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Executive function (EF) underlies broad health and adaptive outcomes. For transgender youth, navigating gender discernment and gender affirmation demand EF. Yet, factors associated with transgender youth EF are unknown. We investigate hypothesized predictors of EF: over-represented conditions among transgender youth (anxiety and depression symptoms, autism spectrum disorder [ASD]) and gender-affirming care. One-hundred twenty-four transgender 11−21-year-olds participated. Parents/caregivers completed EF and mental health report measures. ASD diagnostics and gender-affirming medication histories were collected. 21 % of non-autistic and 69 % of autistic transgender youth had clinically elevated EF problems. Membership in the gender-affirming hormone treatment group was associated with better EF. ASD, anxiety symptoms, and membership in the long-duration pubertal suppression group were associated with poorer EF. Given the importance of EF skills for multiple outcomes, and the unique and additional EF demands specific to transgender youths’ experiences, EF skill monitoring—and when appropriate, supports—should be considered for transgender youth.

The ability to recognize others' emotions based on vocal emotional prosody follows a protracted developmental trajectory during adolescence. However, little is known about the neural mechanisms supporting this maturation. The current study investigated age-related differences in neural activation during a vocal emotion recognition (ER) task. Listeners aged 8 to 19 years old completed the vocal ER task while undergoing functional magnetic resonance imaging. The task of categorizing vocal emotional prosody elicited activation primarily in temporal and frontal areas. Age was associated with a) greater activation in regions in the superior, middle, and inferior frontal gyri, b) greater functional connectivity between the left precentral and inferior frontal gyri and regions in the bilateral insula and temporo-parietal junction, and c) greater fractional anisotropy in the superior longitudinal fasciculus, which connects frontal areas to posterior temporo-parietal regions. Many of these age-related differences in brain activation and connectivity were associated with better performance on the ER task. Increased activation in, and connectivity between, areas typically involved in language processing and social cognition may facilitate the development of vocal ER skills in adolescence.

Magnetic resonance imaging (MRI) is a powerful radiologic tool with the ability to generate a variety of proton-based signal contrast from tissues. Owing to this immense flexibility in signal generation, new MRI techniques are constantly being developed, tested, and optimized for clinical utility. In addition, the safe and nonionizing nature of MRI makes it a suitable modality for imaging in children. In this review article, we summarize a few of the most popular advances in MRI techniques in recent years. In particular, we highlight how these new developments have affected brain, spine, and neuromuscular imaging and focus on their applications in pediatric patients. In the first part of the review, we discuss new approaches such as multiphase and multidelay arterial spin labeling for quantitative perfusion and angiography of the brain, amide proton transfer MRI of the brain, MRI of brachial plexus and lumbar plexus nerves (i.e., neurography), and T2 mapping and fat characterization in neuromuscular diseases. In the second part of the review, we focus on describing new data acquisition strategies in accelerated MRI aimed collectively at reducing the scan time, including simultaneous multislice imaging, compressed sensing, synthetic MRI, and magnetic resonance fingerprinting. In discussing the aforementioned, the review also summarizes the advantages and disadvantages of each method and their current state of commercial availability from MRI vendors.

Background Early childhood social reticence (SR) and preadolescent social anxiety (SA) symptoms increase the risk for more severe SA in later adolescence. Yet, not all at-risk youth develop more severe SA. The emergence of distinct patterns of neural response to socially evocative contexts during pivotal points in development may help explain this discontinuity. We tested the extent to which brain function during social interactions in preadolescence influenced the effects of SA and early childhood SR on predicting SA symptoms in midadolescence. Methods Participants (N = 53) were assessed for SR from ages 2 to 7. At age 11, SA symptoms were assessed and brain function was measured using functional magnetic resonance imaging (fMRI) as participants anticipated social evaluation from purported peers with a reputation for being unpredictable, nice, and mean. At age 13, SA symptoms were re-assessed. Moderated-mediation models tested the extent to which early childhood SR, preadolescent SA, and preadolescent brain function predicted midadolescent SA. Results In individuals with preadolescent SA, the presence of early childhood SR and SR-linked differences in brain activation predicted more severe SA in midadolescence. Specifically, in those who exhibited preadolescent SA, greater early childhood SR was associated with enhanced bilateral insula engagement while anticipating unpredictable-versus-nice social evaluation in preadolescence, and more severe SA in midadolescence. Conclusions SR-linked neural responses to socially evocative peer interactions may predict more severe SA symptoms in midadolescence among individuals with greater preadolescent SA symptoms and childhood SR. This same pattern of neural response may not be associated with more severe SA symptoms in youth with only one risk factor.

Behavioral Inhibition (BI) is a temperament type that predicts social withdrawal in childhood and anxiety disorders later in life. However, not all BI children develop anxiety. Attention bias (AB) may enhance the vulnerability for anxiety in BI children, and interfere with their development of effective emotion regulation. In order to fully probe attention patterns, we used traditional measures of reaction time (RT), stationary eye-tracking, and recently emerging mobile eye-tracking measures of attention in a sample of 5- to 7-year-olds characterized as BI (N = 23) or non-BI (N = 58) using parent reports. There were no BI-related differences in RT or stationary eye-tracking indices of AB in a dot-probe task. However, findings in a subsample from whom eye-tracking data were collected during a live social interaction indicated that BI children (N = 12) directed fewer gaze shifts to the stranger than non-BI children (N = 25). Moreover, the frequency of gazes toward the stranger was positively associated with stationary AB only in BI, but not in non-BI, children. Hence, BI was characterized by a consistent pattern of attention across stationary and ambulatory measures. We demonstrate the utility of mobile eye-tracking as an effective tool to extend the assessment of attention and regulation to social interactive contexts.

Objective Many transgender adolescents experience clinically elevated anxiety and depression. Testosterone (T), used as a gender affirming treatment, may reduce symptoms of anxiety and depression. We assessed the effect of gender affirming T treatment on internalizing symptoms, body image dissatisfaction, and activation patterns within the amygdala-prefrontal cortex circuit in transgender adolescent boys. Method Symptoms of generalized anxiety, social anxiety, depression, suicidality and body image dissatisfaction were measured by self-report and brain activation was measured during a face processing task with functional MRI in a group of 19 adolescent transgender boys receiving T treatment and 23 not receiving gonadal hormone treatment (UT). Results Severity of anxiety and depression was significantly lower in the T treated group relative to the UT group, along with a trend of lower suicidality. The T group also reported less distress with body features and exhibited stronger connectivity within the amygdala-prefrontal cortex circuit compared to the UT group. Finally, group differences on depression and suicidality were directly associated with body image dissatisfaction, and anxiety symptoms were moderated by amygdala-prefrontal cortex connectivity differences between groups. Conclusion T treatment is associated with lower levels of internalizing symptoms among transgender adolescent boys. T is also associated with greater body satisfaction and greater connectivity in a neural circuit associated with anxiety and depression. Satisfaction with body image was found to overlap with the association between T and both depression and suicidality, and amygdala-prefrontal co-activation moderated the role of T on anxiety.

