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Recent technological and analytical progress in brain imaging has enabled the examination of brain organization and connectivity at unprecedented levels of detail. The Human Connectome Project in Development (HCP-D) is exploiting these tools to chart developmental changes in brain connectivity. When complete, the HCP-D will comprise approximately ∼1750 open access datasets from 1300+healthy human participants, ages 5-21 years, acquired at four sites across the USA. The participants are from diverse geographical, ethnic, and socioeconomic backgrounds. While most participants are tested once, others take part in a three-wave longitudinal component focused on the pubertal period (ages 9-17 years). Brain imaging sessions are acquired on a 3T Siemens Prisma platform and include structural, functional (resting state and task-based), diffusion, and perfusion imaging, physiological monitoring, and a battery of cognitive tasks and self-reports. For minors, parents additionally complete a battery of instruments to characterize cognitive and emotional development, and environmental variables relevant to development. Participants provide biological samples of blood, saliva, and hair, enabling assays of pubertal hormones, health markers, and banked DNA samples. This paper outlines the overarching aims of the project, the approach taken to acquire maximally informative data while minimizing participant burden, preliminary analyses, and discussion of the intended uses and limitations of the dataset.

Introduction The Trier Social Stress Test (TSST) is the most widely used protocol for activating a stress response of the hypothalamic-pituitary-adrenocortical (HPA) axis and other stress-mediating systems. A number of variants of the TSST exist, including ones for children, groups, and virtual reality. All of these versions, though, require in-person assessment. The COVID-19 pandemic has made in-person assessment impossible or extremely difficult and potentially dangerous. The purpose of this study was to validate a completely remote, online, version of the TSST for children. Method A sample of 68 (27 female) 15- and 16-year old participants were administered the TSST-Online (TSST-OL) during the late afternoon hours (3–6 p.m. start time). The participants, judges (one male, one female), and experimenter (female) all joined the assessment from their own homes via the online platform, ZOOM™. Two sessions were conducted, one to obtain consent, explain procedures, work with the family to arrange the computer and room set-up for the TSST-OL and one within two weeks to conduct the procedure. The participants were trained to take their own saliva samples and a saliva sampling kit was mailed to the home in between the first and second session. The samples were then mailed to the researchers within a day of collection. The participant was observed during saliva collection to determine correct procedures were followed. Salivary cortisol, salivary α-amylase and self-reports of stress were measured multiple times over the second session. Results rmANOVAs yielded a significant effect of trials, for cortisol, F(1.37,90.46) = 15.13, p = .001, sAA, F(2.75,146.68) = 6.91, p = .001, and self-rated stress, F(3.43,222.69) = 118.73, p = .001. There were no significant sex by trials interactions for any measure, although females reported more stress than males, F(1,65) = 9.14, p = .004. For cortisol, from baseline to expected peak (30 min after the onset of speech preparation), the Cohen’s effect size was dz = 0.57. Using 1.5 nmol/l (or 0.54 μg/dl) as the criterion for a response (Miller, Plessow, Kirschaum, & Stalder, 2013), 63% of the participants produced a significant increase in cortisol. Conclusions The responses to the TSST-OL are consistent with in-person responses among children and adolescents (see recent meta-analysis (Seddon et al., 2020). The protocol is a viable way of assessing reactivity of the HPA axis and other stress systems without needing to bring the participant into the research laboratory. This method will be useful during periods of widespread infection. It should also work to study populations who all live too far from the research laboratory to be assessed in person.

Highlights • Previously institutionalized (PI) youth exhibit altered frontolimbic connectivity. • Resting-state functional connectivity is associated with IQ in early adolescence. • PI and comparison youth differ in dorsal attention network connectivity. • Between-system connectivity is associated with internalizing in early adolescence., Psychosocial acceleration theory and other frameworks adapted from life history predict a link between early life stress and accelerated maturation in several physiological systems. Those findings led researchers to suggest that the emotion-regulatory brain circuits of previously-institutionalized (PI) youth are more mature than youth raised in their biological families (non-adopted, or NA, youth) during emotion tasks. Whether this accelerated maturation is evident during resting-state fMRI has not yet been established. Resting-state fMRI data from 83 early adolescents (Mage = 12.9 years, SD = 0.57 years) including 41 PI and 42 NA youth, were used to examine seed-based functional connectivity between the amygdala and ventromedial prefrontal cortex (vmPFC). Additional whole-brain analyses assessed group differences in functional connectivity and associations with cognitive performance and behavior. We found group differences in amygdala – vmPFC connectivity that may be consistent with accelerated maturation following early life stress. Further, whole-brain connectivity analyses revealed group differences associated with internalizing and externalizing symptoms. However, the majority of whole-brain results were not consistent with an accelerated maturation framework. Our results suggest early life stress in the form of institutional care is associated with circuit-specific alterations to a frontolimbic emotion-regulatory system, while revealing limited differences in more broadly distributed networks.

Although behavioral studies have demonstrated that executive function (EF) develops rapidly during early childhood, few studies have investigated neural systems supporting EF during the preschool years. These systems are sensitive to variations in children's early life experiences, including preterm birth. The current study collected behavioral and event related potential (ERP) data during an EF task (directional Stroop) in a sample of 150 full-term and low-risk preterm children aged 4-years. Children's IQ and processing speed (WPPSI-III), and parent report of EF (BRIEF-P), were also measured. Forty-nine children born full-term and 43 low-risk preterm children provided useable ERP data. Similar to prior studies with adults and older children, preschool-aged children showed modulation of ERP components (N2, P3) by cognitive conflict. Effects of trial type were also present for early attentional components (N1 and P2). Exploratory analyses demonstrated that ERP measures of EF were correlated with individual differences in cognitive and behavioral functioning in both full-term and low-risk preterm populations. Future research investigating the neural correlates of early measures of EF in low-risk preterm children and other at-risk groups is warranted to better understand how trajectories of EF development are altered in the first years of life.

Objective Depression is linked to alterations in both emotion and self-processing. The current study used functional magnetic resonance imaging (fMRI) to assess neural activation in healthy and depressed youth to a novel task that combined emotion processing with self-face recognition. Methods An fMRI study involving 81 adolescents (50.6% females; Mage=14.61, SD=1.65) comprised of depressed (DEP, n=43), and healthy controls (HC, n=38). Participants completed a clinical interview and self-report measures during an initial assessment. In the scanner, adolescents completed a face recognition task, viewing emotional (happy, sad, neutral) images of their own face (self) or the face of another youth (other). Results DEP youth showed higher activity in the cuneus (F=26.29) and post and precentral gyri (F=20.76), across all conditions compared to HC. Sad faces elicited higher posterior cingulate cortex, precuneus (F=10.36) and inferior parietal cortex activity (F=11.0), and self faces elicited higher precuneus, fusiform (F=16.39), insula and putamen (F=16.82) activity in all youth. DEP showed higher middle temporal activity to neutral faces but lower activity to sad faces compared to HC, who showed the opposite pattern (F=12.86). DEP also showed hypoactive mid-temporal limbic activity relative to controls when identifying their self happy face vs. neutral face, yet showed hyperactivity when identifying the other happy face vs. neutral face, and HC showed the opposite pattern (F=10.94). Conclusions The neurophysiology of self-face recognition is altered in adolescent depression. Specifically, depression was associated with decreased activity in neural areas that support emotional and associative processing for positive self-faces and increased processing for neutral self-faces. These results suggest that depression in adolescents is associated with hypoactive emotional processing and encoding of positive self-related visual information. This abnormal neural activity at the intersection of reward and self-processing among depressed youth might have long lasting impact in self-formation and future adult self-representations, given that adolescence is a sensitive period for self-development.

