Highlights d Biomimetic hybrid sensory encodings are perceived as highly natural d Biomimetic hybrid sensory encodings restore rich tactile sensitivity d Biomimetic hybrid sensory encodings improve manual dexterity and accuracy d Biomimetic hybrid sensory encodings enhance prosthesis embodiment

Current myoelectric prostheses allow transradial amputees to regain voluntary motor control of their artificial limb by exploiting residual muscle function in the forearm. However, the overreliance on visual cues resulting from a lack of sensory feedback is a common complaint. Recently, several groups have provided tactile feedback in upper limb amputees using implanted electrodes, surface nerve stimulation, or sensory substitution. These approaches have led to improved function and prosthesis embodiment. Nevertheless, the provided information remains limited to a subset of the rich sensory cues available to healthy individuals. More specifically, proprioception, the sense of limb position and movement, is predominantly absent from current systems. Here, we show that sensory substitution based on intraneural stimulation can deliver position feedback in real time and in conjunction with somatotopic tactile feedback. This approach allowed two transradial amputees to regain high and close-to-natural remapped proprioceptive acuity, with a median joint angle reproduction precision of 9.1° and a median threshold to detection of passive movements of 9.5°, which was comparable with results obtained in healthy participants. The simultaneous delivery of position information and somatotopic tactile feedback allowed both amputees to discriminate the size and compliance of four objects with high levels of performance (75.5%). These results demonstrate that tactile information delivered via somatotopic neural stimulation and position information delivered via sensory substitution can be exploited simultaneously and efficiently by transradial amputees. This study paves a way to more sophisticated bidirectional bionic limbs conveying richer, multimodal sensations.

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 six months clinical study with three trans-radial 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 the subjects, notwithstanding their important clinical differences, reported stimulationinduced 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.

Recent studies have shown that direct nerve stimulation can be used to provide sensory feedback to hand amputees. The intensity of the elicited sensations can be modulated using the amplitude or frequency of the injected stimuli. However, a comprehensive comparison of the effects of these two encoding strategies on the amputees’ ability to control a prosthesis has not been performed. In this paper, we assessed the performance of two trans-radial amputees controlling a myoelectric hand prosthesis while receiving grip force sensory feedback encoded using either linear modulation of amplitude (LAM) or linear modulation of frequency (LFM) of direct nerve stimulation (namely, bidirectional prostheses). Both subjects achieved similar and significantly above-chance performance when they were asked to exploit LAM or LFM in different tasks. The feedbacks allowed them to discriminate, during manipulation through the robotic hand, objects of different compliances and shapes or different placements on the prosthesis. Similar high performances were obtained when they were asked to apply different levels of force in a random order on a dynamometer using LAM or LFM. In contrast, only the LAM strategy allowed the subjects to continuously modulate the grip pressure on the dynamometer. Furthermore, when long-lasting trains of stimulation were delivered, LFM strategy generated a very fast adaptation phenomenon in the subjects, which caused them to stop perceiving the restored sensations. Both encoding approaches were perceived as very different from the touch feelings of the healthy limb (natural). These results suggest that the choice of specific sensory feedback encodings can have an effect on user performance while grasping. In addition, our results invite the development of new approaches to provide more natural sensory feelings to the users, which could be addressed by a more biomimetic strategy in the future.

No abstract

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.

Objective. Tactile afferents in the human hand provide fundamental information about handenvironment interactions, which is used by the brain to adapt the motor output to the physical properties of the object being manipulated. A hand amputation disrupts both afferent and efferent pathways from/to the hand, completely invalidating the individual's motor repertoire. Although motor functions may be partially recovered by using a myoelectric prosthesis, providing functionally effective sensory feedback to users of prosthetics is a largely unsolved challenge. While past studies using invasive stimulation suggested that sensory feedback may help in handling fragile objects, none explored the underpinning, relearned, motor coordination during grasping. In this study, we aimed at showing for the first time that intraneural sensory feedback of the grip force improves the sensorimotor control of a transradial amputee controlling a myoelectric prosthesis. Approach. We performed a longitudinal study testing a single subject (clinical trial registration number NCT02848846). A stacking cups test (CUP) performed over two weeks aimed at measuring the subject's ability to finely regulate the grip force applied with the prosthesis. A pick and lift test (PLT), performed at the end of the study, measured the level of motor coordination, and whether the subject transferred the motor skills learned in the CUP to an alien task. Main results. The results show that intraneural sensory feedback increases the subject's ability in regulating the grip force and allows for improved performance over time. Additionally, the PLT Page 2 of 14 demonstrated that the subject was able to generalize and transfer her manipulation skills to an unknown task and to improve her motor coordination. Significance. Our findings suggest that intraneural sensory feedback holds the potential of restoring functionally effective tactile feedback. This opens up new possibilities to improve the quality of life of amputees using a neural prosthesis.

Objective. Bioelectronic medicine is opening new perspectives for the treatment of some major chronic diseases through the physical modulation of autonomic nervous system activity. Being the main peripheral route for electrical signals between central nervous system and visceral organs, the vagus nerve (VN) is one of the most promising targets. Closed-loop VN stimulation (VNS) would be crucial to increase effectiveness of this approach. Therefore, the extrapolation of useful physiological information from VN electrical activity would represent an invaluable source for single-target applications. Here, we present an advanced decoding algorithm novel to VN studies and properly detecting different functional changes from VN signals. Approach. VN signals were recorded using intraneural electrodes in anaesthetized pigs during cardiovascular and respiratory challenges mimicking increases in arterial blood pressure, tidal volume and respiratory rate. We developed a decoding algorithm that combines discrete wavelet transformation, principal component analysis, and ensemble learning made of classification trees. Main results. The new decoding algorithm robustly achieved high accuracy levels in identifying different functional changes and discriminating among them. Interestingly our findings suggest that electrodes positioning plays an important role on decoding performances. We also introduced a new index for the characterization of recording and decoding performance of neural interfaces. Finally, by combining an anatomically validated hybrid neural model and discrimination analysis, we provided new evidence suggesting a functional topographical organization of VN fascicles. Significance. This study represents an important step towards the comprehension of VN signaling, paving the way for the development of effective closed-loop VNS systems.