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Adolescence is characterized by the maturation of cortical microstructure and connectivity supporting complex cognition and behavior. Axonal myelination influences brain connectivity during development by enhancing neural signaling speed and inhibiting plasticity. However, the maturational timing of cortical myelination during human adolescence remains poorly understood. Here, we take advantage of recent advances in high-resolution cortical T1w/T2w mapping methods, including principled correction of B1+ transmit field effects, using data from the Human Connectome Project in Development (HCP-D; N = 628, ages 8–21). We characterize microstructural changes relevant to myelination by estimating age-related differences in T1w/T2w throughout the cerebral neocortex from childhood to early adulthood. We apply Bayesian spline models and clustering analysis to demonstrate graded variation in age-dependent cortical T1w/T2w differences that are correlated with the sensorimotor-association (S-A) axis of cortical organization reported by others. In sensorimotor areas, T1w/T2w ratio measures start at high levels at early ages, increase at a fast pace, and decelerate at later ages (18–21). In intermediate multimodal areas along the S-A axis, T1w/T2w starts at intermediate levels and increases linearly at an intermediate pace. In transmodal/paralimbic association areas, T1w/T2w starts at low levels and increases linearly at the slowest pace. These data provide evidence for graded variation of the T1w/T2w ratio along the S-A axis that may reflect cortical myelination changes during adolescence underlying the development of complex information processing and psychological functioning. We discuss the implications of these results as well as caveats in interpreting magnetic resonance imaging (MRI)-based estimates of myelination. SIGNIFICANCE STATEMENT Myelin is a lipid membrane that is essential to healthy brain function. Myelin wraps axons to increase neural signaling speed, enabling complex neuronal functioning underlying learning and cognition. Here, we characterize the developmental timing of myelination across the cerebral cortex during adolescence using a noninvasive proxy measure, T1w/T2w mapping. Our results provide new evidence demonstrating graded variation across the cortex in the timing of T1w/T2w changes during adolescence, with rapid T1w/T2w increases in lower-order sensory areas and gradual T1w/T2w increases in higher-order association areas. This spatial pattern of microstructural brain development closely parallels the sensorimotor-to-association axis of cortical organization and plasticity during ontogeny.

The human brain is active at rest, and spontaneous fluctuations in functional MRI BOLD signals reveal an intrinsic functional architecture. During childhood and adolescence, functional networks undergo varying patterns of maturation, and measures of functional connectivity within and between networks differ as a function of age. However, many aspects of these developmental patterns (e.g. trajectory shape and directionality) remain unresolved. In the present study, we characterised age-related differences in within- and between-network resting-state functional connectivity (rsFC) and integration (i.e. participation coefficient, PC) in a large cross-sectional sample of children and adolescents (n = 628) aged 8–21 years from the Lifespan Human Connectome Project in Development. We found evidence for both linear and non-linear differences in cortical, subcortical, and cerebellar rsFC, as well as integration, that varied by age. Additionally, we found that sex moderated the relationship between age and putamen integration where males displayed significant age-related increases in putamen PC compared with females. Taken together, these results provide evidence for complex, non-linear differences in some brain systems during development.

BackgroundAlcohol, cannabis, and nicotine use are highly comorbid and alarmingly prevalent in young adults. The hippocampus may be particularly sensitive to substance exposure. This remains largely untested in humans and familial risk may confound exposure effects. We extend prior work on alcohol and hippocampal volume in women by testing common and unique substance use effects and the potential moderating role of sex on hippocampal volume during emerging adulthood. A quasi-experimental cotwin control (CTC) design was used to separate familial risk from exposure consequences.MethodsIn a population-based sample of 435 24-year-old same-sex twins (58% women), dimensional measures (e.g. frequency, amount) of alcohol, cannabis, and nicotine use across emerging adulthood were assessed. Hippocampal volume was assessed using MRI.ResultsGreater substance use was significantly associated with lower hippocampal volume for women but not men. The same pattern was observed for alcohol, cannabis, and nicotine. CTC analyses provided evidence that hippocampal effects likely reflected familial risk and the consequence of substance use in general and alcohol and nicotine in particular; cannabis effects were in the expected direction but not significant. Within-pair mediation analyses suggested that the effect of alcohol use on the hippocampus may reflect, in part, comorbid nicotine use.ConclusionsThe observed hippocampal volume deviations in women likely reflected substance-related premorbid familial risk and the consequences of smoking and, to a lesser degree, drinking. Findings contribute to a growing body of work suggesting heightened risk among women toward experiencing deleterious effects of substance exposure on the still-developing young adult hippocampus.

