Design of a Multi-Feature Classification Scheme for Infant Epileptic Seizures.

Neonatal epileptic seizures take place in the early childhood years, accounting for a severe condition with several deaths and neurological problems in newborn neonates. Despite the early advancements on the diagnosis and/or treatment of this condition, as a major difficulty accounts the inability of the physicians to identify and characterize a seizure, as one a small percentage gets detected in neonatal intensive care units (NICU). An important step towards any kind of seizure classification is the detection and reduction of non-cerebral activity. Towards this direction, our multi-feature approach contains spectral and statistical characteristics of EEG signals of 79 infants with suspicion of seizure and assesses the performance of two classification algorithms iteratively. The trained models (Support Vector Machine (SVM) and Random Forest classifiers) yielded high classification performance (>80% and >85% respectively). A robust neonatal seizure classification scheme is thus proposed, along with nine high scoring spectrum and statistical features. The importance of embedding an artefact reduction approach is also discussed, since the complex artifacts spread throughout the signals have great impact on the accuracy of the algorithms. The nine extracted high scoring spectral and statistical features might be used as potential biomarkers for neonatal seizure prediction in a clinical setting.

EEG Source Analysis with a Convolutional Neural Network and Finite Element Analysis.

To reconstruct the electrophysiological activity of brain responses, source analysis is performed through the solution of the forward and inverse problems. The former contains a unique solution while the latter is ill-posed. In this regard, many algorithms have been suggested relying on different prior information for solving the inverse problem. Recently, neural networks have been used to deal with source analysis. However, their underlying training for inverse solutions is based on suboptimal forward modeling. In this work, we propose a CNN that is able to reconstruct EEG brain activity. To train our proposed CNN, a skull-conductivity calibrated and white matter anisotropic head model. Based on this model, we generate simulated EEG data and used them to train our CNN. We first evaluate the performance of our CNN using the simulated EEG data while a realistic application with somatosensory evoked potentials follows. From the results, we observed that the CCN correctly localized the P20/N20 component at the subject-specific Brodmann area 3b and it can potentially localize deeper sources. A comparison is also presented with well-known inverse solutions (single dipole scans and sLORETA) showing similar localization performance. Through these results, an emerging potential for real applications appears on the basis of realistic head modeling.

ECG-Based Semi-Supervised Anomaly Detection for Early Detection and Monitoring of Epileptic Seizures.

Epilepsy is one of the most common brain diseases, characterized by frequent recurrent seizures or "ictal" states. A patient experiences uncontrollable muscular contractions, inducing loss of mobility and balance, which may result in injury or even death during these ictal states. Extensive investigation is vital to establish a systematic approach for predicting and informing patients about oncoming seizures ahead of time. Most methodologies developed are focused on the detection of abnormalities using mostly electroencephalogram (EEG) recordings. In this regard, research has indicated that certain pre-ictal alterations in the Autonomic Nervous System (ANS) can be detected in patient electrocardiogram (ECG) signals. The latter could potentially provide the basis for a robust seizure prediction approach. The recently proposed ECG-based seizure warning systems utilize machine learning models to classify a patient's condition. Such approaches require the incorporation of large, diverse, and thoroughly annotated ECG datasets, limiting their application potential. In this work, we investigate anomaly detection models in a patient-specific context with low supervision requirements. Specifically, we consider One-Class SVM (OCSVM), Minimum Covariance Determinant (MCD) Estimator, and Local Outlier Factor (LOF) models to quantify the novelty or abnormality of pre-ictal short-term (2-3 min) Heart Rate Variability (HRV) features of patients, trained on a reference interval considered to contain stable heart rate as the only form of supervision. Our models are evaluated against labels that were either hand-picked or automatically generated (weak labels) by a two-phase clustering procedure for samples of the "Post-Ictal Heart Rate Oscillations in Partial Epilepsy" (PIHROPE) dataset recorded by the Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, achieving detection in 9 out of 10 cases, with average AUCs of over 93% across all models and warning times ranging from 6 to 30 min prior to seizure. The proposed anomaly detection and monitoring approach can potentially pave the way for early detection and warning of seizure incidents based on body sensor inputs.

Brainstorm-DUNEuro: An integrated and user-friendly Finite Element Method for modeling electromagnetic brain activity.

