Biomimetic sensory feedback through peripheral nerve stimulation improves dexterous use of a bionic hand.

We describe use of a bidirectional neuromyoelectric prosthetic hand that conveys biomimetic sensory feedback. Electromyographic recordings from residual arm muscles were decoded to provide independent and proportional control of a six-DOF prosthetic hand and wrist-the DEKA LUKE arm. Activation of contact sensors on the prosthesis resulted in intraneural microstimulation of residual sensory nerve fibers through chronically implanted Utah Slanted Electrode Arrays, thereby evoking tactile percepts on the phantom hand. With sensory feedback enabled, the participant exhibited greater precision in grip force and was better able to handle fragile objects. With active exploration, the participant was also able to distinguish between small and large objects and between soft and hard ones. When the sensory feedback was biomimetic-designed to mimic natural sensory signals-the participant was able to identify the objects significantly faster than with the use of traditional encoding algorithms that depended on only the present stimulus intensity. Thus, artificial touch can be sculpted by patterning the sensory feedback, and biologically inspired patterns elicit more interpretable and useful percepts.

Restoring motor control and sensory feedback in people with upper extremity amputations using arrays of 96 microelectrodes implanted in the median and ulnar nerves.

OBJECTIVE: An important goal of neuroprosthetic research is to establish bidirectional communication between the user and new prosthetic limbs that are capable of controlling >20 different movements. One strategy for achieving this goal is to interface the prosthetic limb directly with efferent and afferent fibres in the peripheral nervous system using an array of intrafascicular microelectrodes. This approach would provide access to a large number of independent neural pathways for controlling high degree-of-freedom prosthetic limbs, as well as evoking multiple-complex sensory percepts. APPROACH: Utah Slanted Electrode Arrays (USEAs, 96 recording/stimulating electrodes) were implanted for 30 days into the median (Subject 1-M, 31 years post-amputation) or ulnar (Subject 2-U, 1.5 years post-amputation) nerves of two amputees. Neural activity was recorded during intended movements of the subject's phantom fingers and a linear Kalman filter was used to decode the neural data. Microelectrode stimulation of varying amplitudes and frequencies was delivered via single or multiple electrodes to investigate the number, size and quality of sensory percepts that could be evoked. Device performance over time was assessed by measuring: electrode impedances, signal-to-noise ratios (SNRs), stimulation thresholds, number and stability of evoked percepts. MAIN RESULTS: The subjects were able to proportionally, control individual fingers of a virtual robotic hand, with 13 different movements decoded offline (r = 0.48) and two movements decoded online. Electrical stimulation across one USEA evoked >80 sensory percepts. Varying the stimulation parameters modulated percept quality. Devices remained intrafascicularly implanted for the duration of the study with no significant changes in the SNRs or percept thresholds. SIGNIFICANCE: This study demonstrated that an array of 96 microelectrodes can be implanted into the human peripheral nervous system for up to 1 month durations. Such an array could provide intuitive control of a virtual prosthetic hand with broad sensory feedback.

The foreign body response to the Utah Slant Electrode Array in the cat sciatic nerve.

As the field of neuroprosthetic research continues to grow, studies describing the foreign body reaction surrounding chronic indwelling electrodes or microelectrode arrays will be critical for assessing biocompatibility. Of particular importance is the reaction surrounding penetrating microelectrodes that are used to stimulate and record from peripheral nerves used for prosthetic control, where such studies on axially penetrating electrodes are limited. Using the Utah Slant Electrode Array and a variety of histological methods, we investigated the foreign body response to the implanted array and its surrounding silicone cuff over long indwelling periods in the cat sciatic nerve. We observed that implanted nerves were associated with increased numbers of activated macrophages at the implant site, as well as distal to the implant, at all time points examined, with the longest observation being 350 days after implantation. We found that implanted cat sciatic nerves undergo a compensatory regenerative response after the initial injury that is accompanied by shifts in nerve fiber composition toward nerve fibers of smaller diameter and evidence of axons growing around microelectrode shafts. Nerve fibers located in fascicles that were not penetrated by the array or were located more than a few hundred microns from the implant appeared normal when examined over the course of a year-long indwelling period.

