Non-invasive, Brain-controlled Functional Electrical Stimulation for Locomotion Rehabilitation in Individuals with Paraplegia

Spinal cord injury (SCI) impairs the flow of sensory and motor signals between the brain and the areas of the body located below the lesion level. Here, we describe a neurorehabilitation setup combining several approaches that were shown to have a positive effect in patients with SCI: gait training by means of non-invasive, surface functional electrical stimulation (sFES) of the lower-limbs, proprioceptive and tactile feedback, balance control through overground walking and cue-based decoding of cortical motor commands using a brain-machine interface (BMI). The central component of this new approach was the development of a novel muscle stimulation paradigm for step generation using 16 sFES channels taking all sub-phases of physiological gait into account. We also developed a new BMI protocol to identify left and right leg motor imagery that was used to trigger an sFES-generated step movement. Our system was tested and validated with two patients with chronic paraplegia. These patients were able to walk safely with 65-70% body weight support, accumulating a total of 4,580 steps with this setup. We observed cardiovascular improvements and less dependency on walking assistance, but also partial neurological recovery in both patients, with substantial rates of motor improvement for one of them.

A brain-spine interface alleviating gait deficits after spinal cord injury in primates

Quentin Barraud, Jocelyne Bloch, David Allenson Borton, Marco Capogrosso, Grégoire Courtine, Simone Ellen Joze Duis, Jérôme Gandar, Eduardo Martin Moraud, Silvestro Micera, Jean-Baptiste Mignardot, Tomislav Milekovic, Elodie Rey, Fabien Bertrand Paul Wagner

Spinal cord injury disrupts the communication between the brain and the spinal circuits that orchestrate movement. To bypass the lesion, brain-computer interfaces(1-3) have directly linked cortical activity to electrical stimulation of muscles, and have thus restored grasping abilities after hand paralysis(1,4). Theoretically, this strategy could also restore control over leg muscle activity for walking(5). However, replicating the complex sequence of individual muscle activation patterns underlying natural and adaptive locomotor movements poses formidable conceptual and technological challenges(6,7). Recently, it was shown in rats that epidural electrical stimulation of the lumbar spinal cord can reproduce the natural activation of synergistic muscle groups producing locomotion(8-10). Here we interface leg motor cortex activity with epidural electrical stimulation protocols to establish a brain-spine interface that alleviated gait deficits after a spinal cord injury in non-human primates. Rhesus monkeys (Macaca mulatta) were implanted with an intracortical microelectrode array in the leg area of the motor cortex and with a spinal cord stimulation system composed of a spatially selective epidural implant and a pulse generator with realtime triggering capabilities. We designed and implemented wireless control systems that linked online neural decoding of extension and flexion motor states with stimulation protocols promoting these movements. These systems allowed the monkeys to behave freely without any restrictions or constraining tethered electronics. After validation of the brain-spine interface in intact (uninjured) monkeys, we performed a unilateral corticospinal tract lesion at the thoracic level. As early as six days post-injury and without prior training of the monkeys, the brain-spine interface restored weight-bearing locomotion of the paralysed leg on a treadmill and overground. The implantable components integrated in the brain-spine interface have all been approved for investigational applications in similar human research, suggesting a practical translational pathway for proof-of-concept studies in people with spinal cord injury.

Nature Publishing Group2016

Long-Term Training with a Brain-Machine Interface-Based Gait Protocol Induces Partial Neurological Recovery in Paraplegic Patients

Hannes Bleuler, Simon Gallo, Miguel Nicolelis, Solaiman Shokur

Brain-machine interfaces (BMIs) provide a new assistive strategy aimed at restoring mobility in severely paralyzed patients. Yet, no study in animals or in human subjects has indicated that long-term BMI training could induce any type of clinical recovery. Eight chronic (3-13 years) spinal cord injury (SCI) paraplegics were subjected to long-term training (12 months) with a multi-stage BMI-based gait neurorehabilitation paradigm aimed at restoring locomotion. This paradigm combined intense immersive virtual reality training, enriched visual-tactile feedback, and walking with two EEG-controlled robotic actuators, including a custom-designed lower limb exoskeleton capable of delivering tactile feedback to subjects. Following 12 months of training with this paradigm, all eight patients experienced neurological improvements in somatic sensation (pain localization, fine/crude touch, and proprioceptive sensing) in multiple dermatomes. Patients also regained voluntary motor control in key muscles below the SCI level, as measured by EMGs, resulting in marked improvement in their walking index. As a result, 50% of these patients were upgraded to an incomplete paraplegia classification. Neurological recovery was paralleled by the reemergence of lower limb motor imagery at cortical level. We hypothesize that this unprecedented neurological recovery results from both cortical and spinal cord plasticity triggered by long-term BMI usage.

Nature Publishing Group2016

Brain-controlled neuroprosthetic interventions to restore locomotion after contusion spinal cord injury in the rat

Marco Bonizzato

Spinal cord injury (SCI), second only to stroke, is the leading cause of paralysis. Therapies based on electrical stimulation of the spinal cord and other locomotor areas of the Nervous System improve motor control in people with neurotrauma. Neuromodulation of the sensorimotor systems can indeed reactivate circuitries that are left dormant after SCI and turn them into an active locomotor state. These results have been found in animal models and translated to clinical fruition. Recent medical research has demonstrated that the involvement of volition and motor intent is a decisive factor for success of rehabilitation therapies that involve functional electrical stimulation of spinal cord and muscles. A key brain area that encodes information related to the conscious processing and execution of movement is the primary sensory-motor cortex. In this thesis I present two novel neuroprosthetic systems for neuromodulation based on cortical population activity in rats with SCI. We tested the hypotheses that neurons in the motor cortex could provide a reliable input for closed-loop neuroprosthetic systems designed to electrically stimulate different locomotor areas of the nervous system in a locomotor-phase-specific manner and thus enhance the locomotor output. During the experiments, we connected cortical correlates of intended movements with patterns of stimulation delivered either at the midbrain or at the sublesional spinal cord. Our brain-controlled functional stimulation reduced locomotor deficits caused by spinal cord injury and restored voluntary control of foot movement. These findings and the control policies we developed could be applied to clinical trials to improve the results of neurorehabilitation, for the benefit of people living with SCI.

EPFL2017

A brain-spine interface alleviating gait deficits after spinal cord injury in primates

Nature Publishing Group2016