Motor Neuroprostheses.

Neuroprostheses (NPs) are electrical stimulators that activate nerves, either to provide sensory input to the central nervous system (sensory NPs), or to activate muscles (motor NPs: MNPs). The first MNPs were belts with inbuilt batteries and electrodes developed in the 1850s to exercise the abdominal muscles. They became enormously popular among the general public, but as a result of exaggerated therapeutic claims they were soon discredited by the medical community. In the 1950s, MNPs reemerged for the serious purpose of activating paralyzed muscles. Neuromuscular electrical stimulation (NMES), when applied in a preset sequence, is called therapeutic electrical stimulation (TES). NMES timed so that it enhances muscle contraction in intended voluntary movements is called functional electrical stimulation (FES) or functional neuromuscular stimulation (FNS). It has been 50 years since the first FES device, a foot-drop stimulator, was described and 40 years since the first implantable version was tested in humans. A commercial foot-drop stimulator became available in the 1970s, but for various reasons, it failed to achieve widespread use. With advances in technology, such devices are now more convenient and reliable. Enhancing upper limb function is a more difficult task, but grasp-release stimulators have been shown to provide significant benefits. This chapter deals with the technical aspects of NMES, the therapeutic and functional benefits of TES and FES, delayed-onset and carryover effects attributable to "neuromodulation" and the barriers and opportunities in this rapidly developing field. © 2019 American Physiological Society. Compr Physiol 9:127-148, 2019.

Histological evaluation of flexible neural implants; flexibility limit for reducing the tissue response?

OBJECTIVE: Flexible neural probes are hypothesized to reduce the chronic foreign body response (FBR) mainly by reducing the strain-stress caused by an interplay between the tethered probe and the brain's micromotion. However, a large discrepancy of Young's modulus still exists (3-6 orders of magnitude) between the flexible probes and the brain tissue. This raises the question of whether we need to bridge this gap; would increasing the probe flexibility proportionally reduce the FBR? APPROACH: Using novel off-stoichiometry thiol-enes-epoxy (OSTE+) polymer probes developed in our previous work, we quantitatively evaluated the FBR to four types of probes with different softness: silicon (~150 GPa), polyimide (1.5 GPa), OSTE+Hard (300 MPa), and OSTE+Soft (6 MPa). MAIN RESULTS: We observed a significant reduction in the fluorescence intensity of biomarkers for activated microglia/macrophages and blood-brain barrier (BBB) leakiness around the three soft polymer probes compared to the silicon probe, both at 4 weeks and 8 weeks post-implantation. However, we did not observe any consistent differences in the biomarkers among the polymer probes. SIGNIFICANCE: The results suggest that the mechanical compliance of neural probes can mediate the degree of FBR, but its impact diminishes after a hypothetical threshold level. This infers that resolving the mechanical mismatch alone has a limited effect on improving the lifetime of neural implants.