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Biomedical subjects

J Timmer

Publications and source records attributed to J Timmer.

At least 37 records · Page 2Linked to original sources
PubMed2003

Dynamic synchronisation of central oscillators in essential tremor.

OBJECTIVE: Coherence analysis of electromyography (EMG) signals in essential tremor (ET) suggests that tremor in the right and left arm is induced by independent central oscillators. The sensorimotor cortex seems to be part of the tremor-generating neuronal network in ET. Here, we investigated using electroencephalography (EEG) whether the independence of central oscillators in ET is supported by the analysis of cortical activity. METHODS: In 8 patients with ET, bilateral hand tremor was activated by wrist extension. EMGs from the wrist flexors and extensors were recorded simultaneously with an EEG. EEG-EMG coherence was estimated for 74 epochs of 60 s duration. RESULTS: In 42.6% of the cases, EEG-EMG coherence at the tremor frequency existed only with the contralateral sensorimotor cortex. However, 21.6% of the tremor-EMGs were coherent with EEG activity over both the contralateral and ipsilateral sensorimotor cortex. Bilateral and exclusively contralateral EEG-EMG coherence could alternate within the same recording. Bilateral EEG-EMG coherence was associated with increased right-left EEG-EEG coherence, increased right-left EMG-EMG coherence as well as with increased tremor strength. CONCLUSIONS: In ET, central oscillators in the right and left brain are not entirely independent of each other. They may dynamically synchronise, presumably by interhemispheric coupling via the corpus callosum.

Adult↗
PubMed2003

The seizure prediction characteristic: a general framework to assess and compare seizure prediction methods.

The unpredictability of seizures is a central problem for all patients suffering from uncontrolled epilepsy. Recently, numerous methods have been suggested that claim to predict from the EEG the onset of epileptic seizures. In parallel, new therapeutic devices are in development that could control upcoming seizures provided that their onset is known in advance. A reliable clinical application controlling seizures, consisting of a seizure prediction method and an intervention system, would improve patient quality of life. The question therefore arises as to whether the performance of the seizure prediction methods is already sufficient for clinical applications. The answer requires assessment criteria to judge and compare these methods, but recognized criteria still do not exist. Based on clinical, behavioral, and statistical considerations, we suggest the "seizure prediction characteristic" to evaluate seizure prediction methods. Results of this approach are exemplified by its application to the "dynamical similarity index" seizure prediction method using 582 hours of intracranial EEG data, including 88 seizures.

Electroencephalography↗
PubMed2003

Transfer function analysis for clinical evaluation of dynamic cerebral autoregulation--a comparison between spontaneous and respiratory-induced oscillations.

Oscillations of arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV) can be used for non-invasive assessment of cerebral autoregulation using transfer function analysis. Either spontaneous oscillations (SPO) around 0.1 Hz or respiratory induced oscillations during deep breathing (DB) at a rate of 6/min have been used so far. We investigated 168 patients with severe carotid stenosis or occlusion to evaluate transfer function analysis and compare the SPO and DB approaches. ABP was assessed non-invasively (Finapres), CBFV was measured in the middle cerebral artery using transcranial Doppler sonography. Transfer function phase (P) and gain (G) were extracted from the respective spectra in a low (0.06-0.12 Hz) and high (0.20-0.30 Hz) frequency range (LF, HF) of SPO and from the 0.1 (LF) and 0.2 (HF) Hz peaks induced by DB. For SPO, significant side-to-side differences and differences between groups of severe and critical stenosis were found for P(LF), while P(HF) did not prove to be a significant parameter. G(LF) showed significant side-to-side differences, while G(HF) additionally differed significantly between severe and critical stenosis and occlusion, respectively. For DB, significant side-to-side differences were found for P(LF, HF). Mainly G(HF) differed significantly between the affected and contralateral sides, while both HF and LF gains showed lower values in groups with a higher degree of stenosis. Correlation between G and P values was generally poor. Using Bland-Altman plots a poor inter-method agreement was found mainly for P. Correlations between SPO and DB were higher for G than for P (LF r = 0.64 versus 0.44, HF 0.69 versus 0.28). Analysing reproducibility in 16 patients, only for P(LF, HF) of DB was a highly significant correlation found (Spearman's r up to 0.78). For G(LF, HF) correlations were significant for both SPO and DB with slightly higher r coefficients for SPO. In conclusion, the present study showed that (1) transfer functions P and G represent different information for characterization of dynamic cerebral autoregulation in the frequency domain. (2) Inter-method agreement between DB and SPO is poor for P and moderate for G values. (3) P extracted from DB has a higher reproducibility. (4) The extraction of P and G from the SPO phase spectra is critical and future work on standardizing this process is needed. (5) At present, the DB protocol might be slightly advantageous as a routine diagnostic tool.

