EEG source localization: comparative study of classical and neural network methods.

We address the problem of estimating biopotential sources within the brain, based on EEG signals observed on the scalp. This problem, known as the inverse problem of electrophysiology, has no closed-form solution, and requires iterative techniques such as the Levenberg-Marquardt (LM) algorithm. Considering the nonlinear nature of the inverse problem, and the low signal to noise ratio inherent in EEG signals, a backpropagation neural network (BPN) has been recently proposed as a solution. The technique has not been properly compared with classical techniques such as the LM method, or with more recent neural network techniques such as the Radial Basis Function (RBF) network. In this paper, we provide improved strategies based on BPN and consider RBF networks in solving the inverse problem. We compare the performances of BPN, RBF and a hybrid technique with that of the classical LM method.     

脑磁源的定位研究

在脑电脑磁研究中,常将大脑视为一电磁系统,利用准静态近似下的麦克斯韦方程,可以发现代表脑神经元活动的原在电流密度与脑外磁场之间呈线性关系。在高斯哭喊杨存在的情况下,采用极大似然估计理论,讨论了一种基于脑磁场时域－罕注解磁源定位问题的一般方法。球对称导体模型下的模拟计算表明,这一方法是有效的。对于考虑真实头模型下的磁源定位问题求解磁源定位,提出了一种联合使用脑磁脑电数据的近似方法。     

Use of a neural mass model for the analysis of effective connectivity among cortical regions based on high resolution EEG recordings

Assessment of brain connectivity among different brain areas during cognitive or motor tasks is a crucial problem in neuroscience today. Aim of this work is to use a neural mass model to assess the effect of various connectivity patterns in cortical electroencephalogram (EEG) power spectral density, and investigate the possibility to derive connectivity circuits from EEG data. To this end, a model of an individual region of interest (ROI) has been built as the parallel arrangement of three populations, each described as in Wendling et al. (Eur J Neurosci 15:1499–1508, 2002). Connectivity among ROIs includes three parameters, which specify the strength of connection in the different frequency bands. The following main steps have been followed: (1) we analyzed how the power spectral density (PSD) is significantly modified by the kind of coupling hypothesized among the ROIs; (2) with the model, and using an automatic fitting procedure, we looked for a simple connectivity circuit able to reproduce PSD of cortical EEG in three ROIs during a finger-movement task. The estimated parameters represent the strength of connections among the ROIs in the different frequency bands. Cortical EEGs were computed with an inverse propagation algorithm, starting from measurement performed with 96 electrodes on the scalp. The present study suggests that the model can be used as a simulation tool, able to mimic the effect of connectivity on EEG. Moreover, it can be used to look for simple connectivity circuits, able to explain the main features of observed cortical PSD. These results may open new prospectives in the use of neurophysiological models, instead of empirical models, to assess effective connectivity from neuroimaging information.     

Measurement of the hyperelastic properties of ex vivo brain tissue slices

The elastic and hyperelastic properties of brain tissue are of interest to the medical research community as there are several applications where accurate characterization of these properties is crucial for an accurate outcome. The linear response is applicable to brain elastography, while the non-linear response is of interest for surgical simulation programs. Because of the biological differences between gray and white matter, it is reasonable to expect a difference in their mechanical properties. The goal of this work is to characterize the elastic and hyperelastic properties of the brain gray and white matter. In this method, force-displacement data of these tissues were acquired from 25 different brain samples using an indentation apparatus. These data were processed with an inverse problem algorithm using finite element method as the forward problem solver. Young's modulus and the hyperelastic parameters corresponding to the commonly used Polynomial, Yeoh, Arruda-Boyce, and Ogden models were obtained. The parameters characterizing the linear and non-linear mechanical behavior of gray and white matters were found to be significantly different. Young's modulus was 1787±186 and 1195±157Pa for white matter and gray matter, respectively. Among hyperelastic models, due to its accuracy, fewer parameters and shorter computational time requirements, Yeoh model was found to be the most suitable. Due to the significant differences between the linear and non-linear tissue response, we conclude that incorporating these differences into brain biomechanical models is necessary to increase accuracy.     

