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An extensive literature shows that race information can impact cognitive performance. Two key findings include an attentional bias to Black racial cues in U.S. samples and diminished recognition of other-race faces compared to same-race faces in predominantly White adult samples. Yet face stimuli are increasingly used in psychological research often unrelated to race (Conley et al., 2018) or without consideration for how race information may influence cognitive performance, especially among developmental participants from different racial groups. In the current study we used open-access data from the Adolescent Brain Cognitive Development SM (ABCD) Study® 4.0.1 release to test for developmentally similar other- and same-race effects of Black and White face stimuli on attention, working memory, and recognition memory in 9- and 10-year-old Black and White children (n=5,659) living in the U.S. Black and White children showed better performance when attending to Black versus White faces. We also show an advantage in recognition memory of same-race compared to other-race faces in White children that did not generalize to Black children. Together the findings highlight how race information, even when irrelevant to an experiment, may indirectly lead to misinterpretation of group differences in cognitive performance in children of different racial backgrounds., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Pediatric obesity is a growing public health concern. Previous work has observed diet to impact nucleus accumbens (NAcc) inflammation in rodents, measured by the reactive proliferation of glial cells. Recent work in humans has demonstrated a relationship between NAcc cell density-a proxy for neuroinflammation-and weight gain in youth; however, the directionality of this relationship in the developing brain and association with diet remains unknown., Methods: Waist circumference (WC) and NAcc cell density were collected in a large cohort of children (n > 2,000) participating in the Adolescent Brain Cognitive Development (ABCD) Study (release 3.0) at baseline (9-10 y) and at a Year 2 follow-up (11-12 y). Latent change score modeling (LCSM) was used to disentangle contributions of baseline measures to two-year changes in WC percentile and NAcc cellularity. In addition, the role of NAcc cellularity in mediating the relationship between diet and WC percentile was assessed using dietary intake data collected at Year 2., Results: LCSM indicates that baseline WC percentile influences change in NAcc cellularity and that baseline NAcc cell density influences change in WC percentile. NAcc cellularity was significantly associated with WC percentile at Year 2 and mediated the relationship between dietary fat consumption and WC percentile., Conclusions: These results implicate a vicious cycle whereby NAcc cell density biases longitudinal changes in WC percentile and vice versa. Moreover, NAcc cell density may mediate the relationship between diet and weight gain in youth. These findings suggest that diet-induced inflammation of reward circuitry may lead to behavioral changes that further contribute to weight gain., (Copyright © 2022 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The Adolescent Brain Cognitive Development ™ Study (ABCD Study®) is an open-science, multi-site, prospective, longitudinal study following over 11,800 9- and 10-year-old youth into early adulthood. The ABCD Study aims to prospectively examine the impact of substance use (SU) on neurocognitive and health outcomes. Although SU initiation typically occurs during teen years, relatively little is known about patterns of SU in children younger than 12., Methods: This study aims to report the detailed ABCD Study® SU patterns at baseline (n = 11,875) in order to inform the greater scientific community about cohort's early SU. Along with a detailed description of SU, we ran mixed effects regression models to examine the association between early caffeine and alcohol sipping with demographic factors, externalizing symptoms and parental history of alcohol and substance use disorders (AUD/SUD)., Primary Results: At baseline, the majority of youth had used caffeine (67.6 %) and 22.5 % reported sipping alcohol (22.5 %). There was little to no reported use of other drug categories (0.2 % full alcohol drink, 0.7 % used nicotine, <0.1 % used any other drug of abuse). Analyses revealed that total caffeine use and early alcohol sipping were associated with demographic variables (p's<.05), externalizing symptoms (caffeine p = 0002; sipping p = .0003), and parental history of AUD (sipping p = .03)., Conclusions: ABCD Study participants aged 9-10 years old reported caffeine use and alcohol sipping experimentation, but very rare other SU. Variables linked with early childhood alcohol sipping and caffeine use should be examined as contributing factors in future longitudinal analyses examining escalating trajectories of SU in the ABCD Study cohort., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The prevalence of risky behavior such as substance use increases during adolescence; however, the neurobiological precursors to adolescent substance use remain unclear. Predictive modeling may complement previous work observing associations with known risk factors or substance use outcomes by developing generalizable models that predict early susceptibility. The aims of the current study were to identify and characterize behavioral and brain models of vulnerability to future substance use. Principal components analysis (PCA) of behavioral risk factors were used together with connectome-based predictive modeling (CPM) during rest and task-based functional imaging to generate predictive models in a large cohort of nine- and ten-year-olds enrolled in the Adolescent Brain & Cognitive Development (ABCD) study (NDA release 2.0.1). Dimensionality reduction (n = 9,437) of behavioral measures associated with substance use identified two latent dimensions that explained the largest amount of variance: risk-seeking (PC1; e.g., curiosity to try substances) and familial factors (PC2; e.g., family history of substance use disorder). Using cross-validated regularized regression in a subset of data (Year 1 Fast Track data; n>1,500), functional connectivity during rest and task conditions (resting-state; monetary incentive delay task; stop signal task; emotional n-back task) significantly predicted individual differences in risk-seeking (PC1) in held-out participants (partial correlations between predicted and observed scores controlling for motion and number of frames [r p ]: 0.07-0.21). By contrast, functional connectivity was a weak predictor of familial risk factors associated with substance use (PC2) (r p : 0.03-0.06). These results demonstrate a novel approach to understanding substance use vulnerability, which-together with mechanistic perspectives-may inform strategies aimed at early identification of risk for addiction., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In the United States over one-third of the population, including children and adolescents, are overweight or obese. Despite the prevalence of obesity, few studies have examined how food cravings and the ability to regulate them change throughout development. Here, we addressed this gap in knowledge by examining structural brain and behavioral changes associated with regulation of craving across development. In a longitudinal design, individuals ages 6-26 completed two structural scans as well as a behavioral task where they used a cognitive regulatory strategy to decrease the appetitive value of foods. Behaviorally, we found that the ability to regulate craving improved with age. Neurally, improvements in regulatory ability were associated with cortical thinning in medial and lateral prefrontal cortex. We also found that models with cortical thickness measurements and age chosen by a lasso-based variable selection method could predict an individual's regulation behavior better than age and other behavioral factors alone. Additionally, when controlling for age, smaller ventral striatal volumes were associated with higher body mass index and predicted greater increases in weight two years later. Taken together, these results demonstrate a role for structural brain changes in supporting the ability to resist cravings for appetitive foods across development., (Copyright © 2019 Columbia University. Published by Elsevier Ltd.. All rights reserved.)

