Stabilometry as a diagnostic tool in clinical medicine.

Stabilomety, a method of measuring stability of stance or postural equilibrium in man, consists of transforming the mechanical oscillations of man''s "physiologic gravicentre" into electric signals, then amplifying, recording and analysing the signals. The frequency, duration and mean and maximum amplitudes of oscillations, and coefficients reflecting the influence of vision, differ in patients with various neurologic diseases and from values in healthy subjects. The method is highly sensitive and accurate, simple and rapid to use, lacks danger and discomfort and permits screening of a large number of people in a short time.     

Organ temperature measurement in a microwave oven by resonance frequency shift

An experimental system has been developed that can indirectly measure temperature in a high-intensity microwave field over a broad range of conditions. A RF amplifier connected closed-loop around a high Q cavity oscillates at one of the natural modes of the oven. A bandpass filter selects the mode of interest. As the frozen sample is thawed, an increase in dielectric constant occurs, decreasing the resonance frequency of the cavity. Calibration of the system is performed by measuring the frequency shift for samples whose temperatures are known, Rotation of samples during thawing often causes oscillations of the resonance frequency. These oscillations are generated by asymmetric sample properties and geometry, and hot spots developed during the thaw. Development of a method that would predict hot spot location from these resonance frequency oscillations and permit modulation of the magnetron or sample rotation to minimize thermal runaway is suggested.     

Oscillometric measurement of systolic and diastolic blood pressures validated in a physiologic mathematical model

ABSTRACT: BACKGROUND: The oscillometric method of measuring blood pressure with an automated cuff yields valid estimates of mean pressure but questionable estimates of systolic and diastolic pressures. Existing algorithms are sensitive to differences in pulse pressure and artery stiffness. Some are closely guarded trade secrets. Accurate extraction of systolic and diastolic pressures from the envelope of cuff pressure oscillations remains an open problem in biomedical engineering. METHODS: A new analysis of relevant anatomy, physiology and physics reveals the mechanisms underlying the production of cuff pressure oscillations as well as a way to extract systolic and diastolic pressures from the envelope of oscillations in any individual subject. Stiffness characteristics of the compressed artery segment can be extracted from the envelope shape to create an individualized mathematical model. The model is tested with a matrix of possible systolic and diastolic pressure values, and the minimum least squares difference between observed and predicted envelope functions indicates the best fit choices of systolic and diastolic pressure within the test matrix. RESULTS: The model reproduces realistic cuff pressure oscillations. The regression procedure extracts systolic and diastolic pressures accurately in the face of varying pulse pressure and arterial stiffness. The root mean squared error in extracted systolic and diastolic pressures over a range of challenging test scenarios is 0.3 mmHg. CONCLUSIONS: A new algorithm based on physics and physiology allows accurate extraction of systolic and diastolic pressures from cuff pressure oscillations in a way that can be validated, criticized, and updated in the public domain.     

Effect of diamide on force generation and axial stiffness of the cochlear outer hair cell.

We found that diamide, which affects spectrin, reduces the axial stiffness of the cochlear outer hair cell, the cylindrically shaped mechanoreceptor cell with a unique voltage-sensitive motility. This effect thus provides a means of examining the relationship between the stiffness and the motility of the cell. For measuring axial stiffness and force production, we used an experimental configuration in which an elastic probe was attached to the cell near the cuticular plate and the other end of the cell was held with a patch pipette in the whole-cell recording mode. Diamide at concentrations of up to 5 mM reduced the axial stiffness in a dose-dependent manner to 165 nN per unit strain from 502 nN for untreated cells. The isometric force elicited by voltage pulses under whole-cell voltage clamp was also reduced to 35 pN/mV from 105 pN/mV for untreated cells. Thus the isometric force was approximately proportional to the axial stiffness. Our observations suggest a series connection between the motor and cytoskeletal elements and can be explained by the area motor model previously proposed for the outer hair cell.     

