Cerebellar and premotor activity during a non-fatiguing grip task reflects motor fatigue in relapsing-remitting multiple sclerosis

TY - JOUR

T1 - Cerebellar and premotor activity during a non-fatiguing grip task reflects motor fatigue in relapsing-remitting multiple sclerosis

AU - Svolgaard, Olivia

AU - Andersen, Kasper Winther

AU - Bauer, Christian

AU - Madsen, Kristoffer Hougaard

AU - Blinkenberg, Morten

AU - Selleberg, Finn

AU - Siebner, Hartwig Roman

PY - 2018/10

Y1 - 2018/10

N2 - Fatigue is a common and highly disabling symptom of multiple sclerosis. Patients experience an effort-independent general subjective feeling of fatigue as well as excessive fatigability when engaging in physical or mental activity. Previous research using functional magnetic resonance imaging (fMRI) has revealed heterogeneous findings, but some evidence implicates the motor system. To identify brain correlates of fatigue, 44 mildly impaired patients with relapsing-remitting multiple sclerosis and 25 age- and gender-matched healthy controls underwent functional magnetic resonance imaging at 3 Tesla, while they performed alternating blocks of rest and a non-fatiguing precision grip task. We investigated neural correlates of fatigue using the motor subscore of Fatigue Scale for Motor and Cognitive Functions (FSMCMOTOR) using the bilateral motor cerebellum, putamen, and dorsal premotor cortex as regions of interest. Patients and healthy controls performed the grip force task equally well without being fatigued. In patients, task-related activity in lobule VI of right motor cerebellum changed in proportion with individual FSMCMOTOR scores. In right dorsal premotor cortex, linear increases in activity across consecutive task blocks scaled with individual FSMCMOTOR scores in healthy controls, but not in patients. In premotor and dorsomedial prefrontal areas, patients were impaired at upscaling task-related activity the more they were affected by motor fatigue. The results support the notion that increased sensorimotor processing in the cerebellum contributes to the experience of motor fatigue and fatigability in multiple sclerosis. Additionally, downscaling of motivational input or sensorimotor processing in prefrontal and premotor areas may constitute an additional pathophysiological factor.

AB - Fatigue is a common and highly disabling symptom of multiple sclerosis. Patients experience an effort-independent general subjective feeling of fatigue as well as excessive fatigability when engaging in physical or mental activity. Previous research using functional magnetic resonance imaging (fMRI) has revealed heterogeneous findings, but some evidence implicates the motor system. To identify brain correlates of fatigue, 44 mildly impaired patients with relapsing-remitting multiple sclerosis and 25 age- and gender-matched healthy controls underwent functional magnetic resonance imaging at 3 Tesla, while they performed alternating blocks of rest and a non-fatiguing precision grip task. We investigated neural correlates of fatigue using the motor subscore of Fatigue Scale for Motor and Cognitive Functions (FSMCMOTOR) using the bilateral motor cerebellum, putamen, and dorsal premotor cortex as regions of interest. Patients and healthy controls performed the grip force task equally well without being fatigued. In patients, task-related activity in lobule VI of right motor cerebellum changed in proportion with individual FSMCMOTOR scores. In right dorsal premotor cortex, linear increases in activity across consecutive task blocks scaled with individual FSMCMOTOR scores in healthy controls, but not in patients. In premotor and dorsomedial prefrontal areas, patients were impaired at upscaling task-related activity the more they were affected by motor fatigue. The results support the notion that increased sensorimotor processing in the cerebellum contributes to the experience of motor fatigue and fatigability in multiple sclerosis. Additionally, downscaling of motivational input or sensorimotor processing in prefrontal and premotor areas may constitute an additional pathophysiological factor.

KW - Adult

KW - Brain/pathology

KW - Brain Mapping

KW - Case-Control Studies

KW - Cerebellum/diagnostic imaging

KW - Cognition

KW - Female

KW - Hand Strength/physiology

KW - Humans

KW - Image Processing, Computer-Assisted

KW - Magnetic Resonance Imaging

KW - Male

KW - Middle Aged

KW - Motor Cortex/diagnostic imaging

KW - Motor Skills

KW - Multiple Sclerosis, Relapsing-Remitting/pathology

KW - Muscle Fatigue

KW - Prefrontal Cortex/diagnostic imaging

KW - Psychomotor Performance/physiology

KW - Surveys and Questionnaires

KW - Young Adult

U2 - 10.1371/journal.pone.0201162

DO - 10.1371/journal.pone.0201162

M3 - Journal article

C2 - 30356315

SN - 1932-6203

VL - 13

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 10

M1 - e0201162

ER -