Human brain activity generates scalp potentials (electroencephalography - EEG), intracranial potentials (iEEG), and external magnetic fields (magnetoencephalography - MEG). These electrophysiology (e-phys) signals can often be measured simultaneously for research and clinical applications. The forward problem involves modeling these signals at their sensors for a given equivalent current dipole configuration within the brain. While earlier researchers modeled the head as a simple set of isotropic spheres, today's magnetic resonance imaging (MRI) data allow for a detailed anatomic description of brain structures and anisotropic characterization of tissue conductivities. We present a complete pipeline, integrated into the Brainstorm software, that allows users to automatically generate an individual and accurate head model based on the subject's MRI and calculate the electromagnetic forward solution using the finite element method (FEM). The head model generation is performed by integrating the latest tools for MRI segmentation and FEM mesh generation. The final head model comprises the five main compartments: white-matter, gray-matter, CSF, skull, and scalp. The anisotropic brain conductivity model is based on the effective medium approach (EMA), which estimates anisotropic conductivity tensors from diffusion-weighted imaging (DWI) data. The FEM electromagnetic forward solution is obtained through the DUNEuro library, integrated into Brainstorm, and accessible with either a user-friendly graphical interface or scripting. With tutorials and example data sets available in an open-source format on the Brainstorm website, this integrated pipeline provides access to advanced FEM tools for electromagnetic modeling to a broader neuroscience community.

Can individually targeted and optimized multi-channel tDCS outperform standard bipolar tDCS in stimulating the primary somatosensory cortex?

BACKGROUND: Transcranial direct current stimulation (tDCS) has emerged as a non-invasive neuro-modulation technique. Most studies show that anodal tDCS increases cortical excitability, however, with variable outcomes. Previously, we have shown in computer simulations that our multi-channel tDCS (mc-tDCS) approach, the distributed constrained maximum intensity (D-CMI) method can potentially lead to better controlled tDCS results due to the improved directionality of the injected current at the target side for individually optimized D-CMI montages. OBJECTIVE: In this study, we test the application of the D-CMI approach in an experimental study to stimulate the somatosensory P20/N20 target source in Brodmann area 3b and compare it with standard bipolar tDCS and sham conditions. METHODS: We applied anodal D-CMI, the standard bipolar and D-CMI based Sham tDCS for 10 min to target the 20 ms post-stimulus somatosensory P20/N20 target brain source in Brodmann area 3b reconstructed using combined magnetoencephalography (MEG) and electroencephalography (EEG) source analysis in realistic head models with calibrated skull conductivity in a group-study with 13 subjects. Finger-stimulated somatosensory evoked fields (SEF) were recorded and the component at 20 ms post-stimulus (M20) was analyzed before and after the application of the three tDCS conditions in order to read out the stimulation effect on Brodmann area 3b. RESULTS: Analysis of the finger stimulated SEF M20 peak before (baseline) and after tDCS shows a significant increase in source amplitude in Brodmann area 3b for D-CMI (6-16 min after tDCS), while no significant effects are found for standard bipolar (6-16 min after tDCS) and sham (6-16 min after tDCS) stimulation conditions. For the later time courses (16-26 and 27-37 min post-stimulation), we found a significant decrease in M20 peak source amplitude for standard bipolar and sham tDCS, while there was no effect for D-CMI. CONCLUSION: Our results indicate that targeted and optimized, and thereby highly individualized, mc-tDCS can outperform standard bipolar stimulation and lead to better control over stimulation outcomes with, however, a considerable amount of additional work compared to standard bipolar tDCS.

Chronic Mild Traumatic Brain Injury: Aberrant Static and Dynamic Connectomic Features Identified Through Machine Learning Model Fusion.

