The future of upper extremity rehabilitation robotics: research and practice

The loss of upper limb motor function can have a devastating effect on people’s lives. To restore upper limb control and functionality, researchers and clinicians have developed interfaces to interact directly with the human body’s motor system. In this invited review, we aim to provide details on the peripheral nerve interfaces and brain‐machine interfaces that have been developed in the past 30 years for upper extremity control, and we highlight the challenges that still remain to transition the technology into the clinical market. The findings show that peripheral nerve interfaces and brain‐machine interfaces have many similar characteristics that enable them to be concurrently developed. Decoding neural information from both interfaces may lead to novel physiological models that may one day fully restore upper limb motor function for a growing patient population.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155489/1/mus26860_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155489/2/mus26860.pd

Experimental testing of bionic peripheral nerve and muscle interfaces: animal model considerations

Introduction: Man-machine interfacing remains the main challenge for accurate and reliable control of bionic prostheses. Implantable electrodes in nerves and muscles may overcome some of the limitations by significantly increasing the interface's reliability and bandwidth. Before human application, experimental preclinical testing is essential to assess chronic in-vivo biocompatibility and functionality. Here, we analyze available animal models, their costs and ethical challenges in special regards to simulating a potentially life-long application in a short period of time and in non-biped animals. Methods: We performed a literature analysis following the PRISMA guidelines including all animal models used to record neural or muscular activity via implantable electrodes, evaluating animal models, group size, duration, origin of publication as well as type of interface. Furthermore, behavioral, ethical, and economic considerations of these models were analyzed. Additionally, we discuss experience and surgical approaches with rat, sheep, and primate models and an approach for international standardized testing. Results: Overall, 343 studies matched the search terms, dominantly originating from the US (55%) and Europe (34%), using mainly small animal models (rat: 40%). Electrode placement was dominantly neural (77%) compared to muscular (23%). Large animal models had a mean duration of 135 ± 87.2 days, with a mean of 5.3 ± 3.4 animals per trial. Small animal models had a mean duration of 85 ± 11.2 days, with a mean of 12.4 ± 1.7 animals. Discussion: Only 37% animal models were by definition chronic tests (>3 months) and thus potentially provide information on long-term performance. Costs for large animals were up to 45 times higher than small animals. However, costs are relatively small compared to complication costs in human long-term applications. Overall, we believe a combination of small animals for preliminary primary electrode testing and large animals to investigate long-term biocompatibility, impedance, and tissue regeneration parameters provides sufficient data to ensure long-term human applications

Upper limb prostheses: bridging the sensory gap

Replacing human hand function with prostheses goes far beyond only recreating muscle movement with feedforward motor control. Natural sensory feedback is pivotal for fine dexterous control and finding both engineering and surgical solutions to replace this complex biological function is imperative to achieve prosthetic hand function that matches the human hand. This review outlines the nature of the problems underlying sensory restitution, the engineering methods that attempt to address this deficit and the surgical techniques that have been developed to integrate advanced neural interfaces with biological systems. Currently, there is no single solution to restore sensory feedback. Rather, encouraging animal models and early human studies have demonstrated that some elements of sensation can be restored to improve prosthetic control. However, these techniques are limited to highly specialized institutions and much further work is required to reproduce the results achieved, with the goal of increasing availability of advanced closed loop prostheses that allow sensory feedback to inform more precise feedforward control movements and increase functionality

Regenerative peripheral nerve interfaces for real-time, proportional control of a Neuroprosthetic hand

Abstract Introduction Regenerative peripheral nerve interfaces (RPNIs) are biological constructs which amplify neural signals and have shown long-term stability in rat models. Real-time control of a neuroprosthesis in rat models has not yet been demonstrated. The purpose of this study was to: a) design and validate a system for translating electromyography (EMG) signals from an RPNI in a rat model into real-time control of a neuroprosthetic hand, and; b) use the system to demonstrate RPNI proportional neuroprosthesis control. Methods Animals were randomly assigned to three experimental groups: (1) Control; (2) Denervated, and; (3) RPNI. In the RPNI group, the extensor digitorum longus (EDL) muscle was dissected free, denervated, transferred to the lateral thigh and neurotized with the residual end of the transected common peroneal nerve. Rats received tactile stimuli to the hind-limb via monofilaments, and electrodes were used to record EMG. Signals were filtered, rectified and integrated using a moving sample window. Processed EMG signals (iEMG) from RPNIs were validated against Control and Denervated group outputs. Results Voluntary reflexive rat movements produced signaling that activated the prosthesis in both the Control and RPNI groups, but produced no activation in the Denervated group. Signal-to-Noise ratio between hind-limb movement and resting iEMG was 3.55 for Controls and 3.81 for RPNIs. Both Control and RPNI groups exhibited a logarithmic iEMG increase with increased monofilament pressure, allowing graded prosthetic hand speed control (R2 = 0.758 and R2 = 0.802, respectively). Conclusion EMG signals were successfully acquired from RPNIs and translated into real-time neuroprosthetic control. Signal contamination from muscles adjacent to the RPNI was minimal. RPNI constructs provided reliable proportional prosthetic hand control.https://deepblue.lib.umich.edu/bitstream/2027.42/146521/1/12984_2018_Article_452.pd

