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Introduction Approximately 89% of all service members with amputations do not return to duty. Restoring intuitive neural control with somatosensory sensation is a key to improving the safety and efficacy of prosthetic locomotion. However, natural somatosensory feedback from lower-limb prostheses has not yet been incorporated into any commercial prostheses Materials and Methods We developed a neuroprosthesis with intuitive bidirectional control and somatosensation and evoking phase-dependent locomotor reflexes, we aspire to significantly improve the prosthetic rehabilitation and long-term functional outcomes of U.S. amputees. We implanted the skin and bone integrated pylon with peripheral neural interface pylon into the cat distal tibia, electromyographic electrodes into the residual gastrocnemius muscle, and nerve cuff electrodes on the distal tibial and sciatic nerves. Results. The bidirectional neural interface that was developed was integrated into the existing passive Free-Flow Foot and Ankle prosthesis, WillowWood, Mount Sterling, OH. The Free-Flow Foot was chosen because it had the highest Index of Anthropomorphicity among lower-limb prostheses and was the first anthropomorphic prosthesis brought to market. Conclusion. The cats walked on a treadmill with no cutaneous feedback from the foot in the control condition and with their residual distal tibial nerve stimulated during the stance phase of walking [ABSTRACT FROM AUTHOR]

To determine the efficacy of neural interface–based neurorehabilitation, including brain-computer interface, through conventional and individual patient data (IPD) meta-analysis and to assess clinical parameters associated with positive response to neural interface–based neurorehabilitation. PubMed, EMBASE, and Cochrane Library databases up to February 2022 were reviewed. Studies using neural interface–controlled physical effectors (functional electrical stimulation and/or powered exoskeletons) and reported Fugl-Meyer Assessment–upper-extremity (FMA-UE) scores were identified. This meta-analysis was prospectively registered on PROSPERO (#CRD42022312428). PRISMA guidelines were followed. Changes in FMA-UE scores were pooled to estimate the mean effect size. Subgroup analyses were performed on clinical parameters and neural interface parameters with both study-level variables and IPD. Forty-six studies containing 617 patients were included. Twenty-nine studies involving 214 patients reported IPD. FMA-UE scores increased by a mean of 5.23 (95% confidence interval [CI]: 3.85-6.61). Systems that used motor attempt resulted in greater FMA-UE gain than motor imagery, as did training lasting >4 vs ≤4 weeks. On IPD analysis, the mean time-to-improvement above minimal clinically important difference (MCID) was 12 weeks (95% CI: 7 to not reached). At 6 months, 58% improved above MCID (95% CI: 41%-70%). Patients with severe impairment (P =.042) and age >50 years (P =.0022) correlated with the failure to improve above the MCID on univariate log-rank tests. However, these factors were only borderline significant on multivariate Cox analysis (hazard ratio [HR] 0.15, P =.08 and HR 0.47, P =.06, respectively). Neural interface–based motor rehabilitation resulted in significant, although modest, reductions in poststroke impairment and should be considered for wider applications in stroke neurorehabilitation. [ABSTRACT FROM AUTHOR]

Abstract Background Implantable vagus nerve stimulation is a promising approach for restoring autonomic cardiovascular functions after heart transplantation. For successful treatment a system should have multiple electrodes to deliver precise stimulation and complex neuromodulation patterns. Methods This paper presents an implantable multi-channel stimulation system for vagal-cardiac neuromodulation studies in swine species. The system comprises an active electrode array implant percutaneously connected to an external wearable controller. The active electrode array implant has an integrated stimulator ASIC mounted on a ceramic substrate connected to an intraneural electrode array via micro-rivet bonding. The implant is silicone encapsulated for biocompatibility and implanted lifetime. The stimulation parameters are remotely transmitted via a Bluetooth telemetry link. Results The size of the encapsulated active electrode array implant is 8 mm × 10 mm × 3 mm. The stimulator ASIC has 10-bit current amplitude resolution and 16 independent output channels, each capable of delivering up to 550 µA stimulus current and a maximum voltage of 20 V. The active electrode array implant was subjected to in vitro accelerated lifetime testing at 70 °C for 7 days with no degradation in performance. After over 2 h continuous stimulation, the surface temperature change of the implant was less than 0.5 °C. In addition, in vivo testing on the sciatic nerve of a male Göttingen minipig demonstrated that the implant could effectively elicit an EMG response that grew progressively stronger on increasing the amplitude of the stimulation. Conclusions The multi-channel stimulator is suitable for long term implantation. It shows potential as a useful tool in vagal-cardiac neuromodulation studies in animal models for restoring autonomic cardiovascular functions after heart transplantation.

Background: Implantable vagus nerve stimulation is a promising approach for restoring autonomic cardiovascular functions after heart transplantation. For successful treatment a system should have multiple electrodes to deliver precise stimulation and complex neuromodulation patterns. Methods: This paper presents an implantable multi-channel stimulation system for vagal-cardiac neuromodulation studies in swine species. The system comprises an active electrode array implant percutaneously connected to an external wearable controller. The active electrode array implant has an integrated stimulator ASIC mounted on a ceramic substrate connected to an intraneural electrode array via micro-rivet bonding. The implant is silicone encapsulated for biocompatibility and implanted lifetime. The stimulation parameters are remotely transmitted via a Bluetooth telemetry link. Results: The size of the encapsulated active electrode array implant is 8 mm × 10 mm × 3 mm. The stimulator ASIC has 10-bit current amplitude resolution and 16 independent output channels, each capable of delivering up to 550 µA stimulus current and a maximum voltage of 20 V. The active electrode array implant was subjected to in vitro accelerated lifetime testing at 70 °C for 7 days with no degradation in performance. After over 2 h continuous stimulation, the surface temperature change of the implant was less than 0.5 °C. In addition, in vivo testing on the sciatic nerve of a male Göttingen minipig demonstrated that the implant could effectively elicit an EMG response that grew progressively stronger on increasing the amplitude of the stimulation. Conclusions: The multi-channel stimulator is suitable for long term implantation. It shows potential as a useful tool in vagal-cardiac neuromodulation studies in animal models for restoring autonomic cardiovascular functions after heart transplantation. [ABSTRACT FROM AUTHOR]

