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Individuals with complete cervical spinal cord injury suffer from a permanent paralysis of upper limbs which prevents them from achieving most of the activities of daily living. We developed a neuroprosthetic solution to restore hand motor function. Electrical stimulation of the radial and median nerves by means of two epineural electrodes enabled functional movements of paralyzed hands. We demonstrated in two participants with complete tetraplegia that selective stimulation of nerve fascicles by means of optimized spreading of the current over the active contacts of the multicontact epineural electrodes induced functional and powerful grasping movements which remained stable over the 28 days of implantation. We also showed that participants were able to trigger the activation of movements of their paralyzed limb using an intuitive interface controlled by voluntary actions and that they were able to perform useful functional movements such as holding a can and drinking through a straw., (© 2022. The Author(s).)

Multi-contact epineural electrical stimulation is a technique that can be used to restore grip movements in people with complete tetraplegia. However, neural stimulation can induce undesired H-reflex. This reflex is known to induce a global lower recruitment threshold together with a steepest recruitment curve leading to a degraded selective response. In this study, during stimulation of the median nerve using a multi-contact cuff electrode, a H-reflex response was observed for one muscle (the pronator teres i.e. PT) among the five recorded. As both M-wave and H-wave were separately recorded, we compared the changes of recruitment, recruitment order and se-lectivity with and without the H-reflex and found that blocking the reflex would have enhance the selectivity and increase the range of the intensity amplitude while providing a higher level of gripping force. Thus, blocking H-reflex is an important issue to further enhance epineural multicontact selective stimulation.

Two multi-contact epineural electrodes were placed around radial and median nerves of two subjects with high tetraplegia C4, American Spinal Injury Association Impairment Scale (AIS) A, group 0 of the International Classification for Surgery of the Hand in Tetraplegia. The purpose was to study the safety and capability of these electrodes to generate synergistic motor activation and functional movements and to test control interfaces that allow subjects to trigger pre-programmed stimulation sequences. The device consists of a pair of neural cuff electrodes and percutaneous cables with two extracorporeal connection cables inserted during a surgical procedure and maintained for 28 days. Continuity tests of the electrodes, selectivity of movements induced, motor capacities for grasping and gripping, conformity of the control order, tolerance, and acceptability were assessed. Neither of the two participants showed general and local comorbidity. Acceptability was optimal. None of the stimulation configurations generated contradictory movements. The success rate in task execution by the electro-stimulated hand exceeded the target of 50% (54% and 51% for patients 1 and 2, respectively). The compliance rate of the control orders in both patients was >90% using motion inertial measurement unit (IMU)-based detection and 100% using electromyography (EMG)-based detection in patient 1. These results support the relevance of neural stimulation of the tetraplegic upper limb with a more selective approach, using multi-contact epineural electrodes with nine and six contact points for the median and radial nerve respectively.

Implanted stimulation restores hand movement in patients with complete spinal cord injuries. However, assessing the response by surface evoked EMG recordings is challenging because the forearm muscles are small and overlapping. Moreover, M-waves are dependent because they are induced by a single stimulation paradigm. We hypothesized that the M-waves of each muscle has a specific time-frequency signature and we have developed a method to reconstruct the recruitment curves using the energy of this specific time-frequency signature. Orthogonal wavelets are used to analyze individual M-waves. As the selection of the wavelet family and the determination of the time-frequency signature were not trivial, the impact of these choices was evaluated. First, we were able to discriminate the 2 relevant M-waves related to the studied muscles thanks to their specific time-frequency representations. Second, the Meyer family, compared to the Daubechies 2 and 4 families, is the most robust choice against the uncertainty of the time-frequency region definition. Finally, the results are consistent with the semi-quantitative evaluation performed with the MRC scoring. The Meyer wavelet transform combined with the definition of a specific area of interest for each individual muscle allows us to quantitatively and objectively evaluate the evoked EMG in a robust manner., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Working towards the development of robust motion recognition systems for assistive technology control, the widespread approach has been to use a plethora of, often times, multi-modal sensors. In this paper, we develop single-sensor motion recognition systems. Utilising the peripheral nature of surface electromyography (sEMG) data acquisition, we optimise the information extracted from sEMG sensors. This allows the reduction in sEMG sensors or provision of contingencies in a system with redundancies. In particular, we process the sEMG readings captured at the trapezius descendens and platysma muscles. We demonstrate that sEMG readings captured at one muscle contain distinct information on movements or contractions of other agonists. We used the trapezius and platysma muscle sEMG data captured in able-bodied participants and participants with tetraplegia to classify shoulder movements and platysma contractions using white-box supervised learning algorithms. Using the trapezius sensor, shoulder raise is classified with an accuracy of 99%. Implementing subject-specific multi-class classification, shoulder raise , shoulder forward and shoulder backward are classified with a 94% accuracy amongst object raise and shoulder raise-and-hold data in able bodied adults. A three-way classification of the platysma sensor data captured with participants with tetraplegia achieves a 95% accuracy on platysma contraction and shoulder raise detection.

