Measuring-off of Time Intervals: Correlations Between Peculiarities of Their Estimation and Parameters of EEG Phenomena, and Influence of the Subjects' Personality Features

In 76 healthy persons (right-handed men and women), we recorded background EEG and event-related potentials from the C3 and C4 sites; tests were performed within the framework of an experimental situation requiring internal measuring-off of the time intervals. To limit the interval, the tested person had to push a button; he/she did not know the precise value of the interval, which was preset by the experimenter, and was informed only of the lower and upper limits of this interval, 17 to 23 sec. The person obtained information about the coincidence/noncoincidence of the measured-off and preset intervals via visual feedback; the respective signal was presented 2 sec after measuring-off had been completed. In the case where the intervals coincided with each other, the person should confirm this by pushing the button next time (confirming push). We characterized the parameters of the measured-off time interval by the following indices: (i) measuring-off efficacy (accuracy of fitting the preset interval), (ii) estimation tendency (measured-off interval/preset standard interval ratio), and (iii) coefficient of variation (CV) of the measured-off interval. Features of the subject's personality were estimated using Eysenck's (PEN) and Cattell's (16PF) questionnaires. We found correlations of the powers of the background EEG rhythms (beta1, beta2, and alpha/theta ratio) and characteristics of the measured-off time interval. In addition, we observed significant positive correlations between the estimation tendency and extraversion index and between CV of the interval and urge toward domination and protension indices. Negative correlations were observed between the measuring-off efficacy and protension (suspiciousness), between the estimation tendency and anxiety, and between the CV of the interval and age of the subjects. We support the conclusion that correlations between the patterns of EEG potentials, peculiarities of measuring-off of the time interval, and psychological features of the personality are to a noticeable extent mediated by the individual specificity of the neurodynamics.     

肺动脉血流时间间期法评估肺动脉压

为评价肺动脉血流时间间期法评估肺动脉压的价值,本文观察了37例左向右分流先天性心脏病患者。在相同体位及取样容积位置下测量心室射血前期(PEP)、射血时间(ET)、加速时间(AT)、加速度(ACC)、F[F=PEP/(ATET)];计算肺动脉/主动脉血流时间间期比(FPA/FAO),并以各项比例系数与肱动脉压(BAP)的乘积作为肺动脉压的估测值。结果显示:肺动脉/主动脉血流时间间期比与右心导管估测的肺动脉收缩压(PASP)、平均压(PAMP)取得了较好的相关性(r分别为0.84、0.81);ACC次之(r分别为0.72、0.65);PEP/AT较差(r分别为0.53、0.50)。提示:肺动脉/主动脉血流时间间期比为无创定量评估肺动脉压的最佳方法。     

Computation of Time-Specified Tolerance Intervals for Hybrid Time Series with Nonequidistant Sampling,Illustrated for Plasma Growth Hormone

The ideal reference interval for a variable of clinical interest would be specific for all deterministic factors affecting that variable, including the time of sampling in relation to biological rhythms. In particular, growth hormone is characterized in children by circadian and ultradian variability, with high peaks of secretion occurring mainly during sleep. For clinical applications, the use of tolerance intervals has been recommended, and they should substitute, whenever possible, for prediction limits. In the case of hybrid data (time series of data collected from a group of subjects), such a tolerance interval could be very difficult to determine following a parametric approach similar to the procedure used for the computation of prediction intervals, especially when consideration of both within-subjects and among-subjects variances is wanted. Accordingly, we have developed a nonparametric method for the computation of such tolerance intervals. Because the method is based on bootstrap techniques, it does not require the assumption of normality or symmetry in the data and is also more appropriate when dealing with small samples. The method was used to establish time-qualified reference limits for a series of growth hormone sampled around the clock in groups of prepubertal children differentiated according to stature. The use of these tolerance intervals may eliminate many false-positive and false-negative diagnoses that might be obtained when relying on time-unspecified single samples. The provision of such tolerance limits introduces time-specification and time-structure evaluation into prevention, diagnosis, and treatment of growth disorders. (Chronobiology International, 14(4), 409–425, 1997)     

Scheffy's Confidence Intervals in the Models of Analysis of Covariance

Scheffe's confidence intervals for linear functions of some subvectors of a vector of parameters are presented. The considered subvectors are such that covariance matrices of their estimators are known non-negative definite matrices multiplied by unknown positive constants. This property is characteristic of the least squares estimators of vectors of main and interaction effects in the analysis of covariance models of the following experimental designs: split-block, split-plot, completely randomized two-factor design and randomized complete block design. The formulas for confidence intervals for linear functions of vectors of main or interaction effects in the designs mentioned above are given in the paper. The practical example is given as an illustration.     

