Closed-loop neuromodulation of spinal sensorimotor circuits controls refined locomotion after complete spinal cord injury.

Neuromodulation of spinal sensorimotor circuits improves motor control in animal models and humans with spinal cord injury. With common neuromodulation devices, electrical stimulation parameters are tuned manually and remain constant during movement. We developed a mechanistic framework to optimize neuromodulation in real time to achieve high-fidelity control of leg kinematics during locomotion in rats. We first uncovered relationships between neuromodulation parameters and recruitment of distinct sensorimotor circuits, resulting in predictive adjustments of leg kinematics. Second, we established a technological platform with embedded control policies that integrated robust movement feedback and feed-forward control loops in real time. These developments allowed us to conceive a neuroprosthetic system that controlled a broad range of foot trajectories during continuous locomotion in paralyzed rats. Animals with complete spinal cord injury performed more than 1000 successive steps without failure, and were able to climb staircases of various heights and lengths with precision and fluidity. Beyond therapeutic potential, these findings provide a conceptual and technical framework to personalize neuromodulation treatments for other neurological disorders.

Spatially distributed sequential stimulation reduces fatigue in paralyzed triceps surae muscles: a case study.

Functional electrical stimulation (FES) is limited by the rapid onset of muscle fatigue caused by localized nerve excitation repeatedly activating only a subset of motor units. The purpose of this study was to investigate reducing fatigue by sequentially changing, pulse by pulse, the area of stimulation using multiple surface electrodes that cover the same area as one electrode during conventional stimulation. Paralyzed triceps surae muscles of an individual with complete spinal cord injury were stimulated, via the tibial nerve, through four active electrodes using spatially distributed sequential stimulation (SDSS) that was delivered by sending a stimulation pulse to each electrode one after another with 90° phase shift between successive electrodes. For comparison, single electrode stimulation was delivered through one active electrode. For both modes of stimulation, the resultant frequency to the muscle as a whole was 40 Hz. Isometric ankle torque was measured during fatiguing stimulations lasting 2 min. Each mode of stimulation was delivered a total of six times over 12 separate days. Three fatigue measures were used for comparison: fatigue index (final torque normalized to maximum torque), fatigue time (time for torque to drop by 3 dB), and torque-time integral (over the entire trial). The measures were all higher during SDSS (P < 0.001), by 234, 280, and 171%, respectively. The results are an encouraging first step toward addressing muscle fatigue, which is one of the greatest problems for FES.

Wearable neural prostheses. Restoration of sensory-motor function by transcutaneous electrical stimulation.

In this article, we focus on the least invasive interface: transcutaneous ES (TES), i.e., the use of surface electrodes as an interface between the stimulator and sensory-motor systems. TES is delivered by a burst of short electrical charge pulses applied between pairs of electrodes positioned on the skin. Monophasic or charge-balanced biphasic (symmetric or asymmetric) stimulation pulses can be delivered. The latter ones have the advantage to provide contraction force while minimizing tissue damage.

The influence of electrode size on selectivity and comfort in transcutaneous electrical stimulation of the forearm.

Transcutaneous electrical stimulation (TES) is a technique to artificially activate motor nerves and muscles. It can be used for rehabilitation or the restoration of lost motor functions, e.g., in subjects with brain or spinal cord lesions. Apart from selectively activating motor nerves and muscles, TES activates sensory fibers and pain receptors, producing discomfort and pain. Clinicians try to minimize discomfort by optimizing stimulation parameters, electrode location, and electrode size. There are some studies that found optimal electrode sizes for certain stimulation sites (e.g., gastrocnemius), however the underlying effects why certain electrode sizes are preferred by patients is not well understood. We used a TES model consisting of a finite element (FE) model and a nerve model to assess the influence of different electrode sizes on the selectivity and the perceived comfort for various anatomies. Motor thresholds calculated using the TES model were compared with motor thresholds that were obtained from measurements performed on the forearm of ten human volunteers. Results of the TES model indicate that small electrodes (0.8 x 0.8 cm(2)) are more comfortable for thin fat layers (0.25 cm) and superficial nerves (0.1 cm) and larger electrodes (4.1 x 4.1 cm(2)) are more comfortable for thicker fat layers (2 cm) and deeper nerves (1.1 cm) at a constant recruitment.

Array electrode design for transcutaneous electrical stimulation: a simulation study.

Array electrodes are a promising technology that is likely to bring transcutaneous electrical stimulation (TES) a step forward. The dynamic adaptation of electrode size and position helps to simplify the use of electrical stimulation systems and to increase their clinical efficacy. However, up to now array electrodes were built by trial and error and it is unclear how, for example, the gaps between the array elements or the resistivity of the electrode-skin interface material influence the current distribution. A TES model that comprises a finite element model and a nerve model has been used to analyze the influence of array electrode gaps and gel resistivities on nerve activation. Simulation results indicate that the resistivity of the electrode-skin interface layer should be adapted depending on the size of the gaps between the array elements. Furthermore, the gap sizes should be smaller than 3mm in order to keep losses small.

A model for transcutaneous current stimulation: simulations and experiments.

Complex nerve models have been developed for describing the generation of action potentials in humans. Such nerve models have primarily been used to model implantable electrical stimulation systems, where the stimulation electrodes are close to the nerve (near-field). To address if these nerve models can also be used to model transcutaneous electrical stimulation (TES) (far-field), we have developed a TES model that comprises a volume conductor and different previously published non-linear nerve models. The volume conductor models the resistive and capacitive properties of electrodes, electrode-skin interface, skin, fat, muscle, and bone. The non-linear nerve models were used to conclude from the potential field within the volume conductor on nerve activation. A comparison of simulated and experimentally measured chronaxie values (a measure for the excitability of nerves) and muscle twitch forces on human volunteers allowed us to conclude that some of the published nerve models can be used in TES models. The presented TES model provides a first step to more extensive model implementations for TES in which e.g., multi-array electrode configurations can be tested.

New multi-channel transcutaneous electrical stimulation technology for rehabilitation.

Transcutaneous (surface) electrical stimulation (TES) is a widely applied technique for muscle atrophy treatment, muscle force training, endurance training, pain treatment, functional movement therapy, and the restoration of motor functions. We present a new TES technology based on a multi-channel stimulation approach, which allows us to perform real-time spatial and temporal variations of the electrical current density on the skin surface and in deeper tissue layers. This new approach can generate a better muscle selectivity and improved muscle activation patterns compared to state of art TES systems, which operate with predetermined electrode positions. In simulations using a finite element model (FEM) of the distal arm we could show that the nerve activation in the muscle layer is not significantly influenced by the structure of the multi-channel electrode, if the gap between elements is less than 2 mm. Experiments in healthy volunteers allowed us to measure the selectivity of single finger activations. We could also show in stroke subjects that this novel multi-channel approach was able to generate selective finger and wrist extension movements that were strong enough to overcome flexion hyperactivity. For future applications in rehabilitation a full integration of the stimulation hardware into a garment sleeve would be helpful. Once fully integrated, this new technology has a high potential to increase the ease of use, stimulation and wear comfort. It is able to improve muscle selectivity compared to state of the art TES systems, and allows the implementation of a variety of new applications for the medical and consumer market.