Refractory focal epilepsy (rFE) is commonly comorbid with impaired social functioning, which significantly reduces quality of life. Previous research has identified a mentalizing network in the brain-composed of the anterior temporal cortex, medial prefrontal cortex (mPFC), posterior temporal sulcus (pSTS), and temporoparietal junction-that is thought to play a critical role in social cognition. In typically-developing (TD) youth, this network undergoes a protracted developmental process with cortical thinning and white matter expansion occurring across adolescence. Because epilepsy is associated with both social dysfunction and irregular neural development, we investigated whether gray and white matter in the mentalizing network differed between youth with rFE (n = 22) and TD youth (n = 41) aged 8-21 years. Older age was associated with reduced cortical thickness in the bilateral mPFC in TD youth, but not in rFE youth. Compared to TD youth, rFE youth had greater white matter density in the right pSTS. Our findings suggest that rFE youth show atypical patterns of cortical thickness and white matter density in regions of the brain that are typically associated with social information processing, potentially as a result of ongoing seizures, comorbid conditions, or other illness-related factors. These results encourage future research to examine whether such variations in neural structure are predictive of specific social deficits in rFE youth.

Pediatric anxiety and depression significantly impair youth’s social and emotional functioning. The increased emergence of affective disorders during adolescence points to the involvement of several developing systems at the neural and behavioral level. This chapter characterizes deficits in social information processing and their underlying neural correlates in pediatric affective disorders. While typically-developing adolescents show enhanced amygdala response to salient stimuli in the context of deficient prefrontal cortex (PFC) regulation, anxious and depressed youth show hyperactivation in both regions in response to negative or threatening cues. Additionally, depressed adolescents show reduced limbic response to positive stimuli, suggesting deficits in appetitive motivational systems. These behavioral and neural patterns are related to phenotypic symptoms characteristic of anxiety and depression in youth.

Highlights • Brain response to social feedback varies by age and social anxiety severity in youth. • Younger, anxious youth show greater activation to unpredictable negative feedback. • Different associations emerge among older, anxious adolescents., Adolescence is a sensitive period for the development of adaptive social behaviors and social anxiety, possibly due to aspects of brain development. However, research is needed to examine interactions among age, social anxiety, and social dynamics previously shown to influence neural responding. The current functional magnetic resonance imaging (fMRI) study examines brain function in 8–18 year-olds with varying levels of social anxiety. Interactions are examined among age, social anxiety, and two key task factors: valence and predictability of social interactions. Results demonstrate age, social anxiety severity, and each of the two key task-based factors interact to predict neural response in the caudate, middle and superior temporal gyri. In particular, among adolescents less-than 13 years of age, higher social anxiety predicted greater responding to unpredictable negative evaluations. However, in this same age group, the opposite pattern emerged during receipt of unpredictable positive evaluations, with less neural response in more anxious youth. Adolescents aged 13 and older overall showed less robust effects. We discuss these findings in terms of age- and anxiety-related differences in socioemotional processing.

Objective: Socially anxious adolescents report distress during social decision-making, wherein their favorable view of peers directly conflicts with their expectation to be viewed negatively by peers; a phenomenon we refer to as “mismatch bias.” The present study utilizes a novel paradigm with dynamic social stimuli to explore the correlates of mismatch biases in anxious and healthy youth. Method: The behavioral and neural correlates of mismatch biases were assessed in healthy (N = 17) and anxious (N = 14) youth during functional MRI. Participants completed a novel task where they viewed silent videos of unknown peers. After viewing each video, participants appraised the social desirability of the peer (“How much do you think you would like them [if you met them]”) or predicted how socially desirable the peer would find them (“How much do you think they would like you [if you met them]”). Each participant's mismatch bias was calculated as the difference between their appraisal of peers and their prediction of peers' appraisal of them. Results: We found that anxious youth exhibited mismatch bias: they rated unknown peers as more desirable than they predicted peers would rate them. This effect was not present in the healthy group. Mismatch biases were associated with increased engagement of the ventrolateral prefrontal cortex (vlPFC), a region broadly involved in flexible cognitions and behavioral selection. In addition, greater mismatch biases and vlPFC activation during mismatch biases were associated with more severe anxiety symptoms. Conclusions: The findings highlight the importance of understanding mismatch biases to inform treatments that target distress elicited by discrepant social appraisals in anxious youth.

During adolescence, youth may experience heightened attention bias to socially relevant stimuli; however, it is unclear if attention bias toward social threat may be exacerbated for adolescents with a history of anxiety. This study evaluated attentional bias during the Chatroom-Interact task with 25 adolescents with a history of anxiety (18F, Mage = 13.6) and 22 healthy adolescents (13F, Mage = 13.8). In this task, participants received feedback from fictional, virtual peers who either chose them (acceptance) or rejected them (rejection). Overall, participants were faster to orient toward and spent longer time dwelling on their own picture after both rejection and acceptance compared to non-feedback cues. Social feedback was associated with greater pupillary reactivity, an index of cognitive and emotional neural processing, compared to non-feedback cues. During acceptance feedback (but not during rejection feedback), anxious youth displayed greater pupil response compared to healthy youth, suggesting that positive feedback from peers may differentially influence youth with a history of an anxiety disorder.

Purpose The aim of the study was to examine reproductive health attitudes and behaviors related to contraception use, provider counseling, parenthood goals, and fertility preservation (FP) in TNB adolescents. Methods A 24-item survey was administered to 44 TNB adolescents aged 12–19 years. Results Contraceptive use was variable even among the 46% who reported sexual activity. Half denied or were unsure if they had been offered options from their provider to prevent sexually transmitted infections, and more than one third denied or were unsure about the offer of pregnancy prevention options. Importantly, the majority did not desire more information about contraceptive options. Few used FP, although many thought their feelings about parenthood may change in the future. Conclusions TNB adolescents are at risk for sexually transmitted infections, unplanned pregnancies, and future infertility, yet many do not desire more information about contraception or FP. Tailored counseling strategies should be developed and researched to protect this vulnerable group of youth.

Adolescence is a period of intensive development in body, brain, and behaviour. Potentiated by changes in hormones and neural response to social stimuli, teenagers undergo a process of social re-orientation away from their caregivers and towards expanding peer networks. The current study examines how relative relational closeness to peers (compared to parents) during adolescence is linked to neural response to the facial emotional expressions of other teenagers. Self-reported closeness with friends (same- and opposite-sex) and parents (mother and father), and neural response to facial stimuli during fMRI, was assessed in 8- to 19-year-old typically-developing youth (n = 40, mean age = 13.90 years old, SD = 3.36; 25 female). Youth who reported greater relative closeness with peers than with parents showed decreased activation in the dorsolateral prefrontal cortex (dlPFC) during stimulus presentation, which may reflect lessened inhibitory control or regulatory response to peer-aged faces. Functional connectivity between the dlPFC and dorsal striatum was greatest in older youth who were closer to peers; in contrast, negative coupling between these regions was noted for both younger participants who were closer to peers and older participants who were closer to their parents. In addition, the association between relative closeness to peers and neural activation in regions of the social brain varied by emotion type and age. Results suggest that the re-orientation towards peers that occurs during adolescence is accompanied by changes in neural response to peer-aged social signals in social cognitive, prefrontal, and subcortical networks.