Characterization of a 3D optrode array for infrared neural stimulation.

This paper characterizes the Utah Slant Optrode Array (USOA) as a means to deliver infrared light deep into tissue. An undoped crystalline silicon (100) substrate was used to fabricate 10 × 10 arrays of optrodes with rows of varying lengths from 0.5 mm to 1.5 mm on a 400-µm pitch. Light delivery from optical fibers and loss mechanisms through these Si optrodes were characterized, with the primary loss mechanisms being Fresnel reflection, coupling, radiation losses from the tapered shank and total internal reflection in the tips. Transmission at the optrode tips with different optical fiber core diameters and light in-coupling interfaces was investigated. At λ = 1.55µm, the highest optrode transmittance of 34.7%, relative to the optical fiber output power, was obtained with a 50-µm multi-mode fiber butt-coupled to the optrode through an intervening medium of index n = 1.66. Maximum power is directed into the optrodes when using fibers with core diameters of 200 µm or less. In addition, the output power varied with the optrode length/taper such that longer and less tapered optrodes exhibited higher light transmission efficiency. Output beam profiles and potential impacts on physiological tests were also examined. Future work is expected to improve USOA efficiency to greater than 64%.

Coordinated, multi-joint, fatigue-resistant feline stance produced with intrafascicular hind limb nerve stimulation.

The production of graceful skeletal movements requires coordinated activation of multiple muscles that produce torques around multiple joints. The work described herein is focused on one such movement, stance, that requires coordinated activation of extensor muscles acting around the hip, knee and ankle joints. The forces evoked in these muscles by external stimulation all have a complex dependence on muscle length and shortening velocities, and some of these muscles are biarticular. In order to recreate sit-to-stand maneuvers in the anesthetized feline, we excited the hind limb musculature using intrafascicular multielectrode stimulation (IFMS) of the muscular branch of the sciatic nerve, the femoral nerve and the main branch of the sciatic nerve. Stimulation was achieved with either acutely or chronically implanted Utah Slanted Electrode Arrays (USEAs) via subsets of electrodes (1) that activated motor units in the extensor muscles of the hip, knee and ankle joints, (2) that were able to evoke large extension forces and (3) that manifested minimal coactivation of the targeted motor units. Three hind limb force-generation strategies were investigated, including sequential activation of independent motor units to increase force, and interleaved or simultaneous IFMS of three sets of six or more USEA electrodes that excited the hip, knee and ankle extensors. All force-generation strategies evoked stance, but the interleaved IFMS strategy also reduced muscle fatigue produced by repeated sit-to-stand maneuvers compared with fatigue produced by simultaneous activation of different motor neuron pools. These results demonstrate the use of interleaved IFMS as a means to recreate coordinated, fatigue-resistant multi-joint muscle forces in the unilateral hind limb. This muscle activation paradigm could provide a promising neuroprosthetic approach for the restoration of sit-to-stand transitions in individuals who are paralyzed by spinal cord injury, stroke or disease.

Non-invasive method for selection of electrodes and stimulus parameters for FES applications with intrafascicular arrays.

High-channel-count intrafascicular electrode arrays provide comprehensive and selective access to the peripheral nervous system. One practical difficulty in using several electrode arrays to evoke coordinated movements in paralyzed limbs is the identification of the appropriate stimulation channels and stimulus parameters to evoke desired movements. Here we present the use of a six degree-of-freedom load cell placed under the foot of a feline to characterize the muscle activation produced by three 100-electrode Utah Slanted Electrode Arrays (USEAs) implanted into the femoral nerves, sciatic nerves, and muscular branches of the sciatic nerves of three cats. Intramuscular stimulation was used to identify the endpoint force directions produced by 15 muscles of the hind limb, and these directions were used to classify the forces produced by each intrafascicular USEA electrode as flexion or extension. For 451 USEA electrodes, stimulus intensities for threshold and saturation muscle forces were identified, and the 3D direction and linearity of the force recruitment curves were determined. Further, motor unit excitation independence for 198 electrode pairs was measured using the refractory technique. This study demonstrates the utility of 3D endpoint force monitoring as a simple and non-invasive metric for characterizing the muscle-activation properties of hundreds of implanted peripheral nerve electrodes, allowing for electrode and parameter selection for neuroprosthetic applications.