Control of voluntary limb movement is predominantly attributed to the contralateral motor cortex. However, increasing evidence suggests the involvement of ipsilateral cortical networks in this process, especially in motor tasks requiring bilateral coordination, such as locomotion. In this study, we combined a unilateral thoracic spinal cord injury (SCI) with a cortical neuroprosthetic approach to investigate the functional role of the ipsilateral motor cortex in rat movement through spared contralesional pathways. Our findings reveal that in all SCI rats, stimulation of the ipsilesional motor cortex promoted a bilateral synergy. This synergy involved the elevation of the contralateral foot along with ipsilateral hindlimb extension. Additionally, in two out of seven animals, stimulation of a sub-region of the hindlimb motor cortex modulated ipsilateral hindlimb flexion. Importantly, ipsilateral cortical stimulation delivered after SCI immediately alleviated multiple locomotor and postural deficits, and this effect persisted after ablation of the homologous motor cortex. These results provide strong evidence of a causal link between cortical activation and precise ipsilateral control of hindlimb movement. This study has significant implications for the development of future neuroprosthetic technology and our understanding of motor control in the context of SCI.

Based on electrophysiological activity, neuroprostheses can effectively monitor and control neural activity. Currently, electrophysiological neuroprostheses are widely utilized in treating neurological disorders, particularly in restoring motor, visual, auditory, and somatosensory functions after nervous system injuries. They also help alleviate inflammation, regulate blood pressure, provide analgesia, and treat conditions such as epilepsy and Alzheimer’s disease, offering significant research, economic, and social value. Enhancing the targeting capabilities of neuroprostheses remains a key objective for researchers. Modeling and simulation techniques facilitate the theoretical analysis of interactions between neuroprostheses and the nervous system, allowing for quantitative assessments of targeting efficiency. Throughout the development of neuroprostheses, these modeling and simulation methods can save time, materials, and labor costs, thereby accelerating the rapid development of highly targeted neuroprostheses. This article introduces the fundamental principles of neuroprosthesis simulation technology and reviews how various simulation techniques assist in the design and performance enhancement of neuroprostheses. Finally, it discusses the limitations of modeling and simulation and outlines future directions for utilizing these approaches to guide neuroprosthesis design.

Facial paralysis is a highly burdening condition, resulting in a patient's inability to move his mimic musculature on one or both sides of his face. This condition compromises the patient's communication and facial expressions, and thus dramatically reduces his quality of life. The current treatment for chronic facial paralysis relies on a complex reconstructive surgery. This publication proposes a novel, less invasive approach for dynamic facial reanimation. The use of a smart material, namely a Dielectric Elastomer Actuator (DEA) is proposed for facial motion restoration, thus avoiding the traditional two-stage free muscle transfer procedure and allowing for a faster recovery of the patient. DEAs are a type of electroactive polymers, showing promising properties similar to natural muscles such as the fact that they are soft, lightweight and allow for large displacements. As a result, a study of the facial muscles and neural interfaces, notably the ones responsible for mouth movement, was performed, in order to implement a realistic setup. In this paper, a non-invasive neural interface based on myoelectric signal is used in order to establish a real-time control of the actuator. Visible motion of a skin model is produced in real time, by synchronizing the actuator to the activity of a healthy muscle, with a maximal delay of 108 ​ms resulting from the signal processing and a delay of less than 30 ​ms related to the actuation of the DEA. This shows that the usage of DEA combined with a neural interface presents a promising approach for treatment of facial paralysis.

Brain-computer interfaces (BCI) that directly decode speech from brain activity aim to restore communication in people with paralysis who cannot speak. Despite recent advances, neural inference of speech remains imperfect, limiting the ability for speech BCIs to enable experiences such as fluent conversation that promote agency - that is, the ability for users to author and transmit messages enacting their intentions. Here, we make recommendations for promoting agency based on existing and emerging strategies in neural engineering. The focus is on achieving fast, accurate, and reliable performance while ensuring volitional control over when a decoder is engaged, what exactly is decoded, and how messages are expressed. Additionally, alongside neuroscientific progress within controlled experimental settings, we argue that a parallel line of research must consider how to translate experimental successes into real-world environments. While such research will ultimately require input from prospective users, here we identify and describe design choices inspired by human-factors work conducted in existing fields of assistive technology, which address practical issues likely to emerge in future real-world speech BCI applications.