Individual personality-related characteristics of event-related EEG potentials recorded in an experimental situation requiring production of time intervals

Event-related EEG potentials (ERP) were recorded from 75 tested adult men and women; recording was performed from C3 and C4 points. The experimental situation required internal counting of time intervals limited by two pushes of a button. The experimental paradigm provided a substantial level of uncertainty, and a high level of attention needed to be maintained. The tested subjects were not informed by the experimenter about the precise value of the preset time interval; they knew only its limits, 17–23 sec. The subject obtained information about the agreement or disagreement between the produced interval and its value preset by the experimenter by visual feedback signals obtained 2 sec after termination of counting; in the case of agreement the subject had to perform a confirming (third) push of the button. Pushes were preceded by readiness potentials (RP); contingent negative variation (CNV) developed before the feedback signals, and the latter were accompanied by P300 potentials. Significant positive correlations were found between the parameters of RP and P300 in both hemispheres. In general, ERP were characterized by very high interindividual variability, which in a few respects correlated with the personality-related characteristics of tested subjects evaluated by psychological testing with the use of corresponding questionnaires. In particular, under the experimental conditions used, negative correlations were observed between the RP amplitude and psychotism indices, CNV amplitude and emotional stability; CNV amplitude and extroversive features, and P300 amplitude and domination properties of a person. Positive correlations were observed between the CNV amplitude and autia factor (according to Eysenck’s PEN and Cattell’s 16 PF questionnaires). We suppose that correlations between the personal psychical features and ERP parameters are grounded in both inherited constitutional specificities of the nervous system and neurochemical/structural modifications in the brain determined by the acquired vital experience.     

Adjustment of Prediction Intervals in Nonlinear Regression

By treating the nonlinear model as if it were linear in the parameterization θ in the neighbourhood of the least squares estimate θC, two-sided nominally-q-prediction intervals can be constructed by applying the usual linear model theory. The quadratic approximation of the expected coverage of the prediction intervals is derived for a p-parameter nonlinear model. An adjustment of the nominally-q-prediction intervals is proposed. It is shown that, to the extent that quadratic approximation is adequate, the actual expected coverage of the adjusted prediction intervals is q.     

Processing of Auditory Midbrain Interspike Intervals by Model Neurons

A question central to sensory processing is how signal information is encoded and processed by single neurons. Stimulus features can be represented through rate coding (via firing rate), temporal coding (via firing synchronization to temporal periodicities), or temporal encoding (via intricate patterns of spike trains). Of the three, examples of temporal encoding are the least documented. One region in which temporal encoding is currently being explored is the auditory midbrain. Midbrain neurons in the plainfin midshipman generate different interspike interval (ISI) distributions depending on the frequencies of the concurrent vocal signals. However, these distributions differ only along certain lengths of ISIs, so that any neurons trying to distinguish the distributions would have to respond selectively to specific ISI ranges. We used this empirical observation as a realistic challenge with which to explore the plausibility of ISI-tuned neurons that could validate this form of temporal encoding. The resulting modeled cells—point neurons optimized through multidimensional searching—were successfully tuned to discriminate patterns in specific ranges of ISIs. Achieving this task, particularly with simplified neurons, strengthens the credibility of ISI coding in the brain and lends credence to its role in auditory processing.     

