Cervical spinal cord stimulation (SCS) improves upper-limb function in individuals with chronic post-stroke hemiparesis, yet how it shapes motor control of arm movement remains unclear. During goal-directed reaching in healthy individuals, movements consist of a coordinated acceleration phase toward the target followed by a deceleration phase that stabilizes the limb near the endpoint. Disruptions in neuromotor control post-stroke can be partially restored by SCS, with prominent improvements occurring in the deceleration phase. To quantitatively characterize these effects, we used a proportional–derivative (PD) control model to fit planar reaching data from 12 healthy and 5 stroke participants. Movements were well described by the model, with proportional gain terms capturing the acceleration phase and derivative gain terms capturing velocity-dependent deceleration. In healthy individuals, model fits revealed a consistent balance between position and velocity-dependent torques that closely matched the optimal solution for smooth and stable reaching predicted by optimal feedback control simulations. In stroke, this balance was altered and partially normalized by SCS, with the most consistent changes observed in the velocity-dependent term. While the prevailing hypothesis is that SCS boosts motor drive to weak agonistic muscles, these results indicate a synergistic and potentially dominant effect in suppressing hyperexcitability of antagonistic muscles controlling the deceleration phase of movement. Finally, the PD controller model revealed frequency-dependent effects of SCS, suggesting that the model parameters may serve as biomarkers for guiding the selection of stimulation parameters. This work serves as a framework for characterizing how neuromodulatory therapies influence arm control .

Abstract Volumetric muscle loss (VML) injuries overwhelm the inherent regenerative capacity of skeletal muscle, causing persistent functional deficits with no routinely effective therapies. Electrical stimulation (ES) has been shown to preserve muscle structure in other injury models, but technical barriers have prevented daily delivery during the acute post-injury window when critical regenerative programs are established. Here, we developed a fully implantable bioelectronic system with nanoporous platinum-modified electrodes enabling daily therapeutic stimulation and electromyographic recording without repeated anesthesia in a rat tibialis anterior VML model. Animals receiving ES during the acute post-injury period (10 sessions over days 0–14) showed sustained functional improvement, reaching 90% of baseline torque at 8 weeks compared to 71% in unstimulated controls. This recovery reflected enhanced remodeling of injured muscle rather than synergistic muscle compensation. Histological analysis revealed coordinated early increases in vascularization, pro-regenerative macrophages, and satellite cells. These findings establish early ES as a promising intervention for promoting muscle regeneration after catastrophic injury.

Most individuals with tetraplegia retain some myoelectric function in their forearms, which offers the possibility of using surface electromyographic (sEMG) control for human-computer interaction (HCI). We demonstrate the potential of this approach by showing that people with motor-complete (n=5) and motor-incomplete (n=2) tetraplegia can accurately control myoelectric activity in their forearm to perform discrete button-click and continuous positioning tasks. These control inputs were mapped to the firing rate of motor units detected by a wireless wristband sensor designed for everyday use. Participants completed four testing sessions to assess their speed and accuracy. Motor units that displayed a wide dynamic range in their firing rate performed best during tasks requiring continuous, single-axis control. Interestingly, the level of impairment did not affect performance on the clicking and 1D cursor control tasks. However, those with motor-incomplete injuries showed greater independent control over two motor units than participants with motor-complete injuries, who exhibited stronger coupling between units. Participants also confirmed the practical utility of the device, successfully placing and removing the sEMG wristband on their own and consistently rating it as comfortable and easy to manage. These findings are significant because they offer the first demonstration of motor unit-based control in individuals with cervical spinal cord injury (SCI) using a fully wearable wristband interface, highlighting the feasibility of moving these systems out of the lab and into daily life. ### Competing Interest Statement DJW owns stock in Meta Platforms, Inc. NM, EF, MB, JL, JY, PW, DM, SN, and DAG are employees of Meta Platforms, Inc. Reality Labs at Meta