Objective: Sacral anterior root stimulation (SARS) was developed 40 years ago to restore urinary and bowel functions to individuals with spinal cord injury. Mostly used to restore lower urinary tract function, SARS implantation is coupled with sacral deafferentation to counteract the problems of chronic detrusor sphincter dyssynergia and detrusor overactivity. In this article, we systematically review 40 years of SARS implantation and assess the medical added value of this approach in accordance with the PRISMA guidelines. We identified 4 axes of investigation: 1) impact on visceral functions, 2) implantation safety and device reliability, 3) individuals' quality of life, and 4) additional information about the procedure., Methods: A systematic review was performed. Three databases were consulted: PubMed, EBSCOhost, and Pascal. A total of 219 abstracts were screened and 38 articles were retained for analysis (1147 implantations)., Results: The SARS technique showed good clinical results (85.9% of individuals used their implant for micturition and 67.9% to ease bowel movements) and improved individual quality of life. Conversely, several sources of complications were reported after implantation (e.g., surgical complications and failure)., Conclusions: Despite promising results, a decline in implantations was observed. This decline can be linked to the complication rate, as well as to the development of new therapeutics (e.g., botulinum toxin) and directions for research (spinal cord stimulation) that may have an impact on people. Nevertheless, the lack of alternatives in the short-term suggests that the SARS implant is still relevant for the restoration of visceral functions after spinal cord injury., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Complete tetraplegia can deprive a person of hand function. Assistive technologies may improve autonomy but needs for ergonomic interfaces for the user to pilot these devices still persist. Despite the paralysis of their arms, people with tetraplegia may retain residual shoulder movements. In this work we explored these movements as a mean to control assistive devices., Methods: We captured shoulder movement with a single inertial sensor and, by training a support vector machine based classifier, we decode such information into user intent., Results: The setup and training process take only a few minutes and so the classifiers can be user specific. We tested the algorithm with 10 able body and 2 spinal cord injury participants. The average classification accuracy was 80% and 84%, respectively., Conclusion: The proposed algorithm is easy to set up, its operation is fully automated, and achieved results are on par with state-of-the-art systems., Significance: Assistive devices for persons without hand function present limitations in their user interfaces. Our work presents a novel method to overcome some of these limitations by classifying user movement and decoding it into user intent, all with simple setup and training and no need for manual tuning. We demonstrate its feasibility with experiments with end users, including persons with complete tetraplegia without hand function.

Background: Brain-to-brain evoked potentials constitute a new methodology that could help to understand the network-level correlates of electrical stimulation applied for brain mapping during tumor resection. In this paper, we aimed to describe the characteristics of axono-cortical evoked potentials recorded from distinct, but in the same patient, behaviorally eloquent white matter sites., Methods: We report the intraoperative white matter mapping and axono-cortical evoked potentials recordings observed in a patient operated on under awake condition of a diffuse low-grade glioma in the left middle frontal gyrus. Out of the eight behaviorally eloquent sites identified with 60-Hz electrical stimulation, five were probed with single electrical pulses (delivered at 1 Hz), while recording evoked potentials on two electrodes, covering the inferior frontal gyrus and the precentral gyrus, respectively. Postoperative diffusion-weighted MRI was used to reconstruct the tractograms passing through each of the five stimulated sites., Results: Each stimulated site generated an ACEP on at least one of the recorded electrode contacts. The whole pattern-i.e., the specific contacts with ACEPs and their waveform-was distinct for each of the five stimulated sites., Conclusions: We found that the patterns of ACEPs provided unique electrophysiological signatures for each of the five white matter functional sites. Our results could ultimately provide neurosurgeons with a new tool of intraoperative electrophysiologically based functional guidance., (© 2021. Springer-Verlag GmbH Austria, part of Springer Nature.)

Peripheral Nerve Stimulation (PNS) is a promising approach in functional restoration following neural impairments. Although it proves to be advantageous in the number of implantation sites provided compared with intramuscular or epimysial stimulation and the fact that it does not require daily placement, as is the case with surface electrodes, the further advancement of PNS paradigms is hampered by the limitation of spatial selectivity due to the current spread and variations of nerve physiology. New electrode designs such as the Transverse Intrafascicular Multichannel Electrode (TIME) were proposed to resolve this issue, but their use was limited by a lack of innovative multichannel stimulation devices. In this study, we introduce a new portable multichannel stimulator-called STIMEP-and implement different stimulation protocols in rats to test its versatility and unveil the potential of its combined use with TIME electrodes in rehabilitation protocols. We developed and tested various stimulation paradigms in a single fascicle and thereafter implanted two TIMEs. We also tested its stimulation using two different waveforms. The results highlighted the versatility of this new stimulation device and advocated for the parameterizing of a hyperpolarizing phase before depolarization as well as the use of small pulse widths when stimulating with multiple electrodes.

