The role of corticospinal and extrapyramidal pathways in motor impairment after stroke
Authors: Paul Theresa , Cieslak Matthew , Hensel Lukas , Wiemer Valerie M , Grefkes Christian , Grafton Scott T , Fink Gereon R , Volz Lukas J 
Published: November 2022

Anisotropy of descending motor pathways has repeatedly been linked to the severity of motor impairment following stroke-related damage to the corticospinal tract. Despite promising findings consistently tying anisotropy of the ipsilesional corticospinal tract to motor outcome, anisotropy is not yet utilized as a biomarker for motor recovery in clinical practice as several methodological constraints hinder a conclusive understanding of degenerative processes in the ipsilesional corticospinal tract and compensatory roles of other descending motor pathways. These constraints include estimating anisotropy in voxels with multiple fibre directions, sampling biases and confounds due to ageing-related atrophy. The present study addressed these issues by combining diffusion spectrum imaging with a novel compartmentwise analysis approach differentiating voxels with one dominant fibre direction (one-directional voxels) from voxels with multiple fibre directions. Compartmentwise anisotropy for bihemispheric corticospinal and extrapyramidal tracts was compared between 25 chronic stroke patients, 22 healthy age-matched controls, and 24 healthy young controls and its associations with motor performance of the upper and lower limbs were assessed. Our results provide direct evidence for Wallerian degeneration along the entire length of the ipsilesional corticospinal tract reflected by decreased anisotropy in descending fibres compared with age-matched controls, while ageing-related atrophy was observed more ubiquitously across compartments. Anisotropy of descending ipsilesional corticospinal tract voxels showed highly robust correlations with various aspects of upper and lower limb motor impairment, highlighting the behavioural relevance of Wallerian degeneration. Moreover, anisotropy measures of two-directional voxels within bihemispheric rubrospinal and reticulospinal tracts were linked to lower limb deficits, while anisotropy of two-directional contralesional rubrospinal voxels explained gross motor performance of the affected hand. Of note, the relevant extrapyramidal structures contained fibres crossing the midline, fibres potentially mitigating output from brain stem nuclei, and fibres transferring signals between the extrapyramidal system and the cerebellum. Thus, specific parts of extrapyramidal pathways seem to compensate for impaired gross arm and leg movements incurred through stroke-related corticospinal tract lesions, while fine motor control of the paretic hand critically relies on ipsilesional corticospinal tract integrity. Importantly, our findings suggest that the extrapyramidal system may serve as a compensatory structural reserve independent of post-stroke reorganization of extrapyramidal tracts. In summary, compartment-specific anisotropy of ipsilesional corticospinal tract and extrapyramidal tracts explained distinct aspects of motor impairment, with both systems representing different pathophysiological mechanisms contributing to motor control post-stroke. Considering both systems in concert may help to develop diffusion imaging biomarkers for specific motor functions after stroke.