Traumatic Brain Injury (TBI) is a frequently occurring condition and approximately 90% of TBI cases are classified as mild (mTBI). However, conventional MRI has limited diagnostic and prognostic value, thus warranting the utilization of additional imaging modalities and analysis procedures. The functional connectomic approach using resting-state functional MRI (rs-fMRI) has shown great potential and promising diagnostic capabilities across multiple clinical scenarios, including mTBI. Additionally, there is increasing recognition of a fundamental role of brain dynamics in healthy and pathological cognition. Here, we undertake an in-depth investigation of mTBI-related connectomic disturbances and their emotional and cognitive correlates. We leveraged machine learning and graph theory to combine static and dynamic functional connectivity (FC) with regional entropy values, achieving classification accuracy up to 75% (77, 74 and 76% precision, sensitivity and specificity, respectively). As compared to healthy controls, the mTBI group displayed hypoconnectivity in the temporal poles, which correlated positively with semantic (r = 0.43, p < 0.008) and phonemic verbal fluency (r = 0.46, p < 0.004), while hypoconnectivity in the right dorsal posterior cingulate correlated positively with depression symptom severity (r = 0.54, p < 0.0006). These results highlight the importance of residual FC in these regions for preserved cognitive and emotional function in mTBI. Conversely, hyperconnectivity was observed in the right precentral and supramarginal gyri, which correlated negatively with semantic verbal fluency (r=-0.47, p < 0.003), indicating a potential ineffective compensatory mechanism. These novel results are promising toward understanding the pathophysiology of mTBI and explaining some of its most lingering emotional and cognitive symptoms.

First activity and interactions in thalamus and cortex using raw single-trial EEG and MEG elicited by somatosensory stimulation.

Introduction: One of the primary motivations for studying the human brain is to comprehend how external sensory input is processed and ultimately perceived by the brain. A good understanding of these processes can promote the identification of biomarkers for the diagnosis of various neurological disorders; it can also provide ways of evaluating therapeutic techniques. In this work, we seek the minimal requirements for identifying key stages of activity in the brain elicited by median nerve stimulation. Methods: We have used a priori knowledge and applied a simple, linear, spatial filter on the electroencephalography and magnetoencephalography signals to identify the early responses in the thalamus and cortex evoked by short electrical stimulation of the median nerve at the wrist. The spatial filter is defined first from the average EEG and MEG signals and then refined using consistency selection rules across ST. The refined spatial filter is then applied to extract the timecourses of each ST in each targeted generator. These ST timecourses are studied through clustering to quantify the ST variability. The nature of ST connectivity between thalamic and cortical generators is then studied within each identified cluster using linear and non-linear algorithms with time delays to extract linked and directional activities. A novel combination of linear and non-linear methods provides in addition discrimination of influences as excitatory or inhibitory. Results: Our method identifies two key aspects of the evoked response. Firstly, the early onset of activity in the thalamus and the somatosensory cortex, known as the P14 and P20 in EEG and the second M20 for MEG. Secondly, good estimates are obtained for the early timecourse of activity from these two areas. The results confirm the existence of variability in ST brain activations and reveal distinct and novel patterns of connectivity in different clusters. Discussion: It has been demonstrated that we can extract new insights into stimulus processing without the use of computationally costly source reconstruction techniques which require assumptions and detailed modeling of the brain. Our methodology, thanks to its simplicity and minimal computational requirements, has the potential for real-time applications such as in neurofeedback systems and brain-computer interfaces.

Deep Learning Capabilities for the Categorization of Microcalcification.

Breast cancer is the most common cancer in women worldwide. It is the most frequently diagnosed cancer among women in 140 countries out of 184 reporting countries. Lesions of breast cancer are abnormal areas in the breast tissues. Various types of breast cancer lesions include (1) microcalcifications, (2) masses, (3) architectural distortion, and (4) bilateral asymmetry. Microcalcification can be classified as benign, malignant, and benign without a callback. In the present manuscript, we propose an automatic pipeline for the detection of various categories of microcalcification. We performed deep learning using convolution neural networks (CNNs) for the automatic detection and classification of all three categories of microcalcification. CNN was applied using four different optimizers (ADAM, ADAGrad, ADADelta, and RMSProp). The input images of a size of 299 × 299 × 3, with fully connected RELU and SoftMax output activation functions, were utilized in this study. The feature map was obtained using the pretrained InceptionResNetV2 model. The performance evaluation of our classification scheme was tested on a curated breast imaging subset of the DDSM mammogram dataset (CBIS-DDSM), and the results were expressed in terms of sensitivity, specificity, accuracy, and area under the curve (AUC). Our proposed classification scheme outperforms the ability of previously used deep learning approaches and classical machine learning schemes.

