TY - JOUR

T1 - Motor fatigue is associated with asymmetric connectivity properties of the corticospinal tract in multiple sclerosis

AU - Bauer, Christian

AU - Dyrby, Tim B.

AU - Sellebjerg, Finn

AU - Madsen, Kathrine Skak

AU - Svolgaard, Olivia

AU - Blinkenberg, Morten

AU - Siebner, Hartwig Roman

AU - Andersen, Kasper Winther

PY - 2020

Y1 - 2020

N2 - Multiple Sclerosis (MS) is characterized by demyelination and neurodegeneration of the central nervous system and causes excessive fatigue in more than 80% of the patients. The pathophysiologic mechanisms causing fatigue are still largely unknown. In 46 right-handed patients with relapsing-remitting MS and 25 right-handed controls, we performed diffusion MRI and applied streamline based probabilistic tractography to derive unilateral anatomical connectivity maps for the white matter of the right and left hemispheres. The maps provide an indication how often a streamline has passed through a given voxel. Since tractography based anatomical connectivity mapping (ACM) is sensitive to disease-induced changes in anatomical connectivity, we used ACM to test whether motor fatigue is associated with altered ipsi-hemispherical anatomical connectivity in the major motor output pathway, the corticospinal tract (CST). Patients had higher mean ACM values in the CST than healthy controls. This indicated that a higher number of streamlines, starting from voxels in the same hemisphere, travelled through the CST and may reflect an accumulated disease-induced disintegration of CST. The motor subscale of the Fatigue Scale for Motor and Cognitive functions (FSMCMOTOR) was used to define sub-groups with (n = 29, FSMCMOTOR score ≥ 27) and without motor fatigue (n = 17, FSMSMOTOR score ≤ 26). Patients without fatigue only showed higher ACM values in right CST, while mean ACM values were unaltered in left CST. The higher the mean ACM values in the left relative to the right CST, the more patients reported motor fatigue. Left-right asymmetry in anatomical connectivity outside the CST did not scale with individual motor fatigue. Our results link lateralized changes of tractography-based microstructural properties in the CST with motor fatigue in relapsing-remitting MS.

AB - Multiple Sclerosis (MS) is characterized by demyelination and neurodegeneration of the central nervous system and causes excessive fatigue in more than 80% of the patients. The pathophysiologic mechanisms causing fatigue are still largely unknown. In 46 right-handed patients with relapsing-remitting MS and 25 right-handed controls, we performed diffusion MRI and applied streamline based probabilistic tractography to derive unilateral anatomical connectivity maps for the white matter of the right and left hemispheres. The maps provide an indication how often a streamline has passed through a given voxel. Since tractography based anatomical connectivity mapping (ACM) is sensitive to disease-induced changes in anatomical connectivity, we used ACM to test whether motor fatigue is associated with altered ipsi-hemispherical anatomical connectivity in the major motor output pathway, the corticospinal tract (CST). Patients had higher mean ACM values in the CST than healthy controls. This indicated that a higher number of streamlines, starting from voxels in the same hemisphere, travelled through the CST and may reflect an accumulated disease-induced disintegration of CST. The motor subscale of the Fatigue Scale for Motor and Cognitive functions (FSMCMOTOR) was used to define sub-groups with (n = 29, FSMCMOTOR score ≥ 27) and without motor fatigue (n = 17, FSMSMOTOR score ≤ 26). Patients without fatigue only showed higher ACM values in right CST, while mean ACM values were unaltered in left CST. The higher the mean ACM values in the left relative to the right CST, the more patients reported motor fatigue. Left-right asymmetry in anatomical connectivity outside the CST did not scale with individual motor fatigue. Our results link lateralized changes of tractography-based microstructural properties in the CST with motor fatigue in relapsing-remitting MS.

KW - Anatomical connectivity mapping

KW - Corticospinal tract

KW - Diffusion weighted imaging

KW - Lateralization index

KW - Left-right asymmetry

KW - Motor fatigue

KW - Multiple sclerosis (MS)

U2 - 10.1016/j.nicl.2020.102393

DO - 10.1016/j.nicl.2020.102393

M3 - Journal article

C2 - 32916467

AN - SCOPUS:85090329502

VL - 28

JO - NeuroImage: Clinical

JF - NeuroImage: Clinical

SN - 2213-1582

M1 - 102393

ER -