Dmitriy Melkonian

Sex differences in adult ADHD: a double dissociation in brain activity and autonomic arousal

It is now estimated that up to one-half of attention deficit hyperactivity disorder (ADHD) children continue to manifest symptoms in adulthood. A striking discrepancy between juvenile and adult populations is the increasing proportion of females with an ADHD diagnosis. To shed light on the psychophysiological mechanisms underlying adult ADHD, electroencephalography (EEG) and electrodermal index of arousal (skin conductance level or SCL) measures were employed under conditions of eyes-closed resting activity. Quantitative EEG (QEEG) and SCL were measured simultaneously and continuously (2 min) in 35 ADHD adults (21 males, 14 females) and their age- and sex-matched controls. As a group ADHD adults were found to have EEG and SCL deviations consistent with previous adolescent and juvenile studies. However, adult males (but not females) with ADHD showed increased EEG theta activity. By contrast, adult females (but not males) with ADHD were autonomically hypo-aroused (decreased SCL). These results suggest that distinct mechanisms may underpin adult ADHD in males and females.

Distinct pattern of P3a event-related potential in borderline personality disorder.

P3a and P3b event-related brain potentials to auditory stimuli were recorded for 17 unmedicated patients with borderline personality disorder, 17 matched healthy controls and 100 healthy control participants spanning five decades. Using high-resolution fragmentary decomposition for single-trial event-related potential analysis, distinctive disturbances in P3a in borderline personality disorder patients were found: abnormally enhanced amplitude, failure to habituate and a loss of temporal locking with P3b. Normative age dependencies from 100 controls suggest that natural age-related decline in P3a amplitude is reduced in borderline personality disorder patients and is likely to indicate failure of frontal maturation. On the basis of the theories of Hughlings Jackson, this conceptualization of borderline personality disorder is consistent with an aetiological model of borderline personality disorder.

Is borderline personality a particularly right hemispheric disorder? A study of P3a using single trial analysis

Objective: To test the hypothesis that borderline personality disorder is a manifestation of a particularly right hemispheric disturbance, involving deficient higher order inhibition, and to consider the therapeutic implications of the findings. Methods: A cohort of 17 medication free borderline patients were compared with 17 age and sex matched controls by means of a study of p3a, which reflects the activity of one of the two main generators of the P300 (P3) of the event-related-potential. P3b reflects the output of the other generator. P3a, an aspect of the attentional system, depends upon prefrontally connected neurocircuitry. P3b is underpinned by a particularly parietally connected neural system. Using an oddball paradigm, P3a was extracted from the responses to targets using a novel single trial analysis. Results: In borderline patients, over homologous electrode sites, p3a amplitudes, but not latencies, were significantly larger in the right hemisphere compared with the left. The differences were most marked fronto-centrally. No such difference was shown in the control subjects. P3a at right hemisphere sites was significantly larger in borderline compared with control patients. There was no significant difference between the groups for the left hemisphere sites. Conclusions: The abnormally large amplitudes of P3a at right hemisphere sites in borderline patients together with the failure of habituation of P3a, are consistent with deficient inhibitory activity. Discussion of the findings suggest that they may reflect impeded maturation of the fronto-medial processing systems which, it is argued, may be a consequence of the typical early environment of those with the borderline condition. This suggestion leads to a consideration of optimal therapeutic behaviour in this condition, in particular for ‘matching’ or ‘analogical’ responsiveness.

High-resolution fragmentary decomposition: a model-based method of non-stationary electrophysiological signal analysis

