Development of a multi-electrode array for spinal cord epidural stimulation to facilitate stepping and standing after a complete spinal cord injury in adult rats

Abstract

BackgroundStimulation of the spinal cord has been shown to have great potential for improving function after motor deficits caused by injury or pathological conditions. Using a wide range of animal models, many studies have shown that stimulation applied to the neural networks intrinsic to the spinal cord can result in a dramatic improvement of motor ability, even allowing an animal to step and stand after a complete spinal cord transection. Clinical use of this technology, however, has been slow to develop due to the invasive nature of the implantation procedures, the lack of versatility in conventional stimulation technology, and the difficulty of ascertaining specific sites of stimulation that would provide optimal amelioration of the motor deficits. Moreover, the development of tools available to control precise stimulation chronically via biocompatible electrodes has been limited. In this paper, we outline the development of this technology and its use in the spinal rat model, demonstrating the ability to identify and stimulate specific sites of the spinal cord to produce discrete motor behaviors in spinal rats using this array.MethodsWe have designed a chronically implantable, rapidly switchable, high-density platinum based multi-electrode array that can be used to stimulate at 1–100 Hz and 1–10 V in both monopolar and bipolar configurations to examine the electrophysiological and behavioral effects of spinal cord epidural stimulation in complete spinal cord transected rats.ResultsIn this paper, we have demonstrated the effectiveness of using high-resolution stimulation parameters in the context of improving motor recovery after a spinal cord injury. We observed that rats whose hindlimbs were paralyzed can stand and step when specific sets of electrodes of the array are stimulated tonically (40 Hz). Distinct patterns of stepping and standing were produced by stimulation of different combinations of electrodes on the array located at specific spinal cord levels and by specific stimulation parameters, i.e., stimulation frequency and intensity, and cathode/anode orientation. The array also was used to assess functional connectivity between the cord dorsum to interneuronal circuits and specific motor pools via evoked potentials induced at 1 Hz stimulation in the absence of any anesthesia.ConclusionsTherefore the high density electrode array allows high spatial resolution and the ability to selectively activate different neural pathways within the lumbosacral region of the spinal cord to facilitate standing and stepping in adult spinal rats and provides the capability to evoke motor potentials and thus a means for assessing connectivity between sensory circuits and specific motor pools and muscles.

Advances in functional electrical stimulation (FES)

“…These electrodes can direct the electrical field within the nerve and provide the necessary selective response. The alternative is to use intraneural electrodes, such as transversal intrafascicular electrodes (Boretius et al, 2010;Raspopovic et al, 2014), electrodes such as the Utah slant array (Branner et al, 2001) or electrode arrays that can be positioned along the spinal cord (Gad et al, 2013).…”

A Computational Model for Epidural Electrical Stimulation of Spinal Sensorimotor Circuits

“…With the availability of high-density electrode arrays affording near-infinite stimulating capabilities (Gad et al, 2013), computational models will play an essential role to steer the development of spinal neuroprosthetic systems to improve the recovery of motor functions after neurological disorders.…”

Electronic dura mater for long-term multimodal neural interfaces

“…Most implants used experimentally or clinically to assess and treat neurological disorders are placed above the dura mater (3,(16)(17)(18). The compliance of e-dura enables chronic implantation below the dura mater without extensive durotomy (Fig.…”