Faculty Bibliography

OBJECTIVE: Efforts to promote early brain and child development (EBCD) include initiatives to support healthy parent-child relationships, tools to identify family social-emotional risk factors, and referrals to community programs to address family risk factors. We sought to examine if pediatricians perceive barriers to implementing these activities, and if they utilize resources to address those barriers. METHOD: Data were analyzed from 304 non-trainee pediatricians who practice general pediatrics and completed a 2013 American Academy of Pediatrics Periodic Survey. Sample weights were used to decrease non-response bias. Bivariate comparisons and multivariable regression analyses were conducted. RESULTS: At least half of the pediatricians agreed that barriers to promoting EBCD include: a lack of tools to promote healthy parent-child relationships, a lack of tools to assess the family environment for social-emotional risk factors, and a lack of local resources to address family risks. Endorsing a lack of tools to assess the family environment as a barrier was associated with using fewer screening tools and community resources. Endorsing a lack of local resources as a barrier was associated with using fewer community resources and fewer initiatives to promote parent-child relationships. Interest in pediatric mental health was associated with using more initiatives to promote healthy parent-child relationships, screening tools, and community resources. CONCLUSION: Although the majority of pediatricians perceive barriers to promoting EBCD, few are routinely using available resources to address these barriers. Addressing pediatricians' perceived barriers and encouraging interest in pediatric mental health may increase resource utilization and enhance efforts to promote EBCD.

Resting-state functional Magnetic Resonance Imaging (R-fMRI) holds the promise to reveal functional biomarkers of neuropsychiatric disorders. However, extracting such biomarkers is challenging for complex multi-faceted neuropathologies, such as autism spectrum disorders. Large multi-site datasets increase sample sizes to compensate for this complexity, at the cost of uncontrolled heterogeneity. This heterogeneity raises new challenges, akin to those face in realistic diagnostic applications. Here, we demonstrate the feasibility of inter-site classification of neuropsychiatric status, with an application to the Autism Brain Imaging Data Exchange (ABIDE) database, a large (N=871) multi-site autism dataset. For this purpose, we investigate pipelines that extract the most predictive biomarkers from the data. These R-fMRI pipelines build participant-specific connectomes from functionally-defined brain areas. Connectomes are then compared across participants to learn patterns of connectivity that differentiate typical controls from individuals with autism. We predict this neuropsychiatric status for participants from the same acquisition sites or different, unseen, ones. Good choices of methods for the various steps of the pipeline lead to 67% prediction accuracy on the full ABIDE data, which is significantly better than previously reported results. We perform extensive validation on multiple subsets of the data defined by different inclusion criteria. These enables detailed analysis of the factors contributing to successful connectome-based prediction. First, prediction accuracy improves as we include more subjects, up to the maximum amount of subjects available. Second, the definition of functional brain areas is of paramount importance for biomarker discovery: brain areas extracted from large R-fMRI datasets outperform reference atlases in the classification tasks.

BACKGROUND: Although differences in both neuroanatomical measures and personality traits, in particular neuroticism, have been associated with alcohol use disorders (AUD), whether lifetime AUD diagnosis alters the relationship between neuroticism and neuroanatomical structures remains to be determined. METHODS: Data from 65 patients with lifetime AUD diagnoses and 65 healthy comparisons (HC) group-matched on age, sex and race were extracted from the Nathan Kline Institute - Rockland Sample data set. Each subject completed personality trait measures and underwent MRI scanning. Cortical thickness measures at 68 Desikan-Killiany Atlas regions were obtained using FreeSurfer 5.3.0. Regression analyses were performed to identify brain regions at which the neuroticism-cortical thickness relationship was altered by lifetime AUD status. RESULTS: As expected, AUDs had higher neuroticism scores than HCs. Correlations between neuroticism and cortical thickness in the left insula and right fusiform differed significantly across groups. Higher neuroticism score in AUD and the interaction between the insular cortical thickness-neuroticism correlation and AUD status were confirmed in a replication study using the Human Connectome Project data set. CONCLUSIONS: Results confirmed the relationship between neuroticism and AUD and suggests that specific cortical regions, particularly the left insula, represent anatomic substrates underlying this association in AUD.

