What can Be inferred from surrogate data testing?
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Journal Article↗
Biomedical subjects
J Timmer
Publications and source records attributed to J Timmer.
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↗
The effects of non-identifiability on testing for detailed balance in aggregated Markov models for ion-channel gating.
Aggregated Markov models are a widely used tool to model patch clamp data measured from single ion channels. These channels must obey the principle of detailed balance in thermodynamic equilibrium; otherwise, the channel is driven by an external source of energy. We investigate the power of a likelihood ratio test for detailed balance for a number of data points which is in the order of magnitude of patch clamp experiments. We show that for certain models with nearly equal dwell times, a test for detailed balance suffers from a loss of power to detect violations of detailed balance which is due to the non-identifiability of the transition rates for models with equal dwell times.
Computer Simulation↗
Detection of obstructive sleep apnea by analysis of phase angle using the forced oscillation signal.
Pharyngeal collapse in patients with obstructive sleep apnea syndrome (OSAS) is linked to decreased upper airway muscle activity. We hypothesised that decreased muscle activity causes decreased stiffness of the upper airway wall and assumed that a decrease in wall stiffness would result in a change point (CP) of the morphology of phase angle time series phi(t) obtained by forced oscillation technique (FOT). We developed an algorithm to detect CPs in φ(t) and investigated phi(t) data measured in parallel to all-night polysomnography in seven patients. A total of 2724 CPs were detected by algorithm. The CPs were marked on the polysomnograms and compared with polysomnogram scoring performed jointly by three sleep expert physicians. A total of 791 (67%) of the 1172 handscored respiratory events showed a CP in phi(t) within a time interval of 8 sec before and 6 sec after the marked onset. A total of 672 (57%) respiratory events were detected at an earlier time by algorithm, and 119 (10%) were algorithmically detected later. The average detection time by the CP algorithm was 4.0+/-1.1 sec earlier than the manual scoring. We conjecture that a CP in phi(t) indicates a change in upper airway collapsibility and that phi(t) might be a potentially useful parameter for detection of impending upper airway obstruction.
Adult↗
Tremor-correlated cortical activity detected by electroencephalography.
OBJECTIVE: In this study we investigated whether cortical activity related to Parkinsonian resting tremor can be detected by electroencephalography (EEG). METHODS: Seven patients with idiopathic Parkinson's disease suffering from unilateral tremor participated in the study. Electromyography (EMG) signals arising from the wrist extensor and flexor muscles as well as a high resolution EEG were recorded simultaneously. Coherencies between EEG and EMG were calculated. RESULTS: In all patients, we found highly significant coherencies at the tremor frequency or its first harmonic between the tremor EMG and contralateral EEG channels. There were no significant coherencies between the tremor EMG and ipsilateral EEG channels. Isocoherency maps illustrating the topography of the coherencies over the scalp showed that the maximum coherencies were situated over the cortical motor areas. In one case, a high coherency was also found over the parietal cortex. CONCLUSIONS: The results show for the first time that tremor-correlated cortical activity can be detected by electroencephalography. The findings underline that motor areas of the cerebral cortex are involved in the neuronal network generating resting tremor in Parkinson's disease.
Aged↗
Linear and nonlinear time series analysis of the black hole candidate cygnus X-1
We analyze the variability in the x-ray lightcurves of the black hole candidate Cygnus X-1 by linear and nonlinear time series analysis methods. While a linear model describes the overall second order properties of the observed data well, surrogate data analysis reveals a significant deviation from linearity. We discuss the relation between shot noise models usually applied to analyze these data and linear stochastic autoregressive models. We debate statistical and interpretational issues of surrogate data testing for the present context. Finally, we suggest a combination of tools from linear and nonlinear time series analysis methods as a procedure to test the predictions of astrophysical models on observed data.
Journal Article↗
The n-PI-method for helical cone-beam CT.
A new class of acquisition schemes for helical cone-beam computed tomography (CB-CT) scanning is introduced, and their effect on the reconstruction methods is analyzed. These acquisition schemes are based on a new detector shape that is bounded by the helix. It will be shown that the data acquired with these schemes are compatible with exact reconstruction methods, and the adaptation of exact reconstruction algorithms to the new acquisition geometry is described. At the same time, the so-called PI-sufficiency condition is fulfilled. Moreover, a good fit to the acquisition requirements of the various medical applications of cone-beam CT is achieved. In contrast to other helical cone-beam acquisition and reconstruction methods, the n-PI-method introduced in this publication allows for variable pitches of the acquisition helix. This additional feature will introduce a higher flexibility into the acquisition protocols of future medical cone-beam scanners. An approximative n-PI-filtered backprojection (n-PI-FBP) reconstruction method is presented and verified. It yields convincing image quality.
Image Processing, Computer-Assisted↗
Detection of sleep apnea with the forced oscillation technique compared to three standard polysomnographic signals.
BACKGROUND: The forced oscillation technique (FOT) allows analysis of the upper airway impedance and, hence, detection of obstructive sleep apnea. OBJECTIVE: To evaluate FOT with respect to sensitivity and to specificity in online detection of sleep-disordered breathing patterns and to compare algorithmic onset detection time with manual onset time markers of staff physicians. METHODS: We compared the absolute value mid R:Zmid R: of the impedance with three routinely obtained polysomnographic signals - nasal airflow V(nasal), thoracic excursion Thox and esophageal pressure P(es) - by retrospective analysis of the diagnostic polysomnograms of 51 patients. For each signal we evaluated algorithms for online detection of respiratory events. For each out of five apnea classes, 50 respiratory events marked by staff physicians were drawn randomly from the 51 polysomnograms to optimize the online detection algorithms (learning set). The algorithm analyzes relative changes of signal baseline and amplitude. Again 50 respiratory events were drawn randomly for each apnea class to examine to what extent it is possible to detect event onsets with the algorithms (test set). RESULTS: The sensitivity of the signals varied between 56 and 94% and was on average 74%. The specificity was 96 +/- 1.5% on average. The onset was detected 4-6 s after the initially evaluated onset of the staff physicians. CONCLUSION: We conclude that nasal airflow and FOT are equivalent sensitive measurands for detection of respiratory events.
Adult↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
Parkinsonian and essential tremors: different entities or different manifestations of the same disorder?
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Animals↗
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↗
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↗