Wariness in early childhood manifests as shy, inhibited behavior in novel social situations and is associated with increased risk for developing social anxiety. In youth with childhood wariness, exposure to a potent social stressor, such as peer victimization, may potentiate brain-based sensitivity to unpredictable social contexts, thereby increasing risk for developing social anxiety. To test brain-based associations between early childhood wariness, self-reported peer victimization, and current social anxiety symptoms, we quantified neural responses to different social contexts in low- and high-victimized pre-adolescents with varying levels of early childhood wariness. Measures of early childhood wariness were obtained annually from ages 2-to-7-years. At age 11, participants were characterized as having low (N = 20) or high (N = 27) peer victimization. To index their neural responses to peer evaluation, participants completed an fMRI-based Virtual School paradigm (Jarcho et al. Developmental Cognitive Neuroscience, 13, 21–31, 2013a). In highly victimized, relative to low-victimized participants, wariness was differentially related to right amygdala response based on the valence and predictability of peer evaluation. More specifically, in highly victimized participants, wariness was associated with greater right amygdala response to unpredictably positive peer evaluation. Effects of wariness were not observed in participants who reported low levels of victimization. Moreover, in victimized participants, high wariness and right amygdala response to unpredictably positive peer evaluation was associated with more severe social anxiety symptoms. Results can be interpreted using a diathesis-stress model, which suggests that neural response to unexpectedly positive social feedback is a mechanism by which exposure to peer victimization potentiates the risk for developing social anxiety in individuals exhibiting high levels of early childhood wariness.

Individuals with epilepsy often experience social difficulties and deficits in social cognition. It remains unknown how disruptions to neural networks underlying such skills may contribute to this clinical phenotype. The current study compared the organization of relevant brain circuits—the “mentalizing network” and a salience-related network centered on the amygdala—in youth with and without epilepsy. Functional connectivity between the nodes of these networks was assessed, both at rest and during engagement in a social cognitive task (facial emotion recognition), using functional magnetic resonance imaging. There were no group differences in resting-state connectivity within either neural network. In contrast, youth with epilepsy showed comparatively lower connectivity between the left posterior superior temporal sulcus and the medial prefrontal cortex—but greater connectivity within the left temporal lobe—when viewing faces in the task. These findings suggest that the organization of a mentalizing network underpinning social cognition may be disrupted in youth with epilepsy, though differences in connectivity within this circuit may shift depending on task demands. Our results highlight the importance of considering functional task-based engagement of neural systems in characterizations of network dysfunction in epilepsy.

Adolescents are commonly portrayed as highly emotional, with their behaviors often hijacked by their emotions. Research on the neural substrates of adolescent affective behavior is beginning to paint a more nuanced picture of how neurodevelopmental changes in brain function influence affective behavior, and how these influences are modulated by external factors in the environment. Recent neurodevelopmental models suggest that the brain is designed to promote emotion regulation, learning, and affiliation across development, and that affective behavior reciprocally interacts with age-specific social demands and different social contexts. In this review, we discuss current findings on neurobiological mechanisms of adolescents’ affective behavior and highlight individual differences in and social-contextual influences on adolescents’ emotionality. Neurobiological mechanisms of affective processes related to anxiety and depression are also discussed as examples. As the field progresses, it will be critical to test new hypotheses generated from the foundational empirical and conceptual work and to focus on identifying more precisely how and when neural networks change in ways that promote or thwart adaptive affective behavior during adolescence.

Social anxiety disorder involves biased cognition and altered neural responses to social stimuli. This study further assesses the precise ways in which neural activation associated with perceptual ...

Individuals with epilepsy are at risk for social cognition deficits, including impairments in the ability to recognize nonverbal cues of emotion (i.e., emotion recognition [ER] skills). Such deficits are particularly pronounced in adult patients with childhood-onset seizures and are already evident in children and adolescents with epilepsy. Though these impairments have been linked to blunted neural response to emotional information in faces in adult patients, little is known about the neural correlates of ER deficits in youth with epilepsy. The current study compared ER accuracy and neural response to emotional faces during functional magnetic resonance imaging (fMRI) in youth with intractable focal epilepsy and typically developing youth. Relative to typically developing participants, individuals with epilepsy showed a) reduced accuracy in the ER task and b) blunted response to emotional faces (vs. neutral faces) in the bilateral fusiform gyri and right superior temporal gyrus (STG). Activation in these regions was correlated with performance, suggesting that aberrant response within these face-responsive regions may play a functional role in ER impairments. Reduced engagement of neural circuits relevant to processing socioemotional cues may be markers of risk for social cognitive deficits in youth with focal epilepsy.

Internalizing disorders (i.e., depression and anxiety) are common comorbidities in people with epilepsy. In adults with epilepsy, comorbid depression or anxiety is associated with worse seizure control and reduced quality of life, and may be linked to specific neural biomarkers. Less is known about brain correlates of internalizing symptoms in pediatric populations. In the current study, we performed a retrospective analysis of 45 youth between the ages of 6 and 18 years old with intractable epilepsy. Individuals were evaluated for internalizing symptoms on the Child Behavior Checklist (CBCL) and underwent magnetic resonance (MR) and fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging as part of the clinical evaluation for surgical treatment of epilepsy. Forty-two percent of patients experienced clinically significant internalizing symptoms based on parent report. Compared with individuals who scored in the normal range, youth with clinical levels of internalizing problems showed overall reductions in cortex volume, as well as widespread reductions in cortical thickness and functional activation in the bilateral occipital/parietal lobe, left temporal regions, and left inferior frontal cortex on MR and PET scans. There were no group differences in amygdala or hippocampus volumes, nor other patient- or illness-related variables such as age, sex, or the type, lateralization, or duration of epilepsy. Results suggest that high rates of internalizing disorders are present in youth with refractory epilepsy. Multifocal reductions in cortical thickness and function may be nonspecific risk factors for clinically meaningful internalizing symptoms in youth with chronic epilepsy. As such, the presence of broad cortical thinning and reduced glucose uptake upon radiological examination may warrant more focused clinical evaluation of psychological symptoms.

