Dynamical correlation of non-stationary signals in time domain—A comparative study

In a thorough study, the multitaper (MTM) and the extended continuous wavelet-transform (CWT) coherence-analysis methods were compared in terms of there application in determining the dynamics from the electroencephalogram (EEG) and electromyogram (EMG) signals of patients with Parkinsonian tremor. The main aim of the study in a biological point of view is to analyze whether the basic tremor frequency and its “first harmonic” frequency of Parkinsonian tremor are really harmonically related or are in fact distinct processes.The extension of the CWT is achieved by using a Morlet wavelet as the analysis window with an adjustable relative bandwidth which gives the flexibility in setting a desired frequency resolution. In order to obtain a perspective view of the two methods, they were applied to two different model signals to determine their actual threshold in detecting short-lived changes in the analysis of non-stationary signals and to determine their noise thresholds by adding external noise to the signals to test the reduction in coherence to be not merely due to the random fluctuations in stochastic signals. Beyond applying an autoregressive 2nd-order and a coupled van der Pol model system, however, also true EEG and EMG data from five Parkinson patients were used. The results were compared in terms of the time and frequency resolutions of these two methods, and it was determined that the multitaper method was able to detect reduction in power and coherence as short as 1 s. The extended CWT analysis only revealed gaps that were longer than 3 s.The time gaps in the coherence indicate the loss of connection between the cortex and muscle during the respective time intervals. This more accurate analysis of the MTM was also seen in the dynamical EEG–EMG coherence at the tremor frequency and its “first harmonic” of Parkinsonian patients.In terms of our “biological” aim, this shows distinct prevalence of the corticomuscular coupling at those frequencies over time. Applying this method to biological data reveals important aspects about their dynamics, e.g., the distinct dynamics between basic frequency and “first harmonic” frequency over time in Parkinsonian tremor.     

Effectively desynchronizing deep brain stimulation based on a coordinated delayed feedback stimulation via several sites: a computational study

In detailed simulations we present a coordinated delayed feedback stimulation as a particularly robust and mild technique for desynchronization. We feed back the measured and band-pass filtered local filed potential via several or multiple sites with different delays, respectively. This yields a resounding desynchronization in a naturally demand-controlled way. Our novel approach is superior to previously developed techniques: It is robust against variations of system parameters, e.g., the mean firing rate. It does not require time-consuming calibration. It also prevents intermittent resynchronization typically caused by all methods employing repetitive administration of shocks. We suggest our novel technique to be used for deep brain stimulation in patients suffering from neurological diseases with pathological synchronization, such as Parkinsonian tremor, essential tremor or epilepsy.     

Corticomuscular Transmission of Tremor Signals by Propriospinal Neurons in Parkinson's Disease

Cortical oscillatory signals of single and double tremor frequencies act together to cause tremor in the peripheral limbs of patients with Parkinson''s disease (PD). But the corticospinal pathway that transmits the tremor signals has not been clarified, and how alternating bursts of antagonistic muscle activations are generated from the cortical oscillatory signals is not well understood. This paper investigates the plausible role of propriospinal neurons (PN) in C3–C4 in transmitting the cortical oscillatory signals to peripheral muscles. Kinematics data and surface electromyogram (EMG) of tremor in forearm were collected from PD patients. A PN network model was constructed based on known neurophysiological connections of PN. The cortical efferent signal of double tremor frequencies were integrated at the PN network, whose outputs drove the muscles of a virtual arm (VA) model to simulate tremor behaviors. The cortical efferent signal of single tremor frequency actuated muscle spindles. By comparing tremor data of PD patients and the results of model simulation, we examined two hypotheses regarding the corticospinal transmission of oscillatory signals in Parkinsonian tremor. Hypothesis I stated that the oscillatory cortical signals were transmitted via the mono-synaptic corticospinal pathways bypassing the PN network. The alternative hypothesis II stated that they were transmitted by way of PN multi-synaptic corticospinal pathway. Simulations indicated that without the PN network, the alternating burst patterns of antagonistic muscle EMGs could not be reliably generated, rejecting the first hypothesis. However, with the PN network, the alternating burst patterns of antagonist EMGs were naturally reproduced under all conditions of cortical oscillations. The results suggest that cortical commands of single and double tremor frequencies are further processed at PN to compute the alternating burst patterns in flexor and extensor muscles, and the neuromuscular dynamics demonstrated a frequency dependent damping on tremor, which may prevent tremor above 8 Hz to occur.     

