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Utah Slanted Electrode Arrays (USEAs) implanted in arm nerves. Surgical access to all 3 target nerves was achieved through a single surgical site at either the elbow or the shoulder. In both images, the more proximal limb is at top and the more distal limb at the bottom, and the volar (palm side) surface of the arm is depicted. R, radial nerve; M, median nerve; U, ulnar nerve; *, olecranon process at the elbow. A: left shoulder-level radial, median, and ulnar nerves, each shown implanted with a 100-electrode USEA. Insertion support (subsequently removed) is seen below the median nerve. B: right elbow-level arm nerves, just proximal to the elbow. USEA implants are shown protected by a custom containment system composed of metal mesh and Kwik-Cast silicone (World Precision Instruments).
Source publication
High-count microelectrode arrays implanted in peripheral nerves could restore motor function after spinal cord injury or sensory function after limb loss. In this study, we implanted Utah Slanted Electrode Arrays (USEAs) intrafascicularly, at the elbow or shoulder in arm nerves of rhesus monkeys (n = 4) under isoflurane anesthesia. Input-output cur...
Contexts in source publication
Context 1
... were implanted in nerves just distal to the brachial plexus (Fig. 1A) and near the elbow (Fig. 1B) by means of a high-speed insertion system (Rousche and Normann 1992). Arrays were con- nected to stimulation and recording systems via a modified Integrated Cable Systems (ICS Mfg., Longmont, CO) or a Tucker-Davis Tech- nologies (TDT, Alachua, FL) 96-pin connector and adapter ...
Context 2
... were implanted in nerves just distal to the brachial plexus (Fig. 1A) and near the elbow (Fig. 1B) by means of a high-speed insertion system (Rousche and Normann 1992). Arrays were con- nected to stimulation and recording systems via a modified Integrated Cable Systems (ICS Mfg., Longmont, CO) or a Tucker-Davis Tech- nologies (TDT, Alachua, FL) 96-pin connector and adapter ...
Citations
... To date, peripheral nerve stimulation (PNS) for selective hand muscle recruitment has been tested in NHPs with different interfaces and monopolar stimuli [150][151][152] and in people with tetraplegia using epineural electrodes and multipolar stimuli 153,154 (Table 1). Comparing preclinical studies, it appears that intrafascicular electrodes allow the selective recruitment of a greater number of muscles 152 , probably because more central fascicles are less accessible with monopolar epineural PNS. ...
Full-text available at: https://rdcu.be/daaqL
... Electrophysiological neuromonitoring methods, such as electroencephalography (EEG) and somatosensory-evoked potentials (SEP), provide crucial insight into the functional integrity of neural structures. Although very informative, invasive methods of measuring cortical activity with stimulation, such as skull screws and electrocorticography [1][2][3] are challenging to implement clinically routinely and have less translational potential to demonstrate novel findings in animals. Non-invasive measures, such as EEG, are therefore advantageous to accelerate clinical discovery. ...
Background
Non-invasive measurement of somatosensory-evoked potentials (SEP) in a large animal model is important to translational cognitive research. We sought to develop a methodology for neurophysiological recording via a transcranial electroencephalography (EEG) cap under an effective sedative regimen with dexmedetomidine, midazolam, and butorphanol that will produce sedation instead of anesthesia while not compromising data quality.
Results
Pigs received intramuscular dexmedetomidine, midazolam, and butorphanol for SEP assessment with peroneal nerve stimulation. Semi-quantitative sedation assessment was performed after the animal was sufficiently sedated and 30 min later, during the transcranial SEP recording. SEP data were analyzed with commercial software. Binary qualitative analysis of the recording was categorized by an experienced neurophysiologist. All four animals had adequate surface SEP recordings. Animals received 43 [21–47] mcg/kg of dexmedetomidine, 0.3 [0.2–0.3] mg/kg of midazolam, and 0.3 [0.3–0.3] mg/kg of butorphanol IM. All treatments resulted in moderate to deep sedation (Baseline median sedation score 11.5 [11–12]; median score at 30 min: 11.5 [10.5–12]). Heart rate (median [range]) (55 [49–71] beats per minute), respiratory rate (24 [21–30] breaths per minute), and hemoglobin oxygen saturation (99 [98–100]%) and body temperature (37.7 [37.4–37.9] °C) remained within clinically acceptable ranges. There were no undesirable recovery incidents.
