Faculty Bibliography

Human brain anatomical and resting-state functional connectivity have been comprehensively portrayed using MRI, which are termed anatomical and functional connectomes. A systematic examination of tasks modulated whole brain functional connectivity, which we term as task connectome, is still lacking. We analyzed 6 block-designed and 1 event-related designed functional MRI data, and examined whole-brain task modulated connectivity in various task domains, including emotion, reward, language, relation, social cognition, working memory, and inhibition. By using psychophysiological interaction between pairs of regions from the whole brain, we identified statistically significant task modulated connectivity in 4 tasks between their experimental and respective control conditions. Task modulated connectivity was found not only between regions that were activated during the task but also regions that were not activated or deactivated, suggesting a broader involvement of brain regions in a task than indicated by simple regional activations. Decreased functional connectivity was observed in all the 4 tasks and sometimes reduced connectivity was even between regions that were both activated during the task. This suggests that brain regions that are activated together do not necessarily work together. The current study demonstrates the comprehensive task connectomes of 4 tasks, and suggested complex relationships between regional activations and connectivity changes.

The search for objective biological tests, sufficiently reliable, and predictive enough to be diagnostic of psychiatric disorders, continues apace - yet their discovery remains a distant dream. It seems increasingly unlikely that current diagnostic structures and concepts map biologically in a straight forward way - with heterogeneity within, and sharing across, existing diagnostic boundaries being the biological rule rather than the exception. Indeed, it now appears that the science of biological psychiatry is more likely to redraw those boundaries than it is to confirm and mark them (Sonuga-Barke, Journal of Child Psychology and Psychiatry, 2016, 57, 1). Clinical identification of childhood psychiatric disorders therefore remains, for the foreseeable future at least, an exercise in regulated social perception - reliant on the fallible and subjective judgements of parents, teachers and clinicians. Social perception of this sort is an active and motivated process and therefore prone, like all social perception, to bias and distortions - both systematic and idiosyncratic. Progress has certainly been made over the last 50 years in reducing such judgement bias by, for instance filtering perceptions through the lens of standardised instruments (questionnaires and interviews) with carefully operationalised items and a degree of reliability and validity. However, such instruments often play only a peripheral role in actual diagnostic encounters and when they are used, there is still sufficient ambiguity to leave open plenty of room for interpretation. When we acknowledge that psychiatric diagnoses are social constructions - we are not saying that symptoms of inattention, impulsivity and hyperactivity are not real or do not cluster together in meaningful ways or that they do not cause real distress and disability but that their interpretation and meaning are often informed by social constructs such as ethnic or gender norms and stereotypes (Meyer, Stevenson, & Sonuga-Barke, Journal of Attention Disorders, 2019).

BACKGROUND:Alcohol use disorder (AUD) is a wide-spread, heritable brain disease, but few studies have linked genetic variants or epigenetic factors to brain structures related to AUD in humans, due to many factors including the high-dimensional nature of imaging and genomic data. METHODS:To provide potential insights into the links among epigenetic regulation, brain structure, and AUD, we have performed an integrative analysis of brain structural imaging and blood DNA methylome data from 52 AUD and 58 healthy control (HC) subjects collected in the Nathan Kline Institute-Rockland Sample. RESULTS:We first found that AUD subjects had significantly larger insular surface area than HC in both left and right hemispheres. We then found that 7,827 DNA methylation probes on the HumanMethylation450K BeadChip had significant correlations with the right insular surface area (false discovery rate [FDR] < 0.05). Furthermore, we showed that 44 of the insular surface area-correlated methylation probes were also strongly correlated with AUD status (FDR < 0.05). These AUD-correlated probes are annotated to 36 protein-coding genes, with 16 genes (44%) having been reported by others to be related to AUD or alcohol response, including TAS2R16 and PER2. The remaining 20 genes, in particular ARHGAP22, might represent novel genes involved in AUD or responsive to alcohol. CONCLUSIONS:We have identified 36 insular surface area- and AUD-correlated protein-coding genes that are either known to be AUD- or alcohol-related or not yet reported by prior studies. Therefore, our study suggests that the brain imaging-guided epigenetic analysis has a potential of identifying possible epigenetic mechanisms involved in AUD.

Social support can buffer against stressors often associated with having family members with autism spectrum disorder. This study included 112 parents and typically developing siblings of children with autism spectrum disorder. Relations between self-reported typically developing sibling emotional and behavioral problems and discrepancy between social support frequency and importance were examined via polynomial regression with response surface analysis. Typically developing siblings who described social support as frequent and important reported relatively few problems. Typically developing siblings who reported social support as highly important but infrequent exhibited the highest emotional and behavioral difficulties. Thus, typically developing siblings with little support who view support as highly important may be particularly responsive to social support improvement efforts.

We conducted a qualitative review (n = 15 manuscripts) and meta-analysis (n = 9 manuscripts) of the extant literature to evaluate the prevalence and morbidity of subthreshold Attention Deficit Hyperactivity Disorder (ADHD). Our qualitative review showed that a sizable minority (mean: 17.7%) of clinically referred and non-referred children met a priori definitions of subthreshold ADHD. Those affected exhibited significantly higher rates of family dysfunction, cognitive impairment, executive dysfunction, interpersonal and school deficits, temperament problems, psychiatric comorbidity, and juvenile delinquency compared to children with no ADHD symptoms. These deficits were highly consistent with those observed in children with full threshold ADHD. These findings indicate that children with subthreshold ADHD symptoms are at significantly greater risk for negative outcomes in a wide range of non-overlapping functional domains worthy of further clinical and scientific consideration.

