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We have developed a rechargeable fetal micropacemaker in order to treat severe fetal bradycardia with comorbid hydrops fetalis. The necessarily small form factor of the device, small patient population, and fetal anatomy put unique constraints on the design of the recharging system. To overcome these constraints, a custom high power field generator was built and the recharging process was controlled by utilizing pacing rate as a measure of battery state, a feature of the relaxation oscillator used to generate stimuli. The design and in vitro and in vivo verification of the recharging system is presented here, showing successful generation of recharging current in a fetal lamb model.

Implantation and maintenance of a permanent cardiac pacing system in children remains challenging due to small patient size, congenital heart defects and somatic growth. We are developing a novel epicardial micropacemaker for children that can be implanted on the epicardium within the pericardial space via a minimally-invasive technique. The key design configurations include a novel open-coiled lead in which living tissue replaces the usual polymeric support for the coiled conductor. To better understand and be able to predict the behavior of the implanted lead, we performed a radiographic image-based modeling study on a chronic animal test. We report a pilot study in which two mechanical dummy pacemakers with epicardial leads were implanted into an adult pig model via a minimally invasive approach. Fluoroscopy was obtained on the animal on Post-Operative Days #9, #35 and #56 (necropsy). We then constructed an analytic model to estimate the in vivo stress conditions on the open-coil lead based on the analysis of orthogonal biplane radiographic images. We obtained geometric deformation data of the implanted lead including elongation magnitudes and bending radii from sequenced films of cardiac motion cycles. The lead stress distribution was investigated on each film frame and the point of maximum stress (Mean Stress = 531.4 MPa; Alternating Stress = ± 216.4 MPa) was consistently where one of the leads exited the pericardial space, a deployment that we expected to be unfavorable. These results suggest the modeling approach can provide a basis for further design optimization. More animal tests and modeling will be needed to validate whether the novel lead design could meet the requirements to withstand ~200 million cardiac motion cycles over 5 years.

We have developed a rechargeable fetal micropacemaker in order to treat severe fetal bradycardia with comorbid hydrops fetalis, a life-threatening condition in pre-term non-viable fetuses for which there are no effective treatment options. The small size and minimally invasive form factor of our design limit the volume available for circuitry and a power source. The device employs a fixed-rate and fixed-amplitude relaxation oscillator and a tiny, rechargeable lithium ion power cell. For both research and clinical applications, it is valuable to monitor the electrode-myocardium interface in order to determine that adequate pacemaker output is being provided. This is typically accomplished by observing the minimal stimulus strength that achieves threshold for pacing capture. The output of our simple micropacemaker cannot be programmatically altered to determine this minimal capture threshold, but a safety factor can be inferred by determining the refractory period for ventricular capture at a given stimulus strength. This is done by measuring the minimal timing between naturally occurring QRS complexes and pacing stimuli that successfully generate a premature ventricular contraction. The method was tested in a pilot study in four fetal sheep and the data demonstrate that a relative measure of threshold is obtainable. This method provides valuable real-time information about the electrode-tissue interface.

This paper discusses the technical and safety requirements for cardiac pacing of a human fetus with heart failure and hydrops fetalis secondary to complete heart block. Engineering strategies to meet specific technical requirements were integrated into a systematic design and implementation consisting of a novel fetal micropacemaker, a percutaneous implantation system, and a sterile package that enables device storage and recharging maintenance in a clinical setting. We further analyzed observed problems on myocardial fixation and pacing lead fatigue previously reported in earlier preclinical trials. This paper describes the technical refinements of the implantable fetal micropacemaker to overcome these challenges. The mechanical performance has been extensively tested to verify the improvement of reliability and safety margins of the implantation system.

We have developed and applied new methods to estimate the functional life of miniature, implantable, wireless electronic devices that rely on non-hermetic, adhesive encapsulants such as epoxy. A comb pattern board with a high density of interdigitated electrodes (IDE) could be used to detect incipient failure from water vapor condensation. Inductive coupling of an RF magnetic field was used to provide DC bias and to detect deterioration of an encapsulated comb pattern. Diodes in the implant converted part of the received energy into DC bias on the comb pattern. The capacitance of the comb pattern forms a resonant circuit with the inductor by which the implant receives power. Any moisture affects both the resonant frequency and the Q-factor of the resonance of the circuitry, which was detected wirelessly by its effects on the coupling between two orthogonal RF coils placed around the device. Various defects were introduced into the comb pattern devices to demonstrate sensitivity to failures and to correlate these signals with visual inspection of failures. Optimized encapsulation procedures were validated in accelerated life tests of both comb patterns and a functional neuromuscular stimulator under development. Strong adhesive bonding between epoxy and electronic circuitry proved to be necessary and sufficient to predict 1 year packaging reliability of 99.97% for the neuromuscular stimulator.

We have developed a percutaneously implantable and wireless microstimulator (NuStim) to exercise the pelvic floor muscles for the treatment of stress urinary incontinence. It produces a wide range of charge-regulated electrical stimulation pulses and trains of pulses using a simple electronic circuit that receives power and timing information from an externally generated RF magnetic field. The complete system was validated in vitro and in vivo in preclinical studies demonstrating that the NuStim can be successfully implanted into an effective, low threshold location, and the implant can be operated chronically to produce effective and well-tolerated contractions of skeletal muscle.

