| Cognitive decline is reported in 50-65% of multiple sclerosis (MS) patients and causes severe impairment of daily living activities. However, so far the underlying (patho)biology of these cognitive deficits is poorly understood. In an attempt to locate the cause of cognitive problems, previous research has focused predominantly on white matter (WM) abnormalities. General neuropsychological test outcomes were related to structural MRI measures, such as WM lesion loads and atrophy, but only weak correlations were found. With respect to cognitive decline, it may be more beneficial to examine the grey matter (GM), as it was shown that GM damage in MS is both frequent and extensive, and shows stronger correlations with neuropsychological abnormalities than WM damage. Furthermore, the issue of cognitive impairment has been mainly studied using a whole-brain approach in the past, whereas a region-of-interest approach may be more specific and powerful. As for selecting brain structures to ?zoom in? on, the hippocampus and thalamus are likely candidates: these structures are both known to be heavily involved in cognition. We therefore consider these structures to be promising targets for investigating cognitive decline, specifically memory impairment, in MS. To increase our understanding of the underlying pathobiology of memory impairment, we propose to study the (abnormal) structure and function of the hippocampus and thalamus with task-specific functional MRI (fMRI), diffusion tensor imaging (DTI), and specific neuropsychological testing. |