Aged↗
PubMed2003

Normalization of DNA-microarray data by nonlinear correlation maximization.

Signal data from DNA-microarray ("chip") technology can be noisy; i.e., the signal variation of one gene on a series of repetitive chips can be substantial. It is becoming more and more recognized that a sufficient number of chip replicates has to be made in order to separate correct from incorrect signals. To reduce the systematic fraction of the noise deriving from pipetting errors, from different treatment of chips during hybridization, and from chip-to-chip manufacturing variability, normalization schemes are employed. We present here an iterative nonparametric nonlinear normalization scheme called simultaneous alternating conditional expectation (sACE), which is designed to maximize correlation between chip repeats in all-chip-against-all space. We tested sACE on 28 experiments with 158 Affymetrix one-color chips. The procedure should be equally applicable to other DNA-microarray technologies, e.g., two-color chips. We show that the reduction of noise compared to a simple normalization scheme like the widely used linear global normalization leads to fewer false-positive calls, i.e., to fewer genes which have to be laboriously confirmed by independent methods such as TaqMan or quantitative PCR.

Algorithms↗
PubMed2003

Estimation of delay times in biological systems.

The problem of delay time estimation in biological systems is addressed with the focus on practical applicability of methods. Four delay time estimators are described: a cross correlation method and three increasingly sophisticated interpretations of the phase spectrum, ranging from a pointwise interpretation of the phase spectrum in terms of a delay to a Hilbert transform method. The four methods are compared through simulation studies showing that, in general, the Hilbert transform method performs best. The methods are then used to estimate delay times in three physiological systems: vestibular stimulation, cerebral autoregulation, and human orthostatic tremor. In all three cases, the Hilbert transform method yields the best results, leading in some cases to physiologically more sensible interpretations of experiments than the other methods.

Homeostasis↗
PubMed2002

Comment on "Kullback-Leibler and renormalized entropies: applications to electroencephalograms of epilepsy patients".

In a recent paper Quian Quiroga et al. [R. Quian Quiroga et al., Phys. Rev. E 62, 8380 (2000)] found renormalized entropy, formerly introduced as a complexity measure for the different regimes of a dynamical system, to be closely related to the standard Kullback-Leibler entropy. They assure this finding by reanalyzing electroencephalographic data of epilepsy patients, previously examined by exclusive use of renormalized entropy [K. Kopitzki et al., Phys. Rev. E 58, 4859 (1998)]. We argue that the general considerations undertaken by the authors and the experimental results do not justify this conclusion.

Data Interpretation, Statistical↗
PubMed2002

Artifact analysis of approximate helical cone-beam CT reconstruction algorithms.

In this paper, four approximate cone-beam CT reconstruction algorithms are compared: Advanced single slice rebinning (ASSR) as a representative of algorithms employing a two dimensional approximation, PI, PI-SLANT, and 3-PI which all use a proper three dimensional back-projection. A detailed analysis of the image artifacts produced by these techniques shows that aliasing in the z-direction is the predominant source of artifacts for a 16-row scanner with 1.25 mm nominal slice thickness. For a detector with isotropic resolution of 0.5 mm, we found that ASSR and PI produce different kinds of artifacts which are almost at the same level, while PI-SLANT produces none of these artifacts. It is shown that the use of redundant data in the 3-PI method suppresses aliasing artifacts efficiently for both scanners.

Algorithms↗
PubMed2002

Essential tremor and cerebellar dysfunction: abnormal ballistic movements.

BACKGROUND: Clinical characteristics reminiscent of cerebellar tremor occur in patients with advanced essential tremor. Ballistic movements are known to be abnormal in cerebellar disease. The hypothesis was proposed that ballistic movements are abnormal in essential tremor, reflecting cerebellar dysfunction. OBJECTIVE: To elucidate the role of the cerebellum in the pathophysiology of essential tremor. METHODS: Kinematic parameters and the triphasic electromyographic (EMG) components of ballistic flexion elbow movements were analysed in patients assigned to the following groups: healthy controls (n = 14), pure essential postural tremor (ET(PT); n = 17), and essential tremor with an additional intention tremor component (ET(IT); n = 15). RESULTS: The main findings were a delayed second agonist burst (AG(2)) and a relatively shortened deceleration phase compared with acceleration in both the essential tremor groups. These abnormalities were most pronounced in the ET(IT) group, which had additional prolongation of the first agonist burst (AG(1)) and a delayed antagonist burst (ANT). CONCLUSIONS: Abnormalities of the triphasic pattern and kinematic parameters are consistent with a disturbed cerebellar timing function in essential tremor. These abnormalities were most pronounced in the ET(IT) group. The cerebellar dysfunction in essential tremor could indicate a basic pathophysiological mechanism underlying this disorder. ET(PT) and ET(IT) may represent two expressions within a continuous spectrum of cerebellar dysfunction in relation to the timing of muscle activation during voluntary movements.