A New Multi-Resolution Approach to EEG Brain Modeling Using Local-Global Graphs and Stochastic Petri-Nets.

Recent modeling of brain activities encompasses the fusion of different modalities. However, fusing brain modalities requires not only the efficient and compatible representation of the signals but also the benefits associated with it. For instance, the combination of the functional characteristics of EEGs with the structural features of functional magnetic resonance imaging contributes to a better interpretation localization of brain activities. In this paper, we consider the EEG signals as parallel 2D string images from which we extract their visual abstract representations of EEG features. This representation can benefit not only the EEG modeling of the signals but also a future fusion with another modality, like fMRI. In particular, the new methodology, called Bar-LG, provides a reduced discretization of the EEG signals into selected minima/maxima in order to be used in a form of tokens for EEG brain activities of interest. A formal context-free language is used to express and represent the extracted tokens for the selected active brain regions. Then, a Generalized Stochastic Petri-Nets (GSPN) model is used for expressing the functional associations and interactions of these EEG signals as 2D image regions. An illustrative EEG example of epileptic seizure is presented to show the Bar-LG methodology's abstract capabilities.

Validating EEG, MEG and Combined MEG and EEG Beamforming for an Estimation of the Epileptogenic Zone in Focal Cortical Dysplasia.

MEG and EEG source analysis is frequently used for the presurgical evaluation of pharmacoresistant epilepsy patients. The source localization of the epileptogenic zone depends, among other aspects, on the selected inverse and forward approaches and their respective parameter choices. In this validation study, we compare the standard dipole scanning method with two beamformer approaches for the inverse problem, and we investigate the influence of the covariance estimation method and the strength of regularization on the localization performance for EEG, MEG, and combined EEG and MEG. For forward modelling, we investigate the difference between calibrated six-compartment and standard three-compartment head modelling. In a retrospective study, two patients with focal epilepsy due to focal cortical dysplasia type IIb and seizure freedom following lesionectomy or radiofrequency-guided thermocoagulation (RFTC) used the distance of the localization of interictal epileptic spikes to the resection cavity resp. RFTC lesion as reference for good localization. We found that beamformer localization can be sensitive to the choice of the regularization parameter, which has to be individually optimized. Estimation of the covariance matrix with averaged spike data yielded more robust results across the modalities. MEG was the dominant modality and provided a good localization in one case, while it was EEG for the other. When combining the modalities, the good results of the dominant modality were mostly not spoiled by the weaker modality. For appropriate regularization parameter choices, the beamformer localized better than the standard dipole scan. Compared to the importance of an appropriate regularization, the sensitivity of the localization to the head modelling was smaller, due to similar skull conductivity modelling and the fixed source space without orientation constraint.

Individually optimized multi-channel tDCS for targeting somatosensory cortex.

OBJECTIVE: Transcranial direct current stimulation (tDCS) is a non-invasive neuro-modulation technique that delivers current through the scalp by a pair of patch electrodes (2-Patch). This study proposes a new multi-channel tDCS (mc-tDCS) optimization method, the distributed constrained maximum intensity (D-CMI) approach. For targeting the P20/N20 somatosensory source at Brodmann area 3b, an integrated combined magnetoencephalography (MEG) and electroencephalography (EEG) source analysis is used with individualized skull conductivity calibrated realistic head modeling. METHODS: Simulated electric fields (EF) for our new D-CMI method and the already known maximum intensity (MI), alternating direction method of multipliers (ADMM) and 2-Patch methods were produced and compared for the individualized P20/N20 somatosensory target for 10 subjects. RESULTS: D-CMI and MI showed highest intensities parallel to the P20/N20 target compared to ADMM and 2-Patch, with ADMM achieving highest focality. D-CMI showed a slight reduction in intensity compared to MI while reducing side effects and skin level sensations by current distribution over multiple stimulation electrodes. CONCLUSION: Individualized D-CMI montages are preferred for our follow up somatosensory experiment to provide a good balance between high current intensities at the target and reduced side effects and skin sensations. SIGNIFICANCE: An integrated combined MEG and EEG source analysis with D-CMI montages for mc-tDCS stimulation potentially can improve control, reproducibility and reduce sensitivity differences between sham and real stimulations.