Objective We studied the fundamentals of muscle afferentation by building a Neuro-mechano-morphic system actuating a cadaveric finger. This system is a faithful implementation of the stretch reflex circuitry. It allowed the systematic exploration of the effects of different fusimotor drives to the muscle spindle on the closed-loop stretch reflex response. Approach As in Part I of this work, sensory neurons conveyed proprioceptive information from muscle spindles (with static and dynamic fusimotor drive) to populations of α-motor neurons (with recruitment and rate coding properties). The motor commands were transformed into tendon forces by a Hill-type muscle model (with activation-contraction dynamics) via brushless DC motors. Two independent afferented muscles emulated the forces of flexor digitorum profundus and the extensor indicis proprius muscles, forming an antagonist pair at the metacarpophalangeal joint of a cadaveric index finger. We measured the physical response to repetitions of bi-directional ramp-and-hold rotational perturbations for 81 combinations of static and dynamic fusimotor drives, across four ramp velocities, and three levels of constant cortical drive to the α-motor neuron pool. Main results We found that this system produced responses compatible with the physiological literature. Fusimotor and cortical drives had nonlinear effects on the reflex forces. In particular, only cortical drive affected the sensitivity of reflex forces to static fusimotor drive. In contrast, both static fusimotor and cortical drives reduced the sensitivity to dynamic fusimotor drive. Interestingly, realistic signal-dependent motor noise emerged naturally in our system without having been explicitly modeled. Significance We demonstrate that these fundamental features of spinal afferentation sufficed to produce muscle function. As such, our Neuro-mechano-morphic system is a viable platform to study the spinal mechanisms for healthy muscle function-and its pathologies such as dystonia and spasticity. In addition, it is a working prototype of a robust biomorphic controller for compliant robotic limbs and exoskeletons.

It is possible to replace amputated limbs with mechatronic prostheses, but their operation requires the user's intentions to be detected and converted into control signals to the actuators. Fortunately, the motoneurons (MNs) that controlled the amputated muscles remain intact and capable of generating electrical signals, but these signals are difficult to record. Even the latest microelectrode array technologies and targeted motor reinnervation can provide only sparse sampling of the hundreds of motor units that comprise the motor pool for each muscle. Simple rectification and integration of such records is likely to produce noisy and delayed estimates of the actual intentions of the user. We have developed a novel algorithm for optimal estimation of motor pool excitation based on the recruitment and firing rates of a small number (2-10) of discriminated motor units. We first derived the motor estimation algorithm from normal patterns of modulated MN activity based on a previously published model of individual MN recruitment and asynchronous frequency modulation. The algorithm was then validated on a target motor reinnervation subject using intramuscular fine-wire recordings to obtain single motor units.

During quiet standing, humans tend to sway with a distinctive pattern that has been difficult to capture with simple engineering models. We have developed a nonlinear optimal control model for posture regulation. The proposed model consists of two main components: body dynamics and performance measure. The body dynamics are those of a double inverted pendulum in the sagittal plane controlled by ankle and hip torques. The performance measure is nonlinear quartic in the center of pressure and quadratic in the controls. Realistic values for both sensory and motor delays are included in the dynamic model. This nonlinear quartic regulator problem is solved approximately by the model predictive control technique. The resulting feedback control replicates both the experimentally observed sway and the coordinated nonlinear response. It should also use less muscular energy than other comparable controls. The method can easily be extended to more complex models of posture regulation.

We are developing a cardiac pacemaker with a small, cylindrical shape that permits percutaneous implantation into a fetus to treat complete heart block and consequent hydrops fetalis, which can otherwise be fatal. The device uses off-the-shelf components including a rechargeable lithium cell and a highly efficient relaxation oscillator encapsulated in epoxy and glass. A corkscrew electrode made from activated iridium can be screwed into the myocardium, followed by release of the pacemaker and a short, flexible lead entirely within the chest of the fetus to avoid dislodgement from fetal movement. Acute tests in adult rabbits demonstrated the range of electrical parameters required for successful pacing and the feasibility of successfully implanting the device percutaneously under ultrasonic imaging guidance. The lithium cell can be recharged inductively as needed, as indicated by a small decline in the pulsing rate.

Objective:BIONs™ (BIOnic Neurons) are injectable, wireless microstimulators that make chronic BION Active Seating (BAS) possible for pressure ulcer prevention (PUP). Neuromuscular electrical stimulation (NMES) produces skeletal motion and activates trophic factors, counteracting three major etiological mechanisms leading to pressure ulcers (PUs): immobility, soft-tissue atrophy, and ischemia. Companion papers I and II reviewed prior experience with NMES for PUP, and analyzed the biomechanical considerations, respectively. This paper presents a treatment strategy derived from this analysis, and the clinical results of the first three cases.Methods:Two BIONs implanted (one on inferior gluteal nerve to gluteus maximus (GM), and other on sciatic nerve to hamstrings (HS)), in 3 spinal cord injured (SCI) subjects already undergoing gluteal rotation flaps for PUs. BAS using HS when seated, and BION Conditioning (BC) via GM+HS when non-weightbearing. Follow-up: 1 yr, including 6 mo. treatment window (interface pressure mapping; muscle perfusion scans; MRI, X-ray volume assessments).Results:Successfully implanted and activated both desired muscle groups, selectively, in all. No PU recurrences or wound complications. Two subjects completed protocol. Mean results: Interface: contact pressure −10%; maximum pressure −20%; peak pressure area −15%. Vascularity: GM +20%, HS +110%. Perfusion: GM +70%, HS +440%. Muscle volume: GM +14%, HS +31%. Buttock soft-tissue padding: +49%. 1 BION failed; 1 BION rotated under GM.Conclusions:Promising proof-of-concept data supporting the feasibility of implanted microstimulators to achieve sufficiently strong and selective activation of target muscles for PUP. Ultimate goal is prophylactic deployment through bilateral, nonsurgical injection of BIONs in chronically immobile patients.