A graphical approach for evaluating effective connectivity in neural systems

The identification of effective connectivity from time-series data such as electroencephalogram (EEG) or time-resolved function magnetic resonance imaging (fMRI) recordings is an important problem in brain imaging. One commonly used approach to inference effective connectivity is based on vector autoregressive models and the concept of Granger causality. However, this probabilistic concept of causality can lead to spurious causalities in the presence of latent variables. Recently, graphical models have been used to discuss problems of causal inference for multivariate data. In this paper, we extend these concepts to the case of time-series and present a graphical approach for discussing Granger-causal relationships among multiple time-series. In particular, we propose a new graphical representation that allows the characterization of spurious causality and, thus, can be used to investigate spurious causality. The method is demonstrated with concurrent EEG and fMRI recordings which are used to investigate the interrelations between the alpha rhythm in the EEG and blood oxygenation level dependent (BOLD) responses in the fMRI. The results confirm previous findings on the location of the source of the EEG alpha rhythm.     

脑源定位技术的精度评估及其在实际中的应用

脑源定位技术旨在通过头皮表面的脑电、脑磁信号来识别大脑内的神经活动源，是研究大脑皮层神经活动、认知过程和病理功能的基础。其毫秒级的时间分辨率可以有效弥补功能核磁共振在低时间分辨率方面的不足。然而，理论分析层面中逆问题的不适定性，以及实践操作层面上不同的记录方式、电极数量和头模型构建等过程带来的误差，给脑源定位的准确性带来极大挑战，也在一定程度上限制了脑源定位方法在神经科学和心理学研究以及临床诊断治疗中的实际应用。因此，理论分析和实践操作层面中的精度评估在脑源定位方法的实际使用中至关重要。针对以上问题，本文在对现有脑源定位方法介绍的基础上，着重分析了脑源定位技术的精度评估方法以及其在基础研究和临床诊断治疗中的实际应用。具体地，本文在理论分析中总结了基于空间分辨率、基于点扩散以及串扰函数的评估方法对于不同脑源定位方法中源的重叠程度和其他源对目标源的影响；在实践操作中介绍了记录方式、电极数量和密度、头部容积传导模型等因素对源定位精度的影响；进一步介绍了脑源定位技术在时频分析、连通性分析中的应用，以及其在临床中的应用，包括癫痫、注意缺陷与多动障碍等脑部疾病。     

Identification of BDNF Sensitive Electrophysiological Markers of Synaptic Activity and Their Structural Correlates in Healthy Subjects Using a Genetic Approach Utilizing the Functional BDNF Val66Met Polymorphism

Increasing evidence suggests that synaptic dysfunction is a core pathophysiological hallmark of neurodegenerative disorders. Brain-derived neurotropic factor (BDNF) is key synaptogenic molecule and targeting synaptic repair through modulation of BDNF signalling has been suggested as a potential drug discovery strategy. The development of such “synaptogenic” therapies depend on the availability of BDNF sensitive markers of synaptic function that could be utilized as biomarkers for examining target engagement or drug efficacy in humans. Here we have utilized the BDNF Val66Met genetic polymorphism to examine the effect of the polymorphism and genetic load (i.e. Met allele load) on electrophysiological (EEG) markers of synaptic activity and their structural (MRI) correlates. Sixty healthy adults were prospectively recruited into the three genetic groups (Val/Val, Val/Met, Met/Met). Subjects also underwent fMRI, tDCS/TMS, and cognitive assessments as part of a larger study. Overall, some of the EEG markers of synaptic activity and brain structure measured with MRI were the most sensitive markers of the polymorphism. Met carriers showed decreased oscillatory activity and synchrony in the neural network subserving error-processing, as measured during a flanker task (ERN); and showed increased slow-wave activity during resting. There was no evidence for a Met load effect on the EEG measures and the polymorphism had no effects on MMN and P300. Met carriers also showed reduced grey matter volume in the anterior cingulate and in the (left) prefrontal cortex. Furthermore, anterior cingulate grey matter volume, and oscillatory EEG power during the flanker task predicted subsequent behavioural adaptation, indicating a BDNF dependent link between brain structure, function and behaviour associated with error processing and monitoring. These findings suggest that EEG markers such as ERN and resting EEG could be used as BDNF sensitive functional markers in early clinical development to examine target engagement or drug related efficacy of synaptic repair therapies in humans.     

