EEG-Meta-Microstates: Towards a More Objective Use of Resting-State EEG Microstate Findings Across Studies.

Over the last decade, EEG resting-state microstate analysis has evolved from a niche existence to a widely used and well-accepted methodology. The rapidly increasing body of empirical findings started to yield overarching patterns of associations of biological and psychological states and traits with specific microstate classes. However, currently, this cross-referencing among apparently similar microstate classes of different studies is typically done by "eyeballing" of printed template maps by the individual authors, lacking a systematic procedure. To improve the reliability and validity of future findings, we present a tool to systematically collect the actual data of template maps from as many published studies as possible and present them in their entirety as a matrix of spatial similarity. The tool also allows importing novel template maps and systematically extracting the findings associated with specific microstate maps from ongoing or published studies. The tool also allows importing novel template maps and systematically extracting the findings associated with specific microstate maps in the literature. The analysis of 40 included sets of template maps indicated that: (i) there is a high degree of similarity of template maps across studies, (ii) similar template maps were associated with converging empirical findings, and (iii) representative meta-microstates can be extracted from the individual studies. We hope that this tool will be useful in coming to a more comprehensive, objective, and overarching representation of microstate findings.

Neural Processing of Dynamic Animated Social Interactions in Young Children With Autism Spectrum Disorder: A High-Density Electroencephalography Study.

Background: Atypical neural processing of social visual information contributes to impaired social cognition in autism spectrum disorder. However, evidence for early developmental alterations in neural processing of social contingencies is scarce. Most studies in the literature have been conducted in older children and adults. Here, we aimed to investigate alterations in neural processing of social visual information in children with autism spectrum disorder compared to age-matched typically developing peers. Methods: We used a combination of 129-channel electroencephalography and high-resolution eye-tracking to study differences in the neural processing of dynamic cartoons containing human-like social interactions between 14 male children with autism spectrum disorder and 14 typically developing male children, aged 2-5 years. Using a microstate approach, we identified four prototypical maps in both groups and compared the temporal characteristics and inverse solutions (activation of neural sources) of these maps between groups. Results: Inverse solutions of the group maps that were most dominant during free viewing of the dynamic cartoons indicated decreased prefrontal and cingulate activation, impaired activation of the premotor cortex, and increased activation of parietal, temporal, occipital, and cerebellar regions in children with autism spectrum disorder compared to their typically developing peers. Conclusions: Our findings suggest that impairments in brain regions involved in processing social contingencies embedded in dynamic cartoons are present from an early age in autism spectrum disorder. To the best of our knowledge, this is the first study to investigate neural processing of social interactions of children with autism spectrum disorder using dynamic semi-naturalistic stimuli.

Visual processing deficits in 22q11.2 Deletion Syndrome.

Carriers of the rare 22q11.2 microdeletion present with a high percentage of positive and negative symptoms and a high genetic risk for schizophrenia. Visual processing impairments have been characterized in schizophrenia, but less so in 22q11.2 Deletion Syndrome (DS). Here, we focus on visual processing using high-density EEG and source imaging in 22q11.2DS participants (N = 25) and healthy controls (N = 26) with an illusory contour discrimination task. Significant differences between groups emerged at early and late stages of visual processing. In 22q11.2DS, we first observed reduced amplitudes over occipital channels and reduced source activations within dorsal and ventral visual stream areas during the P1 (100-125 ms) and within ventral visual cortex during the N1 (150-170 ms) visual evoked components. During a later window implicated in visual completion (240-285 ms), we observed an increase in global amplitudes in 22q11.2DS. The increased surface amplitudes for illusory contours at this window were inversely correlated with positive subscales of prodromal symptoms in 22q11.2DS. The reduced activity of ventral and dorsal visual areas during early stages points to an impairment in visual processing seen both in schizophrenia and 22q11.2DS. During intervals related to perceptual closure, the inverse correlation of high amplitudes with positive symptoms suggests that participants with 22q11.2DS who show an increased brain response to illusory contours during the relevant window for contour processing have less psychotic symptoms and might thus be at a reduced prodromal risk for schizophrenia.