The Analysis of the Geometric Structure of the Delayed Time Used in the Embedding Process in Predicting Chaotic Time Series

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Dynamics of EEG potentials at the beginning of a series of EEG-feedback sessions

We studied changes in the amplitudes of event-related EEG potentials (ERPs) and power spectra of background EEG in the course of a series of EEG-feedback sessions directed toward an increase in the ratio of powers of the α vs θ rhythms. The examined group included 70 volunteers divided into an experimental group (n = 37) and a control group (n = 33). The intensity of acoustic white noise overlapping the musical background served as a feedback signal; it became lower with increase in the above ratio, while in the control group it remained constant. The EEG potentials were recorded from C3 and C4 leads. The ERPs were recorded within a paradigm of measuring time intervals. Within a series of EEG-feedback sessions, the α/θ ratio decreased somewhat both in the control and experimental groups, but in subjects of the latter group this decrease was less significant, and the mean intragroup index became significantly greater than the respective value in the control group after the end of the third session. The EEG-feedback sessions also resulted in significant increases in the amplitudes of early components of the readiness potential in both hemispheres and in the amplitude of the contingent negative variation in the right hemisphere. We conclude that, in most healthy subjects, at least three sessions of α/θ training are necessary to form an effective series providing considerable changes in the pattern of EEG potentials. Neirofiziologiya/Neurophysiology, Vol. 39, No. 1, pp. 88–98, January–February, 2007.     

Modifications of EEG Related to Repeated Static Grasp Efforts Developed by the Hand in Humans

The characteristics of EEG recorded before, in the course, and after three sequential static grasp efforts developed by the right hand were analyzed in 14 healthy volunteers of both sexes, 19 to 56 years old. The grasps were 3 min long, and intervals between the sequential trials were 5 min long. The mean intensity was, as a rule, the greatest in the first trial and decreased, because of fatigue, in the second and third trials. In the course of the grasp effort, significant (P ≤ 0.05) or close to significant decreases in the spectral power were observed in all trials within the alpha2 subrange in some frontal, central, and central/temporal leads. This reaction of desynchronization of alpha2 oscillations probably reflects activation of the sensorimotor cortical zones. Within the above period, the power of alpha2 oscillations increased in the occipital leads. In a few leads of the frontal group, the powers of delta, theta1, theta2, and alpha1 oscillations increased significantly (P < 0.05) in the course of the first trial. Such reaction was not observed in the second and third trials, while the powers of delta and alpha1 ranges increased in the occipital sites (P < 0.05). The powers of delta and theta oscillations increased, as compared with the control values, after the second and third grasps. Such specific EEG modifications in sequential trials can be related to the actions of a novelty factor in the first trial and a fatigue factor in the subsequent trials. The coherence coefficient (CC) of alpha and beta oscillations for symmetric leads usually increased in the course of the grasp. This effect reached a significance level (P < 0.05) for alpha2 oscillations in central, posterotemporal, parietal, and occipital pairs. The CC for beta2 oscillations increased in both temporal lead pairs. A drop in the interhemisphere coherence was more typical of the delta and theta1 ranges. Therefore, changes in the CC values show that the structure of interhemisphere interaction undergoes modifications with the development of the grasp static efforts. Neirofiziologiya/Neurophysiology, Vol. 37, No. 4, pp. 362–371, July–August, 2005.     

Correlations between the psychological peculiarities of an individual and the efficacy of a single neurofeedback session (by the EEG characteristics)

Modifications of different EEG rhythms induced by a single neurofeedback session (by the EEG characteristics) directed toward an increase in the ratio of the spectral powers (SPs) of the α vs θ oscillations were compared with the psychological characteristics of the tested subjects (the group included 30 persons). A generally accepted neurofeedback technique was used; the intensity of acoustic white noise served as the feedback signal. EEG potentials were recorded from the C3 and C4 leads. Psychological testing was carried out using Eysenck’s (EPQ), Rusalov’s (OST), and (16 PF) questionnaires. The directions of changes in the SPs of EEG frequency components were found to significantly correlate with some individuality-related peculiarities of the tested subjects. The SP of the δ rhythm correlated with the EPQ scale “neuroticism,” OST scale “social plasticity,” and 16 PF factors H (“parmia”), I (“premsia”), and Q₃ (“self-control of behavior”). The SP of the θ component demonstrated correlations with the OST scales “ergisity,” “plasticity,” and “social temp” and with 16 PF factors M (“autia”), Q₄ (“frustration”), and Q1 (“exvia”). The SP of the α rhythm correlated with 16 PF factors Q₃ (“self-control of behavior”), G (“strength of superEgo”), O (“hypothymia”), L (“protension”), and N (“shrewdness”). The SP of the β rhythm correlated with the OST scale “emotionality,” while that of the γ rhythm showed correlations with the 16 PF indices L (“protension”) and M (“autia”). Changes in the ratio of the α vs θ SPs correlated with the EPQ scale “neuroticism.” Thus, our data confirm the statement that a high individual variability of the results of a single (first in the series) neurofeedback session is to a great extent related to peculiarities of the individual psychological pattern of the subject. Neirofiziologiya/Neurophysiology, Vol. 38, No. 3, pp. 239–247, May–June, 2006.     

