EEG connectivity in infants at risk for autism spectrum disorder

Autism Spectrum Disorder (ASD) is characterized by social and communication difficulties, and restricted and repetitive behaviours, and is typically diagnosed during toddlerhood. Electroencephalographic (EEG) connectivity during infancy may predict later diagnostic outcome, and dimensional traits, although results vary with differences in methods. The aim of this thesis is to examine how infant EEG connectivity relates to familial risk, and later categorical and dimensional outcomes of ASD. A previous study found alpha band hyperconnectivity in 14-month-old infants who developed ASD compared to infants who did not develop ASD at 36 months. Chapter 3 shows that methods used in this previous study indeed provide reliable results. Chapter 4 describes the replication study using identical methods to the previous study. Although the difference between groups was not replicated, the association between alpha connectivity and restricted and repetitive behaviours during toddlerhood was replicated. Chapter 5 tested the hypothesis that social and communication difficulties relate to theta connectivity in response to social and non-social stimuli. Theta connectivity was increased during social compared to non-social stimuli. Network topologies differed between groups with high and low familial risk, but not between categorical outcome groups. Theta connectivity was not associated with dimensional traits at toddlerhood. Chapter 6 showed that graph organisation was not related to familial risk, or diagnostic or dimensional outcomes at toddlerhood. Finally, Chapter 7 combined measures from previous chapters and examined how these relate to dimensional outcomes at childhood. Graph organisation at infancy showed a stronger association with dimensional outcomes at childhood than other connectivity measures. Overall, the results in this thesis illustrate the variability in developmental trajectories in ASD, while emphasizing the complexity of the disorder and use of a dimensional approach to ASD. Chapter 8 further discusses contributions and implications for research of EEG connectivity as early predictive marker for ASD

EEG connectivity in infants at risk for autism spectrum disorder

Autism Spectrum Disorder (ASD) is characterized by social and communication difficulties, and restricted and repetitive behaviours, and is typically diagnosed during toddlerhood. Electroencephalographic (EEG) connectivity during infancy may predict later diagnostic outcome, and dimensional traits, although results vary with differences in methods. The aim of this thesis is to examine how infant EEG connectivity relates to familial risk, and later categorical and dimensional outcomes of ASD. A previous study found alpha band hyperconnectivity in 14-month-old infants who developed ASD compared to infants who did not develop ASD at 36 months. Chapter 3 shows that methods used in this previous study indeed provide reliable results. Chapter 4 describes the replication study using identical methods to the previous study. Although the difference between groups was not replicated, the association between alpha connectivity and restricted and repetitive behaviours during toddlerhood was replicated. Chapter 5 tested the hypothesis that social and communication difficulties relate to theta connectivity in response to social and non-social stimuli. Theta connectivity was increased during social compared to non-social stimuli. Network topologies differed between groups with high and low familial risk, but not between categorical outcome groups. Theta connectivity was not associated with dimensional traits at toddlerhood. Chapter 6 showed that graph organisation was not related to familial risk, or diagnostic or dimensional outcomes at toddlerhood. Finally, Chapter 7 combined measures from previous chapters and examined how these relate to dimensional outcomes at childhood. Graph organisation at infancy showed a stronger association with dimensional outcomes at childhood than other connectivity measures. Overall, the results in this thesis illustrate the variability in developmental trajectories in ASD, while emphasizing the complexity of the disorder and use of a dimensional approach to ASD. Chapter 8 further discusses contributions and implications for research of EEG connectivity as early predictive marker for ASD

