Microstructure of the residual corticofugal projection from primary motor cortex in chronic stroke

Movement dysfunction after stroke is largely due to the inability of cortical motor neurons to activate spinal motor neurons via transmission of descending motor commands along the corticofugal projection from the primary motor cortex. Pathophysiological processes that ensue following injury have mostly resolved and white matter volume within the remodelled tract has mostly stabilized by the chronic stage many months to years after symptom onset. Where along the cranial course of the residual corticofugal projection white matter microstructure explains potential to activate muscles weakened by stroke at this stage is still not well understood. Here, diffusion spectrum imaging was used to reconstruct the descending corticofugal projection and quantify its microstructure in stroke survivors (n = 25) with longstanding hand impairment (7.7 ± 6.5 years). Portions of the residual tract overlapping with abnormalities on structural images were defined as the 'Overlap' compartment, and portions above and below this compartment were defined as 'Rostral' and 'Caudal' compartments, respectively. Maximal precision grip force and size of motor-evoked potentials elicited by transcranial magnetic stimulation were used to quantify activation of paretic hand muscles. Coherence of fibre anisotropy and directional diffusivities between tracts in either cerebral hemisphere was reduced in stroke survivors relative to neurologically-intact controls, with most abnormal asymmetries observed in the 'Overlap' compartment. While differences in fibre anisotropy and diffusivity between residual and intact tracts were detected most prominently in the 'Overlap' compartment, the overall magnitude of unrestricted diffusion within the 'Caudal' compartment was most closely linked to paretic muscle activation. The ability of cortical motor neurons to access spinal motor neuron pools long after stroke onset is therefore associated with microstructural integrity in portions of the residual corticofugal projection subject to secondary degeneration. These findings expand knowledge on white matter adaptation in response to neurological injury and may inform applications that seek to reverse brain pathology long after stroke onset when movement dysfunction tends to persist.