Objective:Pressure ulcers (PUs) are common and debilitating wounds that arise when immobilized patients cannot shift their weight. Treatment is expensive and recurrence rates are high. Pathophysiological mechanisms include reduced bulk and perfusion of chronically atrophic muscles as well as prolonged occlusion of blood flow to soft tissues from lack of voluntary postural shifting of body weight. This has suggested that PUs might be prevented by reanimating the paralyzed muscles using neuromuscular electrical stimulation (NMES). A review of the published literature over the past 2 decades is detailed.Outcomes:Historically gluteus maximus (GM) has been an important target for NMES, but results have been difficult to interpret and suitable technology has been lacking.Conclusions:NMES of the buttock muscles appears to be valuable in terms of its trophic effects, improving vascularity and soft tissue bulk. It remains unclear, however, whether GM can actually achieve sufficient unloading of normal forces to permit blood flow in the capillary beds of the skin and muscle. Analysis of the skeletal biomechanics is required to assess the relative value of GM vs. hamstring (HS) hip extensors in this regard.

Several studies have been made to develop different versions of new leadless, permanently implanted small electronic devices that allow to be injected into muscles (BIONs™). Their circuitry should be protected from body fluids by thin-walled hermetic capsules of rigid and brittle materials such as glass or ceramic to include feed through for their electrodes. These packages experience repetitive stresses due to the muscle contraction from their excitations. This study provides a worst-case analysis of such stresses and methods to test and validate devices intended for such usage, along with the failure analysis and remediation strategy for a design that experienced unanticipated failures in vivo.

An integrated, sensorimotor virtual arm (VA) model has been developed and validated for simulation studies of control of human arm movements. Realistic anatomical features of shoulder, elbow and forearm joints were captured with a graphic modeling environment, SIMM. The model included 15 musculotendon elements acting at the shoulder, elbow and forearm. Muscle actions on joints were evaluated by SIMM generated moment arms that were matched to experimentally measured profiles. The Virtual Muscle (VM) model contained appropriate admixture of slow and fast twitch fibers with realistic physiological properties for force production. A realistic spindle model was embedded in each VM with inputs of fascicle length, gamma static (gamma(stat)) and dynamic (gamma(dyn)) controls and outputs of primary (I(a)) and secondary (II) afferents. A piecewise linear model of Golgi Tendon Organ (GTO) represented the ensemble sampling (I(b)) of the total muscle force at the tendon. All model components were integrated into a Simulink block using a special software tool. The complete VA model was validated with open-loop simulation at discrete hand positions within the full range of alpha and gamma drives to extrafusal and intrafusal muscle fibers. The model behaviors were consistent with a wide variety of physiological phenomena. Spindle afferents were effectively modulated by fusimotor drives and hand positions of the arm. These simulations validated the VA model as a computational tool for studying arm movement control. The VA model is available to researchers at website http://pt.usc.edu/cel .

Neural prostheses for restoration of limb movement in paralyzed and amputee patients tend to be complex systems. Subjective intuition and trial-and-error approaches have been applied to the design and clinical fitting of simple systems with limited functionality. These approaches are time consuming, difficult to apply in larger scale, and not applicable to limbs under development with more anthropomorphic motion and actuation. The field of neural prosthetics is in need of more systematic methods, including tools that will allow users to develop accurate models of neural prostheses and simulate their behavior under various conditions before actual manufacturing or clinical application. Such virtual prototyping would provide an efficient and safe test-bed for narrowing the design choices and tuning the control parameters before actual clinical application. We describe a software environment that we have developed to facilitate the construction and modification of accurate mathematical models of paralyzed and prosthetic limbs and simulate their movement under various neural control strategies. These simulations can be run in real time with a stereoscopic display to enable design engineers and prospective users to evaluate a candidate neural prosthetic system and learn to operate it before actually receiving it.

A bionic neuron (BION) is an inductively powered, miniature implant developed for functional electric stimulation (FES) to reanimate paralyzed limbs. This paper investigates the possibility of reusing the BION antenna coil as a magnetic sensor to provide meaningful posture information for feedback control of FES. A variety of techniques have been developed to model and cancel nonideal effects caused by the shapes of the internal and external coils, ferrite material, and electronic connections. Field warping has been employed to both amplitude and direction to achieve more accurate description of the dipole magnetic field generated by external coils suitable for generating a reference magnetic frame in the environment of a wheelchair. Models of the transmitting coil and the receiving BION coil were validated against experimental data, providing a solid foundation for implementing a sensor system. Based on the established model, a magnetic sensing system combined with customized microelectro-mechanical systems (MEMS) accelerometer has been designed and tested as a prototype on the bench. The sensor output can be employed to compute 6-D position and orientation. A two-step algorithm integrated with multiple error-cancelling techniques demonstrated sufficient accuracy in bench tests to appear promising for control of reach-and-grasp tasks. A sensor fusion step is proposed to estimate the position and orientation of a limb segment using data from multiple implants in muscles, where they will also function as neuromuscular stimulators to produce the movements to be controlled.

