Background; Multiple sclerosis (MS) patients experience fatigue as a chronic symptom that decreases quality of life. Commonly, fatigue in MS patients is manifested as decreased motor function during or after physical activity and is associated with changes in brain metabolism. Objective: To determine brain activation patterns in MS patients and healthy controls during a simple motor task before and after fatiguing hand-grip exercise. Methods: Functional magnetic resonance imaging (fMRI) scans were conducted on 10 MS patients and 13 healthy controls during 4-finger flexion and extension in rested and fatigued states. Results: Before the fatigue protocol, MS patients had greater activation in the contralateral primary motor cortex, insula, and cingulate gyrus than controls. Following fatiguing exercise, controls showed increased activation of precentral gyrus and insula while patients did not show any activation increases and actually decreased activity to the insula. Conclusion: Results indicate that before fatiguing exercise, MS patients marshaled more brain activation compared to controls, which may represent functionally adaptive changes in response to demyelination. This increased activation may suggest that patients require more effort to perform even simple motor tasks, possibly because peripheral or central signals for fatigue are chronically enhanced. When fatigued further by muscle contraction, brain activation cannot be further increased.
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