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Biomedical subjects

G E Loeb

Publications and source records attributed to G E Loeb.

At least 19 recordsLinked to original sources

Advanced modeling environment for developing and testing FES control systems.

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(R) 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.

Computer Simulation↗

Learning from the spinal cord.

The graceful control of multiarticulated limbs equipped with slow, non-linear actuators (muscles) is a difficult problem for which robotic engineering affords no general solution. The vertebrate spinal cord provides an existence proof that such control is, indeed, possible. The biological solution is complex and incompletely known, despite a century of meticulous neurophysiological research, celebrated in part by this symposium. This is frustrating for those who would reanimate paralysed limbs either through promoting regeneration of the injured spinal cord or by functional electrical stimulation. The importance of and general role played by the spinal cord might be more easily recognized by analogy to marionette puppets, another system in which a brain (the puppeteer's) must cope with a large number of partially redundant actuators (strings) moving a mechanical linkage with complex intrinsic properties.

Humans↗

Real-time sonography to estimate muscle thickness: comparison with MRI and CT.

PURPOSE: We investigated the feasibility of using real-time sonography to measure muscle thickness. Clinically, this technique would be used to measure the thickness of human muscles in which intramuscular microstimulators have been implanted to treat or prevent disuse atrophy. METHODS: Porcine muscles were implanted with microstimulators and imaged with sonography, MRI, and CT to assess image artifacts created by the microstimulators and to design protocols for image alignment between methods. Sonography and MRI were then used to image the deltoid and supraspinatus muscles of 6 healthy human subjects. RESULTS: Microstimulators could be imaged with all 3 methods, producing only small imaging artifacts. Muscle-thickness measurements agreed well between methods, particularly when external markers were used to precisely align the imaging planes. The correlation coefficients for sonographic and MRI measurements were 0.96 for the supraspinatus and 0.97 for the deltoid muscle. Repeated sonographic measurements had a low coefficient of variation: 2.3% for the supraspinatus and 3.1% for the deltoid muscle. CONCLUSIONS: Real-time sonography is a relatively simple and inexpensive method of accurately measuring muscle thickness as long as the operator adheres to a strict imaging protocol and avoids excessive pressure with the transducer.

Adult↗

BION system for distributed neural prosthetic interfaces.

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.

Animals↗

Neck muscles in the rhesus monkey. II. Electromyographic patterns of activation underlying postures and movements.

Electromyographic (EMG) activity was recorded in < or = 12 neck muscles in four alert monkeys whose heads were unrestrained to describe the spatial and temporal patterns of neck muscle activation accompanying a large range of head postures and movements. Some head postures and movements were elicited by training animals to generate gaze shifts to visual targets. Other spontaneous head movements were made during orienting, tracking, feeding, expressive, and head-shaking behaviors. These latter movements exhibited a wider range of kinematic patterns. Stable postures and small head movements of only a few degrees were associated with activation of a small number of muscles in a reproducible synergy. Additional muscles were recruited for more eccentric postures and larger movements. For head movements during trained gaze shifts, movement amplitude, velocity, and acceleration were correlated linearly and agonist muscles were recruited without antagonist muscles. Complex sequences of reciprocal bursts in agonist and antagonist muscles were observed during very brisk movements. Turning movements of similar amplitudes that began from different initial head positions were associated with systematic variations in the activities of different muscles and in the relative timings of these activities. Unique recruitment synergies were observed during feeding and head-shaking behaviors. Our results emphasize that the recruitment of a given muscle was generally ordered and consistent but that strategies for coordination among various neck muscles were often complex and appeared to depend on the specifics of musculoskeletal architecture, posture, and movement kinematics that differ substantially among species.

Animals↗

Virtual muscle: a computational approach to understanding the effects of muscle properties on motor control.