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., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Bulimia nervosa (BN) emerges in the late teen years and is characterized by binge eating and related compensatory behaviors. These behaviors often co-occur with periods of negative affect suggesting an association between emotions and control over eating behavior. In the current study, we examined how cognitive control and neural processes change under emotional states of arousal in 46 participants with (n=19) and without (n=27) BN from the ages of 18-33 years. Participants performed a go/nogo task consisting of brief negative, positive and neutral emotional cues and sustained negative, positive and neutral emotional states of arousal during functional magnetic resonance imaging (fMRI). Overall task performance improved with age for healthy participants, but not for patients with BN. These age-dependent behavioral effects were paralleled by diminished recruitment of prefrontal control circuitry in patients with BN with age. Although patients with BN showed no difference in performance on the experimental manipulations of negative emotions, sustained positive emotions related to improved performance among patients with BN. Together the findings highlight a neurodevelopmental approach towards understanding markers of psychopathology and suggest that sustained positive affect may have potential therapeutic effects on maintaining behavioral control in BN., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Understanding how and why affective responses change with age is central to characterizing typical and atypical emotional development. Prior work has emphasized the role of the amygdala and prefrontal cortex (PFC), which show age-related changes in function and connectivity. However, developmental neuroimaging research has only recently begun to unpack whether age effects in the amygdala and PFC are specific to affective stimuli or may be found for neutral stimuli as well, a possibility that would support a general, rather than affect-specific, account of amygdala-PFC development. To examine this, 112 individuals ranging from 6 to 23 years of age viewed aversive and neutral images while undergoing fMRI scanning. Across age, participants reported more negative affect and showed greater amygdala responses for aversive than neutral stimuli. However, children were generally more sensitive to both neutral and aversive stimuli, as indexed by affective reports and amygdala responses. At the same time, the transition from childhood to adolescence was marked by a ventral-to-dorsal shift in medial prefrontal responses to aversive, but not neutral, stimuli. Given the role that dmPFC plays in executive control and higher-level representations of emotion, these results suggest that adolescence is characterized by a shift towards representing emotional events in increasingly cognitive terms., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Developmental differences regarding decision making are often reported in the absence of emotional stimuli and without context, failing to explain why some individuals are more likely to have a greater inclination toward risk. The current study (N=212; 10-25y) examined the influence of emotional context on underlying functional brain connectivity over development and its impact on risk preference. Using functional imaging data in a neutral brain-state we first identify the "brain age" of a given individual then validate it with an independent measure of cortical thickness. We then show, on average, that "brain age" across the group during the teen years has the propensity to look younger in emotional contexts. Further, we show this phenotype (i.e. a younger brain age in emotional contexts) relates to a group mean difference in risk perception - a pattern exemplified greatest in young-adults (ages 18-21). The results are suggestive of a specified functional brain phenotype that relates to being at "risk to be risky.", (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Fear extinction learning is a highly adaptive process that involves the integrity of frontolimbic circuitry. Its disruption has been associated with emotional dysregulation in stress and anxiety disorders. In this article we consider how age, genetics and experiences shape our capacity to regulate fear in cross-species studies. Evidence for adolescent-specific diminished fear extinction learning is presented in the context of immature frontolimbic circuitry. We also present evidence