Whether proprioception is necessary for upper-limb motor control has been debated for decades. Classic studies in deafferented animals and humans suggested that proprioception may be dispensable for rapid, goal-directed movements. However, chronic sensory loss conflates the absence of proprioceptive input with years of compensatory adaptation. As a result, the field has lacked a strong causal test of proprioception's contribution to motor control. Here, we leveraged a clinical trial of cervical spinal cord stimulation (SCS) in individuals with chronic post-stroke hemiparesis to study if electrical stimulation of sensory afferents causally perturbs proprioception and affects arm reaching. We found that turning SCS ON causally impaired proprioceptive perception and postural stabilization in response to force perturbations, and enhanced adaptation to visual errors during implicit learning. Yet visually and non-visually rapid, goal-directed reaching improved in smoothness, straightness and spatial accuracy. These findings provide strong causal evidence that proprioception is not required for rapid, goal-directed action, helping resolve a decades-long debate regarding its necessity for effective movement.

Magnetoelectric nanoparticles (MENPs) provide a fully wireless and minutely invasive platform for bidirectional brain-computer interfaces (BCIs) by locally transducing magnetic fields into electric fields, and vice versa. The achievable spatial and temporal resolutions are governed by the control of magnetic field energy at the nanoparticle level. Since the introduction of the MENP concept a decade and a half ago, independent studies have demonstrated MENP-mediated neural activation in vitro and in vivo, establishing a strong proof of concept for wireless neuromodulation. In contrast, MENP-based neural recording remains largely theoretical, with existing models indicating that in vivo implementation is feasible. However, progress toward scalable and reliable MENP-based BCIs is hindered by an incomplete understanding of the nonlinear physics governing MENP operation and nanoparticle-cell interactions. This study addresses this gap by developing a comprehensive theoretical framework that explicitly incorporates nonlinear effects and correlates neuromodulation predictions with available experimental data. The analysis identifies nanoparticle properties and magnetic field amplitude and frequency as key performance determinants. Properly engineered MENPs are predicted to enable deepbrain and cortical neuromodulation and recording with submillimeter spatial resolution and millisecondscale temporal precision, offering a pathway toward clinically viable BCIs without implanted electrodes or genetic modification.

ABSTRACT Introduction/Aims Amyotrophic lateral sclerosis (ALS) causes progressive motor neuron degeneration, denervation, collateral reinnervation, and altered motor unit organization. Clinical assessments track functional decline but provide limited information about the physiological remodeling that precedes or accompanies weakness. High-density surface electromyography (HD-sEMG) can noninvasively measure motor unit morphology, fatigue-related signal behavior, and spatial patterns of muscle activation. Methods We recorded HD-sEMG from the biceps brachii and tibialis anterior in participants with ALS and healthy controls during sustained isometric contractions at 30% and 50% maximum voluntary contraction. Features were extracted from four domains: fatigue dynamics, motor unit morphology, propagation, and spatial organization. Principal component analysis (PCA) was used to test whether the dominant HD-sEMG feature structure was shared or reorganized differently between groups at baseline and during fatigue. Results Baseline PCA showed highly similar HD-sEMG structure in healthy and ALS muscles. Baseline loading profiles were strongly spatial in both groups, with spatial features contributing 91.1% of loading weight in healthy observations and 89.9% in ALS observations. During fatigue, the composite did not significantly separate groups, but ALS showed a larger shift in loading structure and greater score variability than controls. The fatigue-change composite did not scale linearly with limb function. Exploratory binned analysis showed the greatest variability in the moderate impairment group. Discussion HD-sEMG captured strong spatial organization in both groups during baseline contraction. Sustained contraction exposed more variable ALS responses involving amplitude and spectral dynamics, rather than a single uniform fatigue pattern.