This paper describes a computational approach to modeling the complex mechanical properties of muscles and tendons under physiological conditions of recruitment and kinematics. It is embodied as a software package for use with Matlab and Simulink that allows the creation of realistic musculotendon elements for use in motor control simulations. The software employs graphic user interfaces (GUI) and dynamic data exchange (DDE) to facilitate building custom muscle model blocks and linking them to kinetic analyses of complete musculoskeletal systems. It is scalable in complexity and accuracy. The model is based on recently published data on muscle and tendon properties measured in feline slow- and fast-twitch muscle, and incorporates a novel approach to simulating recruitment and frequency modulation of different fiber-types in mixed muscles. This software is distributed freely over the Internet at http://ami.usc.edu/mddf/virtualmuscle.

Animals↗

What do reflex and voluntary mean? Modern views on an ancient debate.

Are the words reflex and voluntary useful scientific concepts, or are they prescientific terms that should be discarded? Physiologists use these words routinely in their publications, in laboratory experiments and, indeed, like most lay people, in their daily lives. The tacit assumption is that we all know, more or less, what they mean. However, the issue has a rich history of philosophical and scientific debate; and, as this article demonstrates, present-day researchers still cannot reach a consensus on the meaning of the words and on whether it is possible to draw a scientific distinction between them. The five authors present five quite different analyses. In broad terms, they split into two camps: those who equate voluntary behaviours with consciousness and suppressibility and those who view all behaviours as sensorimotor interactions, the complexity of which determines whether they are reflexive or voluntary. According to the first view, most movements of daily life are neither purely reflex nor purely voluntary. They fall into the middle ground of automatic motor programs. According to the second view, as neuroscience advances the class of reflex behaviours will grow and the class of voluntary behaviours will shrink.

Animals↗

Measured and modeled properties of mammalian skeletal muscle: III. the effects of stimulus frequency on stretch-induced force enhancement and shortening-induced force depression.

Stretch-induced force enhancement and shortening-induced force depression were examined in fast-twitch feline caudofemoralis muscle at 37 degrees C. These phenomena were induced by applying ramp length changes during the first 100--200 ms of an otherwise isometric contraction. The effects of various stimulus frequencies ranging from 30 to 120 pps were investigated over lengths ranging from 0.85 to 1.15 L0. Distributed asynchronous stimulation of bundles of ventral roots was employed to produce smooth contractions at sub-tetanic stimulus frequencies in whole muscle. Of the two components of force enhancement identified by Noble (1992) we observed only the transient component that decays with time; we did not observe residual force enhancement. The force depression that we observed was symmetrical in almost all respects to the transient force enhancement, and was unlike the shortening-induced de-activation and residual force depression identified by Edman (Edman. 1975; Edman et al., 1993). Both transient force enhancement and depression were independent of work, load and activation. Reversals in the direction of ramp length changes following either an initial stretch or initial shortening were shown to cancel the effects of both transient force enhancement and transient force depression. The distances over which these cancellations could be achieved were different for the lengthening and shortening effects. This asymmetry can be reconciled with the predictions of Huxley's original cross-bridge mechanism by incorporating the recent suggestion that myosin heads can interact with multiple actin binding sites during a single 'working' stroke. We conclude that the types of force enhancement/ depression that are most likely to be encountered under physiological conditions are the transient effects observed here, but that even these will have relatively little effect on force production during most natural behaviors.

Animals↗

Measured and modeled properties of mammalian skeletal muscle: IV. dynamics of activation and deactivation.

