Greater repertoire and temporal variability of cross-frequency coupling (CFC) modes in resting-state neuromagnetic recordings among children with reading difficulties

Cross-frequency, phase-to-amplitude coupling (PAC) between neuronal oscillations at rest may serve as the substrate that supports information exchange between functionally specialized neuronal populations both within and between cortical regions. The study utilizes novel algorithms to identify prominent instantaneous modes of cross-frequency coupling and their temporal stability in resting state magnetoencephalography (MEG) data from 25 students experiencing severe reading difficulties (RD) and 27 age-matched non-impaired readers (NI). Phase coherence estimates were computed in order to identify the prominent mode of PAC interaction for each sensor, sensor pair, and pair of frequency bands (from δ to γ) at successive time windows of the continuous MEG record. The degree of variability in the characteristic frequency-pair PACf1−f2 modes over time was also estimated. Results revealed a wider repertoire of prominent PAC interactions in RD as compared to NI students, suggesting an altered functional substrate for information exchange between neuronal assemblies in the former group. Moreover, RD students showed significant variability in PAC modes over time. This temporal instability of PAC values was particularly prominent: (a) within and between right hemisphere temporo-parietal and occipito-temporal sensors and, (b) between left hemisphere frontal, temporal, and occipito-temporal sensors and corresponding right hemisphere sites. Altered modes of neuronal population coupling may help account for extant data revealing reduced, task-related neurophysiological and hemodynamic activation in left hemisphere regions involved in the reading network in RD. Moreover, the spatial distribution of pronounced instability of cross-frequency coupling modes in this group may provide an explanation for previous reports suggesting the presence of inefficient compensatory mechanisms to support reading

Classifying children with reading difficulties from non-impaired readers via symbolic dynamics and complexity analysis of MEG resting-state data

Magnetoencephalography (MEG) is a brain imaging method affording real-time temporal, and adequate spatial resolution to reveal aberrant neurophysiological function associated with dyslexia. In this study we analyzed sensor-level resting-state neuromagnetic recordings from 25 reading-disabled children and 27 non-impaired readers under the notion of symbolic dynamics and complexity analysis. We compared two techniques for estimating the complexity of MEG time-series in each of 8 frequency bands based on symbolic dynamics: (a) Lempel-Ziv complexity (LZC) entailing binarization of each MEG time series using the mean amplitude as a threshold, and (b) An approach based on the neural-gas algorithm (NG) which has been used by our group in the context of various symbolization schemes. The NG approach transforms each MEG time series to more than two symbols by learning the reconstructed manifold of each time series with a small error. Using this algorithm we computed a complexity index (CI) based on the distribution of words up to a predetermined length. The relative performance of the two complexity indexes was assessed using a classification procedure based on k-NN and Support Vector Machines. Results revealed the capacity of CI to discriminate impaired from non-impaired readers with 80% accuracy. Corresponding performance of LZC values did not exceed 55%. These findings indicate that symbolization of MEG recordings with an appropriate neuroinformatic approach, such as the proposed CI metric, may be of value in understanding the neural dynamics of dyslexia

Typical and aberrant functional brain flexibility: lifespan development and aberrant organization in traumatic brain injury and dyslexia

Intrinsic functional connectivity networks derived from different neuroimaging methods and connectivity estimators have revealed robust developmental trends linked to behavioural and cognitive maturation. The present study employed a dynamic functional connectivity approach to determine dominant intrinsic coupling modes in resting-state neuromagnetic data from 178 healthy participants aged 8–60 years. Results revealed significant developmental trends in three types of dominant intra- and inter-hemispheric neuronal population interactions (amplitude envelope, phase coupling, and phase-amplitude synchronization) involving frontal, temporal, and parieto-occipital regions. Multi-class support vector machines achieved 89% correct classification of participants according to their chronological age using dynamic functional connectivity indices. Moreover, systematic temporal variability in functional connectivity profiles, which was used to empirically derive a composite flexibility index, displayed an inverse U-shaped curve among healthy participants. Lower flexibility values were found among age-matched children with reading disability and adults who had suffered mild traumatic brain injury. The importance of these results for normal and abnormal brain development are discussed in light of the recently proposed role of cross-frequency interactions in the fine-grained coordination of neuronal population activity

Dynamics of spontaneous alpha activity correlate with language ability in young children.

Early childhood is a period of tremendous growth in both language ability and brain maturation. To understand the dynamic interplay between neural activity and spoken language development, we used resting-state EEG recordings to explore the relation between alpha oscillations (7-10 Hz) and oral language ability in 4- to 6-year-old children with typical development (N = 41). Three properties of alpha oscillations were investigated: a) alpha power using spectral analysis, b) flexibility of the alpha frequency quantified via the oscillation\u27s moment-to-moment fluctuations, and c) scaling behavior of the alpha oscillator investigated via the long-range temporal correlation in the alpha-amplitude time course. All three properties of the alpha oscillator correlated with children\u27s oral language abilities. Higher language scores were correlated with lower alpha power, greater flexibility of the alpha frequency, and longer temporal correlations in the alpha-amplitude time course. Our findings demonstrate a cognitive role of several properties of the alpha oscillator that has largely been overlooked in the literature

