Nikolaos A. Laskaris

Tracking brain dynamics via time-dependent network analysis

Complex network analysis is currently employed in neuroscience research to describe the neuron pathways in the brain with a small number of computable measures that have neurobiological meaning. Connections in biological neural networks might fluctuate over time; therefore, surveillance can provide a more useful picture of brain dynamics than the standard approach that relies on a static graph to represent functional connectivity. Using the application of well-known measures of neural synchrony over short segments of brain activity in a time series, we attempted a time-dependent characterization of brain connectivity by investigating functional segregation and integration. In our implementation, a frequency-dependent time window was employed and regularly spaced (defined as overlapping segments), and a novel, parameter-free method was introduced to derive the required adjacency matrices. The resulting characterization was compared against conventional approaches that rely on static and time-evolving graphs, which are constructed from non-overlapping segments of arbitrarily defined durations. Our approach is demonstrated using EEG recordings during mental calculations. The derived consecutive values of network metrics were then compared with values from randomized networks. The results revealed the dynamic small-world character of the brains functional connectivity, which otherwise can be hidden from estimators that rely on either long or stringent time-windows. Moreover, by involving a network-metric time series (NMTS) in a summarizing procedure that was based on replicator dynamics, consistent hubs that facilitated communication in the underlying networks were identified. Finally, the scale-free character of brain networks was also demonstrated based on the significant edges selected with the introduced approach.

Exploratory data analysis of evoked response single trials based on minimal spanning tree

OBJECTIVE An exploratory data analysis framework, based on minimal spanning tree, is proposed as a means to support the analysis of single trial (ST) electrophysiological signals. The core of this framework is the compact description of the input ST sample in a form of content-dependent ordered lists. Based on the established hierarchies, efficient ways to increase the SNR, extract prototypical responses, visualize possible self-organization trends in the sample and track the course of evoked response along the trial-to-trial dimension, are proposed. METHOD Magnetoencephalographic auditory evoked responses were used for demonstrating and validating the introduced framework. RESULTS AND CONCLUSION The results demonstrate the benefits, from this intelligent manipulation of STs, in understanding and enhancing the actual evoked signal. Specifically we find support for stimulus-induced phase-resetting hypothesis in the 3-20 Hz band, the existence of trials void of the prototypical evoked response, and an order across the single trial set hinting at an underlying process with long time scale.

Characterizing Dynamic Functional Connectivity Across Sleep Stages from EEG

Following a nonlinear dynamics approach, we investigated the emergence of functional clusters which are related with spontaneous brain activity during sleep. Based on multichannel EEG traces from 10 healthy subjects, we compared the functional connectivity across different sleep stages. Our exploration commences with the conjecture of a small-world patterning, present in the scalp topography of the measured electrical activity. The existence of such a communication pattern is first confirmed for our data and then precisely determined by means of two distinct measures of non-linear interdependence between time-series. A graph encapsulating the small-world network structure along with the relative interdependence strength is formed for each sleep stage and subsequently fed to a suitable clustering procedure. Finally the delineated graph components are comparatively presented for all stages revealing novel attributes of sleep architecture. Our results suggest a pivotal role for the functional coupling during the different stages and indicate interesting dynamic characteristics like its variable hemispheric asymmetry and the isolation between anterior and posterior cortical areas during REM.

A generic scheme for color image retrieval based on the multivariate Wald-Wolfowitz test

In this study, a conceptually simple, yet flexible and extendable strategy to contrast two different color images is introduced. The proposed approach is based on the multivariate Wald-Wolfowitz test, a nonparametric test that assesses the commonality between two different sets of multivariate observations. It provides an aggregate gauge of the match between color images, taking into consideration all the (selected) low-level characteristics, while alleviating correspondence issues. We show that a powerful measure of similarity between two color images can emerge from the statistical comparison of their representations in a properly formed feature space. For the sake of simplicity, the RGB-space is selected as the feature space, while we are experimenting with different ways to represent the images within this space. By altering the feature-extraction implementation, complementary ways to portray the image content appear. The reported results, from the application on a diverse collection of images, clearly demonstrate the effectiveness of our method, its superiority over previous methods, and suggest that even further improvements can be achieved along the same line of research. It is not only the unifying character that makes our strategy appealing, but also the fact that the retrieval performance does not increase continuously with the amount of details in the image representation. The latter sets an upper limit to the computational demands and reminds of performance plateaus reached by novel approaches in information retrieval.