Though theory suggests that individual differences in neuroticism (a tendency to experience negative emotions) would be associated with altered functioning of the amygdala (which has been linked with emotionality and emotion dysregulation in childhood, adolescence, and adulthood), results of functional neuroimaging studies have been contradictory and inconclusive. We aimed to clarify the relationship between neuroticism and three hypothesized neural markers derived from functional magnetic resonance imaging during negative emotion face processing: amygdala activation, amygdala habituation, and amygdala-prefrontal connectivity, each of which plays an important role in the experience and regulation of emotions. We used general linear models to examine the relationship between trait neuroticism and the hypothesized neural markers in a large sample of over 500 young adults. Although neuroticism was not significantly associated with magnitude of amygdala activation or amygdala habituation, it was associated with amygdala–ventromedial prefrontal cortex connectivity, which has been implicated in emotion regulation. Results suggest that trait neuroticism may represent a failure in top-down control and regulation of emotional reactions, rather than overactive emotion generation processes, per se. These findings suggest that neuroticism, which has been associated with increased rates of transdiagnostic psychopathology, may represent a failure in the inhibitory neurocircuitry associated with emotion regulation.

Reward/behavioral approach system hypersensitivity is implicated in bipolar disorders (BD) and in normative development during adolescence. Pediatric onset of BD is associated with a more severe illness course. However, little is known about neural processing of rewards in adolescents with BD or developmental (i.e., age) associations with activation of these neural systems. The present study aims to address this knowledge gap. The present sample included 21 adolescents with BD and 26 healthy adolescents, ages 13 to 19. Participants completed a functional magnetic resonance imaging (fMRI) protocol using the Monetary Incentive Delay (MID) task. Behavioral performance was similar between groups. Group differences in BOLD activation during target anticipation and feedback anticipation periods of the task were examined using whole-brain analyses, as were group differences in age effects. During both target anticipation and feedback anticipation, adolescents with BD, compared to adolescents without psychopathology, exhibited decreased engagement of frontal regions involved in cognitive control (i.e., dorsolateral prefrontal cortex). Healthy adolescents exhibited age-related decreases, while adolescents with BD exhibited age-related increases, in activity of other cognitive control frontal areas (i.e., right inferior frontal gyrus), suggesting altered development in the BD group. Longitudinal research is needed to examine potentially abnormal development of cognitive control during reward pursuit in adolescent BD and whether early therapeutic interventions can prevent these potential deviations from normative development., Highlights • We examined reward processing in adolescents with and without bipolar disorders. • Adolescents with BD engaged cognitive control regions less when processing rewards. • Adolescents with BD failed to show age-related activations of frontal regions. • Group and group-by-age effects were not due to comorbidities or symptom state.

Major depressive disorder (MDD) is a significant contributor to lifetime disability and frequently emerges in adolescence, yet little is known about the neural mechanisms of MDD in adolescents. Dynamic causal modeling (DCM) analysis is an innovative tool that can shed light on neural network abnormalities. A DCM analysis was conducted to test several frontolimbic effective connectivity models in 27 adolescents with MDD and 21 healthy adolescents. The best neural model for each person was identified using Bayesian model selection. The findings revealed that the two adolescent groups fit similar optimal neural models. The best across-groups model was then used to infer upon both within-group and between-group tests of intrinsic and modulation parameters of the network connections. First, for model validation, within-group tests revealed robust evidence for bottom-up connectivity, but less evidence for strong top-down connectivity in both groups. Second, we tested for differences between groups on the validated parameters of the best model. This revealed that adolescents with MDD had significantly weaker bottom-up connectivity in one pathway, from amygdala to sgACC (p=0.008), than healthy controls. This study provides the first examination of effective connectivity using DCM within neural circuitry implicated in emotion processing in adolescents with MDD. These findings aid in advancing understanding the neurobiology of early-onset MDD during adolescence and have implications for future research investigating how effective connectivity changes across contexts, with development, over the course of the disease, and after intervention.

The Human Connectome Projects in Development (HCP-D) and Aging (HCP-A) are two large-scale brain imaging studies that will extend the recently completed HCP Young-Adult (HCP-YA) project to nearly the full lifespan, collecting structural, resting-state fMRI, task-fMRI, diffusion, and perfusion MRI in participants from 5 to 100+years of age. HCP-D is enrolling 1300+healthy children, adolescents, and young adults (ages 5-21), and HCP-A is enrolling 1200+healthy adults (ages 36-100+), with each study collecting longitudinal data in a subset of individuals at particular age ranges. The imaging protocols of the HCP-D and HCP-A studies are very similar, differing primarily in the selection of different task-fMRI paradigms. We strove to harmonize the imaging protocol to the greatest extent feasible with the completed HCP-YA (1200+participants, aged 22-35), but some imaging-related changes were motivated or necessitated by hardware changes, the need to reduce the total amount of scanning per participant, and/or the additional challenges of working with young and elderly populations. Here, we provide an overview of the common HCP-D/A imaging protocol including data and rationales for protocol decisions and changes relative to HCP-YA. The result will be a large, rich, multi-modal, and freely available set of consistently acquired data for use by the scientific community to investigate and define normative developmental and aging related changes in the healthy human brain.

Childhood maltreatment is a serious individual, familial, and societal threat that compromises healthy development and is associated with lasting alterations to emotion perception, processing, and regulation (Cicchetti & Curtis, 2005; Pollak, Cicchetti, Hornung, & Reed, 2000; Pollak & Tolley-Schell, 2003). Individuals with a history of maltreatment show altered structural and functional brain development in both frontal and limbic structures (Hart & Rubia, 2012). In particular, previous research has identified hyperactive amygdala responsivity associated with childhood maltreatment (e.g., Dannlowski et al., 2012). However, less is known about the impact of maltreatment on the relationship between the amygdala and other brain regions. The present study employed an emotion processing functional magnetic resonance imaging task to examine task-based activation and functional connectivity in adults who experienced maltreatment as children. The sample included adults with a history of substantiated childhood maltreatment (n = 33) and comparison adults (n = 38) who were well matched on demographic variables, all of whom have been studied prospectively since childhood. The maltreated group exhibited greater activation than comparison participants in the prefrontal cortex and basal ganglia. In addition, maltreated adults showed increased amygdala connectivity with the hippocampus and prefrontal cortex. The results suggest that the intense early stress of childhood maltreatment is associated with lasting alterations to frontolimbic circuitry.

