Preferential activation of proprioceptive and cutaneous sensory fibers compared to motor fibers during cervical transcutaneous spinal cord stimulation: A computational study

Abstract

Objective: Cervical transcutaneous spinal cord stimulation (tSCS) is a promising technology that can support motor function recovery of upper-limbs after spinal cord injury. Its efficacy may depend on the ability to recruit sensory afferents and convey excitatory inputs onto motoneurons. Therefore, understanding its physiological mechanisms is critical to accelerate its development towards clinical applications. In this study, we used an anatomically realistic computational model of the cervical spine to compare α-motor, Aα-sensory, and Aβ-sensory fiber activation thresholds and activation sites. Approach: We developed a tridimensional geometry of the cervical body and tSCS electrodes with a cathode centred at the C7 spinous process and an anode placed over the anterior neck. The geometrical model was used to estimate the electric potential distributions along motor and sensory fiber trajectories at the C7 spinal level using a finite element method. We implemented dedicated motor and sensory fiber models to simulate the α-motor and Aα-sensory fibers using 12, 16, and 20 µm diameter fibers, and Aβ-sensory fibers using 6, 9, and 12 µm diameter fibers. We estimated nerve fiber activation thresholds and sites for a 2 ms monophasic stimulating pulse and compared them across the fiber groups. Main results: Our results showed lower activation thresholds of Aα- and Aβ-sensory fibers compared with α-motor fibers, suggesting preferential sensory fiber activation. We also found no differences between activation thresholds of Aα-sensory and large Aβ-sensory fibers, implying they were co-activated. The activation sites were located at the dorsal and ventral root levels. Significance: Using a realistic computational model, we demonstrated preferential activation of dorsal root Aα- and Aβ-sensory fibers compared with ventral root α-motor fibers during cervical tSCS. These findings suggest high proprioceptive and cutaneous contributions to neural activations during cervical tSCS, which inform the underlying mechanisms of upper-limb functional motor recovery.

Optimizing sensory fiber activation during cervical transcutaneous spinal stimulation using different electrode configurations: A computational analysis

“…Moreover, we also hypothesized that using smaller electrodes would affect how C7 and C8 spinal nerves are activated when the cathode is configured at different positions. Finally, we expected that sensory fibers would have lower activation thresholds compared with motor fibers for both C7 and C8 spinal segments, consistent with previous computational simulations 12 and experimental implications. 20 and from human anatomical proportions.…”

“…The α‐motor and Aα‐sensory fibers were simulated using 14 and 16 μm diameters, respectively, since Aα‐sensory fibers have larger diameters compared with α‐motor fibers 33 . This range of fiber sizes is consistent with that used in previous simulation studies 12,15,18 . The motor and sensory axon fiber models (available for download in https://modeldb.yale.edu/243841) were implemented in Python 3.9 using NEURON 8.0, 34 with no changes to the original implementation.…”

“…Specifically, the distributions of electric potentials along the trajectories of motor and sensory fibers obtained from the FEM simulations (Figure 3A) were linearly scaled (i.e., multiplied by a constant factor) and applied as extraneural potentials to the compartments of the Gaines fiber models. Considering the linear relationship between the FEM‐calculated electric potentials and the current injected at the anode electrode, the scaling factors used to adjust the extraneural potential distributions were a fraction of the 1 A stimulation current initially applied 8,12,30 . A bisection algorithm was used to adjust the scaling factor and estimate the minimum stimulation intensities to the fiber activation, 15,30 that is, the activation thresholds.…”

“…6,[9][10][11][12][13] Specifically, it was suggested that proprioceptive sensory fibers were preferentially recruited at lower stimulation intensities compared with motor fibers. 6,[9][10][11][12] Moreover, activation of nerve fibers at specific spinal segments using different cervical tSCS electrode configurations could be inferred from Zheng et al, 13 which showed that independent and synergistic upper-limb joint movements were enabled during continuous cervical tSCS. Supporting evidence for activation of fibers at specific spinal segments was recently also demonstrated in an experimental study by de Freitas and colleagues who compared activation of hand muscles using different cathode electrode configurations.…”

“…Computational simulations have been developed in the recent years for better understanding nerve fiber recruitment during spinal stimulation 12,14–16 . Specifically, these simulations combine finite element method (FEM) and mathematical models to simulate the fiber membrane dynamics 8,14,15,17–19 .…”