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Biomedical subjects

J Timmer

Publications and source records attributed to J Timmer.

At least 19 recordsLinked to original sources
PubMed1999

Classical conditioning of the electrically elicited blink reflex in humans: a new method of data analysis.

The eyeblink conditioning paradigm is a well-established model to study learning processes in humans and animals. Especially results from animal studies have supplied new insight into physiological pathways and brain structures involved in associative motor learning and memory. An important role of the cerebellum and its afferent fiber systems could be shown. Recent studies in humans have given evidence that results of animal experiments can be applied directly to the human condition. A high variation of baseline EMG activity and/or spontaneous blinks may influence the analysis of classical conditioning of the electrically elicited blink reflex in humans. To optimize differentiation between real conditioned responses and stimulus-independent EMG activity, we developed an algorithm which is fully automated and independent of a possible bias of an examiner. In a first step the algorithm decides whether a subject fulfills the criteria of a successful learning process or not. The second step quantifies the learning process. For quantification of the learning process, the following parameters were calculated: number of conditioned responses, onset of conditioning, time and amount of maximal conditioning, speed of conditioning and speed of habituation. According to our criteria, 80% of the healthy volunteers acquired conditioned responses. There is an age-related decline in eyeblink classical conditioning. Analysis of patient groups with different types of lesions will further improve our knowledge and understanding of pathways involved in learning processes in humans. The proposed new algorithm of data analysis takes less than 10 s on a standard computer, is more sensitive and more specific in detecting conditioned responses and, therefore, may further improve the value and reliability of the eyeblink conditioning paradigm in clinical research.

Adult↗
PubMed1999

Involvement of cranial muscles and high intermuscular coherence in orthostatic tremor.

Electromyographic recordings were conducted from limb, trunk, and cranial muscles in 6 patients with orthostatic tremor. Spectral analysis revealed a high-frequency tremor not only in the muscles of the limbs and trunk, but also in cranial muscles. The cross spectra were analyzed between various pairs of muscles that displayed a high-frequency tremor pattern. The resulting peak correlations were uniformly very high (near one) suggesting a high level of coherence. The involvement of cranial muscles suggests that supraspinal mechanisms are involved in the generation of orthostatic tremor. The high intermuscular coherence between all muscles indicates the existence of either a unique oscillator that generates tremor in all involved muscles on both sides of the body or a linking mechanism probably at a supraspinal level. The high-frequency tremor was only found when the muscles were contracted isometrically, irrespective of body posture. Thus, tremor generation might be more closely linked to mechanisms responsible for isometric force control than to those involved in stance regulation.

Aged↗
PubMed1999

On identification of Na(+) channel gating schemes using moving-average filtered hidden Markov models.

Transitions between distinct kinetic states of an ion channel are described by a Markov process. Hidden Markov models (HMM) have been successfully applied in the analysis of single ion channel recordings with a small signal-to-noise ratio. However, we have recently shown that the anti-aliasing low-pass filter misleads parameter estimation. Here, we show for the case of a Na(+) channel recording that the standard HMM do neither allow parameter estimation nor a correct identification of the gating scheme. In particular, the number of closed and open states is determined incorrectly, whereas a modified HMM considering the anti-aliasing filter (moving-average filtered HMM) is able to reproduce the characteristic properties of the time series and to perform gating scheme identification.

Cell Line↗
PubMed1999

Artefacts in spiral-CT images and their relation to pitch and subject morphology.

This qualitative study is intended to create awareness of artefacts that are associated with spiral-CT imaging. A simple description of spiral-CT reconstruction is used to explain how these artefacts depend on the pitch and subject morphology, and shows when these artefacts are likely to impair the diagnostic value of the acquired images. We scanned a cone and rod phantom with pitch 2, and used the acquired images to demonstrate how spiral data acquisition and interpolation leads to artefacts in the reconstructed images. We then demonstrated the effects of various pitches in scans of a human cadaver, whereas the slice thickness was kept constant. Some patient studies are presented in order to show the possible clinical consequences. Spiral acquisition may cause geometric distortions and apparent inhomogeneity of homogeneous structures. We were able to link these artefacts to the way in the acquisitions were done, and the reconstructions were performed. We have shown how these artefacts can be anticipated in clinical studies. When areas of low contrast, surrounded by hypo- or hyperdense structures, are scanned with a large pitch and viewed with a narrow window, spiral artefacts may influence the diagnostic quality of the images. These effects should be considered when choosing the pitch.