Reconstructing subcortical and cortical somatosensory activity via the RAMUS inverse source analysis technique using median nerve SEP data.

This study concerns reconstructing brain activity at various depths based on non-invasive EEG (electroencephalography) scalp measurements. We aimed at demonstrating the potential of the RAMUS (randomized multiresolution scanning) technique in localizing weakly distinguishable far-field sources in combination with coinciding cortical activity. As we have shown earlier theoretically and through simulations, RAMUS is a novel mathematical method that by employing the multigrid concept, allows marginalizing noise and depth bias effects and thus enables the recovery of both cortical and subcortical brain activity. To show this capability with experimental data, we examined the 14-30 ms post-stimulus somatosensory evoked potential (SEP) responses of human median nerve stimulation in three healthy adult subjects. We aim at reconstructing the different response components by evaluating a RAMUS-based estimate for the primary current density in the nervous tissue. We present source reconstructions obtained with RAMUS and compare them with the literature knowledge of the SEP components and the outcome of the unit-noise gain beamformer (UGNB) and standardized low-resolution brain electromagnetic tomography (sLORETA). We also analyzed the effect of the iterative alternating sequential technique, the optimization technique of RAMUS, compared to the classical minimum norm estimation (MNE) technique. Matching with our previous numerical studies, the current results suggest that RAMUS could have the potential to enhance the detection of simultaneous deep and cortical components and the distinction between the evoked sulcal and gyral activity.

Parametrizing the Conditionally Gaussian Prior Model for Source Localization with Reference to the P20/N20 Component of Median Nerve SEP/SEF.

In this article, we focused on developing the conditionally Gaussian hierarchical Bayesian model (CG-HBM), which forms a superclass of several inversion methods for source localization of brain activity using somatosensory evoked potential (SEP) and field (SEF) measurements. The goal of this proof-of-concept study was to improve the applicability of the CG-HBM as a superclass by proposing a robust approach for the parametrization of focal source scenarios. We aimed at a parametrization that is invariant with respect to altering the noise level and the source space size. The posterior difference between the gamma and inverse gamma hyperprior was minimized by optimizing the shape parameter, while a suitable range for the scale parameter can be obtained via the prior-over-measurement signal-to-noise ratio, which we introduce as a new concept in this study. In the source localization experiments, the primary generator of the P20/N20 component was detected in the Brodmann area 3b using the CG-HBM approach and a parameter range derived from the existing knowledge of the Tikhonov-regularized minimum norm estimate, i.e., the classical Gaussian prior model. Moreover, it seems that the detection of deep thalamic activity simultaneously with the P20/N20 component with the gamma hyperprior can be enhanced while using a close-to-optimal shape parameter value.

Inter-Subject Variability of Skull Conductivity and Thickness in Calibrated Realistic Head Models.

Skull conductivity has a substantial influence on EEG and combined EEG and MEG source analysis as well as on optimized transcranial electric stimulation. To overcome the use of standard literature values, we propose a non-invasive two-level calibration procedure to estimate skull conductivity individually in a group study with twenty healthy adults. Our procedure requires only an additional run of combined somatosensory evoked potential and field data, which can be easily integrated in EEG/MEG experiments. The calibration procedure uses the P20/N20 topographies and subject-specific realistic head models from MRI. We investigate the inter-subject variability of skull conductivity and relate it to skull thickness, age and gender of the subjects, to the individual scalp P20/N20 surface distance between the P20 potential peak and the N20 potential trough as well as to the individual source depth of the P20/N20 source. We found a considerable inter-subject variability for (calibrated) skull conductivity (8.44 ± 4.84 mS/m) and skull thickness (5.97 ± 1.19 mm) with a statistically significant correlation between them (rho = 0.52). Age showed a statistically significant negative correlation with skull conductivity (rho = -0.5). Furthermore, P20/N20 surface distance and source depth showed large inter-subject variability of 12.08 ± 3.21 cm and 15.45 ± 4.54 mm, respectively, but there was no significant correlation between them. We also found no significant differences among gender subgroups for the investigated measures. It is thus important to take the inter-subject variability of skull conductivity and thickness into account by means of using subject-specific calibrated realistic head modeling.