AbstractAim of the StudyMaterials and MethodsResultsConclusionBrain-computer interfaces (BCIs) may help patients with severe neurological deficits communicate with the external world. Based on microelectrocorticography (µECoG) data recorded from the primary somatosensory cortex (S1) of unrestrained behaving rats, this study attempts to decode lever presses in a psychophysical detection task by using machine learning algorithms.16-channel Pt-Ir microelectrode arrays were implanted on the S1 of two rats, and µECoG was recorded during a vibrotactile yes/no detection task. For this task, the rats were trained to press the right lever when they detected the vibrotactile stimulus and the left lever when they did not. The multichannel µECoG data was analysed offline by time-frequency methods and its features were used for binary classification of the lever press at each trial. Several machine learning algorithms were tested as such.The psychophysical sensitivities (A') were similar and low for both rats (0.58). Rat 2 (B'': −0.11) had higher bias for the right lever than Rat 1 (B'': − 0.01). The lever presses could be predicted with accuracies over 66% with all the tested algorithms, and the highest average accuracy (78%) was with the support vector machine.According to the recent studies, sensory feedback increases the benefit of the BCIs. The current proof-of-concept study shows that lever presses can be decoded from the S1; therefore, this area may be utilised for a bidirectional BCI in the future. [ABSTRACT FROM AUTHOR]

Facial paralysis is a highly burdening condition, resulting in a patient's inability to move his mimic musculature on one or both sides of his face. This condition compromises the patient's communication and facial expressions, and thus dramatically reduces his quality of life. The current treatment for chronic facial paralysis relies on a complex reconstructive surgery. This publication proposes a novel, less invasive approach for dynamic facial reanimation. The use of a smart material, namely a Dielectric Elastomer Actuator (DEA) is proposed for facial motion restoration, thus avoiding the traditional two-stage free muscle transfer procedure and allowing for a faster recovery of the patient. DEAs are a type of electroactive polymers, showing promising properties similar to natural muscles such as the fact that they are soft, lightweight and allow for large displacements. As a result, a study of the facial muscles and neural interfaces, notably the ones responsible for mouth movement, was performed, in order to implement a realistic setup. In this paper, a non-invasive neural interface based on myoelectric signal is used in order to establish a real-time control of the actuator. Visible motion of a skin model is produced in real time, by synchronizing the actuator to the activity of a healthy muscle, with a maximal delay of 108 ms resulting from the signal processing and a delay of less than 30 ms related to the actuation of the DEA. This shows that the usage of DEA combined with a neural interface presents a promising approach for treatment of facial paralysis. [ABSTRACT FROM AUTHOR]

Functional electrical stimulation (FES) is a common neuromotor intervention whereby electrically evoked dorsiflexor muscle contractions assist foot clearance during walking. Plantarflexor neurostimulation has recently emerged to assist and retrain gait propulsion; however, safe and effective coordination of dorsiflexor and plantarflexor neurostimulation during overground walking has been elusive, restricting propulsion neuroprostheses to harnessed treadmill walking. We present an overground propulsion neuroprosthesis that adaptively coordinates, on a step-by-step basis, neurostimulation to the dorsiflexors and plantarflexors. In 10 individuals post-stroke, we evaluate the immediate effects of plantarflexor neurostimulation delivered with different onset timings, and retention to unassisted walking (NCT06459401). Preferred onset timing differed across individuals. Individualized tuning resulted in a significant 10% increase in paretic propulsion peak (Δ: 1.41 ± 1.52%BW) and an 8% increase in paretic plantarflexor power (Δ: 0.27 ± 0.23 W/kg), compared to unassisted walking. Post-session unassisted walking speed, paretic propulsion peak, and propulsion symmetry all significantly improved by 9% (0.14 ± 0.09 m/s), 28% (2.24 ± 3.00%BW), and 12% (4.5 ± 6.0%), respectively, compared to pre-session measurements. Here we show that an overground propulsion neuroprosthesis can improve overground walking speed and propulsion symmetry in the chronic phase of stroke recovery. Future studies should include a control group to examine the efficacy of gait training augmented by the propulsion neuroprosthesis compared to gait training alone.

The 'neuropunk revolution' represents an innovative approach focused on the integration of human–machine interfaces through nerve and neural pathways. This cutting-edge concept seeks to push the boundaries of human–machine interaction by exploring the intricate connections between the human nervous system and artificial technologies. Neuropunk delves into the realm of cyborg technologies, blurring the lines between humans and machines and opening up new possibilities for augmenting human capabilities. By tapping into nerve and neural pathways, neuropunk envisions a future where individuals can seamlessly interface with technology, leading to enhanced sensory perception, cognitive abilities, and physical performance. This concept encapsulates a rebellious and unconventional spirit, challenging traditional notions of the human body and its relationship with technology. This paper discusses the challenges and potential of neuropunk, exploring the fusion of scientific exploration, technological innovation, and a punk-inspired ethos in advancing human–machine integration. It highlights the emergence of real-time neurosimulations and neuromorphic computing as key tools to achieve these aspirations. Additionally, the integration of neurological and hormonal bioinspiration is examined as a promising approach to the design of neural interfaces, fostering more efficient and effective technologies that align better with the human body. Finally, the paper addresses ethical considerations and research tasks to responsibly navigate the neuropunk revolution, ensuring a future that maximizes the benefits of neural interfaces while mitigating potential risks and promoting ethical principles. [ABSTRACT FROM AUTHOR]

