Shirley Ryan AbilityLab, Chicago, IL, USA.
Department of Physical Medicine and Rehabilitation, Northwestern University, Chicago, IL.
Ann Neurol. 2023 Jun;93(6):1198-1213. doi: 10.1002/ana.26622. Epub 2023 Mar 30.
Spinal cord injury (SCI) damages synaptic connections between corticospinal axons and motoneurons of many muscles, resulting in devastating paralysis. We hypothesized that strengthening corticospinal-motoneuronal synapses at multiple spinal cord levels through Hebbian plasticity (i.e., "neurons that fire together, wire together") promotes recovery of leg and arm function.
Twenty participants with chronic SCI were randomly assigned to receive 20 sessions of Hebbian or sham stimulation targeting corticospinal-motoneuronal synapses of multiple leg muscles followed by exercise. Based on the results from this study, in a follow-up prospective study, 11 more participants received 40 sessions of Hebbian stimulation targeting corticospinal-motoneuronal synapses of multiple arm and leg muscles followed by exercise. During Hebbian stimulation sessions, 180 paired pulses elicited corticospinal action potentials by magnetic (motor cortex) and/or electrical (thoracic spine) stimulation allowing volleys to arrive at the spinal cord 1-2 milliseconds before motoneurons were activated retrogradely via bilateral electrical stimulation (brachial plexus, ulnar, femoral, and common peroneal nerves) for biceps brachii, first dorsal interosseous, quadriceps femoris, and tibialis anterior muscles as needed.
We found in our randomized study that participants receiving Hebbian stimulation improved their walking speed and corticospinal function to a greater extent than individuals receiving sham stimulation. In agreement, prospective study participants improved their grasping and walking, corticospinal function, and quality of life metrics, exhibiting greater improvements with more sessions that persisted 9-month post-therapy.
Our findings suggest that multisite Hebbian stimulation, informed by the physiology of the corticospinal system, represents an effective strategy to promote functional recovery following SCI. ANN NEUROL 2023;93:1198-1213.
脊髓损伤（SCI）破坏皮质脊髓束轴突和许多肌肉运动神经元之间的突触连接，导致毁灭性瘫痪。我们假设，通过赫布可塑性（即“一起发射的神经元，一起连接”）增强多个脊髓水平的皮质脊髓-运动神经元突触，可促进腿部和手臂功能的恢复。
20 名慢性 SCI 参与者被随机分配接受 20 次针对多个腿部肌肉的皮质脊髓-运动神经元突触的赫布或假刺激，随后进行运动。基于这项研究的结果，在一项后续前瞻性研究中，另外 11 名参与者接受了 40 次针对多个手臂和腿部肌肉的皮质脊髓-运动神经元突触的赫布刺激，随后进行运动。在赫布刺激期间，180 对双脉冲通过磁（运动皮层）和/或电（胸椎）刺激引发皮质脊髓动作电位，使冲动在通过双侧电刺激（臂丛、尺神经、股神经和腓总神经）逆行激活运动神经元之前 1-2 毫秒到达脊髓，以激活肱二头肌、第一背侧骨间肌、股四头肌和胫骨前肌。
我们在随机研究中发现，接受赫布刺激的参与者在行走速度和皮质脊髓功能方面的改善程度大于接受假刺激的参与者。同样，前瞻性研究参与者在抓握和行走、皮质脊髓功能和生活质量指标方面有所改善，随着治疗后 9 个月持续时间更长，改善更为显著。
我们的研究结果表明，基于皮质脊髓系统生理学的多部位赫布刺激是促进 SCI 后功能恢复的有效策略。
