Mining time-resolved functional brain graphs to an EEG-based chronnectomic brain aged index (CBAI)

The brain at rest consists of spatially and temporal distributed but functionally connected regions that called intrinsic connectivity networks (ICNs). Resting state electroencephalography (rs-EEG) is a way to characterize brain networks without confounds associated with task EEG such as task difficulty and performance. A novel framework of how to study dynamic functional connectivity under the notion of functional connectivity microstates (FCμstates) and symbolic dynamics is further discussed. Furthermore, we introduced a way to construct a single integrated dynamic functional connectivity graph (IDFCG) that preserves both the strength of the connections between every pair of sensors but also the type of dominant intrinsic coupling modes (DICM). The whole methodology is demonstrated in a significant and unexplored task for EEG which is the definition of an objective Chronnectomic Brain Aged index (CBAI) extracted from resting-state data (N = 94 subjects) with both eyes-open and eyes-closed conditions. Novel features have been defined based on symbolic dynamics and the notion of DICM and FCμstates. The transition rate of FCμstates, the symbolic dynamics based on the evolution of FCμstates (the Markovian Entropy, the complexity index), the probability distribution of DICM, the novel Flexibility Index that captures the dynamic reconfiguration of DICM per pair of EEG sensors and the relative signal power constitute a valuable pool of features that can build the proposed CBAI. Here we applied a feature selection technique and Extreme Learning Machine (ELM) classifier to discriminate young adults from middle-aged and a Support Vector Regressor to build a linear model of the actual age based on EEG-based spatio-temporal features. The most significant type of features for both prediction of age and discrimination of young vs. adults age groups was the dynamic reconfiguration of dominant coupling modes derived from a subset of EEG sensor pairs. Specifically, our results revealed a very high prediction of age for eyes-open (R2 = 0.60; y = 0.79x + 8.03) and lower for eyes-closed (R2 = 0.48; y = 0.71x + 10.91) while we succeeded to correctly classify young vs. middle-age group with 97.8% accuracy in eyes-open and 87.2% for eyes-closed. Our results were reproduced also in a second dataset for further external validation of the whole analysis. The proposed methodology proved valuable for the characterization of the intrinsic properties of dynamic functional connectivity through the age untangling developmental differences using EEG resting-state recordings

Évaluation de l’impact de la maladie de Kawasaki sur le développement neurocognitif

Essai présenté à la Faculté des arts et des sciences en vue de l’obtention du grade de Doctorat en psychologie (D.Psy.) option neuropsychologie cliniqueIntroduction : La maladie de Kawasaki (MK) est une vascularite immunitaire transitoire se manifestant majoritairement chez les enfants d’âge préscolaire. Différentes atteintes neurologiques ont été répertoriées en phase aigüe, la plus fréquente étant une irritabilité excessive associée à une inflammation du système nerveux central. Les conséquences potentielles de la MK sur le développement cognitif, comportemental et cérébral des enfants demeurent peu étudiées. Objectifs : Cette étude pilote vise à (1) décrire le profil neuropsychologique d’enfants d’âge scolaire primaire ayant eu la MK et (2) explorer les impacts sur des marqueurs électroencéphalographiques (EEG) associés à l’attention et à la maturation cérébrale. Méthode : Quinze enfants (âgés de 8.8±2.5 ans) ont été recrutés pour l’étude, en moyenne 4.9±2.7 ans après avoir eu la MK. Une évaluation des fonctions intellectuelles (Wechsler Intelligence Scale for Children – 5th Edition), de l’attention soutenue auditive (Test of Everyday Attention for Children) et de la mémoire épisodique verbale (California Verbal Learning Test for Children) a été effectuée. Les parents ont répondu à 4 questionnaires standardisés pour évaluer 1) le fonctionnement exécutif (Behavior Rating Inventory of Executive Function); 2) les problèmes internalisés et externalisés (Child Behavior Checklist); 3) les symptômes du Trouble déficitaire de l’attention avec hyperactivité (Conners-3) et 4) les symptômes du Trouble du spectre de l’autisme (Social Responsiveness Scale-2). La fréquence de participants présentant une performance cognitive plus faible (≤ 1 écart-type sous la moyenne normative) et/ou des difficultés comportementales potentielles (≥ 1 écart-type au-dessus de la moyenne normative) a été calculée. Le ratio thêta/bêta et le pic alpha ont été extraits du signal EEG de repos et comparés aux données de 32 enfants contrôles (8.9±2.1 ans). Un algorithme de réduction de dimensions a été utilisé sur la bande alpha pour détecter des tendances inter et intra-groupes. Résultats : Les fonctions intellectuelles et mnésiques des participants se sont avérées dans les normes. Toutefois, une proportion importante d’enfants a performé dans la moyenne faible ou dans la zone limite à la tâche attentionnelle (4/14; 29%). Les réponses parentales ont révélé des proportions considérables d’inattention (6/14; 43%), de difficultés en mémoire de travail (7/14; 50%) et d’hyperactivité-impulsivité (5/14; 36%). Alors qu’aucune différence au niveau du ratio thêta/bêta n’a été soulevée, le ratio d’amplitude du pic alpha du groupe clinique s’est avéré significativement plus faible que celui du groupe contrôle, montrant un pic atténué dans 4 des 6 régions étudiées (p<0.05 au Mann-Whitney). L’algorithme de réduction des paramètres de la bande alpha a révélé une séparation franche des participants MK en deux sous-groupes. Le sous-groupe ayant une bande alpha davantage atténuée comportait plus d’enfants ayant présenté de l’irritabilité en phase aigüe (8 vs 1; test exact de Fisher p = 0.023). Conclusions : Malgré des aptitudes cognitives globalement préservées, nos résultats suggèrent une association potentielle entre la MK et des difficultés attentionnelles ultérieures. Cette première étude en EEG fournit une indication préliminaire d’un pic alpha atténué après la MK, plus particulièrement chez les patients ayant présenté une irritabilité marquée en phase inflammatoire. Des études à plus grande échelle sont nécessaires afin de confirmer les présents résultats et de mieux caractériser la trajectoire développementale des patients

