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: May 2022

Anisotropy of descending motor pathways has repeatedly been linked to the severity of motor impairment following stroke-related damage to the corticospinal tract (CST). Despite promising findings consistently tying anisotropy of the ipsilesional CST to motor outcome, anisotropy is not yet utilized as a biomarker for motor recovery in clinical practice as a conclusive understanding of degenerative processes in the ipsilesional CST and compensatory roles of other descending motor pathways is hindered by methodological constraints such as estimating anisotropy in voxels with multiple fiber directions, sampling biases, and confounds due to aging-related atrophy. The present study addressed these issues by combining diffusion spectrum imaging (DSI) with a novel compartmentwise analysis approach differentiating voxels with one dominant fiber direction (one-directional voxels) from voxels with multiple fiber directions. Compartmentwise anisotropy for bihemispheric CST and extrapyramidal tracts was compared between chronic stroke patients (N=25), age-matched controls (N=22), and young controls (N=24) and its associations with motor performance of the upper and lower limbs were assessed. Our results provide direct evidence for Wallerian degenration along the entire length of the ipsilesional CST reflected by decreased anisotropy in descending fibers compared to age-matched controls, while aging-related atrophy was observed more ubiquitously across compartments. Anisotropy of descending ipsilesional CST voxels showed a highly robust correlation with various aspects of upper and lower limb motor impairment, highlighting the behavioral 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 fibers crossing the midline, fibers potentially mitigating output from brain stem nuclei, and fibers 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 CST lesions, while fine motor control of the paretic hand critically relies on ipsilesional CST 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 CST 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 develop diffusion imaging biomarkers for specific motor functions after stroke.