The interactive effects of length and stimulus frequency on rise and fall times and on sag were investigated in fast-twitch feline caudofemoralis at normal body temperature. The length and stimulus frequency ranges studied were 0.8 1.2 L0 and 15 60 pps. Isometric rise times were shortest under two sets of conditions: short lengths + low stimulus frequencies and long lengths + high stimulus frequencies. In contrast the isometric fall time relationship showed a single minimum at short lengths + low stimulus frequencies. Velocity was shown to have an additional effect on fall time, but only at higher stimulus frequencies (40 60 pps): fall times were shorter during movement in either direction as compared to isometric. The effects of sag were greatest at shorter lengths and lower stimulus frequencies during isometric stimulus trains. Potential mechanisms underlying this last effect were investigated by comparing isometric twitches elicited prior to and immediately following a sag-inducing stimulus train. Post-sag twitches produced less force, reached peak force earlier and initially decayed more quickly compared to pre-sag twitches. However, the final rate of force decay and the initial rate of force rise (during the first 15 ms) were unaffected by sag. We construct a logical argument based on these findings to hypothesize that the predominant mechanism underlying sag is an increase in the rate of sarcoplasmic calcium ion removal. All of the above findings were used to construct a model of activation dynamics for fast-twitch muscle, which was then extrapolated to slow-twitch muscle. When coupled with a previous model of kinematic dynamics, the complete model produced accurate predictions of the forces actually recorded during experiments in which we applied concurrent dynamic changes in length. velocity and stimulus frequency.

Action Potentials↗

Overcomplete musculature or underspecified tasks?

The number of muscles in the body is actually fairly close to the number required to control completely all its degrees of freedom. The apparent need for a coordinating principle arises from the experimental practice of asking subjects to perform simple movements and assuming that they make no implicit assumptions about other constraints. Natural activities include implicit constraints that differ greatly for different tasks and circumstances and that would be met best by a nervous system free of a priori principles.

Biomechanical Phenomena↗

Recruitment properties of intramuscular and nerve-trunk stimulating electrodes.

Functionally useful reanimation of paralyzed limbs generally requires reliable, finely graded control of muscle recruitment and force with minimal fatigue. We used force and electromyographic (EMG) recordings in combination with myofibrillar adenosine triphosphatase activity and glycogen depletion analysis to investigate the recruitment properties of intramuscular (IM) and nerve cuff (NC) stimulating electrodes implanted acutely or chronically in cat hindlimbs. Overall, 32 muscles were submaximally stimulated with current intensities producing approximately 20% of maximal twitch force using 330 ms trains of pulses at 20 and 40 pps. Both the glycogen-depletion and fatigue-test results were found to be difficult to interpret because NC stimulation resulted in surprisingly unstable recruitment during such trains. Fluctuations of force and M-waves within trains of identical stimuli were significantly greater for NC than for IM stimulation. NC stimulation produced much steeper recruitment curves and a reduced tetanus/twitch ratio compared to IM stimulation. IM stimulation produced more reliable and less fatigable recruitment of a mix of motor unit types that tended to be localized in neuromuscular compartments containing, or adjacent to, the IM electrode. We hypothesize that trains of submaximal stimulation applied through NC electrodes resulted in fluctuating recruitment because this electrode configuration magnifies the effects of refractoriness and small changes in axonal excitability during pulse trains.

Acute Disease↗

A hierarchical foundation for models of sensorimotor control.

Successful performance of a sensorimotor task arises from the interaction of descending commands from the brain with the intrinsic properties of the lower levels of the sensorimotor system, including the dynamic mechanical properties of muscle, the natural coordinates of somatosensory receptors, the interneuronal circuitry of the spinal cord, and computational noise in these elements. Engineering models of biological motor control often oversimplify or even ignore these lower levels because they appear to complicate an already difficult problem. We modeled three highly simplified control systems that reflect the essential attributes of the lower levels in three tasks: acquiring a target in the face of random torque-pulse perturbations, optimizing fusimotor gain for the same perturbations, and minimizing postural error versus energy consumption during low- versus high-frequency perturbations. The emergent properties of the lower levels maintained stability in the face of feedback delays, resolved redundancy in over-complete systems, and helped to estimate loads and respond to perturbations. We suggest a general hierarchical approach to modeling sensorimotor systems, which better reflects the real control problem faced by the brain, as a first step toward identifying the actual neurocomputational steps and their anatomical partitioning in the brain.

