George K. Kostopoulos’s research while affiliated with University of Patras and other places

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Publications (90)


EEG-Based Person Identification Using Rhythmic Brain Activity During Sleep: 27th International Conference on Artificial Neural Networks, Rhodes, Greece, October 4–7, 2018, Proceedings, Part III
  • Chapter

October 2018

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51 Reads

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3 Citations

Lecture Notes in Computer Science

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George K. Kostopoulos

In this paper we present a novel approach to the person identification problem using rhythmic brain activity of spindles from whole night EEG recordings. The proposed system consists of a feature extraction module and a K-NN based classifier. Different types of features from time, frequency and wavelet domain are used to highlight the topographic, temporal, morphological, spectral and statistical discriminative information of sleep spindles. The feature set’s efficacy is exhaustively tested in order to find the most significant descriptors that maximize intra-subject separability. Extensive experiments resulted in the optimal number of sensors and features that must be used to form the subject-specific unique descriptors. The proposed system showed significant identification accuracy of 99% ~ 90% for 2–20 subjects, and not lower than 86% when identifying 28 persons, indicating that this new type of modality should be further investigated to be used in EEG based identification applications.


Pharmacologically Induced Animal Models of Absence Seizures

December 2017

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19 Reads

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3 Citations

Understanding absence seizures demands complementary research approaches using diverse animal models, including ones induced by a variety of chemical agents. The characteristics, induction methods, and validation criteria met by several animal models are reviewed, along with a critical comparison of their advantages, limitations, and main contributions to epileptology. The distinction between typical and atypical absence seizures (TAS and AAS) in humans is considered in the respective animal analogs. Emphasis is given to the TAS models produced acutely by systemic administration of γ-hydroxybutyrate (GHB) in the rat, and penicillin in the cat (FGPE), while the validation of other TAS models is considered less complete. Among their contributions to epileptology, GHB first showed the importance of GABAB receptors and tonic inhibition on neurons and glia, while the FGPE first established the current generators and corticothalamic circuit pacing of generalized 3 Hz spike-and-wave discharges. The lifelong occurrence of absences in rats after prepubertal injection of AY-9944 is presented as a chronic model of AAS, allowing experimentation of the limbic involvement, the cognitive impairment, and the worse outcome characterizing the AAS, compared to TAS.


Real-time Spindles Detection for Acoustic Neurofeedback

September 2017

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42 Reads

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3 Citations

Lecture Notes in Computer Science

Real-time neurofeedback plays an increasing role in today’s clinical and basic neuroscience research. In this work, we present a real-time sleep EEG spindles detection algorithm fast enough to be used for real time acoustic feedback stimulation. We further highlight the architecture of a system that implements the algorithm and its experimental evaluation. This system can handle EEG data acquired by various means (i.e. conventional EEG systems, wireless sensors) and a response time of a few msecs has been achieved. The presented algorithm is dynamically adaptive and has accuracy similar to other well-known non real-time algorithms. Comparison and evaluation was performed using EEG data from an open database.


Computers Cannot Learn the Way Humans Do – Partly, Because They Do not Sleep

September 2017

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32 Reads

Lecture Notes in Computer Science

One of the current frontier research themes in informatics relates to the extent to which computers and machines in general can become capable of learning and teaching each other. Hopes have been raised that their education could benefit from emulating mechanisms underlying learning in animal brains. An overview of these mechanisms will be briefly presented with a focus on the recently revealed fundamental role of sleep in memory consolidation and learning., Compared to brains, computers are found very much inferior when it comes to learning. Several road signs are suggested for enriching computers’ repertory in the direction of increasing their capacity to learn by becoming more brain-like. However, the prospect of achieving such goal with state of art technology appears extremely dim.