Limited agreement between biomarkers of neuronal injury at different stages of Alzheimer's disease

New diagnostic criteria for Alzheimers disease (AD) treat different biomarkers of neuronal injury as equivalent. Here, we quantified the degree of agreement between hippocampal volume on structural magnetic resonance imaging, regional glucose metabolism on positron emission tomography, and levels of phosphorylated tau in cerebrospinal fluid (CSF) in 585 subjects from all phases of the AD Neuroimaging Initiative. The overall chance‐corrected agreement was poor (Cohen κ, 0.24–0.34), in accord with a high rate of conflicting findings (26%–41%). Neither diagnosis nor APOE ε4 status significantly influenced the distribution of agreement between the biomarkers. The degree of agreement tended to be higher in individuals with abnormal versus normal CSF β‐amyloid (Aβ1‐42) levels. Prospective diagnostic criteria for AD should address the relative importance of markers of neuronal injury and elaborate a way of dealing with conflicting biomarker findings.

Timing and connectivity in the human somatosensory cortex from single trial mass electrical activity.

Parallel‐distributed processing is ubiquitous in the brain but often ignored by experimental designs and methods of analysis, which presuppose sequential and stereotypical brain activations. We introduce here a methodology that can effectively deal with sequential and distributed activity. Regional brain activations elicited by electrical median nerve stimulation are identified in tomographic estimates extracted from single trial magnetoencephalographic signals. Habituation is identified in both primary somatosensory cortex (SI) and secondary somatosensory cortex (SII), often interrupted by resurgence of strong activations. Pattern analysis is used to identify single trials with homogeneous regional brain activations. Common activity patterns with well‐defined connectivity are identified within each homogeneous group of single trials across the subjects studied. On the contralateral side one encounters distinct sets of single trials following identical stimuli. We observe in one set of trials sequential activation from SI to SII and insula with onset of SII at 60 msec, whereas in the other set simultaneous early co‐activations of the same two areas. Hum. Brain Mapping 15:231–246, 2002.

Altered temporal correlations in resting-state connectivity fluctuations in children with reading difficulties detected via MEG

In this study we investigate systematic patterns of rapidly changing sensor-level interdependencies in resting MEG data obtained from 23 children experiencing reading difficulties (RD) and 27 non-impaired readers (NI). Three-minute MEG time series were band-passed and subjected to blind source separation (BSS) prior to estimating sensor interdependencies using the weighted phase synchronization measure (wPLI). Dynamic sensor-level network properties were then derived for two network metrics (global and local efficiency). The temporal decay of long-range temporal correlations in network metrics (LRTC) was quantified using the scaling exponent (SE) in detrended fluctuation analysis (DFA) plots. Having established the reliability of SE estimates as robust descriptors of network dynamics, we found that RD students displayed significantly reduced (a) overall sensor-level network organization across all frequency bands (global efficiency), and (b) temporal correlations between sensors covering the left temporoparietal region and the remaining sensors in the β3 band (local efficiency). Importantly, both groups displayed scale-free global network connectivity dynamics. The direct application of DFA to MEG signals failed to reveal significant group differences. Results are discussed in relation to prior evidence for disrupted temporoparietal functional circuits for reading in developmental reading disability.