Test-retest reliability of EEG network characteristics in infants

Functional Electroencephalography (EEG) networks in infants have been proposed as useful biomarkers for developmental brain disorders. However, the reliability of these networks and their characteristics has not been established. We evaluated the reliability of these networks and their characteristics in 10-month-old infants. Data were obtained during two EEG sessions 1 week apart and was subsequently analyzed at delta (0.5-3 Hz), theta (3-6 Hz), alpha1 (6-9 Hz), alpha2 (9-12 Hz), beta (12-25 Hz), and low gamma (25-45 Hz) frequency bands. Connectivity matrices were created by calculating the phase lag index between all channel pairs at given frequency bands. To determine the reliability of these connectivity matrices, intra-class correlations were calculated of global connectivity, local connectivity, and several graph characteristics. Comparing both sessions, global connectivity, as well as global graph characteristics (characteristic path length and average clustering coefficient) are highly reliable across multiple frequency bands; the alpha1 and theta band having the highest reliability in general. In contrast, local connectivity characteristics were less reliable across all frequency bands. We conclude that global connectivity measures are highly reliable over sessions. Local connectivity measures show lower reliability over sessions. This research therefore underlines the possibility of these global network characteristics to be used both as biomarkers of neurodevelopmental disorders, but also as important factors explaining development of typical behavior. [Abstract copyright: © 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

Functional EEG connectivity in infants associates with later restricted and repetitive behaviours in autism; a replication study.

We conducted a replication study of our prior report that increased alpha EEG connectivity at 14-months associates with later autism spectrum disorder (ASD) diagnosis, and dimensional variation in restricted interests/repetitive behaviours. 143 infants at high and low familial risk for ASD watched dynamic videos of spinning toys and women singing nursery rhymes while high-density EEG was recorded. Alpha functional connectivity (7-8 Hz) was calculated using the debiased weighted phase lag index. The final sample with clean data included low-risk infants (N = 20), and high-risk infants who at 36 months showed either typical development (N = 47), atypical development (N = 21), or met criteria for ASD (N = 13). While we did not replicate the finding that global EEG connectivity associated with ASD diagnosis, we did replicate the association between higher functional connectivity at 14 months and greater severity of restricted and repetitive behaviours at 36 months in infants who met criteria for ASD. We further showed that this association is strongest for the circumscribed interests subdomain. We propose that structural and/or functional abnormalities in frontal-striatal circuits underlie the observed association. This is the first replicated infant neural predictor of dimensional variation in later ASD symptoms

Real-time monitoring of infant theta power during naturalistic social experiences

Infant-directed speech and direct gaze are important social cues that shape infant’s attention to their parents. Traditional methods for probing their effect on infant attention involve a small number of pre-selected screen-based stimuli, which do not capture the complexity of real-world interactions. Here, we used neuroadaptive Bayesian Optimization (NBO) to search a large ‘space’ of different naturalistic social experiences that systematically varied in their visual (gaze direct to averted) and auditory properties (infant directed speech to nonvocal sounds). We measured oscillatory brain responses (relative theta power) during episodes of naturalistic social experiences in 57 typically developing 6- to 12-month-old infants. Relative theta power was used as input to the NBO algorithm to identify the naturalistic social context that maximally elicited attention in each individual infant. Results showed that individual infants were heterogeneous in the stimulus that elicited maximal theta with no overall stronger attention for direct gaze or infant-directed speech; however, individual differences in attention towards averted gaze were related to interpersonal skills and greater likelihood of preferring speech and direct gaze was observed in infants whose parents showed more positive affect. Our work indicates NBO may be a fruitful method for probing the role of distinct social cues in eliciting attention in naturalistic social contexts at the individual level

Qualitative differences in the spatiotemporal brain states supporting configural face processing emerge in adolescence in autism

BACKGROUND Studying the neural processing of faces can illuminate the mechanisms of compromised social expertise in autism. To resolve a longstanding debate, we examined whether differences in configural face processing in autism are underpinned by quantitative differences in the activation of typical face processing pathways, or the recruitment of non-typical neural systems. METHODS We investigated spatial and temporal characteristics of event-related EEG responses to upright and inverted faces in a large sample of children, adolescents, and adults with and without autism. We examined topographic analyses of variance and global field power to identify group differences in the spatial and temporal response to face inversion. We then examined how quasi-stable spatiotemporal profiles - microstates - are modulated by face orientation and diagnostic group. RESULTS Upright and inverted faces produced distinct profiles of topography and strength in the topographical analyses. These topographical profiles differed between diagnostic groups in adolescents, but not in children or adults. In the microstate analysis, the autistic group showed differences in the activation strength of normative microstates during early-stage processing at all ages, suggesting consistent quantitative differences in the operation of typical processing pathways; qualitative differences in microstate topographies during late-stage processing became prominent in adults, suggesting the increasing involvement of non-typical neural systems with processing time and over development. CONCLUSIONS These findings suggest that early difficulties with configural face processing may trigger later compensatory processes in autism that emerge in later development

