The autism spectrum among transgender youth: default mode functional connectivity.

The common intersection of autism and transgender identities has been described in clinical and community contexts. This study investigates autism-related neurophenotypes among transgender youth. Forty-five transgender youth, evenly balanced across non-autistic, slightly subclinically autistic, and full-criteria autistic subgroupings, completed resting-state functional magnetic resonance imaging to examine functional connectivity. Results confirmed hypothesized default mode network (DMN) hub hyperconnectivity with visual and motor networks in autism, partially replicating previous studies comparing cisgender autistic and non-autistic adolescents. The slightly subclinically autistic group differed from both non-autistic and full-criteria autistic groups in DMN hub connectivity to ventral attention and sensorimotor networks, falling between non-autistic and full-criteria autistic groups. Autism traits showed a similar pattern to autism-related group analytics, and also related to hyperconnectivity between DMN hub and dorsal attention network. Internalizing, gender dysphoria, and gender minority-related stigma did not show connectivity differences. Connectivity differences within DMN followed previously reported patterns by designated sex at birth (i.e. female birth designation showing greater within-DMN connectivity). Overall, findings suggest behavioral diagnostics and autism traits in transgender youth correspond to observable differences in DMN hub connectivity. Further, this study reveals novel neurophenotypic characteristics associated with slightly subthreshold autism, highlighting the importance of research attention to this group.

Depression and anxiety in transgender and non-binary adolescents: prevalence and associations between adolescent and caregiver reports.

Transgender/non-binary (TNB) adolescents are at increased risk for mental health concerns, and caregiver awareness is important to facilitate access to care. Yet, limited research has examined caregiver awareness of TNB mental health. Thus, we examined (1) the prevalence of internalizing symptoms (depression, generalized anxiety, separation anxiety, social anxiety) among TNB adolescents and (2) associations between adolescent and caregiver reports of adolescent mental health symptoms. TNB adolescents (N = 75) aged 12-18 and a caregiver were recruited from a multidisciplinary gender clinic in Ohio. Adolescents self-reported their mental health symptoms via the CDI and SCARED. Caregivers reported their perceptions of the adolescent's mental health symptoms via the CASI-5. Descriptive statistics assessed participant characteristics, adolescent self-reported mental health symptoms, and caregiver proxy reports of adolescent mental health symptoms. Pearson's correlations and scatterplots were used to compare adolescent and caregiver reports and McNemar tests assessed if the differences were statistically significant. Most TNB adolescents reported elevated symptoms of depression (59%), generalized anxiety (75%), separation anxiety (52%), and social anxiety (78%). Caregiver and adolescent reports were significantly correlated for depression (r = .36, p = .002), separation anxiety (r = .39, p < .001), and social anxiety (r = .47, p < .001). Caregiver and adolescent reports of generalized anxiety were not significantly correlated (r = .21, p = .08). McNemar tests were significant (all p < .001), such that adolescents' reports met clinical cutoffs far more than their caregivers' reports. CONCLUSIONS: Though adolescent and caregiver reports were low to moderately correlated, youth reports were consistently higher, suggesting the importance of interventions to increase caregiver understanding of TNB adolescent mental health. WHAT IS KNOWN: • Transgender/non-binary adolescents are at high risk for mental health concerns and caregivers are essential to coordinate care. WHAT IS NEW: • This study expands the diagnostic mental health sub-categories examined in transgender/non-binary adolescents, noting elevated symptoms of separation and social anxiety. • Transgender/non-binary adolescents reported more symptoms of depression, generalized anxiety, separation anxiety, and social anxiety than caregivers.

Internalizing symptoms in intractable pediatric epilepsy: Structural and functional brain correlates.

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.

Blunted neural response to emotional faces in the fusiform and superior temporal gyrus may be marker of emotion recognition deficits in pediatric epilepsy.

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.

Age-related differences in neural activation and functional connectivity during the processing of vocal prosody in adolescence.

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.

Early childhood social reticence and neural response to peers in preadolescence predict social anxiety symptoms in midadolescence.

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.

Stationary and ambulatory attention patterns are differentially associated with early temperamental risk for socioemotional problems: Preliminary evidence from a multimodal eye-tracking investigation.