[Molecular and structural-biological analysis of Nicotiana plumbaginifolia mutants for identification of the site of beta-tubulins interaction with dinitroanilines and phosphorotioamidates].

The identification of point mutation locations on beta-tubulin molecules of amiprophosmethyl- and trifluralin-resistant Nicotiana plumbaginifolia lines have described in the work. It was shown that in the first case this mutation is connected with the substitution ofserine residue on proline in position 248; in the second case--with the substitution of phenilalanine on serine in position 317 of beta-tubulin amino acid sequence. Three-dimensional models of beta-tubulin molecule from Chlamydomonas with well-known location of mutations conferring dinitroaniline- and phosphorotioamidate resistance (substitution of lysine residue to methionine on position 350), and beta-tubulin from Nicotiana plumbaginifolia have been reconstructed. On the basis of analysis of site of interaction with dinitroanilines and phosphorotioamides on Chlamydomonas beta-tubulin molecule it was concluded that the revealed mutations on Nicotiana plumbaginifolia beta-tubulin affect amino acid residues participating in formation of this site.

A wireless integrated circuit for 100-channel charge-balanced neural stimulation.

The authors present the design of an integrated circuit for wireless neural stimulation, along with benchtop and in - vivo experimental results. The chip has the ability to drive 100 individual stimulation electrodes with constant-current pulses of varying amplitude, duration, interphasic delay, and repetition rate. The stimulation is performed by using a biphasic (cathodic and anodic) current source, injecting and retracting charge from the nervous system. Wireless communication and power are delivered over a 2.765-MHz inductive link. Only three off-chip components are needed to operate the stimulator: a 10-nF capacitor to aid in power-supply regulation, a small capacitor (< 100 pF) for tuning the coil to resonance, and a coil for power and command reception. The chip was fabricated in a commercially available 0.6- mum 2P3M BiCMOS process. The chip was able to activate motor fibers to produce muscle twitches via a Utah Slanted Electrode Array implanted in cat sciatic nerve, and to activate sensory fibers to recruit evoked potentials in somatosensory cortex.

In situ measurements of nitrate leaching implicate poor nitrogen and irrigation management on sandy soils.

Minimizing the risk of nitrate contamination along the waterways of the U.S. Great Plains is essential to continued irrigated corn production and quality water supplies. The objectives of this study were to quantify nitrate (NO(3)) leaching for irrigated sandy soils (Pratt loamy fine sand [sandy, mixed, mesic Lamellic Haplustalfs]) and to evaluate the effects of N fertilizer and irrigation management strategies on NO(3) leaching in irrigated corn. Two irrigation schedules (1.0x and 1.25x optimum) were combined with six N fertilizer treatments broadcast as NH(4)NO(3) (kg N ha(-1)): 300 and 250 applied pre-plant; 250 applied pre-plant and sidedress; 185 applied pre-plant and sidedress; 125 applied pre-plant and sidedress; and 0. Porous-cup tensiometers and solution samplers were installed in each of the four highest N treatments. Soil solution samples were collected during the 2001 and 2002 growing seasons. Maximum corn grain yield was achieved with 125 or 185 kg N ha(-1), regardless of the irrigation schedule (IS). The 1.25x IS exacerbated the amount of NO(3) leached below the 152-cm depth in the preplant N treatments, with a mean of 146 kg N ha(-1) for the 250 and 300 kg N preplant applications compared with 12 kg N ha(-1) for the same N treatments and 1.0x IS. With 185 kg N ha(-1), the 1.25x IS treatment resulted in 74 kg N ha(-1) leached compared with 10 kg N ha(-1) for the 1.0x IS. Appropriate irrigation scheduling and N fertilizer rates are essential to improving N management practices on these sandy soils.

Post-light potentiation at type B to A photoreceptor connections in Hermissenda.

