Increased connectivity of hub networks and cognitive impairment in multiple sclerosis

Abstract

Objective: To investigate default-mode network (DMN) and frontoparietal network (FPN) dysfunction in cognitively impaired (CI) patients with multiple sclerosis (MS) because these networks strongly relate to cognition and contain most of the hubs of the brain.Methods: Resting-state fMRI and neuropsychological assessments were performed in 322 patients with MS and 96 healthy controls (HCs). Patients with MS were classified as CI (z score , 22.0 on at least 2 tests; n 5 87), mildly cognitively impaired (z score , 21.5 on at least 2 tests and not CI; n 5 65), and cognitively preserved (CP; n 5 180). Within-network connectivity, connectivity with the rest of the brain, and between-network connectivity were calculated and compared between groups. Connectivity values were normalized for individual means and SDs.Results: Only in CI, both the DMN and FPN showed increased connectivity with the rest of the brain compared to HCs and CP, with no change in within-or between-network connectivity. Regionally, this increased connectivity was driven by the inferior parietal, posterior cingulate, and angular gyri. Increased connectivity with the rest of the brain correlated with worse cognitive performance, namely attention for the FPN as well as information processing speed and working memory for both networks.Conclusions: In CI patients with MS, the DMN and FPN showed increased connectivity with the rest of the brain, while normal within-and between-network connectivity levels were maintained. These findings indicate that cognitive impairment in MS features disturbed communication of hub-rich networks, but only with the more peripheral (i.e., nonhub) regions of the brain. Patients with multiple sclerosis (MS) commonly experience cognitive decline, which is most likely driven by functional network changes. 1-3 Across neurologic disorders, changes in connectivity of especially the default-mode network (DMN) and frontoparietal network (FPN) have been linked to cognitive deficits. [4][5][6] This preferential relationship might be explained by the fact that these networks contain the majority of highly connected regions, commonly described as functional hubs. 7,8 In fact, such hub regions are essential for optimal cognitive function because they ensure efficient integration of information between different brain regions. 9 Previous studies have reported both increased 1,10,11 and decreased 3,12,13 global connectivity levels of the DMN and FPN in relation to cognitive dysfunction in MS. This creates confusion about how these functional connectivity changes, either increased or decreased, may actually influence cognition. 14 Apart from the directionality of these changes, it remains unclear whether these effects are due specifically to changes in within-network connectivity, connectivity with the rest of the brain, or changes in between-network connectivity.

Changes in structural network are associated with cortical demyelination in early multiple sclerosis

“…This reorganization could be a mechanism of the brain, serving to compensate for the damage occurring in the early stages of the disease. Similar results were found in functional MRI (fMRI) studies, showing increased connectivity in the default-mode network and the frontoparietal network in multiple sclerosis patients, as well as in patients with clinically isolated syndrome (De Stefano et al, 2003;Meijer et al, 2017) .…”

Staging of cortical and deep grey matter functional connectivity changes in multiple sclerosis

“…Only positive correlation coefficients were entered in the connectivity matrix while negative correlation coefficients were set to zero given the controversial nature of negative connectivity values 15 16. Relative connectivity scores were computed based on the mean and SD of an individual functional connectivity matrix 12. This step was chosen to be able to look at the ranking of each brain region within its individual brain network and thereby correcting for global intersubject variability in mean connectivity.…”

Frontoparietal connectivity correlates with working memory performance in multiple sclerosis

“…In summary, in spite of a high incidence of cognitive deficits multiple sclerosis and a large body of literature investigating cognitive dysfunction, the specific oscillatory features that drive cognitive deterioration in multiple sclerosis remain unclear (Meijer et al, 2017). Hence, our results demonstrate a specific electrophysiological mechanism underlying the WM deficit in Patients with Multiple Sclerosis.…”