The purpose of this study was to examine whether FKBP5 rs1360780 moderates relations between different forms of life stress/adversity (early institutional rearing and peer victimization) and depressive symptoms in adolescents. As reported previously, PI youth were at risk for being victimized by peers. Here, victimization was associated with elevated depressive symptoms. While FKBP5 did not moderate the association between early life adversity and depressive symptoms for either sex, it moderated the association between current adversity and depressive symptoms for victimized girls carrying the minor allele. Consistent with a differential susceptibility model, girls with the minor allele exhibited more depressive symptoms at higher levels of victimization, but fewer depressive symptoms at lower levels of victimization. Interestingly, boys with the CC genotype had higher rates of depressive symptoms compared to girls with the CC genotype in the context of heightened victimization.

For children reared in institutions for orphaned or abandoned children, multiple aspects of the early environment deviate from species-typical experiences, which may lead to alterations in neurobehavioral development. Although the effects of early deprivation and early life stress have been studied extensively in animal models, less is known about implications for human brain development. This structural neuroimaging study examined the long-term neural correlates of early adverse rearing environments in a large sample of 12-14 year old children (N = 110) who were internationally adopted from institutional care as young children (median age at adoption = 12 months) relative to a same age, comparison group reared with their biological families in the United States. History of institutional rearing was associated with broad changes in cortical volume even after controlling for variability in head size. Results suggested that prefrontal cortex was especially susceptible to early adversity, with significant reductions in volume (driven primarily by differences in surface area rather than cortical thickness) in post-institutionalized youth. Hippocampal volumes showed an association with duration of institutional care, with later-adopted children showing the smallest volumes relative to non-adopted controls. Larger amygdala volumes were not detected in this sample of post-institutionalized children. These data suggest that this temporally discrete period of early deprivation is associated with persisting alterations in brain morphology even years after exposure. Furthermore, these alterations are not completely ameliorated by subsequent environmental enrichment by early adolescence.

Although altered brain activation during reward tasks has been found in a number of heritable psychiatric disorders and health outcomes, the familial nature of reward-related brain activation remains unexplored. In this study, we investigated the degree to which the magnitude of mesocorticolimbic reward system signal intensities in anticipation of reward during the monetary incentive delay (MID) task was similar within forty-six pairs of adolescent, monozygotic twins. Significant within-pair correlations in brain activation during anticipation of gain were found in one third of the 18 reward-related regions investigated. These regions were the right nucleus accumbens, left and right posterior caudate, right anterior caudate, left insula, and anterior cingulate cortex. This serves as evidence for a shared familial contribution to individual differences in reward related brain activity in certain key reward processing regions.

Early life stress in the form of early institutional care has been shown to have wide-ranging impacts on the biological and behavioral development of young children. Studies of brain structure using magnetic resonance imaging have reported decreased prefrontal volumes, and a large literature has detailed decreased executive function (EF) in post-institutionalized (PI) youth. Little is known about how these findings relate to decision-making, particularly in PI youth entering adolescence—a period often characterized by social transition and increased reliance upon EF skills and the still-maturing prefrontal regions that support them. As decision-making in risky situations can be an especially important milestone in early adolescence, a clearer knowledge of the relationship between risky decision making and prefrontal structures in post-institutionalized youth is needed. The youth version of the Balloon Analogue Risk Task and a two-deck variant of the Iowa Gambling Task were used to assess risky decision-making in post-institutionalized youth and a community control group (N = 74, PI = 44, Non-adopted = 30; mean age = 12.93). Participants also completed a structural MRI scan for the assessment of group differences in brain structure. We hypothesized that participants adopted from institutions would display poorer performance on risky-decision making tasks and smaller brain volumes compared to non-adopted youth. Results indicated that later-adopted participants made fewer risky decisions than those experiencing shorter periods of deprivation or no institutional rearing. Further, decreased prefrontal volumes were observed in later-adopted youth and were significantly associated with task performance. Our results suggest that changes in risky-decision making behavior and brain structure are associated with the duration of early institutional care.

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. Keywords: Addiction, Adolescence, Development, Impulsivity, Memory, Reward

BackgroundA number of studies reports reduced hippocampal volume in individuals who engage in problematic alcohol use. However, the magnitude of the difference in hippocampal volume between individuals withv. without problematic alcohol use has varied widely, and there have been null findings. Moreover, the studies comprise diverse alcohol use constructs and samples, including clinically significant alcohol use disorders and subclinical but problematic alcohol use (e.g. binge drinking), adults and adolescents, and males and females.MethodsWe conducted the first quantitative synthesis of the published empirical research on associations between problematic alcohol use and hippocampal volume. In total, 23 studies were identified and selected for inclusion in the meta-analysis; effects sizes were aggregated using a random-effects model.ResultsProblematic alcohol use was associated with significantly smaller hippocampal volume (d= −0.53). Moderator analyses indicated that effects were stronger for clinically significantv. subclinical alcohol use and among adults relative to adolescents; effects did not differ among males and females.ConclusionsProblematic alcohol use is associated with reduced hippocampal volume. The moderate overall effect size suggests the need for larger samples than are typically included in studies of alcohol use and hippocampal volume. Because the existing literature is almost entirely cross-sectional, future research using causally informative study designs is needed to determine whether this association reflects premorbid risk for the development of problematic alcohol use and/or whether alcohol has a neurotoxic effect on the hippocampus.

Integrative, multilevel approaches investigating neurobiological systems relevant to threat detection promise to advance understanding of the pathophysiology of major depressive disorder (MDD). In this study we considered key neuronal and hormonal systems in adolescents with MDD and healthy controls (HC). The goals of this study were to identify group differences and to examine the association of neuronal and hormonal systems. MDD and HC adolescents (N = 79) aged 12–19 years were enrolled. Key brain measures included amygdala volume and amygdala activation to an emotion face-viewing task. Key hormone measures included cortisol levels during a social stress task and during the brain scan. MDD and HC adolescents showed group differences on amygdala functioning and patterns of cortisol levels. Amygdala activation in response to emotional stimuli was positively associated with cortisol responses. In addition, amygdala volume was correlated with cortisol responses, but the pattern differed in depressed versus healthy adolescents, most notably for unmedicated MDD adolescents. The findings highlight the value of using multilevel assessment strategies to enhance understanding of pathophysiology of adolescent MDD, particularly regarding how closely related biological threat systems function together while undergoing significant developmental shifts.