We investigated whether the long (approximately 30-s) or short (approximately 3-s) light stimuli that have been used during behavioral training would induce post-light potentiation (PLP) at the type B to A photoreceptor connections of the isolated nervous system of Hermissenda. We found that a single approximately 30-s light step induced PLP at these connections relative to both pre-light baseline and seawater control preparations, as did a series of nine short (approximately 3-s) light steps. In addition, a 30-s step of depolarization-elicited type B cell activity induced potentiation comparable to that induced by a approximately 30-s light step, indicating that light-elicited type B cell activity contributes to the induction of PLP. By contrast, even though a series of short (3-s) light steps induced potentiation, short steps of depolarization-evoked type B cell activity did not. Hence, light-evoked processes other than type B cell depolarization or activity (e.g., perhaps intracellular Ca2+ release) also contribute to the induction of PLP. Further results suggest that these other light-evoked processes interact nonadditively with type B cell activity to generate PLP. Some but not all instances of synaptic potentiation were accompanied by various changes in parameters of type B cell action potentials and afterhyperpolarizing potentials, suggesting diverse underlying mechanisms, including increases in neurotransmitter release. Given that the type A cells have been proposed to polysynaptically excite the motor neurons that drive phototaxis, a light-evoked potentiation of synaptic strength at the inhibitory type B to A photoreceptor connections may play a mechanistic role in light-elicited nonassociative learning.

The wheat LEA protein Em functions as an osmoprotective molecule in Saccharomyces cerevisiae.

The biased amino acid composition and aperiodic (random coil) configuration of Group 1 late embryogenesis-abundant (LEA) proteins imply that these proteins are capable of binding large amounts of water. While Group 1 LEAs have been predicted to contribute to osmotic stress protection in both embryonic and vegetative tissues, biochemical support has been lacking. We have used Saccharomyces cerevisiae as a model system to test the putative osmoprotective function of a wheat Group 1 LEA protein, Em. We demonstrate that expression of Em protein in yeast cells is not deleterious to growth in media of normal osmolarity and attenuates the growth inhibition normally observed in media of high osmolarity. Enhanced growth is observed in the presence of a variety of osmotically active compounds indicating that Em protein is capable of mitigating the detrimental effect of low water potential in a relatively non-specific manner. These results are the first biochemical demonstration of an osmoprotective function for a Group 1 LEA and suggest that the yeast expression system will be useful in dissecting the mechanism of protection through structure-function studies.

Synaptic depression at type B to A photoreceptor connections in Hermissenda.

We quantified synaptic depression at the type B to A photoreceptor connections of Hermissenda. Type B cell action potentials were evoked at interstimulus intervals (ISIs) of 0.3, 3 or 30 s and the resulting inhibitory postsynaptic potentials (IPSPs) were recorded in a type A cell. A progressive decline in IPSP amplitude occurred at all three ISIs. Synaptic depression was greater at shorter ISIs, as was the level of recovery 2 min after the stimulus series. The profound level of synaptic depression observed (79.0+/-3.2% at the 0.3 s ISI) implies that synaptic depression is an important control process in the neuronal circuitry that drives phototactic behavior.

GABA-induced synaptic facilitation at type B to A photoreceptor connections in Hermissenda.

Gamma-aminobutyric acid (GABA) is a prevalent neurotransmitter in both vertebrate and invertebrate systems. Here we report that, in addition to its usual inhibitory actions, GABA induced synaptic facilitation at type B to A photoreceptor connections of the marine mollusk Hermissenda when applied transiently to the isolated nervous system. Synaptic facilitation also occurred in response to mechanical stimulation of the GABAergic hair cells, which are normally activated by rotational unconditioned stimuli during behavioral training of the intact animal. This synaptic facilitation represents a novel form of GABA-induced neuromodulation which may contribute to learning-dependent suppression of phototaxis in Hermissenda.

Differential responses of Aplysia siphon motor neurons and interneurons to tail and mantle stimuli: implications for behavioral response specificity.

