Activity-dependent competition shapes corticospinal (CS) axon outgrowth in the spinal cord during development. An important question in neural repair is whether activity can be used to promote outgrowth of CS axons in maturity. After injury, spared CS axons sprout and make new connections, but often not enough to restore function. We propose that electrically stimulating spared axons after injury will enhance sprouting and strengthen connections with spinal motor circuits. To study the effects of activity, we electrically stimulated CS tract axons in the medullary pyramid. To study the effects of injury, one pyramid was lesioned. We studied sparse ipsilateral CS projections of the intact pyramid as a model of the sparse connections preserved after CNS injury. We determined the capacity of CS axons to activate ipsilateral spinal motor circuits and traced their spinal projections. To understand the separate and combined contributions of injury and activity, we examined animals receiving stimulation only, injury only, and injury plus stimulation. Both stimulation and injury alone strengthened CS connectivity and increased outgrowth into the ipsilateral gray matter. Stimulation of spared axons after injury promoted outgrowth that reflected the sum of effects attributable to activity and injury alone. CS terminations were densest within the ventral motor territories of the cord, and connections in these animals were significantly stronger than after injury alone, indicating that activity augments injury-induced plasticity. We demonstrate that activity promotes plasticity in the mature CS system and that the interplay between activity and injury preferentially promotes connections with ventral spinal motor circuits.

Surface electromyography (sEMG) can provide multiplexed information about muscle performance. If current sEMG electrodes are stretchable, arrayed, and able to be used multiple times, they would offer adequate high-quality data for continuous monitoring. The lack of these properties delays the widespread use of sEMG in clinics and in everyday life. Here, we address these constraints by design of an adhesive dry electrode using tannic acid, polyvinyl alcohol, and PEDOT:PSS (TPP). The TPP electrode offers superior stretchability (~200%) and adhesiveness (0.58 N/cm) compared to current electrodes, ensuring stable and long-term contact with the skin for recording (>20 dB; >5 days). In addition, we developed a metal-polymer electrode array patch (MEAP) comprising liquid metal (LM) circuits and TPP electrodes. The MEAP demonstrated better conformability than commercial arrays, resulting in higher signal-to-noise ratio and more stable recordings during muscle movements. Manufactured using scalable screen-printing, these MEAPs feature a completely stretchable material and array architecture, enabling real-time monitoring of muscle stress, fatigue, and tendon displacement. Their potential to reduce muscle and tendon injuries and enhance performance in daily exercise and professional sports holds great promise.

The corticospinal tract (CST) has dense contralateral and sparse ipsilateral spinal cord projections that converge with proprioceptive afferents on common spinal targets. Previous studies in adult rats indicate that the loss of dense contralateral spinal CST connections after unilateral pyramidal tract section (PTx), which models CST loss after stroke or spinal cord injury, leads to outgrowth from the spared side into the affected, ipsilateral, spinal cord. The reaction of proprioceptive afferents after this CST injury, however, is not known. Knowledge of proprioceptive afferent responses after loss of the CST could inform mechanisms of maladaptive plasticity in spinal sensorimotor circuits after injury. Here, we hypothesize that the loss of the contralateral CST results in a reactive increase in muscle afferents from the impaired limb and enhancement of their physiological actions within the cervical spinal cord. We found that 10 d after PTx, proprioceptive afferents sprout into cervical gray matter regions denervated by the loss of CST terminations. Furthermore, VGlut1-positive boutons, indicative of group 1A afferent terminals, increased on motoneurons. PTx also produced an increase in microglial density within the gray matter regions where CST terminations were lost. These anatomical changes were paralleled by reduction in frequency-dependent depression of the H-reflex, suggesting hyperreflexia. Our data demonstrate for the first time that selective CST injury induces maladaptive afferent fiber plasticity remote from the lesion. Our findings suggest a novel structural reaction of proprioceptive afferents to the loss of CST terminations and provide insight into mechanisms underlying spasticity.

The corticospinal tract (CST) is the principal motor control pathway for skilled movements. It has a protracted postnatal development, creating a protracted period of vulnerability to perinatal brain and spinal cord injury. Research has shown that the motor signs in cerebral palsy (CP) reflect the loss of CST connections as well as development of abnormal motor systems connections, especially between the developing CST and spinal motor circuits. In this paper, we discuss a feline model of CP that we have developed. The animals develop a pattern of abnormal CST connections that is remarkably similar to that seen in hemiplegic CP and visuomotor impairments. Using this model we devised neural activity‐based therapeutic approaches to repair the abnormal CST connections and restore normal skilled movement control. Our studies stress that more active CST connections are better able to maintain strong synaptic connections with spinal motor circuits. We propose that perinatal trauma initiates a vicious cycle in which CST axons that are spared after an injury are at a disadvantage for maintaining spinal connections, leading to further reductions in connections and motor signs. If this is so, targeted activation of the spared CST might interrupt this process and lead to functional improvement.

This study investigated the requirements for restoring motor function after corticospinal (CS) system damage during early postnatal development. Activity-dependent competition between the CS tracts (CSTs) of the two hemispheres is imperative for normal development. Blocking primary motor cortex (M1) activity unilaterally during a critical period [postnatal week 5 (PW5) to PW7] produces permanent contralateral motor skill impairments, loss of M1 motor map, aberrant CS terminations, and decreases in CST presynaptic sites and spinal cholinergic interneuron numbers. To repair these motor systems impairments and restore function, we manipulated motor experience in three groups of cats after this CST injury produced by inactivation. One group wore a jacket restraining the limb ipsilateral to inactivation, forcing use of the contralateral, impaired limb, for the month after M1 inactivation (PW8–PW13; “restraint alone”). A second group wore the restraint during PW8–PW13 and was also trained for 1 h/d in a reaching task with the contralateral forelimb (“early training”). To test the efficacy of intervention during adolescence, a third group wore the restraint and received reach training during PW20–PW24 (“delayed training”). Early training restored CST connections and the M1 motor map, increased cholinergic spinal interneurons numbers on the contralateral, relative to ipsilateral, side, and abrogated limb control impairments. Delayed training restored CST connectivity and the M1 motor map but not contralateral spinal cholinergic cell counts or motor performance. Restraint alone only restored CST connectivity. Our findings stress the need to reestablish the integrated functions of the CS system at multiple hierarchical levels in restoring skilled motor function after developmental injury.