BackgroundFew studies of cognitive rehabilitation in multiple sclerosis (MS) have targeted working memory specifically.ObjectiveWe examined the effects of n-back working memory training on cognitive performance and brain function in patients with MS.MethodsPatients with MS (n = 12) and healthy controls (HC; n = 12) underwent 20 sessions of n-back working memory training. Before and after training (pre- and posttest) cognitive event-related potential (ERP) measures were obtained during a 3-back task. In addition, a battery of cognitive tests was administered.ResultsFollowing n-back training, both MS patients and HCs showed significant improvement on tests of working memory, processing speed, complex attention, and reasoning ability. MS and HCs also exhibited an enhancement of N2 ERP component amplitude, and earlier N2 and P3 latencies, following n-back training.ConclusionsTargeted training of working memory with the n-back task may improve cognitive function in MS. Enhancement of N2 ERP component amplitude and shorter N2 and P3 latency following training in patients with MS is consistent with plasticity of neural processes that are involved in working memory.

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Multiple sclerosis (MS), a central nervous system (CNS) neurodegenerative disorder, involves lesions of both white and gray matter and reported cognitive impairments that include processing speed (PS), executive function, and working memory (WM). This study closely examined the specifics of these cognitive deficits and their relationship to structural brain damage. A visual n-back task with 3 WM load conditions was used to assess WM performance (task accuracy), PS (reaction time, RT), and a novel measure of processing efficiency (standard deviation of RT, RTSD) in MS patients and controls. These behavioral measures were related to quantitative magnetic resonance imaging (MRI) measures of white and gray matter integrity. Even when MS patients performed as well as controls, as seen for low WM load (0-back), they responded more slowly and were less efficient in their speed of responding. Accuracy findings indicated that the correct match trials were superior to correct nonmatch trials at differentiating MS patients from controls. Further, decreased accuracy during the highest WM load condition was associated with global damage that included both gray and white matter atrophy, while slowed PS and particularly processing inefficiency were associated primarily with white matter atrophy in MS. Importantly, relationships between PS, processing efficiency, performance accuracy, and structural MRI measures were seen only during the highest WM load condition, the condition that required the most executive control. These findings suggest that the MRI/behavioral relationships that were present exclusively during the 2-back condition may reflect connectivity involving frontal cortical systems, the site for executive control.