Aged↗
PubMed1999

Early detection of upper airway obstructions by analysis of acoustical respiratory input impedance.

Repetitive occurrence of partial or total upper airway obstruction characterizes several respiratory dysfunctions such as the obstructive sleep apnea syndrome (OSAS). In OSAS patients, pharyngeal collapses are linked to a decrease in upper airway muscle activity during sleep which causes decreased upper airway wall stiffness. Continuous positive airway pressure (CPAP) is recommended as the treatment of choice. Advancements in CPAP therapy require early detection of respiratory events in real time to adapt the level of the applied pressure to airway collapsibility. The forced oscillation technique (FOT) is a noninvasive method which reflects patients' airway patency by measuring respiratory impedance. The aim of this study was to evaluate by a mathematical model of the respiratory system if FOT can provide an early detection index of total or partial upper airway obstruction. Furthermore, the simulation should suggest which characteristic features are relevant for early apnea detection in measured clinical data. The respiratory system has been treated as a series of cylindrical segments. The oropharynx analog of the model allows simulation of upper airway collapse, mimicking the situation in patients with OSAS. We calculated the input impedance for different degrees of upper airway obstruction ranging from unobstructed airways to total occlusion. Furthermore, we simulated different upper airway wall compliances. We compared the simulation with real data. The results of the study suggest that FOT is a valuable tool for assessing the degree of upper airway obstruction in patients with OSAS. Especially, the phase angle of the impedance seems to be a potentially useful tool for early apnea detection by assessing the upper airway wall collapsibility.

Humans↗
PubMed1999

A software for recording and analysis of human tremor.

For many diseases various methods for the diagnosis and treatment monitoring are available. Presently, such methods are not established for an investigation of tremor diseases, although the different forms of tremor are common neurological symptoms and occur frequently in various neurological diseases and also other conditions. We developed an easy-to-use application for tremor-analysis and recording, running under MS-Windows, that allows us to investigate different forms of tremor by advanced mathematical methods of time series analysis. The application is also applicable for users who are not familiar with these kind of advanced data analysis methods. It provides tools for the diagnosis and treatment monitoring under laboratory conditions, based on previously developed and established methods of spectral and cross spectral analysis of tremor and electromyographic time series.

Electronic Data Processing↗
PubMed1999

Side-to-side correlation of muscle activity in physiological and pathological human tremors.

OBJECTIVE: Many tremors occur always or often bilaterally. The question arises whether this could be explained by a common source or commonly transmitting pathways or by bilaterally represented, independent structures with the same oscillatory properties. A similar tremor frequency does not provide sufficient information to clarify this question. METHODS: We analyze coherencies between surface electromyographies (EMG) to investigate if bilateral physiologic (PT), essential (ET), Parkinsonian (PD) and orthostatic (OT) tremors originate from a common source for both sides of the body. We show that commonly used techniques to test whether coherencies are significant could lead to false positive results for tremor EMGs. A new estimation procedure is proposed to test EMG tremor time series on their linear independence. We apply this test to bilateral tremors. RESULTS: All measured EMG-pairs in OT (n = 7) were highly coherent between both sides with reproducible coherency values of up to 0.99. All other investigated tremors, i.e. PT and enhanced physiological tremors (EPT, n = 117), ET (n = 76) and PD resting and postural tremors (n = 70) do not show a significant side-to-side correlation. CONCLUSIONS: This finding shows that the pathophysiologies of OT and other pathological tremors are definitely different. Either they have different origins or different kinds of transmitting pathways. The proposed method might also be used to investigate other electrophysiological data and is a helpful, easy to use investigation for a daily clinical routine.

Computer Simulation↗
PubMed1998

Central mechanisms in human enhanced physiological tremor.