Botulinum toxin-A (BoNT-A) blocks acetylcholine release at the neuromuscular junction (NMJ) and is widely used for neuromuscular disorders (involuntary spasms, dystonic disorders and spasticity). However, its therapeutic effects are usually measured by clinical scales of questionable validity. Single-fiber electromyography (SFEMG) is a sensitive, validated diagnostic technique for NMJ impairment such as myasthenia. The jitter parameter (µs) represents the variability of interpotential intervals of two muscle fibers from the same motor unit. This narrative review reports SFEMG use in BoNT-A treatment. Twenty-four articles were selected from 175 eligible articles searched in Medline/Pubmed and Cochrane Library from their creation until May 2020. The results showed that jitter is sensitive to early NMJ modifications following BoNT-A injection, with an increase in the early days' post-injection and a peak between Day 15 and 30, when symptoms diminish or disappear. The reappearance of symptoms accompanies a tendency for a decrease in jitter, but always precedes its normalization, either delayed or nonexistent. Increased jitter is observed in distant muscles from the injection site. No dose effect relationship was demonstrated. SFEMG could help physicians in their therapeutic evaluation according to the pathology considered. More data are needed to consider jitter as a predictor of BoNT-A clinical efficacy.

Direct electrical stimulation (DES) is used to perform functional brain mapping during awake surgery and in epileptic patients. DES may be coupled with the measurement of Evoked Potentials (EP) to study the conductive and integrative properties of activated neural ensembles and probe the spatiotemporal dynamics of short- and long-range networks. However, its electrophysiological effects remain by far unknown. We recorded ECoG signals on two patients undergoing awake brain surgery and measured EP on functional sites after cortical stimulations and were the firsts to record three different types of EP on the same patients. Using low-intensity (1-3 mA) to evoke electrogenesis we observed that: (i) "true" remote EPs are attenuated in amplitude and delayed in time due to the divergence of white matter pathways; (ii) "false" remote EPs are attenuated but not delayed: as they originate from the same electrical source; (iii) Singular but reproducible positive components in the EP can be generated when the DES is applied in the temporal lobe or the premotor cortex; and (iv) rare EP can be triggered when the DES is applied subcortically: these can be either negative, or surprisingly, positive. We proposed different activation and electrophysiological propagation mechanisms following DES, based on the nature of activated neural elements and discussed important methodological pitfalls when measuring EP in the brain. Altogether, these results pave the way to map the connectivity in real-time between the DES and the recording sites; to characterize the local electrophysiological states and to link electrophysiology and function. In the future, and in practice, this technique could be used to perform electrophysiological mapping in order to link (non)-functional to electrophysiological responses with DES and could be used to guide the surgical act itself.

Patients with central respiratory paralysis can benefit from diaphragm pacing to restore respiratory function. However, it would be important to develop a continuous respiratory monitoring method to alert on apnea occurrence, in order to improve the efficiency and safety of the pacing system. In this study, we present a preliminary validation of an acoustic apnea detection method on healthy subjects data. Thirteen healthy participants performed one session of two 2-min recordings, including a voluntary respiratory pause. The recordings were post-processed by combining temporal and frequency detection domains, and a new method was proposed-Phonocardiogram-Derived Respiration (PDR). The detection results were compared to synchronized pneumotachograph, electrocardiogram (ECG), and abdominal strap (plethysmograph) signals. The proposed method reached an apnea detection rate of 92.3%, with 99.36% specificity, 85.27% sensitivity, and 91.49% accuracy. PDR method showed a good correlation of 0.77 with ECG-Derived Respiration (EDR). The comparison of R-R intervals and S-S intervals also indicated a good correlation of 0.89. The performance of this respiratory detection algorithm meets the minimal requirements to make it usable in a real situation. Noises from the participant by speaking or from the environment had little influence on the detection result, as well as body position. The high correlation between PDR and EDR indicates the feasibility of monitoring respiration with PDR.

Objective: Micro-fabricated neural interfaces based on polyimide (PI) are achieving increasing importance in translational research. The ability to produce well-defined micro-structures with properties that include chemical inertness, mechanical flexibility and low water uptake are key advantages for these devices., Approach: This paper reports the development of the transverse intrafascicular multichannel electrode (TIME) used to deliver intraneural sensory feedback to an upper-limb amputee in combination with a sensorized hand prosthesis. A failure mode analysis on the explanted devices was performed after a first-in-human study limited to 30 d., Main Results: About 90% of the stimulation contact sites of the TIMEs maintained electrical functionality and stability during the full implant period. However, optical analysis post-explantation revealed that 62.5% of the stimulation contacts showed signs of delamination at the metallization-PI interface. Such damage likely occurred due to handling during explantation and subsequent analysis, since a significant change in impedance was not observed in vivo. Nevertheless, whereas device integrity is mandatory for long-term functionality in chronic implantation, measures to increase the bonding strength of the metallization-PI interface deserve further investigation. We report here that silicon carbide (SiC) is an effective adhesion-promoting layer resisting heavy electrical stimulation conditions within a rodent animal trial. Optical analysis of the new electrodes revealed that the metallization remained unaltered after delivering over 14 million pulses in vivo without signs of delamination at the metallization-PI interface., Significance: Failure mode analysis guided implant stability optimization. Reliable adhesion of thin-film metallization to substrate has been proven using SiC, improving the potential transfer of micro-fabricated neural electrodes for chronic clinical applications. (Document number of Ethical Committee: P/905/CE/2012; Date of approval: 2012-10-04).