Social anxiety disorder typically begins in adolescence, a sensitive period for brain development, when increased complexity and salience of peer relationships requires novel forms of social learning. Disordered social learning in adolescence may explain how brain dysfunction promotes social anxiety. Socially anxious adolescents (n = 15) and adults (n = 19) and non-anxious adolescents (n = 24) and adults (n = 32) predicted, then received, social feedback from high and low-value peers while undergoing functional magnetic resonance imaging (fMRI). A surprise recall task assessed memory biases for feedback. Neural correlates of social evaluation prediction errors (PEs) were assessed by comparing engagement to expected and unexpected positive and negative feedback. For socially anxious adolescents, but not adults or healthy participants of either age group, PEs elicited heightened striatal activity and negative fronto-striatal functional connectivity. This occurred selectively to unexpected positive feedback from high-value peers and corresponded with impaired memory for social feedback. While impaired memory also occurred in socially-anxious adults, this impairment was unrelated to brain-based PE activity. Thus, social anxiety in adolescence may relate to altered neural correlates of PEs that contribute to impaired learning about social feedback. Small samples necessitate replication. Nevertheless, results suggest that the relationship between learning and fronto-striatal function may attenuate as development progresses.

Emerging data indicate that adults with binge eating may exhibit an attentional bias toward highly palatable foods, which may promote obesogenic eating patterns and excess weight gain. However, it is unknown to what extent youth with loss of control (LOC) eating display a similar bias. We therefore studied 76 youth (14.5 ± 2.3 years; 86.8% female; BMI-z 1.7 ± .73) with (n = 47) and without (n = 29) reported LOC eating. Following a breakfast to reduce hunger, youth participated in a computerized visual probe task of sustained attention that assessed reaction time to pairs of pictures consisting of high palatable foods, low palatable foods, and neutral household objects. Although sustained attentional bias did not differ by LOC eating presence and was unrelated to body weight, a two-way interaction between BMI-z and LOC eating was observed (p = .01), such that only among youth with LOC eating, attentional bias toward high palatable foods versus neutral objects was positively associated with BMI-z. These findings suggest that LOC eating and body weight interact in their association with attentional bias to highly palatable foods cues, and may partially explain the mixed literature linking attentional bias to food cues with excess body weight.

BACKGROUND: Pediatric anxiety disorders are among the most common psychiatric mental illnesses in children and adolescents, and are associated with abnormal cognitive control in emotional, particularly threat, contexts. In a series of studies using eye movement saccade tasks, we reported anxiety-related alterations in the interplay of inhibitory control with incentives, or with emotional distractors. The present study extends these findings to working memory (WM), and queries the interaction of spatial WM with emotional stimuli in pediatric clinical anxiety. METHODS: Participants were 33 children/adolescents diagnosed with an anxiety disorder, and 22 age-matched healthy comparison youths. Participants completed a novel eye movement task, an affective variant of the memory-guided saccade task. This task assessed the influence of incidental threat on spatial WM processes during high and low cognitive load. RESULTS: Healthy but not anxious children/adolescents showed slowed saccade latencies during incidental threat in low-load but not high-load WM conditions. No other group effects emerged on saccade latency or accuracy. CONCLUSIONS: The current data suggest a differential pattern of how emotion interacts with cognitive control in healthy youth relative to anxious youth. These findings extend data from inhibitory processes, reported previously, to spatial WM in pediatric anxiety. Language: en

Background The eye region of the face is particularly relevant for decoding threat-related signals, such as fear. However, it is unclear if gaze patterns to the eyes can be influenced by fear learning. Previous studies examining gaze patterns in adults find an association between anxiety and eye gaze avoidance, although no studies to date examine how associations between anxiety symptoms and eye-viewing patterns manifest in children. The current study examined the effects of learning and trait anxiety on eye gaze using a face-based fear conditioning task developed for use in children. Methods Participants were 82 youth from a general population sample of twins (aged 9–13 years), exhibiting a range of anxiety symptoms. Participants underwent a fear conditioning paradigm where the conditioned stimuli (CS+) were two neutral faces, one of which was randomly selected to be paired with an aversive scream. Eye tracking, physiological, and subjective data were acquired. Children and parents reported their child's anxiety using the Screen for Child Anxiety Related Emotional Disorders. Results Conditioning influenced eye gaze patterns in that children looked longer and more frequently to the eye region of the CS+ than CS− face; this effect was present only during fear acquisition, not at baseline or extinction. Furthermore, consistent with past work in adults, anxiety symptoms were associated with eye gaze avoidance. Finally, gaze duration to the eye region mediated the effect of anxious traits on self-reported fear during acquisition. Conclusions Anxiety symptoms in children relate to face-viewing strategies deployed in the context of a fear learning experiment. This relationship may inform attempts to understand the relationship between pediatric anxiety symptoms and learning.

Adolescence is the time of peak onset for many anxiety disorders, particularly Social Anxiety Disorder. Research using simulated social interactions consistently finds differential activation in several brain regions in anxious (vs non-anxious) youth, including amygdala, striatum and medial prefrontal cortex. However, few studies examined the anticipation of peer interactions, a key component in the etiology and maintenance of anxiety disorders. Youth completed the Chatroom Task while undergoing functional magnetic resonance imaging. Patterns of neural activation were assessed in anxious and non-anxious youth as they were cued to anticipate social feedback from peers. Anxious participants evidenced greater amygdala activation and rostral anterior cingulate (rACC)↔amygdala coupling than non-anxious participants during anticipation of feedback from peers they had previously rejected; anxious participants also evidenced less nucleus accumbens activation during anticipation of feedback from selected peers. Finally, anxiety interacted with age in rACC: in anxious participants, age was positively associated with activation to anticipated feedback from rejected peers and negatively for selected peers, whereas the opposite pattern emerged for non-anxious youth. Overall, anxious youth showed greater reactivity in anticipation of feedback from rejected peers and thus may ascribe greater salience to these potential interactions and increase the likelihood of avoidance behavior.

Parenting is often implicated as a potential source of individual differences in youths' emotional information processing. The present study examined whether parental affect is related to an important aspect of adolescent emotional development, response to peer evaluation. Specifically, we examined relations between maternal negative affect, observed during parent-adolescent discussion of an adolescent-nominated concern with which s/he wants parental support, and adolescent neural responses to peer evaluation in 40 emotionally healthy and depressed adolescents. We focused on a network of ventral brain regions involved in affective processing of social information: the amygdala, anterior insula, nucleus accumbens, and subgenual anterior cingulate, as well as the ventrolateral prefrontal cortex. Maternal negative affect was not associated with adolescent neural response to peer rejection. However, longer durations of maternal negative affect were associated with decreased responsivity to peer acceptance in the amygdala, left anterior insula, subgenual anterior cingulate, and left nucleus accumbens. These findings provide some of the first evidence that maternal negative affect is associated with adolescents' neural processing of social rewards. Findings also suggest that maternal negative affect could contribute to alterations in affective processing, specifically, dampening the saliency and/or reward of peer interactions during adolescence. © 2014 The Authors.

