Reconnecting the Hand and Arm to the Brain: Efficacy of Neural Interfaces for Sensorimotor Restoration After Tetraplegia.

BACKGROUND AND OBJECTIVES: Paralysis after spinal cord injury involves damage to pathways that connect neurons in the brain to peripheral nerves in the limbs. Re-establishing this communication using neural interfaces has the potential to bridge the gap and restore upper extremity function to people with high tetraplegia. We report a novel approach for restoring upper extremity function using selective peripheral nerve stimulation controlled by intracortical microelectrode recordings from sensorimotor networks, along with restoration of tactile sensation of the hand using intracortical microstimulation. METHODS: A 27-year-old right-handed man with AIS-B (motor-complete, sensory-incomplete) C3-C4 tetraplegia was enrolled into the clinical trial. Six 64-channel intracortical microelectrode arrays were implanted into left hemisphere regions involved in upper extremity function, including primary motor and sensory cortices, inferior frontal gyrus, and anterior intraparietal area. Nine 16-channel extraneural peripheral nerve electrodes were implanted to allow targeted stimulation of right median, ulnar (2), radial, axillary, musculocutaneous, suprascapular, lateral pectoral, and long thoracic nerves, to produce selective muscle contractions on demand. Proof-of-concept studies were performed to demonstrate feasibility of using a brain-machine interface to read from and write to the brain for restoring motor and sensory functions of the participant's own arm and hand. RESULTS: Multiunit neural activity that correlated with intended motor action was successfully recorded from intracortical arrays. Microstimulation of electrodes in somatosensory cortex produced repeatable sensory percepts of individual fingers for restoration of touch sensation. Selective electrical activation of peripheral nerves produced antigravity muscle contractions, resulting in functional movements that the participant was able to command under brain control to perform virtual and actual arm and hand movements. The system was well tolerated with no operative complications. CONCLUSION: The combination of implanted cortical electrodes and nerve cuff electrodes has the potential to create bidirectional restoration of motor and sensory functions of the arm and hand after neurological injury.

Distally-referred surface electrical nerve stimulation (DR-SENS) for haptic feedback.

Objective.This study's objective is to understand distally-referred surface electrical nerve stimulation (DR-SENS) and evaluates the effects of electrode placement, polarity, and stimulation intensity on the location of elicited sensations in non-disabled individuals.Approach.A two-phased human experiment was used to characterize DR-SENS. In Experiment One, we explored 182 electrode combinations to identify a subset of electrode position combinations that would be most likely to elicit distally-referred sensations isolated to the index finger without discomfort. In Experiment Two, we further examined this subset of electrode combinations to determine the effect of stimulation intensity and electrode position on perceived sensation location. Stimulation thresholds were evaluated using parameter estimation by sequential testing and sensation locations were characterized using psychometric intensity tests.Main Results.We found that electrode positions distal to the wrist can consistently evoke distally referred sensations with no significant polarity dependency. The finger-palm combination had the most occurrences of distal sensations, and the different variations of this combination did not have a significant effect on sensation location. Increasing stimulation intensity significantly expanded the area of the sensation, moved the most distal sensation distally, and moved the vertical centroid proximally. Also, a large anodic-leading electrode at the elbow mitigated all sensation at the anodic-leading electrode site while using symmetric stimulation waveforms. Furthermore, this study showed that the most intense sensation for a given percept can be distally referred. Lastly, for each participant, at least one of the finger-palm combinations evaluated in this study worked at both perception threshold and maximum comfortable stimulation intensities.Significance.These findings show that a non-invasive surface electrical stimulation charge modulated haptic interface can be used to elicit distally-referred sensations on non-disabled users. Furthermore, these results inform the design of novel haptic interfaces and other applications of surface electrical stimulation based haptic feedback on electrodes positioned distally from the wrist.

Tessellation of artificial touch via microstimulation of human somatosensory cortex.