A leukocyte culture and chromosome preparation technique for avian species

Summary A technique for avian leukocyte culture and chromosome analysis is described. The method is simple and allows karyotypic analysis by a variety of chromosome banding methods. It is applicable to a wide variety of species and may be useful in determining the genetic sex of monotypic species in captivity or for population studies of specimens in the wild. This work was supported by Medical Research Council (Canada) Grant MA-4655. B. M. B. is a recipient of a Medical Research Council Fellowship.     

Application of optimal multichannel filtering to simulated nerve signals

The optimal linear filters derived in the preceding paper can be thoroughly evaluated using computer simulations, based on the properties of mammalian sensory and motor nerve fibres. Using reasonable values for action potential waveforms, conduction velocity and electrode noise, good separation of motor and sensory signals can be obtained. The performance of the filters is degraded by 1) increasing the electrode noise, 2) introducing dispersion in the conduction velocities, or 3) variation in the waveform of the action potentials from that used in designing the filters. However, the variations needed to seriously degrade performance are quite large compared to those which are likely to be present in mammalian nerves. Use of these filters to distinguish different classes of sensory (or motor) signals based on conduction velocity is discussed.This work was partially supported by the Technical Research Council of Denmark (Grant 516-6703.E406), the Medical Research Council of Canada (Grant MRC-MT3307) and the National Research Council of Canada (Grant NRC A-4345)     

Mathematical analysis of optimal multichannel filtering for nerve signals

This paper extends recent analyses (Roberts and Hartline, 1975; Ouztöreli and Stein, 1977) of optimal linear filters for separating neural signals from more than one electrode site. Roberts and Hartline's result, using a matched filter criterion, represents one of a class of optimal filters with different, but symmetrical, output waveforms derived by Ouztöreli and Stein (1977). Another narrow bandwidth filter of this class will give the optimal results according to an energy criterion, but may be less useful in practical situations.This work was partially supported by the Medical Research Council of Canada (Grant MRC-MT3307), the Technical Research Council of Denmark (Grant 516-6703 E406) and the National Research Council of Canada (Grant NRC A-4345)     

Optimal filtering of nerve singnals

Recording from multiple electrodes at different sites along a peripheral nerve permits the application of powerful filtering methods to extract the activity of populations of fibres within the nerve which differ in temporal or spectral characteristics. The design of optimal linear filters is initially treated as a general problem in the calculus of variations in which the signals from one population of nerve fibres are extracted so as to minimize those from a second population of nerve fibres or from other sources (noise). A particularly important application arises when the signals at two electrodes are related by weighting functions. In the simplest example the weighting function represents the time delay for nerve impulses to conduct from one electrode to the other, but explicit results are also derivable when there are a range of conduction delays with probabilities distributed according to well-known functions such as the sinc² function.This work was partially supported by the National Research Council of Canada and Medical Research Council of Canada by Grant NRC A-4345 to MNO and Grant MRC MA-3307 to RBS through the University of Alberta     

Evolutionary games for spatially dispersed populations

An evolutionary game model is developed that incorporates both spatial dispersion and density effects in the evolutionary dynamic. It is shown that a stable equilibrium (e.g. an evolutionarily stable strategy) of the non-dispersed frequency dynamic becomes a stable equilibrium of the larger system if population density stabilizes at these fixed frequencies. It is also shown, by example, that other equilibria, whose frequencies change from one location to another, may appear when dispersal rates are relatively small.Research supported by Natural Sciences and Engineering Research Council of Canada Operating Grant A6187Research supported by Natural Sciences and Engineering Research Council of Canada Operating Grant A7822     

Fluorescence coupling across lipid bilayer membranes

Summary An energy transfer between donor and acceptor fluorophores across single lipid bilayer membranes is demonstrated. Anilino-naphthalene sulfonate is used as the donor chromophore: its fluorescence is enhanced by the presence of lipid and thus indicates association with the purely lipid membranes of our preparation of vesicles in suspension. Light emit ted by the donor molecules excites fluorescence of acriflavine, a suitable acceptor enclosed inside the vesicles. Absorption and fluorescence spectra of this system, in its components and as a whole, are presented in evidence for an energy transfer.Supported by a grant from the Medical Research Council of Canada. The results of this work were presented, in part, at the 17th Annual Meeting of the Biophysical Society, February 27–March 2, 1973, Columbus, Ohio.Scholar of the Medical Research Council of Canada.     