for less neural plasticity in fear regulation as a function of early-life stress and by genotype, focusing on the common brain derived neurotrophin factor (BDNF) Val66Met polymorphism. Finally, we discuss this work in the context of exposure-based behavioral therapies for the treatment of anxiety and stress disorders that are based on principles of fear extinction. We conclude by speculating on how such therapies may be optimized for the individual based on the patient's age, genetic profile and personal history to move from standard treatment of care to personalized and precision medicine., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Repetitive transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex (DLPFC) is an established treatment for depression, but its underlying mechanism of action remains unknown. Abnormalities in two large-scale neuronal networks-the frontoparietal central executive network (CEN) and the medial prefrontal-medial parietal default mode network (DMN)-are consistent findings in depression and potential therapeutic targets for TMS. Here, we assessed the impact of TMS on activity in these networks and their relation to treatment response., Methods: We used resting state functional magnetic resonance imaging to measure functional connectivity within and between the DMN and CEN in 17 depressed patients, before and after a 5-week course of TMS. Motivated by prior reports, we focused on connectivity seeded from the DLPFC and the subgenual cingulate, a key region closely aligned with the DMN in depression. Connectivity was also compared with a cohort of 35 healthy control subjects., Results: Before treatment, functional connectivity in depressed patients was abnormally elevated within the DMN and diminished within the CEN, and connectivity between these two networks was altered. Transcranial magnetic stimulation normalized depression-related subgenual hyperconnectivity in the DMN but did not alter connectivity in the CEN. Transcranial magnetic stimulation also induced anticorrelated connectivity between the DLPFC and medial prefrontal DMN nodes. Baseline subgenual connectivity predicted subsequent clinical improvement., Conclusions: Transcranial magnetic stimulation selectively modulates functional connectivity both within and between the CEN and DMN, and modulation of subgenual cingulate connectivity may play an important mechanistic role in alleviating depression. The results also highlight potential neuroimaging biomarkers for predicting treatment response., (Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Due to their unique properties, the use of nanoparticles (NPs) is expanding; these same properties may affect their potential risk to humans. However, standard methods for genotoxicity assessment may not be adequate for NPs; altered tests reported here have been developed to address perceived inadequacies. The bacterial reverse mutation assay is an essential part of the battery of tests to determine genotoxicity. The utility of this test for assessing NPs is currently questioned, due to negative results seemingly caused by failure of particle uptake. To probe uptake issues, we examined the physical state in different media, dose and time dependent association, uptake and mutagenicity of titanium dioxide (TiO2) NPs in Salmonella typhimurium and Escherichia coli. The NPs suspended in water were characterized using dynamic light scattering, NP tracking analysis and transmission electron microscopy. NP association with bacteria was assessed by flow cytometry. Association was found to be time and dose dependent, with maximal association by 60 min. Therefore mutagenicity was assessed after a 60 min pre-incubation in a miniaturized assay demonstrating enhanced sensitivity. To assess potential indirect effects on bacterial mutagenicity, the effect of TiO2 NPs on the action of standard mutagens or on DNA repair capability was also investigated. TiO2 NPs did not affect mutant yields in standard strains of S. typhimurium or E. coli, including those detecting oxidative damage, using the modified methods. Nor did TiO2 NPs affect the action of standard mutagens or DNA excision repair capability. Despite particle association with the bacteria, subsequent analysis using electron microscopy and energy dispersive x-ray spectroscopy indicated that the NPs were not internalized. This work demonstrates that additional studies, including flow cytometry, are valuable tools for understanding the action of NPs in biological systems., (Published by Elsevier B.V.)