Introduction: Individuals with lower limb loss experience an increased risk of falls partly due to the lack of sensory feedback from their missing foot. It is possible to restore plantar sensation perceived as originating from the missing foot by directly interfacing with the peripheral nerves remaining in the residual limb, which in turn has shown promise in improving gait and balance. However, it is yet unclear how these electrically elicited plantar sensation are integrated into the body's natural sensorimotor control reflexes. Historically, the H-reflex has been used as a model for investigating sensorimotor control. Within the spinal cord, an array of inputs, including plantar cutaneous sensation, are integrated to produce inhibitory and excitatory effects on the H-reflex. Methods: In this study, we characterized the interplay between electrically elicited plantar sensations and this intrinsic reflex mechanism. Participants adopted postures mimicking specific phases of the gait cycle. During each posture, we electrically elicited plantar sensation, and subsequently the H-reflex was evoked both in the presence and absence of these sensations. Results: Our findings indicated that electrically elicited plantar sensations did not significantly alter the H-reflex excitability across any of the adopted postures. Conclusion: This suggests that individuals with lower limb loss can directly benefit from electrically elicited plantar sensation during walking without disrupting the existing sensory signaling pathways that modulate reflex responses. [ABSTRACT FROM AUTHOR]

Individuals who sustain a traumatic spinal cord injury (SCI) often have a loss of multiple body systems. Significant functional improvement can be gained by individual SCI through the use of neuroprostheses based on electrical stimulation. The most common actions produced are grasp, overhead reach, trunk posture, standing, stepping, bladder/bowel/sexual function, and respiratory functions. We review the fundamental principles of electrical stimulation, which are established, allowing stimulation to be safely delivered through implanted devices for many decades. We review four common clinical applications for SCI, including grasp/reach, standing/stepping, bladder/bowel function, and respiratory functions. Systems used to implement these functions have many common features, but are also customized based on the functional goals of each approach. Further, neuroprosthetic systems are customized based on the needs of each user. The results to date show that implanted neuroprostheses can have a significant impact on the health, function, and quality of life for individuals with SCI. A key focus for the future is to make implanted neuroprostheses broadly available to the SCI population. [ABSTRACT FROM AUTHOR]

Brain-computer interfaces (BCI) that directly decode speech from brain activity aim to restore communication in people with paralysis who cannot speak. Despite recent advances, neural inference of speech remains imperfect, limiting the ability for speech BCIs to enable experiences such as fluent conversation that promote agency – that is, the ability for users to author and transmit messages enacting their intentions. Here, we make recommendations for promoting agency based on existing and emerging strategies in neural engineering. The focus is on achieving fast, accurate, and reliable performance while ensuring volitional control over when a decoder is engaged, what exactly is decoded, and how messages are expressed. Additionally, alongside neuroscientific progress within controlled experimental settings, we argue that a parallel line of research must consider how to translate experimental successes into real-world environments. While such research will ultimately require input from prospective users, here we identify and describe design choices inspired by human-factors work conducted in existing fields of assistive technology, which address practical issues likely to emerge in future real-world speech BCI applications.

The auditory brainstem implant (ABI) is an auditory neuroprosthesis that provides hearing by electrically stimulating the cochlear nucleus (CN) of the brainstem. Our previous study (McInturff et al., 2022) showed that single-pulse stimulation of the dorsal (D)CN subdivision with low levels of current evokes responses that have early latencies, different than the late response patterns observed from stimulation of the ventral (V)CN. How these differing responses encode more complex stimuli, such as pulse trains and amplitude modulated (AM) pulses, has not been explored. Here, we compare responses to pulse train stimulation of the DCN and VCN, and show that VCN responses, measured in the inferior colliculus (IC), have less adaption, higher synchrony, and higher cross-correlation. However, with high-level DCN stimulation, responses become like those to VCN stimulation, supporting our earlier hypothesis that current spreads from electrodes on the DCN to excite neurons located in the VCN. To AM pulses, stimulation of the VCN elicits responses with larger vector strengths and gain values especially in the high-CF portion of the IC. Additional analysis using neural measures of modulation thresholds indicate that these measures are lowest for VCN. Human ABI users with low modulation thresholds, who score best on comprehension tests, may thus have electrode arrays that stimulate the VCN. Overall, the results show that the VCN has superior response characteristics and suggest that it should be the preferred target for ABI electrode arrays in humans. [ABSTRACT FROM AUTHOR]

Optogenetics is a new approach for controlling neural circuits with numerous applications in both basic and clinical science. In retinal degenerative diseases, the photoreceptors die, but inner retinal cells remain largely intact. By expressing light sensitive proteins in the remaining cells, optogenetics has the potential to offer a novel approach to restoring vision. In the past several years, optogenetics has advanced into an early clinical stage, and promising results have been reported. At the current stage, there is an urgent need to develop hardware and software for clinical training, testing, and rehabilitation in optogenetic therapy, which is beyond the capability of existing ophthalmic equipment. In this paper, we present an engineering platform consisting of hardware and software utilities, which allow clinicians to interactively work with patients to explore and assess their vision in optogenetic treatment, providing the basis for prosthetic design, customization, and prescription. This approach is also applicable to other therapies that utilize light activation of neurons, such as photoswitches.Clinical and Translational Impact Statement–The engineering platform allows clinicians to conduct training, testing, and rehabilitation in optogenetic gene therapy for retinal degenerative diseases, providing the basis for prosthetic design, customization, and prescription.

