UC Irvine

Ten patients with a definite diagnosis of multiple sclerosis and complaints of "fatigue" were studied using (1) reaction times and event-related potentials accompanying the performance of auditory memory tasks (target detection, verbal short-term memory) and (2) motor conduction velocities of the pyramidal tract elicited by cerebral and cervical magnetic stimulation. Patients were studied when "rested" and when fatigued. Reaction times of the patients when rested were significantly delayed in the short-term memory but not the target-detection tasks when compared with normal controls. When patients were fatigued, their reaction times became significantly longer in all tasks compared with when they were rested. Event-related potentials in these tasks consist of N1/P2 sensory components and P3a and P3b cognitive components. The N1 component latency was longer and P3a and P3b amplitudes were reduced in patients compared with controls. Fatigue in patients with multiple sclerosis was accompanied by a shortening of P3a latency and an increase in P3a and P3b amplitudes compared with these measures when patients were rested. Pyramidal tract conduction velocities did not differ between rested and fatigued conditions. Thus, fatigue in patients with multiple sclerosis was associated with a slowing of performance (reaction time) on memory tasks, whereas brain potentials reflecting neural events of stimulus encoding and classification were either unchanged or paradoxically speeded up in latency in the fatigued compared with the rested conditions. We postulate that, in patients with multiple sclerosis, fatigue affects neural processes acting after stimulus evaluation but before activation of the primary motor pathways.