A spinal cord injury (SCI) alters the communication between the brain and spinal cord. The consequences are dramatic impairments of upper-limb and lower-limb motor functions, which have a profound impact on the affected person, their family, and society. Currently, there are no approved therapies for SCI. The resulting costs of care amount to more than 2.5 M? over the lifetime of a person with SCI. Two ERCs combined with two ERC-PoCs enabled us to prototype two brain-spine interfaces (BSIs) that link the intended movements decoded from motor cortex activity to precise electrical stimulations of the spinal cord to promote these movements. These BSIs restored walking and arm/hand movements in nonhuman primate models of SCI, and as we report here, enabled one patient with chronic paralysis to walk again outdoors. These prototypes were partly based on repurposed devices that were not optimized for the intended applications, and thus presented shortcomings. Here, we propose to integrate two breakthrough technologies to develop two fully-implantable BSIs that will remedy these limitations. The first technology consists of the only existing fully-implantable neurosensor for wireless monitoring of cortical activity in humans based on high-density grids positioned over the dura mater. The second technology is the only implantable neurostimulation system dedicated to the recovery of movement after paralysis. This system combines an implantable pulse generator that enables highly reliable, real-time control of spinal cord stimulation, and a portfolio of electrode arrays that have been designed to leverage the mechanisms through which this stimulation restores movement. Two small scale clinical trials will demonstrate that these BSIs restore lower-limb and upper-limb movements in humans with chronic paralysis. These studies will provide specifications for industrial versions of the BSIs, opening the path to a commercially-viable revolution for people living with paralysis.

Nearly 746,000 people sustain a spinal cord injury every year, with dramatic human, societal and economical cost, leading to impairment or even complete loss of motor functions. Motor Brain-Machine Interfaces (BMIs) translate brain neural signals into commands to external effectors. BMIs raise hopes that limb mobility may be restored, providing patients with control over orthoses, prostheses, or over their own limbs using electrical stimulation. In spite of spectacular results, taking neuroprosthetics into daily practice has proven difficult. Currently, neuroprosthetics are restricted to assisted trials in laboratories, and require regular retraining of a decoder in a supervised manner within controlled environments. They include various components (recording device, antennas, base station, computers connected to effectors, etc.) that are complicated to install and to use. Building on the consortium's unique experience in clinical chronic BMIs, the project will address major methodological and technological breakthroughs to achieve the first assistance-free motor neuroprosthetics system. NEMO BMI project will conduct the exploration of assistance-free and easy to use portable neuroprosthetics including wireless neuronal activity recorder, a real-time neuronal activity decoder based on integrated technologies, and a spinal cord stimulator. A first objective is the crucial improvement of usability, by introducing an auto-adaptive framework to train the decoder in an adaptive manner during the neuroprosthetics unsupervised use. Brain-guided spinal cord stimulation activating patients’ limbs with an automatic stimulus pattern optimization is the second project objective. A third objective is the exploration of miniaturized embedded solutions by taking advantage of a novel neuromorphic hardware architecture. NEMO BMI technologies will be studied offline and online in two ongoing clinical trials, and will be critical to specify the next-generation assistance-free BMI.

From violinists to metal welders, finely tuned hand and arm movements are the foundation of craft, while all of us rely on proficient use of hands for the activities of daily life. Yet, more than 25 million people worldwide lost functional movements to subcortical stroke. Subcortical stroke often interrupts the communication between the cortex and the cervical spinal cord circuits, which leads to permanent hand and arm paralysis. The result is a vastly reduced quality of life and enormous socioeconomic burden for the affected, their families, and the society. A treatment that can effectively restore functional movements after subcortical stroke does not yet exist. Still, the motor cortex, which orchestrates movements, and the spinal cord motor circuits that directly control muscles remain largely intact. We aim to reverse the hand and arm paralysis of people with subcortical stroke by developing a digital bridge that reconnects the motor cortex with the cervical spinal motor circuits. This brain-spine interface consists of fully-implantable recording and stimulation systems that link cortical signals to spatiotemporal sequences of epidural electrical stimulation targeting spinal cord regions involved in the production of hand and arm movements. Our preliminary results in people with spinal cord injury strongly indicate that the brain-spine interface can restore natural control of movement and promote neurological recovery. Therefore, we are confident that a cervical brain-spine interface can reverse hand and arm paralysis incurred by stroke and, therefore, become the first viable treatment option for subcortical stroke survivors. Beyond the development and validation of the cervical brain-spine interface for stroke survivors, this project will build the intellectual property necessary to secure funding that will bring this treatment into widespread clinical use.

ReWIRE will combine innovative translational neurotechnologies and rehabilitation interventions for the repair and restoration of neurological functions following injury of the spinal cord (SC). The proposed research program will equip next-generation scientists with unique skills to develop disruptive therapeutic solutions for patients with paralysis. Recent technological breakthroughs have triggered a paradigm shift in the conception of therapies aimed to restore function after spinal cord injury (SCI). Novel drug delivery systems and biomaterial bridges have been engineered to reduce secondary injury and scarring, to stimulate and guide regenerating nerve fibres across the lesion site, and to promote functional reconnection with intact tissue. Additionally, neuromodulation therapies can reactivate spinal circuits below a SCI, allowing people with chronic paralysis to regain voluntary control of walking. In conjunction with rehabilitation, neurological recovery was promoted that persisted without neuromodulation, suggesting a rewiring of the SC as demonstrated in preclinical models. To bypass an injury, neuromodulation has been linked to brain signals to re-establish cortical control over spinal circuits by employing electrical nerve stimulation and robotic systems. Advances in robotics are significantly augmenting the impact of neurorehabilitation by inducing new natural “wired” connections. The aim of ReWIRE is to leverage all these technical and therapeutic breakthroughs in the framework of multiple PhD projects that will continuously interact to converge toward effective combinatorial treatments for SCI. ReWIRE will focus on three inter-woven objectives: i) establish an international, interdisciplinary, and intersectoral educational network, ii) build an SCI clinical data platform, and, iii) position Europe at the forefront of therapy for SCI.