The Effect of Activity on the Waking Temperature Rhythm in Humans

Nine healthy female subjects were studied when exposed to the natural light-dark cycle, but living for 17 “days” on a 27h day (9h sleep, 18h wake). Since the circadian endogenous oscillator cannot entrain to this imposed period, forced desynchronization between the sleep/activity cycle and the endogenous circadian temperature rhythm took place. This enabled the effects of activity on core temperature to be assessed at different endogenous circadian phases and at different stages of the sleep/activity cycle. Rectal temperature was measured at 6-minute intervals, and the activity of the nondominant wrist was summed at 1-minute intervals. Each waking span was divided into overlapping 3h sections, and each section was submitted to linear regression analysis between the rectal temperatures and the total activity in the previous 30 minutes. From this analysis were obtained the gradient (of the change in rectal temperature produced by a unit change in activity) and the intercept (the rectal temperature predicted when activity was zero). The gradients were subjected to a two-factor analysis of variance (ANOVA) (circadian phase/ time awake). There was no significant effect of time awake, but circadian phase was highly significant statistically. Post hoc tests (Newman-Keuls) indicated that gradients around the temperature peak were significantly less than those around its trough. The intercepts formed a sinusoid that, for the group, showed a mesor (±SE) of 36.97 (±0.12) and amplitude (95% confidence interval) of 0.22°C (0.12°C, 0.32°C). We conclude that this is a further method for removing masking effects from circadian temperature rhythm data in order to assess its endogenous component, a method that can be used when subjects are able to live normally. We suggest also that the decreased effect of activity on temperature when the endogenous circadian rhythm and activity are at their peak will reduce the possibility of hyperthermia.     

Correlations of the Peculiarities of the Motivational Sphere and Characteristics of Event-Related EEG Potentials in Humans

We studied the relations between generalized characteristics of the state of the motivational sphere, the levels of need for achievements (N-Ach) and achievement motivation (AchM) typical of an individual, and the parameters of cerebral event-related potentials (ERPs). The examined group included 70 adults of both sexes. The ERPs were recorded in the course of realization of two behavioral test acts with motor components. In task А, the subject should press a button with the minimum delay with respect to an imperative signal preceded by a warning signal (with the measurement of the time of sensorimotor reaction); in this case, the contingent negative variation (CNV) and Р300 potential were recorded. Under conditions of task B, the subject should measure a definite time interval limiting the latter by two pushings of the button; in this case, the readiness potential (RP) was recorded in addition to CNV and Р300. The ERPs were recorded in the С3 and С4 leads (according to the 10-20 system). The peculiarities of the motivational sphere were diagnosed using Orlov’s and Mechrabian’s questionnaires. We found that a relatively high amplitude of the early CNV component (СNV-O) and low amplitudes of the integral CNV and Р300 in task A and a low amplitude of the RP can serve as task B-related EEG markers of a high NA level. In task A, high levels of the AchM correlated with higher amplitudes of the CNV and Р300, and amplitudes of these potentials were higher in the left hemisphere. The observed interrelations were probably determined by a considerable dependence of the N-Ach and AchM characteristics, on the one hand, and CNV amplitude parameters, on the other hand, on the hereditary factors, in particular neurochemical ones. It is obvious that such peculiarities of the neurodynamic constitution of an individual are, to a considerable extent, determined by the specificity of organization and functioning of a few neurotransmitter (in particular aminergic) and neurohumoral systems.     

