Restoration of motor control and proprioceptive and cutaneous sensation in humans with prior upper-limb amputation via multiple Utah Slanted Electrode Arrays (USEAs) implanted in residual peripheral arm nerves.

BACKGROUND: Despite advances in sophisticated robotic hands, intuitive control of and sensory feedback from these prostheses has been limited to only 3-degrees-of-freedom (DOF) with 2 sensory percepts in closed-loop control. A Utah Slanted Electrode Array (USEA) has been used in the past to provide up to 81 sensory percepts for human amputees. Here, we report on the advanced capabilities of multiple USEAs implanted in the residual peripheral arm nerves of human amputees for restoring control of 5 DOF and sensation of up to 131 proprioceptive and cutaneous hand sensory percepts. We also demonstrate that USEA-restored sensory percepts provide a useful source of feedback during closed-loop virtual prosthetic hand control. METHODS: Two 100-channel USEAs were implanted for 4-5 weeks, one each in the median and ulnar arm nerves of two human subjects with prior long-duration upper-arm amputations. Intended finger and wrist positions were decoded from neuronal firing patterns via a modified Kalman filter, allowing subjects to control many movements of a virtual prosthetic hand. Additionally, USEA microstimulation was used to evoke numerous sensory percepts spanning the phantom hand. Closed-loop control was achieved by stimulating via an electrode of the ulnar-nerve USEA while recording and decoding movement via the median-nerve USEA. RESULTS: Subjects controlled up to 12 degrees-of-freedom during informal, 'freeform' online movement decode sessions, and experienced up to 131 USEA-evoked proprioceptive and cutaneous sensations spanning the phantom hand. Independent control was achieved for a 5-DOF real-time decode that included flexion/extension of the thumb, index, middle, and ring fingers, and the wrist. Proportional control was achieved for a 4-DOF real-time decode. One subject used a USEA-evoked hand sensation as feedback to complete a 1-DOF closed-loop virtual-hand movement task. There were no observed long-term functional deficits due to the USEA implants. CONCLUSIONS: Implantation of high-channel-count USEAs enables multi-degree-of-freedom control of virtual prosthetic hand movement and restoration of a rich selection of both proprioceptive and cutaneous sensory percepts spanning the hand during the short 4-5 week post-implant period. Future USEA use in longer-term implants and in closed-loop may enable restoration of many of the capabilities of an intact hand while contributing to a meaningful embodiment of the prosthesis.

A histological analysis of human median and ulnar nerves following implantation of Utah slanted electrode arrays.

For decades, epineurial electrodes have been used in clinical therapies involving the stimulation of peripheral nerves. However, next generation peripheral nerve interfaces for applications such as neuroprosthetics would benefit from an increased ability to selectively stimulate and record from nerve tissue. This increased selectivity may require the use of more invasive devices, such as the Utah Slanted Electrode Array (USEA). Previous research with USEAs has described the histological response to the implantation of these devices in cats and rats; however, no such data has been presented in humans. Therefore, we describe here the degree of penetration and foreign body reaction to USEAs after a four-week implantation period in human median and ulnar nerves. We found that current array designs penetrate a relatively small percentage of the available endoneurial tissue in these large nerves. When electrode tips were located within the endoneurial tissue, labels for axons and myelin were found in close proximity to electrodes. Consistent with other reports, we found activated macrophages attached to explanted devices, as well as within the tissue surrounding the implantation site. Despite this inflammatory response, devices were able to successfully record single- or multi-unit action potentials and elicit sensory percepts. However, modifying device design to allow for greater nerve penetration, as well as mitigating the inflammatory response to such devices, would likely increase device performance and should be investigated in future research.

Acute monitoring of genitourinary function using intrafascicular electrodes: selective pudendal nerve activity corresponding to bladder filling, bladder fullness, and genital stimulation.