Animals↗

Measured and modeled properties of mammalian skeletal muscle. II. The effects of stimulus frequency on force-length and force-velocity relationships.

Interactions between physiological stimulus frequencies, fascicle lengths and velocities were analyzed in feline caudofemoralis (CF), a hindlimb skeletal muscle composed exclusively of fast-twitch fibers. Split ventral roots were stimulated asynchronously to produce smooth contractions at sub-tetanic stimulus frequencies. As described previously, the peak of the sub-tetanic force-length relationship was found to shift to longer lengths with decreases in stimulus frequency, indicating a length dependence for activation that is independent of filament overlap. The sub-tetanic force-velocity (FV) relationship was affected strongly both by stimulus frequency and by length; decreases in either decreased the slope of the FV relationship around isometric. The shapes of the force transients following stretch or shortening revealed that these effects were not due to a change in the instantaneous FV relationship; the relative shape of the force transients following stretch or shortening was independent of stimulus frequency and hardly affected by length. The effects of stimulus frequency and length on the sub-tetanic FV relationship instead appear to be caused by a time delay in the length-dependent changes of activation. In contrast to feline soleus muscle, which is composed exclusively of slow-twitch fibers, CF did not yield at sub-tetanic stimulus frequencies for the range of stretch velocities tested (up to 2 L0/s). The data presented here were used to build a model of muscle that accounted well for all of the effects described. We extended our model to account for slow twitch muscle by comparing our fast-twitch model with previously published data and then changing the necessary parameters to fit the data. Our slow-twitch model accounts well for all previous findings including that of yielding.

Action Potentials↗

Measured and modeled properties of mammalian skeletal muscle. I. The effects of post-activation potentiation on the time course and velocity dependencies of force production.

Activation of mammalian fast-twitch skeletal muscle induces a persistent effect known as post-activation potentiation (PAP), classically defined as an increase in force production at sub-maximal levels of activation. The underlying mechanism is thought to be phosphorylation of the myosin regulatory light chain (MRLC), which leads to an increase in the rate constant for cross-bridge attachment (Sweeney et al., 1993). If true, this suggests the hypothesis that other contractile properties should be affected during PAP. Using a feline fast-twitch whole-muscle preparation (caudofemoralis) at 37 degrees C, we observed that PAP greatly increased tetanic forces during active lengthening decreased isometric tetanic rise times and delayed isometric tetanic force relaxation. The first two of these effects were length dependent with a greater effect occurring at shorter lengths. These findings confirmed that PAP has other functionally important effects beyond a simple increase in sub-maximal isometric forces. Furthermore, length was found to have an effect independent of PAP on the shortening half of the FV relationship (less force was produced at longer lengths) and on the rate of force relaxation during the later stages of isometric tetanic force decay (slower relaxation at longer lengths). All of these findings can be explained with a simplified, two-state model of cross-bridge dynamics that accounts for the interaction of both interfilament spacing and MRLC phosphorylation on the apparent rate constants for cross-bridge attachment and detachment. These findings are largely consistent with data collected previously from reduced preparations such as skinned fibers at cold, unphysiological temperatures (e.g. 5 degrees C). One finding that could not be explained by our model was that twitch fall times in the dispotentiated state were parabolically correlated with length, whereas in the potentiated state the relationship was linear. The time course of decay of this effect did not follow the time course of force dispotentiation, suggesting that there are other activation-dependent processes occurring in parallel with MRLC phosphorylation.

Actin Cytoskeleton↗

Asymmetry of hindlimb muscle activity and cutaneous reflexes after tendon transfers in kittens.

