Proprioceptive Augmentation With Illusory Kinaesthetic Sensation in Stroke Patients Improves Movement Quality in an Active Upper Limb Reach-and-Point Task.

Stroke patients often have difficulty completing motor tasks even after substantive rehabilitation. Poor recovery of motor function can often be linked to stroke-induced damage to motor pathways. However, stroke damage in pathways that impact effective integration of sensory feedback with motor control may represent an unappreciated obstacle to smooth motor coordination. In this study we investigated the effects of augmenting movement proprioception during a reaching task in six stroke patients as a proof of concept. We used a wearable neurorobotic proprioceptive feedback system to induce illusory kinaesthetic sensation by vibrating participants' upper arm muscles over active limb movements. Participants were instructed to extend their elbow to reach-and-point to targets of differing sizes at various distances, while illusion-inducing vibration (90 Hz), sham vibration (25 Hz), or no vibration was applied to the distal tendons of either their biceps brachii or their triceps brachii. To assess the impact of augmented kinaesthetic feedback on motor function we compared the results of vibrating the biceps or triceps during arm extension in the affected arm of stroke patients and able-bodied participants. We quantified performance across conditions and participants by tracking limb/hand kinematics with motion capture, and through Fitts' law analysis of reaching target acquisition. Kinematic analyses revealed that injecting 90 Hz illusory kinaesthetic sensation into the actively contracting (agonist) triceps muscle during reaching increased movement smoothness, movement directness, and elbow extension. Conversely, injecting 90 Hz illusory kinaesthetic sensation into the antagonistic biceps during reaching negatively impacted those same parameters. The Fitts' law analyses reflected similar effects with a trend toward increased throughput with triceps vibration during reaching. Across all analyses, able-bodied participants were largely unresponsive to illusory vibrational augmentation. These findings provide evidence that vibration-induced movement illusions delivered to the primary agonist muscle involved in active movement may be integrated into rehabilitative approaches to help promote functional motor recovery in stroke patients.

Lower-Limb Amputees Adjust Quiet Stance in Response to Manipulations of Plantar Sensation.

Interfering with or temporarily eliminating foot-sole tactile sensations causes postural adjustments. Furthermore, individuals with impaired or missing foot-sole sensation, such as lower-limb amputees, exhibit greater postural instability than those with intact sensation. Our group has developed a method of providing tactile feedback sensations projected to the missing foot of lower-limb amputees via electrical peripheral nerve stimulation (PNS) using implanted nerve cuff electrodes. As a step toward effective implementation of the system in rehabilitation and everyday use, we compared postural adjustments made in response to tactile sensations on the missing foot elicited by our system, vibration on the intact foot-sole, and a control condition in which no additional sensory input was applied. Three transtibial amputees with at least a year of experience with tactile sensations provided by our PNS system participated in the study. Participants stood quietly with their eyes closed on their everyday prosthesis while electrically elicited, vibratory, or no additional sensory input was administered for 20 s. Early and steady-state postural adjustments were quantified by center of pressure location, path length, and average angle over the course of each trial. Electrically elicited tactile sensations and vibration both caused shifts in center of pressure location compared to the control condition. Initial (first 3 s) shifts in center of pressure location with electrically elicited or vibratory sensory inputs often differed from shifts measured over the full 20 s trial. Over the full trial, participants generally shifted toward the foot receiving additional sensory input, regardless of stimulation type. Similarities between responses to electrically elicited tactile sensations projected to the missing foot and responses to vibration in analogous regions on the intact foot suggest that the motor control system treats electrically elicited tactile inputs similarly to native tactile inputs. The ability of electrically elicited tactile inputs to cause postural adjustments suggests that these inputs are incorporated into sensorimotor control, despite arising from artificial nerve stimulation. These results are encouraging for application of neural stimulation in restoring missing sensory feedback after limb loss and suggest PNS could provide an alternate method to perturb foot-sole tactile information for investigating integration of tactile feedback with other sensory modalities.

Ambulatory searching task reveals importance of somatosensation for lower-limb amputees.