The replacement of proprioceptive function, whether for conscious sensation or feedback control, is likely to be an important aspect of neural prosthetic restoration of limb movements. Thus far, however, it has been hampered by the absence of unobtrusive sensors. We propose a method whereby fully implanted, telemetrically operated BIONstrade monitor muscle movement, and thereby detect changes in joint angle(s) and/or limb posture without requiring the use of secondary components attached to limb segments or external reference frames. The sensor system is designed to detect variations in the electrical coupling between devices implanted in neighboring muscles that result from changes in their relative position as the muscles contract and stretch with joint motion. The goal of this study was to develop and empirically validate mathematical models of the sensing scheme and to use computer simulations to provide an early proof of concept and inform design of the overall sensor system. Results from experiments using paired dipoles in a saline bath and finite element simulations have given insight into the current distribution and potential gradients exhibited within bounded anisotropic environments similar to a human limb segment and demonstrated an anticipated signal to noise ratio of at least 8:1 for submillimeter resolution of relative implant movement over a range of implant displacements up to 15 cm

Building and testing novel prosthetic limbs and control algorithms for functional electrical stimulation (FES) is expensive and risky. Here, we describe a virtual reality environment (VRE) to facilitate and accelerate the development of novel systems. In the VRE, subjects/patients can operate a simulated limb to interact with virtual objects. Realistic models of all relevant musculoskeletal and mechatronic components allow the development of entire prosthetic systems in VR before introducing them to the patient. The system is used both by engineers as a development tool and by clinicians to fit prosthetic devices to patients.

The goal of this study was to test the feasibility and efficacy of using microstimulators (BIONs/spl trade/) to correct foot drop, the first human application of BIONs in functional electrical stimulation (FES). A prototype BIONic foot drop stimulator was developed by modifying a WalkAide2 stimulator to control BION stimulation of the ankle dorsiflexor muscles. BION stimulation was compared with surface stimulation of the common peroneal nerve provided by a normal WalkAide2 foot drop stimulator. Compared to surface stimulation, we found that BION stimulation of the deep peroneal nerve produces a more balanced ankle flexion movement without everting the foot. A 3-D motion analysis was performed to measure the ankle and foot kinematics with and without stimulation. Without stimulation, the toe on the affected leg drags across the ground. The BIONic WalkAide elevates the foot such that the toe clears the ground by 3 cm, which is equivalent to the toe clearance in the unaffected leg. The physiological cost index (PCI) was used to measure effort during walking. The PCI is high without stimulation (2.29 /spl plusmn/ 0.37; mean /spl plusmn/ S.D.) and greatly reduced with surface (1.29 /spl plusmn/ 0.10) and BION stimulation (1.46 /spl plusmn/ 0.24). Also, walking speed is increased from 9.4 /spl plusmn/ 0.4 m/min. without stimulation to 19.6 /spl plusmn/ 2.0 m/min. with surface and 17.8 /spl plusmn/ 0.7 m/min. with BION stimulation. We conclude that functional electrical stimulation with BIONs is a practical alternative to surface stimulation and provides more selective control of muscle activation.

When muscles lose neural drive, they atrophy rapidly. Neuromuscular electrical stimulation (NMS) has been used in attempts to prevent or reverse the atrophy, but optimal stimulation programs and parameters are not well defined. In this study, we investigated the effects of four different stimulation patterns on disuse atrophy produced in the tibialis anterior, lateral gastrocnemius, and soleus muscles of rats paralyzed with tetrodotoxin for seven days. Stimulation paradigms differed from one another by their stimulation frequency (2 or 10 pulses/s) and by their stimulation period (2 or 10 h a day). Results showed that stimulation with 2 pulses/s, paradigms were more effective at preventing disuse muscle atrophy than higher-frequency stimulation. The most marked difference was in the slow soleus muscle, which had only 10% mean atrophy when stimulated at 2 pulses/s for 10 h, compared to 26% atrophy when stimulated at 10 pulses/s for either 2 or 10 h and 32% atrophy in unstimulated, paralyzed controls. The level of atrophic change was not correlated with the levels of serum creatine kinase, used as an index of muscle damage. Results suggest that remediation of disuse atrophy may be accomplished using unphysiologically low rates of motor-unit activation despite the relatively low force produced by such unfused contractions. This may have significant implications for the design of therapies for muscle paralysis consequent to upper-motoneuron lesions.

Previous studies have shown that immobilization causes muscle atrophy and that the rate of atrophy depends on the length at which the muscle is immobilized. However, most studies have been carried out in neurologically intact animals that were capable of generating at least some voluntary muscle activation. In this study, tetrodotoxin was applied chronically to the rat sciatic nerve to produce complete paralysis of distal muscles for seven days, and the ankle was immobilized to hold the muscles at long or short lengths. Paralysis without immobilization resulted in relative weight losses of 36% for soleus, 19% for tibialis anterior (TA), and 17% for lateral gastrocnemius (LG) muscles. Casting the ankle in plantarflexion stretched TA and reduced its weight loss to 10%. Soleus and LG were shortened by this intervention and had increased losses of 43% and 28%, respectively. Fixing the limb in dorsiflexion resulted in a posture similar to that adopted by the unrestrained rats and had no significant effect on the amount of muscle atrophy compared to that in unrestrained paralyzed animals.

Realistic models of neuromusculoskeletal systems can provide a safe and convenient environment for the design and evaluation of controllers for functional electrical stimulation (FES) prior to clinical trials. We have developed a set of integrated musculoskeletal modeling tools to facilitate the model building process. Simulink models of musculoskeletal systems are created using two software packages developed in our laboratory, Musculoskeletal Modeling in Simulink (mms) and virtual muscle, in addition to one software package available commercially, simm (Musculographics Inc., USA). mms converts anatomically accurate musculoskeletal models generated by simm into Simulink blocks. It also removes run-time constraints on kinetic simulations in simm, and allows the development of complex musculoskeletal models without writing a line of code. Virtual muscle builds realistic Simulink models of muscles responding to either natural recruitment or FES. Models of sensorimotor control systems can be developed using various Matlab (Mathworks Inc., USA) toolboxes and integrated easily with these musculoskeletal blocks in the graphical environment of Simulink.  2002 IPEM. Published by Elsevier Science Ltd. All rights reserved.

