It has been suggested that neuroplasticity-promoting neuromodulation can restore sensory-motor pathways after spinal cord injury (SCI), reactivating the dormant locomotor neuronal circuitry. We introduce a neuro-rehabilitative approach that leverages locomotor training with multi-segmental spinal cord transcutaneous electrical stimulation (scTS). We hypothesized that scTS neuromodulates spinal networks, complementing the neuroplastic effects of locomotor training, result in a functional progression toward recovery of locomotion. We conducted a case-study to test this approach on a 27-year-old male classified as AIS A with chronic SCI. The training regimen included task-driven non-weight-bearing training (1 month) followed by weight-bearing training (2 months). Training was paired with multi-level continuous and phase-dependent scTS targeting function-specific motor pools. Results suggest a convergence of cross-lesional networks, improving kinematics during voluntary non-weight-bearing locomotor-like stepping. After weight-bearing training, coordination during stepping improved, suggesting an important role of afferent feedback in further improvement of voluntary control and reorganization of the sensory-motor brain-spinal connectome.

Novel Non-invasive Strategy for Spinal Neuromodulation to Control Human Locomotion

Cervical spinal cord injury can disrupt connections between the brain respiratory network and the respiratory muscles which can lead to partial or complete loss of ventilatory control and require ventilatory assistance. Unlike current open-loop technology, a closed-loop diaphragmatic pacing system could overcome the drawbacks of manual titration as well as respond to changing ventilation requirements. We present an original bio-inspired assistive technology for real-time ventilation assistance, implemented in a digital configurable Field Programmable Gate Array (FPGA). The bio-inspired controller, which is a spiking neural network (SNN) inspired by the medullary respiratory network, is as robust as a classic controller while having a flexible, low-power and low-cost hardware design. The system was simulated in MATLAB with FPGA-specific constraints and tested with a computational model of rat breathing; the model reproduced experimentally collected respiratory data in eupneic animals. The open-loop version of the bio-inspired controller was implemented on the FPGA. Electrical test bench characterizations confirmed the system functionality. Open and closed-loop paradigm simulations were simulated to test the FPGA system real-time behavior using the rat computational model. The closed-loop system monitors breathing and changes in respiratory demands to drive diaphragmatic stimulation. The simulated results inform future acute animal experiments and constitute the first step towards the development of a neuromorphic, adaptive, compact, low-power, implantable device. The bio-inspired hardware design optimizes the FPGA resource and time costs while harnessing the computational power of spike-based neuromorphic hardware. Its real-time feature makes it suitable for in vivo applications.

Ventilatory pacing by electrical stimulation of the phrenic nerve or of the diaphragm has been shown to enhance quality of life compared to mechanical ventilation. However, commercially available ventilatory pacing devices require initial manual specification of stimulation parameters and frequent adjustment to achieve and maintain suitable ventilation over long periods of time. Here, we have developed an adaptive, closed-loop, neuromorphic, pattern-shaping controller capable of automatically determining a suitable stimulation pattern and adapting it to maintain a desired breath-volume profile on a breath-by-breath basis. The system adapts the pattern of stimulation parameters based on the error between the measured volume sampled every 40 ms and a desired breath volume profile. In vivo studies in anesthetized male Sprague-Dawley rats without and with spinal cord injury by spinal hemisection at C2 indicated that the controller was capable of automatically adapting stimulation parameters to attain a desired volume profile. Despite diaphragm hemiparesis, the controller was able to achieve a desired volume in the injured animals that did not differ from the tidal volume observed before injury (p = 0.39). Closed-loop adaptive pacing partially mitigated hypoventilation as indicated by reduction of end-tidal CO₂ values during pacing. The closed-loop controller was developed and parametrized in a computational testbed before in vivo assessment. This bioelectronic technology could serve as an individualized and autonomous respiratory pacing approach for support or recovery from ventilatory deficiency.

Functional Electrical Stimulation can be used to restore motor functions loss consecutive to spinal cord injury, such as respiratory deficiency due to paralysis of ventilatory muscles. This paper presents a fully configurable IC-centered stimulator designed to investigate muscle stimulation paradigms. It provides 8 current stimulation channels with high-voltage compliance and real-time operation capabilities, to enable a wide range of FES applications. The stimulator can be used in a standalone mode, or within a closed-loop setup. Primary in vivo results show successful drive of respiratory muscles stimulation using a computer-based dedicated controller.

People with cervical spinal cord injury have partial or complete loss of ventilatory control and require ventilator assist. Open-loop diaphragmatic pacing can be utilized to provide this assist. A closed-loop diaphragmatic pacing system could overcome the drawbacks for manual titration of the stimulation and respond to changing ventilatory requirements. We have developed a versatile custom hardware platform dubbed “Multimed” for biosignal acquisition and parallel real-time computation, data display and storage. We have also developed a new rodent model for diaphragmatic pacing. Using these we illustrate, to our knowledge for the first-time, the successful ability to perform respiratory flow-phase triggered closed-loop diaphragmatic stimulation with resultant changes in respiratory flow and tidal volume.