Mapping the epileptic brain with EEG dynamical connectivity: established methods and novel approaches

Several algorithms rooted in statistical physics, mathematics and machine learning are used to analyze neuroimaging data from patients suffering from epilepsy, with the main goals of localizing the brain region where the seizure originates from and of detecting upcoming seizure activity in order to trigger therapeutic neurostimulation devices. Some of these methods explore the dynamical connections between brain regions, exploiting the high temporal resolution of the electroencephalographic signals recorded at the scalp or directly from the cortical surface or in deeper brain areas. In this paper we describe this specific class of algorithms and their clinical application, by reviewing the state of the art and reporting their application on EEG data from an epileptic patient

Estimating directed connectivity from cortical recordings and reconstructed sources

In cognitive neuroscience, electrical brain activity is most commonly recorded at the scalp. In order to infer the contributions and connectivity of underlying neuronal sources within the brain, it is necessary to reconstruct sensor data at the source level. Several approaches to this reconstruction have been developed, thereby solving the so-called implicit inverse problem Michel et al. (Clin Neurophysiol 115:2195-2222, 2004). However, a unifying premise against which to validate these source reconstructions is seldom available. The dataset provided in this work, in which brain activity is simultaneously recorded on the scalp (non-invasively) by electroencephalography (EEG) and on the cortex (invasively) by electrocorticography (ECoG), can be of a great help in this direction. These multimodal recordings were obtained from a macaque monkey under wakefulness and sedation. Our primary goal was to establish the connectivity architecture between two sources of interest (frontal and parietal), and to assess how their coupling changes over the conditions. We chose these sources because previous studies have shown that the connections between them are modified by anaesthesia Boly et al. (J Neurosci 32:7082-7090, 2012). Our secondary goal was to evaluate the consistency of the connectivity results when analyzing sources recorded from invasive data (128 implanted ECoG sources) and source activity reconstructed from scalp recordings (19 EEG sensors) at the same locations as the ECoG sources. We conclude that the directed connectivity in the frequency domain between cortical sources reconstructed from scalp EEG is qualitatively similar to the connectivity inferred directly from cortical recordings, using both data-driven (directed transfer function) and biologically grounded (dynamic causal modelling) methods. Furthermore, the connectivity changes identified were consistent with previous findings Boly et al. (J Neurosci 32:7082-7090, 2012). Our findings suggest that inferences about directed connectivity based upon non-invasive electrophysiological data have construct validity in relation to invasive recordings

Dynamic causal modelling of seizure activity in a rat model

This paper presents a physiological account of seizure activity and its evolution over time using a rat model of induced epilepsy. We analyse spectral activity recorded in the hippocampi of three rats who received kainic acid injections in the right hippocampus. We use dynamic causal modelling of seizure activity and Bayesian model reduction to identify the key synaptic and connectivity parameters that underlie seizure onset. Using recent advances in hierarchical modelling (parametric empirical Bayes), we characterise seizure onset in terms of slow fluctuations in synaptic excitability of specific neuronal populations. Our results suggest differences in the pathophysiology – of seizure activity in the lesioned versus the non-lesioned hippocampus – with pronounced changes in excitation-inhibition balance and temporal summation on the lesioned side. In particular, our analyses suggest that marked reductions in the synaptic time constant of the deep pyramidal cells and the self-inhibition of inhibitory interneurons (in the lesioned hippocampus) are sufficient to explain changes in spectral activity. Although these synaptic changes are consistent over rats, the resulting electrophysiological phenotype can be quite diverse

Tracking slow modulations in synaptic gain using dynamic causal modelling : validation in epilepsy

In thiswork we propose a proof of principle that dynamic causal modelling can identify plausible mechanisms at the synaptic level underlying brain state changes over a timescale of seconds. As a benchmark example for validation we used intracranial electroencephalographic signals in a human subject. These data were used to infer the (effective connectivity) architecture of synaptic connections among neural populations assumed to generate seizure activity. Dynamic causal modelling allowed us to quantify empirical changes in spectral activity in terms of a trajectory in parameter space -identifying key synaptic parameters or connections that cause observed signals. Using recordings from three seizures in one patient, we considered a network of two sources (within and just outside the putative ictal zone). Bayesian model selection was used to identify the intrinsic (within-source) and extrinsic (between-source) connectivity. Having established the underlying architecture, we were able to track the evolution of key connectivity parameters (e.g., inhibitory connections to superficial pyramidal cells) and test specific hypotheses about the synaptic mechanisms involved in ictogenesis. Our key finding was that intrinsic synaptic changes were sufficient to explain seizure onset, where these changes showed dissociable time courses over several seconds. Crucially, these changes spoke to an increase in the sensitivity of principal cells to intrinsic inhibitory afferents and a transient loss of excitatory-inhibitory balance

Forced swim test induces divergent global transcriptomic alterations in the hippocampus of high versus low novelty-seeker rats