Topography of Generalized Periodic Epileptiform Discharges in Post-anoxic Non-Convulsive Status Epilepticus
  • Article
  • Full-text available

July 2017

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108 Reads

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6 Citations

We studied slow (≤2.5 Hz) nonevolving generalized periodic epileptiform discharges (GPEDs) in the electroencephalogram (EEG) of comatose patients after cardiac arrest (CA) in search of evidence that could assist early diagnosis of possible hypoxic nonconvulsive status epilepticus (NCSE) and its differentiation from terminal brain anoxia (BA), which can present with a similar EEG pattern. We investigated the topography of the GPEDs in the first post‐CA EEGs of 13 patients, using voltage‐mapping, and compared findings between two patients with NCSE and GPEDs > 2.5 Hz (group 1), and 11 with GPEDs ≤ 2 Hz, of whom six had possible NCSE (group 2) and five had terminal BA (group 3). Voltage mapping showed frontal maximum for the negative phase of the GPEDs in all patients of groups 1 and 2, but not in any of the patients of group 3, who invariably showed maximization of the negative phase posteriorly. Morphology, amplitude, and duration of the GPEDs varied across the groups, without distinctive features for possible NCSE. These findings provide evidence that, in hypoxic coma after CA with slow GPEDs, anterior topography of the maximum GPED negativity on voltage mapping may be a distinctive biomarker for possible NCSE contributing to the coma.

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TABLE 1 | Key focal activations. 
The analysis steps used in this paper. The red path, traces the first steps of the analysis as described in Sections Subjects and Overall Experiment Planning, Data Acquisition and Pre-Processing, Displays of the Raw MEG Signal and Auxiliary Channels, and Source Reconstruction. For this early part of the analysis the same methods are used as in our previous two sleep studies, so only the key steps are included more details can be found in Figure 1 of Ioannides et al. (2009). The next two figures with results of this paper (Figures 2, 3) summarize aspects of the recordings (Figure 2) and properties of the EEG and MEG signal (Figure 3). The spectral analysis of the MFT solutions (described in more detail in Sections Fourier Analysis of MFT Solutions, Spectral Statistical Parametric Mapping (sSPM) for Each Subject, and Grand sSPM and Reporting of Statistical Significance) constitutes the main part of the new analysis and it is marked by the black paths with heavy arrows, continuing (from right to left) after the MFT box, with final output Figures 4–11 and Table 1. The parts linked with light black arrows show analysis steps that combine old and new methods (see also Section Regions of Interest and Time Domain Analysis) to produce the last two figures of this paper (Figures 12, 13). These two figures provide a bridge between the results from two distinct types of analysis. In the first, the emphasis is placed on (the peaks of activity in) the time-domain while in the second the emphasis is placed on (spectral properties of regional activity in) the frequency domain. To achieve this integrative role the analysis (and results in Figures 12, 13) combine information from the raw EEG and MEG signals, the MFT tomographic solutions and the grand sSPM results showing the patterns of both raw signal and MFT solutions across widely different timescales from milliseconds to minutes.
Typical example of full night's recording. Five and half hours of one subject's sleep, from 23:50 in the evening to 01:00 the following morning and from 2:20 to 6:20. The break in the recording between the two segments was made after the subject requested to stop the recording to use the toilet; most of the break time is needed for removing and re-placing electrodes and re-checking all acquisition setup. Note how quickly the subject falls asleep after the recording is resumed. The five graphs from top to bottom show: hypnogram of sleep stages, head movements (in cm) during recording (the gray horizontal line marks the 5 mm threshold of selecting segments for detailed analysis), the EMG signal (submental electrode), the EEG signal from C3 electrode and the MEG global field power (GFP) time course. All three electrophysiological signals were smoothed with a 30 s running window after filtering in the 5–98 Hz (EMG) and 3–45 Hz (EEG and MEG) bands. The EMG and EEG signals were rectified after filtering and before smoothing.
Grand average MEG and EEG power spectra. Spectra for a frontal and parietal midline MEG channels and an EEG channel. Logarithmic scale is used on both the frequency and power axes (log-log plot). (A) Comparison of core periods. (B,C) Comparison of NREM2 core period with periods immediately before and during (B) spindles and (C) KCs. The NREM2 core period spectra (green curves) are shown in all figures. For ease of comparisons the same frequency axis (abscissa) is used in all 9 plots, and the same power axis (ordinate) is used in all MEG (first two columns) plots and in all EEG (third column) plots.
Panoramic overview of the changes in activity along the midline sagittal cut. Each column shows the result for a different comparison, specified on the title at the top of the column. The changes displayed for each comparison represent common (for all subjects) increases (red) or decreases (blue) in spectral power at the significance level indicated at the bottom of the column: modest changes (p < 0.05) are denoted by one asterisk (*); prominent changes (p < 0.00001) are denoted by a double asterisk (**). Each row represents the result for a different frequency band as printed (vertically) at the beginning (left) of each row.