Early institutional or orphanage rearing, typically characterized by profound psychosocial deprivation, has been associated with adjustment difficulties that may persist long after adoption (for a review, see Gunnar 2001). In particular, post-institutionalized (PI) youth, especially those having experienced longer durations of adverse care, are more likely to show deficits in social cognition (e.g., Theory of Mind, Colvert et al. 2008b; Tarullo et al. 2007; emotion processing, Parker and Nelson 2005; Wismer Fries and Pollak 2004). These difficulties in recognizing and understanding others’ thoughts and feelings are likely to hinder PI youths’ ability to navigate social interactions with peers, which become increasingly complex in adolescence (Steinberg and Morris 2001). As such, PI youth may become targets of peers’ rebuffs and abuse, common sequelae of social cognitive deficits in normative samples (e.g., Kaukiainen et al. 2002). Indeed, early institutional deprivation has been linked to elevated social problems in broad-based functional assessments (Groze and Ileana 1996; Gunnar et al. 2007; Hawk and McCall 2011), and several studies have described lower peer acceptance and difficulties forming and maintaining intimate friendships years after adoption (e.g., Hodges and Tizard 1989; Tizard and Hodges 1978). Little research to date has examined distinct aspects of peer relations in PI populations. Often, numerous aspects of peer problems such as peer acceptance, isolation, and verbal and physical bullying have been combined into one scale for analysis (e.g., Rutter et al. 2001). Furthermore, because the focus has often been on youths’ behavior (e.g., is she aggressive?) and not treatment by peers (e.g., is she victimized?), our understanding of PI children and adolescents’ peer relations is somewhat one-sided. In one exception, Raaska et al. (2012) assessed self-reported experiences of bullying in 9- to 15-year-old internationally adopted youth, some of whom had experienced institutional care prior to adoption. Compared to youth raised in their natal families, younger adoptees were more likely to be victimized, while older adoptees were less likely to bully others. In turn, rejection and victimization by peers may promote emotional difficulties in PI children and adolescents. In normative samples, peer maltreatment has been associated with increases in internalizing symptoms (e.g., depression, loneliness; for a review, see Hawker and Boulton 2000). However, the relationship between peer victimization and emotional problems has not been examined in PI youth, despite research documenting heightened levels of internalizing problems in this population in adolescence (Colvert et al. 2008a; Tieman et al. 2005). Thus, the present study examined multiple aspects of peer relationships, including peer aggression, victimization and rejection, in PI youth adopted as infants or young children compared to youth who were raised in their families of origin. This comparison group was selected to allow for an approximate match to PI participants on the basis of parent education and family socio-economic status. In addition to measuring overt forms of victimization, we also measured relational victimization (e.g., exclusion, friendship manipulation; Crick and Grotpeter 1995), as research has shown that it makes unique contributions to psychosocial adjustment (Crick and Grotpeter 1996). We expected that PI youth, particularly those having experienced longer durations of institutional care, would experience lower peer acceptance and more peer victimization. We also hypothesized that these experiences would mediate the relation between early institutional care status and internalizing symptoms. Given mixed findings regarding overt aggression in PI youth (e.g., Merz and McCall 2010; Gunnar et al. 2007), and the lack of information about relational aggression, we did not make strong predictions about whether these behaviors would be elevated. We also examined differences in prosocial behavior and social withdrawal, because these behaviors are important predictors of social adjustment (e.g., Boivin et al. 1995; Crick 1996). Based on studies of domestic and international adoptees, we hypothesized that being older at adoption (i.e., 12 months or older) would be associated with more negative outcomes (for a review, see Zeanah et al. 2011). Finally, we explored whether gender moderated the associations between early institutional care and peer functioning. Some studies of PI children have reported more adverse effects for boys compared to girls, for instance, with respect to behavior problems and peer victimization (Bos et al. 2011; Raaska et al. 2012), though others find no gender interactions (Gunnar et al. 2007; Juffer and Van IJzendoorn 2005). Given these mixed findings, we explored but did not make directional predictions for gender effects.

Adaptive behavior requires focusing on relevant tasks while remaining sensitive to novel information. In adult studies of cognitive control, cognitive stability involves maintaining robust cognitive representations while cognitive flexibility involves updating of representations in response to novel information. Previous adult research has shown that the Met allele of the COMT Val(158) Met gene is associated with enhanced cognitive stability whereas the Val allele is associated with enhanced cognitive flexibility. Here we propose that the stability/flexibility framework can also be applied to infant research, with stability mapping onto early indices of behavioral regulation and flexibility mapping onto indices of behavioral reactivity. From this perspective, the present study examined whether COMT genotype was related to 7-month-old infants' reactivity to novel stimuli and behavioral regulation. Cognitive stability and flexibility were assessed using (1) a motor approach task, (2) a habituation task, and (3) a parental-report measure of temperament. Val carriers were faster to reach for novel toys during the motor approach task and received higher scores on the temperament measure of approach to novelty. Met carriers showed enhanced dishabituation to the novel stimulus during the habituation task and received higher scores on the temperament measures of sustained attention and behavioral regulation. Overall, these results are consistent with adult research suggesting that the Met and Val alleles are associated with increased cognitive stability and flexibility, respectively, and thus suggest that COMT genotype may similarly affect cognitive function in infancy.

OBJECTIVE Very preterm birth (< 32 weeks' gestation) affects cognitive development. The impact of late preterm birth (34 to 36 weeks' gestation) on cognition, specifically executive function, is not fully characterized. The aim of this study was to assess whether late preterm children demonstrate impaired executive function compared with full-term children (38 to 42 weeks' gestation). STUDY DESIGN This was a prospective cohort study of 4-year-old children. Preterm (n = 39) and full-term children (n = 44) completed a battery of executive function tasks and the Peabody Picture Vocabulary Test-4. Parents completed the Behavior Rating Inventory of Executive Function-Preschool version. RESULTS Preterm children performed worse on the verbal inhibitory control (p = 0.02) and short-term verbal memory (p = 0.01) tasks. Gestational age predicted performance on the verbal inhibitory control (p = 0.02) and short-term verbal memory (p = 0.04) tasks. There was no group difference in nonverbal inhibitory control (p = 0.45) or spatial memory (p = 0.60). Parents of preterm and full-term children rated their children's behavior similarly (p = 0.79). CONCLUSION Late preterm children demonstrated compromised verbal inhibitory control and short-term verbal memory compared with full-term peers. Late preterm children may not be spared from altered brain development. Further research is indicated to determine whether to screen late preterm children for executive function deficits.