In traditional medical practice, the diagnostic interview is focused on symptom collection, diagnosis, and treatment. The psychiatric interview is based on the medical model, but mental health clinicians lack the tests found in general medicine. Rapport is the most essential tool for the psychiatrist to uncover symptoms and develop a diagnosis and treatment plan. This article brings a scientific lens to the psychiatric interview. Under this microscope the value of eliciting the patient's well-being at the outset of the interview becomes clear. Using positive psychology, an evidenced-based rationale for the positive assessment is outlined and methodology and practice of the assessment reviewed.

Introduction: Short sleep duration promotes metabolic dysregulation and obesity. We have previously shown that acute sleep restriction increases neuronal activity in response to food stimuli in areas of interoception and reward, such as the insula and orbitofrontal cortex. However, whether chronic mild sleep restriction impacts food reward valuation in the brain remains unknown. In an ongoing study, we assess the effects of mild 6-week sleep restriction on intrinsic functional connectivity (iFC) across reward and interoception- related brain circuitry.
Method(s): To date, 16 adult men and women (age 29.0+/-5.3 years and BMI 26.9+/-2.6 kg/m²at study entry) took part in this randomized, crossover, outpatient trial of 2 phases: habitual sleep (HS; >=7 h/night) and sleep restriction (SR; -1.5 h/night relative to HS). All participants were screened with actigraphy over a two-week period to ensure adequate sleep duration of 7-9 h/night (average screening total sleep time: 7.65+/-0.58 h/night). Two resting-state (task-free) functional MRI scans (Siemens Skyra 3T, TR=2.5s, two 5-min runs) were collected during the final week of each phase. Here we report preliminary analyses using the Data Processing & Analysis of Brain Imaging V2.3-170105 toolbox with paired-sample t-tests across the whole brain.
Result(s): Average sleep duration in the HS phase was 7.55+/-0.55 h/ night vs. 6.10+/-0.49 h/night during SR (p<0.0001). Examining iFC of 17 previously studied regions-of-interest relevant to food valuation and interoception yielded two significant results after correction for Gaussian Random Field (p<0.001 at voxel level, cluster p<0.05). iFC was greater following SR than HS for (1) left inferior frontal gyrus with medial prefrontal cortex (mPFC); and (2) mPFC with bilateral superior temporal gyrus.
Conclusion(s): This study provides preliminary evidence of decreased segregation between a key anterior node of the default mode network (mPFC) and nodes of the salience and somatosensory (auditory) networks under prolonged mild SR. Such iFC changes, suggesting atypical network coupling, if confirmed in the completed sample, will be examined in the future in relation to key measures of metabolism and cardiovascular risks

Although prior research suggests that children show rapid change in socioemotional functioning and aggression throughout early childhood, little is known about how these factors may be associated with the development of callous-unemotional (CU) features. This study investigated the parallel development of, and reciprocal relationships between, emotion understanding (EU) and aggression across early childhood, as well as how they play a role in the development of CU features. Parallel latent growth curve modeling was used to examine longitudinal reciprocal relationships between EU and aggression in a sample of 498 primarily Black (i.e., African-American or Afro-Caribbean) preschoolers (49.5% male, 89.2% Black, M_age = 4.1), followed with six waves over a 45-month period from pre-kindergarten through grade 2. CU features were included as a baseline covariate, as well as an outcome, of EU and aggression growth factors. Children with lower levels of EU at age 4 displayed higher linear increases in aggression over time. EU at age 4 had a significant indirect effect on CU features at age 8 via its association with linear increases in aggression. Findings suggest that EU is influential in the early development of aggression, which may in turn influence the development or exacerbation of CU features. Children's EU in early childhood, especially concerning others' distress, may be an important component of preventive intervention efforts for young children at risk for serious antisocial behavior.

Introduction: Child fatigue has been associated with behavioral outcomes, including aggression, hyperactivity, and conduct problems, which may affect academic performance. We explored whether fatigue was associated with external behavioral health outcomes in a predominantly Black (Afro-Caribbean and African-American) student population (90%). Ratings of parent and teacher agreement of child fatigue was evaluated. This analysis was part of a larger research program, which included a cluster randomized controlled trial in ten public elementary schools in historically disinvested neighborhoods.
Method(s): A total of 804 first-graders (7+/- 0.6 years old) participated in the study focused on child self-regulation, mental health achievement, parenting and parent involvement. Externalizing behaviors (i.e., conduct problems, aggression, and hyperactivity) were reported by teachers using the Behavior System for Children (BASC-2). A composite score of teacher-perceived child fatigue was created based on ratings of child fatigue, morning alertness, and falling asleep in class. Parent perception of child fatigue was assessed using the Children's Sleep Habits Questionnaire. Regression analysis was conducted to determine the association between teacher's reports of child fatigue and externalizing behavior problems. Cohen's kappa coefficient assessed parent and teacher agreement of child fatigue based on categorical classification of presence of child fatigue.
Result(s): Children who were perceived as fatigued (i.e., tiredness and falling asleep in class) by their teacher were more likely to have a high BASC externalizing composite score (T=60 cut off) (beta = -0.24, p<.001). Cohen's kappa of 0.004 (p<0.05) showed a slight discordance in perception of child fatigue comparing reports from teachers and parents, although results were not significant.
Conclusion(s): Teacher perception of child fatigue was significantly associated with teacher BASC T-score of child externalizing behavior outcomes. Future studies should explore longitudinal relationships between fatigue and mental health