Background: We hypothesized that a selective neural electrical stimulation of radial and median nerves enables the activation of functional movements in the paralyzed hand of individuals with tetraplegia. Compared to previous approaches for which up to 12 muscles were targeted through individual muscular stimulations, we focused on minimizing the number of implanted electrodes however providing almost all the needed and useful hand movements for subjects with complete tetraplegia., Methods: We performed acute experiments during scheduled surgeries of the upper limb with eligible subjects. We scanned a set of multicontact neural stimulation cuff electrode configurations, pre-computed through modeling simulations. We reported the obtained isolated and functional movements that were considered useful for the subject (different grasping movements)., Results: In eight subjects, we demonstrated that selective stimulation based on multicontact cuff electrodes and optimized current spreading over the active contacts provided isolated, compound, functional and strong movements; most importantly 3 out of 4 had isolated fingers or thumb flexion, one patient performed a Key Grip, another one the Power and Hook Grips, and the 2 last all the 3 Grips. Several configurations were needed to target different areas within the nerve to obtain all the envisioned movements. We further confirmed that the upper limb nerves have muscle specific fascicles, which makes it possible to activate isolated movements., Conclusions: The future goal is to provide patients with functional restoration of object grasping and releasing with a minimally invasive solution: only two cuff electrodes above the elbow. Ethics Committee / ANSM clearance prior to the beginning of the study (inclusion period 2016-2018): CPP Sud Méditerranée, #ID-RCB:2014-A01752-45, first acceptance 10th of February 2015, amended 12th of January 2016., Trial Registration: (www.clinicaltrials.gov): #NCT03721861, Retrospectively registered on 26th of October 2018.

Background: Partial arterial pressure of carbon dioxide (CO 2 ) modulates cerebral blood flow through a vasoreactivity mechanism. Near infrared spectroscopy (NIRS) can be used to record these changes in cerebral hemodynamics. However, no laterality comparison of the NIRS signal has been performed despite being a prerequisite for the use of such a method in a vasoreactivity monitoring context. We propose to investigate the NIRS signal laterality in response to a CO 2 -inhalation-based hypercapnia paradigm in healthy volunteers., Methods: Eleven healthy volunteers (6 women, 5 men, mean age: 31 ± 11) underwent a 3-block-design inhalation paradigm: normoxia (5min, "baseline") - hypercapnia (2min, "stimulation") - normoxia (5min, "post-stimulation"). NIRS signal was measured using a two-channel oximeter (INVOS 5100C, Medtronic, USA) with sensors placed symmetrically on both left and right sides on each subject's forehead. Additional heart rate (HR) monitoring was performed simultaneously. Based on the NIRS mean signal pattern, an a priori model of parametric identification was applied for each channel to quantify parameters of interest (amplitude, time delay, excitation and post-stimulation time) for each inhalation block., Results: HR increased significantly during the stimulation block. The quality of the model was satisfactory: mean absolute errors between modeled and experimental signals were lower than the resolution of the device. No significant lateralization was found between left and right values of most of the parameters., Conclusion: Due to the lack of lateralization, this parametric identification of NIRS responses to hypercapnia could bring light to a potential asymmetry and be used as a biomarker in patients with cerebrovascular diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

This paper presents a wireless distributed Functional Electrical Stimulation (FES) architecture. It is based on a set of, potentially heterogeneous, distributed stimulation and measurement units managed by a wearable controller. Through a proof-of-concept application, the characterization of the wireless network performances was assessed to check the adequacy of this solution with open-loop and closed-loop control requirements. We show the guaranteed time performances over the network through the control of quadriceps and hamstrings stimulation parameters based on the monitoring of the knee joint angle. Our solution intends to be a tool for researchers and therapists to develop closed-loop control algorithms and strategies for rehabilitation, allowing the design of wearable systems for a daily use context., (Copyright © 2020 Andreu, Sijobert, Toussaint, Fattal, Azevedo-Coste and Guiraud.)

Objective: Direct electrical stimulation (DES) at 60 Hz is used to perform real-time functional mapping of the brain, and guide tumour resection during awake neurosurgery. Nonetheless, the electrophysiological effects of DES remain largely unknown, both locally and remotely., Approach: In this study, we lowered the DES frequency to 1-10 Hz and we used a differential recording mode of electro-corticographic (ECoG) signals to improve the focality with a simple algorithm to remove the artefacts due to the response of the acquisition chain., Main Results: Doing so, we were able to observe different components in the evoked potentials triggered by simulating the cortex or the subcortical white matter pathways near the recording electrodes and by stimulating the cortex remotely from the recording site. More particularly, P0 and N1 components were repeatedly observed on raw ECoG signals without the need to average the data., Significance: This new methodology is important to probe the electrophysiological states and the connectivity of the brain in vivo and in real time, namely to perform electrophysiological brain mapping on human patients operated in the neurosurgical room and to better understand the electrophysiological spreading of DES.

