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Objective: To investigate if changes in brain network function and connectivity contribute to the abnormalities in visual event related potentials (ERP) in relapsing-remitting multiple sclerosis (RRMS), and explore their relation to a decrease in cognitive performance., Methods: We evaluated 72 patients with RRMS and 89 healthy control subjects in a cross-sectional study. Visual ERP were generated using illusory and non-illusory stimuli and recorded using 21 EEG scalp electrodes. The measured activity was modelled using Dynamic Causal Modelling. The model network consisted of 4 symmetric nodes including the primary visual cortex (V1/V2) and the Lateral Occipital Complex. Patients and controls were tested with a neuropsychological test battery consisting of 18 cognitive tests covering six cognitive domains., Results: We found reduced cortical connectivity in bottom-up and interhemispheric connections to the right lateral occipital complex in patients (p < 0.001). Furthermore, interhemispherical connections were related to cognitive dysfunction in several domains (attention, executive function, visual perception and organization, processing speed and global cognition) for patients (p < 0.05). No relation was seen between cortical network connectivity and cognitive function in the healthy control subjects., Conclusion: Changes in the functional connectivity to higher cortical regions provide a neurobiological explanation for the changes of the visual ERP in RRMS., Significance: This study suggests that changes in connectivity to higher cortical regions partly explain visual network dysfunction in RRMS where a lower interhemispheric connectivity may contribute to impaired cognitive function., (Copyright © 2019. Published by Elsevier B.V.)

Background: Cognitive impairment in multiple sclerosis (MS) is common and has severe implications. Natalizumab (NZ) has documented effects on relapse rate and radiological disease activity in relapsing-remitting MS (RRMS) but studies regarding its specific effects on cognitive functioning are few. Previous studies have reported improvement, however, often lacking relevant control groups. The objective of the present study was to evaluate the cognitive effects of NZ treatment, compared to patients on stable first-line treatment and healthy control subjects., Methods: MS patients starting NZ (MS-NZ), MS controls with stable interferon beta therapy (MS-C) and healthy control subjects (HC) were evaluated twice with one year interval, using a cognitive test battery covering six cognitive domains. The effects of NZ on levels of self-reported depression, fatigue, daytime sleepiness and perceived health were also examined., Results: MS patients (MS-NZ and MS-C) had significantly lower baseline cognitive performance compared to HC (global score, p=0.002), but there were no significant differences between MS-NZ and MS-C. At follow-up, both MS-NZ and MS-C had improved significantly in four and five cognitive domains, respectively, and in global score (p=0.013 and p<0.001, respectively). HC improved significantly in three cognitive domains but not in global score. A regression analysis including baseline cognitive z-score and z-score change showed that participants with lower baseline scores had a significantly greater improvement, compared to those with better initial performance (p=0.021). There were no significant changes in depression, fatigue, daytime sleepiness or perceived health in MS-NZ or MS-C., Conclusions: Initiation of NZ therapy did not result in true cognitive improvement over one year. Presumably, the increased test performance in both MS groups was artificial and due to retest effects that were stronger in patients with lower baseline performance. Adequate control groups are essential when evaluating cognitive functioning in intervention trials among RRMS patients., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: To explore if cognitive impairment in relapsing-remitting multiple sclerosis (RRMS) is associated with abnormal neural function and if there is evidence of neural compensatory mechanisms., Methods: Seventy-two RRMS patients and 89 healthy control subjects were included in a cross-sectional study. Event-related brain potential (P300) and response time (RT) were recorded with visual and auditory choice reaction tasks. Cognitive function was evaluated with an 18 item test battery., Results: Patients had a decrease in cognitive function (p<0.001 for global score) and increased visual P300 amplitude frontally. P300 amplitude was normal in other brain areas and RT was normal. P300 latency was normal except for an increase in auditory latency occipitally. Cognitive performance correlated positively with parietal P300 amplitude in patients but not in controls. Cognition had stronger correlation (negative) with RT in patients than in controls., Conclusions: Patients with low P300 amplitude and long RT were more often cognitively impaired. This indicates that general factors such as signal amplitude and speed are limiting for cognitive function in RRMS patients. The increase in frontal P300 amplitude may be a compensatory effect., Significance: Our findings suggest that high amplitude and fast speed may be protective against cognitive impairment., (Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)