Structural and Functional Connectivity Substrates of Cognitive Impairment in Multiple Sclerosis

Abstract

Cognitive impairment (CI) occurs in 43 to 70% of multiple sclerosis (MS) patients at both early and later disease stages. Cognitive domains typically involved in MS include attention, information processing speed, memory, and executive control. The growing use of advanced magnetic resonance imaging (MRI) techniques is furthering our understanding on the altered structural connectivity (SC) and functional connectivity (FC) substrates of CI in MS. Regarding SC, different diffusion tensor imaging (DTI) measures (e.g., fractional anisotropy, diffusivities) along tractography-derived white matter (WM) tracts showed relevance toward CI. Novel diffusion MRI techniques, including diffusion kurtosis imaging, diffusion spectrum imaging, high angular resolution diffusion imaging, and neurite orientation dispersion and density imaging, showed more pathological specificity compared to the traditional DTI but require longer scan time and mathematical complexities for their interpretation. As for FC, task-based functional MRI (fMRI) has been traditionally used in MS to brain mapping the neural activity during various cognitive tasks. Analysis methods of resting fMRI (seed-based, independent component analysis, graph analysis) have been applied to uncover the functional substrates of CI in MS by revealing adaptive or maladaptive mechanisms of functional reorganization. The relevance for CI in MS of SC–FC relationships, reflecting common pathogenic mechanisms in WM and gray matter, has been recently explored by novel MRI analysis methods. This review summarizes recent advances on MRI techniques of SC and FC and their potential to provide a deeper understanding of the pathological substrates of CI in MS.

An investigation of the association between focal damage and global network properties in cognitively impaired and cognitively preserved patients with multiple sclerosis

“…Adding to previous knowledge (Charalambous et al, 2019;Welton et al, 2020;Zhang et al, 2021), we also provide evidence that information processing speed is related to global network properties in both HC and pwMS. The correlations varied between groups (Figure 3) with the strongest associations with SDMT and clustering coefficient, efficiency, and mean strength in CIMS compared to the whole patient group and HCs.…”

Applying multilayer analysis to morphological, structural, and functional brain networks to identify relevant dysfunction patterns

“…The atrophy of deep GM areas occurs in early stages of MS, and extends to multimodal cortical regions over time ( Eshaghi et al, 2018 ; Solana et al, 2021 ). In this context, we demonstrated that the network metrics applied to the new multilayer framework can pick up relevant network alterations in MS in most deep GM and in some cortical regions involved in visual areas (bilateral occipital and lingual areas) and cognition ( Gabilondo et al, 2014 ; Riccitelli et al, 2020 ; Zhang et al, 2021 ). The frontal, temporal, and parietal lobes of MS patients are closely associated with new lesions in the first 10 years ( Wybrecht et al, 2017 ).…”

“…The frontal, temporal, and parietal lobes of MS patients are closely associated with new lesions in the first 10 years ( Wybrecht et al, 2017 ). Furthermore, graph theory measures point out that the most atypical patterns in interconnected multilayer networks in MS stem from a weaker topological centrality (measure of degree and strength) and integrity (closeness centrality) measures, and increasing segregation (local efficiency) of node neighbors ( Riccitelli et al, 2020 ; Zhang et al, 2021 ). However, the overall connectivity of the brain network in MS (betweenness centrality) patients is unchanged compared with HV, as reported previously ( Llufriu et al, 2017 ).…”

Coupling of brain activity and structural network in multiple sclerosis: A graph frequency analysis study

“…Meanwhile, recent neuroscientific investigations observed the contemporary presence of widespread reorganizations of brain functional activity in MS (Rocca et al, 2016; Tahedl et al, 2018). Aberrantly increased or decreased functional connectivity (FC) emerged on subcortical regions (i.e., the thalamus, amygdala, and basal ganglia) (Cui et al, 2017; Sbardella et al, 2017; Schoonheim et al, 2014) and the temporal gyrus (Bisecco et al, 2019; Liu et al, 2016) were suggested to exhibit both adaptive (preventing impairment) and maladaptive (worsening impairment) effects (Tahedl et al, 2018; Zhang et al, 2021). Together, evidences suggested that both brain structural network and functional activity played critical roles in MS‐related deficits.…”