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Using MEG to Understand the Progression of Light Sleep and the Emergence and Functional Roles of Spindles and K-Complexes

June 2017

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164 Reads

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27 Citations

We used tomographic analysis of MEG signals to characterize regional spectral changes in the brain at sleep onset and during light sleep. We identified two key processes that may causally link to loss of consciousness during the quiet or “core” periods of NREM1. First, active inhibition in the frontal lobe leads to delta and theta spectral power increases. Second, activation suppression leads to sharp drop of spectral power in alpha and higher frequencies in posterior parietal cortex. During NREM2 core periods, the changes identified in NREM1 become more widespread, but focal increases also emerge in alpha and low sigma band power in frontal midline cortical structures, suggesting reemergence of some monitoring of internal and external environment. Just before spindles and K-complexes (KCs), the hallmarks of NREM2, we identified focal spectral power changes in pre-frontal cortex, mid cingulate, and areas involved in environmental and internal monitoring, i.e., the rostral and sub-genual anterior cingulate. During both spindles and KCs, alpha and low sigma bands increases. Spindles emerge after further active inhibition (increase in delta power) of the frontal areas responsible for environmental monitoring, while in posterior parietal cortex, power increases in low and high sigma bands. KCs are correlated with increase in alpha power in the monitoring areas. These specific regional changes suggest strong and varied vigilance changes for KCs, but vigilance suppression and sharpening of cognitive processing for spindles. This is consistent with processes designed to ensure accurate and uncorrupted memory consolidation. The changes during KCs suggest a sentinel role: evaluation of the salience of provoking events to decide whether to increase processing and possibly wake up, or to actively inhibit further processing of intruding influences. The regional spectral patterns of NREM1, NREM2, and their dynamic changes just before spindles and KCs reveal an edge effect facilitating the emergence of spindles and KCs and defining the precise loci where they might emerge. In the time domain, the spindles are seen in widespread areas of the cortex just as reported from analysis of intracranial data, consistent with the emerging consensus of a differential topography that depends on the kind of memory stored.


Spatiotemporal propagation patterns of generalized ictal spikes in childhood absence epilepsy

June 2017

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176 Reads

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11 Citations

Clinical Neurophysiology

Objective This work investigates the spatial distribution in time of generalized ictal spikes in the typical absences of childhood absence epilepsy (CAE). Methods We studied twelve children with CAE, who had more than two typical absences during their routine video-EEG. Seizures were identified, and ictal spikes were marked over the maximum electronegative peak, clustered, waveform-averaged and spatiotemporaly analyzed in 2D electrode space. Results Consistency of spatiotemporal patterns of ictal spikes was high between the absences of the same child, but low between children. Three main discharge patterns were identified: of anterio-posterior propagation, of posterio-anterior propagation and confined to the frontal/prefrontal regions. In 4 patients, the propagation patterns transformed during the seizure into either a lateralized diminished or a non-lateralized reverse direction form. Most spikes originated fronto-temporaly, all maximized over the frontal/prefrontal electrodes and mostly decayed prefrontaly. In 4 patients, lateralized propagation patterns were identified. Conclusions Ictal spike propagation patterns suggest that epileptogenic CAE networks are personalized, interconnect distal areas in the brain - not the entire cortex - with a tendency to generate bilateral symmetrical discharges, sometimes unsuccessfully. The transformation of propagation patterns during the seizure indicates the existence of dynamic interplay within epileptogenic networks. Significance Our results support the revised concept of ictogenesis of ILAE definition in genetic (also known as idiopathic) generalized epilepsies. Understanding the focal features in CAE avoids misdiagnosis as focal epilepsy and inappropriate treatment.


History of Neuroscience in Greece: From Alkmaion to Austerity

July 2016

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39 Reads

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1 Citation

European Journal of Neuroscience

In the frame of an historical section of the 2015 Featured Regional meeting of FENS in Thessaloniki, I was asked to talk on the "History of Neuroscience in Greece". Realizing the impossibility of the task, I focused on only two points: the dawn of neuroscience in Greece and the current situation which threatens the survival of neuroscience in Greece. Both points are closer to provocative questions than to evidence-based conclusions. This article is protected by copyright. All rights reserved.



