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.
Highlights
It has been nearly 150 years since Charcot described cognitive impairment (CI) in multiple sclerosis (MS) patients as “enfeeblement of memory” and “concepts formed slowly” [1]
Working memory can be measured by various cognitive tests such as Paced Auditory Serial Addition Test (PASAT) [9, 54], Letter–Number Sequencing, and Spatial Span subtests, and can be divided into two processing levels, namely, maintenance and manipulation [99]
Decreased fractional anisotropy (FA) along the left superior longitudinal fascicle, which is one of the major white matter (WM) tracts in the left frontoparietal network, correlated with lower working memory in Relapsing–remitting MS (RRMS), because of the disruption of the connections to the prefrontal regions implicated in this cognitive domain [102]
Summary
It has been nearly 150 years since Charcot described cognitive impairment (CI) in multiple sclerosis (MS) patients as “enfeeblement of memory” and “concepts formed slowly” [1]. CI in MS patients can affect multiple domains including attention, information processing speed (IPS), memory, and executive control [3, 4] and may be present since the early disease stages, being more prevalent in the progressive forms [5] (see Box 1 for a definition of MS phenotypes). In order to overcome the heterogeneity of CI in MS, some studies have proposed cognitive phenotypes, characterized by the prevalent impairment of a specific cognitive domain, based on predefined. Relapsing–remitting MS (RRMS) Presence of relapses with stable neurological disability in between them [14]. Secondary progressive MS (SPMS) Progressive course following an initial relapsing–remitting course [14]. Primary progressive MS (PPMS) Progressive course from disease onset [14]
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