Objective: The 10th International brain computer interface (BCI) Society Meeting, 'Balancing Innovation and Translation', was held from the 6th to 9th of June 2023 in Brussels, Belgium. This report provides a summary of the workshop 'Building Consensus on Clinical Outcome Assessments (COAs) for BCI Devices'. This workshop was intended to give participants an overview of the current state of BCI, future opportunities, and how different countries and regions provide regulatory oversight to support the BCI community to develop safe and effective devices for patients.Approach: Five presentations and a panel discussion including representatives from regulators, industry, and clinical research stakeholders focused on how various stakeholders and the BCI community might best work together to ensure studies provide data that is useful for evaluating safety and effectiveness, including reaching consensus on COAs that represent clinically meaningful benefits and support regulatory and payor requirements. This report focuses on the regulatory and reimbursement requirements for medical devices and how to best measure safety and effectiveness and summarizes the presentations from five experts and the discussion between the panel and the audience.Main results: Consensus was reached on the following items specifically related to BCI: (i) the importance of and need for a new generation of COAs, (ii) the challenges facing the development of appropriate clinical outcome assessments, and (iii) that improvements in COAs should demonstrate obvious and clinically meaningful benefit(s). There was discussion on: (i) clinical trial design for BCIs and (ii) considerations for payor reimbursement and other funding.Significance: Whilst the importance of building community consensus on COAs was apparent, further collaboration will be required to reach consensus on which specific current and/or novel COAs could be used for the BCI field to evolve from research to market.

Surface electromyography (sEMG) is useful for studying muscle function and controlling prosthetics, but cross talk from nearby muscles often limits its effectiveness. High-density surface EMG (HD-sEMG) improves spatial resolution, allowing for the isolation of M-waves in the densely packed forearm muscles. This study assessed HD-sEMG for localizing M-waves and evaluated the impact of spatial filters on cross talk reduction. We administered peripheral nerve stimulation to activate forearm muscles in five participants. We analyzed cross talk by correlating the shape of M-waves between electrodes and used ultrasound to confirm muscle identity and location. At low-stimulation intensities, we successfully isolated M-waves with minimal cross talk without spatial filtering. Higher recruitment levels produced significant cross talk, which was reduced by applying bipolar or tripolar spatial filters. M-waves from the monopolar HD-sEMG montage showed high correlations between electrodes (r = 0.97 transversely; r = 0.95 longitudinally), while bipolar and tripolar montages showed lower correlations (bipolar: r = 0.41 transversely; r = 0.19 longitudinally; tripolar: r = 0.17 transversely; r = 0.01 longitudinally). The tripolar filter significantly reduced cross talk (51.10% amplitude decay one electrode away) compared with no filter (10.32% amplitude decay one electrode away), effectively reducing cross talk to negligible levels at distances >= 2.55 cm. Ultrasound was crucial for distinguishing true activation from artifacts caused by converging signals along muscle boundaries. Spatially filtered HD-sEMG accurately detects and isolates M-waves in the forearm, and ultrasound imaging is useful for verifying the location and identity of the muscles underlying the HD-sEMG grids. NEW & NOTEWORTHY This study introduces an innovative approach to enhancing evoked potential measurements using high-density surface electromyography (HD-sEMG). The precision and localization of evoked potentials are significantly improved by spatial filters and ultrasound imaging, offering a novel method for better assessing motor pathway integrity. These advancements could lead to more accurate tools for detecting and treating neurological deficits, making it a significant contribution to neurophysiological research.

Objective. Evoked compound action potentials (ECAPs) measured during epidural spinal cord stimulation (SCS) can help elucidate fundamental mechanisms for the treatment of pain and inform closed-loop control of SCS. Previous studies have used ECAPs to characterize neural responses to various neuromodulation therapies and have demonstrated that ECAPs are highly prone to multiple sources of artifact, including post-stimulus pulse capacitive artifact, electromyography (EMG) bleed-through, and motion artifact. However, a thorough characterization has yet to be performed for how these sources of artifact may contaminate recordings within the temporal window commonly used to determine activation of A-beta fibers in a large animal model.Approach. We characterized sources of artifacts that can contaminate the recording of ECAPs in an epidural SCS swine model using the Abbott Octrode™ lead.Main results. Spinal ECAP recordings can be contaminated by capacitive artifact, short latency EMG from nearby muscles of the back, and motion artifact. The capacitive artifact can appear nearly identical in duration and waveshape to evoked A-beta responses. EMG bleed-through can have phase shifts across the electrode array, similar to the phase shift anticipated by propagation of an evoked A-beta fiber response. The short latency EMG is often evident at currents similar to those needed to activate A-beta fibers associated with the treatment of pain. Changes in CSF between the cord and dura, and motion induced during breathing created a cyclic oscillation in all evoked components of recorded ECAPs.Significance. Controls must be implemented to separate neural signal from sources of artifact in SCS ECAPs. We suggest experimental procedures and reporting requirements necessary to disambiguate underlying neural response from these confounds. These data are important to better understand the framework for epidural spinal recordings (ESRs), with components such as ECAPs, EMG, and artifacts, and have important implications for closed-loop control algorithms to account for transient motion such as postural changes and cough.

