Matthew A. Schiefer

A neural interface provides long-term stable natural touch perception

Electrical stimulation, using patterned intensity, applied through cuff-type peripheral nerve interfaces provided stable touch perceptions in the fingers, thumb, and hand of two subjects with upper limb loss for 16 to 24 months. To Feel Again! The loss of sensation is a major consequence and unmet challenge for amputees who have suffered limb loss. Tan et al. now demonstrate that a simple electronic cuff placed around nerves in the upper arm of two amputees wearing a replacement neuroprosthetic limb directly activates the neural pathways responsible for hand sensations. This neural interface enabled the two amputees to feel sensations at many locations on the neuroprosthetic hand. Different stimulation patterns transformed the typical “tingling sensation” of electrical stimulation into multiple different natural sensations, enabling the amputees to perform fine motor tasks such as picking up soft fruit and pulling the stalks out of cherries. Touch perception on the fingers and hand is essential for fine motor control, contributes to our sense of self, allows for effective communication, and aids in our fundamental perception of the world. Despite increasingly sophisticated mechatronics, prosthetic devices still do not directly convey sensation back to their wearers. We show that implanted peripheral nerve interfaces in two human subjects with upper limb amputation provided stable, natural touch sensation in their hands for more than 1 year. Electrical stimulation using implanted peripheral nerve cuff electrodes that did not penetrate the nerve produced touch perceptions at many locations on the phantom hand with repeatable, stable responses in the two subjects for 16 and 24 months. Patterned stimulation intensity produced a sensation that the subjects described as natural and without “tingling,” or paresthesia. Different patterns produced different types of sensory perception at the same location on the phantom hand. The two subjects reported tactile perceptions they described as natural tapping, constant pressure, light moving touch, and vibration. Changing average stimulation intensity controlled the size of the percept area; changing stimulation frequency controlled sensation strength. Artificial touch sensation improved the subjects’ ability to control grasping strength of the prosthesis and enabled them to better manipulate delicate objects. Thus, electrical stimulation through peripheral nerve electrodes produced long-term sensory restoration after limb loss.

A Model of Selective Activation of the Femoral Nerve With a Flat Interface Nerve Electrode for a Lower Extremity Neuroprosthesis

Functional electrical stimulation (FES) can restore limb movements through electrically initiated, coordinated contractions of paralyzed muscles. The peripheral nerve is an attractive site for stimulation using cuff electrodes. Many applications will require the electrode to selectively activate many smaller populations of axons within a common nerve trunk. The purpose of this study is to computationally model the performance of a flat interface nerve electrode (FINE) on the proximal femoral nerve for standing and stepping applications. Simulations investigated multiple FINE configurations to determine the optimal number and locations of contacts for the maximum muscular selectivity. Realistic finite element method (FEM) models were developed from digitized cross sections from cadaver femoral nerve specimens. Electrical potentials were calculated and interpolated voltages were applied to a double-cable axon model. Model output was analyzed to determine selectivity and estimate joint moments with a musculoskeletal model. Simulations indicated that a 22-contact FINE will produce the greatest selectivity. Simulations predicted that an eight-contact FINE can be expected to selectively stimulate each of the six muscles innervated by the proximal femoral nerve, producing a sufficient knee extension moment for the sit-to-stand transition and contributing 60% of the hip flexion moment needed during gait. We conclude that, whereas more contacts produce greater selectivity, eight channels are sufficient for standing and stepping with an FES system using a FINE on the common femoral nerve.

Selective stimulation of the human femoral nerve with a flat interface nerve electrode

In humans, we tested the hypothesis that a flat interface nerve electrode (FINE) placed around the femoral nerve trunk can selectively stimulate each muscle the nerve innervates. In a series of intraoperative trials during routine vascular surgeries, an eight-contact FINE was placed around the femoral nerve between the inguinal ligament and the first nerve branching point. The capability of the FINE to selectively recruit muscles innervated by the femoral nerve was assessed with electromyograms (EMGs) of the twitch responses to electrical stimulation. At least four of the six muscles innervated by the femoral nerve were independently and selectively recruited in all subjects. Of these, at least one muscle was a hip flexor and at least two were knee extensors. Results from the intraoperative experiments were used to estimate the potential for the electrode to restore knee extension and hip flexion through functional electrical stimulation. Normalized EMGs and biomechanical simulations were used to estimate joint moments and functional efficacy. Estimated knee extension moments exceed the threshold required for the sit-to-stand transition.