Theoretical and experimental derivation of the function relating the size distribution of spherical particles in a volume element to that obtained from images of sections taken through it

Summary The mathematical formulation of three classes of theories concerning the problem outlined in the title of this study was critically assessed and experimentally evaluated. It was found that only one class of the theories describes the relation between the distribution of particles in a volume element to that observed in sections through this volume in a satisfactory way. The errors in the remaining two classes could be traced and the corrections made after a mathematically rigorous analysis brought these theories to comply with a model which, as we could prove experimentally, deserves a high level of confidence.Supported by a grant from the Medical Research Council of Canada.In partial fulfillment of the requirements for obtention of the degree of a Master of Science. Supported by a Studentship from the Medical Research Council of Canada.Scholar of the Medical Research Council of Canada.     

Ranking species based on the components of equivocation information

Summary The results presented in this paper suggest that for species to be weighted according to their suitability to characterize isolated groups of relevés in a phytosociological table, the equivocation information may serve as a suitable weight. The appropriate formulations are derived and computed for some data from a salt marsh community.Contribution from the Working Group for Data-Processing in Phytosociology, International Society for Vegetation Science.The author thanks the National Research Council of Canada for support given.     

The dye-exclusion test for cell viability: Persistence of differential staining following fixation

Summary A method is described whereby the differential staining of viable and nonviable unfixed cells, as observed by the dye-exclusion method, can be reproduced in glutaraldehyde-fixed preparations by staining with alcian blue. The results suggest that the differential staining is due, at least in part, to structural differences that are retained following aldehyde fixation. This work was supported by grants from the National Cancer Institute of Canada and the National Research Council of Canada. Recipient of a Research Studentship from the National Cancer Institute of Canada.     

The effects of multiple reflex pathways on the oscillations in neuro-muscular systems

Summary A model of mammalian neuro-muscular systems described previously (Ouztöreli and Stein, 1975) has been extended to include multiple reflex pathways, as have been shown to exist in primates, including man (Milner-Brown et al., 1975). A number of general mathematical properties of the extended system are described. In the final section, using computer solutions, it is shown that the presence of multiple reflex pathways can effectively reduce the tendency for oscillation which will exist if high reflex gain were concentrated in a single pathway. High loop gain is desirable for good control in any negative feedback system, so the presence of multiple reflex pathways could improve reflex control, while limiting the magnitude of tremor or other unwanted oscillations in neuromuscular systems.This work was partly supported by the National Research Council of Canada (Grant NRC-A4345) and by the Medical Research Council of Canada (Grant MRC-MA 3307) through the University of Alberta.     

Clinicians’ Tendencies to Under-Rate Parkinsonian Tremors in the Less Affected Hand

The standard assessment method for tremor severity in Parkinson’s disease is visual observation by neurologists using clinical rating scales. This is, therefore, a subjective rating that is dependent on clinical expertise. The objective of this study was to report clinicians’ tendencies to under-rate Parkinsonian tremors in the less affected hand. This was observed through objective tremor measurement with accelerometers. Tremor amplitudes were measured objectively using tri-axis-accelerometers for both hands simultaneously in 53 patients with Parkinson’s disease during resting and postural tremors. The videotaped tremor was rated by neurologists using clinical rating scales. The tremor measured by accelerometer was compared with clinical ratings. Neurologists tended to under-rate the less affected hand in resting tremor when the contralateral hand had severe tremor in Session I. The participating neurologists corrected this tendency in Session II after being informed of it. The under-rating tendency was then repeated by other uninformed neurologists in Session III. Kappa statistics showed high inter-rater agreements and high agreements between estimated scores derived from the accelerometer signals and the mean Clinical Tremor Rating Scale evaluated in every session. Therefore, clinicians need to be aware of this under-rating tendency in visual inspection of the less affected hand in order to make accurate tremor severity assessments.     

Atrial natriuretic factor in the impulse-conduction system of rat cardiac ventricles

