In the first 5-year period of our BRP we had two major objectives: 1) to determine whether we could improve motor function of the lower limbs by neuromodulating the spinal lumbosacral circuitry with epidural stimulation and 2) to begin to develop and improve the technologies associated with electrode arrays and chronic implantable stimulation devices to maximize the neuromodulatory potential. These new technologies have the potential to fine tune the epidural stimulation parameters, to help in understanding some of the underlying mechanisms of epidural stimulation., to examine synergistic effects of epidural stimulation, pharmacological modulation, and examine activity-dependent interventions that might affect the level of recovery of motor function after complete paralysis. We have demonstrated that an adult rat with a complete, mid-thoracic spinal cord transection can regain full weight-bearing stepping over a range of speeds, loads, and even directions when the spinal cord is stimulated tonically to increase the excitability of the lumbosacral locomotor circuitry. Furthermore, we learned that load-bearing sensory information can serve as the controller of these complex motor tasks and that the performance of these tasks can be improved even further with combinations of epidural stimulation, pharmacological, and motor training interventions. We have shown that four humans with a motor complete spinal injury have regained independent standing, assisted stepping, and even a significant level of voluntary control of the lower limbs in the presence of epidural stimulation, with one subject now even having some volitional control without stimulation. Improvement in bladder control, blood pressure, temperature regulation, and even sexual function has been realized. Thus, our present challenge is to develop the capability to selectively activate combinations of neural networks that can enable standing, and probably stepping, by improving the technologies needed to make this intervention available in the clinic and in the home of individuals with complete motor paralysis using a chronic epidural electrode implant. Specifically, we will further improve the electrode array stimulation technology needed for fine-tune control in rats and humans and transform the present hardwired technology for rats to a wireless capability to stimulate and record evoked potentials along the brain-spinal cord-muscle axis in the rat. To advance the clinical potential, we will continue to develop, refine and validate our machine-learning strategies which automatically optimize stimulation parameters for standing, stepping, and voluntary control. We will develop an improved interface between the devices implanted in our present subjects and the control devices for defining the specific stimulation parameters needed for a given subject to perform a motor task in the clinic or at home.

Public Health Relevance

We now have demonstrated that the human lumbosacral spinal cord can be neuromodulated with epidural stimulation to enable recovery of standing and volitional control of the lower limbs and return of some autonomic function after complete motor paralysis. Therefore, our objectives are now to develop the technologies needed to more fully capitalize on this clinical potential and develop home-use technologies to do so.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZRG1-ETTN-B (51))
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Peng, Grace
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University of California Los Angeles
Schools of Arts and Sciences
Los Angeles
United States
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Culaclii, Stanislav; Kim, Brian; Lo, Yi-Kai et al. (2018) Online Artifact Cancelation in Same-Electrode Neural Stimulation and Recording Using a Combined Hardware and Software Architecture. IEEE Trans Biomed Circuits Syst 12:601-613
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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
Liu, Wentai; Wang, Po-Min; Lo, Yi-Kai (2017) Towards Closed-Loop Neuromodulation: A Wireless Miniaturized Neural Implant SoC. Proc SPIE Int Soc Opt Eng 10194:
Lo, Yi-Kai; Chang, Chih-Wei; Kuan, Yen-Cheng et al. (2016) A 176-Channel 0.5cm(3) 0.7g Wireless Implant for Motor Function Recovery after Spinal Cord Injury. Dig Tech Pap IEEE Int Solid State Circuits Conf 2016:382-383
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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
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

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