The Use of a Symbol Processing Computer Language in Point Estimation of Parameters and in Construction of Confidence Intervals

This paper presents a method to generate automatically computer programs which are necessary for parameter estimation, hypothesis tests and construction of confidence intervals by the maximum likelihood method. The spectral or density function of the random variable is arbitrary, but must be known and given in closed form. The programming language used is the symbol processing language LIBAFORM, whose statements are interpreted by a package of LISP-routines. The application of the method is illustrated by the analysis of a linear model whose residuals follow a logarithmic F-distribution, and the analysis of a dose-response curve.     

Correlation of the characteristics of evoked EEG potentials with individual peculiarities of attention in children

We studied correlations of the main parameters of evoked EEG potentials (EP) with individual characteristics of attention in children and teenagers. One hundred and one healthy children (dextrals) took part in the tests. Among them, 26 and 30 children were 5 to 7 and 10 to 12 years old, while the third age group included 45 teenagers (15 to 16 years old). We recorded EP and measured the time of a sensorimotor reaction in the following experimental paradigm. Its program provided automated presentation of a pair of acoustic signals, preliminary and imperative; the subject had to perform a motor reaction, pushing a button with the right thumb, with a minimum delay after the second stimulus. Visual feedback signals informed the subject about the successful or inadequate performance of the reaction (time of reaction was shorter than or exceeded a limit value). Indices characterizing the level of attention were estimated using Find and delete and Schultes tables techniques. A well-manifested N2 component of the EP related to the preliminary signal was a specific feature in the group of 5- to 7-year-old children, while the contingent negative variation (CNV) preceding the motor reaction was poorly developed in this group. The best characteristics of attention in these and older (10 to 12 years old) children were typical of subjects with maximally expressed N1-P2 waves. In teenagers, the best attention was typical of subjects with the highest-amplitude P1 and P2 components, CNV, and P300 wave and with the lowest amplitude of the N1 component.Neirofiziologiya/Neurophysiology, Vol. 36, No. 4, pp. 313–321, July–August, 2004.This revised version was published online in April 2005 with a corrected cover date.     

Humans and viruses determine the nature of virus vaccine production processes

Vaccine production processes result from the interaction between humans with a particular cell and virus system. The factors that control progress lie not only in the nature of the virus and animal cell but also in the history of the environment in which the process is to be developed. This latter constraint strongly influences the nature of the technical process that is chosen for the production of the vaccine rather than the achievement of efficiency based on one or other of the many possible engineering parameters of the virus production process. In addition to this it is also clear that we have much to learn about the production of viruses from animal cells in culture and that we may be aided by changing our present paradigm of the virus as a cellular enemy to that of the viruses are the cell's best friend.Paper presented at Cell Engineering III Meeting, Florida, 1992.     

Quantitative Models of the Dose-Response and Time Course of Inhalational Anthrax in Humans

Anthrax poses a community health risk due to accidental or intentional aerosol release. Reliable quantitative dose-response analyses are required to estimate the magnitude and timeline of potential consequences and the effect of public health intervention strategies under specific scenarios. Analyses of available data from exposures and infections of humans and non-human primates are often contradictory. We review existing quantitative inhalational anthrax dose-response models in light of criteria we propose for a model to be useful and defensible. To satisfy these criteria, we extend an existing mechanistic competing-risks model to create a novel Exposure–Infection–Symptomatic illness–Death (EISD) model and use experimental non-human primate data and human epidemiological data to optimize parameter values. The best fit to these data leads to estimates of a dose leading to infection in 50% of susceptible humans (ID₅₀) of 11,000 spores (95% confidence interval 7,200–17,000), ID₁₀ of 1,700 (1,100–2,600), and ID₁ of 160 (100–250). These estimates suggest that use of a threshold to human infection of 600 spores (as suggested in the literature) underestimates the infectivity of low doses, while an existing estimate of a 1% infection rate for a single spore overestimates low dose infectivity. We estimate the median time from exposure to onset of symptoms (incubation period) among untreated cases to be 9.9 days (7.7–13.1) for exposure to ID₅₀, 11.8 days (9.5–15.0) for ID₁₀, and 12.1 days (9.9–15.3) for ID₁. Our model is the first to provide incubation period estimates that are independently consistent with data from the largest known human outbreak. This model refines previous estimates of the distribution of early onset cases after a release and provides support for the recommended 60-day course of prophylactic antibiotic treatment for individuals exposed to low doses.