Numerous studies have demonstrated differences between males and females in hippocampal structure, function, and plasticity. There also are many studies about the different predisposition of a males and females for disorders where the hippocampus plays an important role. Many of these reports focus on area CA1, but other subfields are also very important, and unlikely to be the same as area CA1 based on what is known. Here we review basic studies of male and female structure, function, and plasticity of area CA3 pyramidal cells of adult rats. The data suggest that the CA3 pyramidal cells of males and females are distinct in structure, function, and plasticity. These sex differences cannot be simply explained by the effects of circulating gonadal hormones. This view agrees with previous studies showing that there are substantial sex differences in the brain that cannot be normalized by removing the gonads and depleting peripheral gonadal hormones. Implications of these comparisons for understanding sex differences in hippocampal function and dysfunction are discussed. (c) 2016 Wiley Periodicals, Inc.

This data descriptor describes a repository of openly shared data from an experiment to assess inter-individual differences in default mode network (DMN) activity. This repository includes cross-sectional functional magnetic resonance imaging (fMRI) data from the Multi Source Interference Task, to assess DMN deactivation, the Moral Dilemma Task, to assess DMN activation, a resting state fMRI scan, and a DMN neurofeedback paradigm, to assess DMN modulation, along with accompanying behavioral and cognitive measures. We report technical validation from n=125 participants of the final targeted sample of 180 participants. Each session includes acquisition of one whole-brain anatomical scan and whole-brain echo-planar imaging (EPI) scans, acquired during the aforementioned tasks and resting state. The data includes several self-report measures related to perseverative thinking, emotion regulation, and imaginative processes, along with a behavioral measure of rapid visual information processing. Technical validation of the data confirms that the tasks deactivate and activate the DMN as expected. Group level analysis of the neurofeedback data indicates that the participants are able to modulate their DMN with considerable inter-subject variability. Preliminary analysis of behavioral responses and specifically self-reported sleep indicate that as many as 73 participants may need to be excluded from an analysis depending on the hypothesis being tested. The present data are linked to the enhanced Nathan Kline Institute, Rockland Sample and builds on the comprehensive neuroimaging and deep phenotyping available therein. As limited information is presently available about individual differences in the capacity to directly modulate the default mode network, these data provide a unique opportunity to examine DMN modulation ability in relation to numerous phenotypic characteristics.

What an animal needs to learn to survive is altered dramatically as they change from dependence on the parent for protection to independence and reliance on self-defense. This transition occurs in most altricial animals, but our understanding of the behavioral neurobiology has mostly relied on the infant rat. The transformation from dependence to independence occurs over three weeks in pups and is accompanied by complex changes in responses to both natural and learned threats and the supporting neural circuitry. Overall, in early life, the threat system is quiescent and learning is biased towards acquiring attachment related behaviors to support attachment to the caregiver and proximity seeking. Caregiver-associated cues learned in infancy have the ability to provide a sense of safety throughout lifetime. This attachment/safety system is activated by learning involving presumably pleasurable stimuli (food, warmth) but also painful stimuli (tailpinch, moderate shock). At about the midway point to independence, pups begin to have access to the adult-like amygdala-dependent threat system and amygdala-dependent responses to natural dangers such as predator odors. However, pups have the ability to switch between the infant and adult-like system, which is controlled by maternal presence and modification of stress hormones. Specifically, if the pup is alone, it will learn fear but if with the mother it will learn attachment (10-15 days of age). As pups begin to approach weaning, pups lose access to the attachment system and rely only on the amygdala-dependent threat system. However, pups learning system is complex and exhibits flexibility that enables the mother to override the control of the attachment circuit, since newborn pups may acquire threat responses from the mother expressing fear in their presence. Together, these data suggest that the development of pups' threat learning system is not only dependent upon maturation of the amygdala, but it is also exquisitely controlled by the environment. Most notably the mother can switch pup learning between attachment to threat learning in a moment's notice. This enables the mother to navigate pup's learning about the world and what is threatening and what is safe.

INTRODUCTION: Asylum seekers are a unique population, particularly those who have endured persecution for their sexual orientation or gender identity. Little data exist about the specific experiences and needs of asylum seekers persecuted due to lesbian, gay, bisexual or transgender (LGBT) identity. METHODS: Quantitative data were gathered regarding demographics, persecution histories, and mental health of 61 clients from a torture survivors program in New York City who reported persecution due to LGBT identity. Thirty-five clients persecuted due to their LGBT identity were matched by country of origin and sex with clients persecuted for other reasons in order to explore how persecution and symptoms may differ for LGBT clients. RESULTS: LGBT asylum seekers have a higher incidence of sexual violence, persecution occurring during childhood, persecution by family members, and suicidal ideation. CONCLUSIONS: Understanding the type of persecution experiences and how these influence mental health outcomes is an essential step towards designing and delivering effective treatments.