BACKGROUND: Many neuropsychiatric disorders, including stress-related mood disorders, are complex multi-parametric syndromes. Susceptibility to stress and depression is individually different. The best animal model of individual differences that can be used to study the neurobiology of affect regards spontaneous reactions to novelty. Experimentally, when naive rats are exposed to the stress of a novel environment, they display a highly variable exploratory activity and are classified as high or low responders (HR or LR, respectively). Importantly, HR and LR rats do not seem to exhibit a substantial differentiation in relation to their ‘depressive-like’ status in the forced swim test (FST), a widely used animal model of ‘behavioral despair’. In the present study, we investigated whether FST exposure would be accompanied by phenotype-dependent differences in hippocampal gene expression in HR and LR rats. RESULTS: HR and LR rats present a distinct behavioral pattern in the pre-test session but develop comparable depressive-like status in the second FST session. At 24 h following the second FST session, HR and LR rats (stressed and unstressed controls) were sacrificed and hippocampal samples were independently analyzed on whole rat genome Illumina arrays. Functional analysis into pathways and networks was performed using Ingenuity Pathway Analysis (IPA) software. Notably, hippocampal gene expression signatures between HR and LR rats were markedly divergent, despite their comparable depressive-like status in the FST. These molecular differences are reflected in both the extent of transcriptional remodeling (number of significantly changed genes) and the types of molecular pathways affected following FST exposure. A markedly higher number of genes (i.e., 2.28-fold) were statistically significantly changed following FST in LR rats, as compared to their HR counterparts. Notably, genes associated with neurogenesis and synaptic plasticity were induced in the hippocampus of LR rats in response to FST, whereas in HR rats, FST induced pathways directly or indirectly associated with induction of apoptotic mechanisms. CONCLUSIONS: The markedly divergent gene expression signatures exposed herein support the notion that the hippocampus of HR and LR rats undergoes distinct transcriptional remodeling in response to the same stress regimen, thus yielding a different FST-related ‘endophenotype’, despite the seemingly similar depressive-like phenotype

NMDA-receptor antibodies alter cortical microcircuit dynamics

NMDA-receptor antibodies (NMDAR-Abs) cause an autoimmune encephalitis with a diverse range of EEG abnormalities. NMDAR-Abs are believed to disrupt receptor function, but how blocking this excitatory synaptic receptor can lead to paroxysmal EEG abnormalities-or even seizures-is poorly understood. Here we show that NMDAR-Abs change intrinsic cortical connections and neuronal population dynamics to alter the spectral composition of spontaneous EEG activity and predispose brain dynamics to paroxysmal abnormalities. Based on local field potential recordings in a mouse model, we first validate a dynamic causal model of NMDAR-Ab effects on cortical microcircuitry. Using this model, we then identify the key synaptic parameters that best explain EEG paroxysms in pediatric patients with NMDAR-Ab encephalitis. Finally, we use the mouse model to show that NMDAR-Ab-related changes render microcircuitry critically susceptible to overt EEG paroxysms when these key parameters are changed, even though the same parameter fluctuations are tolerated in the in silico model of the control condition. These findings offer mechanistic insights into circuit-level dysfunction induced by NMDAR-Ab

ELNAIS: A collaborative network on Aquatic Alien Species in Hellas (Greece)

ELNAIS is a dynamic online information platform aiming to collect and report spatial information on Aquatic Alien Species in Greek waters. It covers freshwater, marine and estuarine waters, including not only established aliens but also casual records and cryptogenic species. The ELNAIS system includes: News, List of Greek experts, Literature of findings in Greece, List of species with information on their first introduction date and source as well as photos and distribution maps. Data providers are the scientific community (publications, grey literature, and databases) as well as citizen scientists. ELNAIS provides a useful tool towards national obligations and commitments under both the European and global frameworks in respect to Non Indigenous Species (CBD, WFD, MSFD).JRC.H.1-Water Resource

The Eurasian Modern Pollen Database (EMPD), version 2

The Eurasian (née European) Modern Pollen Database (EMPD) was established in 2013 to provide a public database of high-quality modern pollen surface samples to help support studies of past climate, land cover, and land use using fossil pollen. The EMPD is part of, and complementary to, the European Pollen Database (EPD) which contains data on fossil pollen found in Late Quaternary sedimentary archives throughout the Eurasian region. The EPD is in turn part of the rapidly growing Neotoma database, which is now the primary home for global palaeoecological data. This paper describes version 2 of the EMPD in which the number of samples held in the database has been increased by 60 % from 4826 to 8134. Much of the improvement in data coverage has come from northern Asia, and the database has consequently been renamed the Eurasian Modern Pollen Database to reflect this geographical enlargement. The EMPD can be viewed online using a dedicated map-based viewer at https://empd2.github.io and downloaded in a variety of file formats at https://doi.pangaea.de/10.1594/PANGAEA.909130 (Chevalier et al., 2019)Swiss National Science Foundation | Ref. 200021_16959

The Eurasian Modern Pollen Database (EMPD), version 2

The Eurasian (nee European) Modern Pollen Database (EMPD) was established in 2013 to provide a public database of high-quality modern pollen surface samples to help support studies of past climate, land cover, and land use using fossil pollen. The EMPD is part of, and complementary to, the European Pollen Database (EPD) which contains data on fossil pollen found in Late Quaternary sedimentary archives throughout the Eurasian region. The EPD is in turn part of the rapidly growing Neotoma database, which is now the primary home for global palaeoecological data. This paper describes version 2 of the EMPD in which the number of samples held in the database has been increased by 60% from 4826 to 8134. Much of the improvement in data coverage has come from northern Asia, and the database has consequently been renamed the Eurasian Modern Pollen Database to reflect this geographical enlargement. The EMPD can be viewed online using a dedicated map-based viewer at https://empd2.github.io and downloaded in a variety of file formats at https://doi.pangaea.de/10.1594/PANGAEA.909130 (Chevalier et al., 2019).Peer reviewe