When we interact with objects, we rely on signals from the hand that convey information about the object and our interaction with it. A basic feature of these interactions, the locations of contacts between the hand and object, is often only available via the sense of touch. Information about locations of contact between a brain-controlled bionic hand and an object can be signaled via intracortical microstimulation (ICMS) of somatosensory cortex (S1), which evokes touch sensations that are localized to a specific patch of skin. To provide intuitive location information, tactile sensors on the robotic hand drive ICMS through electrodes that evoke sensations at skin locations matching sensor locations. This approach requires that ICMS-evoked sensations be focal, stable, and distributed over the hand. To systematically investigate the localization of ICMS-evoked sensations, we analyzed the projected fields (PFs) of ICMS-evoked sensations - their location and spatial extent - from reports obtained over multiple years from three participants implanted with microelectrode arrays in S1. First, we found that PFs vary widely in their size across electrodes, are highly stable within electrode, are distributed over large swaths of each participant's hand, and increase in size as the amplitude or frequency of ICMS increases. Second, while PF locations match the locations of the receptive fields (RFs) of the neurons near the stimulating electrode, PFs tend to be subsumed by the corresponding RFs. Third, multi-channel stimulation gives rise to a PF that reflects the conjunction of the PFs of the component channels. By stimulating through electrodes with largely overlapping PFs, then, we can evoke a sensation that is experienced primarily at the intersection of the component PFs. To assess the functional consequence of this phenomenon, we implemented multichannel ICMS-based feedback in a bionic hand and demonstrated that the resulting sensations are more localizable than are those evoked via single-channel ICMS.

Implanted Electrodes for Functional Electrical Stimulation to Restore Upper and Lower Extremity Function: History and Future Directions.

Functional electrical stimulation (FES) to activate nerves and muscles in paralyzed extremities has considerable promise to improve outcome after neurological disease or injury, especially in individuals who have upper motor nerve dysfunction due to central nervous system pathology. Because technology has improved, a wide variety of methods for providing electrical stimulation to create functional movements have been developed, including muscle stimulating electrodes, nerve stimulating electrodes, and hybrid constructs. However, in spite of decades of success in experimental settings with clear functional improvements for individuals with paralysis, the technology has not yet reached widespread clinical translation. In this review, we outline the history of FES techniques and approaches and describe future directions in evolution of the technology.

Reconnecting the Hand and Arm to the Brain: Efficacy of Neural Interfaces for Sensorimotor Restoration after Tetraplegia.

Background: Paralysis after spinal cord injury involves damage to pathways that connect neurons in the brain to peripheral nerves in the limbs. Re-establishing this communication using neural interfaces has the potential to bridge the gap and restore upper extremity function to people with high tetraplegia. Objective: We report a novel approach for restoring upper extremity function using selective peripheral nerve stimulation controlled by intracortical microelectrode recordings from sensorimotor networks, along with restoration of tactile sensation of the hand using intracortical microstimulation. Methods: A right-handed man with motor-complete C3-C4 tetraplegia was enrolled into the clinical trial. Six 64-channel intracortical microelectrode arrays were implanted into left hemisphere regions involved in upper extremity function, including primary motor and sensory cortices, inferior frontal gyrus, and anterior intraparietal area. Nine 16-channel extraneural peripheral nerve electrodes were implanted to allow targeted stimulation of right median, ulnar (2), radial, axillary, musculocutaneous, suprascapular, lateral pectoral, and long thoracic nerves, to produce selective muscle contractions on demand. Proof-of-concept studies were performed to demonstrate feasibility of a bidirectional brain-machine interface to restore function of the participant's own arm and hand. Results: Multi-unit neural activity that correlated with intended motor action was successfully recorded from intracortical arrays. Microstimulation of electrodes in somatosensory cortex produced repeatable sensory percepts of individual fingers for restoration of touch sensation. Selective electrical activation of peripheral nerves produced antigravity muscle contractions. The system was well tolerated with no operative complications. Conclusion: The combination of implanted cortical electrodes and nerve cuff electrodes has the potential to allow restoration of motor and sensory functions of the arm and hand after neurological injury.

Frequency Shapes the Quality of Tactile Percepts Evoked through Electrical Stimulation of the Nerves.