The effect of stimulation type, head modeling, and combined EEG and MEG on the source reconstruction of the somatosensory P20/N20 component.

Modeling and experimental parameters influence the Electro- (EEG) and Magnetoencephalography (MEG) source analysis of the somatosensory P20/N20 component. In a sensitivity group study, we compare P20/N20 source analysis due to different stimulation type (Electric-Wrist [EW], Braille-Tactile [BT], or Pneumato-Tactile [PT]), measurement modality (combined EEG/MEG - EMEG, EEG, or MEG) and head model (standard or individually skull-conductivity calibrated including brain anisotropic conductivity). Considerable differences between pairs of stimulation types occurred (EW-BT: 8.7 ± 3.3 mm/27.1° ± 16.4°, BT-PT: 9 ± 5 mm/29.9° ± 17.3°, and EW-PT: 9.8 ± 7.4 mm/15.9° ± 16.5° and 75% strength reduction of BT or PT when compared to EW) regardless of the head model used. EMEG has nearly no localization differences to MEG, but large ones to EEG (16.1 ± 4.9 mm), while source orientation differences are non-negligible to both EEG (14° ± 3.7°) and MEG (12.5° ± 10.9°). Our calibration results show a considerable inter-subject variability (3.1-14 mS/m) for skull conductivity. The comparison due to different head model show localization differences smaller for EMEG (EW: 3.4 ± 2.4 mm, BT: 3.7 ± 3.4 mm, and PT: 5.9 ± 6.8 mm) than for EEG (EW: 8.6 ± 8.3 mm, BT: 11.8 ± 6.2 mm, and PT: 10.5 ± 5.3 mm), while source orientation differences for EMEG (EW: 15.4° ± 6.3°, BT: 25.7° ± 15.2° and PT: 14° ± 11.5°) and EEG (EW: 14.6° ± 9.5°, BT: 16.3° ± 11.1° and PT: 12.9° ± 8.9°) are in the same range. Our results show that stimulation type, modality and head modeling all have a non-negligible influence on the source reconstruction of the P20/N20 component. The complementary information of both modalities in EMEG can be exploited on the basis of detailed and individualized head models.

Aberrant Whole-Brain Transitions and Dynamics of Spontaneous Network Microstates in Mild Traumatic Brain Injury.

Dynamic Functional Connectivity (DFC) analysis is a promising approach for the characterization of brain electrophysiological activity. In this study, we investigated abnormal alterations due to mild Traumatic Brain Injury (mTBI) using DFC of the source reconstructed magnetoencephalographic (MEG) resting-state recordings. Brain activity in several well-known frequency bands was first reconstructed using beamforming of the MEG data to determine ninety anatomical brain regions of interest. A DFC graph was formulated using the imaginary part of phase-locking values, which were obtained from 30 mTBI patients and 50 healthy controls (HC). Subsequently, we estimated normalized Laplacian transformations of individual, statistically and topologically filtered quasi-static graphs. The corresponding eigenvalues of each node synchronization were then computed and through the neural-gas algorithm, we quantized the evolution of the eigenvalues resulting in distinct network microstates (NMstates). The discrimination level between the two groups was assessed using an iterative cross-validation classification scheme with features either the NMstates in each frequency band, or the combination of the so-called chronnectomics (flexibility index, occupancy time of NMstate, and Dwell time) with the complexity index over the evolution of the NMstates across all frequency bands. Classification performance based on chronnectomics showed 80% accuracy, 99% sensitivity, and 49% specificity. However, performance was much higher (accuracy: 91-97%, sensitivity: 100%, and specificity: 77-93%) when focusing on the microstates. Exploring the mean node degree within and between brain anatomical networks (default mode network, frontoparietal, occipital, cingulo-opercular, and sensorimotor), a reduced pattern occurred from lower to higher frequency bands, with statistically significant stronger degrees for the HC than the mTBI group. A higher entropic profile on the temporal evolution of the modularity index was observed for both NMstates for the mTBI group across frequencies. A significant difference in the flexibility index was observed between the two groups for the ß frequency band. The latter finding may support a central role of the thalamus impairment in mTBI. The current study considers a complete set of frequency-dependent connectomic markers of mTBI-caused alterations in brain connectivity that potentially could serve as markers to assess the return of an injured subject back to normality.

