Faculty Bibliography

Understanding how the structure of cognition arises from the topographical organization of the cortex is a primary goal in neuroscience. Previous work has described local functional gradients extending from perceptual and motor regions to cortical areas representing more abstract functions, but an overarching framework for the association between structure and function is still lacking. Here, we show that the principal gradient revealed by the decomposition of connectivity data in humans and the macaque monkey is anchored by, at one end, regions serving primary sensory/motor functions and at the other end, transmodal regions that, in humans, are known as the default-mode network (DMN). These DMN regions exhibit the greatest geodesic distance along the cortical surface-and are precisely equidistant-from primary sensory/motor morphological landmarks. The principal gradient also provides an organizing spatial framework for multiple large-scale networks and characterizes a spectrum from unimodal to heteromodal activity in a functional metaanalysis. Together, these observations provide a characterization of the topographical organization of cortex and indicate that the role of the DMN in cognition might arise from its position at one extreme of a hierarchy, allowing it to process transmodal information that is unrelated to immediate sensory input.

Disrupted social behavior is a core symptom of multiple psychiatric and neurodevelopmental disorders. Many of these disorders are exacerbated by adverse infant experiences, including maltreatment and abuse, which negatively affect amygdala development. Although a link between impaired social behavior, abnormal amygdala function and depressive-like behavior following early adversity has been demonstrated in humans and animal models, the developmental emergence of maltreatment-related social deficits and associated amygdala neural activity are unknown. We used a naturalistic rodent model of maternal maltreatment during a sensitive period, postnatal days 8-12 (PN8-12), which produces social behavior deficits that precede adolescent depressive-like behavior and amygdala dysfunction, to examine social behavior in infancy, periweaning and adolescence. Neural activity in response to the social behavior test was assessed via c-Fos immunohistochemistry at these ages. A separate group of animals was tested for adult depressive-like behavior in the forced swim test. Maltreatment spared infant (PN16-18) social behavior but disrupted periweaning (PN20-22) and adolescent (PN42-48) social behavior. Maltreated rats exhibited blunted neural activation in the amygdala and other areas implicated in social functioning, including the medial prefrontal cortex and nucleus accumbens, at these ages and increased adult depressive-like behavior. These findings may suggest corticolimbic involvement in the emergence of maltreatment-induced social deficits that are linked to adult depressive-like behavior, thereby highlighting potential targets for therapeutic intervention. Understanding how infant experiences influence social behavior and age-specific expression across development may provide insights into basic neural mechanisms of social behaviors and disease-relevant social dysfunction exacerbated by early-life stress.

Autism spectrum disorder (ASD) is often associated with cognitive deficits and excessive anxiety. Neuroimaging studies have shown atypical structure and neural connectivity in the hippocampus, medial prefrontal cortex (mPFC), and striatum, regions associated with cognitive function and anxiety regulation. Adult hippocampal neurogenesis is involved in many behaviors that are disrupted in ASD, including cognition, anxiety, and social behaviors. Additionally, glial cells, such as astrocytes and microglia, are important for modulating neural connectivity during development, and glial dysfunction has been hypothesized to be a key contributor to the development of ASD. Cells with astroglial characteristics are known to serve as progenitor cells in the developing and adult brain. Here, we examined adult neurogenesis in the hippocampus, as well as astroglia and microglia in the hippocampus, mPFC, and striatum of two models that display autism-like phenotypes, Cntnap2-/- and Shank3+/DeltaC transgenic mice. We found a substantial decrease in the number of immature neurons and radial glial progenitor cells in the ventral hippocampus of both transgenic models compared with wild-type controls. No consistent differences were detected in the number or size of astrocytes or microglia in any other brain region examined. Future work is needed to explore the functional contribution of adult neurogenesis to autism-related behaviors as well as to temporally characterize glial plasticity as it is associated with ASD.

