bioRxiv Science⌕ Search

bioRxiv · 10.64898/2026.06.14.732127

Selectivity of Lateral Epidural Spinal Cord Stimulation with Varying Electrode Diameters and Stimulation Configurations

Abstract

Objective. Our prior studies have demonstrated that lateral spinal cord stimulation can evoke somatosensory percepts in the missing foot in individuals with a lower-limb amputation. However, subjects reported concurrent sensations in their residual limb. In this study, we evaluate the hypothesis that using high-density paddle electrodes with smaller contact sizes, and multipolar stimulation configurations could evoke more focal sensations in the foot over a wide range of stimulation amplitudes. Approach. We used a combination of electrophysiology and computational modelling methods to investigate the selective activation of distal nerve branches in response to lateral spinal cord stimulation in cats. In six acute feline experiments, we performed an L3-S1 laminectomy and placed custom 32-electrode paddles laterally over the dura of the spinal cord. We recorded antidromic action potentials in the distal branches of the sciatic and femoral nerve trunks in response to stimulation using three contact diameters (150, 500 and 1000 {micro}m) and two stimulation configurations - monopolar and bipolar stimulation. We replicated the neural recruitment patterns from those experiments in a computational model of the feline lumbar spinal cord. We then used the model to examine neural recruitment with 1.8 mm and 2.5 mm contacts, as well as a tripolar guarded-cathode configuration. Main results. In the electrophysiology experiments, the 500 {micro}m-diameter electrodes achieved the most selective nerve activation (68%) compared to 62% for both 150 and 1000 {micro}m-diameter electrodes. The minimum amplitudes for recruiting nerve branches (i.e., threshold) as well as the dynamic ranges were largely similar for the different contact diameters (median: 35 {micro}A) and stimulation configurations (30 {micro}A for bipolar stimulation; 35 {micro}A for monopolar stimulation). The computational model reproduced the finding that selectivity did not differ significantly among the three contact sizes tested in cat experiments, though it revealed that increasing contact diameter above 1000 {micro}m raised the minimum amplitude required for selective activation and reduced spinal root selectivity. Across both approaches, we consistently recruited large-diameter afferents that are critical for somatosensory applications of spinal cord stimulation. Significance. Our results indicate that, relative to clinical electrodes, reducing the contact diameter of stimulation electrodes can evoke focal sensations, but further reductions below 1000 {micro}m may fail to improve selectivity. This study highlights potential constraints with achieving focal selectivity that are not dependent on the design of the electrodes.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Ansah, G. J., Del Brocco, M., Bhowmick, S., Duran, M. A., Gopinath, C. H., Jantz, M. K., Lempka, S. F., Fisher, L.. 2026-06-17. Selectivity of Lateral Epidural Spinal Cord Stimulation with Varying Electrode Diameters and Stimulation Configurations. https://doi.org/10.64898/2026.06.14.732127

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Surfactant-Assisted Colorimetric Signal Enhancement in Paper-Based Glucose Sensing

Paper-based colorimetric sensors offer a low-cost and accessible platform for point-of-care (POC) analysis, but enzyme activity loss during coating and drying can weaken analytical signals and require high enzyme loadings or complex immobilization procedures. Although surfactants are widely used to improve wettability in paper-based assays, their potential contribution to colorimetric performance beyond these effects remains unclear. Here, we investigated surfactant-assisted colorimetric signal enhancement in a glucose assay implemented on a 96-puddle paper plate (96-PPP) and identified Tween 20 as the most effective surfactant. Its effect on detection performance became more pronounced as glucose oxidase (GOx) loading decreased; at 0.1 mg/mL GOx, Tween 20 lowered the limit of detection (LoD) from 0.113 to 0.034 mg/mL (approximately 3.3-fold) over a working range of 0-5 mg/mL, despite no statistically significant change in the measured contact angle at this loading. Tween 20 had no appreciable effect on the reaction in solution but preserved 95% of the apparent reaction rate constant after drying, compared with 11% without it, and atomic force microscopy (AFM) revealed a more dispersed dried enzyme morphology on mica. Tween 20-containing sensors also showed slower signal decay during repeated wetting-drying cycles and thermal stress, retained 77% (vs 26%) of the response at 400 mM NaCl, and exhibited within-PPP and between-batch coefficients of variation (CVs) below 10% (vs 12.3-19.5%), while maintaining glucose selectivity over potentially interfering molecules. These results indicate that Tween 20 enhances paper-based glucose sensing beyond wettability, in part by retaining enzyme cascade activity during drying, although the contributions of the individual enzymes and the underlying mechanism remain to be established.

bioengineering↗

Engineering CAR-T cells to remodel the mucin-rich cancer cell glycocalyx

The dense glycocalyx of cancer cells can restrict immune-cell access to surface antigens and limit CAR-T cell activity. Here, we show that mucin density and epitope position determine how glycocalyx remodeling affects CAR-T cell recognition and killing. We identify KLK5 as a human protease that cleaves tumor-associated mucins, increases access to membrane-proximal antigens, and enhances CAR-T cell function. We then engineer CAR-T cells to display or secrete KLK5, enabling remodeling of the tumor glycocalyx during antigen recognition. KLK5-engineered CAR-T cells improved tumor control across multiple xenograft models, and KLK5-secreting MUC17 CAR-T cells produced the strongest in vivo benefit, prolonging survival compared with conventional MUC17 CAR-T cells. These findings show that CAR-T cells can be engineered to breach the mucin-rich glycocalyx while preserving accessible target epitopes.

bioengineering↗

Wall stiffening is a primary contributor to motility loss in Crohn's disease: an electromechanical modeling study

Fibrotic strictures are among the most disabling complications of Crohn's disease, permanently narrowing the bowel and impairing motility, yet no approved therapy reverses them. Chronic inflammation alters pacemaker-network coupling, smooth-muscle excitability, and calcium-dependent contractility, while fibrosis thickens the bowel wall, narrows the lumen, and changes tissue mechanics. The relative contributions of these coupled electrical, contractile, and structural alterations to motility loss remain unclear. To address this gap, we develop an integrated electromechanical finite-element framework for fibrostenosing Crohn's disease that couples a fibrosis-driven growth model with a FitzHugh-Nagumo electromechanical model. A full-factorial 25 design of experiments is used to quantify the relative effects of electrical diffusivity, excitation threshold, peak active stress, wall stiffness, and hypertrophic remodeling on cyclic lumen-volume deformation. Motility is quantified by the standard deviation of lumen volume over one contraction cycle. Within the parameter ranges examined, increased wall stiffness emerged as the dominant contributor to motility loss, followed by impaired smooth-muscle contractility. Changes in excitation threshold, hypertrophic remodeling, and electrical diffusivity produced substantially smaller effects. Pairwise interactions were small relative to the dominant main effects, indicating that the mechanisms contributed largely through their individual effects. Our findings suggest that limiting wall stiffening while preserving smooth-muscle contractile function may provide a therapeutic strategy for maintaining intestinal motility in fibrostenosing Crohn's disease.

bioengineering↗