A corticospinal neuroprosthesis for lower limb neuromodulation therapies after spinal cord injury

Society for Neuroscience Chicago 2015 Sensorimotor Neuroprosthetics Brain-Machine Interface
Support: European Research Council, ERC “Walk Again” European Union Framework 7, Project “NeuWalk”, Swiss National Science Foundation, Project “Dynamo”. NanoTera Programme, Project “SpineRepair” National Center of Competence in Research in Robotics

A corticospinal neuroprosthesis for lower limb neuromodulation therapies after spinal cord injury

Abstract: Severe spinal cord injuries disrupt the communication between supraspinal centers and spinal circuits coordinating lower limb movements, which leads to profound motor deficits. However, sublesional lumbosacral spinal segments retain the capacity to generate complex motor behaviors, while the motor cortex retains the capacity to control prosthetic devices in rodents and humans. Here we aimed to demonstrate the feasibility of interfacing sensorimotor cortex signals with electrical spinal cord stimulation to improve locomotion during rehabilitation after a severe spinal cord contusion in rats. We found that even early after a functionally complete spinal cord contusion, hind-limb sensorimotor cortex modulations contained information related to the motor state and gait phases. We then designed a hard-real-time infrastructure whereby features of locomotor-related neuronal ensemble modulation from the motor cortex directly triggered and adjusted electrical spinal cord stimulation to facilitate hindlimb movements. This corticospinal neuroprosthesis alleviated various types of lower limb deficits during locomotion, e.g., reducing foot dragging and increasing foot displacement velocity. These results demonstrate the feasibility of establishing an electronic bypass to restore communication between the brain and the spinal cord in order to facilitate rehabilitation after spinal cord injury.

Funding: European Research Council, ERC “Walk Again”; European Union Framework 7 Project “NeuWalk”; Swiss National Science Foundation, Project “Dynamo”; NanoTera Programme, Project “SpineRepair”; National Center of Competence in Research in Robotics.
Disclosures: M. Bonizzato: None. A. Philippides: None. F. DeCecco: None. G. Pidpruzhnykova: None. N. Pavlova: None. S. Duis: None. J. DiGiovanna: None. G. Courtine: None. S. Micera: None.

Authors: *M. BONIZZATO1, A. PHILIPPIDES1, F. DECECCO1, G. PIDPRUZHNYKOVA1, N. PAVLOVA1,2, S. DUIS1, J. DIGIOVANNA1, G. COURTINE1, S. MICERA1; 1École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; 2Pavlov Inst. of Physiology, Russian Acad. of Sci., Saint-Petersburg, Russian Federation

Chronic functionality and biocompatibility assessment of an intraneural stimulating electrode in the rat sciatic nerve

Abstract: Peripheral nerve stimulation has been shown to have the potential to restore sensory feedback after amputation in humans. However, incomplete long term stability assessment of current intraneural electrodes limits their potential for clinical applications. An ensemble of four key criteria defines the success of a stimulating peripheral nerve electrode – stability, selectivity, functionality, and biocompatibility. Here we evaluated these pivotal features for a newly developed self-opening intra-neural electrode (SELINE) using a chronic rat model. A SELINE electrode was implanted in the left sciatic nerve of 5 female Lewis rats, which also received bipolar electrodes into ankle muscles to record electromyographic activity. Weekly evaluations of muscle recruitment curves in response to electrical stimulation through each of the ten active sites of the SELINE implant demonstrated the stability of charge delivery and muscle recruitment selectivity after three to four weeks post-implantation, and for a duration of 4.5 months. The selectivity of the electrodes allowed the preferential recruitment of flexor versus extensor muscles in all the implanted rats. To demonstrate the functionality and controllability of this selective muscle activation, we developed a closed-loop control system whereby real-time adjustment of stimulation frequency through selective electrodes achieved high fidelity control of ankle kinematics and the produced force. Immunohistochemistry of the chronically implanted nerves revealed a loss of myelin and axons around the implant site. In all 5 rats, we also observed a layer of fibroblasts and an accumulation of multi-nucleated cells that encapsulated the implant. The high degree of muscle activation selectivity and functionality of the long term SELINE implants provides promising perspectives for chronic therapeutic applications. In light of the stability of these results, the impact of chronic intra-neural implants on the surrounding neural tissue is undergoing further evaluations to understand the relationship between tissue response and electrode functionality and thereby aid a translation into clinics.

Authors: *S. M. WURTH1, M. CAPOGROSSO1, S. RASPOPOVIC1,3, J. GANDAR2, Q. BARRAUD2, A. CUTRONE4, J. RIGOSA1, N. KINANY1, G. TAVERNI4, G. COURTINE2, S. MICERA1,4; 1Bertarelli Fndn. Chair in Translational Neuroengineering, CNP, STI, 2Intl. Paraplegic Fndn. Chair in Spinal Cord Repair, BMI CNP, EPFL, Lausanne, Switzerland; 4The Biorobotics Inst., 3SSSA, Pisa, Italy

Disclosures: S.M. Wurth: None. M. Capogrosso: None. S. Raspopovic: None. J. Gandar: None. Q. Barraud: None. A. Cutrone: None. J. Rigosa: None. N. Kinany: None. G. Taverni: None. G. Courtine: None. S. Micera: None.

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