Functional neuroimaging studies have identified multiple nodes of dysfunction in frontostriatal and mesocorticolimbic networks in attention-deficit/hyperactivity disorder (ADHD). Yet relatively few studies have examined how structural and functional connectivity between nodes in these networks might relate to the behavioral symptoms of ADHD. Moreover, it is unknown whether abnormalities in connectivity are a primary cause of symptoms or arise secondary to common etiologic mechanisms. We review the most recent diffusion tensor imaging and functional magnetic resonance imaging studies of connectivity in ADHD to characterize associations between frontostriatal connectivity abnormalities and the behavioral symptoms of inattention and impulsivity in ADHD. Furthermore, we examine how structural and functional connectivity measures relate to environmental and genetic pathways to ADHD. Diffusion tensor imaging studies indicate that ADHD is associated with significant irregularities in white matter microstructure, especially in frontostriatal and select corticocortical tracts. Resting state functional magnetic resonance imaging studies implicate altered connectivity within a default mode network of structures active during introspective, task-free processes and disrupted interactions between this network and frontostriatal attentional systems. Deficits in functional connectivity within frontostriatal and mesocorticolimbic networks might give rise, in part, to ADHD symptoms. Conversely, structural connectivity deficits and ADHD symptoms might arise incidentally from a common etiologic mechanism, involving altered modulation of synaptic potentiation and pruning by dopamine and other factors during development. Collectively, these studies suggest that the core symptoms of ADHD might derive from dysregulated modulation of cortical plasticity in the developing brain, resulting in altered patterns of corticocortical connectivity that might persist into adulthood., (Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: Adolescence is a developmental period that entails substantial changes in risk-taking behavior and experimentation with alcohol and drugs. Understanding how the brain is changing during this period relative to childhood and adulthood and how these changes vary across individuals are key in predicting risk for later substance abuse and dependence., Method: This review discusses recent human imaging and animal work in the context of an emerging view of adolescence as characterized by a tension between early emerging "bottom-up" systems that express exaggerated reactivity to motivational stimuli and later maturing "top-down" cognitive control regions. Behavioral, clinical, and neurobiological evidences are reported for dissociating these two systems developmentally. The literature on the effects of alcohol and its rewarding properties in the brain is discussed in the context of these two systems., Results: Collectively, these studies show curvilinear development of motivational behavior and the underlying subcortical brain regions, with a peak inflection from 13 to 17 years. In contrast, prefrontal regions, important in top-down regulation of behavior, show a linear pattern of development well into young adulthood that parallels that seen in behavioral studies of impulsivity., Conclusions: The tension or imbalance between these developing systems during adolescence may lead to cognitive control processes being more vulnerable to incentive-based modulation and increased susceptibility to the motivational properties of alcohol and drugs. As such, behavior challenges that require cognitive control in the face of appetitive cues may serve as useful biobehavioral markers for predicting which teens may be at greater risk for alcohol and substance dependence., (Copyright © 2010 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: Several neuroanatomic abnormalities have been reported in patients with attention-deficit/hyperactivity disorder (ADHD). However, findings are not always consistent, perhaps because of heterogeneous subject samples. Studying youths with documented familial ADHD provides an opportunity to examine a more homogeneous population., Method: Twenty-four youths with a confirmed history of familial ADHD and 10 control youths underwent high-resolution structural magnetic resonance imaging examinations. Archived magnetic resonance imaging scan data from 12 control youths were included in the analysis to increase statistical power. Individually drawn region-of-interest methods were used to examine the frontal lobe gyri and caudate., Results: Cerebral total tissue was similar between groups. The volumes of the right caudate and right inferior frontal lobe were larger in the ADHD youths compared with the control youths. Data from a subgroup of the ADHD youths suggest that increasing left caudate volume is associated with decreasing functional activation of this region., Conclusions: Because previous studies have focused primarily on younger subjects or used an extended age range, the present results may reflect neurodevelopmental changes specific to late adolescence in familial ADHD.