1. Tail shock and mantle shock elicit different forms of siphon responses in Aplysia (flaring and backward bending vs. constriction and forward bending, respectively). Moreover, training with these two unconditioned stimuli (USs) in US-alone or classical conditioning paradigms differentially modifies the direction of the response to a siphon tap subsequently presented. As a first step toward addressing neural mechanisms underlying this response specificity, we systematically mapped the central siphon withdrawal circuit to determine which motor neurons and interneurons are differentially engaged by, and potentially modified by, tail and mantle USs. We utilized semi-intact preparations consisting of the intact mantle organs (including the gill and siphon), the tail, and the abdominal and circumesophageal ganglia. USs were delivered either cutaneously through silver wires implanted in the tail and mantle or via suction electrodes to the tail and branchial nerves. 2. We found that one class of central siphon motor neurons, the LFSB cells, was preferentially activated by tail USs, whereas other siphon motor neurons, the LBs cells and RDs cells, were preferentially activated by mantle USs. These motor neurons thus appear to be the final common path for the differential siphon movements to these USs. In addition, because activation of these cells can elicit neuromuscular facilitation and thereby enhance siphon movements, this differential activation may contribute to behavioral response specificity by imposing a specific response bias. 3. L29 interneurons, which both mediate and modulate the siphon withdrawal response, responded preferentially and exhibited synaptic facilitation selectively in response to tail shock USs. In contrast, L34 and the interneuron II network did not show differential activation. Facilitation at L29-LFSB connections following training with tail shock may contribute to tail-directed siphon responses to siphon tap and may thus be an additional mechanism contributing to behavioral response specificity. Possibly, facilitation at other L29 connections could also enhance its modulatory capabilities. 4. The generation of specific response topographies thus appears to involve the coordinate regulation of diverse neuronal elements and multiple mechanisms, which may contribute to different aspects of learning.

Modeling Hermissenda: I. Differential contributions of IA and IC to type-B cell plasticity.

We developed a multicompartmental Hodgkin-Huxley model of the Hermissenda type-B photoreceptor and used it to address the relative contributions of reductions of two K+ currents, IA and IC, to changes in cellular excitability and synaptic strength that occur in these cells after associative learning. We found that reductions of [symbol: see text] C, the peak conductance of IC, substantially increased the firing frequency of the type-B cell during the plateau phase of a simulated light response, whereas reductions of [symbol: see text] A had only a modest contribution to the plateau frequency. This can be understood at least in part by the contributions of these currents to the light-induced (nonspiking) generator potential, the plateau of which was enhanced by [symbol: see text] C reductions, but not by [symbol: see text] A reductions. In contrast, however, reductions of [symbol: see text] A broadened the type-B cell action potential, increased Ca2+ influx, and increased the size of the postsynaptic potential produced in a type-A cell, whereas similar reductions of [symbol: see text] C had only negligible contributions to these measures. These results suggest that reductions of IA and IC play important but different roles in type-B cell plasticity.

Modeling Hermissenda: II. Effects of variations in type-B cell excitability, synaptic strength, and network architecture.

Because the Hermissenda eye is relatively simple and its cells well characterized, it provides an attractive preparation for detailed computational analysis. To examine the neural mechanisms of learning in this system, we developed multicompartmental models of the type-A and type-B photoreceptors, simulated the eye, and asked three questions: First, how do conductance changes affect cells in a network as compared with those in isolation; second, what are the relative contributions of increases in B-cell excitability and synaptic strength to network output; and third, how do these contributions vary as a function of network architecture? We found that reductions in the type-B cells of two K+ currents, IA and IC, differentially affected the type-B cells themselves, with IC reductions increasing firing rate (excitability) in response to light, and IA reductions increasing quantal output (synaptic strength) onto postsynaptic targets. Increases in either type-B cel excitability or synaptic strength, induced directly or indirectly, each suppressed A-cell photoresponses, and the combined effect of both changes occurring together was greater than either alone. To examine the effects of network architecture, we compared the full network with a simple feedforward B-A pair and intermediate configurations. Compared with a feedforward pair, the complete network exhibited greater A-cell sensitivity to B-cell changes. This was due to many factors, including an increased number of B-cells (which increased B-cell impact on A-cells), A-B feedback inhibition (which slowed both cell types and altered spike timing relationships), and B-B lateral inhibition (which reduced B-cell sensitivity to intrinsic biophysical modifications). These results suggest that an emergent property of the network is an increase both in the rate of information acquisition ("learning") and in the amount of information that can be stored ("memory").