Objective. We developed a detailed model of the spinal circuitry plus musculoskeletal system (SC+MS) for the primate arm and investigated its role in sensorimotor control, learning and storing of movement repertoires. Approach. Recently developed models of spinal circuit connectivity, neurons and muscle force/energetics were integrated and in some cases refined to construct the most comprehensive model of the SC+MS to date. The SC+MS’s potential contributions to center-out reaching movement were assessed by employing an extremely simple model of the brain that issued only step commands. Main results. The SC+MS was able to generate physiological muscle dynamics underlying reaching across different directions, distances, speeds, and even in the midst of strong dynamic perturbations (i.e. viscous curl field). For each task, there were many different combinations of brain inputs that generated physiological performance. Natural patterns of recruitment and low metabolic cost emerged for about half of the learning trials when a purely kinematic cost function was used and for all of the trials when an estimate of metabolic energy consumption was added to the cost function. Solutions for different tasks could be interpolated to generate intermediate movement and the range over which interpolation was successful was consistent with experimental reports. Significance. This is the first demonstration that a realistic model of the SC+MS is capable of generating the required dynamics of center-out reaching. The interpolability observed is important for the feasibility of storing motor programs in memory rather than computing them from internal models of the musculoskeletal plant. Successful interpolation of command programs required them to have similar muscle recruitment patterns, which are thought by many to arise from hard-wired muscle synergies rather than learned as in our model system. These properties of the SC+MS along with its tendency to generate energetically efficient solutions might usefully be employed by motor cortex to generate voluntary behaviors such as reaching to targets.

We have developed the first in a planned series of neural prosthetic interfaces that allow multichannel systems to be assembled from single-channel micromodules called BIONs (BIOnic Neurons). Multiple BION implants can be injected directly into the sites requiring stimulating or sensing channels, where they receive power and digital commands by inductive coupling to an externally generated radio-frequency magnetic field. This article describes some of the novel technology required to achieve the required microminiaturization, hermeticity, power efficiency and clinical performance. The BION1 implants are now being used to electrically exercise paralyzed and weak muscles to prevent or reverse disuse atrophy. This modular, wireless approach to interfacing with the peripheral nervous system should facilitate the development of progressively more complex systems required to address a growing range of clinical applications, leading ultimately to synthesizing complete voluntary functions such as reach and grasp.

The effects of placement of a miniature implantable stimulator on motor unit recruitment were examined in the posterior head of cat biceps femoris. The implantable stimulator (13-mm long/spl times/2-mm diameter) was injected either proximally near the main nerve branch, or distally near the muscle insertion, through a 12-gauge hypodermic needle. Glycogen-depletion methods were used to map the distribution of fibers activated by electrical stimulation. Muscle fibers were found to be depleted at most or all proximodistal levels of the muscle, but the density of depleted fibers varied transversely according to the stimulus strength and proximity of the device to the nerve-entry site. Thus, muscle cross sections often had a "patchy" appearance produced because different proportions of depleted fibers intermingled with undepleted fibers in different parts of the cross section. In other preparations, the force of muscle contraction was measured when stimuli of varying strengths were delivered by the stimulator positioned at the same proximal or distal sites within the muscle. Devices placed close to the nerve-entry site produced the greatest forces. Those placed more distally produced less force. As stimulus current and/or pulse width increased, muscle force increased, often in steps, until a maximum was reached, which was usually limited by the compliance voltage of the device to less than the force produced by whole nerve stimulation.

Chronic foreign-body responses and muscular changes were examined following the implantation of active miniature stimulators into the hind limb muscles of cats for periods of up to three months. The radio-frequency (RF)-powered stimulators were injected into muscles through a 12-gauge hypodermic needle. The tissue responses around the active stimulators were compared histologically to those provoked by passive devices, broken glass, silicone tubing, polyester suture material coated with polybutylate, and two of the internal components of the stimulator (ferrite, integrated circuit chip). Active and passive stimulators produced similar, benign foreign-body reactions that resulted in an essentially identical fibrous capsule over time. The responses were similar to those produced by the internal components and the suture material, and were more modest than those produced by the broken glass. The capsule did not appear to interfere with the functionality of active devices because thresholds measured during the post-implantation survival period did not change significantly over time. Unexpectedly, the severity of the reaction differed significantly amongst the various target muscles. Medial gastrocnemius exhibited the most severe response, whereas tibialis anterior had the least reaction.

We describe the design, fabrication, and output capabilities of a microminiature electrical stimulator that can be injected in or near nerves and muscles. Each single-channel microstimulator consists of a cylindrical glass capsule with hermetically sealed electrodes in either end (2-mm diameter x 13-mm overall length). Power and digital control data can be transmitted to multiple implants (256 unique addresses) via a 2-MHz RF field created by an external AM oscillator and inductive coil. In vitro testing demonstrated accurate control of output pulsewidth (3-258 microseconds in 1-microseconds steps) and current (0-30 mA in two linear ranges of 16 steps each, up to 8.5 V available compliance voltage). Microstimulators were used successfully for chronic stimulation in hindlimb muscles of cats. Design and fabrication issues affecting yield and reliability of the packaging and electronics are discussed.

BION2 is a system based on injectable neuromuscular implants whose main goal is to restore the functional movement of paralyzed limbs. To achieve this objective, the functional requirements of the implanted interfaces include not only stimulation but also integrated sensors in order to detect patient intention, to provide servocontrol of muscle activation and to sense posture to inform more global motor planning and coordination. The technical constraints for managing the system include the efficient use of forward and reverse telemetry channels with limited capacity, minimization of adverse consequences from errors in data transmission or intermittent loss of power to the implants, and ability to adjust stimulation rates and phases to achieve efficient fine control of muscle force while minimizing fatigue. This paper describes a communication and control architecture with several novel features that address these requirements.