Computation of the electroencephalogram (EEG) from network models of point neurons

The electroencephalogram (EEG) is a major tool for non-invasively studying brain function and dysfunction. Comparing experimentally recorded EEGs with neural network models is important to better interpret EEGs in terms of neural mechanisms. Most current neural network models use networks of simple point neurons. They capture important properties of cortical dynamics, and are numerically or analytically tractable. However, point neurons cannot generate an EEG, as EEG generation requires spatially separated transmembrane currents. Here, we explored how to compute an accurate approximation of a rodent’s EEG with quantities defined in point-neuron network models. We constructed different approximations (or proxies) of the EEG signal that can be computed from networks of leaky integrate-and-fire (LIF) point neurons, such as firing rates, membrane potentials, and combinations of synaptic currents. We then evaluated how well each proxy reconstructed a ground-truth EEG obtained when the synaptic currents of the LIF model network were fed into a three-dimensional network model of multicompartmental neurons with realistic morphologies. Proxies based on linear combinations of AMPA and GABA currents performed better than proxies based on firing rates or membrane potentials. A new class of proxies, based on an optimized linear combination of time-shifted AMPA and GABA currents, provided the most accurate estimate of the EEG over a wide range of network states. The new linear proxies explained 85–95% of the variance of the ground-truth EEG for a wide range of network configurations including different cell morphologies, distributions of presynaptic inputs, positions of the recording electrode, and spatial extensions of the network. Non-linear EEG proxies using a convolutional neural network (CNN) on synaptic currents increased proxy performance by a further 2–8%. Our proxies can be used to easily calculate a biologically realistic EEG signal directly from point-neuron simulations thus facilitating a quantitative comparison between computational models and experimental EEG recordings.     

基于模拟退火法由脑磁图推测电流偶极子参数

利用模拟退火（Ｓｉｍｕｌａｔｅｄ Ａｎｎｅａｌｉｎｇ） 算法,由脑磁图（ ＭＥＧ） 数据反演脑内作为磁源的单电流偶极子参数,可以得到理想的结果。在上述工作的基础上,对脑内多电流偶极子参数的反演,则呈现如下状况：即以少于实际源数目的偶极子为源假设反演,目标函数得不到极小优化。反之,目标函数可以得到极小优化, 但出现多余的伪偶极子, 且这些伪偶极子在多次不同条件的反演结果中,处于不稳定状态。若将多次反演结果中处于不稳定状态的偶极子作为伪偶极子的判据而将其排除,则可以得到一种判断磁源偶极子数目的方法     

Localization of brain electrical activity sources and hemodynamic activity foci during motor imagery

The sources of brain activity that make the maximum contribution to EEG patterns corresponding to motor imagery have been studied. The accuracy of their classification determines the efficiency of brain-computer interface (BCI) for controlling external technical devices directly by brain signals, without the involvement of muscle activity. Brain activity sources are identified by independent component analysis. The independent components providing the maximum BCI classification accuracy are considered relevant for the motor imagery task. The two most relevant sources exhibit clearly marked event-related desynchronization and synchronization of the μ-rhythm during the imagery of contra- and ipsilateral hand movements. These sources were localized by solving the inverse EEG problem with due consideration for individual geometry of the brain and its covers, as determined by magnetic resonance imaging. Each of the sources was shown to be localized in the 3a area of the primary somatosensory cortex corresponding to proprioceptive sensitivity of the contralateral hand. Their positions were close to the foci of BOLD activity obtained by fMRI.     

Nonlinear EEG analysis based on a neural mass model

The well-known neural mass model described by Lopes da Silva et al. (1976) and Zetterberg et al. (1978) is fitted to actual EEG data. This is achieved by reformulating the original set of integral equations as a continuous-discrete state space model. The local linearization approach is then used to discretize the state equation and to construct a nonlinear Kalman filter. On this basis, a maximum likelihood procedure is used for estimating the model parameters for several EEG recordings. The analysis of the noise-free differential equations of the estimated models suggests that there are two different types of alpha rhythms: those with a point attractor and others with a limit cycle attractor. These attractors are also found by means of a nonlinear time series analysis of the EEG recordings. We conclude that the Hopf bifurcation described by Zetterberg et al. (1978) is present in actual brain dynamics. Received: 11 August 1997 / Accepted in revised form: 20 April 1999     