Behavioural and neural markers of tactile sensory processing in infants at elevated likelihood of autism spectrum disorder and/or attention deficit hyperactivity disorder

Abstract: Backgrounds: Atypicalities in tactile processing are reported in autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) but it remains unknown if they precede and associate with the traits of these disorders emerging in childhood. We investigated behavioural and neural markers of tactile sensory processing in infants at elevated likelihood of ASD and/or ADHD compared to infants at typical likelihood of the disorders. Further, we assessed the specificity of associations between infant markers and later ASD or ADHD traits. Methods: Ninety-one 10-month-old infants participated in the study (n = 44 infants at elevated likelihood of ASD; n = 20 infants at elevated likelihood of ADHD; n = 9 infants at elevated likelihood of ASD and ADHD; n = 18 infants at typical likelihood of the disorders). Behavioural and EEG responses to pairs of tactile stimuli were experimentally recorded and concurrent parental reports of tactile responsiveness were collected. ASD and ADHD traits were measured at 24 months through standardized assessment (ADOS-2) and parental report (ECBQ), respectively. Results: There was no effect of infants’ likelihood status on behavioural markers of tactile sensory processing. Conversely, increased ASD likelihood associated with reduced neural repetition suppression to tactile input. Reduced neural repetition suppression at 10 months significantly predicted ASD (but not ADHD) traits at 24 months across the entire sample. Elevated tactile sensory seeking at 10 months moderated the relationship between early reduced neural repetition suppression and later ASD traits. Conclusions: Reduced tactile neural repetition suppression is an early marker of later ASD traits in infants at elevated likelihood of ASD or ADHD, suggesting that a common pathway to later ASD traits exists despite different familial backgrounds. Elevated tactile sensory seeking may act as a protective factor, mitigating the relationship between early tactile neural repetition suppression and later ASD traits

Atypical Development of Attentional Control Associates with Later Adaptive Functioning, Autism and ADHD Traits

Funder: H2020 European Research Council; doi: http://dx.doi.org/10.13039/100010663Funder: Research Foundation FlandersFunder: Universiteit Gent; doi: http://dx.doi.org/10.13039/501100004385Funder: Marguerite-Marie DelacroixFunder: Autistica; doi: http://dx.doi.org/10.13039/100011706Funder: Riksbankens Jubileumsfond; doi: http://dx.doi.org/10.13039/501100004472; Grant(s): NHS14-1802:1Funder: K.F. Hein FondsFunder: Scott Family Junior Research FellowshipAbstract: Autism is frequently associated with difficulties with top-down attentional control, which impact on individuals’ mental health and quality of life. The developmental processes involved in these attentional difficulties are not well understood. Using a data-driven approach, 2 samples (N = 294 and 412) of infants at elevated and typical likelihood of autism were grouped according to profiles of parent report of attention at 10, 15 and 25 months. In contrast to the normative profile of increases in attentional control scores between infancy and toddlerhood, a minority (7–9%) showed plateauing attentional control scores between 10 and 25 months. Consistent with pre-registered hypotheses, plateaued growth of attentional control was associated with elevated autism and ADHD traits, and lower adaptive functioning at age 3 years

Neuroadaptive Bayesian Optimisation can allow integrative design spaces at the individual level in the social and behavioural sciences… and beyond

Almaatouq and colleagues (2022) propose an integrative experimental design space combined with large samples for scientific advancement. We argue recent innovative designs combining closed-loop experimental designs and Bayesian Optimisation allow for integrative experiments at an individual level during a single session, circumventing the necessity for large samples. This method can be applied across disciplines, including developmental and clinical research