Direct electrical stimulation (DES) is used to perform functional brain mapping during awake surgery but its electrophysiological effects remain by far unknown. DES may be coupled with the measurement of evoked potentials (EPs) to study the conductive and integrative properties of activated neural ensembles and probe the spatiotemporal dynamics of short- and long-range networks. We recorded ECoG signals on two patients undergoing awake brain surgery and measured EPs on functional sites after cortical stimulations, using combinations of stimulation parameters. EPs were similar in shape but delayed in time and attenuated in amplitude when elicited from a different gyrus or remotely from the recording site. We were able to trigger remote EPs using low stimulation intensities. We propose different activation and electrophysiological propagation mechanisms following DES based on activated neural elements.

Although peripheral nerve stimulation using intraneural electrodes has been shown to be an effective and reliable solution to restore sensory feedback after hand loss, there have been no reports on the characterization of multi-channel stimulation. A deeper understanding of how the simultaneous stimulation of multiple electrode channels affects the evoked sensations should help in improving the definition of encoding strategies for bidirectional prostheses. We characterized the sensations evoked by simultaneous stimulation of median and ulnar nerves (multi-channel configuration) in four transradial amputees who had been implanted with four TIMEs (Transverse Intrafascicular Multichannel Electrodes). The results were compared with the characterization of single-channel stimulation. The sensations were characterized in terms of location, extent, type, and intensity. Combining two or more single-channel configurations caused a linear combination of the sensation locations and types perceived with such single-channel stimulations. Interestingly, this was also true when two active sites from the same nerve were stimulated. When stimulating in multi-channel configuration, the charge needed from each electrode channel to evoke a sensation was significantly lower than the one needed in single-channel configuration (sensory facilitation). This result was also supported by electroencephalography (EEG) recordings during nerve stimulation. Somatosensory potentials evoked by multi-channel stimulation confirmed that sensations in the amputated hand were perceived by the subjects and that a perceptual sensory facilitation occurred. Our results should help the future development of more efficient bidirectional prostheses by providing guidelines for the development of more complex stimulation approaches to effectively restore multiple sensations at the same time.

In this study, we present a new model describing the mechanical behavior of the skeletal muscle during isometric contraction. This model is based on a former Hill-inspired model detailing the electromechanical behavior of the muscle based on the Huxley formulation. However, in this new multiscale model the muscle is represented at the Motor Unit (MU) scale. The proposed model is driven by a physiological input describing the firing moments of the activated MUs. Definition of both voluntary and evoked MU recruitment schemes are described, enabling the study of both contractions in isometric conditions. During this type of contraction, there is no movement of the joints and the tendon-muscle complex remains at the same length. Moreover, some well-established macroscopic relationships such as force-length or force-velocity properties are considered. A comparison with a twitch model using the same input definition is provided with both recruitment schemes exhibiting limitations of twitch type models. Finally, the proposed model is validated with a comparison between simulated and recorded force profiles following eight electrical stimulations pulses in isometric conditions. The simulated muscle force was generated to mimic the one recorded from the quadriceps of a patient implanted with a functional electrical stimulation neuroprosthesis. This validation demonstrates the ability of the proposed model to reproduce realistically the skeletal muscle contractions and to take into account subject-specific parameters., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: The goal of this study was to evaluate the long-term behavior of the surface electrode through electrochemical characterization and follow-up of implanted parylene/platinum microelectrodes., Approach: To this aim, we designed and manufactured specific planar electrodes for cortical implantation for a rat model. This work was included in the INTENSE ® project, one of the goals of which was to prove the feasibility of selective neural recording or stimulation with cuff electrodes around the vagus nerve., Main Results: After a 12-week implantation in a rat model, we can report that these microelectrodes have withstood in vivo use. Regarding the biocompatibility of the electrodes (materials and manufacturing process), no adverse effect was reported. Indeed, after the three-month implantation, we characterized limited tissue reaction beneath the electrodes and showed an increase and a stabilization of their impedance. Interestingly, the follow-up of the electrochemical impedance combined with electrical stimulation highlighted a drop in the impedance up to 60% at 1 kHz after ten minutes of electrical stimulation at 110 Hz., Significance: This study gives evidence of the biocompatibility of the parylene platinum contact array designed for the project and confirms the effect of stimulation on the contact impedance.