Twin studies provide valuable insights into the analysis of genetic and environmental factors influencing human brain development. However, these findings may not generalize to singletons due to differences in pre- and postnatal environments. One would expect the effect of these differences to be greater during the early years of life. To address this concern, we compare longitudinal diffusion data of white matter regions for 26 singletons and 76 twins (monozygotic and dizygotic) from birth to 2 years of age. We use nonlinear mixed effect modeling where the temporal changes in the diffusion parameters are described by the Gompertz function. The Gompertz function describes growth trajectory in terms of intuitive parameters: asymptote, delay, and speed. We analyzed fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) for 21 regions of interest (ROIs). These ROIs included areas in the association, projection, and commissural fiber tracts. We did not find any differences in the diffusion parameters between monozygotic and dizygotic twins. In addition, FA and RD showed no developmental differences between singletons and twins for the regions analyzed. However, the delay parameter of the Gompertz function of AD for the anterior limb of the internal capsule and anterior corona radiata was significantly different between singletons and twins. Further analysis indicated that the differences are small, and twins "catch up" by the first few months of life. These results suggest that the effects of differences of pre- and postnatal environments between twins and singletons are minimal on white matter development and disappear early in life. Hum Brain Mapp, 2016. (c) 2016 Wiley Periodicals, Inc.

Default mode network (DMN) deactivation has been shown to be functionally relevant for goal-directed cognition. In this study, the DMN's role during olfactory processing was investigated using two complementary functional magnetic resonance imaging (fMRI) paradigms with identical timing, visual-cue stimulation, and response monitoring protocols. Twenty-nine healthy, non-smoking, right-handed adults (mean age = 26 +/- 4 years, 16 females) completed an odor-visual association fMRI paradigm that had two alternating odor + visual and visual-only trial conditions. During odor + visual trials, a visual cue was presented simultaneously with an odor, while during visual-only trial conditions the same visual cue was presented alone. Eighteen of the twenty-nine participants (mean age = 27.0 +/- 6.0 years, 11 females) also took part in a control no-odor fMRI paradigm that consisted of a visual-only trial condition which was identical to the visual-only trials in the odor-visual association paradigm. Independent Component Analysis (ICA), extended unified structural equation modeling (euSEM), and psychophysiological interaction (PPI) were used to investigate the interplay between the DMN and olfactory network. In the odor-visual association paradigm, DMN deactivation was evoked by both the odor + visual and visual-only trial conditions. In contrast, the visual-only trials in the no-odor paradigm did not evoke consistent DMN deactivation. In the odor-visual association paradigm, the euSEM and PPI analyses identified a directed connectivity between the DMN and olfactory network which was significantly different between odor + visual and visual-only trial conditions. The results support a strong interaction between the DMN and olfactory network and highlights the DMN's role in task-evoked brain activity and behavioral responses during olfactory processing. Hum Brain Mapp, 2016. (c) 2016 Wiley Periodicals, Inc.

Memory formation requires the temporal coordination of molecular events and cellular processes following a learned event. During Pavlovian threat (fear) conditioning (PTC), sensory and neuromodulatory inputs converge on post-synaptic neurons within the lateral nucleus of the amygdala (LA). By activating an intracellular cascade of signaling molecules, these G-protein-coupled neuromodulatory receptors are capable of recruiting a diverse profile of plasticity-related proteins. Here we report that norepinephrine, through its actions on beta-adrenergic receptors (betaARs), modulates aversive memory formation following PTC through two molecularly and temporally distinct signaling mechanisms. Specifically, using behavioral pharmacology and biochemistry in adult rats, we determined that betaAR activity during, but not after PTC training initiates the activation of two plasticity-related targets: AMPA receptors (AMPARs) for memory acquisition and short-term memory and extracellular regulated kinase (ERK) for consolidating the learned association into a long-term memory. These findings reveal that betaAR activity during, but not following PTC sets in motion cascading molecular events for the acquisition (AMPARs) and subsequent consolidation (ERK) of learned associations.Neuropsychopharmacology accepted article preview online, 20 October 2016. doi:10.1038/npp.2016.238.