Publications

Autism spectrum disorder (ASD), like many other neurodevelopmental conditions, arises from complex interactions between genetics and environmental factors. In the last 50 years, significant efforts have been made to identify biomarkers and risk factors that can improve our understanding of autism etiology. However, high heterogeneity in causes, symptomology, and developmental trajectories has made this task challenging. One strategy to combat heterogeneity is to characterize individuals based on their brain phenotypes, commonly referred to as "neuro-subtyping". In this study, we analyzed electroencephalography (EEG) recordings from 144 infants aged 6-7 months and employed subtyping methods (latent profile analysis and hierarchical clustering) to identify subgroups. Our analyses revealed three distinct subgroups based on various language-associated EEG measures. We found that group membership was predictive of expressive and receptive language trajectories based on the Mullen Scales of Early Learning, with infants displaying high connectivity in language regions and lefthemisphere lateralization achieving the highest scores, while infants with overactivation of connectivity in the auditory network achieved lower scores. Notably, EEGderived subgroups did not predict a later ASD diagnosis, suggesting a lack of evidence for an ASD-specific phenotype during the first year of life. Results from this project contribute to a large body of research that supports using stratification approaches to decode heterogeneity in autism and its role in predicting behavioural outcomes.

The lateralization of brain activity is important for language processing and attention, and atypical patterns of lateralization have been linked to many neurodevelopmental disorders, including autism spectrum disorder (ASD). However, the developmental timing of these patterns and their relationship to emerging ASD characteristics are unclear. In this study, we used data from EEG-IP (International Infant EEG Data Integration Platform), a longitudinal cohort bringing together infants at elevated likelihood for ASD and age-equivalent controls across two sites. We examined brain lateralization in electroencephalography (EEG) power during the first year of life. Overall, we identified differences in gamma band lateralization in infants later diagnosed with ASD at 12 months but not at 6 months. Additionally, we observed a shift from high left gamma band asymmetry at 6 months toward more symmetry by 12 months in our control group, highlighting between-group differences in developmental trajectories in brain oscillatory activity. We found key differences in the lateralization across groups in brain regions within the auditory network, which is thought to be important for language learning. Overall, examining the developmental trajectories of lateralization is a crucial step toward creating more accurate models of brain development and better understanding the underlying mechanisms of neurodevelopmental disorders.

Nonverbal connection is an important aspect of everyday communication. For romantic partners, nonverbal connection is essential for establishing and maintaining feelings of closeness. EEG hyperscanning offers a unique opportunity to examine the link between nonverbal connection and neural synchrony among romantic partners. This current study used an EEG hyperscanning paradigm to collect frontal alpha asymmetry (FAA) signatures from 30 participants (15 romantic dyads) engaged in five different types of nonverbal connection that varied based on physical touch and visual contact. The results suggest that there was a lack of FAA while romantic partners were embracing and positive FAA (i.e., indicating approach) while they were holding hands, looking at each other, or doing both. Additionally, partners' FAA synchrony was greatest at a four second lag while they were holding hands and looking at each other. Finally, there was a significant association between partners' weekly negative feelings and FAA such that as they felt more negative their FAA became more positive. Taken together, this study further supports the idea that fleeting moments of interpersonal touch and gaze are important for the biological mechanisms that may underlie affiliative pair bonding in romantic relationships.

Patients with neurocognitive disorders often battle sleep disturbances. Kynurenic acid is a tryptophan metabolite of the kynurenine pathway implicated in the pathology of these illnesses. Modest increases in kynurenic acid, an antagonist at glutamatergic and cholinergic receptors, result in cognitive impairments and sleep dysfunction. We explored the hypothesis that inhibition of the kynurenic acid synthesising enzyme, kynurenine aminotransferase II, may alleviate sleep disturbances. At the start of the light phase, adult male and female Wistar rats received systemic injections of either: (i) vehicle; (ii) kynurenine (100 mg kg-1; i.p.); (iii) the kynurenine aminotransferase II inhibitor, PF-04859989 (30 mg kg-1; s.c.); or (iv) PF-04859989 and kynurenine in combination. Kynurenine and kynurenic acid levels were evaluated in the plasma and brain. Separate animals were implanted with electroencephalogram and electromyogram telemetry devices to record polysomnography, and evaluate the vigilance states wake, rapid eye movement sleep and non-rapid eye movement sleep following each treatment. Kynurenine challenge increased brain kynurenic acid and resulted in reduced rapid eye movement sleep duration, non-rapid eye movement sleep delta power and sleep spindles. PF-04859989 reduced brain kynurenic acid formation when given prior to kynurenine, prevented disturbances in rapid eye movement sleep and sleep spindles, and enhanced non-rapid eye movement sleep. Our findings suggest that reducing kynurenic acid in conditions where the kynurenine pathway is activated may serve as a potential strategy for improving sleep dynamics.