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Brain activation patterns and cognitive processing speed in patients with pediatric-onset multiple sclerosis

ABSTRACT Objective: This study aimed to determine the extent and pattern of brain activation elicited by a functional magnetic resonance imaging version of the Symbol Digit Modalities Test (fMRI–SDMT), a task of information processing speed, in pediatric-onset multiple sclerosis (MS) patients as compared to sex- and age-matched non-MS self-reported healthy individuals. Method: Participants included 20 right-handed individuals aged 13–24 years with pediatric-onset MS (mean age = 19 years, 15 female) and 16 non-MS self-reported healthy individuals. All participants underwent a 3.0-tesla MRI scan with structural (T1; T2; proton density, PD; fluid-attenuated inversion recovery, FLAIR) and fMRI–SDMT acquisition. Participants were instructed to indicate with a button press whether a single pairing of a symbol to a number matched any of those shown in a key that displays nine possible pairings. Results: Response time (p = .909) and accuracy (p = .832) on the fMRI–SDMT did not differ between groups. However, the MS group demonstrated lower overall activation than the non-MS group in the right middle frontal gyrus (p = .003). Within the MS group, faster response time was associated with greater activation of the right inferior occipital, anterior cingulate, right superior parietal, thalamus, and left superior occipital cortices (all p < .05). A significant interaction effect was demonstrated, indicating that faster response time was associated with greater activation of the left superior occipital region in the pediatric MS group than in the non-MS group (p = .002). Conclusions: Attenuated activation of frontal regions was observed in this cohort of pediatric-onset MS patients when performing the fMRI–SDMT, even in the absence of behaviorally detectable deficits. Within the MS group only, faster response time elicited greater activation, suggesting this to be an adaptive mechanism that may contribute to limiting the impact of disease-related structural pathology.