Brain networks disconnection in early multiple sclerosis cognitive deficits: An anatomofunctional study

Abstract

Severe cognitive impairment involving multiple cognitive domains can occur early during the course of multiple sclerosis (MS). We investigated resting state functional connectivity changes in large-scale brain networks and related structural damage underlying cognitive dysfunction in patients with early MS. Patients with relapsing MS (3-5 years disease duration) were prospectively assigned to two groups based on a standardized neuropsychological evaluation: (1) cognitively impaired group (CI group, n = 15), with abnormal performances in at least 3 tests; (2) cognitively preserved group (CP group, n = 20) with normal performances in all tests. Patients and age-matched healthy controls underwent a multimodal 3T magnetic resonance imaging (MRI) including anatomical T1 and T2 images, diffusion imaging and resting state functional MRI. Structural MRI analysis revealed that CI patients had a higher white matter lesion load compared to CP and a more severe atrophy in gray matter regions highly connected to networks involved in cognition. Functional connectivity measured by integration was increased in CP patients versus controls in attentional networks (ATT), while integration was decreased in CI patients compared to CP both in the default mode network (DMN) and ATT. An anatomofunctional study within the DMN revealed that functional connectivity was mostly altered between the medial prefrontal cortex (MPFC) and the posterior cingulate cortex (PCC) in CI patients compared to CP and controls. In a multilinear regression model, functional correlation between MPFC and PCC was best predicted by PCC atrophy. Disconnection in the DMN and ATT networks may deprive the brain of compensatory mechanisms required to face widespread structural damage.

Functionally Relevant White Matter Degradation in Multiple Sclerosis: A Tract-based Spatial Meta-Analysis

“…Recent research explores the disconnection of widespread brain networks by other approaches 49,50 and is consistent with the structural disconnection phenomenon demonstrated here in suggesting that cognition may be mediated by brain networks' functional connectivity. For example, graph-theoretic analyses with fMRI 51,52 and EEG 53 have…”

The association between intra- and juxta-cortical pathology and cognitive impairment in multiple sclerosis by quantitative T 2 * mapping at 7 T MRI

“…Previous studies highlighted that atrophy in selective cortical areas, including frontal regions, precuneus and cingulate cortex is critical for cognition in MS (Louapre et al, 2014, Morgen et al, 2006, Nocentini et al, 2014, Riccitelli et al, 2011, Sbardella et al, 2013). The specificity of cortical atrophy as primary mechanism leading to MS cognitive impairment, however, can hardly be established, as cortical tissue loss may not necessarily result from local pathological processes, but also be the consequence of retrograde axonal degeneration from distant white matter (WM) lesions (Calabrese et al, 2015b).…”

Increased connectivity of hub networks and cognitive impairment in multiple sclerosis

“…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.…”

“…[1][2][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.…”