Novelty N2-P3a Complex and Theta Oscillations Reflect Improving Neural Coordination Within Frontal Brain Networks During Adolescence

Adolescents are easily distracted by novel items than adults. Maturation of the frontal cortex and its integration into widely distributed brain networks may result in diminishing distractibility with the transition into young adulthood. The aim of this study was to investigate maturational changes of brain activity during novelty processing. We hypothesized that during adolescence, timing and task-relevant modulation of frontal cortex network activity elicited by novelty processing improves, concurrently with increasing cognitive control abilities. A visual novelty oddball task was utilized in combination with EEG measurements to investigate brain maturation between 8–28 years of age (n = 84). Developmental changes of the frontal N2-P3a complex and concurrent theta oscillations (4–7 Hz) elicited by rare and unexpected novel stimuli were analyzed using regression models. N2 amplitude decreased, P3a amplitude increased, and latency of both components decreased with age. Pre-stimulus amplitude of theta oscillations decreased, while inter-trial consistency, task-related amplitude modulation and inter-site connectivity of frontal theta oscillations increased with age. Targets, intertwined in a stimulus train with regular non-targets and novels, were detected faster with increasing age. These results indicate that neural processing of novel stimuli became faster and the neural activation pattern more precise in timing and amplitude modulation. Better inter-site connectivity further implicates that frontal brain maturation leads to global neural reorganization and better integration of frontal brain activity within widely distributed brain networks. Faster target detection indicated that these maturational changes in neural activation during novelty processing may result in diminished distractibility and increased cognitive control to pursue the task

Test-retest reliability of resting-state EEG in young and older adults

The quantification of resting-state electroencephalography (EEG) is associated with a variety of measures. These include power estimates at different frequencies, microstate analysis, and frequency-resolved source power and connectivity analyses. Resting-state EEG metrics have been widely used to delineate the manifestation of cognition and to identify psychophysiological indicators of age-related cognitive decline. The reliability of the utilized metrics is a prerequisite for establishing robust brain-behavior relationships and clinically relevant indicators of cognitive decline. To date, however, test-retest reliability examination of measures derived from resting human EEG, comparing different resting-state measures between young and older participants, within the same adequately powered dataset, is lacking. The present registered report examined test-retest reliability in a sample of 95 young (age range: 20-35 years) and 93 older (age range: 60-80 years) participants. A good-to-excellent test-retest reliability was confirmed in both age groups for power estimates on both scalp and source levels as well as for the individual alpha peak power and frequency. Partial confirmation was observed for hypotheses stating good-to-excellent reliability of microstates measures and connectivity. Equal levels of reliability between the age groups were confirmed for scalp-level power estimates and partially so for source-level power and connectivity. In total, five out of the nine postulated hypotheses were empirically supported and confirmed good-to-excellent reliability of the most commonly reported resting-state EEG metrics

Developmental changes in spontaneous electrocortical activity and network organization from early to late childhood.