Individuals who sustained a spinal cord injury often lose important motor skills, and cannot perform basic daily living activities. Several assistive technologies, including robotic assistance and functional electrical stimulation, have been developed to restore lost functions. However, designing reliable interfaces to control assistive devices for individuals with C4-C8 complete tetraplegia remains challenging. Although with limited grasping ability, they can often control upper arm movements via residual muscle contraction. In this article, we explore the feasibility of drawing upon these residual functions to pilot two devices, a robotic hand and an electrical stimulator. We studied two modalities, supra-lesional electromyography (EMG), and upper arm inertial sensors (IMU). We interpreted the muscle activity or arm movements of subjects with tetraplegia attempting to control the opening/closing of a robotic hand, and the extension/flexion of their own contralateral hand muscles activated by electrical stimulation. Two groups were recruited: eight subjects issued EMG-based commands; nine other subjects issued IMU-based commands. For each participant, we selected at least two muscles or gestures detectable by our algorithms. Despite little training, all participants could control the robot's gestures or electrical stimulation of their own arm via muscle contraction or limb motion.

Lower limb amputation (LLA) destroys the sensory communication between the brain and the external world during standing and walking. Current prostheses do not restore sensory feedback to amputees, who, relying on very limited haptic information from the stump-socket interaction, are forced to deal with serious issues: the risk of falls, decreased mobility, prosthesis being perceived as an external object (low embodiment), and increased cognitive burden. Poor mobility is one of the causes of eventual device abandonment. Restoring sensory feedback from the missing leg of above-knee (transfemoral) amputees and integrating the sensory feedback into the sensorimotor loop would markedly improve the life of patients. In this study, we developed a leg neuroprosthesis, which provided real-time tactile and emulated proprioceptive feedback to three transfemoral amputees through nerve stimulation. The feedback was exploited in active tasks, which proved that our approach promoted improved mobility, fall prevention, and agility. We also showed increased embodiment of the lower limb prosthesis (LLP), through phantom leg displacement perception and questionnaires, and ease of the cognitive effort during a dual-task paradigm, through electroencephalographic recordings. Our results demonstrate that induced sensory feedback can be integrated at supraspinal levels to restore functional abilities of the missing leg. This work paves the way for further investigations about how the brain interprets different artificial feedback strategies and for the development of fully implantable sensory-enhanced leg neuroprostheses, which could drastically ameliorate life quality in people with disability., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Conventional leg prostheses do not convey sensory information about motion or interaction with the ground to above-knee amputees, thereby reducing confidence and walking speed in the users that is associated with high mental and physical fatigue 1-4 . The lack of physiological feedback from the remaining extremity to the brain also contributes to the generation of phantom limb pain from the missing leg 5,6 . To determine whether neural sensory feedback restoration addresses these issues, we conducted a study with two transfemoral amputees, implanted with four intraneural stimulation electrodes 7 in the remaining tibial nerve (ClinicalTrials.gov identifier NCT03350061). Participants were evaluated while using a neuroprosthetic device consisting of a prosthetic leg equipped with foot and knee sensors. These sensors drive neural stimulation, which elicits sensations of knee motion and the sole of the foot touching the ground. We found that walking speed and self-reported confidence increased while mental and physical fatigue decreased for both participants during neural sensory feedback compared to the no stimulation trials. Furthermore, participants exhibited reduced phantom limb pain with neural sensory feedback. The results from these proof-of-concept cases provide the rationale for larger population studies investigating the clinical utility of neuroprostheses that restore sensory feedback.

Neural multicontact cuff electrodes have the potential to activate selectively different groups of muscles and offer more possibilities of electrical configurations compared to whole ring cuffs. Several previous studies explored multicontact electrodes with a limited set of configurations which were sorted using a selectivity index only. The objective of the present study is to classify a larger number of configurations, i.e. the way the current is spread over the 12 contacts of the cuff electrode, using additional criteria such as robustness (i.e. ability to maintain selectivity within a range of current amplitudes) and efficiency (i.e. electrical consumption of the considered multipolar configuration versus the electrical consumption of the reference whole-ring configuration). Experiments were performed on the sciatic nerve of 4 rabbits. Results indicated that the optimal configuration depends on the weights applied to selectivity, robustness and efficiency criteria. Tripolar transverse is the most robust configuration and the less efficient, whereas tripolar longitudinal ring is efficient but not robust. New configurations issued from a previous theoretical study we carried out such as steering current ring appears as good compromise between the 3 criteria., Competing Interests: The authors have read the journal’s policy and the authors of this manuscript have the following competing interests: WT is a paid employee of MxM. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Neuroprostheses are medical devices which, interfaced with the nervous system, are able to provoke the artificial generation of nerve signals. These signals, correctly coded, can then be interpreted by target organs such as the muscles., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Electrical stimulation of the phrenic nerves via implanted devices allows to counteract some disadvantages of mechanical ventilation in patients with high tetraplegia or Ondine's syndrome. Existing devices do not allow to monitor breathing or to adapt the electroventilation to patients' actual needs. A reliable breathing monitor with an inbuilt alarm function would improve patient safety. In our study, a real-time acoustic breathing detection method is proposed as a possible solution to improve implanted phrenic stimulation. A new algorithm to process tracheal sounds has been developed. It combines breathing detection in both temporal and frequency domains. The algorithm has been applied on recordings from 18 healthy participants. The obtained average sensitivity, specificity and accuracy of the detection are: 99.31%, 96.84% and 98.02%, respectively. These preliminary results show a first positive proof of the interest of such an approach. Additional experiments are needed, including longer recordings from individuals with tetraplegia or Ondine Syndrome in various environments to go further in the validation.