Electrical stimulation of the peripheral nerves of human participants provides a unique opportunity to study the neural determinants of perceptual quality using a causal manipulation. A major challenge in the study of neural coding of touch has been to isolate the role of spike timing-at the scale of milliseconds or tens of milliseconds-in shaping the sensory experience. In the present study, we address this question by systematically varying the pulse frequency (PF) of electrical stimulation pulse trains delivered to the peripheral nerves of seven participants with upper and lower extremity limb loss via chronically implanted neural interfaces. We find that increases in PF lead to systematic increases in perceived frequency, up to ∼50 Hz, at which point further changes in PF have little to no impact on sensory quality. Above this transition frequency, ratings of perceived frequency level off, the ability to discriminate changes in PF is abolished, and verbal descriptors selected to characterize the sensation change abruptly. We conclude that sensation quality is shaped by temporal patterns of neural activation, even if these patterns are imposed on a fixed neural population, but this temporal patterning can only be resolved up to ∼50 Hz. These findings highlight the importance of spike timing in shaping the quality of a sensation and will contribute to the development of encoding strategies for conveying touch feedback through bionic hands and feet.SIGNIFICANCE STATEMENT A major challenge in the study of neural coding of touch has been to understand how temporal patterns in neuronal responses shape the sensory experience. We address this question by varying the pulse frequency (PF) of electrical pulse trains delivered through implanted nerve interfaces in seven amputees. We concomitantly vary pulse width to separate the effect of changing PF on sensory quality from its effect on perceived magnitude. We find that increases in PF lead to increases in perceived frequency, a qualitative dimension, up to ∼50 Hz, beyond which changes in PF have little impact on quality. We conclude that temporal patterning in the neuronal response can shape quality and discuss the implications for restoring touch via neural interfaces.

Measuring embodiment: A review of methods for prosthetic devices.

The development of neural interfaces to provide improved control and somatosensory feedback from prosthetic limbs has initiated a new ability to probe the various dimensions of embodiment. Scientists in the field of neuroprosthetics require dependable measures of ownership, body representation, and agency to quantify the sense of embodiment felt by patients for their prosthetic limbs. These measures are critical to perform generalizable experiments and compare the utility of the new technologies being developed. Here, we review outcome measures used in the literature to evaluate the senses of ownership, body-representation, and agency. We categorize these existing measures based on the fundamental psychometric property measured and whether it is a behavioral or physiological measure. We present arguments for the efficacy and pitfalls of each measure to guide better experimental designs and future outcome measure development. The purpose of this review is to aid prosthesis researchers and technology developers in understanding the concept of embodiment and selecting metrics to assess embodiment in their research. Advances in the ability to measure the embodiment of prosthetic devices have far-reaching implications in the improvement of prosthetic limbs as well as promoting a broader understanding of ourselves as embodied agents.

The experience of sensorimotor integration of a lower limb sensory neuroprosthesis: A qualitative case study.

Introduction: Lower limb prosthesis users often struggle to navigate uneven terrain or ambulate in low light conditions where it can be challenging to rely on visual cues for balance and walking. Sensory feedback about foot-floor interactions may allow users to reduce reliance on secondary sensory cues and improve confidence and speed when navigating difficult terrain. Our group has developed a Sensory Neuroprosthesis (SNP) to restore sensation to people with lower limb amputation by pairing electrical stimulation of nerves in the residual limb applied via implanted neurotechnology with pressure sensors in the insole of a standard prosthesis. Stimulation applied to the nerves evoked sensations perceived as originating on the missing leg and foot. Methods: This qualitative case study reports on the experiences of a 68-year-old with a unilateral trans-tibial amputation who autonomously used the SNP at home for 31 weeks. Interview data collected throughout the study period was analyzed using a grounded theory approach with constant comparative methods to understand his experience with this novel technology and its impacts on his daily life. Results: A conceptual model was developed that explained the experience of integrating SNP-provided sensory feedback into his body and motor plans. The model described the requirements of integration, which were a combination of a low level of mental focus and low stimulation levels. While higher levels of stimulation and focus could result in distinct sensory percepts and various phantom limb experiences, optimal integration was associated with SNP-evoked sensation that was not readily perceivable. Successful sensorimotor integration of the SNP resulted in improvements to locomotion, a return to a more normal state, an enhancement of perceived prosthesis utility, and a positive outlook on the experience. Discussion: These outcomes emerged over the course of the nearly 8 month study, suggesting that findings from long-term home studies of SNPs may differ from those of short-term in-laboratory tests. Our findings on the experience of sensorimotor integration of the SNP have implications for the optimal training of SNP users and the future deployment of clinical SNP systems for long-term home use.

Combination of Simultaneous Artificial Sensory Percepts to Identify Prosthetic Hand Postures: A Case Study.