This study examined the long-term effects of fluoxetine administered to juvenile rhesus monkeys who, as young adults, were imaged with positron emission tomography for two serotonergic markers: serotonin transporter (SERT) and serotonin 1A (5-HT1A) receptor. An equal number of monkeys separated from their mothers at birth-an animal model of human childhood stress-were also studied.At birth, 32 male rhesus monkeys were randomly assigned to either maternal separation or normal rearing conditions. At age 2, half (N=8) of each group was randomly assigned to fluoxetine (3 mg/kg) or placebo for 1 year. To eliminate the confounding effects of residual drug in the brain, monkeys were scanned at least 1.5 years after drug discontinuation. Social interactions were assessed both during and after drug administration.Fluoxetine persistently upregulated SERT, but not 5-HT1A receptors, in both the neocortex and the hippocampus. Whole-brain voxel-wise analysis revealed that fluoxetine had a significant effect in the lateral temporal and cingulate cortices. In contrast, neither maternal separation by itself nor the rearing-by-drug interaction was significant for either marker. Fluoxetine had no significant effect on the behavioral measures.Fluoxetine administered to juvenile monkeys upregulates SERT into young adulthood. Implications regarding the efficacy or potential adverse effects of SSRIs in patients cannot be directly drawn from this study. Its purpose was to investigate effects of SSRIs on brain development in nonhuman primates using an experimental approach that randomly assigned long-term SSRI treatment or placebo.

Children with disinhibited eating behaviors rarely meet full criteria for DSM-defined eating disorders. Further, there is overwhelming agreement that the current system of psychiatric diagnosis does not adequately address the symptoms and problems with which patients of all ages present. With advances in neuroscience, questions have been raised regarding the degree to which measures of brain function can be used to address these problems in psychiatric nosology. The National Institute of Mental Health’s Research Domain Criteria (RDoC) program provides a guide for attempts to incorporate such measures into psychiatric classification by encouraging research on dimensions of observable behavior and neurobiology.1 In brief, RDoC is a framework that integrates advances in neuroscience and research in psychopathology. In order to facilitate basic and clinical research, fundamental components or “domains” were identified (See Table 1 for RDoC matrix). These domains isolated specific behaviors and their presumed underlying neural architecture, focusing on behaviors that manifest across multiple disorders currently classified as nosologically distinct. RDoC includes domains and associated brain systems tied to negative valence, positive valence, cognitive, social processes, and arousal/regulation that are broken down further into constructs.2 Units of analysis integrate genetic, neurobiological, physiological, behavioral, environmental, and experiential assessments. In line with its dimensional approach, RDoC aims to determine the full range of variation, from normal to abnormal, within a population of individuals with similar psychological symptoms. Unlike current nosology that is organized around clinical presentations, RDoC domains are structured based on brain-behavior relationships. Thus, RDoC is atheoretical in terms of its connections with existing theories of psychiatric classification. Table 1 Constructs to assess for a multi-modal study of early disinhibited eating and outcomes. RDoC is an exciting proposal both because it acknowledges vexing problems in current psychiatric classification and because it prioritizes research in neuroscience as a solution. Yet, moving from the current broad RDoC framework to tangible research questions and associated designs involves developing an approach that is both feasible and specific. A particular set of clinically important behaviors must be selected that are also tractable from the perspective of neuroscience. The current “Idea Worth Researching” applies the RDoC approach to research on disinhibited eating behavior, viewed from a developmental perspective. We propose a design highly specific in nature by determining selected units of analysis that may be linked based upon prior literature. Although our proposed study focuses solely on one domain, we conclude by broadly discussing how the other domains might fit into a more exhaustive, future RDoC study of disinhibited eating. We readily acknowledge that there are numerous other neural, genetic, physiological, and behavioral constructs that are relevant to disinhibited eating and the development of adverse outcomes. We also fully recognize that the constructs that we suggest for study may be relevant to multiple domains.

Background Associations between a functional polymorphism in the serotonin transporter gene and amygdala activation have been found in healthy, depressed, and anxious adults. This study explored these gene–brain associations in adolescents by examining predictive effects of serotonin transporter gene variants (S and L G allele carriers vs. L A allele homozygotes) and their interaction with diagnosis (healthy vs. patients) on amygdala responses to emotional faces. Methods Functional magnetic resonance data were collected from 33 healthy adolescents (mean age: 13.71, 55% female) and 31 medication-free adolescents with current anxiety or depressive disorders (or both; mean age: 13.58, 56% female) while viewing fearful, angry, happy, and neutral facial expressions under varying attention states. Results A significant three-way genotype-by-diagnosis-by-face-emotion interaction characterized right amygdala activity while subjects monitored internal fear levels. This interaction was decomposed to map differential gene–brain associations in healthy and affected adolescents. First, consistent with healthy adult data, healthy adolescents with at least one copy of the S or L G allele showed stronger amygdala responses to fearful faces than healthy adolescents without these alleles. Second, patients with two copies of the L A allele exhibited greater amygdala responses to fearful faces relative to patients with S or L G alleles. Third, although weaker, genotype differences on amygdala responses in patients extended to happy faces. All effects were restricted to the fear-monitoring attention state. Conclusions S/L G alleles in healthy adolescents, as in healthy adults, predict enhanced amygdala activation to fearful faces. Contrary findings of increased activation in patients with L A L A relative to the S or L G alleles require further exploration.

Peer rejection powerfully predicts adolescent anxiety. While cognitive differences influence anxious responses to social feedback, little is known about neural contributions. Twelve anxious and twelve age-, gender-and IQ-matched, psychiatrically healthy adolescents received "not interested" and "interested" feedback from unknown peers during a chat room task administered in a neuroimaging scanner. No group differences emerged in subjective ratings to peer feedback, but all participants reported more negative emotion at being rejected (than accepted) by peers to whom they had assigned high-desirability ratings. Further highlighting the salience of such feedback, all adolescents, independently of anxiety levels, manifested elevated responses in the amygdala-hippocampal complex bilaterally, during the anticipation of feedback. However, anxious adolescents differed from healthy adolescents in their patterns of persistent amygdala-hippocampal activation following rejection. These data carry interesting implications for using neuroimaging data to inform psychotherapeutic approaches to social anxiety. © The Author(s) 2011.

Social reticence is expressed as shy, anxiously avoidant behavior in early childhood. With development, overt signs of social reticence may diminish but could still manifest themselves in neural responses to peers. We obtained measures of social reticence across 2 to 7 years of age. At age 11, preadolescents previously characterized as high (n = 30) or low (n = 23) in social reticence completed a novel functional-MRI-based peer-interaction task that quantifies neural responses to the anticipation and receipt of distinct forms of social evaluation. High (but not low) social reticence in early childhood predicted greater activity in dorsal anterior cingulate cortex and left and right insula, brain regions implicated in processing salience and distress, when participants anticipated unpredictable compared with predictable feedback. High social reticence was also associated with negative functional connectivity between insula and ventromedial prefrontal cortex, a region commonly implicated in affect regulation. Finally, among participants with high social reticence, negative evaluation was associated with increased amygdala activity, but only during feedback from unpredictable peers.