Background: In the context of morbid obesity, vagus nerve stimulation could be used to control gastric function targeting the small afferent B-fibers and C-fibers. Compared to large A-fibers, activation thresholds of these small efferent fibers are 10 to 100 times greater, inducing technical constraints and possible nerve damages. Although rectangular waveform is commonly used in nerve stimulation, recent modeling and experimental studies suggest that non-rectangular waveforms could reduced the charge injected by the stimulator., New Method: The objective of the present study is to evaluate the charge injection of complex waveforms such as the ramp, quarter sine and chopped pulses in the context of vagus nerve stimulation. We performed in-vivo study on the porcine abdominal vagus nerves and evaluated charge injection at activation thresholds. A modeling study was performed to further extent the results obtained in-vivo., Comparison With Existing Method: Compared to the rectangular pulse, the ramp and quarter sine waveforms activated gastric fibers with the lowest charge injection: -23.2% and -30.1% respectively. The efficacy of chopped pulses is questioned through the consideration of the strength-duration curve., Conclusion: Continuous ramp and quarter sine waveforms effectively activate small diameter fibers. These pulse shapes may be considered for long-term vagus nerve stimulation. The results predicted by computational models were qualitatively consistent with experiments. This suggested the relevance of using modeling in the context of complex waveforms prior to future in-vivo tests., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Spinal cord injuries (SCIs) result in loss of movement and sensory feedback, but also organ dysfunction. Nearly all patients with complete SCI lose bladder control and are prone to kidney failure if intermittent catheterization is not performed. Electrical stimulation of sacral spinal roots was initially considered to be a promising approach for restoring continence and micturition control, but many patients are discouraged by the need for surgical deafferentation as it could lead to a loss of sensory functions and reflexes. Nevertheless, recent research findings highlight the renewed interest in spinal cord stimulation (SCS). It is thought that synergic recruitment of spinal fibers could be achieved by stimulating the spinal neural networks involved in regulating physiological processes. Paradoxically, most of these recent studies focused on locomotor issues, while few addressed visceral dysfunction. This could at least partially be attributed to the lack of methodological tools. In this study, the authors aim to fill this gap by presenting a comprehensive method for investigating the potential of SCS to restore visceral functions in domestic pigs, a large-animal model considered to be a close approximation to humans., Methods: This methodology was tested in 7 female pigs (Landrace pig breed, 45-60 kg, 4 months old) during acute experiments. A combination of morphine and propofol was used for anesthesia when transurethral catheterization and lumbosacral laminectomy (L4-S4) were performed. At the end of the operation, spinal root stimulation (L6-S5) and urodynamic recordings were performed to compare the evoked responses with those observed intraoperatively in humans., Results: Nervous excitability was preserved despite long-term anesthesia (mean 8.43 ± 1.5 hours). Transurethral catheterization and conventional laminectomy were possible while motor responses (gluteus muscle monitoring) were unaffected throughout the procedure. Consistent detrusor (approximately 25 cm H2O) and sphincter responses were obtained, whereas spinal root stimulation elicited detrusor and external urethral sphincter co-contractions similar to those observed intraoperatively in humans., Conclusions: Pigs represent an ideal model for SCS studies aimed at visceral function investigation and restoration because of the close similarities between female domestic pigs and humans, both in terms of anatomical structure and experimental techniques implemented. This article provides methodological keys for conducting experiments with equipment routinely used in clinical practice.

Objective: Hand amputation is a highly disabling event, which significantly affects quality of life. An effective hand replacement can be achieved if the user, in addition to motor functions, is provided with the sensations that are naturally perceived while grasping and moving. Intraneural peripheral electrodes have shown promising results toward the restoration of the sense of touch. However, the long-term usability and clinical relevance of intraneural sensory feedback have not yet been clearly demonstrated., Methods: To this aim, we performed a 6-month clinical study with 3 transradial amputees who received implants of transverse intrafascicular multichannel electrodes (TIMEs) in their median and ulnar nerves. After calibration, electrical stimulation was delivered through the TIMEs connected to artificial sensors in the digits of a prosthesis to generate sensory feedback, which was then used by the subjects while performing different grasping tasks., Results: All subjects, notwithstanding their important clinical differences, reported stimulation-induced sensations from the phantom hand for the whole duration of the trial. They also successfully integrated the sensory feedback into their motor control strategies while performing experimental tests simulating tasks of real life (with and without the support of vision). Finally, they reported a decrement of their phantom limb pain and a general improvement in mood state., Interpretation: The promising results achieved with all subjects show the feasibility of the use of intraneural stimulation in clinical settings. ANN NEUROL 2019;85:137-154., (© 2018 American Neurological Association.)