The contribution of somatosensation to locomotor deficits in below-knee amputees (BKAs) has not been fully explored. Unilateral disruption of plantar sensation causes able-bodied individuals to adopt locomotor characteristics that resemble those of unilateral BKAs, suggesting that restoring somatosensation may improve locomotion for amputees. In prior studies, we demonstrated that electrically stimulating the residual nerves of amputees elicited somatosensory percepts that were felt as occurring in the missing foot. Subsequently, we developed a sensory neuroprosthesis that modulated stimulation-evoked sensation in response to interactions between the prosthesis and the environment. To characterize the impact of the sensory neuroprosthesis on locomotion, we created a novel ambulatory searching task. The task involved walking on a horizontal ladder while blindfolded, which engaged plantar sensation while minimizing visual compensation. We first compared the performance of six BKAs to 14 able-bodied controls. Able-bodied individuals demonstrated higher foot placement accuracy than BKAs, indicating that the ladder test was sensitive enough to detect locomotor deficits. When three of the original six BKAs used the sensory neuroprosthesis, the tradeoff between speed and accuracy significantly improved for two of them. This study advanced our understanding of how cutaneous plantar sensation can be used to acquire action-related information during challenging locomotor tasks.

Long-Term Home-Use of Sensory-Motor-Integrated Bidirectional Bionic Prosthetic Arms Promotes Functional, Perceptual, and Cognitive Changes.

Cutaneous sensation is vital to controlling our hands and upper limbs. It helps close the motor control loop by informing adjustments of grasping forces during object manipulations and provides much of the information the brain requires to perceive our limbs as a part of our bodies. This sensory information is absent to upper-limb prosthesis users. Although robotic prostheses are becoming increasingly sophisticated, the absence of feedback imposes a reliance on open-loop control and limits the functional potential as an integrated part of the body. Experimental systems to restore physiologically relevant sensory information to prosthesis users are beginning to emerge. However, the impact of their long-term use on functional abilities, body image, and neural adaptation processes remains unclear. Understanding these effects is essential to transition sensate prostheses from sophisticated assistive tools to integrated replacement limbs. We recruited three participants with high-level upper-limb amputation who previously received targeted reinnervation surgery. Each participant was fit with a neural-machine-interface prosthesis that allowed participants to operate their device by thinking about moving their missing limb. Additionally, we fit a sensory feedback system that allowed participants to experience touch to the prosthesis as touch on their missing limb. All three participants performed a long-term take-home trial. Two participants used their neural-machine-interface systems with touch feedback and one control participant used his prescribed, insensate prosthesis. A series of functional outcome metrics and psychophysical evaluations were performed using sensate neural-machine-interface prostheses before and after the take-home period to capture changes in functional abilities, limb embodiment, and neural adaptation. Our results demonstrated that the relationship between users and sensate neural-machine-interface prostheses is dynamic and changes with long-term use. The presence of touch sensation had a near-immediate impact on how the users operated their prostheses. In the multiple independent measures of users' functional abilities employed, we observed a spectrum of performance changes following long-term use. Furthermore, after the take-home period, participants more appropriately integrated their prostheses into their body images and psychophysical tests provided strong evidence that neural and cortical adaptation occurred.

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.

Visual inputs and postural manipulations affect the location of somatosensory percepts elicited by electrical stimulation.

The perception of somatosensation requires the integration of multimodal information, yet the effects of vision and posture on somatosensory percepts elicited by neural stimulation are not well established. In this study, we applied electrical stimulation directly to the residual nerves of trans-tibial amputees to elicit sensations referred to their missing feet. We evaluated the influence of congruent and incongruent visual inputs and postural manipulations on the perceived size and location of stimulation-evoked somatosensory percepts. We found that although standing upright may cause percept size to change, congruent visual inputs and/or body posture resulted in better localization. We also observed visual capture: the location of a somatosensory percept shifted toward a visual input when vision was incongruent with stimulation-induced sensation. Visual capture did not occur when an adopted posture was incongruent with somatosensation. Our results suggest that internal model predictions based on postural manipulations reinforce perceived sensations, but do not alter them. These characterizations of multisensory integration are important for the development of somatosensory-enabled prostheses because current neural stimulation paradigms cannot replicate the afferent signals of natural tactile stimuli. Nevertheless, multisensory inputs can improve perceptual precision and highlight regions of the foot important for balance and locomotion.

Characterization of the Sense of Agency over the Actions of Neural-machine Interface-operated Prostheses.

This work describes a methodological framework that can be used to explicitly and implicitly characterize the sense of agency developed over the neural-machine interface (NMI) control of sensate virtual or robotic prosthetic hands. The formation of agency is fundamental in distinguishing the actions that we perform with our limbs as being our own. By striving to incorporate advanced upper-limb prostheses into these same perceptual mechanisms, we can begin to integrate an artificial limb more closely into the user's existing cognitive framework for limb control. This has important implications in promoting user acceptance, use, and effective control of advanced upper-limb prostheses. In this protocol, participants control a virtual prosthetic hand and receive kinesthetic sensory feedback through their preexisting NMIs. A series of virtual grasping tasks are performed and perturbations are systematically introduced to the kinesthetic feedback and virtual hand movements. Two separate measures of agency are employed: established psychophysical questionnaires (to capture the explicit experience of agency) and a time interval estimate task to capture the implicit sense of agency (intentional binding). Results of this protocol (questionnaire scores and time interval estimates) can be analyzed to quantify the extent of agency formation.