In humans, temperament plays an important role in socialization and personality. Some temperaments, such as behavioral inhibition are associated with an increased risk for psychopathology. Nonhuman primates can serve as a model for neurobiological and developmental contributions to emotional development and several recent studies have begun to investigate temperament in nonhuman primates. In rhesus monkeys, dominance rank is inherited from the mother and is associated with social and emotional tendencies that resemble differences in temperament. The current study assessed differences in temperament in infant rhesus monkeys as a function of maternal dominance rank. Temperament was assessed in 26 infants (13 males) from birth until 6 months of age with a battery that included Brazelton test, human intruder test, human intruder-startle, cortisol stress reactivity, and home cage observations of interactions with peers and the mother. Throughout testing, infants lived with their mothers and a small group of other monkeys in indoor/outdoor runs. Dominance rank of the mothers within each run was rated as either low/middle (N = 18, 9 male) or high/alpha (N = 8, 4 female). Infants of high-ranking mothers displayed more intruder-directed aggression and reduced startle potentiation in the human intruder tests. Dominant offspring also had reduced levels cortisol and startle across development and spent more time away from mothers in the interaction tests. These results suggest that dominance of the mother may be reflected in behavioral reactivity of infants early in life. These findings set up future studies, which may focus on contributing factors to both dominance and temperament such as genetics, rearing, and socialization. Such factors are likely to interact across development in meaningful ways. These results also suggest future human-based studies of a similar relationship may be warranted, although social dominance is clearly more complex in human than macaque societies.

Youth with bipolar disorder (BD) show behavioral and neural deficits in cognitive flexibility; however, whether such deficits exist among youths at risk for BD has not been explored.The current fMRI study examined the neural basis of cognitive flexibility in BD youth (n = 28), unaffected youth at risk for BD (AR; n = 13), and healthy volunteer youth (HV; n = 21) by comparing brain activation patterns while participants performed the change task. On change trials, subjects must inhibit a prepotent response and execute an alternate one.During successful change trials, both BD and AR youth had increased right ventrolateral prefrontal and inferior parietal activity, compared to HV youth. During failed change trials, both BD and AR youth exhibited increased caudate activation relative to HV youth, but BD youth showed increased activation in the subgenual anterior cingulate cortex (ACC) relative to the other two groups.Abnormal activity in ventrolateral prefrontal cortex, inferior parietal cortex, and striatum during a cognitive flexibility task may represent a potential BD endophenotype, but subgenual ACC dysfunction may represent a marker of BD illness itself.

Over the last several years a number of studies in both humans and animals have suggested that the orbitofrontal and ventrolateral prefrontal cortices play an important role in generating flexible behavior. We suggest that input from these brain regions contribute to three functions involved in generating flexible behavior within social contexts: valuation, inhibition, and rule use. Recent studies have also demonstrated that the prefrontal cortex undergoes a prolonged course of maturation that extends well after puberty. Here, we review evidence that the prolonged development of these prefrontal regions parallels a slowly emerging ability for flexible social behavior. We also speculate on the possibility that sensitive periods for organizing social behavior may be embedded within this developmental time-fame. Finally, we discuss the role of prefrontal cortex in adolescent mood and anxiety disorders, particularly as orbitofrontal and ventrolateral prefrontal cortices are engaged in a social context.

While studies among adults implicate the amygdala and interconnecting brain regions in encoding emotional stimuli, few studies have examined whether developmental changes occur within this emotional-memory network during adolescence. The present study examined whether adolescents and adults differentially engaged the amygdala and hippocampus during successful encoding of emotional pictures, with either positive or negative valence. Eighteen adults and twelve adolescents underwent event-related fMRI while encoding emotional pictures. Approximately 30 min later, outside the scanner, subjects were asked to recall the pictures seen during the scan. Age group differences in brain activity in the amygdala and hippocampus during encoding of the pictures that were later successfully and unsuccessfully recalled were separately compared for the positive and negative pictures. Adolescents, relative to adults, demonstrated enhanced activity in the right amygdala during encoding of positive pictures that were later recalled compared to not recalled. There were no age group differences in amygdala or hippocampal activity during successful encoding of negative pictures. The findings of preferential activity within the adolescent right amygdala during successful encoding of positive pictures may have implications for the increased reward and novelty seeking behavior, as well as elevated rates of psychopathology, observed during this distinct developmental period.

Neural correlates of social-cognition were assessed in 9- to- 17-year-olds (N = 34) using functional magnetic resonance imaging. Participants appraised how unfamiliar peers they had previously identified as being of high or low interest would evaluate them for an anticipated online chat session. Differential age- and sex-related activation patterns emerged in several regions previously implicated in affective processing. These included the ventral striatum, hippocampus, hypothalamus, and insula. In general, activation patterns shifted with age in older relative to younger females but showed no association with age in males. Relating these neural response patterns to changes in adolescent social-cognition enriches theories of adolescent social development through enhanced neurobiological understanding of social behavior.

Several lines of evidence implicate the amygdala in face-emotion processing, particularly for fearful facial expressions. Related findings suggest that face-emotion processing engages the amygdala within an interconnected circuitry that can be studied using a functional-connectivity approach. Past work also underscores important functional changes in the amygdala during development. Taken together, prior research on amygdala function and development reveals a need for more work examining developmental changes in the amygdala's response to fearful faces and in amygdala functional connectivity during face processing. The present study used event-related functional magnetic resonance imaging to compare 31 adolescents (9–17 years old) and 30 adults (21–40 years old) on activation to fearful faces in the amygdala and other regions implicated in face processing. Moreover, these data were used to compare patterns of amygdala functional connectivity in adolescents and adults. During passive viewing, adolescents demonstrated greater amygdala and fusiform activation to fearful faces than did adults. Functional connectivity analysis revealed stronger connectivity between the amygdala and the hippocampus in adults than in adolescents. Within each group, variability in age did not correlate with amygdala response, and sex-related developmental differences in amygdala response were not found. Eye movement data collected outside of the magnetic resonance imaging scanner using the same task suggested that developmental differences in amygdala activation were not attributable to differences in eye-gaze patterns. Amygdala hyperactivation in response to fearful faces may explain increased vulnerability to affective disorders in adolescence; stronger amygdala-hippocampus connectivity in adults than adolescents may reflect maturation in learning or habituation to facial expressions.

Alterations in brain development may contribute to chronic mental disorders. Novel treatments targeted toward the early-childhood manifestations of such chronic disorders may provide unique therapeutic opportunities. However, attempts to develop and deliver novel treatments face many challenges. Work on pediatric anxiety disorders illustrates both the inherent challenges as well as the unusual opportunities for therapeutic advances. The present review summarizes three aspects of translational research on pediatric anxiety disorders as the work informs efforts to develop novel interventions. First, the review summarizes data on developmental conceptualizations of anxiety from both basic neuroscience and clinical perspectives. This summary is integrated with a discussion of the two best-established treatments, cognitive behavioral therapy and selective serotonin reuptake inhibitors. Second, the review summarizes work on attention bias to threat, considering implications for both novel treatments and translational research on neural circuitry functional development. This illustrates the manner in which clinical findings inform basic systems neuroscience research. Finally, the review summarizes work in basic science on fear learning, as studied in fear conditioning, consolidation, and extinction paradigms. This summary ends by describing potential novel treatments, illustrating the manner in which basic neuroscience informs therapeutics.

