A neurorobotic platform for locomotor prosthetic development in rats and mice

Objectives. We aimed to develop a robotic interface capable of providing finely-tuned, multidirectional trunk assistance adjusted in real-time during unconstrained locomotion in rats and mice. Approach. We interfaced a large-scale robotic structure actuated in four degrees of freedom to exchangeable attachment modules exhibiting selective compliance along distinct directions. This combination allowed high-precision force and torque control in multiple directions over a large workspace. We next designed a neurorobotic platform wherein real-time kinematics and physiological signals directly adjust robotic actuation and prosthetic actions. We tested the performance of this platform in both rats and mice with spinal cord injury. Main Results. Kinematic analyses showed that the robotic interface did not impede locomotor movements of lightweight mice that walked freely along paths with changing directions and height profiles. Personalized trunk assistance instantly enabled coordinated locomotion in mice and rats with severe hindlimb motor deficits. Closed-loop control of robotic actuation based on ongoing movement features enabled real-time control of electromyographic activity in anti-gravity muscles during locomotion. Significance. This neurorobotic platform will support the study of the mechanisms underlying the therapeutic effects of locomotor prosthetics and rehabilitation using high-resolution genetic tools in rodent models

Quantitative Comparison of 4D MRI Flow Measurements to 3D Computational Fluid Dynamics Simulation of Cerebrospinal Fluid Movement in the Spinal Subarachnoid Space

Computational fluid dynamic (CFD) simulations have provided detailed information about the complex flow and pressure field within the cerebrospinal fluid (CSF) system. The solutions of these simulations are sensitive to boundary conditions and thus need validation with in vivo measurements. However, validation of CFD flow results and MRI CSF flow measurements have been limited to through-plane pcMR measurements

Wireless closed-loop optogenetics across the entire dorsoventral spinal cord in mice

Optoelectronic systems can exert precise control over targeted neurons and pathways throughout the brain in untethered animals, but similar technologies for the spinal cord are not well established. In the present study, we describe a system for ultrafast, wireless, closed-loop manipulation of targeted neurons and pathways across the entire dorsoventral spinal cord in untethered mice. We developed a soft stretchable carrier, integrating microscale light-emitting diodes (micro-LEDs), that conforms to the dura mater of the spinal cord. A coating of silicone–phosphor matrix over the micro-LEDs provides mechanical protection and light conversion for compatibility with a large library of opsins. A lightweight, head-mounted, wireless platform powers the micro-LEDs and performs low-latency, on-chip processing of sensed physiological signals to control photostimulation in a closed loop. We use the device to reveal the role of various neuronal subtypes, sensory pathways and supraspinal projections in the control of locomotion in healthy and spinal-cord injured mice.ISSN:1546-1696ISSN:1087-015

Walking naturally after spinal cord injury using a brain–spine interface

International audienceAbstract A spinal cord injury interrupts the communication between the brain and the region of the spinal cord that produces walking, leading to paralysis 1,2 . Here, we restored this communication with a digital bridge between the brain and spinal cord that enabled an individual with chronic tetraplegia to stand and walk naturally in community settings. This brain–spine interface (BSI) consists of fully implanted recording and stimulation systems that establish a direct link between cortical signals 3 and the analogue modulation of epidural electrical stimulation targeting the spinal cord regions involved in the production of walking 4–6 . A highly reliable BSI is calibrated within a few minutes. This reliability has remained stable over one year, including during independent use at home. The participant reports that the BSI enables natural control over the movements of his legs to stand, walk, climb stairs and even traverse complex terrains. Moreover, neurorehabilitation supported by the BSI improved neurological recovery. The participant regained the ability to walk with crutches overground even when the BSI was switched off. This digital bridge establishes a framework to restore natural control of movement after paralysis

A spinal cord neuroprosthesis for locomotor deficits due to Parkinson’s disease

International audiencePeople with late-stage Parkinson’s disease (PD) often suffer from debilitating locomotor deficits that are resistant to currently available therapies. To alleviate these deficits, we developed a neuroprosthesis operating in closed loop that targets the dorsal root entry zones innervating lumbosacral segments to reproduce the natural spatiotemporal activation of the lumbosacral spinal cord during walking. We first developed this neuroprosthesis in a non-human primate model that replicates locomotor deficits due to PD. This neuroprosthesis not only alleviated locomotor deficits but also restored skilled walking in this model. We then implanted the neuroprosthesis in a 62-year-old male with a 30-year history of PD who presented with severe gait impairments and frequent falls that were medically refractory to currently available therapies. We found that the neuroprosthesis interacted synergistically with deep brain stimulation of the subthalamic nucleus and dopaminergic replacement therapies to alleviate asymmetry and promote longer steps, improve balance and reduce freezing of gait. This neuroprosthesis opens new perspectives to reduce the severity of locomotor deficits in people with PD

Cortico-reticulo-spinal circuit reorganization enables functional recovery after severe spinal cord contusion.

Severe spinal cord contusions interrupt nearly all brain projections to lumbar circuits producing leg movement. Failure of these projections to reorganize leads to permanent paralysis. Here we modeled these injuries in rodents. A severe contusion abolished all motor cortex projections below injury. However, the motor cortex immediately regained adaptive control over the paralyzed legs during electrochemical neuromodulation of lumbar circuits. Glutamatergic reticulospinal neurons with residual projections below the injury relayed the cortical command downstream. Gravity-assisted rehabilitation enabled by the neuromodulation therapy reinforced these reticulospinal projections, rerouting cortical information through this pathway. This circuit reorganization mediated a motor cortex-dependent recovery of natural walking and swimming without requiring neuromodulation. Cortico-reticulo-spinal circuit reorganization may also improve recovery in humans

Spatiotemporal neuromodulation therapies engaging muscle synergies improve motor control after spinal cord injury.

International audienceElectrical neuromodulation of lumbar segments improves motor control after spinal cord injury in animal models and humans. However, the physiological principles underlying the effect of this intervention remain poorly understood, which has limited the therapeutic approach to continuous stimulation applied to restricted spinal cord locations. Here we developed stimulation protocols that reproduce the natural dynamics of motoneuron activation during locomotion. For this, we computed the spatiotemporal activation pattern of muscle synergies during locomotion in healthy rats. Computer simulations identified optimal electrode locations to target each synergy through the recruitment of proprioceptive feedback circuits. This framework steered the design of spatially selective spinal implants and real-time control software that modulate extensor and flexor synergies with precise temporal resolution. Spatiotemporal neuromodulation therapies improved gait quality, weight-bearing capacity, endurance and skilled locomotion in several rodent models of spinal cord injury. These new concepts are directly translatable to strategies to improve motor control in humans