The sites of the central nervous structures involved in enhanced physiological tremor (EPT) are still unclear. The syndrome of persistent mirror movements (PMM) is characterized by abnormal bilateral corticospinal projections. If a supraspinal mechanism is involved in EPT, the activity of EPT should be coherent between both sides in subjects with this abnormality. We investigated three PMM subjects and three normal controls. Focal transcranial magnetic stimulation (TMS) resulted in contralateral hand muscle responses in the controls. The PMM subjects, in contrast, had bilateral responses. Similarly, long-latency reflexes (LLR) in PMM could be recorded bilaterally, while the control subjects showed responses only on the stimulated side. EPT was evoked by intravenous salbutamol. EMG time series were recorded bilaterally from the wrist extensor muscles and cross spectra were calculated. If there was a significant right-left-coherence, phase analysis was performed. No control subject showed a significant right-left-coherence of tremor activity. In contrast, a significant coherence was found in PMM between 8 and 12 Hz. When the mechanical tremor frequency of one hand was reduced by loading, coherences and phase spectra of the EMGs remained unchanged. By comparing the results from TMS, LLR and cross spectral analysis we come to the conclusion, that the 8 to 12 Hz component of EPT is transmitted transcortically, most likely originating from two separate generators for both sides.

Adult↗
PubMed1998

Detecting multimodality in saccadic reaction time distributions in gap and overlap tasks.

In many cases the distribution of saccadic reaction times (SRT) deviates considerably from a unimodal distribution and may often exhibit several peaks. We present a statistical approach to determining the number and form of the individual peaks. The overall density of the reaction times fi(t), i = 1...M obtained in M different experiments with the same subject is described as the sum of K basis functions xk(t), k = 1...K with different weights and an error term. A change in the experimental conditions is assumed to cause a change in the weights, not in the basis functions. We minimize the square of the difference (measured data minus approximation), divided by the error of the data. Incrementing K step by step we determine the necessary number of basis functions. This method is applied to data of six subjects tested in different saccade tasks. We detect five different modes: two in the range 80-140 ms (express modes), two in the range 145-190 ms (fast-regular mode) and one at about 230 ms (slow-regular mode). These modes are located at about the same positions for different subjects. The method presented here not only proves statistically the existence of several modes in SRT distributions but also allows the distributions to be described by a few characteristic numbers that go beyond the mean values and standard deviations.

Adult↗
PubMed1998

Cross-spectral analysis of physiological tremor and muscle activity. I. Theory and application to unsynchronized electromyogram.

We investigate the relationship between the extensor electromyogram (EMG) and tremor times series in physiological hand tremor by cross-spectral analysis. Special attention is directed to the phase spectrum and the effects of observational noise. We calculate the theoretical phase spectrum for a second-order linear stochastic process and compare the results to measured tremor data recorded from subjects who did not show a synchronized EMG activity in the corresponding extensor muscle. The results show that physiological tremor is well described by the proposed model and that the measured EMG represents a Newtonian force by which the muscle acts on the hand.

Biomechanical Phenomena↗
PubMed1998

Cross-spectral analysis of physiological tremor and muscle activity. II. Application to synchronized electromyogram.

We investigated the relationship between synchronized muscle activity and tremor time series in (enhanced) physiological tremor by cross-spectral analysis. Special attention was directed to the phase spectrum and its potential to clarify the contribution of reflex mechanisms to physiological tremor. The phase spectra are investigated assuming that the electromyogram (EMG) synchronization was caused by a reflex or a central oscillator. Comparing these results to phase spectra of measured data, we found a significant contribution of reflexes. But reflexes only modify existing peaks in the power spectrum. The main agents of physiological tremor are an efferent pace and the resonant behavior of the biomechanical system.

Biomechanical Phenomena↗
PubMed1998

Numerical methods to determine calcium release flux from calcium transients in muscle cells.

Several methods are currently in use to estimate the rate of depolarization-induced calcium release in muscle cells from measured calcium transients. One approach first characterizes calcium removal of the cell. This is done by determining parameters of a reaction scheme from a fit to the decay of elevated calcium after the depolarizing stimulus. In a second step, the release rate during depolarization is estimated based on the fitted model. Using simulated calcium transients with known underlying release rates, we tested the fidelity of this analysis in determining the time course of calcium release under different conditions. The analysis reproduced in a satisfactory way the characteristics of the input release rate, even when the assumption that release had ended before the start of the fitting interval was severely violated. Equally good reconstructions of the release rate time course could be obtained when the model used for the analysis differed in structure from the one used for simulating the data. We tested the application of a new strategy (multiple shooting) for fitting parameters in nonlinear differential equation systems. This procedure rendered the analysis less sensitive to ill-chosen initial guesses of the parameters and to noise. A locally adaptive kernel estimator for calculating numerical derivatives allowed good reconstructions of the original release rate time course from noisy calcium transients when other methods failed.