Fascicular Perineurium Thickness, Size, and Position Affect Model Predictions of Neural Excitation

The number of applications using neural prosthetic interfaces is expanding. Computer models are a valuable tool to evaluate stimulation techniques and electrode designs. Although our understanding of neural anatomy has improved, its impact on the effects of neural stimulation is not well understood. This study evaluated the effects of fascicle perineurial thickness, diameter, and position on axonal excitation thresholds and population recruitment using finite element models and NEURON simulations. The perineurial thickness of human fascicles was found to be 3.0% plusmn 1.0% of the fascicle diameter. Increased perineurial thickness and fascicle diameter increased activation thresholds. The presence of a large neighboring fascicle caused a significant change in activation of a smaller target fascicle by as much as 80% plusmn 11% of the total axon population. Smaller fascicles were recruited at lower amplitudes than neighboring larger fascicles. These effects were further illustrated in a realistic model of a human femoral nerve surrounded by a nerve cuff electrode. The data suggest that fascicular selectivity is strongly dependent upon the anatomy of the nerve being stimulated. Therefore, accurate representations of nerve anatomy are required to develop more accurate computer models to evaluate and optimize nerve electrode designs for neural prosthesis applications.

Sites of neuronal excitation by epiretinal electrical stimulation

Action potentials arising from retinal ganglion cells ultimately create visual percepts. In persons blind from retinitis pigmentosa and age-related macular degeneration, viable retinal ganglion cells remain, and the retina can be stimulated electrically to restore partial sight. However, it is unclear what neuronal elements in the retina are activated by epiretinal electrical stimulation. This study investigated the effects of cellular geometry, electrode to neuron distance, stimulus duration, and stimulus polarity on excitation of a retinal ganglion cell with an epiretinal electrode. Computer-based compartmental models representing simplified retinal ganglion cell morphology provided evidence that the threshold for excitation was lower when an electrode was located in proximity to the characteristic 90/spl deg/ bend in the axon of the retinal ganglion cell than when it was located over a passing axon of the nerve fiber layer. This electrode-position-dependent difference in threshold occurred with both cathodic and anodic monophasic stimuli, with point source and disk electrodes, at multiple electrode-to-neuron distances, and was robust to changes in the electrical properties of the model. This finding reveals that the physical geometry of the retinal ganglion cells produces stimulation thresholds that depend strongly on electrode position. The low excitation thresholds near the bend in the axon will result in activation of cells local to the electrode at lower currents than required to excite passing axons. This pattern of activation provides a potential explanation of how epiretinal electrical stimulation results in the production of punctuate, rather than diffuse or streaky phosphenes.

Sensory feedback by peripheral nerve stimulation improves task performance in individuals with upper limb loss using a myoelectric prosthesis.

OBJECTIVE Tactile feedback is critical to grip and object manipulation. Its absence results in reliance on visual and auditory cues. Our objective was to assess the effect of sensory feedback on task performance in individuals with limb loss. APPROACH Stimulation of the peripheral nerves using implanted cuff electrodes provided two subjects with sensory feedback with intensity proportional to forces on the thumb, index, and middle fingers of their prosthetic hand during object manipulation. Both subjects perceived the sensation on their phantom hand at locations corresponding to the locations of the forces on the prosthetic hand. A bend sensor measured prosthetic hand span. Hand span modulated the intensity of sensory feedback perceived on the thenar eminence for subject 1 and the middle finger for subject 2. We performed three functional tests with the blindfolded subjects. First, the subject tried to determine whether or not a wooden block had been placed in his prosthetic hand. Second, the subject had to locate and remove magnetic blocks from a metal table. Third, the subject performed the Southampton Hand Assessment Procedure (SHAP). We also measured the subjects sense of embodiment with a survey and his self-confidence. MAIN RESULTS Blindfolded performance with sensory feedback was similar to sighted performance in the wooden block and magnetic block tasks. Performance on the SHAP, a measure of hand mechanical function and control, was similar with and without sensory feedback. An embodiment survey showed an improved sense of integration of the prosthesis in self body image with sensory feedback. SIGNIFICANCE Sensory feedback by peripheral nerve stimulation improved object discrimination and manipulation, embodiment, and confidence. With both forms of feedback, the blindfolded subjects tended toward results obtained with visual feedback.