PURPOSE: Adolescents are low users of medical care. Psychological factors and perceived reasons to not seek routine medical care may increase risk of nonuse by adolescents with undiagnosed asthma. This study tests if psychological factors were associated with seeing a medical provider for asthma-like symptoms; identifies adolescents' perceived reasons for not obtaining care; explores if psychological factors are associated with these perceptions; and explores if asthma severity moderates the relationships with psychological factors. METHODS: We analyzed cross-sectional data from a baseline assessment of 349 urban, primarily ethnic minority adolescents with moderate to severe asthma-like symptoms but no asthma diagnosis who were enrolled in a controlled trial. RESULTS: The odds of seeing a provider for their asthma-like symptoms were significantly higher for those with asthma-related anxiety (odds ratio [OR]: 1.644; 95% confidence interval [CI]: 1.242-2.176) and depressive symptoms (OR: 1.031; 95% CI: 1.004-1.059). The most commonly endorsed reason for noncare included a characterization of symptoms as not serious, past medical visits not diagnosed as asthma, fear of diagnosis, busy lifestyles, and not wanting medication. Psychological factors were not related to the number of reasons or to most of the commonly endorsed reasons. Adolescents with more asthma-related anxiety were less likely to characterize their breathing problems as serious (OR = .0583; 95% CI: .424-.802) and were more likely to report busy lifestyles (OR = 1.593; 95% CI: 1.122-2.261). CONCLUSIONS: Adolescent-perceived reasons for noncare were not pragmatic, but instead highlighted denial. Asthma-related anxiety was the most robust psychological factor associated with the decision to seek medical care.

Children and adolescents afflicted with psychiatric illness are at particularly high risk for becoming part of the juvenile justice system. More than two thirds of justice-involved youth have psychiatric disorders (Abram et al., 2003; Shufelt & Cocozza, 2006; Teplin et al., 2002). Given the involvement of the legal system, youth being separated from families, and a host of other factors, mental health service delivery in a juvenile detention facility poses unique challenges. This article focuses on an overview of the problems commonly encountered in this setting. A clinical vignette will be used to highlight key points. The role and significance of trauma, common psychiatric disorders, and relevant medication rationale will be explored.

Long tolerated as a rite of passage into adulthood, bullying is now recognized as a major and preventable public health problem. The consequences of bullying-for those who are bullied, the perpetrators of bullying, and the witnesses-include poor physical health, anxiety, depression, increased risk for suicide, poor school performance, and future delinquent and aggressive behavior. Despite ongoing efforts to address bullying at the law, policy, and programmatic levels, there is still much to learn about the consequences of bullying and the effectiveness of various responses. In 2016, the National Academies of Sciences, Engineering, and Medicine published a report entitled Preventing Bullying Through Science, Policy and Practice, which examined the evidence on bullying, its impact, and responses to date. This article summarizes the report's key findings and recommendations related to bullying prevention.

Social attachment is a biological and affective need. When this need is not met, people experience loneliness. Loneliness is associated with impaired social cognition, and is a risk factor for broad based morbidity across the adult lifespan even after controlling for multiple factors. However, little is known about loneliness in schizophrenia. Eighty-seven non-depressed individuals with schizophrenia or schizoaffective disorder (including 51 inpatients) and 58 control subjects completed the revised UCLA Loneliness scale. Social cognition was assessed with a self-report questionnaire and a performance-based task. Social trait perception was assessed with a facial task. Comorbid medical diagnoses were available for all inpatients. Patients reported greater loneliness levels than controls, while in- and out-patients did not significantly differ. In patients, loneliness was associated with self-report measures of social cognition. Patients' loneliness scores predicted a diagnosis of drug abuse/dependence, number of drugs used, hypertension and abnormal hemoglobin A1c levels. Patients experienced higher levels of loneliness than controls, independently of their objective social isolation. Loneliness did not rely on the same psychological processes in patients than in controls. Loneliness in schizophrenia is a symptom that deserves more scrutiny, particularly as it relates to the high prevalence of metabolic syndrome in this population.