Objective: Quantification of the skeletal muscle response can help better understand the fundamentals of the musculoskeletal system and can serve as a diagnostic measure or recovery assessment tool during rehabilitation for neurological injuries. Surface electromyography (EMG) is commonly used to measure muscle activity, but it is limited to detecting myoelectric signals without anatomy associated information. In this study, we proposed to use ultra-fast ultrasound imaging and introduced a new image analysis methodology to quantify a muscle's spatialtemporal mechanical response. Methods: The methodology is based on analyzing the spatial-temporal change of the impulsive kinetic energy during the period of muscle contraction. The analysis can derive an anatomy-registered muscle activation metric map that localizes regions of muscle activation. To demonstrate this, we intentionally evoked regional muscle responses in five participants without disabilities by electrically stimulating the median nerve and individual forearm muscle groups, respectively. Both ultrasound images and high-density EMG (HD-EMG) data were recorded and processed. Results: We presented the ultrasound image-derived activation localization from five participants and compared the results with HD-EMG measurements. Conclusion: The comparison indicates a good resemblance for describing muscle recruitment pattern. Significance: The proposed methodology can potentially become an alternative or complementary approach to surface EMG for the study of skeletal muscle activation and for diagnosis and prognosis in clinical settings

Background:Implanted brain-computer interfaces (iBCIs) establish direct communication with the brain and hold the potential to enable people with severe disability to achieve control of digital devices, enabling communication and digital activities of daily living. The ability to access brain signals reliably and continuously over many years post-implantation is crucial for iBCIs to be effective and feasible. This study investigates the signal characteristics and long-term stability of neural activity recorded with a stent-electrode array over 1 year post-implant. Methods:We report on five participants with paralysis who were enrolled in an early feasibility clinical trial of an endovascular iBCI (Stentrode; ClinicalTrials.gov, NCT05035823). Each participant was implanted with a 16-channel stent-electrode array, deployed in the superior sagittal sinus to record bilaterally from the primary motor cortices. Neural activity was recorded during home-based sessions while the participants performed a set of standardized tasks. Metrics including motor signal strength during attempted movement, resting state signal features, and electrode impedances were quantified over time. Results:Motor-related modulation in neural activity was exhibited in the high-frequency bands (30-200 Hz) during attempted movements, with rest and attempted movement states showing sustained differentiation over time. Impedance and resting state band power for most channels did not change significantly over time. Conclusions:These findings provide strong evidence that the endovascular BCIs may be suitable for long-term neural signal acquisition in the home environment, demonstrating the ability to record movement-related modulation over one year.

Brain-computer interfaces (BCIs) are an emerging assistive technology for individuals with motor impairments, enabling the command of digital devices using neural signals. The Stentrode BCI is an implant, positioned within the brain's neurovasculature, that can record movement-related electrocortical activity. Over 5 years, 10 participants (8 amyotrophic lateral sclerosis, 1 primary lateral sclerosis, 1 brainstem stroke) have been implanted with a Stentrode BCI and significant inter-participant variability has been observed in the recorded motor signal strength. This variability warrants a critical investigation to characterize potential predictors of signal strength to promote more successful BCI control in future participants. Therefore, we investigated the relationship between Stentrode BCI motor signal strength and a variety of user-specific factors: (1) clinical status, (2) pre-implant functional activity, (3) peri-implant neuroanatomy, (4) peri-implant neurovasculature, and (5) Stentrode device integrity. Data from 10 implanted participants, including clinical demographics, pre- and post-implant neuroimaging and longitudinal Stentrode BCI motor signal assessments were acquired over a year. Across all potential predictors, the strongest predictor of Stentrode motor signal strength was the degree to which the Stentrode BCI's deployment position overlapped with primary motor cortex (M1). These findings highlight the importance of targeting M1 during device deployment and, more generally, provides a scientific framework for investigating the role of user-specific factors on BCI device outcomes.

