Lesion location changes the association between brain excitability and motor skill acquisition post-stroke

Abstract Background The capacity to reacquire motor skills lost after a stroke is crucial to promote upper-limb motor recovery but the impact of lesion location on motor skill acquisition and the underlying neurophysiological mechanisms remain uncertain. Methods We used transcranial magnetic stimulation to investigate associations between excitatory and inhibitory cortico-spinal excitability measures and the capacity to acquire a novel motor skill with the most affected hand in 103 individuals with cortical (n=34) or subcortical (n=69) lesions. Results Both groups showed similar motor skill acquisition, but subcortical lesions exhibited more impairment in the most affected hand and lower excitability in the ipsilesional hemisphere. In cortical lesions, motor skill acquisition was associated with lower motor thresholds (β=-0.25, 95% CI [−0.47,-0.03]; p=0.024) and higher intracortical inhibition (β=-3.93, 95% CI [−6.89,-0.98]; p=0.011) in the ipsilesional hemisphere. In contrast, in subcortical lesions motor skill acquisition was associated with smaller motor evoked potentials (β=-4.46, 95% CI [−8.54,-0.38]; p=0.033), less intracortical inhibition (β=3.45, 95% CI [0.34,6.56]; p=0.030) and higher facilitation (β=1.34,95% CI [0.15,2.54]; p= 0.028) ipsilesionally. Sensitivity analyses revealed that associations with intracortical inhibition and facilitation in the subcortical group were driven by lesions affecting the corticospinal tract. No associations were found in the contralesional hemisphere. Conclusions Reinforcing the existence of lesion-specific neurophysiological patterns, individuals with cortical and subcortical lesions show divergent associations between cortico-spinal excitability and motor skill acquisition. The use of cortico-spinal excitability as a biomarker to predict upper-limb recovery post-stroke or guide motor recovery interventions such as non-invasive brain stimulation should consider lesion location.