Connectivity Measures in EEG Microstructural Sleep Elements

February 2016

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1,036 Reads

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11 Citations

Dimitris Sakellariou

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George K. Kostopoulos

During Non-Rapid Eye Movement sleep (NREM) the brain is relatively disconnected from the environment, while connectedness between brain areas is also decreased. Evidence indicates, that these dynamic connectivity changes are delivered by microstructural elements of sleep: short periods of environmental stimuli evaluation followed by sleep promoting procedures. The connectivity patterns of the latter, among other aspects of sleep microstructure, are still to be fully elucidated. We suggest here a methodology for the assessment and investigation of the connectivity patterns of EEG microstructural elements, such as sleep spindles. The methodology combines techniques in the preprocessing, estimation, error assessing and visualization of results levels in order to allow the detailed examination of the connectivity aspects (levels and directionality of information flow) over frequency and time with notable resolution, while dealing with the volume conduction and EEG reference assessment. The high temporal and frequency resolution of the methodology will allow the association between the microelements and the dynamically forming networks that characterize them, and consequently possibly reveal aspects of the EEG microstructure. The proposed methodology is initially tested on artificially generated signals for proof of concept and subsequently applied to real EEG recordings via a custom built MATLAB-based tool developed for such studies. Preliminary results from 843 fast sleep spindles recorded in whole night sleep of 5 healthy volunteers indicate a prevailing pattern of interactions between centroparietal and frontal regions. We demonstrate hereby, an opening to our knowledge attempt to estimate the scalp EEG connectivity that characterizes fast sleep spindles via an "EEG-element connectivity" methodology we propose. The application of the latter, via a computational tool we developed suggests it is able to investigate the connectivity patterns related to the occurrence of EEG microstructural elements. Network characterization of specified physiological or pathological EEG microstructural elements can potentially be of great importance in the understanding, identification, and prediction of health and disease.


Citations (59)


... One of the closed-loop research areas that has progressed the fastest using non-invasive neurophysiological recordings (i.e., EEG) and brain stimulation techniques is studying memory consolidation processes in sleep [1,[9][10][11]. A first target has been slow oscillations (SOs: 0.5 -1.5 Hz), which are high amplitude waves that appear in non-rapid eye movement (NREM) sleep and are known to be involved in memory consolidation (i.e., the process by which recent learned experiences are transformed into long-term memory) [1]. Using auditory stimulation to SO up-states, when neural tissue is partly depolarized and more excitable, Ngo et al. enhanced the amplitude of SOs and reported an overnight improvement in memory performance, a result that has now been replicated multiple times (see [12][13][14] for reviews). ...

Reference:

The Portiloop: A deep learning-based open science tool for closed-loop brain stimulation
Real-time Spindles Detection for Acoustic Neurofeedback
  • Citing Conference Paper
  • September 2017

Lecture Notes in Computer Science

... IEDs are microscale EEG elements, typically consisting of single or multiple cycles of spikes or spikes-and-waves, lasting from a few milliseconds to a couple of seconds. Despite that numerous neurophysiological events in the temporal microscale have been widely documented and linked to a variety of abnormal states and neurological conditions [2][3][4][5][6][7] , their dynamic network features remain largely unexplored. ...

Topography of Generalized Periodic Epileptiform Discharges in Post-anoxic Non-Convulsive Status Epilepticus

... Due its superior temporal and spatial resolution, the spectral features of MEG signals have been extensively linked to specific sleep events, such as sleep spindles 35 , cognitive changes during sleep 36 , and general sleep stages [37][38][39] . Recently, Brancaccio et al. demonstrated that those spectral features of brain MEG activity vary with different sleep stages and across various brain regions 37 . ...

