A set of face stimuli called the NimStim Set of Facial Expressions is described. The goal in creating this set was to provide facial expressions that untrained individuals, characteristic of research participants, would recognize. This set is large in number, multiracial, and available to the scientific community online. The results of psychometric evaluations of these stimuli are presented. The results lend empirical support for the validity and reliability of this set of facial expressions as determined by accurate identification of expressions and high intra-participant agreement across two testing sessions, respectively.

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Background-Adolescence is a transition period from childhood to adulthood that is often characterized by emotional instability. This period is also a time of increased incidence of anxiety and depression underscoring the importance of understanding biological substrates of behavioral and emotion regulation during adolescence. Developmental changes in the brain in concert with individual predispositions for anxiety may underlie the increased risk for poor outcomes reported during adolescence. We tested the hypothesis that difficulties in regulating behavior in emotional contexts in adolescents may be due to competition between heightened activity in subcortical emotional processing systems and immature top-down prefrontal systems. Individual differences in emotional reactivity may put some teens at greater risk during this sensitive transition in development.

Under typical conditions, medial prefrontal cortex (mPFC) connections with the amygdala are immature during childhood and become adult-like during adolescence. Rodent models show that maternal deprivation accelerates this development, prompting examination of human amygdala-mPFC phenotypes following maternal deprivation. Previously institutionalized youths, who experienced early maternal deprivation, exhibited atypical amygdalamPFC connectivity. Specifically, unlike the immature connectivity (positive amygdala-mPFC coupling) of comparison children, children with a history of early adversity evidenced mature connectivity (negative amygdala-mPFC coupling) and thus, resembled the adolescent phenotype. This connectivity pattern was mediated by the hormone cortisol, suggesting that stress-induced modifications of the hypothalamic-pituitary-adrenal axis shape amygdala-mPFC circuitry. Despite being age-atypical, negative amygdala-mPFC coupling conferred some degree of reduced anxiety, although anxiety was still significantly higher in the previously institutionalized group. These findings suggest that accelerated amygdala-mPFC development is an ontogenetic adaptation in response to early adversity.fMRI | emotion regulation | stress | neurodevelopment

Recent human imaging and animal studies highlight the importance of frontoamygdala circuitry in the regulation of emotional behavior and its disruption in anxiety-related disorders. While tracing studies have suggested changes in amygdala-cortical connectivity through the adolescent period in rodents, less is known about the reciprocal connections within this circuitry across human development, when these circuits are being fine-tuned and substantial changes in emotional control are observed. The present study examined developmental changes in amygdala-prefrontal circuitry across the ages of 4 to 22 years using task-based functional magnetic resonance imaging (fMRI). Results suggest positive amygdala-prefrontal connectivity in early childhood that switches to negative functional connectivity during the transition to adolescence. Amygdala-mPFC functional connectivity was significantly positive (greater than zero) among participants younger than ten, whereas functional connectivity was significantly negative (less than zero) among participants ten years and older, over and above the effect of amygdala reactivity. The developmental switch in functional connectivity was paralleled by a steady decline in amygdala reactivity. Moreover, the valence switch might explain age-related improvement in task performance and a developmentally normative decline in anxiety. Initial positive connectivity followed by a valence shift to negative connectivity provides a neurobiological basis for regulatory development and may present novel insight into a more general process of developing regulatory connections.

Early adversity, for example poor caregiving, can have profound effects on emotional development. Orphanage rearing, even in the best circumstances, lies outside of the bounds of a species-typical caregiving environment. The long-term effects of this early adversity on the neurobiological development associated with socio-emotional behaviors are not well understood. Seventy-eight children, who include those who have experienced orphanage care and a comparison group, were assessed. Magnetic resonance imaging (MRI) was used to measure volumes of whole brain and limbic structures (e.g. amygdala, hippocampus). Emotion regulation was assessed with an emotional go-nogo paradigm, and anxiety and internalizing behaviors were assessed using the Screen for Child Anxiety Related Emotional Disorders, the Child Behavior Checklist, and a structured clinical interview. Late adoption was associated with larger corrected amygdala volumes, poorer emotion regulation, and increased anxiety. Although more than 50% of the children who experienced orphanage rearing met criteria for a psychiatric disorder, with a third having an anxiety disorder, the group differences observed in amygdala volume were not driven by the presence of an anxiety disorder. The findings are consistent with previous reports describing negative effects of prolonged orphanage care on emotional behavior and with animal models that show long-term changes in the amygdala and emotional behavior following early postnatal stress. These changes in limbic circuitry may underlie residual emotional and social problems experienced by children who have been internationally adopted.

A review of the human developmental neuroimaging literature that investigates outcomes following exposure to psychosocial adversity is presented with a focus on two subcortical structures – the hippocampus and the amygdala. Throughout this review, we discuss how a consideration of developmental timing of adverse experiences and age at measurement might provide insight into the seemingly discrepant findings across studies. We use findings from animal studies to suggest some mechanisms through which timing of experiences may result in differences across time and studies. The literature suggests that early life may be a time of heightened susceptibility to environmental stressors, but that expression of these effects will vary by age at measurement.

Mouse models are useful for studying genes involved in behavior, but whether they are relevant for human behavior is unclear. Here, we identified parallel phenotypes in mice and humans resulting from a common single-nucleotide polymorphism in the brain-derived neurotrophic factor (BDNF) gene, which is involved in anxiety-related behavior. An inbred genetic knock-in mouse strain expressing the variant BDNF recapitulated the phenotypic effects of the human polymorphism. Both were impaired in extinguishing a conditioned fear response, which was paralleled by atypical frontoamygdala activity in humans. Thus, this variant BDNF allele may play a role in anxiety disorders showing impaired learning of cues that signal safety versus threat, and in the efficacy of treatments that rely on extinction mechanisms such as exposure therapy.Genetically modified mice provide useful model systems for testing the role of candidate genes in behavior. The extent to which such genetic manipulations in the mouse and the resulting phenotype can be translated across species, from mouse to human, is less clear. In this report we focused on identifying biologically valid phenotypes across species. We utilized a common single nucleotide polymorphism (SNP) in the brain-derived neurotrophic factor (BDNF) gene that leads to a valine (Val) to methionine (Met) substitution at codon 66 (Val66Met). In an inbred genetic knock-in mouse strain that expresses the variant BDNF allele to recapitulate the specific phenotypic properties of the human polymorphism in vivo, we found the BDNF Val66Met genotype was associated with treatment resistant forms of anxiety-like behavior (1). The objective of this study was to test if the Val66Met genotype could impact extinction learning in our mouse model, and if such findings could be generalized to human populations.BDNF mediates synaptic plasticity associated with learning and memory (2,3) specifically in fear learning and extinction (4,5). BDNF-dependent forms of fear learning have known biological substrates, and lie at the core of a number of clinical disorders (6,7) associated with the variant BDNF (8-10). Fear learning paradigms require the ability to recognize and +To whom correspondence should be addressed. fas2002@med.cornell.edu or bjc2002@med.cornell.edu. remember cues that signal safety or threat and to extinguish these associations when they no longer exist. These abilities are impaired in anxiety disorders such as posttraumatic stress disorder and phobias (11,12). Behavioral treatments for these disorders such as exposure therapy rely on basic principles of extinction learning (13) in which an individual is repeatedly exposed to an event that was previously associated with aversive consequences. Understanding the effect of the BDNF Met allele on these forms of learning can provide insight into the mechanism of risk for anxiety disorders, refine existing treatments, and may lead to genotypebased personalized medicine. NIH Public AccessWe examined the impact of the variant BDNF on classic fear...