Nearly all spinal cord injured (SCI) individuals lose bladder control and are prone to kidney complications if intermittent catheterization is not applied. Electrical stimulation of the sacral anterior roots with an implantable neuroprosthesis is one means to restore continence and control micturition. However, only a small percentage of the SCI population benefits from this solution because of its drawbacks, e.g., section of sacral posterior roots with loss of spared sensitivity. There has been renewed interest in spinal cord stimulation in recent years, but most studies have focused on locomotion and only few have reported the impact on visceral functions. Moreover, even though the lumbosacral spinal cord is the location of many pre-cabled neural networks (involved in locomotion, bladder, and bowel management), the functional selectivity of spinal stimulations has never been investigated in detail. Here, we present: 1) a methodology designed to study lumbosacral epispinal-intradural stimulation selectivity; 2) preliminary results assessing the impact of epispinal stimulation on bladder and bowel functions in two domestic pigs; and 3) a comparison of these visceral responses with abdominal and lower limb activities. Our experiments resulted in selective bladder and rectal responses, i.e., without hind paw responses, thus reaffirming the rehabilitation potential of spinal cord stimulation.

Slow-growing, infiltrative brain tumours may modify the electrophysiological balance between the two hemispheres. To determine whether and how asymmetry of EEG rhythms during motor preparation might occur following "awake brain surgery" for this type of tumour, we recorded electroencephalograms during a simple visuo-manual reaction time paradigm performed by the patients between 3 and 12 months after surgery and compared them to a control group of 8 healthy subjects. Frequency analyses revealed imbalances between the injured and healthy hemispheres. More particularly, we observed a power increase in the δ frequency band near the lesion site and a power increase in the α and β frequency bands. Interestingly, these alterations seem to decrease for the two patients whose surgery were anterior to 9 months, independently of the size of the lesion. Reaction times did not reflect this pattern as they were clearly not inversely related to the anteriority of the surgery. Electrophysiology suggests here different processes of recovery compared to behavioral data and brings further insights for the understanding of EEG rhythms that should not be systematically confounded or assimilated with cognitive performances. EEG monitoring is rare for these patients, especially after awake brain surgery, however it is important., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Multipolar cuff electrode can selectively stimulate areas of peripheral nerves and therefore enable to control independent functions. However, the branching and fascicularization are known for a limited set of nerves and the specific organization remains subject-dependent. This paper presents general modeling and optimization methods in the context of multipolar stimulation using a cuff electrode without a priori knowledge of the nerve structure. Vagus nerve stimulation experiments based on the optimization results were then investigated., Approach: The model consisted of two independent components: a lead field matrix representing the transfer function from the applied current to the extracellular voltage present on the nodes of Ranvier along each axon, and a linear activation model. The optimization process consisted in finding the best current repartition (ratios) to reach activation of a targeted area depending on three criteria: selectivity, efficiency and robustness., Main Results: The results showed that state-of-the-art configurations (tripolar transverse, tripolar longitudinal) were part of the optimized solutions but new ones could emerge depending on the trade-off between the three criteria and the targeted area. Besides, the choice of appropriate current ratios was more important than the choice of the stimulation amplitude for a stimulation without a priori knowledge of the nerve structure. We successfully assessed the solutions in vivo to selectively induce a decrease in cardiac rhythm through vagus nerve stimulation while limiting side effects. Compared to the standard whole ring configuration, a selective solution found by simulation provided on average 2.6 less adverse effects., Significance: The preliminary results showed the rightness of the simulation, using a generic nerve geometry. It suggested that this approach will have broader applications that would benefit from multicontact cuff electrodes to elicit selective responses. In the context of the vagus nerve stimulation for heart failure therapy, we show that the simulation results were confirmed and improved the therapy while decreasing the side effects.

Functional electrical stimulation (FES) is a neuroprosthetic technique to help restore motor function of spinal cord-injured (SCI) patients. Through delivery of electrical pulses to muscles of motor-impaired subjects, FES is able to artificially induce their muscle contractions. Evoked electromyography (eEMG) is used to record such FES-induced electrical muscle activity and presents a form of [Formula: see text]-wave. In order to monitor electrical muscle activity under stimulation and ensure safe stimulation configurations, closed-loop FES control with eEMG feedback is needed to be developed for SCI patients who lose their voluntary muscle contraction ability. This work proposes a closed-loop FES system for real-time control of muscle activation on the triceps surae and tibialis muscle groups through online modulating pulse width (PW) of electrical stimulus. Subject-specific time-variant muscle responses under FES are explicitly reflected by muscle excitation model, which is described by Hammerstein system with its input and output being, respectively, PW and eEMG. Model predictive control is adopted to compute the PW based on muscle excitation model which can online update its parameters. Four muscle activation patterns are provided as desired control references to validate the proposed closed-loop FES control paradigm. Real-time experimental results on three able-bodied subjects and five SCI patients in clinical environment show promising performances of tracking the aforementioned reference muscle activation patterns based on the proposed closed-loop FES control scheme.