We investigated the development of spontaneous (resting state) cerebral electric fields and their network organization from early to late childhood in a large community sample of children. Critically, we examined electrocortical maturation across one-year windows rather than creating aggregate averages that can miss subtle maturational trends. We implemented several novel methodological approaches including a more fine grained examination of spectral features across multiple electrodes, the use of phase-lagged functional connectivity to control for the confounding effects of volume conduction and applying topological network analyses to weighted cortical adjacency matrices. Overall, there were major decreases in absolute EEG spectral density (particularly in the slow wave range) across cortical lobes as a function of age. Moreover, the peak of the alpha frequency increased with chronological age and there was a redistribution of relative spectral density toward the higher frequency ranges, consistent with much of the previous literature. There were age differences in long range functional brain connectivity, particularly in the alpha frequency band, culminating in the most dense and spatially variable networks in the oldest children. We discovered age-related reductions in characteristic path lengths, modularity and homogeneity of alpha-band cortical networks from early to late childhood. In summary, there is evidence of large scale reorganization in endogenous brain electric fields from early to late childhood, suggesting reduced signal amplitudes in the presence of more functionally integrated and band limited coordination of neuronal activity across the cerebral cortex

The Role of Parent-Child Interaction Therapy in Modifying Children’s Neural Profiles: A Resting EEG Study of Children’s Response to Experience

The neural networks responsible for coordinating top-down self-regulatory processes, or executive functions, undergo intense fine-tuning and reorganization in early childhood. For children faced with prolonged stress (e.g., chaotic household environment, uncertainty) or adversity (e.g., poverty, maltreatment), these executive function processes are sculpted to aid in retaining information about threats to well-being, which may be protective short-term, but can become particularly maladaptive over time. Interventions that modify the caregiving environment have been shown to buffer the effects of adversity on children’s neural development. Parent-Child Interaction Therapy (PCIT) is one such intervention that has been shown to improve both parenting behavior and child outcomes in meta-analyses and is one of the only interventions evidenced to reduce child maltreatment recidivism. The present study sought to evaluate the effects of PCIT on 3-8-year-old children’s theta/beta ratio, a neural marker of attention regulation as measured by electroencephalogram (EEG). Next, this study sought to examine whether individual differences in parenting changes across the PCIT intervention were related to children’s theta/beta ratio, for the PCIT group only. Data for this dissertation were drawn from a randomized control trial investigating the biobehavioral mechanisms of change in parent and child self-regulation skills as a result of PCIT for child-welfare involved families (NIDA R01 036533; PIs: Skowron & Fisher). 204 parent-child dyads with a history of child welfare involvement were referred into the study by the local Lane County Department of Human Services and randomized to PCIT or services-as-usual control conditions. The hypothesis that adversity-exposed children in PCIT would show lower theta/beta ratios, indicative of better attention regulation, after accounting for psychosocial risk, was supported for the eyes-closed but not the eyes-open condition. The hypothesis that individual differences in parenting skill change in PCIT group would be associated with children’s post-treatment theta/beta ratio was not supported. Taken together, this study fills a valuable gap in understanding whether parenting intervention, namely PCIT, can modify children’s neural markers of attention regulation after accounting for early adversity exposure

Development of Brain Functional Connectivity and Its Relation To Infant Sustained Attention In The First Year Of Life