Individuals who are born very preterm (< 32 weeks gestation) show differential development of prefrontal cortex structure, function, and dependent behaviors, including executive function (EF) skills, beginning during late infancy and extending into adulthood. Preschool-aged children born moderate-to-late preterm (PT; 32–36 weeks gestation) show smaller discrepancies in EF development, but it is unclear whether these differences first emerge during the early childhood years, when EF is rapidly developing, or if they arise from alterations in complex cognitive skills measurable in late infancy. In the current study, we examined whether differences in complex attention, memory, and inhibition skills (precursor skills to EF) are altered in healthy infants born moderate-to-late PT at 9-months corrected age. Infants born PT demonstrated poorer memory at test following habituation than their full-term peers. Furthermore, lower gestational age at birth was associated with poorer performance on five of the six early EF tasks. Results indicate that even in the context of low medical and environmental risk, performance on the Bayley within the normal range, and no group-level differences in processing speed, infants born moderate-to-late PT show subtle alterations in cognitive skills presumed to be dependent on prefrontal cortex by 9-months of age, likely setting the stage for long-term differences in EF development.

Non-suicidal self-injury (NSSI) is a significant mental health problem among adolescents. Research is needed to clarify the neurobiology of NSSI and identify candidate neurobiological targets for interventions. Based on prior research implicating heightened negative affect and amygdala hyperactivity in NSSI, we pursued a systems approach to characterize amygdala functional connectivity networks during rest (resting-state functional connectivity [RSFC)]) and a task (task functional connectivity [TFC]) in adolescents with NSSI.We examined amygdala networks in female adolescents with NSSI and healthy controls (n = 45) using resting-state fMRI and a negative emotion face-matching fMRI task designed to activate the amygdala. Connectivity analyses included amygdala RSFC, amygdala TFC, and psychophysiological interactions (PPI) between amygdala connectivity and task conditions.Compared to healthy controls, adolescents with NSSI showed atypical amygdala-frontal connectivity during rest and task; greater amygdala RSFC in supplementary motor area (SMA) and dorsal anterior cingulate; and differential amygdala-occipital connectivity between rest and task. After correcting for depression symptoms, amygdala-SMA RSFC abnormalities, among others, remained significant.This study's limitations include its cross-sectional design and its absence of a psychiatric control group.Using a multi-modal approach, we identified widespread amygdala circuitry anomalies in adolescents with NSSI. While deficits in amygdala-frontal connectivity (driven by depression symptoms) replicates prior work in depression, hyperconnectivity between amygdala and SMA (independent of depression symptoms) has not been previously reported. This circuit may represent an important mechanism underlying the link between negative affect and habitual behaviors. These abnormalities may represent intervention targets for adolescents with NSSI.

The authors sought to test the hypothesis that in patients with borderline personality disorder, the ventromedial prefrontal cortex and associated regions would not be activated during a task requiring motor inhibition in the setting of negative emotion. Such a finding would provide a plausible neural basis for the difficulty borderline patients have in modulating their behavior during negative emotional states and a potential marker for treatment interventions.A specifically designed functional magnetic resonance imaging (fMRI) activation probe was used, with statistical parametric mapping analyses, to test hypotheses concerning decreased prefrontal inhibitory function in the context of negative emotion in patients with borderline personality disorder (N=16) and healthy comparison subjects (N=14). 3-T fMRI scanning was used to study brain activity while participants performed an emotional linguistic go/no-go task.Analyses confirmed that under conditions associated with the interaction of behavioral inhibition and negative emotion, borderline patients showed relatively decreased ventromedial prefrontal activity (including medial orbitofrontal and subgenual anterior cingulate) compared with healthy subjects. In borderline patients, under conditions of behavioral inhibition in the context of negative emotion, decreasing ventromedial prefrontal and increasing extended amygdalar-ventral striatal activity correlated highly with measures of decreased constraint and increased negative emotion, respectively.These findings suggest specific frontolimbic neural substrates associated with core clinical features of emotional and behavioral dyscontrol in borderline personality disorder.

Developmental changes in structure and functioning are thought to make the adolescent brain particularly sensitive to the negative effects of alcohol. Although alcohol use disorders are relatively rare in adolescence, the initiation of alcohol use, including problematic use, becomes increasingly prevalent during this period. The present study examined associations between normative drinking (alcohol initiation, binge drinking, intoxication) and brain morphometry in a sample of 96 adolescent monozygotic twins. A priori regions of interest included 11 subcortical and 20 cortical structures implicated in the existing empirical literature as associated with normative alcohol use in adolescence. In addition, co-twin control analyses were used to disentangle risk for alcohol use from consequences of alcohol exposure on the developing brain. Results indicated significant associations reflecting preexisting vulnerability toward problematic alcohol use, including reduced volume of the amygdala, increased volume of the cerebellum, and reduced cortical volume and thickness in several frontal and temporal regions, including the superior and middle frontal gyri, pars triangularis, and middle and inferior temporal gyri. Results also indicated some associations consistent with a neurotoxic effect of alcohol exposure, including reduced volume of the ventral diencephalon and the middle temporal gyrus.

In the current study we examined the influence of preceding context on attentional conflict and response competition using a flanker paradigm. Nine healthy right-handed adults participated in a rapid mixed trial event-related functional magnetic resonance imaging (fMRI) study, in which increasing numbers of either compatible or incompatible trials preceded an incompatible trial. Behaviorally, reaction times on incompatible trials increased as a function of the number of preceding compatible trials. Several brain regions showed monotonic changes to the preceding context manipulation. The most common pattern was observed in anterior cingulate, dorsolateral prefrontal, and superior parietal regions. These areas showed an increase in activity for incompatible trials as the number of preceding compatible trials increased and a decrease in activity for incompatible trials as the number of preceding incompatible trials increased. Post hoc analysis showed that while the MR signal in the anterior cingulate and dorsolateral prefrontal regions peaked before the superior parietal region, the dorsolateral prefrontal MR signal peaked early and remained at this level. These findings are consistent with the conflict monitoring theory that postulates that the anterior cingulate cortex detects or monitors conflict, while PFC is involved in control adjustments that may then lead to modulation of superior parietal cortex in top-down biasing of attention.

Background Cognitive control, defined as the ability to suppress inappropriate thoughts and actions, is compromised in attention-deficit/hyperactivity disorder (ADHD). This study examines the neural basis of this deficit. Methods We used a paradigm that incorporates a parametric manipulation within a go/nogo task, so that the number of go trials preceding a nogo trial is varied to tax the neural systems underlying cognitive control with increasing levels of interference. Results Using this paradigm in combination with event-related functional magnetic resonance imaging (fMRI), we show that children without ADHD have increased susceptibility to interference with increasing numbers of go trials preceding a nogo trial, but children with ADHD have difficulty even with a single go trial preceding a nogo trial. In addition, children with ADHD do not activate frontostriatal regions in the same manner as normally developing children, but rather rely on a more diffuse network of regions, including more posterior and dorsolateral prefrontal regions. Conclusions Normal immature cognition may be characterized as being susceptible to interference and supported by the maturation of frontostriatal circuitry. ADHD children show a slightly different cognitive profile at 6 to 10 years of age that is paralleled by a relative lack of or delay in the maturation of ventral frontostriatal circuitry.

