The healthy controls (HC) will serve as reference comparison group to patients for atrophy iron, cognitive and response to herpesvirus outcomes. We considered alternative study designs as listed below. The head-to-head comparison with untreated or comparator-treated patients are difficult to conduct and can not be performed without proper randomization and double-blinding which is costly and unfeasible in mechanistical study like is the one proposed. The inclusion of a HC group provides a valuable baseline, allowing evaluation of the proposed techniques for normal variation between individuals, against which changes in the proposed outcomes could be compared. Use of HCs for comparison with a patient population in prospective longitudinal pilot studies of non-conventional MRI, including measurement of thalamic atrophy and iron deposition, may become an attractive approach in the future for several reasons. First, the ultimate goal of therapy is to normalize patient changes over time, to those observed in HCs over the same time period. HCs also experience brain changes over time and so the notion of arresting disease progression as measured by proposed outcomes requires validation by reference to a comparator without disease progression to account for age-related changes. Second, ethical considerations preclude placebo-controlled studies using an established MS treatment versus placebo-treatment in patients with RRMS.