Constrained maximum intensity optimized multi-electrode tDCS targeting of human somatosensory network.

Transcranial direct current stimulation (tDCS) is a noninvasive method that delivers current through the scalp to enhance or suppress brain activity. The standard way of applying tDCS is by the use of two large rectangular sponge electrodes on the scalp. The resulting currents often stimulate a broad region of the brain distributed over brain networks. In order to address this issue, recently, multi-electrode transcranial direct current stimulation with optimized montages has been used to stimulate brain regions of interest (ROI) with improved trade-off between focality and intensity of the electrical current at the target brain region. However, in many cases only the location of target region is considered and not the orientation. Here we emphasize the importance of calculating the individualized target location and orientation by combined electroencephalography and magnetoencephalography (EMEG) source analysis in individualized skull-conductivity calibrated finite element method (FEM) head models and stimulate the target region by four different tDCS montages. We have chosen the generator of the P20/N20 component, located at Brodmann area 3b and oriented mainly from posterior to anterior directions as our target for stimulation because it can be modeled as a single dipole source with a fixed position and orientation. The simulations will deliver optimized excitatory and inhibitory electrode montages that are in future investigations compared to standard and sham tDCS in a somatosensory experiment. We also present a new constrained maximum intensity (CMI) optimization approach that better distributes the currents over multiple electrodes, therefore should lead to less tingling and burning sensations at the skin, and thus allows an easier realization of the sham condition significantly reducing the current intensity parallel to the target.

Data-Driven Topological Filtering Based on Orthogonal Minimal Spanning Trees: Application to Multigroup Magnetoencephalography Resting-State Connectivity.

In the present study, a novel data-driven topological filtering technique is introduced to derive the backbone of functional brain networks relying on orthogonal minimal spanning trees (OMSTs). The method aims to identify the essential functional connections to ensure optimal information flow via the objective criterion of global efficiency minus the cost of surviving connections. The OMST technique was applied to multichannel, resting-state neuromagnetic recordings from four groups of participants: healthy adults (n = 50), adults who have suffered mild traumatic brain injury (n = 30), typically developing children (n = 27), and reading-disabled children (n = 25). Weighted interactions between network nodes (sensors) were computed using an integrated approach of dominant intrinsic coupling modes based on two alternative metrics (symbolic mutual information and phase lag index), resulting in excellent discrimination of individual cases according to their group membership. Classification results using OMST-derived functional networks were clearly superior to results using either relative power spectrum features or functional networks derived through the conventional minimal spanning tree algorithm.

Altered Rich-Club and Frequency-Dependent Subnetwork Organization in Mild Traumatic Brain Injury: A MEG Resting-State Study.

Functional brain connectivity networks exhibit "small-world" characteristics and some of these networks follow a "rich-club" organization, whereby a few nodes of high connectivity (hubs) tend to connect more densely among themselves than to nodes of lower connectivity. The Current study followed an "attack strategy" to compare the rich-club and small-world network organization models using Magnetoencephalographic (MEG) recordings from mild traumatic brain injury (mTBI) patients and neurologically healthy controls to identify the topology that describes the underlying intrinsic brain network organization. We hypothesized that the reduction in global efficiency caused by an attack targeting a model's hubs would reveal the "true" underlying topological organization. Connectivity networks were estimated using mutual information as the basis for cross-frequency coupling. Our results revealed a prominent rich-club network organization for both groups. In particular, mTBI patients demonstrated hyper-synchronization among rich-club hubs compared to controls in the δ band and the δ-γ1, θ-γ1, and ß-γ2 frequency pairs. Moreover, rich-club hubs in mTBI patients were overrepresented in right frontal brain areas, from θ to γ1 frequencies, and underrepresented in left occipital regions in the δ-ß, δ-γ1, θ-ß, and ß-γ2 frequency pairs. These findings indicate that the rich-club organization of resting-state MEG, considering its role in information integration and its vulnerability to various disorders like mTBI, may have a significant predictive value in the development of reliable biomarkers to help the validation of the recovery from mTBI. Furthermore, the proposed approach might be used as a validation tool to assess patient recovery.