Tasks involving conflict between stimulus dimensions have been shown to activate dorsal anterior cingulate and prefrontal areas. It has been proposed that the dorsal anterior cingulate is involved a domain general process of monitoring conflict, while prefrontal areas are involved in resolving conflict. We examine three tasks that all require people to respond based on one stimulus dimension while ignoring another conflicting dimension, but which vary in the source of conflict. One of the tasks uses language stimuli (Stroop effect) and two use nonlanguage spatial conflicts appropriate for children and nonhuman animals. In Experiment 1, 12 participants were studied with event-related functional magnetic resonance imaging (fMRI) while performing each of the three tasks. Reaction times for each of the three tasks were significantly longer in the incongruent condition compared with the congruent condition, demonstrating that each task elicits a conflict. By studying the same people in the same session, we test the hypothesis that conflict activates a similar brain network in the three tasks. Significant activations were found in the anterior cingulate and left prefrontal cortex for all three conflict tasks. Within these regions, the conflict component demonstrated evidence for significant common activation across the three tasks, although the peak activation point and spatial extent were not identical. Other areas demonstrated activation unique to each task. Experiments 2-4 provide behavioral evidence indicating considerable independence between conflict operations involved in the tasks. The behavioral and fMRI results taken together seem to argue against a single unified network for processing conflict, but instead support either distinct networks for each conflict task or a single network that monitors conflict with different sites used to resolve the conflict.

We consider whether disruption of a specific neural circuit related to self-regulation is an underlying biological deficit in borderline personality disorder (BPD). Because patients with BPD exhibit a poor ability to regulate negative affect, we hypothesized that brain mechanisms thought to be involved in such self-regulation would function abnormally even in situations that seem remote from the symptoms exhibited by these patients. To test this idea, we compared the efficiency of attentional networks in BPD patients with controls who were matched to the patients in having very low self-reported effortful control and very high negative emotionality and controls who were average in these two temperamental dimensions. We found that the patients exhibited significantly greater difficulty in their ability to resolve conflict among stimulus dimensions in a purely cognitive task than did average controls but displayed no deficit in overall reaction time, errors, or other attentional networks. The temperamentally matched group did not differ significantly from either group. A significant correlation was found between measures of the ability to control conflict in the reaction-time task and self-reported effortful control.

In this study we combined event-related fMRI with a parametric manipulation of the go nogo paradigm to examine the effect of preceding context on inhibitory processes. Nogo trials were preceded by either 1, 3, or 5 go trials and then compared to one another. Two distinct patterns of activation were associated with behavioral inhibition: First, the ventral prefrontal cortex, cingulate gyrus, and superior parietal regions showed a context effect with an increase in MR signal to nogo trials with increasing number of preceding go trials. Second, anterior regions in the supplementary and premotor cortex showed an increase in MR signal on the nogo condition after 5 preceding go trials, but not after only 1 or 3. A model using the BOLD response in our data was used to verify that the effect of context was not an artifact of the randomization scheme used in the design.

Background: Major depressive disorder (MDD) often begins during adolescence when the brain is still maturing. To better understand the neurobiological underpinnings of MDD early in development, this study examined brain function in response to emotional faces in adolescents with MDD and healthy (HC) adolescents using functional magnetic resonance imaging (fMRI). Method: Thirty-two unmedicated adolescents with MDD and 23 healthy age- and gender-matched controls completed an fMRI task viewing happy and fearful faces. Fronto-limbic regions of interest (ROI; bilateral amygdala, insula, subgenual and rostral anterior cingulate cortices) and whole-brain analyses were conducted to examine between-group differences in brain function. Results: ROI analyses revealed that patients had greater bilateral amygdala activity than HC in response to viewing fearful versus happy faces, which remained significant when controlling for comorbid anxiety. Whole-brain analyses revealed that adolescents with MDD had lower activation compared to HC in a right hemisphere cluster comprised of the insula, superior/middle temporal gyrus, and Heschl's gyrus when viewing fearful faces. Brain activity in the subgenual anterior cingulate cortex was inversely correlated with depression severity. Limitations: Limitations include a cross-sectional design with a modest sample size and use of a limited range of emotional stimuli. Conclusions: Results replicate previous studies that suggest emotion processing in adolescent MDD is associated with abnormalities within fronto-limbic brain regions. Findings implicate elevated amygdalar arousal to negative stimuli in adolescents with depression and provide new evidence for a deficit in functioning of the saliency network, which may be a future target for early intervention and MDD treatment.

The present study used a monozygotic (MZ) cotwin-control (CTC) design to investigate associations between alcohol use and performance on the Iowa gambling task (IGT) in a sample of 96 adolescents (half female). The MZ CTC design is well suited to shed light on whether poor decision-making, as reflected on IGT performance, predisposes individuals to abuse substances or is a consequence of use. Participants completed structural MRI scans as well, from which we derived gray matter volumes for cortical and subcortical regions involved in IGT performance and reduced in adolescents with problematic alcohol use. Drinking was associated with poorer task performance and with reduced volume of the left lateral orbital-frontal cortex. CTC analyses indicated that the former was due to differences between members of twin pairs in alcohol use (suggesting a causal effect of alcohol), whereas the latter was due to factors shared by twins (consistent with a pre-existing vulnerability for use). Although these preliminary findings warrant replication, they suggest that normative levels of alcohol use may diminish the quality of adolescent decision-making and thus have potentially important public health implications.

Background: The amygdala plays a central role in the human response to affective or emotionally charged stimuli, particularly fear-producing stimuli. We examined the specificity of the amygdala response to facial expressions in adults and children. Methods: Six adults and 12 children were scanned in a 1.5-T scanner during passive viewing of fearful and neutral faces using an EPI BOLD sequence. All scans were registered to a reference brain, and analyses of variance were conducted on the pooled data to examine interactions with age and gender. Results: Overall, we observed predominantly left amygdala and substantia innominata activity during the presentation of nonmasked fearful faces relative to fixation, and a decrease in activation in these regions with repeated exposure to the faces. Adults showed increased left amygdala activity for fearful faces relative to neutral faces. This pattern was not observed in the children who showed greater amygdala activity with neutral faces than with fearful faces. For the children, there was an interaction of gender and condition whereby boys but not girls showed less activity with repeated exposure to the fearful faces. Conclusions: This is the first study to examine developmental differences in the amygdala response to facial expressions using functional magnetic resonance imaging.

The present study sought to compare adult and infant ERP responses in analogous tests of visual recognition memory. Adults were tested under two test conditions, in which they were given either explicit instructions to respond to a previously-seen stimulus, or no instructions. Testing in both conditions took place after either a 1- or 5-min delay between familiarization and test. Eight-month-old infants were tested under the same 'passive' (no instruction) conditions as adults. ERP morphology differed across age groups. Adults evinced a P300 that was larger under 'active' as compared to 'passive' test conditions, and a late positive slow wave response that was greater to novel than familiar stimuli. There was no evidence in infants of a P300, although infants did demonstrate a late positive slow wave that was greater to familiar than to novel stimuli. Parallels between the infant and adult findings are discussed and in particular, whether the infant slow wave response is the precursor to the adult P300.

