INTRA-INDIVIDUAL VARIABILITY IS AN IMPORTANT CHARACTERISTIC OF COGNITIVE FUNCTIONING IN PERSONS WITH MULTIPLE SCLEROSIS

Abstract

Cognitive deficits are highly prevalent in multiple sclerosis (MS) and have a negative impact on daily life. Impairments in information processing speed are among the most commonly reported deficits in MS and are generally assessed by evaluating mean-level performance on time-limited tests. However, this approach to assessing performance ignores potential within-subject differences that may be useful for characterizing cognitive difficulties in MS. An alternative method of measuring performance on timed cognitive tasks is to examine the degree of within-subject variability, termed intraindividual variability (IIV). IIV provides information about the characteristics of an individual’s performance and may provide novel information about cognitive functioning in MS and other neurodegenerative disorders. The research presented in this dissertation examined IIV in performance as an indicator of cognitive functioning in persons with MS and explored the relations of performance variability to measures of neuronal connectivity derived from resting state functional magnetic resonance imaging (rsfMRI). Individuals with MS were found to be both slower and more variable on tests of information processing speed and attention. This variability was observed even when controlling for sensorimotor confounds and other systematic variables that may influence variability, such as practice and learning effects. IIV in performance was found to better distinguish MS patients from matched groups of healthy control subjects when compared to common clinical measures of cognitive performance or average response speed. These differences in IIV were also found consistently across six monthly assessments in a group with MS who remained clinically stable over this period. This stability in IIV suggests its feasibility as a measure of changes in longitudinal cognitive or clinical status. Using rsfMRI, greater stability in performance (i.e., lower IIV) was associated with greater functional connectivity between frontal lobe regions (i.e., ventral medial prefrontal cortex and frontal pole) in persons with MS. This increased connectivity appears to represent potential compensatory processes within mildly affected MS individuals. Together the findings demonstrate that IIV is an important characteristic of cognitive performance that may provide new insights into the cognitive deficits present in MS.