Using MEG to Understand the Progression of Light Sleep and the Emergence and Functional Roles of Spindles and K-Complexes

... Within the CTC network, feed-forward inhibition (FFI) is essential to prevent runaway excitation and is mediated by fast-spiking parvalbuminexpressing (PV+) inhibitory interneurons. Studies conducted using the well-established stargazer mouse model of absence epilepsy have shown defects in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) expression at excitatory synapses in feed-forward inhibitory PV+ interneurons in the somatosensory cortex (SScortex) (Maheshwari et al., 2013;Adotevi and Leitch, 2016, 2017 and reticular thalamic nuclei (RTN) (Menuz and Nicoll, 2008;Barad et al., 2012) of the CTC network. The loss of synaptic AMPARs is the result of a genetic mutation in stargazin, a transmembrane AMPAR regulatory protein (TARP) (Noebels et al., 1990;Letts et al., 1998) that traffics AMPARs to the synapse. ...

Pharmacologically Induced Animal Models of Absence Seizures
  • Citing Chapter
  • December 2017

... The pathophysiology of CAE has been extensively carried out in both animal and human models over the past decade (Meeren et al., 2005;Sitnikova and Luijtelaar, 2006;van Luijtelaar et al., 2011). Dynamic changes in the spatiotemporal course have been studied in CAE using EEG (Kokkinos et al., 2013(Kokkinos et al., , 2017Leitgeb et al., 2020). However, most studies have focused on the generation and propagation of ictal spike-wave discharges during seizures. ...

Spatiotemporal propagation patterns of generalized ictal spikes in childhood absence epilepsy

Clinical Neurophysiology

... An equally important challenge for such comparative studies would be the confirmation of the seminal finding of Meeren et al. (2002), in relation to the fundamental issue of focal origin of absences. Avoli et al. (1983), Depaulis et al. (1988a), Fariello (1979), Gloor (1984), Gloor and Testa (1974), Guberman et al. (1975), Kwan andBrodie (2000), Meldrum (2002), Quesney (1984), and Roth and Giarman (1969). ...

In Vitro Electrophysiology of a Genetic Model of Generalized Epilepsy
  • Citing Chapter
  • January 1990

... The K-complex and sleep spindle are the cornerstones of the sleep-EEG microstructural architecture. These electrophysiological microelements play an important role in understanding sleep's neurophysiological and functional aspects [2,7]. Sleep spindles are EEG rhythms especially prominent during NREM 2 [6]. ...

Connectivity Measures in EEG Microstructural Sleep Elements

... Because of the voltage dependence of the activation and inactivation properties of IT, it has been suggested that burst responses evoked by EPSPs or IPSPs may only occur when the membrane potential is set to values more negative or positive than around -65 mV, respectively. This interpretation has strongly influenced ideas concerning the setting of the membrane potential of different neurones within the thalamocortical network during different stages of arousal (see Steriade et al. 1993) and in neurological disorders (Avoli, Gloor & Kostopoulos, 1990). In the present study, we have shown that burst responses may be evoked by different forms of input: so, for example, from holding potentials set more positive than -65 mV, large amplitude hyperpolarizin-g voltage responses terminated by the burst firing of action potentials, were triggered by small (< 5 mV), physiologically relevant, postsynaptic potentials irrespective of their sign (excitatory or inhibitory) or duration. ...

Focal and Generalized Epileptiform Activity in the Cortex: In Search of Differences in Synaptic Mechanisms, Ionic Movements, and Long-Lasting Changes in Neuronal Excitability
  • Citing Chapter
  • January 1990

... Relatively low RI may uncover local recurrent excitatory connections, which have been found more abundant in VH than in DH (Vreugdenhil et al. 2001; see also example inFig. 3a), and thus contribute to epileptogenesis (Kostopoulos et al. 2005). Disinhibited VH slices are more prone to display spontaneous discharges than DH ones (Borck and JeVerys 1999; C. Papatheodoropoulos 2004, unpublished observations). ...

Functional differentiation along the longitudinal axis of hippocampus and its possible relevance to epileptogenesis
  • Citing Article
  • June 2005

... Gotman and Kostopoulos [93] in and update of neural correlates of loss of consciousness in absences raise the possibility that the "deactivation of the DMN may fully or partially be responsible for diminished self-awareness during spike-wave discharges, together with the presence of an abnormally active thalamus, and this may contribute to a partial blocking of sensory information reaching normally the cortex, thus reducing the awareness of the external world. " ...

Absence Seizures
  • Citing Article
  • March 2013