Towards a large-scale model of patient-specific epileptic spike-wave discharges

Clinical electroencephalographic (EEG) recordings of the transition into generalised epileptic seizures show a sudden onset of spike-wave dynamics from a low-amplitude irregular background. In addition, non-trivial and variable spatio-temporal dynamics are widely reported in combined EEG/fMRI studies on the scale of the whole cortex. It is unknown whether these characteristics can be accounted for in a large-scale mathematical model with fixed heterogeneous long-range connectivities. Here, we develop a modelling framework with which to investigate such EEG features. We show that a neural field model composed of a few coupled compartments can serve as a low-dimensional prototype for the transition between irregular background dynamics and spike-wave activity. This prototype then serves as a node in a large-scale network with long-range connectivities derived from human diffusion-tensor imaging data. We examine multivariate properties in 42 clinical EEG seizure recordings from 10 patients diagnosed with typical absence epilepsy and 50 simulated seizures from the large-scale model using 10 DTI connectivity sets from humans. The model can reproduce the clinical feature of stereotypy where seizures are more similar within a patient than between patients, essentially creating a patient-specific fingerprint. We propose the approach as a feasible technique for the investigation of patient-specific large-scale epileptic features in space and time.     

Localizational concepts in epilepsy: past, present and future

The clinical seizure pattern, particularly the initial phenomena, plus the EEG, when satisfactory recording of the seizure onset can be achieved, determine the primary localization of epileptic phenomena. The EEG has also demonstrated, by the presence of interictal epileptiform spike discharges, the presence of a second-order localization of epileptic phenomena, namely, the location and extent of cortex adjacent to the site of origin of the neuronal seizure discharge that is recruited into action in a clinical epileptic seizure. Experience with cortical resection in the treatment of focal epilepsy has demonstrated the importance of a third-order localization of epileptic phenomena, namely, how much of the potentially epileptogenic cortex must be excised in order to produce a satisfactory reduction of the seizure tendency.     

Synchronization regulation in a model of coupled neural masses

A model of coupled neural masses can generate seizure-like events and dynamics similar to those observed during interictal to ictal transitions and thus can be used for theoretical study of the control of epileptic seizures. In an effort to understand the mechanisms underlying epileptic seizures and how to avoid them, we added a control input to this model. Epileptic seizures are always accompanied by hypersynchronous firing of neurons, so research on synchronization among cortical areas is significant for seizure control. In this study, principal component analysis (PCA) was used to identify synchronization clusters composed of several neural masses. A method for calculating the synchronization cluster strength and participation rate is presented. The synchronization cluster strength can be used to identify synchronization clusters and the participation rate can be employed to identify neural masses that participate in the clusters. Each synchronization cluster is controlled as a whole using a proportional-integral-derivative (PID) controller. We illustrate these points using coupled neural mass models of synchronization to show their responses to increased (between node) coupling with and without control. Experiment results indicated that PID control can effectively regulate synchronization between neural masses and has the potential for seizure prevention.     

Experimental observation of increased fluctuations in an order parameter before epochs of extended brain synchronization

The identification of epileptic seizure precursors has potential clinical relevance. It is conjectured that seizures may be represented by dynamical bifurcations and that an adequate order parameter to characterize brain dynamics is the phase difference in the oscillatory activity of neural systems. In this study, the critical point hypothesis that seizures, or more generally periods of widespread high synchronization, represent bifurcations is empirically tested by monitoring the growth of fluctuations in the putative order parameter of phase differences between magnetoencephalographic and electroencephalographic signals in nearby brain regions in patients with epilepsy and normal subjects during hyperventilation. Implications of the results with regard to epileptic phenomena are discussed.     

Automatic detection of epileptic EEG signals using higher order cumulant features

The unpredictability of the occurrence of epileptic seizures makes it difficult to detect and treat this condition effectively. An automatic system that characterizes epileptic activities in EEG signals would allow patients or the people near them to take appropriate precautions, would allow clinicians to better manage the condition, and could provide more insight into these phenomena thereby revealing important clinical information. Various methods have been proposed to detect epileptic activity in EEG recordings. Because of the nonlinear and dynamic nature of EEG signals, the use of nonlinear Higher Order Spectra (HOS) features is a seemingly promising approach. This paper presents the methodology employed to extract HOS features (specifically, cumulants) from normal, interictal, and epileptic EEG segments and to use significant features in classifiers for the detection of these three classes. In this work, 300 sets of EEG data belonging to the three classes were used for feature extraction and classifier development and evaluation. The results show that the HOS based measures have unique ranges for the different classes with high confidence level (p-value < 0.0001). On evaluating several classifiers with the significant features, it was observed that the Support Vector Machine (SVM) presented a high detection accuracy of 98.5% thereby establishing the possibility of effective EEG segment classification using the proposed technique.     

