System for selective spatiotemporal stimulation of the spinal cord

The present disclosure refers to systems for electrical neurostimulation of a spinal cord of a subject in need of nervous system function support. In one example, a system comprises a signal processing device configured to receive signals from the subject and operate signal-processing algorithms to elaborate stimulation parameter settings; one or more multi-electrode arrays suitable to cover a portion of the spinal cord of the subject; and an Implantable Pulse Generator (IPG) configured to receive the stimulation parameter settings from the signal processing device and simultaneously deliver independent current or voltage pulses to the one or more multiple electrode arrays, wherein the independent current or voltage pulses provide multipolar spatiotemporal stimulation of spinal circuits and/or dorsal roots. Such system advantageously enables effective control of nervous system functions in the subject by stimulating the spinal cord, such as the dorsal roots of the spinal cord, with spatiotemporal selectivity.

Jocelyne Bloch, Marco Capogrosso, Grégoire Courtine, Silvestro Micera, Nikolaus Wenger

2017

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

Selective electrical and optical neuromodulation of the central nervous system with conformable microfabricated implants

Amélie Anne Guex

Neuroprosthetic systems are designed to interface with the nervous system, for the replacement or restoration of damaged functions in the motor and/or sensory systems. In order to have an efficient communication with the nervous tissue leading to optimized clinical outcomes, achieving neural stimulation with high selectivity is essential. This thesis aims at finding technological routes to enable spatial, structural and cell-type selective surface neuromodulation using electrical and optogenetic stimulation and to validate them in in vivo models. Thin and conformable electrode arrays enable close contact with the target tissue, thereby leading to minimal distances with the target neurons and maximal spatial selectivity. Flexible polymer technologies based on polyimide (PI) are used to design thin (< 10 ÎŒm thick) electrode arrays with small feature size (< 100 ÎŒm), resulting in miniaturized conformable arrays for surface stimulation. PEDOT conducting polymer coatings are used on the miniaturized electrical stimulation sites (100 ÎŒm diameter) to improve their charge injection properties. This implant is used for auditory brainstem stimulation in a rat model, and is shown to generate robust activation of the auditory system. Analysis of the multiunit recordings obtained from the inferior colliculus (IC), an auditory structure of the midbrain, led to the identification of different phases in the responses, with various frequency tuning properties. The stimulation configuration is shown to influence the tonotopic organisation of the frequency-tuned responses. Bipolar stimulation with small interelectrode distances (400 ÎŒm) is shown to generate responses that are more frequency-selective than with larger interelectrode distances (800 ÎŒm). The orientation of the electrode pair and the waveformof stimulation current are also shown to influence the response properties. An updated design of the clinical auditory brainstem implant(ABI) is then proposed, integrating higher electrode density and guidelines for a more tissue-conformal format. The main steps in the road towards improvement of ABI outcomes are then discussed, with proposed changes in the stimulation protocol and electrode array in parallel. Another approach to cell-specific neuromodulation is the implementation of optogenetics. This requires not only genetic engineering of the neurons but also the manufacturing of implantable light-emitting devices. Here, we introduce a fabrication process for the integration of thin (50 ÎŒm) LEDs into a polyimide-based device. A proof-of-concept in vivo study shows that stimulation of the spinal cord of a mouse model generates robust EMG responses in both legs over the course of several weeks. The walking integrity is confirmed, showing the absence of functional damages to the spinal cord. These results show that the presented LED array can provide a way of stimulating key elements of the locomotor neural circuitry, potentially leading to a greater understanding of the role of each neuronal subtypes in the spinal cord. Through the applications of ABI and spinal cord stimulation, this thesis thus highlights the importance and potential use of specifically tailored technologies enabling selective surface stimulation of the nervous system.

EPFL2017

Selective electrical and optical neuromodulation of the central nervous system with conformable microfabricated implants

Amélie Anne Guex

EPFL2017

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

Nature Publishing Group2016