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 might underlie the increased risk for poor outcomes reported during adolescence. We tested the hypothesis that difficulties in regulating behavior in emotional contexts in adolescents might be due to competition between heightened activity in subcortical emotional processing systems and immature top-down prefrontal systems. Individual differences in emotional reactivity might put some teens at greater risk during this sensitive transition in development., Methods: We examined the association between emotion regulation and frontoamygdala circuitry in 60 children, adolescents, and adults with an emotional go-nogo paradigm. We went beyond examining the magnitude of neural activity and focused on neural adaptation within this circuitry across time with functional magnetic resonance imaging., Results: Adolescents showed exaggerated amygdala activity relative to children and adults. This age-related difference decreased with repeated exposures to the stimuli, and individual differences in self-ratings of anxiety predicted the extent of adaptation or habituation in amygdala. Individuals with higher trait anxiety showed less habituation over repeated exposures. This failure to habituate was associated with less functional connectivity between ventral prefrontal cortex and amygdala., Conclusions: These findings suggest that exaggerated emotional reactivity during adolescence might increase the need for top-down control and put individuals with less control at greater risk for poor outcomes.

Objective: Familial vulnerability to attention-deficit/hyperactivity disorder (ADHD) has been shown to be related to atypical prefrontal activity during cognitive control tasks. However, ADHD is associated with deficits in the cerebellum as well as deficits in frontostriatal circuitry and associated cognitive control. In this study, we investigated whether cerebellar systems are sensitive to familial risk for ADHD in addition to frontostriatal circuitry., Method: We used an event-related, rapid mixed-trial functional magnetic resonance imaging design. The paradigm was a variation on a go/no-go task, with expected (go) and unexpected (no-go) events at expected and unexpected times. A total of 36 male children and adolescents completed the study, including 12 sibling pairs discordant for ADHD and 12 matched controls., Results: Children and adolescents with ADHD were less accurate on unexpected events than control subjects. Performance by unaffected siblings was intermediate, between that of children and adolescents with ADHD and controls. Functional neuroimaging results showed dissociation between activation in the cerebellum and anterior cingulate cortex: Activity in the anterior cingulate cortex was decreased for subjects with ADHD and their unaffected siblings compared with controls for manipulations of stimulus type (no-go trials), but not timing. In contrast, cerebellar activity was decreased for subjects with ADHD and their unaffected siblings for manipulations of timing, but not stimulus type., Conclusions: These findings suggest that activity in both the prefrontal cortex and cerebellum is sensitive to familial vulnerability to ADHD. Unaffected siblings of individuals with ADHD show deficits similar to affected probands in prefrontal areas for unexpected events and in cerebellum for events atunexpected times.