Cognitive Workload Assessment Based on the Tensorial Treatment of EEG Estimates of Cross-Frequency Phase Interactions

The decoding of conscious experience, based on non-invasive measurements, has become feasible by tailoring machine learning techniques to analyse neuroimaging data. Recently, functional connectivity graphs (FCGs) have entered into the picture. In the related decoding scheme, FCGs are treated as unstructured data and, hence, their inherent format is overlooked. To alleviate this, tensor subspace analysis (TSA) is incorporated for the parsimonious representation of connectivity data. In addition to the particular methodological innovation, this work also makes a contribution at a conceptual level by encoding in FCGs cross-frequency coupling apart from the conventional frequency-specific interactions. Working memory related tasks, supported by networks oscillating at different frequencies, are good candidates for assessing the novel approach. We employed surface EEG recordings when the subjects were repeatedly performing a mental arithmetic task of five cognitive workload levels. For each trial, an FCG was constructed based on phase interactions within and between Frontalθ and Parieto-Occipitalα2 neural activities, which are considered to reflect the function of two distinct working memory subsystems. Based on the TSA representation, a remarkably high correct-recognition-rate (96%) of the task difficulties was achieved using a standard classifier. The overall scheme is computational efficient and therefore potentially useful for real-time and personalized applications.

On the Quantization of Time-Varying Phase Synchrony Patterns into Distinct Functional Connectivity Microstates (FCμstates) in a Multi-trial Visual ERP Paradigm

The analysis of functional brain connectivity has been supported by various techniques encompassing spatiotemporal interactions between distinct areas and enabling the description of network organization. Different brain states are known to be associated with specific connectivity patterns. We introduce here the concept of functional connectivity microstates (FCμstates) as short lasting connectivity patterns resulting from the discretization of temporal variations in connectivity and mediating a parsimonious representation of coordinated activity in the brain. Modifying a well-established framework for mining brain dynamics, we show that a small sized repertoire of FCμstates can be derived so as to encapsulate both the inter-subject and inter-trial response variability and further provide novel insights into cognition. The main practical advantage of our approach lies in the fact that time-varying connectivity analysis can be simplified significantly by considering each FCμstate as prototypical connectivity pattern, and this is achieved without sacrificing the temporal aspects of dynamics. Multi-trial datasets from a visual ERP experiment were employed so as to provide a proof of concept, while phase synchrony was emphasized in the description of connectivity structure. The power of FCμstates in knowledge discovery is demonstrated through the application of network topology descriptors. Their time-evolution and association with event-related responses is explored.

A novel biomarker of amnestic MCI based on dynamic cross-frequency coupling patterns during cognitive brain responses

The detection of mild cognitive impairment (MCI), the transitional stage between normal cognitive changes of aging and the cognitive decline caused by AD, is of paramount clinical importance, since MCI patients are at increased risk of progressing into AD. Electroencephalographic (EEG) alterations in the spectral content of brainwaves and connectivity at resting state have been associated with early-stage AD. Recently, cognitive event-related potentials (ERPs) have entered into the picture as an easy to perform screening test. Motivated by the recent findings about the role of cross-frequency coupling (CFC) in cognition, we introduce a relevant methodological approach for detecting MCI based on cognitive responses from a standard auditory oddball paradigm. By using the single trial signals recorded at Pz sensor and comparing the responses to target and non-target stimuli, we first demonstrate that increased CFC is associated with the cognitive task. Then, considering the dynamic character of CFC, we identify instances during which the coupling between particular pairs of brainwave frequencies carries sufficient information for discriminating between normal subjects and patients with MCI. In this way, we form a multiparametric signature of impaired cognition. The new composite biomarker was tested using data from a cohort that consists of 25 amnestic MCI patients and 15 age-matched controls. Standard machine-learning algorithms were employed so as to implement the binary classification task. Based on leave-one-out cross-validation, the measured classification rate was found reaching very high levels (95%). Our approach compares favorably with the traditional alternative of using the morphology of averaged ERP response to make the diagnosis and the usage of features from spectro-temporal analysis of single-trial responses. This further indicates that task-related CFC measurements can provide invaluable analytics in AD diagnosis and prognosis.