This study investigated the changing relation between emotion and inhibitory control during adolescence. One hundred participants between 11 and 25 years of age performed a go-nogo task in which task-relevant stimuli (letters) were presented at the center of large task-irrelevant images depicting negative, positive, or neutral scenes selected from the International Affective Picture System. Longer reaction times for negative trials were found across all age groups, suggesting that negative but not positive emotional images captured attention across this age range. However, age differences in accuracy on inhibitory trials suggest that response inhibition is more readily disrupted by negative emotional distraction in early adolescence relative to late childhood, late adolescence, or early adulthood.

Aim Although hematopoietic cell transplantation (HCT) arrests the cognitive decline in mucopolysaccharidosis type IH (Hurler syndrome, MPS IH), these children continue to have neuropsychological deficits as they age. Both compromised attention and effects on white matter have been observed in cancer patients who have had chemotherapy. Therefore, we explored the effects of disease and treatment on brain function in children with MPS I who have had HCT with those with attenuated MPS I treated with enzyme replacement therapy (ERT). Methods Subjects: 7 MPS IH participants at least 5 years post-HCT were compared with 7 attenuated participants who were treated with ERT. Measures: IQ, attention, spatial ability, and memory were assessed. Medical history and an unsedated MRI scan using diffusion tensor imaging (DTI) were acquired. Results Despite clinically equivalent IQ and memory, children with MPS IH had poorer attention span than those with attenuated MPS I as well as decreased fractional anisotropy (FA) of the corpus callosum. A relationship between attention scores and FA was found in the MPS IH group but not the attenuated group. FA was also related to the frequency of medical events. Interpretation In children with MPS IH, both the treatment and the disease affect attention functions associated with poor white matter integrity.

Despite vast knowledge on the behavioral processes mediating the development of episodic memory, little is known about the neural mechanisms underlying these changes. We used event-related fMRI to examine the neural correlates of both encoding and recall processes during an episodic memory task in two different groups of school age children (8–9 and 12–13 years). The memory task was composed of an encoding phase in which children were presented with a series of unrelated pictorial pairs, and a retrieval phase during which one of these items acted as a cue to prompt recall of the paired item. Age-related differences in activations were observed for both encoding and recall. Younger children recruited additional regions in the right dorsolateral prefrontal and right temporal cortex compared to older children during successful encoding of the pairs. During successful recall, older children recruited additional regions in the left ventrolateral prefrontal and left inferior parietal cortex compared to younger children. The results suggest that the prefrontal cortex contributes to not only the formation of memories but also access to them, and this contribution changes with development. The protracted development of the prefrontal cortex has implications for our understanding of the development of episodic memory.

The development of contextual cueing specifically in relation to attention was examined in two experiments. Adult and 10-year-old participants completed a context cueing visual search task (Jiang & Chun, The Quarterly Journal of Experimental Psychology, 54A(4), 1105–1124, 2001) containing stimuli presented in an attended (e.g., red) and unattended (e.g., green) color. When the spatial configuration of stimuli in the attended and unattended color was invariant and consistently paired with the target location, adult reaction times improved, demonstrating learning. Learning also occurred if only the attended stimuli’s configuration remained fixed. In contrast, while 10 year olds, like adults, showed incrementally slower reaction times as the number of attended stimuli increased, they did not show learning in the standard paradigm. However, they did show learning when the ratio of attended to unattended stimuli was high, irrespective of the total number of attended stimuli. Findings suggest children show efficient attentional guidance by color in visual search but differences in contextual cueing.

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.

This study examined the cognitive and neural development of attention switching using a simple forced-choice attention task and functional magnetic resonance imaging. Fourteen children and adults made discriminations among stimuli based on either shape or color. Performance on these trials was compared to performance during blocked trials requiring all color or all shape discriminations. Magnetic resonance echo planar images were acquired during performance of the task. Both children and adults showed robust bilateral activity of the caudate nucleus when switching attention between color and shape discriminations that correlated negatively with mean response latency on these trials. However, neither switching costs nor caudate activity correlated with age, suggesting early development of the underlying neural circuitry involved in switching between salient stimulus sets. Overall, children and adults differed in performance and patterns of brain activity on the task, with adults responding more accurately and faster than children, and recruiting more prefrontal and parietal regions. These results suggest an important role of subcortical regions (i.e. caudate nucleus) in non-cued attention switching, with increasing recruitment of cortical regions with age.

Prevailing theories of implicit or unaware learning propose a developmental invariance model, with implicit function maturing early in infancy or childhood despite prolonged improvements in explicit or intentional learning and memory systems across childhood. Neuroimaging studies of adult visuomotor sequence learning have associated fronto-striatal brain regions with implicit learning of spatial sequences. Given evidence of continued development in these brain regions during childhood, we compare implicit sequence learning in adults and 7- to 11-year-old children to examine potential developmental differences in the recruitment of fronto-striatal circuitry during implicit learning. Participants performed a standard serial reaction time task. Stimuli alternately followed a fixed 10-step sequence of locations or were presented in a pseudorandom order of locations. Adults outperformed children, achieving a significantly larger sequence learning effect and showing learning more quickly than children. Age-related differences in activity were observed in the premotor cortex, putamen, hippocampus, inferotemporal cortex, and parietal cortex. We observed differential recruitment of cortical and subcortical motor systems between groups, presumably reflecting age differences in motor response execution. Adults showed greater hippocampal activity for sequence trials, whereas children demonstrated greater signal during random trials. Activity in the right caudate correlated significantly with behavioral measures of implicit learning for both age groups, although adults showed greater signal change than children overall, as would be expected given developmental differences in sequence learning magnitude. These results challenge the idea of developmental invariance in implicit learning and instead support a view of parallel developments in implicit and explicit learning systems.

The current study examined the development of cognitive and neural systems involved in overriding a learned action in favor of a new one using a stimulus-response compatibility task and functional magnetic resonance imaging. Eight right-handed adults (mean age, 22-30 years), and eight children (7-11 years) were scanned while they performed a task. Both children and adults were less accurate for incompatible stimulus-response mappings than compatible ones; the children's performance was significantly worse. The comparison of the incompatible and compatible conditions showed large volumes of activity in the ventral prefrontal cortex, ventral caudate nucleus, thalamus, and hippocampus. Striatal activity correlated with the percentage of errors in overriding the old stimulus-response association. The hippocampal activity correlated with the reaction time to make a response to a new stimulus-response mapping that required the reversal of a prior association between a stimulus and a response location. Developmental differences were observed in the volume of striatal/pallidal and hippocampal/parahippocampal activity in that these regions were larger and extended more ventrally in children relative to adults. These results suggest that with maturation and learning, projections to and from these regions may become more refined and focal. Moreover, these findings are consistent with the role of ventral frontostriatal circuitry in overriding habitual and well learned actions and hippocampal systems in learning and reversing associations between a given stimulus and spatial location.