Dipole characterization of single neurons from their extracellular action potentials

The spatial variation of the extracellular action potentials (EAP) of a single neuron contains information about the size and location of the dominant current source of its action potential generator, which is typically in the vicinity of the soma. Using this dependence in reverse in a three-component realistic probe + brain + source model, we solved the inverse problem of characterizing the equivalent current source of an isolated neuron from the EAP data sampled by an extracellular probe at multiple independent recording locations. We used a dipole for the model source because there is extensive evidence it accurately captures the spatial roll-off of the EAP amplitude, and because, as we show, dipole localization, beyond a minimum cell-probe distance, is a more accurate alternative to approaches based on monopole source models. Dipole characterization is separable into a linear dipole moment optimization where the dipole location is fixed, and a second, nonlinear, global optimization of the source location. We solved the linear optimization on a discrete grid via the lead fields of the probe, which can be calculated for any realistic probe + brain model by the finite element method. The global source location was optimized by means of Tikhonov regularization that jointly minimizes model error and dipole size. The particular strategy chosen reflects the fact that the dipole model is used in the near field, in contrast to the typical prior applications of dipole models to EKG and EEG source analysis. We applied dipole localization to data collected with stepped tetrodes whose detailed geometry was measured via scanning electron microscopy. The optimal dipole could account for 96% of the power in the spatial variation of the EAP amplitude. Among various model error contributions to the residual, we address especially the error in probe geometry, and the extent to which it biases estimates of dipole parameters. This dipole characterization method can be applied to any recording technique that has the capabilities of taking multiple independent measurements of the same single units.     

Explicit-duration hidden Markov model inference of UP-DOWN states from continuous signals

Neocortical neurons show UP-DOWN state (UDS) oscillations under a variety of conditions. These UDS have been extensively studied because of the insight they can yield into the functioning of cortical networks, and their proposed role in putative memory formation. A key element in these studies is determining the precise duration and timing of the UDS. These states are typically determined from the membrane potential of one or a small number of cells, which is often not sufficient to reliably estimate the state of an ensemble of neocortical neurons. The local field potential (LFP) provides an attractive method for determining the state of a patch of cortex with high spatio-temporal resolution; however current methods for inferring UDS from LFP signals lack the robustness and flexibility to be applicable when UDS properties may vary substantially within and across experiments. Here we present an explicit-duration hidden Markov model (EDHMM) framework that is sufficiently general to allow statistically principled inference of UDS from different types of signals (membrane potential, LFP, EEG), combinations of signals (e.g., multichannel LFP recordings) and signal features over long recordings where substantial non-stationarities are present. Using cortical LFPs recorded from urethane-anesthetized mice, we demonstrate that the proposed method allows robust inference of UDS. To illustrate the flexibility of the algorithm we show that it performs well on EEG recordings as well. We then validate these results using simultaneous recordings of the LFP and membrane potential (MP) of nearby cortical neurons, showing that our method offers significant improvements over standard methods. These results could be useful for determining functional connectivity of different brain regions, as well as understanding network dynamics.     

Estimation of synaptic currents by recordings from extracellular electrodes

A method for estimating the synaptic current distribution is described, which is based on solving the inverse problem for a system of homogeneously distributed parallel cylinders as a model of dendrites of the pyramidal neurons. The estimates are compared with the data known from literature and those obtained in an independent model.     

Identification of movement-related cortical potentials with optimized spatial filtering and principal component analysis

We present a method for detecting movement intention from multichannel electroencephalographic (EEG) recordings. Movement intention is expressed as a slow negative deflection in amplitude of the EEG signal recorded above the motor cortex. This deflection is known as a movement-related cortical potential (MRCP). Detection of movement intention implies discrimination between MRCPs and noise. The signal-to-noise ratio of MRCPs was improved by an optimized spatial filter. Features were extracted with principal component analysis or locality preserving projections from the spatially filtered signals and classification between MRCPs and noise was performed with a k-nearest neighbors algorithm, modified by adjusting the decision rule to improve specificity, and a support vector machine approach. In one representative subject the sensitivity and specificity in detection were in the range 80–90% and 98–99.5%, respectively. The method seems promising for the development of asynchronous brain–computer interfaces (BCIs) based on MRCPs.     