Objective: The dopamine transporter (DAT1) gene has been implicated in attention-deficit/hyperactivity disorder (ADHD), although the mechanism by which it exerts its effects remains unknown. The polymorphism associated with ADHD has been shown to affect expression of the transporter in vitro and in vivo. Dopamine transporters are predominantly expressed in the striatum, but also in the cerebellar vermis. Stimulant medication is often effective in ADHD and is believed to exert its effects by blocking dopamine transporters in the striatum. We set out to investigate the effect of the DAT1 genotype in ADHD in a small, preliminary study. We hypothesized that the DAT1 genotype would affect brain activation patterns in a manner similar to that of stimulant medication, with the lesser expressing allele mirroring its effects., Method: We investigated DAT1 gene effects on brain activation patterns in an all-male sample of sibling pairs discordant for ADHD (n = 20) and controls (n = 9). All of the subjects participated in a functional magnetic resonance imaging session using a go/no-go paradigm and provided a DNA sample for analysis., Results: DAT1 genotype affected activation in the striatum and cerebellar vermis. The genotype interacted with familial risk of ADHD in the striatum but not the vermis., Conclusions: These preliminary results suggest that the DAT1 gene effects in the striatum are involved in translating the genetic risk of ADHD into a neurobiological substrate. As such, this study represents a first step in elucidating the neurobiological mechanisms underlying genetic influences in ADHD. Furthermore, these results may contribute to long-term possibilities for the development of new treatments: If the DAT1 genotype has differential effects on striatal activation, then it may be useful as a surrogate endpoint in individualized treatments targeting genotype/functional magnetic resonance imaging activation profiles.

Background: Attention-deficit hyperactivity disorder (ADHD) is a heritable neuropsychiatric disorder, associated with atypical patterns of brain activation in functional imaging studies. Neuroimaging measures may serve as an intermediate phenotype in genetic studies of ADHD, as they are putatively more closely linked to gene expression than a clinical diagnosis., Methods: We used rapid, mixed-trial, event-related functional magnetic resonance imaging (fMRI) to investigate changes in brain activation during a go no-go task in boys with ADHD, their unaffected siblings, and matched control subjects., Results: On the hardest inhibitory trials in our task, children and adolescents with ADHD had lower accuracy than control subjects, whereas their unaffected siblings did not. Control subjects activated a network of regions, including ventral prefrontal and inferior parietal cortex. Both children and adolescents with ADHD and their unaffected siblings showed decreased activation in these areas, as well as fewer correlations between performance and activation., Conclusions: These findings suggest that the magnitude of activation during successful inhibitions is sensitive to genetic vulnerability for ADHD in a number of regions, including ventral prefrontal cortex. If this can be replicated in future studies, this suggests that neuroimaging measures related to inhibitory control may be suitable as intermediate phenotypes in studies investigating gene effects in ADHD.

Background: Emotional information can facilitate or interfere with cognitive processes. In this study, we examined the influence of emotional information in biasing performance and the biological basis underlying this influence., Methods: Ten human subjects (five female) were scanned with functional magnetic resonance imaging while performing an emotional go/nogo task., Results: Subjects were slower to approach fearful target expressions and had more difficulty avoiding happy nontarget expressions. The amygdala was recruited most for negative emotional context, and activity in this region was positively correlated with response time when detecting negative expressions. Increased signal in the right caudate nucleus was observed when avoiding nontargets and was negatively correlated with the number of false alarms subjects made., Conclusions: Emotional context can alter behavioral and biological responses when approaching or avoiding a stimulus. We showed that recruitment of the amygdala, a region implicated in evaluating emotional significance, was associated with longer response latencies when approaching negative information, whereas recruitment of the caudate nucleus, a structure previously implicated in reward and impulse control, was most active when avoiding positive information. Our findings have significant implications for exaggerated and inhibited emotional responses that are characteristic of a number of psychiatric disorders.

