Abnormal adaptation over time of motor network recruitment in multiple sclerosis patients with fatigue.
Using functional magnetic resonance imaging (fMRI) during a motor task, we investigated the functional correlates of central fatigue in multiple sclerosis (MS), and adaptation of motor network recruitment during a prolonged effort.



Motor fMRI was obtained from 79 MS patients (50 fatigued (F), 29 non-fatigued (nF)) and 26 matched healthy controls (HC). Cognitive and physical fatigue were rated using the Modified Fatigue Impact Scale (MFIS).



Compared to HC and nF patients, F-MS patients experienced reduced activations of the left middle temporal gyrus, left supplementary motor area (SMA), bilateral superior frontal gyrus, left postcentral gyrus and basal ganglia regions. They also showed increased activation of the right middle frontal gyrus (MFG). Time-modulation analysis showed a reduced activity of the SMA and right precentral gyrus, and increased activity of the basal ganglia in HC. Such a trend was impaired in F-MS patients. In MS patients, increased MFG activity was related to MFIS scores. Physical MFIS score was related to a reduced recruitment of the right thalamus and SMA.



Abnormalities and impaired timing of activation between different areas of the motor and executive networks occur in F-MS patients. The dysfunction of critical cortical areas contributes to the occurrence of central fatigue.
Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Italy/Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Italy.
Maria A
MA
Rocca
Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Italy.
Alessandro
A
Meani
Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Italy.
Gianna C
GC
Riccitelli
Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Italy.
Bruno
B
Colombo
Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Italy.
Mariaemma
M
Rodegher
Department of Neuroradiology and CERMAC, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Italy.
Andrea
A
Falini
Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Italy.
Giancarlo
G
Comi
Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Italy/Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Italy filippi.massimo@hsr.it.
Massimo
M
Filippi
D000222:Adaptation, Physiological; D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001931:Brain Mapping / Q000379:methods; D016022:Case-Control Studies; D003071:Cognition; D056344:Executive Function; D005221:Fatigue / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology* / Q000523:psychology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D009046:Motor Neurons; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000523:psychology; D009483:Neuropsychological Tests; D011999:Recruitment, Neurophysiological; D013997:Time Factors
Multiple sclerosis; cognitive fatigue; fMRI; motor network adaptation; physical fatigue