Objective: Cognitive slowing is a core neuropsychological symptom of Multiple Sclerosis (MS). We aimed to assess the extent to which cognitive slowing in MS was predicted by changes in dorsolateral prefrontal networks. Method: We assessed patients with relapsing-remitting MS and healthy controls (HCs) on measures of processing speed. Participants underwent a functional MRI while performing a processing speed task to allow assessment of task-based connectivity. Results: Patients were slower than HCs on the processing speed tasks. Patients showed attenuated connectivity between right and left dorsolateral prefrontal cortex (DLPFC) and task-relevant brain regions compared to HCs during processing speed task performance. Patients’ connectivity with DLPFC in these group-disparate networks accounted for significant variability in their performance on processing speed measures administered both in and out of the imaging environment. Specifically, patients who had stronger functional connections with DLPFC in group-disparate networks performed faster than patients with weaker connections with DLPFC in group-disparate networks. Conclusion: Results suggest that MS-related cognitive slowing can be accounted for by systemic alterations in executive functional networks.
