Pascual-Leone Andrés, Tyagi Vishweshwar, Asan Ahmet S, Rocha-Flores Pedro Emanuel, Rodriguez-Lopez Ovidio, Voit Walter, McIntosh James R, Carmel Jason B
bioRxiv. 2025 Sep 11:2025.09.05.674051. doi: 10.1101/2025.09.05.674051.
Cervical epidural spinal cord stimulation (SCS) can facilitate upper-limb motor recovery, but electrode configurations that optimally recruit motor circuits remain unclear. This study systematically evaluated how electrode position, size, orientation, and waveform influence the efficacy of forelimb motor activation in rats, with the goal of identifying configurations that minimize stimulation thresholds of evoked responses across multiple muscles.
Custom microfabricated arrays of electrodes were implanted over the C6 dorsal root entry zone (DREZ) in eight adult female Sprague Dawley rats. A circular array was used to vary current orientation in 45° increments, while a linear array was used to optimize mediolateral electrode position. The linear array included both small (250 µm) and large (500 µm) contacts to assess size effects at mediolateral positions. Stimulation consisted of biphasic and pseudomonophasic waveforms with bipolar or distant return, and a high-definition montage to probe spatial focality around the DREZ. Motor-evoked potentials (MEPs) recorded via implanted EMG electrodes were analyzed in six forelimb muscles. Thresholds, estimated from recruitment curves using a hierarchical Bayesian model, were compared within-rat using pairwise t-tests with correction for multiple comparisons.
Stimulation over the DREZ yielded the lowest thresholds and efficacy decreased progressively with medial or lateral displacement relative to DREZ. In the circular array, rostro-caudal current orientation was most effective, reducing thresholds by up to 58% relative to latero-medial orientation ( = 0.0007). In the linear array, large contacts were significantly more effective than small contacts at the lateral position, reducing thresholds by 45% ( = 0.034). Cathodal stimulation was more effective than anodal, and high-definition montages reduced efficacy compared to distant returns. Across all tested parameters, position and orientation had the greatest influence on efficacy, with optimal conditions combining DREZ targeting and rostro-caudal oriented current flow.
Maximum efficacy was achieved for cervical SCS with electrodes positioned over the DREZ, rostro-caudal current flow, larger contacts, and cathodal stimulation. These design principles that more effectively engage spinal circuitry could reduce the current required and thereby improve SCS systems for upper-limb motor restoration.
颈段硬膜外脊髓刺激（SCS）可促进上肢运动恢复，但能最佳募集运动回路的电极配置仍不明确。本研究系统评估了电极位置、大小、方向和波形对大鼠前肢运动激活效果的影响，目的是确定能使多块肌肉诱发反应的刺激阈值最小化的配置。
在8只成年雌性Sprague Dawley大鼠的C6背根进入区（DREZ）上方植入定制的微制造电极阵列。使用圆形阵列以45°增量改变电流方向，同时使用线性阵列优化内外侧电极位置。线性阵列包括小（250μm）和大（500μm）的触点，以评估内外侧位置的大小效应。刺激包括双相和伪单相波形，采用双极或远场返回，以及用于探测DREZ周围空间聚焦性的高清蒙太奇刺激。通过植入的肌电图电极记录的运动诱发电位（MEP）在6块前肢肌肉中进行分析。使用分层贝叶斯模型从募集曲线估计阈值，并在大鼠体内使用配对t检验进行比较，并对多重比较进行校正。
在DREZ上方进行刺激产生的阈值最低，相对于DREZ，向内侧或外侧移位时效果逐渐降低。在圆形阵列中，头端-尾端电流方向最有效，相对于外侧-内侧方向，阈值降低高达58%（P = 0.0007）。在线性阵列中，外侧位置的大触点比小触点明显更有效，阈值降低45%（P = 0.034）。阴极刺激比阳极刺激更有效，与远场返回相比，高清蒙太奇刺激降低了效果。在所有测试参数中，位置和方向对效果影响最大，最佳条件是结合靶向DREZ和头端-尾端电流流动。
将电极置于DREZ上方、采用头端-尾端电流流动、较大触点和阴极刺激的颈段SCS可实现最大效果。这些能更有效地激活脊髓回路的设计原则可减少所需电流，从而改进用于上肢运动恢复的SCS系统。