Tremor and other oscillations in neuromuscular systems

A model has been analyzed which is based on recent experimental evidence concerning the properties of muscles and the sensory feedback pathways from muscles. Damped oscillations can arise in the absence of sensory feedback due to the interaction of a muscle with inertial loads. These mechanical oscillations can have a wide range of frequencies depending on the inertial and elastic loads that are attached to the muscle. Small amounts of sensory feedback will tend to reduce deviations from a steady muscle length, but larger amounts of feedback can produce oscillations. The frequency of these reflex oscillations is determined by the properties of the muscle and feedback pathway, and is rather independent of load. If the strength of the sensory feedback is sufficient, either the mechanical oscillations or the reflex oscillations or both can grow, rather than decay, with time. The growth of these oscillations is limited by saturation non-linearities in the muscle receptors and the muscle itself, so that the oscillations approach a steady amplitude and frequency. Using typical properties of muscles and spinal reflex pathways, the frequency of reflex oscillations will be within the range 8–12 Hz found for physiological tremor. With the longer latency found for supraspinal reflexes, oscillations will occur in the range 4–6 Hz which is characteristic of Parkinson's and cerebellar diseases. The role of longer latency reflexes in the generation of these tremors is discussed.     

The effects of pH on force and stiffness development in mouse muscles

Changes in force and stiffness during contractions of mouse extensor digitorum longus and soleus muscles were measured over a range of extracellular pH from 6.4 to 7.4. Muscle stiffness was measured using small amplitude (less than 0.1% of muscle length), high frequency (1.5 kHz) oscillations in length. Twitch force was not significantly affected by changes in pH, but the peak force during repetitive stimulation (2, 3, and 20 pulses) was decreased significantly as the pH was reduced. Changes in muscle stiffness with pH were in the same direction, but smaller in extent. If the number of attached cross-bridges in the muscle can be determined from the measurement of small amplitude, high frequency muscle stiffness, then these findings suggest that (a) the number of cross-bridges between thick and thin filaments declines in low pH and (b) the average force per cross-bridge also declines in low pH. The decline in force per cross-bridge could arise from a reduction in the ability of cross-bridges to generate force during their state of active force production and (or) in an increased percentage of bonds in a low force, "rigor" state.     

A physical model of acoustic effects of ultrahigh frequency fields on biological systems

A physical model of radiosound based on the stimulation of mechanical oscillations in liquid media at adsorption of SHF impulse energy is presented. It is shown that a limited liquid volume can be considered as an acoustic resonator with self oscillation frequency. At definite relationships between the succession frequency and impulse duration interference takes place. Oscillograms of recorded mechanical oscillations are presented. The low frequency type of radiosound is explained. A conclusion is made concerning the reliability of the proposed method for investigating radiosound.     

The Micromechanics of Biological and Biomimetic Staggered Composites

Natural materials such as bone,tooth and nacre achieve attractive properties through the “staggered structure",which consists of stiff,parallel inclusions of large aspect ratio bonded together by a more ductile and tougher matrix.This seemingly simple structure displays sophisticated micromechanics which lead to unique combinations of stiffness,strength and toughness.In this article we modeled the staggered structure using finite elements and small Representative Volume Elements (RVEs) in order to explore microstructure-property relationships.Larger aspect ratio of inclusions results in greater stiffness and strength,and also significant amounts of energy dissipation provided the inclusions do not fracture in a brittle fashion.Interestingly the ends of the inclusions (the junctions) behave as crack-like features,generating theoretically infinite stresses in the adjacent inclusions.A fracture mechanics criterion was therefore used to predict the failure of the inclusions,w hich led to new insights into how the interfaces act as a "soft wrap" for the itclusions,completely shielding them from excessive stresses.The effect of statistics on the mechanics of the staggered structure was also assessed using larger scale RVEs.Variations in the microstructure did not change the modulus of the material,but slightly decreased the strength and significantly decreased the failure strain.This is explained by strain localization,which can in turn be delayed by incorporating vaviness to the inclusions.In addition,we show that the columnar and random arrangements,displaying different deformation mechanisms,lead to similar overall properties.The guidelines presented in this study can be used to optimize the design of staggered synthetic composites to achieve mechanical performances comparable to natural materials.     

Numerical simulation of collapsible-tube flows with sinusoidal forced oscillations

Collapsible-tube flow with self-excited oscillations has been extensively investigated. Though physiologically relevant, forced oscillation coupled with self-excited oscillation has received little attention in this context. Based on an ODE model of collapsible-tube flow, the present study applies modern dynamics methods to investigate numerically the responses of forced oscillation to a limit-cycle oscillation which has topological characteristics discovered in previous unforced experiments. A devil's staircase and period-doubling cascades are presented with forcing frequency and amplitude as control parameters. In both cases, details are provided in a bifurcation diagram. Poincaré sections, a frequency spectrum and the largest Lyapunov exponents verify the existence of chaos in some circumstances. The thin fractal structure found in the strange attractors is believed to be a result of high damping and low stiffness in such systems.     