Abstract Background Restoring or improving seated stability after spinal cord injury (SCI) can improve the ability to perform activities of daily living by providing a dynamic, yet stable, base for upper extremity motion. Seated stability can be obtained with activation of the otherwise paralyzed trunk and hip musculature with neural stimulation, which has been shown to extend upper limb reach and improve seated posture. Methods We implemented a proportional, integral, derivative (PID) controller to maintain upright seated posture by simultaneously modulating both forward flexion and lateral bending with functional neuromuscular stimulation. The controller was tested with a functional reaching task meant to require trunk movements and impart internal perturbations through rapid changes in inertia due to acquiring, moving, and replacing objects with one upper extremity. Five subjects with SCI at various injury levels who had received implanted stimulators targeting their trunk and hip muscles participated in the study. Each subject was asked to move a weighted jar radially from a center home station to one of three target stations. The task was performed with the controller active, inactive, or with a constant low level of neural stimulation. Trunk pitch (flexion) and roll (lateral bending) angles were measured with motion capture and plotted against each other to generate elliptical movement profiles for each task and condition. Postural sway was quantified by calculating the ellipse area. Additionally, the mean effective reach (distance between the shoulder and wrist) and the time required to return to an upright posture was determined during reaching movements. Results Postural sway was reduced by the controller in two of the subjects, and mean effective reach was increased in three subjects and decreased for one. Analysis of the major direction of motion showed return to upright movements were quickened by 0.17 to 0.32 s. A 15 to 25% improvement over low/no stimulation was observed for four subjects. Conclusion These results suggest that feedback control of neural stimulation is a viable way to maintain upright seated posture by facilitating trunk movements necessary to complete reaching tasks in individuals with SCI. Replication of these findings on a larger number of subjects would be necessary for generalization to the various segments of the SCI population.

As humanity improves its use of technologies that can replace parts of a biological organism with ones containing mechanical or electronic components, it raises important legal and political issues. For example, the successful implantation of devices in human bodies could lead to the emergence of new cognitive and motor abilities, thereby resulting in the creation of a new class of people. Undoubtedly, this new class of people with extraordinary abilities would require a legal and governmental response. However, the question that arises is what legal rights might be given to these people, considering that they are more similar to machines than to men or women. The following legal aspects are of the utmost importance: the legal rights and responsibilities of cyborgs; the regulation of access to neuroprosthetic devices by third parties; and the limitation of the illegal use of the damaging capabilities of cyborgs. This article examines a number of laws and regulations from various jurisdictions in the United States, the European Union, South Korea and China that apply to cyborg technologies, with a particular focus on a legal doctrine that applies to neuroprostheses.

The utility of currently available cortical prosthetic vision systems is disappointing. The essential features of a neuromorphic device that is predicted to enhance vision provided by available systems follow from a hypothesis which states that the objective and subjective aspects of cortical prosthetic vision jointly constitute patterns that emerge from specified synaptic interactions. The research reported here completes several required steps in developing an emulation of this device: (1) replication of small-scale simulations that are consistent with the hypothesis using the NEST (Écublens, Vaud, Switzerland) simulator, which can also be used for full-scale network emulation by a neuromorphic computer; (2) testing whether results consistent with the hypothesis survive increasing the scale and duration of simulations; (3) establishing a method that uses numbers of spikes produced by network neurons to report the number of phosphenes produced by cortical stimulation; and (4) simulating essential functions of a neuromorphic device which is predicted to enhance current prosthetic systems. NEST simulations replicated early results and increasing their scale and duration produced results consistent with the hypothesis. A decision function created using multinomial logistic regression correctly reported the expected number of phosphenes for three sets of 2080 spike number distributions in which half of each set arises from simulations expected to yield continuous visual forms by engaging a desired visual geometry. A process for modulating electrical stimulation amplitude based on intermittent population recordings that is predicted to produce desired visual geometries was successfully simulated. Implications of these results for future research are discussed.

Brain-machine interfaces (BMI) have developed rapidly in recent years, but still face critical issues such as accuracy and stability. Ideally, a BMI system would be an implantable neuroprosthesis that would be tightly connected and integrated into the brain. However, the heterogeneity of brains and machines hinders deep fusion between the two. Neuromorphic computing models, which mimic the structure and mechanism of biological nervous systems, present a promising approach to developing high-performance neuroprosthesis. The biologically plausible property of neuromorphic models enables homogeneous information representation and computation in the form of discrete spikes between the brain and the machine, promoting deep brain-machine fusion and bringing new breakthroughs for high-performance and long-term usable BMI systems. Furthermore, neuromorphic models can be computed at ultra-low energy costs and thus are suitable for brain-implantable neuroprosthesis devices. The intersection of neuromorphic computing and BMI has great potential to lead the development of reliable, low-power implantable BMI devices and advance the development and application of BMI. [ABSTRACT FROM AUTHOR]

Sensory feedback restoration in upper-limb neuroprosthetics can significantly enhance amputees' quality of life. Neural interfaces allow the elicitation of sensory information through current stimuli. Stimulation studies can be useful to evaluate the electric potential distribution into the nerve in response to a current stimulus and therefore the activation of fibers. In this paper, hybrid FEM-Neuron computational models are used to study nerve fiber activation in different nerve models that resemble the human median nerve. To conduct a comprehensive study, the variability in fascicular topography and different configurations of active sites of two types of electrodes (intraneural and extraneural) has been considered. Furthermore, the simulation results (in terms of the percentage of fiber activation in nerve fascicles, their location in the nerve section models, and the order of their activation when the stimulus increases) are evaluated according to the sensation intensity perceived by a human amputee in an experimental trial. The obtained results let us infer the effect of using intraneural and extraneural electrodes on the number and position of activated fascicles when the minimum values of electric charges considered in the experimental trial are used, and the dependence of the order of fiber activation into the fascicles on the current stimulus. [ABSTRACT FROM AUTHOR]