We are developing a self-contained cardiac pacemaker with a small, cylindrical shape (~3 × 20 mm) that permits it to be implanted percutaneously into a fetus to treat complete heart block and consequent hydrops fetalis, which is otherwise fatal. The device uses off-the-shelf components including a rechargeable lithium cell and a highly efficient relaxation oscillator encapsulated in epoxy and glass. A corkscrew electrode made from activated iridium can be screwed into the myocardium, followed by release of the pacemaker and a short, flexible lead entirely within the chest of the fetus to avoid dislodgement from fetal movement. The feasibility of implanting the device percutaneously under ultrasonic imaging guidance was demonstrated in acute adult rabbit experiments.

A comparative study of 5 different designs of nerve cuff electrodes was undertaken to determine their relative merits for stimulating and recording whole-nerve activity over extended periods of chronic implantation on large and small peripheral nerves in 8 cats. Four of the designs represent novel fabrication strategies, including 2 based on flexible, thin-film substrates and 2 based on dip-coating silicone elastomer on a cylindrical mandrel. Various advantages and shortcomings of these materials and designs are discussed in the context of the biophysical factors that influence these electrophysiological interfaces, particularly the problem of recording microvolt-level neurograms in the presence of millivolt-level electromyograms from adjacent muscles in freely behaving subjects. The most effective design was one in which a thin sheath of silicone rubber was wrapped around and intra-operatively sealed to a longitudinally slit, tripolar cuff made by dip-coating silicone over stranded stainless steel leads that were prepositioned on a mandrel using polyvinyl alcohol as a temporary adhesive. When properly installed, these electrodes had stable impedances, recruitment thresholds and relatively interference-free recording properties for the duration of this study (up to 9 weeks).

We provide a general method for producing a variety of small, complex electrode arrays based on injection molds produced using computer-aided drafting and machining (CAD-CAM) procedures and a novel method for connecting to the very fine electrical leads associated with the individual contacts of such arrays. Cat-sized cochlear electrode arrays with up to eight contacts were built according to these methods and their electrical contacts were characterized in vitro by impedance spectroscopy and in vivo by monitoring impedance for over 1 year of intermittent stimulation in chronically instrumented animals.

Humans have been shown to be good at using active touch to perceive subtle differences in compliance. They tend to use highly stereotypical exploratory strategies, such as applying normal force to a surface. We developed similar exploratory and perceptual algorithms for a mechatronic robotic system (Barrett arm/hand system) equipped with liquid-filled, biomimetic tactile sensors (BioTac® from SynTouch LLC). The distribution of force on the fingertip was measured by the electrical resistance of the conductive liquid trapped between the elastomeric skin and a cluster of four electrodes on the flat fingertip surface of the rigid core of the BioTac. These signals provided closed-loop control of exploratory movements, while the distribution of skin deformations, measured by more lateral electrodes and by the hydraulic pressure, were used to estimate material properties of objects. With this control algorithm, the robot plus tactile sensor was able to discriminate the relative compliance of various rubber samples.

In order to endow robots with humanlike abilities to characterize and identify objects, they must be provided with tactile sensors and intelligent algorithms to select, control and interpret data from useful exploratory movements. Humans make informed decisions on the sequence of exploratory movements that would yield the most information for the task, depending on what the object may be and prior knowledge of what to expect from possible exploratory movements. This study is focused on texture discrimination, a subset of a much larger group of exploratory movements and percepts that humans use to discriminate, characterize, and identify objects. Using a testbed equipped with a biologically inspired tactile sensor (the BioTac®) we produced sliding movements similar to those that humans make when exploring textures. Measurement of tactile vibrations and reaction forces when exploring textures were used to extract measures of textural properties inspired from psychophysical literature (traction, roughness, and fineness). Different combinations of normal force and velocity were identified to be useful for each of these three properties. A total of 117 textures were explored with these three movements to create a database of prior experience to use for identifying these same textures in future encounters. When exploring a texture, the discrimination algorithm adaptively selects the optimal movement to make and property to measure based on previous experience to differentiate the texture from a set of plausible candidates, a process we call Bayesian exploration. Performance of 99.6% in correctly discriminating pairs of similar textures was found to exceed human capabilities. Absolute classification from the entire set of 117 textures generally required a small number of well-chosen exploratory movements (median=5) and yielded a 95.4% success rate. The method of Bayesian exploration developed and tested in this paper may generalize well to other cognitive problems.

The goal of the Caltech group is to gain insight into the processes that occur within the primate nervous system during dexterous reaching and grasping and to see whether natural recovery from local brain damage can be accelerated by artificial means. We will create computational models of the nervous system embodying this insight and explain a variety of clinically observed neurological deficits in human subjects using these models.

C5/C6 tetraplegic patients and transhumeral amputees may be able to use voluntary shoulder motion as command signals for a functional electrical stimulation system or transhumeral prosthesis. Stereotyped relationships, termed “postural synergies,” among the shoulder, forearm, and wrist joints emerge during goal-oriented reaching and transport movements as performed by able-bodied subjects. Thus, the posture of the shoulder can potentially be used to infer the desired posture of the elbow and forearm joints during reaching and transporting movements. We investigated how well able-bodied subjects could learn to use a noninvasive command scheme based on inferences from these postural synergies to control a simulated transhumeral prosthesis in a virtual reality task. We compared the performance of subjects using the inferential command scheme (ICS) with subjects operating the simulated prosthesis in virtual reality according to complete motion tracking of their actual arm and hand movements. Initially, subjects performed poorly with the ICS but improved rapidly with modest amounts of practice, eventually achieving performance only slightly less than subjects using complete motion tracking. Thus, inferring the desired movement of distal joints from voluntary shoulder movements appears to be an intuitive and noninvasive approach for obtaining command signals for prostheses to restore reaching and grasping functions.