High-density peripheral nerve cuffs restore natural sensation to individuals with lower-limb amputations.

OBJECTIVE: Sensory input in lower-limb amputees is critically important to maintaining balance, preventing falls, negotiating uneven terrain, responding to unexpected perturbations, and developing the confidence required for societal participation and public interactions in unfamiliar environments. Despite noteworthy advances in robotic prostheses for lower-limb amputees, such as microprocessor knees and powered ankles, natural somatosensory feedback from the lost limb has not yet been incorporated in current prosthetic technologies. APPROACH: In this work, we report eliciting somatic sensation with neural stimulation delivered by chronically-implanted, non-penetrating nerve cuff electrodes in two transtibial amputees. High-density, flexible, 16-contact nerve cuff electrodes were surgically implanted for the selective activation of sensory fascicles in the nerves of the posterior thigh above the knee. Electrical pulses at safe levels were delivered to the nerves by an external stimulator via percutaneous leads attached to the cuff electrodes. MAIN RESULTS: The neural stimulation was perceived by participants as sensation originating from the missing limb. We quantitatively and qualitatively ascertained the intensity, modality as well as the location and stability of the perceived sensations. Stimulation through individual contacts within the nerve cuffs evoked repeatable sensations of various modalities and at discrete locations projected to the missing toes, foot and ankle, as well as in the residual limb. In addition, we observed a high overlap in reported locations between distal versus proximal cuffs suggesting that the same sensory responses could be elicited from more proximal points on the nerve. SIGNIFICANCE: Based on these findings, the high-density cuff technology is suitable for restoring natural sensation to lower-limb amputees and could be utilized in developing a neuroprosthesis with natural sensory feedback. The overlap in reported locations between proximal and distal cuffs indicates that our approach might be applicable to transfemoral amputees where distal muscles and branches of sciatic nerve are not available.

Illusory movement perception improves motor control for prosthetic hands.

To effortlessly complete an intentional movement, the brain needs feedback from the body regarding the movement's progress. This largely nonconscious kinesthetic sense helps the brain to learn relationships between motor commands and outcomes to correct movement errors. Prosthetic systems for restoring function have predominantly focused on controlling motorized joint movement. Without the kinesthetic sense, however, these devices do not become intuitively controllable. We report a method for endowing human amputees with a kinesthetic perception of dexterous robotic hands. Vibrating the muscles used for prosthetic control via a neural-machine interface produced the illusory perception of complex grip movements. Within minutes, three amputees integrated this kinesthetic feedback and improved movement control. Combining intent, kinesthesia, and vision instilled participants with a sense of agency over the robotic movements. This feedback approach for closed-loop control opens a pathway to seamless integration of minds and machines.

Identifying classifier input signals to predict a cross-slope during transtibial amputee walking.

Advanced prosthetic foot designs often incorporate mechanisms that adapt to terrain changes in real-time to improve mobility. Early identification of terrain (e.g., cross-slopes) is critical to appropriate adaptation. This study suggests that a simple classifier based on linear discriminant analysis can accurately predict a cross-slope encountered (0°, -15°, 15°) using measurements from the residual limb, primarily from the prosthesis itself. The classifier was trained and tested offline using motion capture and in-pylon sensor data collected during walking trials in mid-swing and early stance. Residual limb kinematics, especially measurements from the foot, shank and ankle, successfully predicted the cross-slope terrain with high accuracy (99%). Although accuracy decreased when predictions were made for test data instead of the training data, the accuracy was still relatively high for one input signal set (>89%) and moderate for three others (>71%). This suggests that classifiers can be designed and generalized to be effective for new conditions and/or subjects. While measurements of shank acceleration and angular velocity from only in-pylon sensors were insufficient to accurately predict the cross-slope terrain, the addition of foot and ankle kinematics from motion capture data allowed accurate terrain prediction. Inversion angular velocity and foot vertical velocity were particularly useful. As in-pylon sensor data and shank kinematics from motion capture appeared interchangeable, combining foot and ankle kinematics from prosthesis-mounted sensors with shank kinematics from in-pylon sensors may provide enough information to accurately predict the terrain.