Adult↗
PubMed2001

Delay estimation for cortico-peripheral relations.

In neurophysiology, time delays between concurrently measured time series are usually estimated from the slope of a straight line fitted to the phase spectrum. We point out that this estimate is valid only in the case in which, one signal is a mere time-delayed copy of the other one. We present a procedure for delay estimation that applies to a much wider class of systems with nontrivial phase spectrum like for example lowpass filters. The procedure is based on the Hilbert transform relation between the phase of a linear system and its log gain. The Hilbert transform relation is nonlocal in frequency space, a fact that limits its applicability to experimental data. We explore these limits, and demonstrate that the method is applicable to neurophysiological time series. We present the successful application of the Hilbert transform behavior method to concurrently recorded epicortical brain activity and peripheral tremor. We point out and explain physiologically unreasonable delay estimates given by the traditional method. Finally, we discuss the assumptions underlying the applicability of the Hilbert transform method in the neuroscience context.

Cerebral Cortex↗
PubMed2001

A rational approach to dose reduction in CT: individualized scan protocols.

The aim of this study was to demonstrate that dose reduction and constant image quality can be achieved by adjusting X-ray dose to patient size. To establish the relation between patient size, image quality and dose we scanned 19 patients with reduced dose. Image noise was measured. Four radiologists scored image quality subjectively, whereby a higher score meant less image quality. A reference patient diameter was determined for which the dose was just sufficient. Then 22 patients were scanned with the X-ray dose adjusted to their size. Again, image noise was measured and subjective image quality was scored. The dose reduction compared with the standard protocol was calculated. In the first group the measured noise was correlated to the patient diameter (rho=0.78). This correlation is lost in the second group (rho=-0.13). The correlation between patient diameter and subjective image quality scores changes from rho=0.60 (group 1) to rho=-0.69 (group 2). Compared with the standard protocol, the dose was reduced (mean 28%, range 0-76%) in 19 of 22 patients (86%). Dose reduction and constant noise can be achieved when the X-ray dose is adjusted to the patient diameter. With constant image noise the subjective image quality increases with larger patients.

Anthropometry↗
PubMed2001

Identifying physical properties of a CO2 laser by dynamical modeling of measured time series.

We estimate internal parameters of a Q-switched CO2 laser by fitting trajectories of the four-level model to measured scalar time series. The four-level model is a five-dimensional nonlinear system of ordinary differential equations. A multiple shooting technique is used to construct the unobserved time courses of the population densities and to reveal the dependence of the parameters on the excitation current. For excitations barely above the laser threshold large pulse variations are identified as an effect of small variations of the pump parameter.

Journal Article↗
PubMed2001

Model selection in non-nested hidden Markov models for ion channel gating.

An important task in the application of Markov models to the analysis of ion channel data is the determination of the correct gating scheme of the ion channel under investigation. Some prior knowledge from other experiments can reduce significantly the number of possible models. If these models are standard statistical procedures nested like likelihood ratio testing, provide reliable selection methods. In the case of non-nested models, information criteria like AIC, BIC, etc., are used. However, it is not known if any of these criteria provide a reliable selection method and which is the best one in the context of ion channel gating. We provide an alternative approach to model selection in the case of non-nested models with an equal number of open and closed states. The models to choose from are embedded in a properly defined general model. Therefore, we circumvent the problems of model selection in the non-nested case and can apply model selection procedures for nested models.

Animals↗
PubMed2001

Tremor-correlated cortical activity in essential tremor.

BACKGROUND: In patients with parkinsonian resting tremor, tremor-correlated activity in the contralateral sensorimotor cortex has been studied by both magnetoencephalography (MEG) and electroencephalography (EEG). In essential tremor, MEG failed to detect cortical involvement. The objective of this study was to investigate whether EEG recording can reveal tremor-correlated cortical activity in patients with essential tremor or enhanced physiological tremor. METHODS: Seven patients with essential tremor and three patients with enhanced physiological tremor participated in the study. Unilateral postural tremor was activated by wrist extension on the right or on the left side. Electromyography (EMG) signals arising from the wrist extensor and flexor muscles, and a high-resolution EEG were recorded simultaneously. Coherences between the time series of the rectified tremor EMG and the EEG were estimated. FINDINGS: In five of nine arms with essential tremor, we found highly significant coherences at the tremor frequency between the tremor EMG and the EEG. Isocoherence maps illustrating the topography of significant coherences over the scalp showed that the maximum coherences were located over the contralateral sensorimotor cortex. In the patients with enhanced physiological tremor, we were unable to detect consistent significant corticomuscular coherences at the tremor frequency. INTERPRETATION: Using simultaneous EEG-EMG recordings, we showed that significant corticomuscular coherences at the tremor frequency can be found in essential tremor. This finding contrasts with a recent study based on MEG recordings. The results suggest that the sensorimotor cortex is involved in the generation of essential tremor, in a similar way to that previously shown in parkinsonian resting tremor.