Electroencephalographic Resting-State Networks: Source Localization of Microstates.

Using electroencephalography (EEG) to elucidate the spontaneous activation of brain resting-state networks (RSNs) is nontrivial as the signal of interest is of low amplitude and it is difficult to distinguish the underlying neural sources. Using the principles of electric field topographical analysis, it is possible to estimate the meta-stable states of the brain (i.e., the resting-state topographies, so-called microstates). We estimated seven resting-state topographies explaining the EEG data set with k-means clustering (N = 164, 256 electrodes). Using a method specifically designed to localize the sources of broadband EEG scalp topographies by matching sensor and source space temporal patterns, we demonstrated that we can estimate the EEG RSNs reliably by measuring the reproducibility of our findings. After subtracting their mean from the seven EEG RSNs, we identified seven state-specific networks. The mean map includes regions known to be densely anatomically and functionally connected (superior frontal, superior parietal, insula, and anterior cingulate cortices). While the mean map can be interpreted as a "router," crosslinking multiple functional networks, the seven state-specific RSNs partly resemble and extend previous functional magnetic resonance imaging-based networks estimated as the hemodynamic correlates of four canonical EEG microstates.

Deviant dynamics of EEG resting state pattern in 22q11.2 deletion syndrome adolescents: A vulnerability marker of schizophrenia?

Previous studies have repeatedly found altered temporal characteristics of EEG microstates in schizophrenia. The aim of the present study was to investigate whether adolescents affected by the 22q11.2 deletion syndrome (22q11DS), known to have a 30 fold increased risk to develop schizophrenia, already show deviant EEG microstates. If this is the case, temporal alterations of EEG microstates in 22q11DS individuals could be considered as potential biomarkers for schizophrenia. We used high-density (204 channel) EEG to explore between-group microstate differences in 30 adolescents with 22q11DS and 28 age-matched controls. We found an increased presence of one microstate class (class C) in the 22q11DS adolescents with respect to controls that was associated with positive prodromal symptoms (hallucinations). A previous across-age study showed that the class C microstate was more present during adolescence and a combined EEG-fMRI study associated the class C microstate with the salience resting state network, a network known to be dysfunctional in schizophrenia. Therefore, the increased class C microstates could be indexing the increased risk of 22q11DS individuals to develop schizophrenia if confirmed by our ongoing longitudinal study comparing both the adult 22q11DS individuals with and without schizophrenia, as well as schizophrenic individuals with and without 22q11DS.

EEG source imaging of brain states using spatiotemporal regression.

Relating measures of electroencephalography (EEG) back to the underlying sources is a long-standing inverse problem. Here we propose a new method to estimate the EEG sources of identified electrophysiological states that represent spontaneous activity, or are evoked by a stimulus, or caused by disease or disorder. Our method has the unique advantage of seamlessly integrating a statistical significance of the source estimate while efficiently eliminating artifacts (e.g., due to eye blinks, eye movements, bad electrodes). After determining the electrophysiological states in terms of stable topographies using established methods (e.g.: ICA, PCA, k-means, epoch average), we propose to estimate these states' time courses through spatial regression of a General Linear Model (GLM). These time courses are then used to find EEG sources that have a similar time-course (using temporal regression of a second GLM). We validate our method using both simulated and experimental data. Simulated data allows us to assess the difference between source maps obtained by the proposed method and those obtained by applying conventional source imaging of the state topographies. Moreover, we use data from 7 epileptic patients (9 distinct epileptic foci localized by intracranial EEG) and 2 healthy subjects performing an eyes-open/eyes-closed task to elicit activity in the alpha frequency range. Our results indicate that the proposed EEG source imaging method accurately localizes the sources for each of the electrical brain states. Furthermore, our method is particularly suited for estimating the sources of EEG resting states or otherwise weak spontaneous activity states, a problem not adequately solved before.

Altered auditory processing in frontal and left temporal cortex in 22q11.2 deletion syndrome: a group at high genetic risk for schizophrenia.