Emergent properties of electrically coupled smooth muscle cells

Asynchronous and synchronous calcium oscillations occur in a variety of cells. A well-established pathway for intercellular communication is provided by gap junctions which connect adjacent cells and can mediate electrical and chemical coupling. Several experimental studies report that cells presenting only a transient increase when freshly dispersed may oscillate when they are coupled. Such observations suggest that the role of gap junctions is not only to coordinate calcium oscillations of adjacent cells. Gap junctions may also be important to generate oscillations. Here we illustrate the emergent properties of electrically coupled smooth muscle cells using a model that we recently proposed. A bifurcation analysis in the case of two cells reveals that synchronous and asynchronous calcium oscillations can be induced by electrical coupling. In a larger population of smooth muscle cells, electrical coupling may result in the creation of groups of cells presenting synchronous calcium oscillations. The elements of one group may be distant from each other. Moreover, our results highlight a general mechanism by which gap junctional electrical coupling can give rise to out of phase calcium oscillations in smooth muscle cells that are non-oscillating when uncoupled. All these observations remain true in the case of non-identical cells, except that the solution corresponding to synchronous calcium oscillations disappears and that the formation of groups is sensitive to the degree of heterogeneity. The first two authors contributed equally to this work.     

Effects of volatile anesthetics on stiffness of mammalian ventricular muscle.

To assess the effects of halothane, isoflurane, and sevoflurane on cross bridges in intact cardiac muscle, electrically stimulated (0.25 Hz, 25 degrees C) right ventricular ferret papillary muscles (n = 14) were subjected to sinusoidal load oscillations (37-182 Hz, 0.2-0.5 mN peak to peak) at the instantaneous self-resonant frequency of the muscle-lever system. At resonance, stiffness is proportional to m * omega(2) (where m is equivalent moving mass and omega is angular frequency). Dynamic stiffness was derived by relating total stiffness to values of passive stiffness at each length during shortening and lengthening. Shortening amplitude and dynamic stiffness were decreased by halothane > isoflurane > or = sevoflurane. At equal peak shortening, dynamic stiffness was higher in halothane or isoflurane in high extracellular Ca(2+) concentration than in control. Halothane and isoflurane increased passive stiffness. The decrease in dynamic stiffness and shortening results in part from direct effects of volatile anesthetics at the level of cross bridges. The increase in passive stiffness caused by halothane and isoflurane may reflect an effect on weakly bound cross bridges and/or an effect on passive elastic elements.     

Smooth muscle stiffness variation due to external longitudinal oscillations

This research focuses on an in vitro investigation of the stiffness changes of contracted airway smooth muscles (ASM) subjected to external longitudinal oscillations. ASM tissues were dissected from excised pig tracheas and stimulated by a chemical stimulus (acetylcholine, 10(-3) M) to produce maximum contractions. The tissues were then systematically excited with external oscillations. Various frequencies, amplitudes and durations were used in the experiments to determine stiffness changes in response to these variations. Force changes were recorded to reflect the muscle stiffness changes. Two stiffness definitions were used to quantify the results, dynamic stiffness to reflect variations during oscillation and static stiffness to reflect the net effect of oscillation. Under isometric contractions, these two stiffnesses were determined before, during and after oscillations. Incorporating an empirical stiffness equation, a two-dimensional finite element model (FEM) was developed to generalize the tissue responses to oscillation. The main outcomes from this work are: the dynamic stiffness has the tendency to decrease as the frequency and/or amplitude of external oscillation increases; the static stiffness has the tendency of decreasing with an increase in the frequency and/or amplitude of excitation until it reaches almost a constant value for frequencies at and above 25 Hz. The difference in the behavior of the dynamic and static stiffness changes may be attributed to the effect of elasticity and mass inertia that are involved in the dynamic motion. The findings of this research are in agreement with the hypothesis that oscillations exert a direct action on the contractile processes by causing an increased rate of actin-myosin detachments.     