电突触耦合Chay神经元同步振荡的研究

从微观解释异常神经元构建组织时癫痫样波形的相互制约关系对神经系统疾病的研究很有意义,而两神经元耦合特性的探索是重要的基础工作。采用Chay提供的Pacemaker神经元模型以电突触耦合来研究不同耦合强度对神经元动态时序的影响,并指出突触作用过程的混沌特征。给出并讨论了不同状态神经元相耦合时非线性振荡的数值计算结果,即：起搏神经元与处于冲动混沌状态神经元、处于冲动混沌和独态冲动状态的异常神经元、异常神经元与处于静息状态神经元的动态时序,还给出了部分相图以及Ca 离子浓度变化的特点。神经元这种负载特性的讨论有助于研究在活组织中癫痫发作的机理、传输和控制。     

A spatially extended model for macroscopic spike-wave discharges

Spike-wave discharges are a distinctive feature of epileptic seizures. So far, they have not been reported in spatially extended neural field models. We study a space-independent version of the Amari neural field model with two competing inhibitory populations. We show that this competition leads to robust spike-wave dynamics if the inhibitory populations operate on different time-scales. The spike-wave oscillations present a fold/homoclinic type bursting. From this result we predict parameters of the extended Amari system where spike-wave oscillations produce a spatially homogeneous pattern. We propose this mechanism as a prototype of macroscopic epileptic spike-wave discharges. To our knowledge this is the first example of robust spike-wave patterns in a spatially extended neural field model.     

Dissociation, forced normalization and dynamic multi-stability of the brain

Dissociated states represent pathological conditions where psychological trauma may emerge in a variety of forms such as psychic dissociative symptoms (hallucinations, derealization etc.) or on the other hand as somatoform symptoms (paroxysms, loss of motor control, involuntary movements etc.). Recent findings suggest that neurophysiological level of dissociative phenomena may be linked to the same neurophysiological principles that emerge in multi-stable perception of ambiguous stimuli likely caused by competing interpretations with mutual exclusivity. At this time there is evidence that temporal lobe seizure activity can produce dissociative syndrome and from these findings may be inferred that temporal lobe epileptic activity existing independently of neurological focal may share common neurobiological mechanism with dissociative symptoms. This conceptualization of dissociative phenomena is also in accordance with findings that originate from the study of the relationship between epilepsy and mental illness. The relationship was for the first time described in Meduna's concept of antagonism between epilepsy and psychosis and from the study of forced normalization introduced by Landolt in 1950s. The findings reported similar pathological conditions as in dissociative states when psychopathological symptoms and paroxysms may represent two different forms of the pathological process. Following the concept of forced normalization Tellenbach in 1965 introduced the term alternative psychosis implicating that stopping seizures does not mean vanishing or inactivity of the pathological state and that the epilepsy is still active subcortically and supplies energy for psychopathological symptoms. In the present review chaos in brain neural networks as a possible explanation of the relationship between dissociation and epileptic activity has been suggested that represents testable hypothesis for future research.     

A comparative study of a theoretical neural net model with MEG data from epileptic patients and normal individuals

Objective  

The aim of this study was to compare a theoretical neural net model with MEG data from epileptic patients and normal individuals.     

Modeling of pain using artificial neural networks

In dealing with human nervous system, the sensation of pain is as sophisticated as other physiological phenomena. To obtain an acceptable model of the pain, physiology of the pain has been analysed in the present paper. Pain mechanisms are explained in block diagram representation form. Because of the nonlinear interactions existing among different sections in the diagram, artificial neural networks (ANNs) have been exploited. The basic patterns associated with chronic and acute pain have been collected and then used to obtain proper features for training the neural networks. Both static and dynamic representations of the ANNs were used in this regard. The trained networks then were employed to predict response of the body when it is exposed to special excitations. These excitations have not been used in the training phase and their behavior is interesting from the physiological view. Some of these predictions can be inferred from clinical experimentations. However, more clinical tests have to be accomplished for some of the predictions.     