Fragmentary decomposition (FD) is a recently developed method of non-stationary electrophysiological signal analysis addressed to mass potentials, such as electromyogram (EMG), event-related potential (ERP), evoked potential, electroencephalogram (EEG), electroretinogram, etc. Being supported by the generally accepted physiological notion that a peak is a functionally meaningful component of a mass potential, FD provides a way to avoid averaging and, instead, quantifies the component composition of complex electrophysiological signals directly from single-trials. The major computational procedures of FD include adaptive segmentation, the frequency domain component identification, and creation of the signal model as a linear aggregation of multiple components, with the generic mass potential (GMP) being the universal component template. This paper presents an improved, high-resolution FD technique which allows the resolution of overlapping sub-components and supports each identified component by an individual model. On the basis of this methodological innovation, we define two fundamental categories of multi-peak component waveforms: complex components (CC), comprised of multiple sub-components (GMPs), versus monolithic components (MC), involving a single GMP. We show that quantification of MCs and CCs from single-trial eyeblink EMG and single-trial ERP provides a more comprehensive analysis of these signals. Given single-trial eyeblink EMG, we find that the stimulus elicits strong though short-term (phasic) effects on MCs and moderate but long-lasting (tonic) effects on CCs. A new realm of single-trial ERP quantification is possible in that the MC appears as a marker of a single cognitive variable whereas the CC appears as a marker of a series of functionally related cognitive variables. The engagement of the brain in a specific cognitive task is accompanied by an increase of CCs in single-trial ERPs, which is especially informative with respect to the P3 cognitive potential. New methodology provides evidence for the three basic types of single-trial P3 sub-components: monolithic P3a, monolithic P3b, and a complex component, P3ab, which includes both P3a and P3b as sub-components.

Dynamic spectral analysis findings in first episode and chronic schizophrenia.

The quantified analysis of the electroencephalogram (qEEG) has enabled the extraction of additional psychophysiological information from the raw EEG, but in turn has introduced a number of distortions. This study compared Dynamic Spectral Analysis (DSA), a novel and mathematically stringent technique for the evaluation of qEEG activity with conventional power spectral analysis in subjects with both first episode and chronic schizophrenia and matched controls. Advantages of the technique in the automated processing of data, rejection of artefact, avoidance of artefact introduced by the mathematical trans-formation of the data and the identification of irregular low frequency artefactual activity “pi” are discussed in detail. Using this method, the study has confirmed past observations of increased slow wave activity in schizophrenia, and identified a decrease in peak frequency in the alpha band in the subjects with chronic schizophrenia. The two clinical groups differed in mean peak frequency in the delta band with the first episode schizophrenia subjects having a raised mean peak frequency and the subjects with chronic schizophrenia having a lowered mean peak frequency. The results suggest continued change in the EEG with illness chronicity in schizophrenia. These changes were most evident in the frequency domain emphasizing the importance of routine measurement of mean band frequencies in qEEG studies.

Single-event-related potential analysis by means of fragmentary decomposition

Abstract. A recently developed fragmentary decomposition method is employed to analyse single-trial event-related potentials (ERPs), thereby extending the traditional method of averaging. Using a conventional auditory oddball paradigm with 40 target stimuli, single-trial ERPs in 40 normal subjects were analysed for midline scalp (Fz, Cz and Pz) recording sites. The normalization effect, reported in our previous study of eye blink EMGs and proposed to be a characteristic property of a wide class of non-stationary physiological processes, was found to apply to these single-trial ERPs. Fragmentary decomposition of single-trial ERPs may be regarded as re-statement of the normalization effect. This allows both pre-stimulus EEGs and post-stimulus ERPs to be regarded as overlapping generic mass potentials (GMPs), with a characteristic Gaussian amplitude spectrum. On theoretical and empirical grounds we uniquely deduce a model GMP using an introduced “bud” function, and physically support it by the resting and transient conditions. The model takes into account the shape of the component, which suggests a simple relationship between the peak latency and the time of the component onset. Given that GMPs may be manipulated and sorted out, we present principles of the fragmentary synthesis, i.e. probabilistic ERP reconstructions on the basis of individual and ensemble properties of its identified components. Summarizing the component quantification in the form of the dynamic model provides for the first time the opportunity to quantify all significant components in single-trial ERPs. This method of single-trial analysis opens up new possibilities of exploring the dynamical ERP changes within a recording trial, particularly in late component “cognitive” paradigms.