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.

Associations Between Anxious and Depressive Symptoms and the Recognition of Vocal Socioemotional Expressions in Youth.

The current study examined the associations between internalizing symptoms and adolescents' recognition of vocal socioemotional expressions produced by youth. Fifty-seven youth (8-17 years old, M = 12.62, SD = 2.66; 29 anxious, 28 nonanxious; 32 female, 25 male) were asked to identify the intended expression in auditory recordings of youth's portrayals of basic emotions and social attitudes. Recognition accuracy increased with age, suggesting that the ability to recognize vocal affect continues to develop into adolescence. Anxiety symptoms were not associated with recognition ability, but youth's depressive symptoms were related to poorer identification of anger and happiness. Youth experiencing symptoms of depression may be likely to misinterpret vocal expressions of happiness and anger.

Differences in adult and adolescent listeners' ratings of valence and arousal in emotional prosody.

Judgments of emotional stimuli's valence and arousal can differ based on the perceiver's age. With most of the existing literature on age-related changes in such ratings based on perceptions of visually-presented pictures or words, less is known about how youth and adults perceive and rate the affective information contained in auditory emotional stimuli. The current study examined age-related differences in adolescent (n = 31; 45% female; aged 12-17, M = 14.35, SD = 1.68) and adult listeners' (n = 30; 53% female; aged 21-30, M = 26.20 years, SD = 2.98) ratings of the valence and arousal of spoken words conveying happiness, anger, and a neutral expression. We also fitted closed curves to the average ratings for each emotional expression to determine their relative position on the valence-arousal plane of an affective circumplex. Compared to adults, adolescents' ratings of emotional prosody were generally higher in valence, but more constricted in range for both valence and arousal. This pattern of ratings is suggestive of lesser differentiation amongst emotional categories' holistic properties, which may have implications for the successful recognition and appropriate response to vocal emotional cues in adolescents' social environments.

Attention to Peer Feedback Through the Eyes of Adolescents with a History of Anxiety and Healthy Adolescents.

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.

A systematic review of attentional biases in disorders involving binge eating.

OBJECTIVE: Attentional bias (AB) may be one mechanism contributing to the development and/or maintenance of disordered eating. AB has traditionally been measured using reaction time in response to a stimulus. Novel methods for AB measurement include eye tracking to measure visual fixation on a stimulus, and electroencephalography to measure brain activation in response to a stimulus. This systematic review summarizes, critiques, and integrates data on AB gathered using the above-mentioned methods in those with binge eating behaviors, including binge eating, loss of control eating, and bulimia nervosa. METHOD: Literature searches on PubMed and PsycInfo were conducted using combinations of terms related to binge eating and biobehavioral AB paradigms. Studies using AB paradigms with three categories of stimuli were included: food, weight/shape, and threat. For studies reporting means and standard deviations of group bias scores, Hedges' g effect sizes for group differences in AB were calculated. RESULTS: Fifty articles met inclusion criteria and were reviewed. Individuals who binge eat in the absence of compensatory behaviors show an increased AB to food cues, but few studies have examined such individuals' AB toward weight/shape and threatening stimuli. Individuals with bulimia nervosa consistently show an increased AB to shape/weight cues and socially threatening stimuli, but findings for AB to food cues are mixed. DISCUSSION: While there are important research gaps, preliminary evidence suggests that the combination of AB to disorder-specific cues (i.e., food and weight/shape) and AB toward threat may be a potent contributor to binge eating. This conclusion underscores previous findings on the interaction between negative affect and AB to disorder-specific cues. Recommendations for future research are provided.

Anxiety symptoms and children's eye gaze during fear learning.

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.

Early-Childhood Social Reticence Predicts Brain Function in Preadolescent Youths During Distinct Forms of Peer Evaluation.

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.

Depressed Adolescents' Pupillary Response to Peer Acceptance and Rejection: The Role of Rumination.

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.

Neural activation during anticipated peer evaluation and laboratory meal intake in overweight girls with and without loss of control eating.

