New Insights on the Pathophysiology of Fatigue in MS: A fMRI Study of the Motor Network (P6.141)

OBJECTIVE: We investigated the functional correlates of cognitive and motor fatigue in multiple sclerosis (MS) and the influence of disease duration on these findings. Adaptation of motor network recruitment during prolonged effort were also assessed. BACKGROUND: An abnormal recruitment of the network connecting the basal ganglia to the frontal lobes occurs in fatigued MS patients. DESIGN/METHODS: Motor fMRI was obtained from 79 MS patients (50 with fatigue [F] and 29 without fatigue [nF]) and 26 matched healthy controls (HC). The severity of cognitive and physical fatigue was rated using the Modified Fatigue Impact Scale (MFIS). Full factorial and multiple regression analyses were performed (SPM8). RESULTS:Compared with HC, nF and F-MS patients had increased activations of the right precentral gyrus, right inferior temporal gyrus (ITG) and bilateral cerebellum. Compared to HC and nF patients, F-MS patients had reduced activations of the left middle temporal gyrus, left supplementary motor area (SMA), bilateral superior frontal gyrus, left postcentral gyrus, left putamen and bilateral caudate nucleus. They also showed selective increased activation of the right middle frontal gyrus, which was mainly driven from F MS patients with disease duration longer than 5 years. HC showed a reduced activity of the SMA and right precentral gyrus and increased activity of the basal ganglia over time. Such a behaviour was significantly impaired in F MS patients. In MS patients, higher MFG activity was related to cognitive and physical MFIS score. Physical MFIS score was related to reduced activity within the right thalamus and SMA. CONCLUSIONS: Distributed abnormalities of activation and impaired timing of communication between different areas of the motor network occur in fatigued MS patients. The involvement of specific GM regions may contribute to explain differences between cognitive and motor fatigue. Study Supported by: The Italian Ministry of Health (GR-2008-1138784 and GR-2009-1529671).