The neural response properties and cortical organization of a rapidly adapting muscle sensory group response that overlaps with the frequencies that elicit the kinesthetic illusion.

Kinesthesia is the sense of limb movement. It is fundamental to efficient motor control, yet its neurophysiological components remain poorly understood. The contributions of primary muscle spindles and cutaneous afferents to the kinesthetic sense have been well studied; however, potential contributions from muscle sensory group responses that are different than the muscle spindles have not been ruled out. Electrophysiological recordings in peripheral nerves and brains of male Sprague Dawley rats with a degloved forelimb preparation provide evidence of a rapidly adapting muscle sensory group response that overlaps with vibratory inputs known to generate illusionary perceptions of limb movement in humans (kinesthetic illusion). This group was characteristically distinct from type Ia muscle spindle fibers, the receptor historically attributed to limb movement sensation, suggesting that type Ia muscle spindle fibers may not be the sole carrier of kinesthetic information. The sensory-neural structure of muscles is complex and there are a number of possible sources for this response group; with Golgi tendon organs being the most likely candidate. The rapidly adapting muscle sensory group response projected to proprioceptive brain regions, the rodent homolog of cortical area 3a and the second somatosensory area (S2), with similar adaption and frequency response profiles between the brain and peripheral nerves. Their representational organization was muscle-specific (myocentric) and magnified for proximal and multi-articulate limb joints. Projection to proprioceptive brain areas, myocentric representational magnification of muscles prone to movement error, overlap with illusionary vibrational input, and resonant frequencies of volitional motor unit contraction suggest that this group response may be involved with limb movement processing.

The effects of prosthetic foot stiffness on transtibial amputee walking mechanics and balance control during turning.

BACKGROUND: Little evidence exists regarding how prosthesis design characteristics affect performance in tasks that challenge mediolateral balance such as turning. This study assesses the influence of prosthetic foot stiffness on amputee walking mechanics and balance control during a continuous turning task. METHODS: Three-dimensional kinematic and kinetic data were collected from eight unilateral transtibial amputees as they walked overground at self-selected speed clockwise and counterclockwise around a 1-meter circle and along a straight line. Subjects performed the walking tasks wearing three different ankle-foot prostheses that spanned a range of sagittal- and coronal-plane stiffness levels. FINDINGS: A decrease in stiffness increased residual ankle dorsiflexion (10-13°), caused smaller adaptations (<5°) in proximal joint angles, decreased residual and increased intact limb body support, increased residual limb propulsion and increased intact limb braking for all tasks. While changes in sagittal-plane joint work due to decreased stiffness were generally consistent across tasks, effects on coronal-plane hip work were task-dependent. When the residual limb was on the inside of the turn and during straight-line walking, coronal-plane hip work increased and coronal-plane peak-to-peak range of whole-body angular momentum decreased with decreased stiffness. INTERPRETATION: Changes in sagittal-plane kinematics and kinetics were similar to those previously observed in straight-line walking. Mediolateral balance improved with decreased stiffness, but adaptations in coronal-plane angles, work and ground reaction force impulses were less systematic than those in sagittal-plane measures. Effects of stiffness varied with the residual limb inside versus outside the turn, which suggests that actively adjusting stiffness to turn direction may be beneficial.

The influence of poly(ethylene oxide) grafting via siloxane tethers on protein adsorption.

Amphiphilic PEO-silanes (a-c) having siloxane tethers of varying lengths with the general formula alpha-(EtO)3Si-(CH2)2-oligodimethylsiloxane(n)-block-poly(ethylene oxide)8-OCH3 [n=0 (a), n=4 (b), and n=13 (c)] were grafted onto silicon wafers and resistance to adsorption of plasma proteins was measured. Distancing the PEO segment from the hydrolyzable triethoxysilane [(EtO)3Si] grafting group by a oligodimethylsiloxane tether represents a new method of grafting PEO chains to surfaces. Properties of surfaces grafted with a-c were compared to surfaces grafted with a traditional PEO-silane containing a propyl spacer [(EtO)3Si-(CH2)3-poly(ethylene oxide)8-OCH3, PEO control]. As the siloxane tether length increased, chain density of PEO-silanes grafted onto oxidized silicon wafers decreased and hydrophobicity of the PEO-silane increased which led to a decrease in surface hydrophilicity. Despite decreased surface hydrophilicity, resistance to the adsorption of bovine serum albumin (BSA) increased in the order: PEO control