Research on control of human movement and development of tools for restoration and rehabilitation of movement after spinal cord injury and amputation can benefit greatly from software tools for creating precisely timed animation sequences of human movement. Despite their ability to create sophisticated animation and high quality rendering, existing animation software are not adapted for application to neural prostheses and rehabilitation of human movement. We have developed a software tool known as MSMS (MusculoSkeletal Modeling Software) that can be used to develop models of human or prosthetic limbs and the objects with which they interact and to animate their movement using motion data from a variety of offline and online sources. The motion data can be read from a motion file containing synthesized motion data or recordings from a motion capture system. Alternatively, motion data can be streamed online from a real-time motion capture system, a physics-based simulation program, or any program that can produce real-time motion data. Further, animation sequences of daily life activities can be constructed using the intuitive user interface of Microsoft's PowerPoint software. The latter allows expert and nonexpert users alike to assemble primitive movements into a complex motion sequence with precise timing by simply arranging the order of the slides and editing their properties in PowerPoint. The resulting motion sequence can be played back in an open-loop manner for demonstration and training or in closed-loop virtual reality environments where the timing and speed of animation depends on user inputs. These versatile animation utilities can be used in any application that requires precisely timed animations but they are particularly suited for research and rehabilitation of movement disorders. MSMS's modeling and animation tools are routinely used in a number of research laboratories around the country to study the control of movement and to develop and test neural prostheses for patients with paralysis or amputations.

Muscles convert metabolic energy into mechanical work. A computational model of muscle would ideally compute both effects efficiently for the entire range of muscle activation and kinematic conditions (force and length). We have extended the original Virtual Muscle algorithm (Cheng , 2000) to predict energy consumption for both slow- and fast-twitch muscle fiber types, partitioned according to the activation process (E(a)), cross-bridge cycling (E(xb)) and ATP/PCr recovery (E(recovery)). Because the terms of these functions correspond to identifiable physiological processes, their coefficients can be estimated directly from the types of experiments that are usually performed and extrapolated to dynamic conditions of natural motor behaviors. We also implemented a new approach to lumped modeling of the gradually recruited and frequency modulated motor units comprising each fiber type, which greatly reduced computational time. The emergent behavior of the model has significant implications for studies of optimal motor control and development of rehabilitation strategies because its trends were quite different from traditional estimates of energy (e.g., activation, force, stress, work, etc.). The model system was scaled to represent three different human experimental paradigms in which muscle heat was measured during voluntary exercise; predicted and observed energy rate agreed well both qualitatively and quantitatively.

A family of digitally controlled devices is constructed for functional electrical stimulation in which each module is an hermetically sealed glass capsule that is small enough to be injected through the lumen of a hypodermic needle. The overall design and component characteristics of microstimulators that receive power and command signals by inductive coupling from a single, externally worn coil are described. Each device stores power between stimulus pulses by charging an electrolytic capacitor formed by its two electrodes, made of sintered, anodised tantalum and electrochemically activated iridium, respectively. Externally, a highly efficient class E amplifier provides power and digitally encoded command signals to control the amplitude, duration and timing of pulses from up to 256 such microstimulators.

The intrinsic viscoelastic properties of muscle are central to many theories of motor control. Much of the debate over these theories hinges on varying interpretations of these muscle properties. In the present study, we describe methods whereby a comprehensive musculoskeletal model can be used to make inferences about motor control strategies that would account for behavioral data. Muscle activity and kinematic data from a monkey were recorded while the animal performed a single degree-of-freedom pointing task in the presence of pseudo-random torque perturbations. The monkey's movements were simulated by a musculoskeletal model with accurate representations of musculotendon morphometry and contractile properties. The model was used to quantify the impedance of the limb while moving rapidly, the differential action of synergistic muscles, the relative contribution of reflexes to task performance and the completeness of recorded EMG signals. Current methods to address these issues in the absence of musculoskeletal models were compared with the methods used in the present study. We conclude that musculoskeletal models and kinetic analysis can improve the interpretation of kinematic and electrophysiological data, in some cases by illuminating shortcomings of the experimental methods or underlying assumptions that may otherwise escape notice.

Restoration of motor function to paralyzed limbs by functional electrical stimulation (FES) has been hampered by the lack of precise and gradual control over muscle recruitment. A suitable interface should provide selective stimulation of individual muscles with graded recruitment of force. The BION was developed to enable neuromuscular stimulation through a miniature, self-contained implant designed to be injected in or near muscles and peripheral nerves. In this study, recruitment properties and comfort of the BION implanted electrical stimulation were systematically evaluated in subjects who participated in a clinical trial. Recruitment properties were qualitatively similar to other methods of implanted neuromuscular stimulation: thresholds and steepness of recruitment were negatively correlated and depended on stimulus charge (product of pulse current and duration). Perceived comfort was not affected by the choice of stimulus parameters, thus their choice can be based purely on technical considerations such as efficiency or resolution of recruitment.

The injection of small implants into precisely localized sites within the body is a difficult task usually undertaken by surgeons or interventive radiologists. We have designed, produced and tested a simple tool for implanting BION™ wireless microstimulators as an outpatient office procedure. The ability of BIONs to elicit a desired muscle contraction depends on their placement near the motor fibers that innervate the muscle fibers, providing both the requirement and a means for achieving accurate placement. The implant is preloaded into the tip of the cannula of a two-piece insertion tool made from non-conductive polymers. Trial stimulation pulses are generated by the implant as the tool is manipulated into the desired position. The implant is released by withdrawing the cannula over the implant, preserving both the relative location of the implant’s electrodes with respect to the target and determining its desired axial orientation, which is important for implants containing motion sensors. The BION Insertion Tool has been used for over 30 BION implants in human subjects to date.

