Faculty Bibliography

Differences in speech prosody are a widely observed feature of Autism Spectrum Disorder (ASD). However, it is unclear how prosodic differences in ASD manifest across different languages that demonstrate cross-linguistic variability in prosody. Using a supervised machine-learning analytic approach, we examined acoustic features relevant to rhythmic and intonational aspects of prosody derived from narrative samples elicited in English and Cantonese, two typologically and prosodically distinct languages. Our models revealed successful classification of ASD diagnosis using rhythm-relative features within and across both languages. Classification with intonation-relevant features was significant for English but not Cantonese. Results highlight differences in rhythm as a key prosodic feature impacted in ASD, and also demonstrate important variability in other prosodic properties that appear to be modulated by language-specific differences, such as intonation.

Frontal power asymmetry (FA), a measure of brain function derived from electroencephalography, is a potential biomarker for major depressive disorder (MDD). Though FA is functional in nature, it is typically reduced to a scalar value prior to analysis, possibly obscuring its relationship with MDD and leading to a number of studies that have provided contradictory results. To overcome this issue, we sought to fit a functional regression model to characterize the association between FA and MDD status, adjusting for age, sex, cognitive ability, and handedness using data from a large clinical study that included both MDD and healthy control (HC) subjects. Since nearly 40% of the observations are missing data on either FA or cognitive ability, we propose an extension of multiple imputation (MI) by chained equations that allows for the imputation of both scalar and functional data. We also propose an extension of Rubin's Rules for conducting valid inference in this setting. The proposed methods are evaluated in a simulation and applied to our FA data. For our FA data, a pooled analysis from the imputed data sets yielded similar results to those of the complete case analysis. We found that, among young females, HCs tended to have higher FA over the θ, α, and β frequency bands, but that the difference between HC and MDD subjects diminishes and ultimately reverses with age. For males, HCs tended to have higher FA in the β frequency band, regardless of age. Young male HCs had higher FA in the θ and α bands, but this difference diminishes with increasing age in the α band and ultimately reverses with increasing age in the θ band.

The complex process of regulating physiological functions and homeostasis during external and internal disruptions develops slowly in altricial species, with parental care functioning as a co-regulator of infant physiological and emotional homeostasis. Here, we review our current understanding of the infant's use of parental behaviors for neurobehavioral regulation and its disruption with harsh parental care. Taking a cross-species view, we briefly review the human developmental literature that highlights the importance of the caregiver in scaffolding the child's physiological and emotional regulation, especially under threat and stress. We then use emerging corresponding animal literature within the phylogenetically preserved attachment system to help define neural systems supporting caregiver regulation and its supporting causal mechanism to provide translational bridges to inform causation and mechanisms impossible to define in children. Next, we briefly review animal research highlighting the impact of specific sensory stimuli imbedded in parental care as important for infant physiological and emotion regulation. We then highlight the importance of parental sensory stimuli gaining hedonic value to go beyond simple sensory stimuli to further impact neurobehavioral regulation, with poor quality of care compromising the infant's ability to use these cues for regulation. Clinically, parental regulation of the infant is correlated with later-life neurobehavioral outcome and quality of life. We suggest an understanding of this parental regulation of the infant's immediate neurobehavioral functioning within the context of attachment quality, that may provide insights into the complex processes during early life, initiating the pathway to pathology.

Current clinical literature and supporting animal literature have shown that repeated and profound early-life adversity, especially when experienced within the caregiver-infant dyad, disrupts the trajectory of brain development to induce later-life expression of maladaptive behavior and pathology. What is less well understood is the immediate impact of repeated adversity during early life with the caregiver, especially since attachment to the caregiver occurs regardless of the quality of care the infant received including experiences of trauma. The focus of the present manuscript is to review the current literature on infant trauma within attachment, with an emphasis on animal research to define mechanisms and translate developmental child research. Across species, the effects of repeated trauma with the attachment figure, are subtle in early life, but the presence of acute stress can uncover some pathology, as was highlighted by Bowlby and Ainsworth in the 1950s. Through rodent neurobehavioral literature we discuss the important role of repeated elevations in stress hormone corticosterone (CORT) in infancy, especially if paired with the mother (not when pups are alone) as targeting the amygdala and causal in infant pathology. We also show that following induced alterations, at baseline infants appear stable, although acute stress hormone elevation uncovers pathology in brain circuits important in emotion, social behavior, and fear. We suggest that a comprehensive understanding of the role of stress hormones during infant typical development and elevated CORT disruption of this typical development will provide insight into age-specific identification of trauma effects, as well as a better understanding of early markers of later-life pathology.

Attention-Deficit Hyperactivity Disorder (ADHD) is a complex and heterogeneous neurodevelopmental condition for which curative treatments are lacking. Whilst pharmacological treatments are generally effective and safe, there is considerable inter-individual variability among patients regarding treatment response, required dose, and tolerability. Many of the non-pharmacological treatments, which are preferred to drug-treatment by some patients, either lack efficacy for core symptoms or are associated with small effect sizes. No evidence-based decision tools are currently available to allocate pharmacological or psychosocial treatments based on the patient's clinical, environmental, cognitive, genetic, or biological characteristics. We systematically reviewed potential biomarkers that may help in diagnosing ADHD and/or stratifying ADHD into more homogeneous subgroups and/or predict clinical course, treatment response, and long-term outcome across the lifespan. Most work involved exploratory studies with cognitive, actigraphic and EEG diagnostic markers to predict ADHD, along with relatively few studies exploring markers to subtype ADHD and predict response to treatment. There is a critical need for multisite prospective carefully designed experimentally controlled or observational studies to identify biomarkers that index inter-individual variability and/or predict treatment response.