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±1.6y) 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<.005). Moreover, functional coupling between vmPFC and striatum for peer rejection (vs. acceptance) interacted with LOC status: coupling was positive for LOC+, but negative in LOC- (p<.005). Activity of fusiform face area (FFA) during negative peer feedback from high-value peers also interacted with LOC status (p<.005). A positive association between FFA activation and intake during the meal was observed among only those with LOC eating. In conclusion, overweight and obese girls with LOC eating may be distinguished by a failure to engage regions of prefrontal cortex implicated in emotion regulation in response to social distress. The relationship between FFA activation and food intake supports the notion that heightened sensitivity to incoming interpersonal cues and perturbations in socio-emotional neural circuits may lead to overeating in order to cope with negative affect elicited by social discomfort in susceptible youth.

Role of contingency in striatal response to incentive in adolescents with anxiety.

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's action-that is, when there is a direct link between one's action and the outcome of the action. Past findings in adolescents with anxiety or at risk for anxiety have revealed hypersensitive 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. Findings suggest that contingency modulates the neural response to incentive magnitude differently in the two groups. Specifically, during the contingent condition, right-striatal response tracks incentive value in anxious, but not healthy, adolescents. During the noncontingent condition, striatal response is bilaterally stronger to low than to high incentive in anxious adolescents, while healthy adolescents exhibit the expected opposite pattern. Both contingency and reward magnitude differentiate striatal activation in anxious versus healthy adolescents. 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.

Incidental threat during visuospatial working memory in adolescent anxiety: an emotional memory-guided saccade task.

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.

Attentional bias to food cues in youth with loss of control eating.

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.

Lasting associations between early-childhood temperament and late-adolescent reward-circuitry response to peer feedback.

Behavioral inhibition, a temperament identifiable in infancy, is associated with heightened withdrawal from social encounters. Prior studies raise particular interest in the striatum, which responds uniquely to monetary gains in behaviorally inhibited children followed into adolescence. Although behavioral manifestations of inhibition are expressed primarily in the social domain, it remains unclear whether observed striatal alterations to monetary incentives also extend to social contexts. In the current study, imaging data were acquired from 39 participants (17 males, 22 females; ages 16-18 years) characterized since infancy on measures of behavioral inhibition. A social evaluation task was used to assess neural response to anticipation and receipt of positive and negative feedback from novel peers, classified by participants as being of high or low interest. As with monetary rewards, striatal response patterns differed during both anticipation and receipt of social reward between behaviorally inhibited and noninhibited adolescents. The current results, when combined with prior findings, suggest that early-life temperament predicts altered striatal response in both social and nonsocial contexts and provide support for continuity between temperament measured in early childhood and neural response to social signals measured in late adolescence and early adulthood.

Distinct neural signatures of threat learning in adolescents and adults.

Most teenage fears subside with age, a change that may reflect brain maturation in the service of refined fear learning. Whereas adults clearly demarcate safe situations from real dangers, attenuating fear to the former but not the latter, adolescents' immaturity in prefrontal cortex function may limit their ability to form clear-cut threat categories, allowing pervasive fears to manifest. Here we developed a discrimination learning paradigm that assesses the ability to categorize threat from safety cues to test these hypotheses on age differences in neurodevelopment. In experiment 1, we first demonstrated the capacity of this paradigm to generate threat/safety discrimination learning in both adolescents and adults. Next, in experiment 2, we used this paradigm to compare the behavioral and neural correlates of threat/safety discrimination learning in adolescents and adults using functional MRI. This second experiment yielded three sets of findings. First, when labeling threats online, adolescents reported less discrimination between threat and safety cues than adults. Second, adolescents were more likely than adults to engage early-maturing subcortical structures during threat/safety discrimination learning. Third, adults' but not adolescents' engagement of late-maturing prefrontal cortex regions correlated positively with fear ratings during threat/safety discrimination learning. These data are consistent with the role of dorsolateral regions during category learning, particularly when differences between stimuli are subtle [Miller EK, Cohen JD (2001) Annu Rev Neurosci 24:167-202]. These findings suggest that maturational differences in subcortical and prefrontal regions between adolescent and adult brains may relate to age-related differences in threat/safety discrimination.