Decoding of sensorimotor information is essential for brain-computer interfaces (BCIs) as well as in normal functioning organisms. In this study, Bayesian models were developed for the prediction of binary decisions of 10 awake freely-moving male/female rats based on neural activity in a vibrotactile yes/no detection task. The vibrotactile stimuli were 40-Hz sinusoidal displacements (amplitude: 200 µm, duration: 0.5 s) applied on the glabrous skin. The task was to depress the right lever for stimulus detection and left lever for stimulus-off condition. Spike activity was recorded from 16-channel microwire arrays implanted in the hindlimb representation of primary somatosensory cortex (S1), overlapping also with the associated representation in the primary motor cortex (M1). Single-/multi-unit average spike rate (Rd) within the stimulus analysis window was used as the predictor of the stimulus state and the behavioral response at each trial based on a Bayesian network model. Due to high neural and psychophysical response variability for each rat and also across subjects, mean Rd was not correlated with hit and false alarm rates. Despite the fluctuations in the neural data, the Bayesian model for each rat generated moderately good accuracy (0.60–0.90) and good class prediction scores (recall, precision, F1) and was also tested with subsets of data (e.g. regular vs. fast spike groups). It was generally observed that the models were better for rats with lower psychophysical performance (lower sensitivity index A'). This suggests that Bayesian inference and similar machine learning techniques may be especially helpful during the training phase of BCIs or for rehabilitation with neuroprostheses. [ABSTRACT FROM AUTHOR]

Intracortical recordings can be used to voluntarily control external devices via brain-machine interfaces (BMI). Multiple factors, including the foreign body response (FBR), limit the stability of these neural signals over time. Current clinically approved devices consist of multi-electrode arrays with a single electrode site at the tip of each shank, confining the recording interface to a single layer of the cortex. Advancements in manufacturing technology have led to the development of high-density electrodes that can record from multiple layers. However, the long-term stability of neural recordings and the extent of neuronal cell loss around the electrode across different cortical depths have yet to be explored. To answer these questions, we recorded neural signals from rats chronically implanted with a silicon-substrate microelectrode array spanning the layers of the cortex. Our results show the long-term stability of intracortical recordings varies across cortical depth, with electrode sites around L4-L5 having the highest stability. Using machine learning guided segmentation, our novel histological technique, DeepHisto, revealed that the extent of neuronal cell loss varies across cortical layers, with L2/3 and L4 electrodes having the largest area of neuronal cell loss. These findings suggest that interfacing depth plays a major role in the FBR and long-term performance of intracortical neuroprostheses. [ABSTRACT FROM AUTHOR]

Bone conduction is a promising haptic feedback modality for upper-limb prosthesis users, however, its potential and characteristics as a non-invasive feedback modality have not been thoroughly investigated. This study aimed to establish the temporal and spatial characteristics of non-invasive bone conduction as a sensory feedback interface for upper-limb prostheses. Psychometric human-subject experiments were conducted on three bony landmarks of the elbow, with a vibrotactile transducer affixed to each to provide the stimulus. The study characterized the temporal domain by testing perception threshold and resolution in amplitude and frequency. The spatial domain was evaluated by assessing the ability of subjects to detect the number of simultaneous active stimulation sites. The experiment was conducted with ten able-bodied subjects and compared to two subjects with trans-radial amputation. The psychometric evaluation of the proposed non-invasive bone conduction feedback showed results comparable to invasive methods. The experimental results demonstrated similar amplitude and frequency resolution of the interface for all three stimulation sites for both able-bodied subjects and subjects with trans-radial amputation, highlighting its potential as a non-invasive feedback modality for upper-limb prostheses. [ABSTRACT FROM AUTHOR]

The effect of inhibitory management is usually underestimated in artificial control systems, using biological analogy. According to our hypothesis, the muscle hypertonus could be effectively compensated via stimulation by bio-plausible patterns. We proposed an approach for the compensatory stimulation device as implementation of previously presented architecture of the neurointerface, where (1) the neuroport is implemented as a DAC and stimulator, (2) neuroterminal is used for neurosimulation of a set of oscillator motifs on one-board computer. In the set of experiments with five volunteers, we measured the efficacy of motor neuron inhibition via the antagonistmuscle or nerve stimulation registeringmuscle force with and without antagonist stimulation. For the agonist activation, we used both voluntary activity and electrical stimulation. In the case of stimulation of both the agonist and the antagonist muscles and nerves, we experimented with delays between muscle stimulation in the range of 0–20 ms. We registered the subjective discomfort rate. We did not identify any significant difference between the antagonist muscle and nerve stimulation in both voluntary activity and electrical stimulation of cases showing agonist activity. We determined the most effective delay between the stimulation of the agonist and the antagonist muscles and nerves as 10–20 ms. [ABSTRACT FROM AUTHOR]

Multisegmental transcutaneous electrical stimulation of the spinal cord (sсTS), affecting spinal neural networks and motor pools of leg muscles, was used to correct treadmill walking in stroke patients. The study involved 15 patients in the recovery period after acute cerebrovascular accidents. A noninvasive spinal neuroprosthesis with a multichannel stimulator and a system for detecting phases of the walking cycle ("Cosima", Russia) was used to activate motor pools of leg flexor muscles in the transfer phase, activation of motor pools of extensor muscles in the stance phase in combination with continuous activation of spinal locomotor networks. Using of sсTS during walking on a treadmill increased the amplitude of movements in the ankle joint and the stride length on the paresis side, as well as a decreased the asymmetry of both legs in the phases of the gait cycle. The clearance of the paretic leg lift increased in 80% of patients. With a combination of continuous and phase-dependent stimulation, the increase in the range of motion in the joints was maximal compared to phase-dependent or only constant stimulation. The obtained data demonstrate that the proposed algorithm of the sсTS modulates the parameters of walking movements in patients with the consequences of cerebral circulation accidents and can be considered as a promising method of motor rehabilitation. [ABSTRACT FROM AUTHOR]