Objective. The goal of this study was to examine the effects of spinal cord stimulation (SCS) on muscle activity during walking after lower-limb amputation. Amputation results in a loss of sensory feedback and alterations in gait biomechanics, including co-contractions of antagonist muscles about the knee and ankle, and reduced pelvic obliquity range-of-motion and pelvic drop. SCS can restore sensation in the missing limb, but its effects on muscle activation and gait biomechanics have not been studied in people with lower-limb amputation.Approach. This case study included a participant with transtibial amputation who was implanted percutaneously with SCS electrodes over the lumbosacral enlargement for 84 d. SCS was used during in-lab experiments to provide somatosensory feedback from the missing limb, relaying a sense of plantar pressure when the prosthesis was in the stance phase of the gait cycle. We used electromyography (EMG) to record muscle activity from the residual and intact limbs, and 3D motion capture to measure pelvic obliquity and knee and ankle joint angles. EMG signals were recorded during walking with and without SCS at early (Day 30) and late (Day 63) time points across the implant duration.Main results. During walking, co-contraction of knee antagonist muscles was reduced following multiple sessions of SCS-mediated sensory restoration. Additionally, the activation of the hip abductor (tensor fasciae latae) muscle increased activity during gait with SCS-mediated sensory restoration, which corresponded to an increase in pelvic obliquity range-of-motion and pelvic drop, towards normal.Significance. Restoring sensation in the missing limb using SCS altered muscle activity during walking led to improved coordination and pelvic motion in an individual with lower-limb amputation.

People with lower-limb amputation lack sensory inputs from their missing limb, which increases their risk of falling. We recently demonstrated that spinal cord stimulation (SCS) can restore sensation in the missing lower limb. Previous studies have shown that SCS can affect motor control by exciting spinal reflex pathways after stroke or spinal cord injury. The effects of SCS on spinal reflex activation have not been studied in people with lower-limb amputation. Furthermore, it is unknown if SCS-evoked spinal reflex activation would perturb walking. Therefore, the goal of this study was to characterize SCS-evoked spinal reflexes in people with lower-limb amputation and quantify effects on gait parameters, including step cycle duration and limb alternation symmetry. We implanted percutaneous SCS electrodes over the lumbosacral enlargement in 3 people with transtibial amputation (2 diabetic neuropathy; 1 traumatic) for 28 or 84 days. SCS was delivered to restore sensation in the missing limb during walking based on signals from a pressure-sensing insole in the shoe under the prosthesis. We used electromyography (EMG) to record posterior root-muscle (PRM) reflexes in the residual limb while participants were seated, standing, or walking. We characterized rate-dependent depression and recruitment properties of the PRM reflexes. We used pressure data from instrumented insoles to measure the step cycle duration and limb alternation symmetry with and without SCS. SCS evoked PRM reflexes in the residual limb muscles in all participants, which was confirmed by the presence of rate-dependent depression at stimulation frequencies ≥ 2 Hz. Overall, there was broad activation of residual limb muscles with SCS that varied with the position of the stimulating electrode relative to the lumbar spinal cord. PRM reflexes were also activated during walking, as confirmed by the presence of rate-dependent depression. However, SCS-evoked PRM reflexes did not disrupt gait, with similar step cycle duration or limb alternation symmetry with and without SCS. Restoring sensation in the missing limb using SCS excites spinal reflexes according to the expected rostral-caudal myotomes but does not disrupt the step cycle duration or limb alternation symmetry in people with transtibial amputation. Therefore, SCS can restore sensory feedback in the missing limb without disrupting the existing motor activation of the residual limb muscles.