OBJECTIVE: To investigate the use of a microelectrode array with a high spatial density of penetrating intrafascicular electrodes for selective recording of pudendal nerve activity evoked by a variety of genitourinary stimuli. MATERIALS AND METHODS: Felines were anesthetized with alpha-chloralose and high-density Utah slanted electrode arrays (48 microelectrodes; 200-µm spacing) were implanted into the pudendal nerve for acute experimentation. Neural activity was recorded during bladder filling, spontaneous reflexive distention-evoked bladder contractions, and tactile somatosensory stimulation. RESULTS: The intrafascicularly implanted pudendal nerve electrodes were able to selectively record neural activity that corresponded to various genitourinary stimuli. Across all seven experimental animals, a total of 10 microelectrodes recorded neural units that were selectively driven by bladder filling or distention-evoked bladder contractions. Twenty-two electrodes were selectively driven by tactile stimulation. CONCLUSION: Microelectrode arrays implanted intrafascicularly into the pudendal nerve can be used to selectively record the neural responses that reflect bladder status and urogenital tactile stimulation. This work sets the stage for developing future implantable closed-loop neuroprosthetic devices for restoration of bladder function.

Assessment of rat sciatic nerve function following acute implantation of high density Utah slanted electrode array (25 electrodes/mm(2) ) based on neural recordings and evoked muscle activity.

INTRODUCTION: High density Utah slanted electrode arrays (HD-USEAs) have been developed recently for intrafascicular access to submillimeter neural structures. Insertion of such high electrode density devices may cause nerve crush injury, counteracting the intended improved selective nerve fiber access. METHODS: HD-USEAs were implanted into sciatic nerves of anesthetized rats. Nerve function was assessed before and after HD-USEA implantation by measuring changes in evoked muscle and nerve compound action potentials and single unit neuronal recordings. RESULTS: Neural activity was recorded with over half of all implanted electrodes. Average decreases of 38%, 36%, and 13% in nerve, medial gastrocnemius, and tibialis anterior compound action potential amplitudes, respectively, were observed following array implantation. Only 1 of 8 implantations resulted in loss of all signals. CONCLUSIONS: These studies demonstrate that HD-USEAs provide a useful neural interface without causing a nerve crush injury that would otherwise negate their use in acute preparations (<12 h).

Using multiple high-count electrode arrays in human median and ulnar nerves to restore sensorimotor function after previous transradial amputation of the hand.

Peripheral nerve interfaces that can record from and stimulate large numbers of different nerve fibers selectively and independently may help restore intuitive and effective motor and sensory function after hand amputation. To this end, and extending previous work in two subjects, two 100-electrode Utah Slanted Electrode Arrays (USEAs) were implanted for four weeks in the residual ulnar and median nerves of a 50-year-old male whose left, dominant hand had been amputated 21 years previously. Subsequent experiments involved 1) recording from USEAs for real-time control of a virtual prosthetic hand; 2) stimulation to evoke somatosensory percepts; and 3) closed-loop sensorimotor control. Overall, partial motor control and sensation were achieved using USEAs. 1) Isolated action potentials recorded from nerve motor fibers, although sparse at these distal implant sites, were activated during fictive movements of the phantom hand. Unlike in our previous two subjects, electromyographic (EMG) activity contributed to most online recordings and decodes, but was reduced in offline analyses using common average referencing. Online and offline Kalman-filter decodes of thresholded neural or EMG spikes independently controlled different digits of the virtual hand with one or two degrees of freedom. 2) Microstimulation through individual electrodes of the two USEAs evoked up to 106 different percepts, covering much of the phantom hand. The subject discriminated among five perceived stimulus locations, and between two somatosensory submodalities at a single location. 3) USEA-evoked percepts, mimicking contact with either a near or distal virtual target, were used to terminate movements of the virtual hand controlled with USEA recordings comprised wholly or mostly of EMG. These results further indicate that USEAs can help restore sensory and motor function after hand loss.

Muscle-selective block using intrafascicular high-frequency alternating current.

High-frequency alternating current (HFAC) applied to a peripheral nerve can reversibly block skeletal muscle contractions. We evaluated the ability of HFAC delivered via intrafascicular electrodes to selectively block activation of targeted muscles without affecting activation of other muscles. Utah slanted electrode arrays (USEAs) were implanted into the sciatic nerves of five cats, and HFAC was delivered to individual USEA electrodes. The effects of HFAC block were monitored by recording evoked electromyograms (EMGs) and three-dimensional endpoint forces. In each animal, activity evoked in targeted muscles by nerve cuff stimulation could be selectively abolished by HFAC delivered via individual USEA electrodes. Two mechanisms of blockade were evoked: selective neuromuscular blocks were achieved with 500-8000-HZ HFAC, and selective nerve conduction block was achieved in one animal using 16-kHZ HFAC. These results show that intrafascicular HFAC can be used to block selected muscles independent of activation of other muscles.