NGF-TrkA signaling dictates neural ingrowth and aberrant osteochondral differentiation after soft tissue trauma

: Pain is a central feature of soft tissue trauma, which under certain contexts, results in aberrant osteochondral differentiation of tissue-specific stem cells. Here, the role of sensory nerve fibers in this abnormal cell fate decision is investigated using a severe extremity injury model in mice. Soft tissue trauma results in NGF (Nerve growth factor) expression, particularly within perivascular cell types. Consequently, NGF-responsive axonal invasion occurs which precedes osteocartilaginous differentiation. Surgical denervation impedes axonal ingrowth, with significant delays in cartilage and bone formation. Likewise, either deletion of Ngf or two complementary methods to inhibit its receptor TrkA (Tropomyosin receptor kinase A) lead to similar delays in axonal invasion and osteochondral differentiation. Mechanistically, single-cell sequencing suggests a shift from TGFβ to FGF signaling activation among pre-chondrogenic cells after denervation. Finally, analysis of human pathologic specimens and databases confirms the relevance of NGF-TrkA signaling in human disease. In sum, NGF-mediated TrkA-expressing axonal ingrowth drives abnormal osteochondral differentiation after soft tissue trauma. NGF-TrkA signaling inhibition may have dual therapeutic use in soft tissue trauma, both as an analgesic and negative regulator of aberrant stem cell differentiation

Regenerative peripheral nerve interfaces (RPNIs): current status and future direction

Despite significant advancements in neuroprosthetic control strategies, current peripheral nerve interfacing techniques are limited in their ability to facilitate accurate and reliable long-term control. The regenerative peripheral nerve interface (RPNI) is a biologically stable bioamplifier of efferent motor action potentials with demonstrated long-term stability. This innovative, straightforward, and reproducible surgical technique has shown enormous potential in improving prosthetic control for individuals with upper limb amputations. The RPNI consists of an autologous free muscle graft secured around the end of a transected peripheral nerve or individual fascicles within a residual limb. This construct facilitates EMG signal transduction from the residual peripheral nerve to a neuroprosthetic device using indwelling bipolar electrodes on the muscle surface. This review article focuses on the development of the RPNI and its use for intuitive and enhanced prosthetic control and sensory feedback. In addition, this article also highlights the use of RPNIs for the prevention and treatment of postamputation pain

Sensory nerve regeneration and reinnervation in muscle following peripheral nerve injury

Sensory afferent fibers are an important component of motor nerves and compose the majority of axons in many nerves traditionally thought of as “pure” motor nerves. These sensory afferent fibers innervate special sensory end organs in muscle, including muscle spindles that respond to changes in muscle length and Golgi tendons that detect muscle tension. Both play a major role in proprioception, sensorimotor extremity control feedback, and force regulation. After peripheral nerve injury, there is histological and electrophysiological evidence that sensory afferents can reinnervate muscle, including muscle that was not the nerve’s original target. Reinnervation can occur after different nerve injury and muscle models, including muscle graft, crush, and transection injuries, and occurs in a nonspecific manner, allowing for cross-innervation to occur. Evidence of cross-innervation includes the following: muscle spindle and Golgi tendon afferent-receptor mismatch, vagal sensory fiber reinnervation of muscle, and cutaneous afferent reinnervation of muscle spindle or Golgi tendons. There are several notable clinical applications of sensory reinnervation and cross-reinnervation of muscle, including restoration of optimal motor control after peripheral nerve repair, flap sensation, sensory protection of denervated muscle, neuroma treatment and prevention, and facilitation of prosthetic sensorimotor control. This review focuses on sensory nerve regeneration and reinnervation in muscle, and the clinical applications of this phenomena. Understanding the physiology and limitations of sensory nerve regeneration and reinnervation in muscle may ultimately facilitate improvement of its clinical applications.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/174928/1/mus27661_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/174928/2/mus27661.pd