Background Alterations in amygdala function have been implicated in the pathophysiological characteristics of adult anxiety and depressive disorders. Studies with healthy adults and children, as well as with adults who have amygdala lesions, have found facial expressions of emotion to be useful probes of amygdala activity. Our study examined the amygdala response to fearful and neutral facial expressions in healthy, anxious, and depressed children. We hypothesized that children with anxiety and depression may show atypical amygdala responses to emotional stimuli. Methods Twelve children (8-16 years of age) with generalized anxiety or panic disorder and 12 healthy comparison children underwent noninvasive functional magnetic resonance imaging while viewing photographs of fearful and neutral facial expressions. In a second comparison, 5 girls with major depressive disorder were compared with 5 anxious and 5 healthy girls from the previous sample. Results Children with anxiety disorders showed an exaggerated amygdala response to fearful faces compared with healthy children, whereas depressed children showed a blunted amygdala response to these faces. In addition, the magnitude of the amygdala's signal change between fearful and neutral faces was positively correlated with the severity of everyday anxiety symptoms. Conclusions Our results suggest that amygdala function is affected in both anxiety and depression during childhood and adolescence. Moreover, this disruption appears to be specific to the child's own rating of everyday anxiety.

Visuomotor sequence learning was assessed in 4- to 10-year-old children using a serial reaction time (SRT) task with both random and sequenced trials. One-half of the children received exposure to the sequence prior to performing the reaction time (RT) task. In Experiment 1, 7- and 10-year-old children demonstrated sequence-specific decreases in RT. As in the adult SRT literature, participants with explicit awareness of the sequence at the end of the session showed larger sequence-specific reaction time decrements than those without explicit awareness. Contrary to expectation, preexposure to the sequence did not reliably predict the level of awareness attained. Results from Experiment 2 indicate that 4-year-olds also demonstrate significant sequence learning on a variant of the SRT task. This article provides preliminary data regarding developmental changes in sequential learning and the development and use of implicit and explicit knowledge. Age-related differences emerged primarily in explicit rather than implicit knowledge.

Electrophysiological studies suggest sensitivity of the prefrontal cortex to changes in the probability of an event. The purpose of this study was to determine if subregions of the prefrontal cortex respond differentially to changes in target probabilities using functional magnetic resonance imaging (fMRI). Ten right-handed adults were scanned using a gradient-echo, echo planar imaging sequence during performance of an oddball paradigm. Subjects were instructed to respond to any letter but “X”. The frequency of targets (i.e., any letter but X) varied across trials. The results showed that dorsal prefrontal regions were active during infrequent events and ventral prefrontal regions were active during frequent events. Further, we observed an inverse relation between the dorsal and ventral prefrontal regions such that when activity in dorsal prefrontal regions increased, activity in ventral prefrontal regions decreased, and vice versa. This finding may index competing cognitive processes or capacity limitations. Most importantly, these findings taken as a whole suggest that any simple theory of prefrontal cortex function must take into account the sensitivity of this region to changes in target probability. Hum. Brain Mapping 13:26–33, 2001. © 2001 Wiley-Liss, Inc.

Background: The neurodevelopment of childhood anxiety disorders is not well understood. Basic research has implicated the amygdala and circuits related to these nuclei as being central to several aspects of fear and fear-related behaviors in animals. Methods: Magnetic resonance imaging was used to measure amygdala volumes and comparison brain regions in 12 child and adolescent subjects with generalized anxiety disorder and 24 comparison subjects. Groups were matched on age, sex, height, and handedness and were also similar on measures of weight, socioeconomic status, and full scale IQ. Results: Right and total amygdala volumes were significantly larger in generalized anxiety disorder subjects. Intracranial, cerebral, cerebral gray and white matter, temporal lobe, hippocampal, and basal ganglia volumes and measures of the midsagittal area of the corpus callosum did not differ between groups. Conclusions: Although these data are preliminary and from a small sample, the results are consistent with a line of thinking that alterations in the structure and function of the amygdala may be associated with pediatric generalized anxiety disorder.

Two different attentional networks have been associated with visuospatial attention and conflict resolution. In most situations either one of the two networks is active or both are increased in activity together. By using functional magnetic resonance imaging and a flanker task, we show conditions in which one network (anterior attention system) is increased in activity whereas the other (visuospatial attention system) is reduced, showing that attentional conflict and selection are separate aspects of attention. Further, we distinguish between neural systems involved in different forms of conflict. Specifically, we dissociate patterns of activity in the basal ganglia and insula cortex during simple violations in expectancies (i.e., sudden changes in the frequency of an event) from patterns of activity in the anterior attention system specifically correlated with response conflict as evidenced by longer response latencies and more errors. These data provide a systems-level approach in understanding integrated attentional networks.

Functional magnetic resonance imaging (fMRI) was used to examine patterns of cortical activity in children during performance of a spatial working memory task. Six children (8-10 years) and six adults (19-26 years) searched a linear array of four boxes for the appearance of a dot. In the visual blocks, participants made no response. In the motor blocks, participants were instructed to indicate the location of the dot on each trial using a button-press response. In the working memory blocks, participants were instructed to indicate at which location the dot had appeared 1 or 2 trials previously. Both children and adults showed activity in the left precentral and postcentral gyri, as well as the right cerebellum for the motor condition as compared to the visual condition. Comparison of the memory and motor conditions revealed reliable activity in the right superior frontal gyrus (BA 8), right dorsolateral prefrontal cortex (BA 10/46), right superior parietal cortex, and bilateral inferior parietal cortex for both adults and children. These results suggest that spatial working memory tasks activate very similar cortical regions for school-age children and adults. The findings differ from previous imaging studies of nonspatial working memory tasks in that the prefrontal activations observed in the current work tend to be more dorsal. Results are discussed in light of the significant behavioral performance differences observed between child and adult participants.

The relationship of task relevance and stimulus probability to P300 morphology, latency and distribution was assessed. Eight year olds and adults completed visual oddball tasks of recognition memory with frequent non-target (60%), infrequent target (20%), and infrequent novel (20%) stimuli. Stimuli consisted of 2 female faces posing neutral expressions, and 40 trial unique novel photographs depicting scenes, animals, objects or abstract patterns. Event-related potentials were recorded from 17 electrodes over frontal, central and parietal scalp, including lateral temporal sites. All stimuli elicited P300 responses at parietal electrodes, with the largest responses to the target stimuli (relevant and infrequent). The P300 responses of adults and children were morphologically dissimilar, with children showing broader peaks and latency shifts across electrodes. In addition, the eight year olds displayed a frontal negativity to novel stimuli which was absent in the responses of adult participants. Results suggest that different anatomical or functional circuitry may be involved in the processing of novelty for adults as compared to eight year olds.