The mechanical actions of various ankle muscles were changed by surgically crossing or transferring the tendons in kittens. After the kittens grew to adults, both hindlimbs were implanted with multiple electromyogram (EMG) recording and cutaneous nerve stimulation electrodes to compare the activity of altered and normal muscles. The tendon transfers showed a remarkable tendency to regrow toward normal or only slightly altered mechanical action. In these animals and in the sham-operation controls, the patterns of muscle activity and reflexes were symmetrical in corresponding muscles of the two legs, although they could differ substantially between animals, particularly for the cutaneous reflexes. Eleven animals had at least some persistent alterations in muscle action. Their cutaneous reflex patterns tended to be asymmetric, in some cases quite markedly. EMG activity during unperturbed locomotion and paw-shaking was more symmetrical, but there were some changes in altered muscles and their synergists. The central pattern generators for locomotion and paw-shaking and particularly for cutaneous reflexes during locomotion appear to be at least partially malleable rather than entirely hardwired. This may provide a tool for studying their development and spinal plasticity in general.

Animals↗

Feline caudofemoralis muscle. Muscle fibre properties, architecture, and motor innervation.

Feline caudofemoralis (CF) is a promising preparation in which to study the properties of mammalian fast-twitch skeletal muscle, but little is known about its muscle fiber properties, architecture, and motor innervation. We used histochemical techniques to confirm that it contained predominantly type IIB fibers (95+/-2%, n=8, with six of eight muscles composed exclusively of type IIA and IIB fibers), but physiological experiments showed less fatiguability than for the type IIB component of medial gastrocnemius. This may be related to the surprisingly strong and regular recruitment of CF during repetitive tasks such as walking and trotting, which we demonstrated electromyographically. We measured muscle length over the anatomical range of motion for CF (approximately 0.6-1.2 L0) and estimated working length during walking and trotting (approximately 0.95-1.15 L0). The specific tension was similar to that of the exclusively slow-twitch soleus muscle (31.2+/-4.7 N/cm2 compared with 31.8+/-4.1 N/cm2; P>0.8). Single fiber dissections of CF revealed a series-fibered architecture with a mean of 2.3 fibers, each 2.5 cm long, required to span the fascicle length. We identified two neuromuscular compartments in CF by cutting one of the two nerve branches innervating CF and depleting the glycogen stores in the intact motor units. These compartments were in parallel and extended the length of the muscle; their electromyographic activity was similar during various natural behaviors. CF and gluteus maximus motoneurons were labeled concurrently with a combination of fluorescent, retrograde tracers including Fluororuby, Fluorogold and Fast Blue. The CF motor nucleus was located in L7-S1, overlapping and intermingling extensively with the nucleus of the adjacent gluteus maximus muscle. Distributions of CF motoneuron diameter revealed one large peak around 50-55 microm, with relatively few small-diameter (less than 35 microm) cells. Using estimates of the total number of fibers in three muscles and the estimated number of alpha-motoneurons for those same muscles, we calculated a mean innervation ratio of approximately 270, which is at the low end of the innervation ratios for type IIB motor units from other feline muscles and more similar to type IIA motor units. In general, CF appears to be a useful preparation in which to study the properties of fast-twitch muscle, but these properties may vary somewhat from type IIB fibers from different muscles.

Acetylcholinesterase↗

Design for an inexpensive but effective cochlear implant.

Widespread application of cochlear implants is limited by cost, especially in developing countries. In this article we present a design for a low-cost but effective cochlear implant system. The system includes a speech processor, four pairs of transmitting and receiving coils, and an electrode array with four monopolar electrodes. All implanted components are passive, reducing to a minimum the complexity of manufacture and allowing high reliability. A four-channel continuous interleaved sampling strategy is used for the speech processor. The processor and transmission link have been evaluated in tests with a subject previously implanted with the Ineraid electrode array and percutaneous connector. A prototype of the link, consisting of four pairs of transmitting and external receiving coils, was used, with the outputs of the receiving coils directed to four intracochlear electrodes through the percutaneous connector. The subject achieved speech reception scores with the prototype system that were equivalent to those achieved with a standard laboratory implementation of a continuous interleaved sampling processor with current-controlled stimuli.

Cochlear Implantation↗