Multiple sources of sensory information are combined to develop hand posture percepts in the intact system, but the combination of multiple artificial somatosensory percepts by human prosthesis users has not been studied. Here, we report on a case study in which a person with transradial amputation identified prosthetic hand postures using artificial somatosensory feedback. He successfully combined five artificial somatosensory percepts to achieve above-chance performance of 95.0% and 75.7% in identifying four and seven postures, respectively. We studied how artificial somatosensation and the extant hand representation are combined in the decision-making process by providing two mappings between the prosthetic sensor and the location of the sensory percept: (1) congruent, and (2) incongruent. The participant's ability to combine and engage with the sensory feedback significantly differed between the two conditions. The participant was only able to successfully generalize prior knowledge to novel postures in the congruent mapping. Further, he learned postures more accurately and quickly in the congruent mapping. Finally, he developed an understanding of the relationships between postures in the congruent mapping instead of simply memorizing each individual posture. These experimental results are corroborated by a Bayesian decision-making model which tracked the participant's learning.

Neural engineering: the process, applications, and its role in the future of medicine.

OBJECTIVE: Recent advances in neural engineering have restored mobility to people with paralysis, relieved symptoms of movement disorders, reduced chronic pain, restored the sense of hearing, and provided sensory perception to individuals with sensory deficits. APPROACH: This progress was enabled by the team-based, interdisciplinary approaches used by neural engineers. Neural engineers have advanced clinical frontiers by leveraging tools and discoveries in quantitative and biological sciences and through collaborations between engineering, science, and medicine. The movement toward bioelectronic medicines, where neuromodulation aims to supplement or replace pharmaceuticals to treat chronic medical conditions such as high blood pressure, diabetes and psychiatric disorders is a prime example of a new frontier made possible by neural engineering. Although one of the major goals in neural engineering is to develop technology for clinical applications, this technology may also offer unique opportunities to gain insight into how biological systems operate. MAIN RESULTS: Despite significant technological progress, a number of ethical and strategic questions remain unexplored. Addressing these questions will accelerate technology development to address unmet needs. The future of these devices extends far beyond treatment of neurological impairments, including potential human augmentation applications. Our task, as neural engineers, is to push technology forward at the intersection of disciplines, while responsibly considering the readiness to transition this technology outside of the laboratory to consumer products. SIGNIFICANCE: This article aims to highlight the current state of the neural engineering field, its links with other engineering and science disciplines, and the challenges and opportunities ahead. The goal of this article is to foster new ideas for innovative applications in neurotechnology.

Learning of Artificial Sensation Through Long-Term Home Use of a Sensory-Enabled Prosthesis.

Upper limb prostheses are specialized tools, and skilled operation is learned by amputees over time. Recently, neural prostheses using implanted peripheral nerve interfaces have enabled advances in artificial somatosensory feedback that can improve prosthesis outcomes. However, the effect of sensory learning on artificial somatosensation has not been studied, despite its known influence on intact somatosensation and analogous neuroprostheses. Sensory learning involves changes in the perception and interpretation of sensory feedback and may further influence functional and psychosocial outcomes. In this mixed methods case study, we examined how passive learning over 115 days of home use of a neural-connected, sensory-enabled prosthetic hand influenced perception of artificial sensory feedback in a participant with transradial amputation. We examined perceptual changes both within individual days of use and across the duration of the study. At both time scales, the reported percept locations became significantly more aligned with prosthesis sensor locations, and the phantom limb became significantly more extended toward the prosthesis position. Similarly, the participant's ratings of intensity, naturalness, and contact touch significantly increased, while his ratings of vibration and movement significantly decreased across-days for tactile channels. These sensory changes likely resulted from engagement of cortical plasticity mechanisms as the participant learned to use the artificial sensory feedback. We also assessed psychosocial and functional outcomes through surveys and interviews, and found that self-efficacy, perceived function, prosthesis embodiment, social touch, body image, and prosthesis efficiency improved significantly. These outcomes typically improved within the first month of home use, demonstrating rapid benefits of artificial sensation. Participant interviews indicated that the naturalness of the experience and engagement with the prosthesis increased throughout the study, suggesting that artificial somatosensation may decrease prosthesis abandonment. Our data showed that prosthesis embodiment was intricately related to naturalness and phantom limb perception, and that learning the artificial sensation may have modified the body schema. As another indicator of successfully learning to use artificial sensation, the participant reported the emergence of stereognosis later in the study. This study provides the first evidence that artificial somatosensation can undergo similar learning processes as intact sensation and highlights the importance of sensory restoration in prostheses.