Brain connectivity analysis: a short survey

This short survey the reviews recent literature on brain connectivity studies. It encompasses all forms of static and dynamic connectivity whether anatomical, functional, or effective. The last decade has seen an ever increasing number of studies devoted to deduce functional or effective connectivity, mostly from functional neuroimaging experiments. Resting state conditions have become a dominant experimental paradigm, and a number of resting state networks, among them the prominent default mode network, have been identified. Graphical models represent a convenient vehicle to formalize experimental findings and to closely and quantitatively characterize the various networks identified. Underlying these abstract concepts are anatomical networks, the so-called connectome, which can be investigated by functional imaging techniques as well. Future studies have to bridge the gap between anatomical neuronal connections and related functional or effective connectivities

Aberrant resting-state functional brain networks in dyslexia: Symbolic mutual information analysis of neuromagnetic signals

Neuroimaging studies have identified a variety of structural and functional connectivity abnormalities in students experiencing reading difficulties. The present study adopted a novel approach to assess the dynamics of resting-state neuromagnetic recordings in the form of symbolic sequences (i.e., repeated patterns of neuromagnetic fluctuations within and/or between sensors). Participants were 25 students experiencing severe reading difficulties (RD) and 27 agematched non-impaired readers (NI) aged 7-14 years. Sensor-level data were first represented as symbolic sequences in eight conventional frequency bands. Next, dominant types of sensorto- sensor interactions in the form of intra and cross-frequency coupling were computed and subjected to graph modeling to assess group differences in global network characteristics. As a group RD students displayed predominantly within-frequency interactions between neighboring sensors which may reflect reduced overall global network efficiency and cost-efficiency of information transfer. In contrast, sensor networks among NI students featured a higher proportion of cross-frequency interactions. Brain-reading achievement associations highlighted the role of left hemisphere temporo-parietal functional networks, at rest, for reading acquisition and ability

Developing multidimensional metrics for evaluating paediatric neurodevelopmental disorders

Healthy brain functioning depends on efficient communication of information between brain regions, forming complex networks. By quantifying synchronisation between brain regions, a functionally connected brain network can be articulated. In neurodevelopmental disorders, where diagnosis is based on measures of behaviour and tasks, a measure of the underlying biological mechanisms holds promise as a potential clinical tool. Graph theory provides a tool for investigating the neural correlates of neuropsychiatric disorders, where there is disruption of efficient communication within and between brain networks. This research aimed to use recent conceptualisation of graph theory, along with measures of behaviour and cognitive functioning, to increase understanding of the neurobiological risk factors of atypical development. Using magnetoencephalography to investigate frequency-specific temporal dynamics at rest, the research aimed to identify potential biological markers derived from sensor-level whole-brain functional connectivity. Whilst graph theory has proved valuable for insight into network efficiency, its application is hampered by two limitations. First, its measures have hardly been validated in MEG studies, and second, graph measures have been shown to depend on methodological assumptions that restrict direct network comparisons. The first experimental study (Chapter 3) addressed the first limitation by examining the reproducibility of graph-based functional connectivity and network parameters in healthy adult volunteers. Subsequent chapters addressed the second limitation through adapted minimum spanning tree (a network analysis approach that allows for unbiased group comparisons) along with graph network tools that had been shown in Chapter 3 to be highly reproducible. Network topologies were modelled in healthy development (Chapter 4), and atypical neurodevelopment (Chapters 5 and 6). The results provided support to the proposition that measures of network organisation, derived from sensor-space MEG data, offer insights helping to unravel the biological basis of typical brain maturation and neurodevelopmental conditions, with the possibility of future clinical utility

Altered rich club and frequency-dependent subnetworks 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 hypersynchronization among rich-club hubs compared to controls in the d band and the d-g1, "-g1, and b-g2 frequency pairs. Moreover, rich-club hubs in mTBI patients were overrepresented in right frontal brain areas, from " to g1 frequencies, and underrepresented in left occipital regions in the d-b, d-g1, "-b, and b-g2 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 frommTBI. Furthermore, the proposed approachmight be used as a validation tool to assess patient recovery

Altered cross-frequency coupling in resting-state MEG after mild traumatic brain injury

Cross-frequency coupling (CFC) is thought to represent a basic mechanism of functional integration of neural networks across distant brain regions. In this study, we analyzed CFC profiles from resting state Magnetoencephalographic (MEG) recordings obtained from 30 mild traumatic brain injury (mTBI) patients and 50 controls. We used mutual information (MI) to quantify the phase-to-amplitude coupling (PAC) of activity among the recording sensors in six nonoverlapping frequency bands. After forming the CFC-based functional connectivity graphs, we employed a tensor representation and tensor subspace analysis to identify the optimal set of features for subject classification as mTBI or control. Our results showed that controls formed a dense network of stronger local and global connections indicating higher functional integration compared to mTBI patients. Furthermore, mTBI patients could be separated from controls with more than 90% classification accuracy. These findings indicate that analysis of brain networks computed from resting-state MEG with PAC and tensorial representation of connectivity profiles may provide a valuable biomarker for the diagnosis of mTBI