Summary A complex network of atrial natriuretic factor-producing cells has been delineated by biochemical and morphological techniques in the rat ventricular myocardium. The chordae tendineae spuriae (CTS; false tendons) contain ANF mRNA and the ANF propeptide (Asn 1-Tyr 126) as assessed by Northern blot analysis, high-pressure liquid chromatography and immunohisto- and -cytochemistry, using three different affinity-purified antibodies: monoclonal and polyclonal antibodies against C-terminal ANF (Arg 101-Tyr 126) and polyclonal antibodies against N-terminal ANF (Asp 11-Ala 37). Two types of cells harboring ANF-containing secretory granules constitute the CTS: the majority (Purkinje type I) have ultrastructural similarities with both atrial and classical Purkinje fibers. Purkinje type-II fibers resemble working ventricular cardiocytes. Both cell types harbor a large paranuclear Golgi complex. The subendocardial Purkinje network is also made up of these two cell types. In this location, Purkinje type-I fibers form cable-like structures while Purkinje type-II fibers are either located beneath the former or abut directly on the endocardium. The latter are not separated from adjacent working ventricular cardiocytes by connective tissue septa. Coronary arteries and arterioles, as in birds, are surrounded by a cushion of Purkinje type-II fibers which blend with the surrounding myocardium. These results indicate that, in the rat, the entire intraventricular conduction system is constituted of endocrine cells producing ANF.Supported by a Medical Research Council of Canada Group Grant to the Multidisciplinary Research Group on Hypertension, by the National Research Council of Canada, the Pfizer Company (England), Bio-Méga Inc. and the Canadian Heart Foundation     

Characterizing Deep Brain Stimulation effects in computationally efficient neural network models

Background  

Recent studies on the medical treatment of Parkinson's disease (PD) led to the introduction of the so called Deep Brain Stimulation (DBS) technique. This particular therapy allows to contrast actively the pathological activity of various Deep Brain structures, responsible for the well known PD symptoms. This technique, frequently joined to dopaminergic drugs administration, replaces the surgical interventions implemented to contrast the activity of specific brain nuclei, called Basal Ganglia (BG). This clinical protocol gave the possibility to analyse and inspect signals measured from the electrodes implanted into the deep brain regions. The analysis of these signals led to the possibility to study the PD as a specific case of dynamical synchronization in biological neural networks, with the advantage to apply the theoretical analysis developed in such scientific field to find efficient treatments to face with this important disease. Experimental results in fact show that the PD neurological diseases are characterized by a pathological signal synchronization in BG. Parkinsonian tremor, for example, is ascribed to be caused by neuron populations of the Thalamic and Striatal structures that undergo an abnormal synchronization. On the contrary, in normal conditions, the activity of the same neuron populations do not appear to be correlated and synchronized.     

Species ordering on a variance criterion

Summary A technique for ordering, to identify diagnostic species, based on variance ratios has been described. The method was illustrated with river terrace data.The author would like to thank Dr. László Orlóci for permission to use the vegetation data employed in the illustration of the algorithm. This work was supported by a grant from the National Research Council of Canada.     

Purification and properties of two distinct groups of ADH isozymes from Chinese hamster liver

Two major classes of alcohol dehydrogenase isozymes have been purified from Chinese hamster liver. The two isozyme classes have the same subunit molecular weights but different electrophoretic mobilities. They have a similar range of substrates but different KROM values and sensitivities to the inhibitor pyrazole. The ADHs are immunologically related as determined by Ouchterlony double diffusion experiments. These results suggest that the isozymes are encoded by different structural gene loci derived from a common ancestral gene.Financial support was provided by the National Cancer Institute of Canada and the Medical Research Council of Canada, Grant MT4860. J.-P. Thirion is a Research Scholar of the Science Research Council of Quebec.     

Pathological tremors as diffusional processes

 Two types of pathological tremors, essential and Parkinsonian, are studied using dynamical systems theory. It is shown that pathological tremors can be characterized as diffusional processes. The time-scale range for the diffusional scaling law to be valid starts from about one to several tens of the mean oscillation period. This time-scale range contrasts sharply with the predictable time scale for deterministic chaos, which is usually only a small fraction of the mean oscillation period. The diffusions in pathological tremors are usually anomalous. A number of quantities are designed to characterize the diffusions in the tremor. Their relevance to potential clinical applications is discussed. It is argued that in order to discriminate between Parkinsonian and essential tremors, quantities not of purely dynamical origin may be more useful, since purely dynamical quantities emphasize more the dynamical similarities between the two types of tremors. Received: 30 May 2001 / Accepted in revised form: 6 November 2001     

Constant-rate stocking of predator-prey systems

We examine the qualitative effects of constant-rate stocking of either or both species in a predator-prey system. The hypotheses are made as mild as possible so that several types of systems with different qualitative alternatives may be studied.Sponsored by the United States Army under Contract No. DAAG29-75-C-0024 and the National Research Council of Canada under Grant No. A-3138.The authors wish to thank Mr. Al Mackenzie for drawing the numerous figures which appear in this paper.