Intraspinal microstimulation for the recovery of function following spinal cord injury

Abstract

Spinal cord injury is a devastating neurological trauma, often resulting in the impairment of bladder, bowel, and sexual function as well as the loss of voluntary control of muscles innervated by spinal cord segments below the lesion site. Research is ongoing into several classes of therapies to restore lost function. These include the encouragement of neural sparing and regeneration of the affected tissue, and the intervention with pharmacological and rehabilitative means to improve function. This review will focus on the application of electrical current in the spinal cord in order to reactivate extant circuitry which coordinates and controls smooth and skeletal muscle below the injury. We first present a brief historical review of intraspinal microstimulation (ISMS) focusing on its use for restoring bladder function after spinal cord injury as well as its utilization as a research tool for mapping spinal cord circuits that coordinate movements. We then present a review of our own results related to the use of ISMS for restoring standing and walking movements after spinal cord injury. We discuss the mechanisms of action of ISMS and how they relate to observed functional outcomes in animal models. These include the activation of fibers-in-passage which lead to the transsynaptic spread of activation through the spinal cord and the ability of ISMS to produce fatigue-resistant, weight-bearing movements. We present our thoughts on the clinical potential for ISMS with regard to implantation techniques, stability, and damage induced by mechanical and electrical factors. We conclude by suggesting improvements in materials and techniques that are needed in preparation for a clinical proof-of-principle and review our current attempts to achieve these.

Fig. 1

Forces produced by stimulation of spinal cord gray matter in frog are measured at multiple locations in a grid. Force vectors are interpolated and a convergent force field is produced representing the equilibrium point for the generated movement. A limited number of distinct force fields (movement primitives) are identified. In theory, movement primitives could be combined in a modular manner to produce the full range of possible movements. Reproduced with permission from Bizzi et al. (1995).

Fig. 2

ISMS for bladder control. A drawing of the early spinal stimulation methods used in animals and humans to restore bladder function after spinal cord injury. Reproduced with permission from Nashold et al. (1972).

Fig. 3

A drawing of the ISMS implant array. Multiple microwires can be inserted at varying lengths along the spinal cord, creating a bilateral array of possible stimulation sites. The microwires are covered in plastic film and routed through a silicon tube to a headpiece. Reproduced with permission from Prochazka et al. (2001).

Fig. 4

Summary of ISMS microwire tip locations and evoked responses. The locations of stimulation across multiple cat experiments are displayed in (a). A variety of movements could be produced from microstimulation but the most reliable came from microstimulation of lamina IX. Flexion movements were most common at all spinal segments tested; however, extension and alternation could also be reliably produced (b). Reproduced with permission from Guevremont et al. (2006).

Fig. 5

Fatigue characteristics of interleaved stimulation. Normalized tetanic forces produced by stimulating cat spinal cord through two independent electrodes (A and B) are shown. Single forces were produced by stimulating through either electrode A or B individually at 50 Hz (single A and single B). Refractory AB forces were produced by stimulating electrode B at 50 Hz during the refractory period for neurons activated by electrode A. Interleaved stimulation was produced by stimulating through each electrode in an interleaved manner at 25 Hz, yielding an aggregate stimulation frequency of 50 Hz. Not only did interleaved stimulation produced greater force, but it also reduced fatigue. Reproduced with permission from Mushahwar and Horch (1997).