Visuotactile synchrony of stimulation-induced sensation and natural somatosensation.

OBJECTIVE: Previous studies suggest that somatosensory feedback has the potential to improve the functional performance of prostheses, reduce phantom pain, and enhance embodiment of sensory-enabled prosthetic devices. To maximize such benefits for amputees, the temporal properties of the sensory feedback must resemble those of natural somatosensation in an intact limb. APPROACH: To better understand temporal perception of artificial sensation, we characterized the perception of visuotactile synchrony for tactile perception restored via peripheral nerve stimulation. We electrically activated nerves in the residual limbs of two trans-tibial amputees and two trans-radial amputees via non-penetrating nerve cuff electrodes, which elicited sensations referred to the missing limbs. MAIN RESULTS: Our findings suggest that with respect to vision, stimulation-induced sensation has a point of subjective simultaneity (PSS; processing time) and just noticeable difference (JND; temporal sensitivity) that are similar to natural touch. The JND was not significantly different between the participants with upper- and lower-limb amputations. However, the PSS indicated that sensations evoked in the missing leg must occur significantly earlier than those in the hand to be perceived as maximally synchronous with vision. Furthermore, we examined visuotactile synchrony in the context of a functional task during which stimulation was triggered by pressure applied to the prosthesis. Stimulation-induced sensation could be delayed up to 111 ± 62 ms without the delay being reliably detected. SIGNIFICANCE: The quantitative temporal properties of stimulation-induced perception were previously unknown and will contribute to design specifications for future sensory neuroprostheses.

The benefits of sensation on the experience of a hand: A qualitative case series.

BACKGROUND: The experience of upper limb loss involves loss of both functional capabilities and the sensory connection of a hand. Research studies to restore sensation to persons with upper limb loss with neural interfaces typically measure outcomes through standardized functional tests or quantitative surveys. However, these types of metrics cannot fully capture the personal experience of living with limb loss or the impact of sensory restoration on this experience. Qualitative studies can demonstrate the viewpoints and priorities of specific persons or groups and reveal the underlying conceptual structure of various aspects of their experiences. METHODS AND FINDINGS: Following a home use trial of a neural-connected, sensory-enabled prosthesis, two persons with upper limb loss were interviewed about their experiences using the sensory restoration system in unsupervised, unconstrained settings. We used grounded theory methodology to examine their experiences, perspectives, and opinions about the sensory restoration system. We then developed a model to describe the impact of sensation on the experience of a hand for persons with upper limb loss. CONCLUSIONS: The experience of sensation was complex and included concepts such as the naturalness of the experience, sensation modality, and the usefulness of the sensory information. Sensation was critical for outcome acceptance, and contributed to prosthesis embodiment, confidence, reduced focus and attention for using the prosthesis, and social interactions. Embodiment, confidence, and social interactions were also key determinants of outcome acceptance. This model provides a unified framework to study and understand the impact of sensation on the experience of limb loss and to understand outcome acceptance following upper limb loss more broadly.

Artificial tactile and proprioceptive feedback improves performance and confidence on object identification tasks.

Somatosensory feedback of the hand is essential for object identification. Without somatosensory feedback, individuals cannot reliably determine the size or compliance of an object. Electrical nerve stimulation can restore localized tactile and proprioceptive feedback with intensity discrimination capability similar to natural sensation. We hypothesized that adding artificial somatosensation improves object recognition accuracy when using a prosthesis. To test this hypothesis, we provided different forms of sensory feedback-tactile, proprioceptive, or both-to two subjects with upper limb loss. The subjects were asked to identify the size or mechanical compliance of different foam blocks placed in the prosthetic hand while visually and audibly blinded. During trials, we did not inform the subjects of their performance, but did ask them about their confidence in correctly identifying objects. Finally, we recorded applied pressures during object interaction. Subjects were free to use any strategy they chose to examine the objects. Object identification was most accurate with both tactile and proprioceptive feedback. The relative importance of each type of feedback, however, depended on object characteristics and task. Sensory feedback increased subject confidence and was directly correlated with accuracy. Subjects applied less pressure to the objects when they had tactile pressure feedback. Artificial somatosensory feedback improves object recognition and the relative importance of tactile versus proprioceptive feedback depends on the test set. We believe this test battery provides an effective means to assess the impact of sensory restoration and the relative contribution of different forms of feedback (tactile vs. kinesthetic) within the neurorehabilitation field.

