Based on the combined efforts of a multidisciplinary and multi-university team, this research program will develop a novel, flexible, high density electrode array technology for epidural spinal cord stimulation. This technology has the potential to significantly improve the recovery of posture and locomotion in individuals with a severe spinal cord injury. High density epidural electrode arrays will enable us to take advantage of two key features of spinal cord circuitry that are essential for rehabilitating posture and locomotion. First, the spinal circuitry interprets and transduces sensory information into state-dependent motor activity. Second, the locomotor network is highly plastic and adapts when provided with persistent sensory cues during training, thus enabling recovery to occur. Epidural stimulation facilitates both of these important processes and we hypothesize that it will be particularly beneficial after an SCI, when descending motor control is lost. Since sensory and motor processing occurs throughout the dorsal spinal cord, the distributed stimulation capability of the proposed high density electrode arrays will provide comprehensive access to the diffusely located components of the locomotor network. We hypothesize that, when combined with motor training, multi-site epidural stimulation will enable finer and more robust control of locomotion of SCI subjects than previously possible. This research program is composed of two parallel tracks. The first, and major, track focuses on developing, testing, and characterizing the arrays in a complete SCI rat model. Our preliminary animal experiments have demonstrated success in promoting recovery of stepping of complete spinal cord injured rats when the hindlimbs are trained regularly with robotic devices and when the spinal cord is stimulated epidurally at a single or at two sites. In this research program, we will design, fabricate, and test a series of electrode arrays that vary in size, electrode count, and density. We will test these high density arrays on SCI rats using various design combinations, culminating in an experiment that will test a combined therapy using a high density stimulating array coupled with assist-as-needed robotic training. A second parallel track will explore the use of conventional electrode technology, which historically has been used mainly for suppressing spasticity and back pain, to facilitate standing and stepping in human subjects with a severe spinal cord injury. We hypothesize that the combination of epidural stimulation with task specific motor training will enable individuals with an injury that presently precludes independent stepping and standing, to regain these functions. The combined results of our animal studies and human studies would prepare our team for subsequent work that focused on translating the high density array technologies to human clinical studies. This proposal will be conducted as a collaboration between the University of California (Los Angeles), Caltech, and the University of Louisville, with assistance from an expert team of clinicians, engineers, and scientists located in Vienna, Austria.

Public Health Relevance

In this proposal we will develop new multielectrode arrays, which will be surgically placed on the connective tissue sheath surrounding the spinal cord, that can be used to stimulate specific regions of the spinal cord to help SCI subjects recover the ability to stand or step. These electrode arrays will help us take advantage of two built-in features of the spinal cord neural circuits that are associated with the ability to stand and step: 1) interpretation of complicated, dynamic sensory information and 2) use-dependent plasticity of these spinal circuits. We hypothesize that the combination of stimulation of the spinal cord and either stand or step training will allow individuals with a spinal cord injury to regain these functions.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-NT-K (01))
Program Officer
Peng, Grace
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Los Angeles
Schools of Arts and Sciences
Los Angeles
United States
Zip Code
Rejc, Enrico; Angeli, Claudia A; Atkinson, Darryn et al. (2017) Motor recovery after activity-based training with spinal cord epidural stimulation in a chronic motor complete paraplegic. Sci Rep 7:13476
Hoffman, Haydn; Sierro, Tiffany; Niu, Tianyi et al. (2017) Rehabilitation of hand function after spinal cord injury using a novel handgrip device: a pilot study. J Neuroeng Rehabil 14:22
Lo, Yi-Kai; Kuan, Yen-Cheng; Culaclii, Stanislav et al. (2017) A Fully Integrated Wireless SoC for Motor Function Recovery After Spinal Cord Injury. IEEE Trans Biomed Circuits Syst 11:497-509
Lu, Daniel C; Edgerton, V Reggie; Modaber, Morteza et al. (2016) Engaging Cervical Spinal Cord Networks to Reenable Volitional Control of Hand Function in Tetraplegic Patients. Neurorehabil Neural Repair 30:951-962
Gad, Parag N; Roy, Roland R; Zhong, Hui et al. (2016) Neuromodulation of the neural circuits controlling the lower urinary tract. Exp Neurol 285:182-189
Gerasimenko, Yury; Sayenko, Dimitry; Gad, Parag et al. (2016) Feed-Forwardness of Spinal Networks in Posture and Locomotion. Neuroscientist :1073858416683681
Desautels, Thomas A; Choe, Jaehoon; Gad, Parag et al. (2015) An Active Learning Algorithm for Control of Epidural Electrostimulation. IEEE Trans Biomed Eng 62:2443-2455
Gad, Parag; Roy, Roland R; Choe, Jaehoon et al. (2015) Electrophysiological mapping of rat sensorimotor lumbosacral spinal networks after complete paralysis. Prog Brain Res 218:199-212
Rejc, Enrico; Angeli, Claudia; Harkema, Susan (2015) Effects of Lumbosacral Spinal Cord Epidural Stimulation for Standing after Chronic Complete Paralysis in Humans. PLoS One 10:e0133998
Gad, Parag; Roy, Roland R; Choe, Jaehoon et al. (2015) Electrophysiological biomarkers of neuromodulatory strategies to recover motor function after spinal cord injury. J Neurophysiol 113:3386-96

Showing the most recent 10 out of 48 publications