The ABCD study is recruiting and following the brain development and health of over 10,000 9–10 year olds through adolescence. The imaging component of the study was developed by the ABCD Data Analysis and Informatics Center (DAIC) and the ABCD Imaging Acquisition Workgroup. Imaging methods and assessments were selected, optimized and harmonized across all 21 sites to measure brain structure and function relevant to adolescent development and addiction. This article provides an overview of the imaging procedures of the ABCD study, the basis for their selection and preliminary quality assurance and results that provide evidence for the feasibility and age-appropriateness of procedures and generalizability of findings to the existent literature.

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...

The nature of immature reward processing and the influence of rewards on basic elements of cognitive control during adolescence are currently not well understood. Here, during functional magnetic resonance imaging, healthy adolescents and adults performed a modified antisaccade task in which trial-by-trial reward contingencies were manipulated. The use of a novel fast, event-related design enabled developmental differences in brain function underlying temporally distinct stages of reward processing and response inhibition to be assessed. Reward trials compared with neutral trials resulted in faster correct inhibitory responses across ages and in fewer inhibitory errors in adolescents. During reward trials, the blood oxygen level–dependent signal was attenuated in the ventral striatum in adolescents during cue assessment, then overactive during response preparation, suggesting limitations during adolescence in reward assessment and heightened reactivity in anticipation of reward compared with adults. Importantly, heightened activity in the frontal cortex along the precentral sulcus was also observed in adolescents during reward-trial response preparation, suggesting reward modulation of oculomotor control regions supporting correct inhibitory responding. Collectively, this work characterizes specific immaturities in adolescent brain systems that support reward processing and describes the influence of reward on inhibitory control. In sum, our findings suggest mechanisms that may underlie adolescents’ vulnerability to poor decision-making and risk-taking behavior.

We examined the neural basis of self-regulation in individuals from a cohort of preschoolers who performed the delay-ofgratification task 4 decades ago. Nearly 60 individuals, now in their mid-forties, were tested on "hot" and "cool" versions of a go/ nogo task to assess whether delay of gratification in childhood predicts impulse control abilities and sensitivity to alluring cues (happy faces). Individuals who were less able to delay gratification in preschool and consistently showed low self-control abilities in their twenties and thirties performed more poorly than did high delayers when having to suppress a response to a happy face but not to a neutral or fearful face. This finding suggests that sensitivity to environmental hot cues plays a significant role in individuals' ability to suppress actions toward such stimuli. A subset of these participants (n = 26) underwent functional imaging for the first time to test for biased recruitment of frontostriatal circuitry when required to suppress responses to alluring cues. Whereas the prefrontal cortex differentiated between nogo and go trials to a greater extent in high delayers, the ventral striatum showed exaggerated recruitment in low delayers. Thus, resistance to temptation as measured originally by the delay-of-gratification task is a relatively stable individual difference that predicts reliable biases in frontostriatal circuitries that integrate motivational and control processes.reward | behavioral suppression | functional MRI | inferior frontal gyrus | longitudinal T he ability to resist temptation in favor of long-term goals is an essential component of individual, societal, and economical success. Developmentally, this ability has been assessed by measuring how long a young child can resist an immediate reward (e.g., a cookie) in favor of a larger, later reward (e.g., two cookies) (1). Even as adults we vary in our ability to resist temptations. Alluring situations can diminish our control (2-4); what serves as an alluring situation that requires a capacity to control our impulses, however, changes as a function of age (e.g., from cookies to social acceptance). In the present study we examined the extent to which individual differences in delay of gratification assessed when participants were in preschool and in their 20s and 30s predict control over impulses and sensitivity to social cues at the behavioral and neural level when the participants were in their 40s.Delay of gratification depends importantly on cognitive control (5). Cognitive control refers to the ability to suppress competing inappropriate thoughts or actions in favor of appropriate ones (6-11). Previously, we have shown that performance on the delay-of-gratification task in childhood predicts the efficiency with which the same individuals perform a cognitive control task (the go/nogo task) as adolescents and young adults (5). Individuals who as preschoolers directed their attention toward rewarding aspects of the classic delay-of-gratification situation, such as focusing on the cookie...