Conclusions
In this pilot study, we demonstrate the feasibility of SEP recording via a transcranial EEG cap under an effective sedative regimen in pigs. Our approach will expand the use of a large animal model in neurotranslational research.
... Their location makes them able to record and stimulate small groups of axons with high selectivity after implantation, seen in several amputees with meaningful sensory feedback [58] . The transverse intra-fascicular multichannel electrode implant is placed perpendicular to the nerve to access several fascicles [59] . In rat sciatic nerve, high selectively enabled activation of multiple downstream muscles. ...
Limb loss is disabling and carries significant functional and psychological repercussions to both the individual and society. The numbers of amputees are forecasted to double by 2050 from vascular disease and diabetes alone. Europe has 4.66 million amputees (431,000 amputations per year) and the United States 2 million amputees (185,000 amputations per year). Microvascular expertise is now more commonplace, increasing the likelihood of limb salvage and replantation. Further reconstructive input can take advantage of nerve and tendon grafting/transfers, free tissue transfer, and complex bone reconstruction. When this strategy does not satisfy individual needs, such as that seen with unstable soft tissues, amputation may be requested or offered. In part, the decision for salvage, replantation, or amputation in the future is likely to be guided by the sophistication of limb substitutes. This review will introduce the growing domain of bionics and where research in this area may deliver a sought clinical need.
... Neuroprostheses hold the potential to restore motor functions to people with paralyzed limbs due to neurological disorders or injuries, such as stroke or spinal cord injury. Various neuroprosthetic systems have been developed to restore and assist lower and upper extremity movements by electrically stimulating the spinal cord [1][2][3][4][5][6], skeletal muscles [7][8][9][10][11][12][13][14][15][16] or peripheral nerves [17][18][19][20][21][22][23], through different interfaces. Among the existing solutions, polyimide-based intraneural electrodes [24,25] have shown high biocompatibility and long-term stability [19,26] as well as good performance in restoring fine motor functions in rats [27] and monkeys [28]. ...
Objective.Motor neuroprostheses require the identification of stimulation protocols that effectively produce desired movements. Manual search for these protocols can be very time-consuming and often leads to suboptimal solutions, as several stimulation parameters must be personalized for each subject for a variety of target motor functions. Here, we present an algorithm that efficiently tunes peripheral intraneural stimulation protocols to elicit functionally relevant distal limb movements.Approach.We developed the algorithm using Bayesian optimization (BO) with multi-output Gaussian Processes (GPs) and defined objective functions based on coordinated muscle recruitment. We applied the algorithm offline to data acquired in rats for walking control and in monkeys for hand grasping control and compared different GP models for these two systems. We then performed a preliminary online test in a monkey to experimentally validate the functionality of our method.Main results.Offline, optimal intraneural stimulation protocols for various target motor functions were rapidly identified in both experimental scenarios. Using the model that performed best, the algorithm converged to stimuli that evoked functionally consistent movements with an average number of actions equal to 20% of the search space size in both the rat and monkey animal models. Online, the algorithm quickly guided the observations to stimuli that elicited functional hand gestures, although more selective motor outputs could have been achieved by refining the objective function used.Significance.These results demonstrate that BO can reliably and efficiently automate the tuning of peripheral neurostimulation protocols, establishing a translational framework to configure peripheral motor neuroprostheses in clinical applications. The proposed method can also potentially be applied to optimize motor functions using other stimulation modalities.
... However, because the contacts lie on the surface of the nerve and thereby far from the individual nerve fibers, epineural interfaces are prone to inverse efferent recruitment and require relatively large currents of stimulation, leading to the undesired activation of the deepest nerve structures (16). Intrafascicular stimulation offers an alternative opportunity to enhance recruitment selectivity (17) by positioning the implant within multiple nerve fascicles near efferent axons of different muscles (18)(19)(20)(21). The proximity of the implant's active sites with motor fibers reduces the influence of the motor fiber diameter on the selective axon recruitment, thereby minimizing the inverse recruitment observed with extra neural stimulation and thus reducing the onset of fatigue (18,19,22). ...
... To further compare our approach with the high-density intrafascicular implants used by Ledbetter and colleagues (21), we computed the muscular selectivity obtained through the Mk-TIME using their definition of selectivity (see Materials and Methods and fig. S6E). ...
... Previous anatomical examinations of the upper limb muscles and nerves in monkeys and humans (25)(26)(27)57) revealed that the structural organization of the arm is preserved within primates, suggesting that our approach could be directly translated to humans. The larger number of fascicles in the human median nerve and the interindividual variations in motor fiber organization (25,27) may indicate the possible need for additional Mk-TIME implants, or denser electrode arrays (21), to achieve similar results. ...