We are developing a novel, robust tactile sensor array that mimics the human fingertip and its distributed set of touch receptors. The mechanical components are similar to a fingertip, with a rigid core surrounded by a weakly conductive fluid contained within an elastomeric skin. It uses the deformable properties of the finger pad as part of the transduction process. Multiple electrodes are mounted on the surface of the rigid core and connected to impedance measuring circuitry within the core. External forces deform the fluid path around the electrodes, resulting in a distributed pattern of impedance changes containing information about those forces and the objects that applied them. Here we report preliminary results with prototypes of the sensor, and we propose strategies for extracting features related to the mechanical inputs and using this information for reflexive grip control.

Several groups are developing different versions of a new class of leadless, permanently implanted electronic devices with a size and form factor that allows them to be injected into muscles (BIONs™). Their circuitry is protected from body fluids by thin-walled hermetic capsules made from rigid and brittle materials (glass or ceramic) that include feedthroughs to their electrodes. These packages experience repetitive stresses from the very contractions that they excite. We here provide a worst-case analysis of such stresses and methods for testing and validation of devices intended for such usage, along with the failure analysis and remediation strategy for a design that experienced unanticipated failures in vivo.

This paper describes the highlights of presentations and discussions during the Third International BCI Meeting in a workshop that evaluated potential brain-computer interface (BCI) signals and currently available recording methods. It defined the main potential user populations and their needs, addressed the relative advantages and disadvantages of noninvasive and implanted (i.e., invasive) methodologies, considered ethical issues, and focused on the challenges involved in translating BCI systems from the laboratory to widespread clinical use. The workshop stressed the critical importance of developing useful applications that establish the practical value of BCI technology.

Sencils™ (sensory cilia) are chemical sensors that are minimally invasive, disposable and easily readable to make frequent measurements of various analytes in vivo over a period of 1-3 months. A percutaneous optical fiber permits precise, reliable photonic measurement of chemical reactions in a nano-engineered polymer matrix attached to the internal end of the fiber. The first Sencils sense interstitial glucose based on measurement of fluorescence resonance energy transfer (FRET) between fluorophores bound to betacyclodextrin and Concanavalin A (Con A) in a polyethylene glycol (PEG) matrix. In vitro experiments demonstrate a rapid and precise relationship between the ratio of the two fluorescent emissions and concentration of glucose in saline over the physiological range of 0-500mg/dl. Chronic implantation in pigs has demonstrated biocompatibility. The Sencil platform can be adapted to detect other analytes in interstitial fluids.

Sencilstrade (sensory cilia) are chemical sensors that are minimally invasive, disposable and easily readable to make frequent measurements of various analytes in vivo over a period of 1-3 months. A percutaneous optical fiber permits precise, reliable photonic measurement of chemical reactions in a nano-engineered polymer matrix attached to the internal end of the fiber. The first Sencils sense interstitial glucose based on measurement of fluorescence resonance energy transfer (FRET) between fluorophores bound to betacyclodextrin and Concanavalin-A in a polyethylene glycol (PEG) matrix. In vitro experiments demonstrate a rapid and precise relationship between the ratio of the two fluorescent emissions and concentration of glucose in saline over the physiological range of 0-500 mg/dl. Chronic implantation in pigs has demonstrated biocompatibility. The materials and fabrication methods to produce Sencil implants are robust and inexpensive. Systematic nano-engineering of binding affinities, fluorophore attachment, reactant entrapment and matrix structure provides the key to a wide range of clinical applications

The functional reanimation of paralyzed limbs has been a longstanding goal of neural prosthetic research, but clinically successful applications have been elusive. Natural voluntary limb movement requires four major elements: actuators (i.e., motor units), sensors (i.e., somatosensory afferents), commands (i.e., cerebral cortical activity), and control (i.e., integration of the previous three elements at various levels of the neuraxis). Prosthetic equivalents of each of these elements are, as yet, primitive and often cumbersome to deploy, but new technologies promise substantial improvements for all. This article focuses on one such technology, bionic neuon (BION) modular microimplants, and its relationship to alternative and complementary technologies. The challenge remains to select and integrate them into systems that can be tailored efficiently to the widely disparate needs of patients with various patterns of weakness and paralysis.

Both pulsatile (AC) and continuous (DC) electrical fields have been reported to increase growth or healing or otherwise modify the structure of various tissues, including nerves, bones and skin. Systematic application of these techniques in both animal research and clinical treatment has been hampered by the limitations of currently available technology. We describe a new modular approach in which one or more wireless, microminiature, programmable current generators can be injected or implanted in a wide range of sites. Each device has its own address and can be powered and commanded via an external RF field to produce 10, 100 or 500 /spl mu/A DC and/or pulse trains of 0.2-30 mA at 4-512 /spl mu/s duration. The implants are 2 mm in diameter and 16 mm long. They are made from hermetically sealed, biocompatible materials, so they can be used indefinitely or left in situ after treatment is complete.

BIONs/spl trade/ are chronically implanted, individually addressable, single channel electrical stimulators that are now in clinical trials. They receive power and command signals from an externally worn RF transmission coil. The electronic circuitry is packaged in a glass capsule that can be injected through a hypodermic needle to provide distributed multichannel FES systems. The small size (2 mm OD /spl times/ 16 mm long), external electrodes and long design life (>10 years) pose a challenge for hermetic sealing and testing. We here describe several novel packaging techniques that have been integrated into a single workstation to enable efficient and reliable production of BION implants.