Enhanced Recruitment During Executive Control Processing in Cognitively Preserved Patients With Pediatric-Onset MS

Objectives: Youth and young adults with pediatric-onset multiple sclerosis (MS) are vulnerable to executive dysfunction; however, some patients do not demonstrate functional deficits despite showing abnormalities on structural magnetic resonance imaging (MRI). Cognitively intact adults with MS have shown enhanced activation patterns relative to healthy controls on working memory tasks. We aim to evaluate whether cognitively preserved pediatric-onset MS patients engage compensatory recruitment strategies to facilitate age-normative performance on a task of working memory. Methods: Twenty cognitively preserved patients (mean age=18.7 +/- 2.7 years; 15 female) and 20 age- and sex-matched controls (mean age=18.5 +/- 2.9 years; 15 female) underwent neuropsychological testing and 3.0 Tesla MRI, including structural and functional acquisitions. Patterns of activation during the Alphaspan task, a working memory paradigm with two levels of executive control demand, were examined via whole-brain and region of interest (ROI) analyses. Results: Across all participants, lower accuracy and greater activation of regions implicated in working memory were observed during the high demand condition. MS patients demonstrated 0.21 s longer response time than controls. ROI analyses revealed enhanced activation for pediatric-onset MS patients relative to controls in the right middle frontal, left paracingulate, right supramarginal, and left superior parietal gyri during the low executive demand condition, over and above differences in response time. MS patients also demonstrated heightened activation in the right supramarginal gyrus in the high executive demand condition. Conclusions: Our findings suggest that pediatric-onset MS patients may engage compensatory recruitment strategies during working memory processing. (JINS, 2019, 25, 432-442)