Electrokinetic membrane processes in relation to properties of excitable tissues. I. Experiments on oscillatory transport phenomena in artificial membranes

An artificial system is studied consisting of salt solutions of different concentrations separated by a porous, "charged" membrane, through which a constant electric current is passed. Experiments on such systems demonstrate rhythmic variations of the transmembrane potential and the membrane resistance, which are concomitant with an oscillatory streaming of water solution across the membrane. The repetitive oscillations can be of a damped or undamped type dependent on the "stimulating" current density. A qualitative discussion of the mechanism of the oscillations is given. It centers around the periodic resistance changes in the membrane, which result from a complicated interplay between the driving forces present. The importance of electro-osmotic effects is emphasized. A few comparisons relating to possible electrophysiological implications are presented. In the metastable state of this membrane oscillator, "make" and "break" responses can be triggered by electric as well as by mechanical (pressure) "stimuli."     

Modeling of a simple motor task in man: intentional arrest of an ongoing movement

Normal subjects and cerebellar patients were instructed to arrest “as soon as possible” a ballistically initiated flexion movement of the forearm. The intentional actions consist essentially of a downward torque, the peak value of which has almost a constant latency (about 200 msec) from the beginning of the movement. A variable number of oscillations precede the arrest of the movement, the characteristics of which depend on the initial velocity of the flexion and on the mass with which the forearm is loaded. The motor commands responsible for the intentionally produced downward torque are controlled centrally as to leave the ratio between the peak values of the angular velocity which precede and follow the peak of the torque almost constant, under all conditions. To describe the oscillations a simple analytical model was proposed which includes the mechanical as well as the reflex factors, the latter under the form of a delayed velocity term. The satisfactory fitting of this model to the experimental findings permitted to establish the following points:

1. The oscillations are sustained by both a mechanical and a reflex stiffness. The contribution of the reflex loop is however quantitatively dominant since it accounts for about 75% of the inertial torque. It is fairly constant over the range of frequency of the oscillations considered.
2. Under the imposed experimental conditions angular velocity appears to be the parameter of the movement which is predominantly sensed and fed back by the reflex loop.

Data were also presented on the performance of the motor task by patients who underwent surgical ablations of the cerebellar cortex. Comparison of these results with those of normal subjects strongly supports the hypothesis that cerebellar-related activities are instrumental in determining the sensitivity of the stretch reflex to angular velocity.     

The frequency of calcium oscillations in mouse eggs at fertilization is modulated by the number of fused sperm.

In a variety of calcium signaling systems, the frequency of intracellular calcium oscillations is physiologically important. Probably multiple factors control the frequency of calcium oscillations in the egg after fertilization and many of these remain to be identified. In this study, we present the first rigorous set of data showing that monospermic fertilization is important for setting the physiological calcium oscillation frequency. Recordings in 152 zona-free eggs show that the general pattern of the calcium oscillations is identical in monospermic and polyspermic eggs; however, the oscillation frequency is higher in polyspermic eggs (P < 10(-6)). The frequency of the late oscillations increases with the number of sperm heads incorporated: 5.2 +/- 0.3 spikes per hour (mean +/- SEM; n = 55) in monospermic eggs, 6.6 +/- 0.3 (n = 62) in dispermic eggs, 8.7 +/- 0.7 (n = 23) in trispermic eggs, and 8.9 +/- 0.9 (n = 12) in eggs with four or more sperm heads. The frequency of the early oscillations is also increased in polyspermic eggs. Seventy-eight additional eggs were divided into two groups and inseminated with two different sperm concentrations ("low" and "high") to obtain one group mainly monospermic and the other mainly polyspermic. The two groups of eggs oscillated at different frequencies (P < 10(-5)). These data rule out the possibility of an egg effect in which some eggs would have the dual properties of oscillating faster and of being able to fuse with several sperm cells. These data instead suggest that the sperm modulates the frequency of the oscillations in a dose-dependent manner.     

Measuring the Characteristic Topography of Brain Stiffness with Magnetic Resonance Elastography

Purpose

To develop a reliable magnetic resonance elastography (MRE)-based method for measuring regional brain stiffness.

Methods

First, simulation studies were used to demonstrate how stiffness measurements can be biased by changes in brain morphometry, such as those due to atrophy. Adaptive postprocessing methods were created that significantly reduce the spatial extent of edge artifacts and eliminate atrophy-related bias. Second, a pipeline for regional brain stiffness measurement was developed and evaluated for test-retest reliability in 10 healthy control subjects.

