神经损伤与修复
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Figure 1｜Phase-coherent cortical stimulation improves recovery of skilled walking after incomplete spinal cord injury.
Knowledge of the cortical mechanisms of functional recovery has informed neurostimulation strategies that we have recently developed (Bonizzato and Martinez, 2021). In our studies, we have used a rat model of incomplete SCI consisting of a unilateral hemisection at T9 that produces highly reproducible lesions and locomotor deficits (Brown and Martinez, 2019). Unilateral disruption of sensorimotor pathways induces unilateral deficits in foot control that chronically persist, impeding the ability of rats to perform complex voluntary motor tasks (such as crossing a ladder) (Brown and Martinez, 2018) (Figure 1A).
We developed a novel neurostimulation approach that directly targets the motor cortex, intending to recruit spared connections between the motor cortex and sublesional spinal circuits. Intracortical electrode arrays were used to deliver electrical stimulation within the hindlimb motor cortex in behaving rats (Bonizzato and Martinez, 2021) (Figure 1B).
Because phase-coherent intracortical stimulation was effective in acutely alleviating locomotor deficits after SCI, we next tested whether the daily neuroprosthetic intervention could facilitate locomotor recovery after SCI. We imbedded this neurostimulation strategy into locomotor training on a treadmill, from week one to four after SCI. Because treadmill walking is primarily modulated by subcortical and spinal circuits (Barbeau and Rossignol, 1987), introducing cortical stimulation was expected to help the brain to regain high-level control over spinal circuits. Voluntary locomotor control was evaluated on an untrained task, the horizontal ladder, which requires cortical control to correctly position the foot on the rungs. After three weeks of daily neurostimulation (30 min/d during treadmill walking), rats improved voluntary control of their foot. Such improvement in voluntary motor skills was not observed in rats submitted to cortical stimulation in the cage and additionally trained to walk on the treadmill. These rats did not display better performance than rats trained to treadmill walking without cortical stimulation or rats that were allowed to recover spontaneously in the cage (Figure 1C).