Home Use of a Neural-connected Sensory Prosthesis Provides the Functional and Psychosocial Experience of Having a Hand Again.

The loss of a hand has many psychosocial repercussions. While advanced multi-articulated prostheses can improve function, without sensation, they cannot restore the full experience and connection of a hand. Direct nerve interfaces can restore naturalistic sensation to amputees. Our sensory restoration system produced tactile and proprioceptive sensations on the hand via neural stimulation through chronically implanted electrodes. In this study, upper limb amputees used a sensory-enabled prosthesis in their homes and communities, autonomously and unconstrained to specific tasks. These real-life conditions enabled us to study the impact of sensation on prosthetic usage, functional performance, and psychosocial experience. We found that sensory feedback fundamentally altered the way participants used their prosthesis, transforming it from a sporadically-used tool into a readily and frequently-used hand. Functional performance with sensation improved following extended daily use. Restored sensation improved a wide range of psychosocial factors, including self-efficacy, prosthetic embodiment, self-image, social interaction, and quality of life. This study demonstrates that daily use of a sensory-enabled prosthesis restores the holistic experience of having a hand and more fully reconnects amputees with the world.

Sensory adaptation to electrical stimulation of the somatosensory nerves.

OBJECTIVE: Sensory systems adapt their sensitivity to ambient stimulation levels to improve their responsiveness to changes in stimulation. The sense of touch is also subject to adaptation, as evidenced by the desensitization produced by prolonged vibratory stimulation of the skin. Electrical stimulation of nerves elicits tactile sensations that can convey feedback for bionic limbs. In this study, we investigate whether artificial touch is also subject to adaptation, despite the fact that the peripheral mechanotransducers are bypassed. APPROACH: Using well-established psychophysical paradigms, we characterize the time course and magnitude of sensory adaptation caused by extended electrical stimulation of the residual somatosensory nerves in three human amputees implanted with cuff electrodes. MAIN RESULTS: We find that electrical stimulation of the nerve also induces perceptual adaptation that recovers after cessation of the stimulus. The time course and magnitude of electrically-induced adaptation are equivalent to their mechanically-induced counterparts. SIGNIFICANCE: We conclude that, in natural touch, the process of mechanotransduction is not required for adaptation, and artificial touch naturally experiences adaptation-induced adjustments of the dynamic range of sensations. Further, as it does for native hands, adaptation confers to bionic hands enhanced sensitivity to changes in stimulation and thus a more natural sensory experience.

The neural basis of perceived intensity in natural and artificial touch.

Electrical stimulation of sensory nerves is a powerful tool for studying neural coding because it can activate neural populations in ways that natural stimulation cannot. Electrical stimulation of the nerve has also been used to restore sensation to patients who have suffered the loss of a limb. We have used long-term implanted electrical interfaces to elucidate the neural basis of perceived intensity in the sense of touch. To this end, we assessed the sensory correlates of neural firing rate and neuronal population recruitment independently by varying two parameters of nerve stimulation: pulse frequency and pulse width. Specifically, two amputees, chronically implanted with peripheral nerve electrodes, performed each of three psychophysical tasks-intensity discrimination, magnitude scaling, and intensity matching-in response to electrical stimulation of their somatosensory nerves. We found that stimulation pulse width and pulse frequency had systematic, cooperative effects on perceived tactile intensity and that the artificial tactile sensations could be reliably matched to skin indentations on the intact limb. We identified a quantity we termed the activation charge rate (ACR), derived from stimulation parameters, that predicted the magnitude of artificial tactile percepts across all testing conditions. On the basis of principles of nerve fiber recruitment, the ACR represents the total population spike count in the activated neural population. Our findings support the hypothesis that population spike count drives the magnitude of tactile percepts and indicate that sensory magnitude can be manipulated systematically by varying a single stimulation quantity.