Implanted neural interfaces are electronic devices that stimulate or record from neurons with the purpose of improving the quality of life of people who suffer from neural injury or disease. Devices have been designed to interact with neurons throughout the body to treat a growing variety of conditions. The development and use of implanted neural interfaces is increasing steadily and has shown great success, with implants lasting for years to decades and improving the health and quality of life of many patient populations. Despite these successes, implanted neural interfaces face a multitude of challenges to remain effective for the lifetime of their users. The devices are comprised of several electronic and mechanical components that each may be susceptible to failure. Furthermore, implanted neural interfaces, like any foreign body, will evoke an immune response. The immune response will differ for implants in the central nervous system and peripheral nervous system, as well as over time, ultimately resulting in encapsulation of the device. This review describes the challenges faced by developers of neural interface systems, particularly devices already in use in humans. The mechanical and technological failure modes of each component of an implant system is described. The acute and chronic reactions to devices in the peripheral and central nervous system and how they affect system performance are depicted. Further, physical challenges such as micro and macro movements are reviewed. The clinical implications of device failures are summarized and a guide for determining the severity of complication was developed and provided. Common methods to diagnose and examine mechanical, technological, and biological failure modes at various stages of development and testing are outlined, with an emphasis on chronic in vivo characterization of implant systems. Finally, this review concludes with an overview of some of the innovative solutions developed to reduce or resolve the challenges faced by implanted neural interface systems.

Objective.This study examined the strength and stability of motor signals in low gamma and high gamma bands of vascular electrocorticograms (vECoG) recorded with endovascular stent-electrode arrays (Stentrodes) implanted in the superior sagittal sinus of two participants with severe paralysis due to amyotrophic lateral sclerosis.Approach.vECoG signals were recorded from two participants in the COMMAND trial, an Early Feasibility Study of the Stentrode brain-computer interface (BCI) (NCT05035823). The participants performed attempted movements of their ankles or hands. The signals were band-pass filtered to isolate low gamma (30-70 Hz) and high gamma (70-200 Hz) components. The strength of vECoG motor activity was measured as signal-to-noise ratio (SNR) and the percentage change in signal amplitude between the rest and attempted movement epochs, which we termed depth of modulation (DoM). We trained and tested classifiers to evaluate the accuracy and stability of detecting motor intent.Main results.Both low gamma and high gamma were modulated during attempted movements. For Participant 1, the average DoM across channels and sessions was 125.41 ± 17.53% for low gamma and 54.23 ± 4.52% for high gamma, with corresponding SNR values of 6.75 ± 0.37 dB and 3.69 ± 0.28 dB. For Participant 2, the average DoM was 22.77 ± 4.09% for low gamma and 22.53 ± 2.04% for high gamma, with corresponding SNR values of 1.72 ± 0.25 dB and 1.73 ± 0.13 dB. vECoG amplitudes remained significantly different between rest and move periods over the 3 month testing period, with >90% accuracy in discriminating attempted movement from rest epochs for both participants. For Participant 1, the average DoM was strongest during attempted movements of both ankles, while for Participant 2, the DoM was greatest for attempted movement of the right hand. The overall classification accuracy was 91.43% for Participant 1 and 70.37% for Participant 2 in offline decoding of multiple attempted movements and rest conditions.Significance.By eliminating the need for open brain surgery, the Stentrode offers a promising BCI alternative, potentially enhancing access to BCIs for individuals with severe motor impairments. This study provides preliminary evidence that the Stentrode can detect discriminable signals indicating motor intent, with motor signal modulation observed over the 3 month testing period reported here.

High-density electromyography (HDEMG) can detect myoelectric activity as control inputs to a variety of electronically-controlled devices. Furthermore, HDEMG sensors may be built into a variety of clothing, allowing for a non-intrusive myoelectric interface that is integrated into a user’s routine. In our work, we introduce an easily-producible HDEMG device that interfaces with the control of a mobile manipulator to perform a range of household and physically assistive tasks. Mobile manipulators can operate throughout the home and are applicable for a spectrum of assistive and daily tasks in the home. We evaluate the use of real-time myoelectric gesture recognition using our device to enable precise control over the intricate mobility and manipulation functionalities of an 8 degree-of-freedom mobile manipulator. Our evaluation, involving 13 participants engaging in challenging self-care and household activities, demonstrates the potential of our wearable HDEMG system to control a mobile manipulator in the home.