Influence of nasal respiration upon normal EEG and epileptic electrographic activities in frog and turtle.

The electrographic respiratory response (ERR) was elicited by nasal air flow in the brain of the frog and turtle. It had the shape of a spindle of high voltage rhythmic activity and was propagated from the olfactory bulb predominantly into the ipsilateral hippocampal region in the frog and into the pyriform cortex in the turtle. In both animals, thalamic propagation of the ERR was also found. In both animals epileptic electrographic phenomena, were enhanced, created by local penicillin application. In the turtle epileptic electrographic manifestations were also elicited in the intact brain by simple nasal air insufflation. Diazepam (intraperitoneal administration) had no effect either on the ERR or on its triggering effect on epileptic phenomena. The possible physiological and pathophysiological interpretations of these findings are discussed.     

Psychophysical tests of the hypothesis of a bottom-up saliency map in primary visual cortex

A unique vertical bar among horizontal bars is salient and pops out perceptually. Physiological data have suggested that mechanisms in the primary visual cortex (V1) contribute to the high saliency of such a unique basic feature, but indicated little regarding whether V1 plays an essential or peripheral role in input-driven or bottom-up saliency. Meanwhile, a biologically based V1 model has suggested that V1 mechanisms can also explain bottom-up saliencies beyond the pop-out of basic features, such as the low saliency of a unique conjunction feature such as a red vertical bar among red horizontal and green vertical bars, under the hypothesis that the bottom-up saliency at any location is signaled by the activity of the most active cell responding to it regardless of the cell's preferred features such as color and orientation. The model can account for phenomena such as the difficulties in conjunction feature search, asymmetries in visual search, and how background irregularities affect ease of search. In this paper, we report nontrivial predictions from the V1 saliency hypothesis, and their psychophysical tests and confirmations. The prediction that most clearly distinguishes the V1 saliency hypothesis from other models is that task-irrelevant features could interfere in visual search or segmentation tasks which rely significantly on bottom-up saliency. For instance, irrelevant colors can interfere in an orientation-based task, and the presence of horizontal and vertical bars can impair performance in a task based on oblique bars. Furthermore, properties of the intracortical interactions and neural selectivities in V1 predict specific emergent phenomena associated with visual grouping. Our findings support the idea that a bottom-up saliency map can be at a lower visual area than traditionally expected, with implications for top-down selection mechanisms.     

How training and testing histories affect generalization: a test of simple neural networks

We show that a simple network model of associative learning can reproduce three findings that arise from particular training and testing procedures in generalization experiments: the effect of (i) 'errorless learning', (ii) extinction testing on peak shift, and (iii) the central tendency effect. These findings provide a true test of the network model which was developed to account for other phenomena, and highlight the potential of neural networks to study the phenomena that depend on sequences of experiences with many stimuli. Our results suggest that at least some such phenomena, e.g. stimulus range effects, may derive from basic mechanisms of associative memory rather than from more complex memory processes.     

Late Brain Recovery Processes after Drug Overdose

Though recovery of consciousness after drug overdose may occur within a day or two, the drug itself may not finally leave the brain for another one to three weeks, and at this late time a withdrawal syndrome can occur, with insomnia, restlessness, raised paradoxical (R.E.M.) sleep, epileptic phenomena, and even delirium. It is proposed that a high degree of drug-tolerance and dependence can be rapidly acquired after overdose.Abnormal sleep features of 10 patients resolved only slowly over a period of up to two months after overdose. The data support the view that R.E.M. sleep is concerned with processes of brain repair.     

A neural network model with feature selection for Korean speech act classification

A speech act is a linguistic action intended by a speaker. Speech act classification is an essential part of a dialogue understanding system because the speech act of an utterance is closely tied with the user's intention in the utterance. We propose a neural network model for Korean speech act classification. In addition, we propose a method that extracts morphological features from surface utterances and selects effective ones among the morphological features. Using the feature selection method, the proposed neural network can partially increase precision and decrease training time. In the experiment, the proposed neural network showed better results than other models using comparatively high-level linguistic features. Based on the experimental result, we believe that the proposed neural network model is suitable for real field applications because it is easy to expand the neural network model into other domains. Moreover, we found that neural networks can be useful in speech act classification if we can convert surface sentences into vectors with fixed dimensions by using an effective feature selection method.     