Invasive brain-computer interfaces hold promise to alleviate disabilities in individuals with neurologic injury, with fully implantable brain-computer interface systems expected to reach the clinic in the upcoming decade. Children with severe neurologic disabilities, like quadriplegic cerebral palsy or cervical spine trauma, could benefit from this technology. However, they have been excluded from clinical trials of intracortical brain-computer interface to date. In this manuscript, we discuss the ethical considerations related to the use of invasive brain-computer interface in children with severe neurologic disabilities. We first review the technical hardware and software considerations for the application of intracortical brain-computer interface in children. We then discuss ethical issues related to motor brain-computer interface use in pediatric neurosurgery. Finally, based on the input of a multidisciplinary panel of experts in fields related to brain-computer interface (functional and restorative neurosurgery, pediatric neurosurgery, mathematics and artificial intelligence research, neuroengineering, pediatric ethics, and pragmatic ethics), we then formulate initial recommendations regarding the clinical use of invasive brain-computer interfaces in children. [ABSTRACT FROM AUTHOR]

Intracortical recordings can be used to voluntarily control external devices via brain-machine interfaces (BMI). Multiple factors, including the foreign body response (FBR), limit the stability of these neural signals over time. Current clinically approved devices consist of multi-electrode arrays with a single electrode site at the tip of each shank, confining the recording interface to a single layer of the cortex. Advancements in manufacturing technology have led to the development of high-density electrodes that can record from multiple layers. However, the long-term stability of neural recordings and the extent of neuronal cell loss around the electrode across different cortical depths have yet to be explored. To answer these questions, we recorded neural signals from rats chronically implanted with a silicon-substrate microelectrode array spanning the layers of the cortex. Our results show the long-term stability of intracortical recordings varies across cortical depth, with electrode sites around L4-L5 having the highest stability. Using machine learning guided segmentation, our novel histological technique, DeepHisto, revealed that the extent of neuronal cell loss varies across cortical layers, with L2/3 and L4 electrodes having the largest area of neuronal cell loss. These findings suggest that interfacing depth plays a major role in the FBR and long-term performance of intracortical neuroprostheses.

Bone conduction is a promising haptic feedback modality for upper-limb prosthesis users, however, its potential and characteristics as a non-invasive feedback modality have not been thoroughly investigated. This study aimed to establish the temporal and spatial characteristics of non-invasive bone conduction as a sensory feedback interface for upper-limb prostheses. Psychometric human-subject experiments were conducted on three bony landmarks of the elbow, with a vibrotactile transducer affixed to each to provide the stimulus. The study characterized the temporal domain by testing perception threshold and resolution in amplitude and frequency. The spatial domain was evaluated by assessing the ability of subjects to detect the number of simultaneous active stimulation sites. The experiment was conducted with ten able-bodied subjects and compared to two subjects with trans-radial amputation. The psychometric evaluation of the proposed non-invasive bone conduction feedback showed results comparable to invasive methods. The experimental results demonstrated similar amplitude and frequency resolution of the interface for all three stimulation sites for both able-bodied subjects and subjects with trans-radial amputation, highlighting its potential as a non-invasive feedback modality for upper-limb prostheses.

Background: Restoring or improving seated stability after spinal cord injury (SCI) can improve the ability to perform activities of daily living by providing a dynamic, yet stable, base for upper extremity motion. Seated stability can be obtained with activation of the otherwise paralyzed trunk and hip musculature with neural stimulation, which has been shown to extend upper limb reach and improve seated posture. Methods: We implemented a proportional, integral, derivative (PID) controller to maintain upright seated posture by simultaneously modulating both forward flexion and lateral bending with functional neuromuscular stimulation. The controller was tested with a functional reaching task meant to require trunk movements and impart internal perturbations through rapid changes in inertia due to acquiring, moving, and replacing objects with one upper extremity. Five subjects with SCI at various injury levels who had received implanted stimulators targeting their trunk and hip muscles participated in the study. Each subject was asked to move a weighted jar radially from a center home station to one of three target stations. The task was performed with the controller active, inactive, or with a constant low level of neural stimulation. Trunk pitch (flexion) and roll (lateral bending) angles were measured with motion capture and plotted against each other to generate elliptical movement profiles for each task and condition. Postural sway was quantified by calculating the ellipse area. Additionally, the mean effective reach (distance between the shoulder and wrist) and the time required to return to an upright posture was determined during reaching movements. Results: Postural sway was reduced by the controller in two of the subjects, and mean effective reach was increased in three subjects and decreased for one. Analysis of the major direction of motion showed return to upright movements were quickened by 0.17 to 0.32 s. A 15 to 25% improvement over low/no stimulation was observed for four subjects. Conclusion: These results suggest that feedback control of neural stimulation is a viable way to maintain upright seated posture by facilitating trunk movements necessary to complete reaching tasks in individuals with SCI. Replication of these findings on a larger number of subjects would be necessary for generalization to the various segments of the SCI population. [ABSTRACT FROM AUTHOR]