Dynamic spectral analysis of event-related potentials

This paper presents a new method for the identification of individual event related potential (ERP) components in both frequency and time domains. Using the similar basis function (SBF) algorithm the method provides a time to frequency transform, representing a frequency domain equivalent of the component waveform. Notable features of the SBF algorithm are that it allows for unevenly spaced sampled functions in both the time and frequency domains, and estimates of spectral densities are obtained by numerical computation of finite Fourier integrals. Application of this method to ERP data from 20 normal subjects demonstrated a similar shape of component amplitude frequency characteristics for traditional late component waveforms (N1, P2, N2 and P3). On this basis, a low-frequency band was found where the component amplitude frequency characteristic was described by a Gaussian function, while the component phase frequency characteristic was a linear function of frequency. These relationships are interpreted as frequency domain equivalents of the component. Transformed to the time domain, they provided an analytical description of the ERP as the sum of positive- and negative-going monopolar waves. The study points to similar mechanisms underlying these component waveforms, and analytically defines dynamic properties for the components both in the frequency and time domains.

Numerical fourier transform spectroscopy of EMG half-waves: fragmentary-decomposition-based approach to nonstationary signal analysis.

Abstract. A nonstationary signal analysis technique is introduced, which regards an oscillatory physiological signal as a sum of its fragments, presented in the form of a fragmentary decomposition (FD). The virtue of FD is that it is free of the necessity to choose a priori the basis functions intended for signal analysis or synthesis. FD uses an unchanged signal fragment between adjacent zero-crossings, as a natural basis function called the half-wave function (HWF). To show that such a function is a physically meaningful object, Fourier transform methods were employed, supported by the similar basis function (SBF) algorithm, which provides the means for numerical Fourier transform spectroscopy of separate half-waves and their frequency domain description in terms of both amplitude and phase. The application of this method to parameter identification of 751 EMG half-waves from the eye blink EMG records of ten normal subjects showed that HWFs frequency domain image represents a Gaussian distribution, which applies over a defined range of relative frequencies. This empirical evidence shows that HWFs are produced by a specific system of first-order nonlinear differential equations, whose dependency on a number of random factors is characteristic of deterministic chaos. The particular form of solutions indicates that statistical regularities relevant to the central limit theorem are likely to underlie the genesis of the mass potentials studied. FD shows potential utility in a range of nonstationary physiological signals.

Transient analysis of a chemical synaptic transmission

The statistical dynamics of an impulse induced quanta turnover is studied by means of a nonstationary stochastic model — double barrier synapse — resulting from a previously developed mathematical theory of chemical synaptic transmission. An essential aspect of nonstationarities of the model is that the interpool quanta transfers follow binomial distribution at impulse arrival time, while in the absence of stimulation they obey Yule-Furry statistics.Under a variety of conditions, corresponding to those in actual experiments, the transient behaviour of the model is simulated and analysed in detail. As a result, the quantitative description of immediate and delayed components of synaptic action is introduced. If simulations of quantal fluctuations are performed numerically, then for the treatment of dynamic regularities, besides numerical procedures, an analytical method of envelopes is developed. It is supported, by the theorems which reduce behaviour of the double-barrier synapse to the super-position of simpler solutions for single-barrier systems.With short-term facilitation quantitative analysis and simulations, the synaptic resonance phenomenon is theoretically predicted: different resonant frequencies are found at different levels of facilitation. The importance of this phenomenon treated as a clue to the information processing capabilities of a chemical synapse is discussed.

Stochastic particle formulation of the vesicle hypothesis. Relevance to short-term phenomena.

Based on the vesicle hypothesis, the modes of elementary quantum-vesicle interactions have been formulated in terms of probabilities of induced and spontaneous interstate quanta transitions and generalized within the framework of the previously developed theory of the double barrier synapse. Among the three allowed states for a quantum, the transition state is a novel formulation for the fraction of immediately available quanta governed by both vesicle and presynaptic membranes. The parameters of the model were determined by fitting solutions to the experimental curves representing effects of single pulse and short train activation on transmitter release at the frog neuromuscular junction. Qualitative differences in particle physics of transmitter release found under low quantal outputs on one hand and normal transmission on the other allowed the formulation of the uncertainty hypothesis and the quantum condition of synaptic homeostasis.