Background: Healthy individuals performing response suppression tasks activate anterior cingulate cortex with occurrence of false alarm error responses to nontargets. Fundamental questions include whether this error-related activation provides a signal contributing to behavioral control and, given generally poorer performance on such tasks by addicts, whether this signal is disrupted in addiction., Methods: We used rapid, event-related functional magnetic resonance imaging to study 13 individuals with opiate dependence and 26 healthy control individuals performing a Go/NoGo task., Results: Compared with controls, opiate addicts exhibited an attenuated anterior cingulate cortex error signal and significantly poorer task performance. In controls, the individual level of event-related anterior cingulate cortex activation accompanying false alarm error positively predicted task performance, particularly sensitivity in discriminating targets from nontargets., Conclusions: The attenuation of this error signal in anterior cingulate cortex may play a role in loss of control in addiction and other forms of impulsive behavior.

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.

Objective: To critically review and integrate the existing literature on magnetic resonance imaging (MRI) studies of the normally developing brain in childhood and adolescence and discuss the implications for clinical MRI studies., Method: Changes in regional brain volume with age and differences between the sexes are summarized from reports in refereed journal articles pertaining to MRI of the developing human brain., Results: White matter volume increases with age. Gray matter volumes increase during childhood and then decrease before adulthood. On average, boys have larger brains than girls; after correction for overall brain volume the caudate is relatively larger in girls, and the amygdala is relatively larger in boys. Differences are of clinical interest given gender-related differences in the age of onset, symptomatology, and prevalence noted for nearly all childhood-onset psychiatric disorders. Attention-deficit/hyperactivity disorder is frequently used as an example to demonstrate these points., Conclusions: Understanding the developmental trajectories of normal brain development and differences between the sexes is important for the interpretation of clinical imaging studies.

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.

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.

Background: Previous investigations suggest that maltreated children with a diagnosis of posttraumatic stress disorder (PTSD) evidence alterations of biological stress systems. Increased levels of catecholaminergic neurotransmitters and steroid hormones during traumatic experiences in childhood could conceivably adversely affect brain development., Methods: In this study, 44 maltreated children and adolescents with PTSD and 61 matched controls underwent comprehensive psychiatric and neuropsychological assessments and an anatomical magnetic resonance imaging (MRI) brain scan., Results: PTSD subjects had smaller intracranial and cerebral volumes than matched controls. The total midsagittal area of corpus callosum and middle and posterior regions remained smaller; while right, left, and total lateral ventricles were proportionally larger than controls, after adjustment for intracranial volume. Brain volume robustly and positively correlated with age of onset of PTSD trauma and negatively correlated with duration of abuse. Symptoms of intrusive thoughts, avoidance, hyperarousal or dissociation correlated positively with ventricular volume, and negatively with brain volume and total corpus callosum and regional measures. Significant gender by diagnosis effect revealed greater corpus callosum area reduction in maltreated males with PTSD and a trend for greater cerebral volume reduction than maltreated females with PTSD. The predicted decrease in hippocampal volume seen in adult PTSD was not seen in these subjects., Conclusions: These data suggest that the overwhelming stress of maltreatment experiences in childhood is associated with adverse brain development.

Objective: To examine the relation between specific frontostriatal structures (prefrontal cortex and basal ganglia) and response inhibition deficits observed in attention-deficit/hyperactivity disorder (ADHD)., Method: Children with ADHD and age-matched normal controls were scanned using magnetic resonance imaging (MRI) and tested on three response inhibition tasks. Behavioral performance was correlated with MRI-based anatomical measures of frontostriatal circuitry (prefrontal cortex and basal ganglia) implicated in ADHD., Results: First, significant differences in performance by children with ADHD and normal volunteers were observed on all three response inhibition tasks. Second, performance on these tasks correlated only with those anatomical measures of frontostriatal circuitry observed to be abnormal in children with ADHD (e.g., the region of the prefrontal cortex, caudate, and globus pallidus, but not the putamen) in the authors' previous study. Third, significant correlations between task performance and anatomical measures of the prefrontal cortex and caudate nuclei were predominantly in the right hemisphere, supporting a role of right frontostriatal circuitry in response inhibition and ADHD., Conclusion: The data suggest a role of the right prefrontal cortex in suppressing responses to salient, but otherwise irrelevant events while the basal ganglia appear to be involved in executing these behavioral responses.