Restoring dexterous hand control is critical for people with paralysis. Approaches based on surface or intramuscular stimulation provide limited finger control, generate insufficient force to recover functional movements, and require numerous electrodes. Here, we show that intrafascicular peripheral electrodes could produce functional grasps and sustained forces in three monkeys. We designed an intrafascicular implantable electrode targeting the motor fibers of the median and radial nerves. Our interface selectively and reliably activated extrinsic and intrinsic hand muscles, generating multiple functional grips, hand opening, and sustained contraction forces for up to 2 months. We extended those results to a behaving monkey with transient hand paralysis and used intracortical signals to control simple stimulation protocols that enabled this animal to perform a functional grasping task. Our findings show that just two intrafascicular electrodes can generate a rich portfolio of dexterous and functional hand movements with important implications for clinical applicability.
... Norman at the University of Utah developed the Utah arrays, which consist of long and sharp penetrating silicon (22,23). These arrays were used extensively for basic research but were also implanted in monkeys and humans (24)(25)(26)(27)(28)(29). Beyond its electrical and mechanical properties, silicon also offers superb optical properties. ...
The field of neurostimulation has evolved over the last few decades from a crude, low-resolution approach to a highly sophisticated methodology entailing the use of state-of-the-art technologies. Neurostimulation has been tested for a growing number of neurological applications, demonstrating great promise and attracting growing attention in both academia and industry. Despite tremendous progress, long-term stability of the implants, their large dimensions, their rigidity and the methods of their introduction and anchoring to sensitive neural tissue remain challenging. The purpose of this review is to provide a concise introduction to the field of high-resolution neurostimulation from a technological perspective and to focus on opportunities stemming from developments in materials sciences and engineering to reduce device rigidity while optimizing electrode small dimensions. We discuss how these factors may contribute to smaller, lighter, softer and higher electrode density devices.
... The Utah Slanted Electrode Array (USEA) consists of a 10 × 10 grid of electrodes with depths from 0.5 to 1.5 mm that penetrate peripheral nerves to enable single-unit neural recordings and intraneural microstimulation [1]. USEAs implanted in the peripheral nerves serve as a bi-directional sensorimotor neural interface, and have now been used to reanimate motionless limbs [2,3], to provide intuitive control of and sensory feedback from bionic arms [4][5][6][7][8][9], and to alleviate neuropathic pain [10,11]. The high electrode count and intrafascicular nature of the USEA yields improved specificity [6,12]. ...
Objective:
We explore the long-term performance and stability of seven percutaneous Utah Slanted Electrode Arrays (USEAs) and intramuscular recording leads (iEMGs) implanted chronically in the residual arm nerves and muscles of three human participants as a means to permanently restore sensorimotor function after transradial amputations.
Approach:
We quantify the number of functional recording and functional stimulating electrodes over time. We also calculate the signal-to-noise ratio (SNR) of USEA and iEMG recordings and quantify the stimulation current necessary to evoke detectable sensory percepts. Furthermore, we quantify the consistency of the sensory modality, receptive field location, and receptive field size of USEA-evoked percepts.
Main results:
In the most recent subject, involving USEAs with technical improvements, neural recordings persisted for 502 d (entire implant duration) and the number of functional recording electrodes for one USEA increased over time. However, for six out of seven USEAs across the three participants, the number of functional recording electrodes decreased within the first 2 months after implantation. The SNR of neural recordings and electromyographic recordings stayed relatively consistent over time. Sensory percepts were consistently evoked over the span of 14 months, were not significantly different in size, and highlighted the nerves' fascicular organization. The percentage of percepts with consistent modality or consistent receptive field location between sessions (∼1 month apart) varied between 0%-86.2% and 9.1%-100%, respectively. Stimulation thresholds and electrode impedances increased initially but then remained relatively stable over time.
Significance:
This work demonstrates improved performance of USEAs, and provides a basis for comparing the longevity and stability of USEAs to that of other neural interfaces. USEAs provide a rich repertoire of neural recordings and sensory percepts. Although their performance still generally declines over time, functionality can persist long-term. Future work should leverage the results presented here to further improve USEA design or to develop adaptive algorithms that can maintain a high level of performance.