The utility of currently available cortical prosthetic vision systems is disappointing. The essential features of a neuromorphic device that is predicted to enhance vision provided by available systems follow from a hypothesis which states that the objective and subjective aspects of cortical prosthetic vision jointly constitute patterns that emerge from specified synaptic interactions. The research reported here completes several required steps in developing an emulation of this device: (1) replication of small-scale simulations that are consistent with the hypothesis using the NEST (Écublens, Vaud, Switzerland) simulator, which can also be used for full-scale network emulation by a neuromorphic computer; (2) testing whether results consistent with the hypothesis survive increasing the scale and duration of simulations; (3) establishing a method that uses numbers of spikes produced by network neurons to report the number of phosphenes produced by cortical stimulation; and (4) simulating essential functions of a neuromorphic device which is predicted to enhance current prosthetic systems. NEST simulations replicated early results and increasing their scale and duration produced results consistent with the hypothesis. A decision function created using multinomial logistic regression correctly reported the expected number of phosphenes for three sets of 2080 spike number distributions in which half of each set arises from simulations expected to yield continuous visual forms by engaging a desired visual geometry. A process for modulating electrical stimulation amplitude based on intermittent population recordings that is predicted to produce desired visual geometries was successfully simulated. Implications of these results for future research are discussed. [ABSTRACT FROM AUTHOR]

Abstract Electrical stimulation is used to elicit muscle contraction and can be utilized for neurorehabilitation following spinal cord injury when paired with voluntary motor training. This technology is now an important therapeutic intervention that results in improvement in motor function in patients with spinal cord injuries. The purpose of this review is to summarize the various forms of electrical stimulation technology that exist and their applications. Furthermore, this paper addresses the potential future of the technology.

The direct neural stimulation of peripheral or central nervous systems has been shown as an effective tool to treat neurological conditions. The electrical activation of the nervous sensory pathway can be adopted to restore the artificial sense of touch and proprioception in people suffering from sensory‐motor disorders. The modulation of the neural stimulation parameters has a direct effect on the electrically induced sensations, both when targeting the somatosensory cortex and the peripheral somatic nerves. The properties of the artificial sensations perceived, as their location, quality and intensity are strongly dependent on the direct modulation of pulse width, amplitude and frequency of the neural stimulation. Different sensory encoding schemes have been tested in patients showing distinct effects and outcomes according to their impact on the neural activation. Here, I reported the most adopted neural stimulation strategies to artificially encode somatosensation into the peripheral nervous system. The real‐time implementation of these strategies in bionic devices is crucial to exploit the artificial sensory feedback in prosthetics. Thus, neural stimulation becomes a tool to directly communicate with the human nervous system. Given the importance of adding artificial sensory information to neuroprosthetic devices to improve their control and functionality, the choice of an optimal neural stimulation paradigm could increase the impact of prosthetic devices on the quality of life of people with sensorimotor disabilities. [ABSTRACT FROM AUTHOR]

Foot sole somatosensory impairment associated with peripheral neuropathy (PN) is prevalent and a strong independent risk factor for gait disturbance and falls in older adults. Walkasins, a lower-limb sensory prosthesis, has been shown to improve gait and mobility in people with PN by providing afferent input related to foot sole pressure distributions via lower-leg mechanical tactile stimulation. Given that gait and mobility are regulated by sensorimotor and cognitive brain networks, it is plausible improvements in gait and mobility from wearing the Walkasins may be associated with elicited neuroplastic changes in the brain. As such, this study aimed to examine changes in brain network connectivity after 26 weeks of daily use of the prosthesis among individuals with diagnosed PN and balance problems. In this exploratory investigation, assessments of participant characteristics, Functional Gait Assessment (FGA), and resting-state functional magnetic resonance imaging were completed at study baseline and 26 weeks follow-up. We found that among those who have completed the study (N = 8; mean age 73.7 years) we observed a fivepoint improvement in FGA performance as well as significant changes in network connectivity over the 26 weeks that were correlated with improved FGA performance. Specifically, greater improvement in FGA score over 26 weeks was associated with increased connectivity within the Default Mode Network (DMN; p < 0.01), the Somatosensory Network (SMN; p < 0.01), and the Frontoparietal Network (FPN; p < 0.01). FGA improvement was also correlated with increased connectivity between the DMN and the FPN (p < 0.01), and decreased connectivity between the SMN and both the FPN (p < 0.01) and cerebellum (p < 0.01). These findings suggest that 26 weeks of daily use of the Walkasins device may provide beneficial neural modulatory changes in brain network connectivity via the sensory replacement stimulation that are relevant to gait improvements among older adults with PN. [ABSTRACT FROM AUTHOR]

Feedback control of functional neuromuscular stimulation has the potential to improve daily function for individuals with spinal cord injuries (SCIs) by enhancing seated stability. Our fully implanted networked neuroprosthesis (NNP) can provide real-time feedback signals for controlling the trunk through accelerometers embedded in modules distributed throughout the trunk. Typically, inertial sensors are aligned with the relevant body segment. However, NNP implanted modules are placed according to surgical constraints and their precise locations and orientations are generally unknown. We have developed a method for calibrating multiple randomly oriented accelerometers and fusing their signals into a measure of trunk orientation. Six accelerometers were externally attached in random orientations to the trunks of six individuals with SCI. Calibration with an optical motion capture system resulted in RMSE below 5° and correlation coefficients above 0.97. Calibration with a handheld goniometer resulted in RMSE of 7° and correlation coefficients above 0.93. Our method can obtain trunk orientation from a network of sensors without a priori knowledge of their relationships to the body anatomical axes. The results of this study will be invaluable in the design of feedback control systems for stabilizing the trunk of individuals with SCI in combination with the NNP implanted technology. [ABSTRACT FROM AUTHOR]