Sharma Pawan, Shah Prithvi K
Division of Rehabilitation Sciences, Department of Physical Therapy, School of Health Technology and Management, Stony Brook University, Stony Brook, NY, 11727, USA.
J Physiol. 2021 Jun;599(12):3121-3150. doi: 10.1113/JP281146. Epub 2021 May 31.
To electrophysiologically determine the predominant neural structures activated with cervical epidural stimulation (ES), well-established electrophysiological protocols (single-pulse, paired-pulse and multiple frequency stimulation) were delivered at rest, during motor activity and under anaesthesia in adult rats. Cervical ES resulted in spinal evoked motor responses with three different waveforms - early response (ER), middle response (MR) and late response (LR). ERs remained unmodulated by repeated stimulation protocols. In contrast, MRs and LRs were modulated by repeated stimulation protocols and volitional motor activity. ERs are consequential to the direct activation of motor efferents; MRs are secondary to type-I sensory afferent activation and LRs result from the engagement of wider spinal interneuronal circuitry with potential influence from supraspinal pathways. Evidence from this work is fundamental in enhancing our understanding of cervical ES, and critical in refining the design of neuromodulation-based rehabilitative strategies and in the construction of neuroprosthetics.
Epidural stimulation (ES) of the lumbar spinal cord has demonstrated significant improvements in various physiological functions after a traumatic spinal cord injury in humans. Electrophysiological evidence from rodent, human and computational studies collectively suggest that the functional recovery following lumbar ES is mediated via direct activation of sensory afferent fibres. However, the mechanisms underlying cervical ES have not been comprehensively studied, which greatly limits our understanding of its effectiveness in restoring upper limb function. In this work, we determined the predominant neural structures that are activated with cervical ES using in vivo cervical spinal evoked motor responses (SEMRs). Standard electrophysiological protocols (single-pulse, paired-pulse and multiple frequency stimulation) were implemented in 11 awake and anaesthetized rats in four experimental stages. Three distinct types of cervical SEMRs were identified based on latency of their appearance: early response (ER), middle response (MR) and late response (LR). ERs remained unmodulated by repeated stimulation protocols. MRs and LRs were modulated by repeated stimulation protocols and volitional motor activity. Except for LRs being completely abolished under urethane, ketamine or urethane anaesthesia did not affect the appearance of cervical SEMRs. Our data, backed by literature, suggest that ERs are secondary to the direct activation of motor efferents, MRs are elicited by activation of type-I sensory afferents and LRs result from the engagement of interneuronal circuitry with potential influence from supraspinal pathways. The gathered information paves the way to designing motor rehabilitation strategies that can utilize cervical ES to recover upper limb function following neurological deficits.
为了通过电生理学方法确定颈段硬膜外刺激（ES）激活的主要神经结构，在成年大鼠休息、运动活动期间和麻醉状态下，采用成熟的电生理方案（单脉冲、双脉冲和多频率刺激）。颈段ES引发了具有三种不同波形的脊髓诱发运动反应——早期反应（ER）、中期反应（MR）和晚期反应（LR）。重复刺激方案对ER没有调节作用。相比之下，MR和LR受重复刺激方案和自主运动活动的调节。ER是运动传出纤维直接激活的结果；MR继发于I型感觉传入纤维的激活，而LR是更广泛的脊髓中间神经元回路参与的结果，可能受到脊髓上通路的影响。这项工作的证据对于增进我们对颈段ES的理解至关重要，对于完善基于神经调节的康复策略设计和神经假体的构建也至关重要。
腰段脊髓硬膜外刺激（ES）已证明在人类脊髓损伤后多种生理功能有显著改善。来自啮齿动物、人类和计算研究的电生理证据共同表明，腰段ES后的功能恢复是通过感觉传入纤维的直接激活介导的。然而，颈段ES的潜在机制尚未得到全面研究，这极大地限制了我们对其恢复上肢功能有效性的理解。在这项工作中，我们利用体内颈段脊髓诱发运动反应（SEMRs）确定了颈段ES激活的主要神经结构。在四个实验阶段，对11只清醒和麻醉的大鼠实施了标准电生理方案（单脉冲、双脉冲和多频率刺激）。根据其出现的潜伏期，识别出三种不同类型的颈段SEMR：早期反应（ER）、中期反应（MR）和晚期反应（LR）。重复刺激方案对ER没有调节作用。MR和LR受重复刺激方案和自主运动活动的调节。除了在氨基甲酸乙酯、氯胺酮或氨基甲酸乙酯麻醉下LR完全消失外，这些麻醉对颈段SEMR的出现没有影响。我们的数据，得到文献支持，表明ER是运动传出纤维直接激活的结果，MR是由I型感觉传入纤维的激活引起的，而LR是中间神经元回路参与的结果，可能受到脊髓上通路的影响。所收集的信息为设计运动康复策略铺平了道路，这些策略可以利用颈段ES来恢复神经功能缺损后的上肢功能。
