Abstract
ObjectivesCognitive dysfunction is present in at least half of patients with Multiple Sclerosis. The purpose of this study was to examine functional connectivity abnormalities in patients with multiple sclerosis (MS) using resting state fMRI (rsfMRI).MethodsConventional MRI, rsfMRI and diffusion tensor imaging (DTI) data was acquired from 10 patients with relapsing-remitting multiple sclerosis (RRMS) and 20 healthy controls. Cross-correlation of the resting state average signal among the voxels in each brain region of the five cognitive networks: default mode network (DMN), attention, verbal memory, memory, and visuospatial working memory network, was calculated. Voxelwise analyses were used to investigate fractional anisotropy (FA) of white matter tracts. The normalized gray matter (GM), white matter and thalamus volumes were calculated.ResultsCompared to controls, significant deficit in MS patients at each of five networks, attention (p=0.026), DMN (p=0.004), verbal memory (p<0.001), memory (p=0.001), visuospatial working memory (p=0.003) was found. Significant reduction (p=0.034) in the normalized GM volume and asymmetry in thalamus volume (p=0.041) was detected in MS patients compared to controls.ConclusionWide spread of functional abnormalities are present within different cognitive networks in patients with RRMS, suggesting that DMN may not be sufficient for measurement of MS cognitive impairment. Larger and longitudinal studies should ascertain whether rsfMRI of cognitive networks and changes in GM and thalamus volume can be used as tools for assessment of cognition in clinical trials in MS.
Highlights
Multiple Sclerosis (MS) is a demyelinating disease of the central nervous system which affects more than 2.5 million individuals worldwide and is one of the most common causes of neurological disability in young adults
We previously reported a framework that we designed for studying changes in the functional connectivity network for stroke patients using resting state fMRI images [41]
In our preliminary study, decrease in functional connectivity was present within different cognitive networks in patients with relapsing-remitting multiple sclerosis (RRMS) along with asymmetry of the thalamus volume and atrophy of the cortical areas
Summary
Multiple Sclerosis (MS) is a demyelinating disease of the central nervous system which affects more than 2.5 million individuals worldwide and is one of the most common causes of neurological disability in young adults. Cognitive impairment is recognized in 40%70% of patients with MS [1,2] affecting multiple domains of cognition including attention [3], memory, and speed of information processing [4,5,6]. Over 50% of the patients with MS are unemployed within 10 years of diagnosis; and this is often attributed to a decline in cognition [7]. Memory decline in patients with MS may evolve steadily from the onset of the disease and is not correlated with standard magnetic resonance imaging (MRI) parameters of the disease or clinical disease activity (relapses) [14]. Cognitive impairment is seen in patients with disabling MS and in milder forms, so called “benign” MS [15]. Cognitive impairment is seen in patients with disabling MS and in milder forms, so called “benign” MS [15]. fMRI studies in MS have focused mainly on working memory, using a modified PASAT (Paced Auditory Serial Addition Test) or N-back test for mapping brain activity during the cognitive tasks [16,17,18,19] suggesting that there are different activation patterns in working memory in MS
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