Corticospinal recruitment of spinal motor neurons in human stroke survivors

Key points Muscle weakness after stroke results from damage to corticospinal fibres that structurally and functionally connect cerebral cortex to the spinal cord. Here, we show an asymmetry in corticospinal recruitment of spinal motor neurons that is linked to maximal voluntary output of hand muscles weakened by stroke. Spike timing-dependent plasticity of synapses between corticospinal and spinal motor neurons transiently reversed recruitment failures in some survivors. These modulatory effects were strongly associated with recruitment asymmetry and hand impairment. Our findings highlight the functional relevance of spinal motor neuron recruitment by corticospinal inputs and the viability of corticospinal motor neuronal synapses for restoring activation of lower motor neurons after stroke. Corticospinal input to spinal motor neurons is structurally and functionally altered by hemiparetic stroke. The pattern and extent to which corticospinal recruitment of spinal motor neurons is reorganized and whether such changes are linked to the severity of motor impairments is not well understood. Here, we performed experiments using the triple stimulation technique to quantify corticospinal recruitment of spinal motor neurons serving paretic and non-paretic intrinsic hand muscles of humans with longstanding motor impairment secondary to stroke (n = 13). We also examined whether recruitment failures could be transiently reversed by strengthening corticospinal-motoneuronal synaptic connectivity via targeted, temporally controlled non-invasive stimulation to elicit spike timing-dependent plasticity (STDP). Asymmetries were detected in corticospinal recruitment of spinal motor neurons, central conduction time and motor-evoked potential (MEP) latency. However, only recruitment asymmetry correlated with maximal voluntary motor output from the paretic hand. STDP-like effects were observed as an increase in spinal motor neuron recruitment. Control experiments to isolate the locus of plasticity demonstrated a modulation in MEPs elicited by electrical stimulation of primary motor cortex but not F-wave size or persistence, suggesting that plasticity was mediated through enhanced efficacy of residual corticospinal-motor neuronal synapses. The modulation in recruitment was strongly associated with baseline recruitment asymmetry and impairment severity. Our findings demonstrate that asymmetry in corticospinal recruitment of spinal motor neurons is directly related to impairments experienced by stroke survivors. These recruitment deficits may be partially and transiently reversed by spike timing-dependent plasticity of synapses between upper and lower motor neurons in the spinal cord, downstream of supraspinal circuits damaged by stroke.

Automated summary

The asymmetry in corticospinal recruitment of spinal motor neurons post-stroke is directly correlated with hand impairments. Spike timing-dependent plasticity can transiently reverse recruitment failures, and this modulation is strongly associated with recruitment asymmetry and impairment severity.