Adult↗
PubMed2001

The use of in ovo electroporation for the rapid analysis of neural-specific murine enhancers.

The identification and characterization of DNA sequences necessary for proper gene expression have provided insights into gene regulation and generated tools useful for further experimentation. Studies of developmentally regulated genes have demonstrated how transcription factors interact at enhancers to generate restricted patterns of expression during embryogenesis. In vertebrates, the pursuit of such studies has relied on the generation of transgenic mice and thus has been limited by the time and expense required generating and characterizing these mice. The recently developed technique of in ovo electroporation allows the rapid introduction of exogenous DNA into developing chicken embryos. Here we have used this technique to introduce DNA containing murine enhancer/reporter constructs into cells of the chicken neural tube, resulting in appropriate expression of the reporter. This technique has the potential to greatly reduce the effort involved in the study of vertebrate enhancers. Furthermore, we have characterized factors such as timing of electroporation, concentration of DNA, and choice of basal promoters and found that they can influence the degree to which expression of enhancer constructs reflects endogenous gene expression.

Animals↗
PubMed2001

Variability of frequency and phase between antagonistic muscle pairs in pathological human tremors.

We investigated the electromyographic activity (EMG) of flexor and extensor muscles with different hand positions in patients with essential (ET) and parkinsonian (PD) tremor. Using a previously developed bootstrap method and standard cross-spectral analysis, we performed statistical tests to assess the effect of hand position on: (1) the frequency of the EMG; and (2) the phase between the EMGs recorded from antagonistic muscle pairs. Frequency as well as phases changed significantly with different positions of the hands but not during the recordings when the position was left unchanged. Besides confirmation that frequency and phase are stationary and reliable parameters during short-term recordings under controlled laboratory conditions, these results are of particular interest for ambulatory long-term tremor measurements. A higher variability of the estimated parameters reported in long-term recordings may perhaps reflect a patient's mobility only. Our study shows that long-term recording systems should have the means to monitor the patient's movements to provide reliable results.

Diagnosis, Differential↗
PubMed2001

Analysis of forced expired volume signals using multi-exponential functions.

Patients with pulmonary disease are often unable to complete forced expiration manoeuvres. The aim of the study is to evaluate whether forced vital capacity (FVC), the volume exhaled at the end of completed forced expiration, can be estimated by extrapolating volume-time curves obtained from uncompleted manoeuvres. The suitability of mono-, bi-, and tri-exponential functions to characterise complete volume-time curves from 50 subjects is investigated. Mono-exponential modelling is insufficient, whereas bi-exponential fitting yields an adequate description for 47 data sets. Tri-exponential models lead to overfitting in all but three cases (normalised sum of least squares: 50.2 +/- 34.5 for mono-, 2.76 +/- 4.11 for bi-, 2.74 +/- 4.19 for tri-exponential modelling; condition number of the correlation matrix: 1.0025 +/- 0.0004 for mono-, 1.08 +/- 0.08 for bi-, 34.7 +/- 100.1 for tri-exponential fitting (mean +/- SD)). Thus, FVC is estimated by the extrapolation of 27 uncompleted spirograms using bi- or tri-exponential models, depending on their accordance with measured data and on the identifiability of their parameters. This algorithm yields unbiased estimates (difference from measured inspiratory vital capacity: 0.01 +/- 0.21 L). This method can be used for investigation of the lung function of subjects who cannot complete the forced expiration manoeuvre.

Adolescent↗
PubMed2000

Selecting relevant electrode positions for classification tasks based on the electro-encephalogram.

The aim is to describe a general approach to determining important electrode positions when measured electro-encephalogram signals are used for classification. The approach is exemplified in the frame of the brain-computer interface, which crucially depends on the classification of different brain states. To classify two brain states, e.g. planning of movement of right and left index fingers, three different approaches are compared: classification using a physiologically motivated set of four electrodes, a set determined by principal component analysis and electrodes determined by spatial pattern analysis. Spatial pattern analysis enhances the classification rate significantly from 61.3 +/- 1.8% (with four electrodes) to 71.8 +/- 1.4%, whereas the classification rate using principal component analysis is significantly lower (65.2 +/- 1.4%). Most of the 61 electrodes used have no influence on the classification rate, so that, in future experiments, the setup can be simplified drastically to six to eight electrodes without loss of information.

Electrodes↗