Erratum: 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

Stimulation 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. We 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. In 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. Therefore 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.

[1]  D.C. Rodger,et al.  Microelectronic packaging for retinal prostheses , 2005, IEEE Engineering in Medicine and Biology Magazine.

[2]  V. Edgerton,et al.  Hindlimb stepping movements in complete spinal rats induced by epidural spinal cord stimulation , 2005, Neuroscience Letters.

[3]  Christie K. Ferreira,et al.  Effect of epidural stimulation of the lumbosacral spinal cord on voluntary movement, standing, and assisted stepping after motor complete paraplegia: a case study , 2011, The Lancet.

[4]  S. Grillner Locomotion in vertebrates: central mechanisms and reflex interaction. , 1975, Physiological reviews.

[5]  Y. Gerasimenko,et al.  Significance of peripheral feedback in the generation of stepping movements during epidural stimulation of the spinal cord , 2007, Neuroscience and Behavioral Physiology.

[6]  Yu-Chong Tai,et al.  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 , 2013, Journal of neuroengineering and rehabilitation.

[7]  V. Edgerton,et al.  Plasticity of the spinal neural circuitry after injury. , 2004, Annual review of neuroscience.

[8]  H. Forssberg Stumbling corrective reaction: a phase-dependent compensatory reaction during locomotion. , 1979, Journal of neurophysiology.

[9]  Igor A. Lavrov,et al.  Epidural spinal cord stimulation plus quipazine administration enable stepping in complete spinal adult rats. , 2007, Journal of neurophysiology.

[10]  S. G. Nelson,et al.  Projection of single knee flexor Ia fibers to homonymous and heteronymous motoneurons. , 1978, Journal of neurophysiology.

[11]  A. McComas,et al.  Longitudinal structure and innervation of two mammalian hindlimb muscles , 1988, Muscle & nerve.

[12]  James D. Weiland,et al.  Scalable high lead-count parylene package for retinal prostheses , 2006 .

[13]  C. Rivero-Melián Organization of hindlimb nerve projections to the rat spinal cord: A choleragenoid horseradish peroxidase study , 1996, The Journal of comparative neurology.

[14]  Hui Zhong,et al.  Plasticity of spinal cord reflexes after a complete transection in adult rats: relationship to stepping ability. , 2006, Journal of neurophysiology.

[15]  B. Dobkin,et al.  Can the mammalian lumbar spinal cord learn a motor task? , 1994, Medicine and science in sports and exercise.

[16]  Hui Zhong,et al.  Step Training Reinforces Specific Spinal Locomotor Circuitry in Adult Spinal Rats , 2008, The Journal of Neuroscience.

[17]  Roland R Roy,et al.  Use of robotics in assessing the adaptive capacity of the rat lumbar spinal cord. , 2002, Progress in brain research.

[18]  V R Edgerton,et al.  EMG patterns of rat ankle extensors and flexors during treadmill locomotion and swimming. , 1991, Journal of applied physiology.

[19]  Igor A. Lavrov,et al.  Transformation of nonfunctional spinal circuits into functional states after the loss of brain input , 2009, Nature Neuroscience.

[20]  Hui Zhong,et al.  Facilitation of Stepping with Epidural Stimulation in Spinal Rats: Role of Sensory Input , 2008, The Journal of Neuroscience.

[21]  V. Edgerton,et al.  Somatosensory control of balance during locomotion in decerebrated cat. , 2012, Journal of neurophysiology.

[22]  David J. Reinkensmeyer,et al.  Chapter 11 Use of robotics in assessing the adaptive capacity of the rat lumbar spinal cord , 2002 .

[23]  A. Lev-Tov,et al.  Long and Short Multifunicular Projections of Sacral Neurons Are Activated by Sensory Input to Produce Locomotor Activity in the Absence of Supraspinal Control , 2010, The Journal of Neuroscience.

[24]  V R Edgerton,et al.  Chronic spinal cord-injured cats: surgical procedures and management. , 1992, Laboratory animal science.

[25]  V. Reggie Edgerton,et al.  A parylene-based microelectrode array implant for spinal cord stimulation in rats , 2011, 2011 IEEE 24th International Conference on Micro Electro Mechanical Systems.

[26]  V. Reggie Edgerton,et al.  Coordination of motor pools controlling the ankle musculature in adult spinal cats during treadmill walking , 1991, Brain Research.

[27]  B. Dobkin,et al.  Human lumbosacral spinal cord interprets loading during stepping. , 1997, Journal of neurophysiology.

[28]  O. A. Nikitin,et al.  Initiation of Locomotor Activity in Spinal Cats by Epidural Stimulation of the Spinal Cord , 2003, Neuroscience and Behavioral Physiology.