Algorithms↗
PubMed1998

Evaluation of forced oscillation technique for early detection of airway obstruction in sleep apnea: a model study.

The forced oscillation technique (FOT) is a non-invasive method which may be suitable for assessing upper airway obstruction in obstructive sleep apnea/hypopnea syndrome (OSAS) patients. The aim of this study was to determine in vitro if FOT can provide an early detection index of total or partial upper airway occlusion. A respiratory system analog was developed which includes an upper airway analog that allows simulation of upper airway collapse (thus mimicking the situation in patients with OSAS). We simulated different degrees of upper airway obstructions ranging from 0 (unobstructed airways) to 1 (total occlusion). Furthermore, we imitated the collapsible upper airway wall by means of elastic membranes with ten different wall compliances ranging from 3.3 x 10(-4) to 1 1/mbar. For the two stiffest rubber membranes (Cwall = 0.01 and 3.3 x 10(-4) l/mbar) the absolute value of the impedance (¿Z¿) showed a marked increase for obstructions greater than 0.6. For the two membranes with the highest wall compliances (Cwall = 0.03 and 1 1/mbar) obstructions with an increase in ¿Z¿ could not be detected before the obstruction reached 0.8. For degrees of obstruction less than 0.6 the phase angle of collapsible membranes with low compliance (stiff airway wall) were about 1.5pi which significantly differed from phase angles of 1.77pi measured in membranes with high compliance (elastic airway wall); p < 0.01. We hypothesized that stiffness of upper airway walls corresponds with their muscle tone, i.e., stiff airway walls are related with high muscle tone and vice versa. Thus, a decrease in upper airway muscle activity would cause an increase of upper airway wall elasticity that enables upper airway collapse. As a consequence the phase angle phi could be expected to change from values characterizing stiff membranes to values characterizing more elastic membranes which could be used as early indicator for obstructive respiratory events. We have frequently observed such changes in morphology of phi(t) data obtained from patients with OSAS.

Airway Obstruction↗
PubMed1997

Saccadic reaction times: a statistical analysis of multimodal distributions.

The distributions of saccadic reaction times (SRT) often deviate from unimodal normal distributions. An excess-mass procedure was used to detect peaks in 963 data sets containing 90,927 reaction times from 170 subjects. About 55% showed one, 30% two, 12% three and 3% four peaks. According to their clustering along the reaction time scale the modes could be classified into express (90-120 msec), fast regular (135-170 msec) and slow regular (200-220 msec) modes. Among the unimodal distributions 29% had peaks in the range of the express mode and 46% had peaks in the range of the fast regular mode. Therefore, 87% of the data sets support the notion of saccadic reaction time distributions being the superposition of three modes. All experimental distributions were fitted by as many gamma distributions as determined by the excess-mass test. The significance of the multimodality for saccade generation processes is discussed.

Fixation, Ocular↗
PubMed1997

Modeling volatility using state space models.

In time series problems, noise can be divided into two categories: dynamic noise which drives the process, and observational noise which is added in the measurement process, but does not influence future values of the system. In this framework, we show that empirical volatilities (the squared relative returns of prices) exhibit a significant amount of observational noise. To model and predict their time evolution adequately, we estimate state space models that explicitly include observational noise. We obtain relaxation times for shocks in the logarithm of volatility ranging from three weeks (for foreign exchange) to three to five months (for stock indices). In most cases, a two-dimensional hidden state is required to yield residuals that are consistent with white noise. We compare these results with ordinary autoregressive models (without a hidden state) and find that autoregressive models underestimate the relaxation times by about two orders of magnitude since they do not distinguish between observational and dynamic noise. This new interpretation of the dynamics of volatility in terms of relaxators in a state space model carries over to stochastic volatility models and to GARCH models, and is useful for several problems in finance, including risk management and the pricing of derivative securities. Data sets used: Olsen & Associates high frequency DEM/USD foreign exchange rates (8 years). Nikkei 225 index (40 years). Dow Jones Industrial Average (25 years).

Artificial Intelligence↗