... The Utah Slanted Electrode Array (USEA) consists of a 10 × 10 grid of electrodes with depths from 0.5 to 1.5 mm that penetrate peripheral nerves to enable single-unit neural recordings and intraneural microstimulation [1]. USEAs implanted in the peripheral nerves serve as a bi-directional sensorimotor neural interface, and have now been used to reanimate motionless limbs [2,3], to provide intuitive control of and sensory feedback from bionic arms [4][5][6][7][8][9], and to alleviate neuropathic pain [10,11]. The high electrode count and intrafasicular nature of the USEA yields improved specificity [6,12]. ...
Objective
We explore the long-term performance and stability of seven percutanous Utah Slanted Electrode Arrays (USEAs) and intramuscular recording leads (iEMGs) implanted chronically in the residual arm nerves and muscles of three human amputees as a means to permanently restore sensorimotor function after upper-limb.
Approach
We quantify the number of functional recording and functional stimulating electrodes over time. We also calculate the signal-to-noise ratio of USEA and iEMG recordings and quantify the stimulation amplitude necessary to evoke detectable sensory percepts. Furthermore, we quantify the consistency of the sensory modality, receptive field location, and receptive field size of USEA-evoked percepts.
Main Results
In the most recent subject, involving USEAs with technical improvements, neural recordings persisted for 502 days (entire implant duration) and the number of functional recording electrodes for one USEA increased over time. However, for six out of seven USEAs the number of functional recording electrodes decreased within the first two months after implantation. The signal-to-noise ratio of neural recordings and electromyographic recordings stayed relatively consistent over time. Sensory percepts were consistently evoked over the span of 14 months, were not significantly different in size, and highlighted the nerves’ fascicular organization. The percentage of percepts with consistent modality or consistent receptive field location between sessions (~1 month apart) varied between 0–86.2% and 9.1–100%, respectively. Stimulation thresholds and electrode impedances increased initially but then remained relatively stable over time.
Significance
This work demonstrates improved performance of USEAs, and provides a basis for comparing the longevity and stability of USEAs to that of other neural interfaces. Although USEAs provide a rich repertoire of neural recordings and sensory percepts, performance still generally declines over time. Future work should leverage the results presented here to further improve USEA design or to develop adaptive algorithms that can maintain a high level of performance.
... In a study done with four monkeys, the USEA implantation on elbow level and shoulder level promoted precise muscle activation. In particular, the extrinsic muscles of the hand were activated selectively, whereas the intrinsic muscles grouped for similar functions were often activated together [112]. In another study with two upper extremity amputees, the USEA was inserted in the median nerve of one subject and in the ulnar nerve of the other. ...
The field of prosthetics has been evolving and advancing over the past decade, as patients with missing extremities are expecting to control their prostheses in as normal a way as possible. Scientists have attempted to satisfy this expectation by designing a connection between the nervous system of the patient and the prosthetic limb, creating the field of neuroprosthetics. In this paper, we broadly review the techniques used to bridge the patient’s peripheral nervous system to a prosthetic limb. First, we describe the electrical methods including myoelectric systems, surgical innovations and the role of nerve electrodes. We then describe non-electrical methods used alone or in combination with electrical methods. Design concerns from an engineering point of view are explored, and novel improvements to obtain a more stable interface are described. Finally, a critique of the methods with respect to their long-term impacts is provided. In this review, nerve electrodes are found to be one of the most promising interfaces in the future for intuitive user control. Clinical trials with larger patient populations, and for longer periods of time for certain interfaces, will help to evaluate the clinical application of nerve electrodes.
... While the early safety and efficacy studies were performed in animal models (e.g., Ledbetter et al., 2013;Brill et al., 2018), translating peripheral nerve technology to human amputees revolutionized somatosensory prosthetics due to the ability to collect verbal feedback from research participants about induced somatosensory percepts. To track the effects of peripheral stimulation on sensation, researchers use "perceptive field" maps that pictorially demonstrate where sensation is felt on the amputated limb. ...
Background:
Peripheral nerve interfaces have emerged as alternative solutions for a variety of therapeutic and performance improvement applications. The Defense Advanced Research Projects Agency (DARPA) has widely invested in these interfaces to provide motor control and sensory feedback to prosthetic limbs, identify non-pharmacological interventions to treat disease, and facilitate neuromodulation to accelerate learning or improve performance on cognitive, sensory, or motor tasks. In this commentary, we highlight some of the design considerations for optimizing the safety and efficacy of peripheral nerve interfaces based on application space. We also discuss some of the ethical considerations that accompany these advances.
