EXAMINING SINGLE-SUBJECT RELIABILITY OF FUNCTIONAL MAGNETIC RESONANCE IMAGING IN ESTABLISHED MULTIPLE SCLEROSIS

Abstract

Multiple sclerosis (MS) is the most common chronic inflammatory and neurodegenerative disease affecting the central nervous system. Conventional magnetic resonance imaging (MRI) has an invaluable role in the early diagnosis of MS. However, its use to monitor ongoing disease activity is less effective. This shortcoming is likely related to the limited sensitivity of conventional MRI to subclinical brain pathology and functional compensation. Functional MRI (fMRI) is more sensitive to these pathological changes, and may be of value in clinical settings to better characterize pathology and to monitor disease activity in established MS. A useful way to monitor disease activity in MS is assessing specific cognitive function, an important marker of neurological integrity. A few prior studies applied fMRI to monitor treatment effect in patients by using cognitive paradigms, however, intra-subject reliability of fMRI in MS has not been established. Consequently, we compared single-subject test-retest fMRI reliability between patients with MS and age-matched controls. For this purpose, we have chosen three paradigms based on their relevance in MS, the Symbol Digit Modalities Test (SDMT), the Poffenberger Task, and resting state (RS). The data were collected in three sessions a week apart. Our results showed relatively high and stable cluster overlap reliability (COR) for controls. Further, COR values were overall higher for controls compared to patients. This was particularly true for brain regions which comprise white matter. We also detected associations between disability scores (i.e. Extended Disease Status Scale) and COR, and between COR of RS and reaction time and accuracy (i.e. information processing speed) collected during the SDMT and from the Poffenberger Task. Similar to previous findings, we also observed larger recruited brain areas and inferior cognitive performance in patients compared to controls in response to the tasks. Our data obtained from controls suggest that adequate short-term fMRI reliability can be achieved. Conversely, the instability of COR seen in patients indicates that COR itself could be used as a marker of neuronal integrity in MS. Although there is much work ahead, our results are promising in view of implementing fMRI as a monitoring tool in clinical care of MS.