Cognitive brain–Computer interface and probable aspects of its practical application

A new type of brain-computer interface was elaborated. It considers a variety of brain activity parameters to determine the type of mental operation being performed at the moment. The corresponding algorithm previously developed in the lab was modified for real-time application. The possibility of interface application for cognitive skills training was investigated. In the proposed paradigm, as soon as the EEG spectral pattern was adequate for the current task, some clue to the solution was presented. As we supposed, such positive biofeedback should facilitate memorization of the current brain state. After just one learning session, the differences in EEG spectra, corresponding to two types of tasks, were concentrated in more narrow frequency ranges. It indicates a decrease in mental effort. Moreover, the majority of subjects succeeded in solving the tasks faster, which is evidence of increased efficiency. The developed interface could be used for the new type of training, based on objective features of brain activity.     

EEG analysis by means of the Parcor coefficients

The present study demonstrates the statistical qualities of electrical brain activity by using Parcor coefficients. As a result, the statistical interference of the EEG samples under consideration turns out to be relatively small, implying constraints on the interpretion of the spectra, as well as on the operational calculus of the Wiener criterion. An algorithm based on the linear prediction filter is provided which, moreover, makes use of the Toeplitz structure of the covariance matrix. Although not discussed here, the application of the Parcor coefficients to the general problem of model building is apparent.     

A quantitative model for differential motility of gliomas in grey and white matter

We have extended a mathematical model of gliomas based on proliferation and diffusion rates to incorporate the effects of augmented cell motility in white matter as compared to grey matter. Using a detailed mapping of the white and grey matter in the brain developed for a MRI simulator, we have been able to simulate model tumours on an anatomically accurate brain domain. Our simulations show good agreement with clinically observed tumour geometries and suggest paths of submicroscopic tumour invasion not detectable on CT or MRI images. We expect this model to give insight into microscopic and submicroscopic invasion of the human brain by glioma cells. This method gives insight in microscopic and submicroscopic invasion of the human brain by glioma cells. Additionally, the model can be useful in defining expected pathways of invasion by glioma cells and thereby identify regions of the brain on which to focus treatments.     

Electric Field Encephalography as a Tool for Functional Brain Research: A Modeling Study

We introduce the notion of Electric Field Encephalography (EFEG) based on measuring electric fields of the brain and demonstrate, using computer modeling, that given the appropriate electric field sensors this technique may have significant advantages over the current EEG technique. Unlike EEG, EFEG can be used to measure brain activity in a contactless and reference-free manner at significant distances from the head surface. Principal component analysis using simulated cortical sources demonstrated that electric field sensors positioned 3 cm away from the scalp and characterized by the same signal-to-noise ratio as EEG sensors provided the same number of uncorrelated signals as scalp EEG. When positioned on the scalp, EFEG sensors provided 2–3 times more uncorrelated signals. This significant increase in the number of uncorrelated signals can be used for more accurate assessment of brain states for non-invasive brain-computer interfaces and neurofeedback applications. It also may lead to major improvements in source localization precision. Source localization simulations for the spherical and Boundary Element Method (BEM) head models demonstrated that the localization errors are reduced two-fold when using electric fields instead of electric potentials. We have identified several techniques that could be adapted for the measurement of the electric field vector required for EFEG and anticipate that this study will stimulate new experimental approaches to utilize this new tool for functional brain research.     

Seizure source localization using a hybrid second order blind identification and extended rival penalized competitive learning algorithm

Localization of seizure sources prior to neurosurgery is crucial. In this paper, a new method is proposed to localize the seizure sources from multi-channel electroencephalogram (EEG) signals. Blind source separation based on second order blind identification (SOBI) is primarily applied to estimate the brain source signals in each window of the EEG signals. A new clustering method based on rival penalized competitive learning (RPCL) is then developed to cluster the rows of the estimated unmixing matrices in all the windows. The algorithm also includes pre and post-processing stages. By multiplying each cluster center to the EEG signals, the brain signal sources are approximated. According to a complexity value measure, the main seizure source signal is separated from the others. This signal is projected back to the electrodes’ space and is subjected to the dipole source localization using a single dipole model. The simulation results verify the accuracy of the system. In addition, correct localization of the seizure source is consistent with the clinical tests derived using the simultaneous intracranial recordings.