OBJECTIVE: Considerable research examines fear conditioning in adult anxiety disorders but few studies examine youths. Adult data suggest that anxiety disorders involve elevated fear but intact differential conditioning. We used a novel paradigm to assess fear conditioning in pediatric anxiety patients. METHOD: Sixteen individuals with anxiety disorders and 38 healthy comparisons viewed two photographs of actresses displaying neutral expressions. One picture served as the conditioned stimulus (CS), paired with a fearful expression and a shrieking scream (CS+), whereas the other picture served as a CS unpaired with the aversive outcome (CS-). Conditioning was indexed by self-reported fear. Subjects participated in two visits involving conditioning and extinction trials. RESULTS: Both groups developed greater fear of the CS+ relative to CS-. Higher fear levels collapsed across each CS characterized anxious relative to healthy subjects, but no significant interaction between group and stimulus type emerged. Fear levels at visit 1 predicted avoidance of visit 2. Fear levels to both CS types showed stability even after extinction. CONCLUSIONS: Consistent with adult data, pediatric anxiety involves higher fear levels following conditioning but not greater differential conditioning. Extending these methods to neuroimaging studies may elucidate neural correlates of fear conditioning. Implications for exposure therapies are discussed.

Objectives: Previous studies have indicated abnormalities in response flexibility in pediatric bipolar disorder (BD). Dysfunction in response flexibility may contribute to the pattern of behavioral and emotional dysregulation that is characteristic of BD, since depressed and manic patients respond inflexibly to emotional stimuli (i.e., anhedonia in the case of depression or inappropriate positive affect in the case of mania). The present study was undertaken to determine if neuronal responses differed between BD and control subjects on a simple motor response flexibility task. Methods: To elucidate the neural substrates mediating response flexibility in pediatric BD, we studied 25 youth with BD and 17 age-, gender- and IQ-matched controls (CON) as they performed the change task while undergoing event-related functional magnetic resonance imaging (fMRI). The change task is a new fMRI task that requires subjects to both inhibit and replace a prepotent motor response with another motor response after the initial response has been cued. Results: On correctly performed change trials relative to correctly performed go trials, BD patients generated significantly more activity in the left dorsolateral prefrontal cortex (DLPFC) and in the primary motor cortex than did healthy controls, even though performance levels did not differ across groups. Conclusions: These results indicate that functional deficits within the left DLPFC may mediate deficits in response flexibility in pediatric BD. This deficit may extend beyond the realm of motor control and also affect emotion regulation.

This study examined patterns of behavioral and emotional responses to conflict and cooperation in adolescents with anxiety/mood disorders and healthy peers. We compared performance on and emotional responses to the Prisoner's Dilemma (PD) game, an economic exchange task involving conflict and cooperation, between adolescents with anxiety/depressive disorders (A/D) (N=21) and healthy comparisons (n = 29). Participants were deceived to believe their co-player (a pre-programmed computer algorithm) was another study participant. A/D adolescents differed significantly from comparisons in patterns of play and emotional response to the game. Specifically, A/D participants responded more cooperatively to cooperative overtures from their co-players; A/D girls also reported more anger toward co-players than did comparison girls. Our findings indicate that A/D adolescents, particularly females, respond distinctively to stressful social interchanges. These findings offer a first step toward elucidating the mechanisms underlying social impairment in youth with internalizing disorders.

The current study examines anxiety and age associations with attention allocation and physiological response to threats and rewards. Twenty-two healthy-adults, 20 anxious-adults, 26 healthy-youth, and 19 anxious-youth completed two eye-tracking tasks. In the Visual Scene Task (VST), participants’ fixations were recorded while they viewed a central neutral image flanked by two threatening or two rewarding stimuli. In the Negative Words Task (NWT), physiological response was measured by means of pupil diameter change while negative and neutral words were presented. For both tasks, no interaction was found between anxiety and age-group. In the VST, anxious participants avoided the threatening images when groups were collapsed across age. Similarly, adults but not adolescents avoided the threatening images when collapsed across anxiety. No differences were found for rewarding images. In NWT, all subjects demonstrated increase in pupil dilation after word presentation. Only main effect of age emerged with stronger pupil dilation in adults than children. Finally, maximum pupil change was correlated with threat avoidance bias in the scene task. Gaze patterns and pupil dilation show that anxiety and age are associated with attention allocation to threats. The relations between attention and autonomic arousal point to a complex interaction between bottom-up and top-down processes as they relate to attention allocation.

© 2015, Springer Science+Business Media New York. Heightened emotional reactivity to peer feedback is predictive of adolescents’ depression risk. Examining variation in emotional reactivity within currently depressed adolescents may identify subgroups that struggle the most with these daily interactions. We tested whether trait rumination, which amplifies emotional reactions, explained variance in depressed adolescents’ physiological reactivity to peer feedback, hypothesizing that rumination would be associated with greater pupillary response to peer rejection and diminished response to peer acceptance. Twenty currently depressed adolescents (12–17) completed a virtual peer interaction paradigm where they received fictitious rejection and acceptance feedback. Pupillary response provided a time-sensitive index of physiological arousal. Rumination was associated with greater initial pupil dilation to both peer rejection and acceptance, and diminished late pupillary response to peer acceptance trials only. Results indicate that depressed adolescents high on trait rumination are more reactive to social feedback regardless of valence, but fail to sustain cognitive-affective load on positive feedback.

Background.Pediatric loss-of-control (LOC) eating is a robust behavioral precursor to binge-type eating disorders. Elucidating precursors to LOC eating and binge-type eating disorders may refine developmental risk models of eating disorders and inform interventions.Method.We review evidence within constructs of the Negative Valence Systems (NVS) domain, as specified by the Research Domain Criteria framework. Based on published studies, we propose an integrated NVS model of binge-type eating-disorder risk.Results.Data implicate altered corticolimbic functioning, neuroendocrine dysregulation, and self-reported negative affect as possible risk factors. However, neuroimaging and physiological data in children and adolescents are sparse, and most prospective studies are limited to self-report measures.Conclusions.We discuss a broad NVS framework for conceptualizing early risk for binge-type eating disorders. Future neural and behavioral research on the developmental trajectory of LOC and binge-type eating disorders is required.