In order to investigate electroencephalographic (EEG) biomarkers of auditory processing for schizophrenia, we studied a group with a well known high-risk profile: patients with 22q11.2 deletion syndrome (22q11 DS) have a 30% risk of developing schizophrenia during adulthood. We performed high-density EEG source imaging to measure auditory gating of the P50 component of the evoked potential and middle to late latency auditory processing in 21 participants with the 22q11.2 deletion and 17 age-matched healthy controls. While we found no indication of altered P50 suppression in 22q11 DS, we observed marked differences for the first N1 component with increased amplitudes on central electrodes, corresponding to increased activations in dorsal anterior cingulate and medial frontal cortex. We also found a left lateralized reduction of activation of primary and secondary auditory cortex during the second N1 (120ms) and the P2 component in 22q11 DS. Our results show that sensory gating and activations until 50ms were preserved in 22q11 DS, while impairments appear at latencies that correspond to higher order auditory processing. While the increased activation of cingulate and medial frontal cortex could reflect developmental changes in 22q11 DS, the reduced activity seen in left auditory cortex might serve as a biomarker for the development of schizophrenia, if confirmed by longitudinal research protocols.

Validating atlas-guided DOT: a comparison of diffuse optical tomography informed by atlas and subject-specific anatomies.

We describe the validation of an anatomical brain atlas approach to the analysis of diffuse optical tomography (DOT). Using MRI data from 32 subjects, we compare the diffuse optical images of simulated cortical activation reconstructed using a registered atlas with those obtained using a subject's true anatomy. The error in localization of the simulated cortical activations when using a registered atlas is due to a combination of imperfect registration, anatomical differences between atlas and subject anatomies and the localization error associated with diffuse optical image reconstruction. When using a subject-specific MRI, any localization error is due to diffuse optical image reconstruction only. In this study we determine that using a registered anatomical brain atlas results in an average localization error of approximately 18 mm in Euclidean space. The corresponding error when the subject's own MRI is employed is 9.1 mm. In general, the cost of using atlas-guided DOT in place of subject-specific MRI-guided DOT is a doubling of the localization error. Our results show that despite this increase in error, reasonable anatomical localization is achievable even in cases where the subject-specific anatomy is unavailable.

Anatomical atlas-guided diffuse optical tomography of brain activation.

We describe a neuroimaging protocol that utilizes an anatomical atlas of the human head to guide diffuse optical tomography of human brain activation. The protocol is demonstrated by imaging the hemodynamic response to median-nerve stimulation in three healthy subjects, and comparing the images obtained using a head atlas with the images obtained using the subject-specific head anatomy. The results indicate that using the head atlas anatomy it is possible to reconstruct the location of the brain activation to the expected gyrus of the brain, in agreement with the results obtained with the subject-specific head anatomy. The benefits of this novel method derive from eliminating the need for subject-specific head anatomy and thus obviating the need for a subject-specific MRI to improve the anatomical interpretation of diffuse optical tomography images of brain activation.

Effective scattering coefficient of the cerebral spinal fluid in adult head models for diffuse optical imaging.

An efficient computation of the time-dependent forward solution for photon transport in a head model is a key capability for performing accurate inversion for functional diffuse optical imaging of the brain. The diffusion approximation to photon transport is much faster to simulate than the physically correct radiative transport equation (RTE); however, it is commonly assumed that scattering lengths must be much smaller than all system dimensions and all absorption lengths for the approximation to be accurate. Neither of these conditions is satisfied in the cerebrospinal fluid (CSF). Since line-of-sight distances in the CSF are small, of the order of a few millimeters, we explore the idea that the CSF scattering coefficient may be modeled by any value from zero up to the order of the typical inverse line-of-sight distance, or approximately 0.3 mm(-1), without significantly altering the calculated detector signals or the partial path lengths relevant for functional measurements. We demonstrate this in detail by using a Monte Carlo simulation of the RTE in a three-dimensional head model based on clinical magnetic resonance imaging data, with realistic optode geometries. Our findings lead us to expect that the diffusion approximation will be valid even in the presence of the CSF, with consequences for faster solution of the inverse problem.