Results

This technique indicates high test-retest repeatability with a typical coefficient of variation of less than 1% for global brain stiffness and less than 2% for the lobes of the brain and the cerebellum. Furthermore, this study reveals that the brain possesses a characteristic topography of mechanical properties, and also that lobar stiffness measurements tend to correlate with one another within an individual.

Conclusion

The methods presented in this work are resistant to noise- and edge-related biases that are common in the field of brain MRE, demonstrate high test-retest reliability, and provide independent regional stiffness measurements. This pipeline will allow future investigations to measure changes to the brain’s mechanical properties and how they relate to the characteristic topographies that are typical of many neurologic diseases.     

Human gamma oscillations during slow wave sleep

Neocortical local field potentials have shown that gamma oscillations occur spontaneously during slow-wave sleep (SWS). At the macroscopic EEG level in the human brain, no evidences were reported so far. In this study, by using simultaneous scalp and intracranial EEG recordings in 20 epileptic subjects, we examined gamma oscillations in cerebral cortex during SWS. We report that gamma oscillations in low (30-50 Hz) and high (60-120 Hz) frequency bands recurrently emerged in all investigated regions and their amplitudes coincided with specific phases of the cortical slow wave. In most of the cases, multiple oscillatory bursts in different frequency bands from 30 to 120 Hz were correlated with positive peaks of scalp slow waves ("IN-phase" pattern), confirming previous animal findings. In addition, we report another gamma pattern that appears preferentially during the negative phase of the slow wave ("ANTI-phase" pattern). This new pattern presented dominant peaks in the high gamma range and was preferentially expressed in the temporal cortex. Finally, we found that the spatial coherence between cortical sites exhibiting gamma activities was local and fell off quickly when computed between distant sites. Overall, these results provide the first human evidences that gamma oscillations can be observed in macroscopic EEG recordings during sleep. They support the concept that these high-frequency activities might be associated with phasic increases of neural activity during slow oscillations. Such patterned activity in the sleeping brain could play a role in off-line processing of cortical networks.     

Temporal coding in the guinea-pig auditory cortex as revealed by optical imaging and its pattern-time-series analysis

The neural network structure of a guinea-pig's primary auditory cortex is estimated by applying pattern-time-series analysis to the auditory evoked responses. Spatiotemporal patterns in click-evoked responses, observed by optical recording with voltage-sensitive dye, are analyzed by time series analysis using a multivariable autoregressive (MAR) model. Oscillatory neural activities with a distribution of about 10 40 Hz in the click-induced evoked responses are found in the cortical response field. The cortical regions where the distributed neural oscillations are generated are identified by pattern-time-series analysis. In addition, two types of cortico-cortical connections, unilateral and bilateral connections between the cortical points, are speculated to be the causes of oscillatory neural activity transfer. It can be said that the so-called synchronized neural oscillation, in the sense of coherency or correlation between the two evoked responses at the oscillatory frequency, does not necessarily represent real corticocortical neural connections at the evoked response points.     

Membrane Potential Oscillations Produced by Excitatory Amino Acids in Isolated Spinal Neurons of the Lamprey Lampetra fluviatilis

Membrane potential (MP) oscillations produced by excitatory amino acids (EAA) have been studied in branching neurons isolated by an enzymatic-mechanical method from the lamprey spinal cord. It was shown that (1) all studied EAA (glutamate, kainate, NMDA, aspartate, and quisqualate) evoke an ion current and a short-term reversible depolarization in studied cells; (2) EAA added to perfusion solution may produce MP oscillations, with kinetic parameters and duration of the oscillation depending on the amino acid used (the most effective are kainate and NMDA, the least effective, quisqualate); (3) oscillations can be irregular (of the type of a synaptic noise or of a long-term plateau of depolarization with action potentials—AP) or regular, with frequency of 0.5–1.5 Hz. Amplitude of both oscillation types depends on MP level, frequency is more steady for each cell and less depends on MP. In 68 out of 128 studied cells, oscillations could be evoked, which indicates that a significant part of lamprey spinal neurons have intrinsic capability for MP oscillations and probably pacemaker properties. The functional role of oscillations can be different. They can take cells out from the profound inhibition state, synchronize activity of rhythm generation neurons and/or be the base for trigger signals (AP firing) sent by locomotor neuronal circuits to trunk muscles.