Epilepsy seizure detection using eigen-system spectral estimation and Multiple Layer Perceptron neural network

In this paper, a new approach based on eigen-systems pseudo-spectral estimation methods, namely Eigenvector (EV) and MUSIC, and Multiple Layer Perceptron (MLP) neural network is introduced. In this approach, the calculated EEG (electroencephalogram) spectrum is divided into smaller frequency sub-bands. Then, a set of features, {maximum, entropy, average, standard deviation, mobility}, are extracted from these sub-bands. Next, incorporating a set of the EEG time domain features {standard deviation, complexity measure} with the spectral feature set, a feature vector is formed. The feature vector is then fetched into a MLP neural network to classify the signal into the following three states: normal (healthy), epileptic patient signal in a seizure-free interval (inter-ictal), and epileptic patient signal in a full seizure interval (ictal). The experimental results show that the classification of the EEG signals maybe achieved with approximately 97.5% accuracy and the variance of 0.095% using an available public EEG signals database. The results are among the best reported methods for classifying the three states aforementioned. This is a high speed with high accuracy as well as low misclassifying rate method so it can make the practical and real-time detection of this chronic disease feasible.     

Neural diffusivity and pre-emptive epileptic seizure intervention

The propagation of epileptic seizure activity in the brain is a widespread pathophysiology that, in principle, should yield to intervention techniques guided by mathematical models of neuronal ensemble dynamics. During a seizure, neural activity will deviate from its current dynamical regime to one in which there are significant signal fluctuations. In silico treatments of neural activity are an important tool for the understanding of how the healthy brain can maintain stability, as well as of how pathology can lead to seizures. The hope is that, contained within the mathematical foundations of such treatments, there lie potential strategies for mitigating instabilities, e.g. via external stimulation. Here, we demonstrate that the dynamic causal modelling neuronal state equation generalises to a Fokker-Planck formalism if one extends the framework to model the ways in which activity propagates along the structural connections of neural systems. Using the Jacobian of this generalised state equation, we show that an initially unstable system can be rendered stable via a reduction in diffusivity–i.e., by lowering the rate at which neuronal fluctuations disperse to neighbouring regions. We show, for neural systems prone to epileptic seizures, that such a reduction in diffusivity can be achieved via external stimulation. Specifically, we show that this stimulation should be applied in such a way as to temporarily mirror the activity profile of a pathological region in its functionally connected areas. This counter-intuitive method is intended to be used pre-emptively–i.e., in order to mitigate the effects of the seizure, or ideally even prevent it from occurring in the first place. We offer proof of principle using simulations based on functional neuroimaging data collected from patients with idiopathic generalised epilepsy, in which we successfully suppress pathological activity in a distinct sub-network prior to seizure onset. Our hope is that this technique can form the basis for future real-time monitoring and intervention devices that are capable of treating epilepsy in a non-invasive manner.     

Transfer of an avian genetic reflex epilepsy by embryonic brain graft: a tissue autonomous process?

Electroencephalographic characteristics and clinical symptoms of an avian genetic reflex epilepsy have been transferred from Fayoumi epileptic (Fepi) chickens to non-epileptic chickens by embryonic homotopic grafts of brain neuroepithelium. Transplanted tissues belonging to the prosencephalic vesicle transferred epileptic electrical features while tissues from the mesencephalic vesicle were responsible for seizure motor manifestations of the disease. Thus each of these tissues can express their own specificity when grafted separately in a normal host, but they co-operate to produce the complete epileptic phenotype when grafted together.     

Short-term and long-term memory in single cells

Many approaches have been used to study short- and long-term memory. Bacteria detect chemical gradients using a memory obtained by the combination of a fast excitation process and a slow adaptation process. This model system, which has the advantages of extensive genetic and biochemical information, shows no features of long-term memory. To study long-term memory, neural cell line systems have been developed that exhibit two phenomena associated with learning and memory, habituation and potentiation. The expression of these phenomena in clonal cell lines, devoid of synaptic connections, makes it possible to study the biochemical and molecular mechanisms that contribute to short-term and long-term memory.