This dissertation project studies the development of infant sustained attention and its relation to brain functional connectivity from 6 to 12 months of age. Chapter 1 is a general introduction of the dissertation project. Chapter 2 is a review of the existing literature on the development of infant sustained attention. This chapter includes theories on infant sustained attention and findings from studies using behavioral and psychophysiological measurements. Chapter 3 is a review of the recent advances made in the study of the development of functional connectivity in brain networks. This chapter covers some empirical evidence for the development of functional networks using EEG and fMRI techniques. In Chapter 4 I introduce an experiment that examined the potential relation between infant sustained attention and distinct patterns of brain functional connectivity suggested by the literature reviewed in Chapter 2 and 3. The sample of the experiment consisted of 59 participants aged from 6 to 12 months. Infant sustained attention and inattention were defined by measuring infant heart rate changes. Functional connectivity was estimated with high-density EEG recordings from the electrodes on the scalp and with the reconstructed cortical source activities in brain regions. Graph theory measures were applied to give a broader view of the architecture of brain functional networks. It was found that infant sustained attention was accompanied by attenuated functional connectivity in the dorsal attention and default mode networks in the alpha band. Graph theory analyses showed that there was an increase in path length and a decrease in clustering coefficient during infant sustained attention. The functional connectivity in brain networks and the graph theory measures of path length and clustering coefficient were found to increase with age. The small-worldness was found for infants at 6 and 8 months in the alpha and beta bands. These findings lend support to the hypothesis of the relation between the distinct patterns of brain functional connectivity and infant sustained attention. The current findings also provide convergent evidence for the rapid development of functional connectivity in brain networks during infancy

Modulation génétique de la dynamique cérébrale dans les troubles neurodéveloppementaux : impact des CNVs pathogéniques sur l’EEG de repos

Bien que la majeure partie du génome humain soit présente en deux copies (une copie héritée de chaque parent), certains segments peuvent être délétés (une copie) ou dupliqués (trois copies). La recherche a montré que plusieurs variations du nombre de copies (CNVs) augmentent le risque de troubles neurodéveloppementaux (e.g. autisme, TDAH, schizophrénie). Or, on connait peu les effets des CNVs sur le développement et le fonctionnement cérébral. L’électroencéphalographie (EEG) au repos s’avère être une méthode adaptée pour étudier les perturbations de l’activité neuronale chez les porteurs de CNVs. L’objectif de ce projet était de déterminer s’il existe des signatures EEG à l’état de repos qui sont caractéristiques des enfants porteurs de CNVs pathogéniques. L’activité cérébrale au repos de 109 porteurs de CNVs (66 délétions, 43 duplications) âgés de 3 à 17 ans a été enregistrée en EEG durant 4 minutes. Pour mieux prendre en compte les variations développementales, les indices EEG (puissance spectrale et connectivité fonctionnelle) ont été corrigés avec un modèle normatif estimé à partir de 256 contrôles du Heatlhy Brain Network. Les résultats ont montré une puissance bêta et gamma accrue dans les régions postérieures ainsi qu’une sous-connectivité globale à des échelles temporelles distinctes chez les porteurs de CNVs. Les porteurs d’une délétion et d’une duplication pouvaient être différenciés par leur connectivité dans les fréquences bas-alpha: la connectivité des porteurs d’une duplication était plus perturbée que celle des porteurs d’une délétion. Les perturbations distinctives en connectivité se sont avérées plus proéminentes à l’adolescence. Les résultats suggèrent que les porteurs de CNVs présentent des altérations électrophysiologiques par rapport aux témoins neurotypiques, indépendamment de la région génomique affectée.Although most of the human genome is present in two copies (one copy inherited from each parent), some segments can be deleted (one copy) or duplicated (three copies). Research has shown that many copy number variations (CNVs) increase the risk of neurodevelopmental disorders (e.g. autism, ADHD, schizophrenia). However, little is known about the effects of CNVs on brain development and function. Resting-state electroencephalography (EEG) is a suitable method to study the disturbances of neuronal functioning in CNVs. We aimed to determine whether there are resting-state EEG signatures that are characteristic of children with pathogenic CNVs. Resting-state brain activity of 109 CNVs carriers (66 deletions, 43 duplications) aged 3 to 17 years was recorded in EEG for 4 minutes. To better account for developmental variations, EEG indices (power spectral density and functional connectivity) were corrected with a normative model estimated from 256 Heatlhy Brain Network controls. Results showed increased beta and gamma power in posterior regions as well as a global under-connectivity at distinct frequency bands in CNVs carriers. Deletion and duplication carriers can be differentiated by their connectivity in low alpha frequencies: the connectivity of the duplication carriers was more disrupted than that of the deletion carriers. The distinctive connectivity perturbations were found to be most prominent during adolescence. The results suggest that CNVs carriers show electrophysiological alterations compared to neurotypical controls, regardless of the gene dosage effect and of their affected genomic region. Moreover, a specific signature of the molecular alterations associated with deletions was found