| Multiple Sclerosis, a neurodegenerative disease of the central nervous system currently affects about 1,000,000 people worldwide. It is considered to be the second leading cause of physical disability in young adults and severely affects several aspects of functioning including physical, cognitive and emotional. This dissertation was conducted in an attempt to understand the nature of cognitive impairments seen in those with relapsing remitting multiple sclerosis (RRMS), the most prevalent sub-type of multiple sclerosis. Using both behavioral and neuroimaging techniques, I provide evidence of severe cognitive impairments in those with MS, most notably in the domains of motor functioning; memory and learning; and attention and executive functioning. Neuroimaging data was further used to understand the concomitant changes in brain activation patterns that might accompany the change in cognitive functioning. I found that individuals with MS recruit additional cortical resources in tasks that severely challenge the neural system, however in tasks with lower demands, MS individuals show comparable brain activation patterns relative to healthy controls. It was further noted that the functional connectivity of the task-relevant network and the default network in the absence of higher task demands was intact in those with MS. In addition to the study of functional alterations in the presence of MS, I also examined the structural decline in those with MS and its association with cardiorespiratory fitness; a lifestyle factor that is increasingly being recognized to have neuroprotective effects. Employing voxel-based techniques, I found that those with MS show significant global and regional gray matter atrophy, along with a reduction in fractional anisotropy values in anterior and posterior white matter tracts. Higher levels of aerobic fitness were associated with preserved gray matter and higher FA values in a number of cortical regions, which were further associated with better processing speed. The results of this cross-sectional study provides promising evidence for the existence of a relationship between fitness, cognition and structural indices of gray matter and white matter decline in MS. Future longitudinal studies will provide critical information on the role of exercise on preserved cognitive functioning of those with MS. |