This study examines the effect of contingency on reward function in anxiety. We define contingency as the aspect of a situation in which the outcome is determined by one' sa ction—that is, whenthere is a direct link between one's action and the outcome of the action. Past findings in adoles- cents with anxiety or at risk for anxiety have revealed hyper- sensitive behavioral and neural responses to higher value rewards with correct performance. This hypersensitivity to highly valued (salient) actions suggests that the value of actions is determined not only by outcome magnitude, but also by the degree to which the outcome is contingent on correct performance. Thus, contingency and incentive value might each modulate reward responses in unique ways in anxiety. Using fMRI with a monetary reward task, striatal response to cue anticipation is compared in 18 clinically anxious and 20 healthy adolescents. This task manipulates orthogonally reward contingency and incentive value. Find- ings suggest that contingency modulates the neural response to incentive magnitude differently in the two groups. Specif- ically, during the contingent condition, right-striatal response tracks incentive value in anxious, but not healthy, adolescents. During the noncontingent condition, striatal response is bilat- erally stronger to low than to high incentive in anxious ado- lescents, while healthy adolescents exhibit the expected opposite pattern. Both contingency and reward magnitude differentiate striatal activation in anxious versus healthy ado- lescents. These findings may reflect exaggerated concern about performance and/or alterations of striatal coding of reward value in anxious adolescents. Abnormalities in reward function in anxiety may have treatment implications.

Adolescents' propensity for risk-taking and reward-seeking behaviors suggests a heightened sensitivity for reward, reflected by greater feedback-related activity changes in reward circuitry (e.g., nucleus accumbens), and/or a lower sensitivity to potential harm reflected by weaker feedback-related activity changes in avoidance circuitry (e.g., amygdala) relative to adults. Responses of nucleus accumbens and amygdala to valenced outcomes (reward receipt and reward omission) were assayed using an event-related functional magnetic resonance imaging procedure paired with a monetary reward task in 14 adults and 16 adolescents. Bilateral amygdala and nucleus accumbens showed significantly greater activation when winning than when failing to win in both groups. Group comparisons revealed stronger activation of left nucleus accumbens by adolescents, and of left amygdala by adults. When examining responses to reward receipts and to reward omissions separately, the most robust group difference was within the amygdala during reward omission. The reduction of the fMRI BOLD signal in the amygdala in response to reward omission was larger for adults than for adolescents. Correlations showed a close link between negative emotion and amygdala decreased BOLD signal in adults, and between positive emotion and nucleus accumbens activation in adolescents. Overall, these findings support the notion that the signal differences between positive and negative outcomes involve the nucleus accumbens more in adolescents than in adults, and the amygdala more in adults than in adolescents. These developmental differences, if replicated, may have important implications for the development of early-onset disorders of emotion and motivation.

Positive affect elicited in a mother toward her newborn infant may be one of the most powerful and evolutionarily preserved forms of positive affect in the emotional landscape of human behavior. This study examined the neurobiology of this form of positive emotion and in so doing, sought to overcome the difficulty of eliciting robust positive affect in response to visual stimuli in the physiological laboratory. Six primiparous human mothers with no indications of postpartum depression brought their infants into the laboratory for a photo shoot. Approximately 6 weeks later, they viewed photographs of their infant, another infant, and adult faces during acquisition of functional magnetic resonance images (fMRI). Mothers exhibited bilateral activation of the orbitofrontal cortex (OFC) while viewing pictures of their own versus unfamiliar infants. While in the scanner, mothers rated their mood more positively for pictures of their own infants than for unfamiliar infants, adults, or at baseline. The orbitofrontal activation correlated positively with pleasant mood ratings. In contrast, areas of visual cortex that also discriminated between own and unfamiliar infants were unrelated to mood ratings. These data implicate the orbitofrontal cortex in a mother's affective responses to her infant, a form of positive emotion that has received scant attention in prior human neurobiological studies. Furthermore, individual variations in orbitofrontal activation to infant stimuli may reflect an important dimension of maternal attachment.

We examined neural activations during decision-making using fMRI paired with the wheel of fortune task, a newly developed two-choice decision-making task with probabilistic monetary gains. In particular, we assessed the impact of high-reward/risk events relative to low-reward/risk events on neural activations during choice selection and during reward anticipation. Seventeen healthy adults completed the study. We found, in line with predictions, that (i) the selection phase predominantly recruited regions involved in visuo-spatial attention (occipito-parietal pathway), conflict (anterior cingulate), manipulation of quantities (parietal cortex), and preparation for action (premotor area), whereas the anticipation phase prominently recruited regions engaged in reward processes (ventral striatum); and (ii) high-reward/risk conditions relative to low-reward/risk conditions were associated with a greater neural response in ventral striatum during selection, though not during anticipation. Following an a priori ROI analysis focused on orbitofrontal cortex, we observed orbitofrontal cortex activation (BA 11 and 47) during selection (particularly to high-risk/reward options), and to a more limited degree, during anticipation. These findings support the notion that (1) distinct, although overlapping, pathways subserve the processes of selection and anticipation in a two-choice task of probabilistic monetary reward; (2) taking a risk and awaiting the consequence of a risky decision seem to affect neural activity differently in selection and anticipation; and thus (3) common structures, including the ventral striatum, are modulated differently by risk/reward during selection and anticipation.

Under standard conditions involving isolation and cooling, it has been documented that intraoral infusion of milk and injection of the intestinal peptide cholecystokinin (CCK) result in an attenuation in ultrasonic vocalizations (USV) emitted by infant rat pups. One of the most effective stimuli in inhibiting ingestion in suckling rat pups is gastric distension, but the effect of gastric distension on USV production has not been reported. In this experiment, we subjected infant rats to intragastric infusion of isotonic saline (2% body weight) to produce a natural level of gastric distension and hydration. We found that this stimulus resulted in a powerful reduction in USV emissions in isolated 10-day-old rats. In a subsequent experiment, we found that gastric saline infusion also diminished brown adipose tissue (BAT) thermogenesis. There were different time courses of the gastric saline infusion effects on BAT thermogenesis and on USV emissions, however, suggesting that these processes may be independently regulated. We hypothesize that this stimulus induces a transient activation of the parasympathetic nervous system, which overrides the sympathetic control of BAT and USV production.

The interpersonal model of loss of control (LOC) eating proposes that socially distressing situations lead to anxious states that trigger excessive food consumption. Self-reports support these links, but the neurobiological underpinnings of these relationships remain unclear. We therefore examined brain regions associated with anxiety in relation to LOC eating and energy intake in the laboratory. Twenty-two overweight and obese (BMIz: 1.9 ± 0.4) adolescent (15.8 ± 1.6 y) girls with LOC eating (LOC +, n = 10) and without LOC eating (LOC −, n = 12) underwent functional magnetic resonance imaging (fMRI) during a simulated peer interaction chatroom paradigm. Immediately after the fMRI scan, girls consumed lunch ad libitum from a 10,934-kcal laboratory buffet meal with the instruction to “let yourself go and eat as much as you want.” Pre-specified hypotheses regarding activation of five regions of interest were tested. Analysis of fMRI data revealed a significant group by peer feedback interaction in the ventromedial prefrontal cortex (vmPFC), such that LOC + had less activity following peer rejection (vs. acceptance), while LOC − had increased activity (p