from disruptions in multiple neurotransmitter systems, including nondopaminergic nuclei, but research on these aspects of the disease has been hindered by a lack of sensitive MRI biomarkers for the affected structures. Chapter 5 presents new multispectral MRI tools that visualize the SNc and the cholinergic basal forebrain (BF). We applied these methods to test the hypothesis that degenerative processes in PD affect the SNc before the BF. This experiment lays important groundwork for future studies that will examine the relative contribution of the SNc and BF to cognitive impairments in PD.