Stability and selectivity of a chronic, multi-contact cuff electrode for sensory stimulation in human amputees

Multi-contact cuff electrodes were implanted in the median, ulnar, and radial nerves of an upper-limb amputee. 19 of 20 contacts produced selective, sensory response in the phantom limb from nerve stimulation. The neural interface has been stable for the duration of this ongoing chronic study, 12 months post-implant, with consistent threshold and impedance measures.

The neural basis of perceived intensity in natural and artificial touch

Electrical connections between nerves and a prosthetic device enable amputees to discern precise, graded sensory intensity ranging from light touch to intense pressure. Perceived intensity: A touchy subject for neuroprostheses Without tactile sensory input, amputees discern a firm handshake from a bone-crushing grip by visual cues and learned behavior. Next-generation prostheses aim to lend a more natural feel to artificial touch by transmitting nuanced sensory feedback. Graczyk et al. looked at direct stimulation of the radial, ulnar, and median nerves via implanted electrodes in two amputees to understand how levels of intensity are perceived and how tactile sensory feedback is transmitted. By modulating the number of nerve fibers stimulated and the frequency of stimulation, sensory information could be transmitted such that the amputees could distinguish distinct levels of tactile intensity, that is, the difference between a 7 and a 10 on a scale of intensity. 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.

Intraoperative evaluation of the spiral nerve cuff electrode on the femoral nerve trunk

Evaluation of the Case Western Reserve University spiral nerve cuff electrode on the femoral nerve trunk was performed intraoperatively in four subjects undergoing femoral-popliteal bypass surgery. The threshold, nerve size and selective activation capabilities of the electrode were examined. The activation thresholds for the first muscle to be recruited were 6.3, 9, 10.6, and 37.4 nC with pulse amplitudes ranging from 0.3 to 1 mA. The femoral nerve was found to have an elliptical cross-section with a major axis average length of 9 mm (8-12 mm) and a minor axis length of 1.5 mm. In all four subjects selective activation of the sartorius was obtained. In two subjects, the rectus femoris could also be selectively activated and in one subject the vastus medialis was selectively activated. Each electrode had four independent contacts that were evaluated separately. Small air bubbles were formed in the space over some contacts, preventing stimulation. This occurred in one contact in each electrode, leaving three effective stimulation channels. This issue has been corrected for future studies.

Selective activation of the human tibial and common peroneal nerves with a flat interface nerve electrode

OBJECTIVE Electrical stimulation has been shown effective in restoring basic lower extremity motor function in individuals with paralysis. We tested the hypothesis that a flat interface nerve electrode (FINE) placed around the human tibial or common peroneal nerve above the knee can selectively activate each of the most important muscles these nerves innervate for use in a neuroprosthesis to control ankle motion. APPROACH During intraoperative trials involving three subjects, an eight-contact FINE was placed around the tibial and/or common peroneal nerve, proximal to the popliteal fossa. The FINEs ability to selectively recruit muscles innervated by these nerves was assessed. Data were used to estimate the potential to restore active plantarflexion or dorsiflexion while balancing inversion and eversion using a biomechanical simulation. MAIN RESULTS With minimal spillover to non-targets, at least three of the four targets in the tibial nerve, including two of the three muscles constituting the triceps surae, were independently and selectively recruited in all subjects. As acceptable levels of spillover increased, recruitment of the target muscles increased. Selective activation of muscles innervated by the peroneal nerve was more challenging. SIGNIFICANCE Estimated joint moments suggest that plantarflexion sufficient for propulsion during stance phase of gait and dorsiflexion sufficient to prevent foot drop during swing can be achieved, accompanied by a small but tolerable inversion or eversion moment.