Background Impairments in inhibitory control and its underlying brain networks (control/salience areas) are associated with substance misuse. Research often assumes a causal substance exposure effect on brain structure. This assumption remains largely untested, and other factors (e.g., familial risk) may confound exposure effects. We leveraged a genetically informative sample of twins aged 24 years and a quasi-experimental co-twin control design to separate alcohol or cannabis exposure effects during emerging adulthood from familial risk on control/salience network cortical thickness. Methods In a population-based sample of 436 twins aged 24 years, dimensional measures of alcohol and cannabis use (e.g., frequency, density, quantity, intoxications) across emerging adulthood were assessed. Cortical thickness of control/salience network areas were assessed using magnetic resonance imaging and defined by a fine-grained cortical atlas. Results Greater alcohol, but not cannabis, misuse was associated with reduced thickness of prefrontal (e.g., dorso/ventrolateral, right frontal operculum) and frontal medial cortices, as well as temporal lobe, intraparietal sulcus, insula, parietal operculum, precuneus, and parietal medial areas. Effects were predominately (pre)frontal and right lateralized. Co-twin control analyses suggested that the effects likely reflect both the familial predisposition to misuse alcohol and, specifically for lateral prefrontal, frontal/parietal medial, and right frontal operculum, an alcohol exposure effect. Conclusions This study provides novel evidence that alcohol-related reductions in cortical thickness of control/salience brain networks likely represent the effects of alcohol exposure and premorbid characteristics of the genetic predisposition to misuse alcohol. The dual effects of these two alcohol-related causal influences have important and complementary implications regarding public health and prevention efforts to curb youth drinking.

Background/aims Research linking orbitofrontal cortex (OFC) structure and substance use disorders (SUDs) is largely correlational and often implies a causal effect of addiction/substance exposure on the brain, but familial risk factors (e.g. genetic liability) may confound these associations. We tested whether associations between alcohol, cannabis and tobacco use disorders and OFC thickness reflected the potential causal effects of familial risk or SUDs-related consequences (e.g. substance exposure). Design A co-twin control/discordant twin design separated familial risk confounding from SUD-related consequences. Setting/participants A population-based sample of 436 24-year-old twins (62% monozygotic) from the Minnesota Twin Family Study, USA. Measurements Alcohol, cannabis and tobacco use disorders were assessed using the Composite International Diagnostic Interview-Substance Abuse Module. Cortical thickness of the medial and lateral OFC (mOFC and lOFC, respectively) was assessed using magnetic resonance imaging (MRI). Findings Lower mOFC (P-values ≤ 0.006) but not lOFC (P-values ≥ 0.190) thickness was observed in diagnosed individuals (n = 185) relative to non-SUD controls (n = 251). Co-twin control analyses offered evidence that mOFC associations were consistent with familial risk across SUDs (between-pair effect: P-values ≤ 0.047) and the independent consequences of having an alcohol or cannabis use disorder (within-pair effect: P-values ≤ 0.024). That is, within alcohol/cannabis discordant twin pairs, affected twins had significantly lower mOFC thickness compared with their unaffected co-twins. Conclusions A confounder-adjusted analysis of the Minnesota Twin Family Study appeared to indicate that, beyond a substance use disorders general familial risk effect, the experience of an alcohol or cannabis use disorder in emerging adulthood reduces the thickness of the medial orbitofrontal cortex, a region associated with value-guided decision-making.

Understanding individual differences in neural responses to stressful environments is an important avenue of research throughout development. These differences may be especially critical during adolescence, which is characterized by opportunities for healthy development and increased susceptibility to the development of psychopathology. While the neural correlates of the psychosocial stress response have been investigated in adults, these links have not been explored during development. Using a new task, the Minnesota Imaging Stress Test in Children (MISTiC), differences in activation are found in fusiform gyrus, superior frontal gyrus, insula, and anterior cingulate cortex when comparing a stressful math task to a nonstressful math task. The MISTiC task successfully elicits cortisol responses in a similar proportion of adolescents as in behavioral studies while collecting brain imaging data. Cortisol responders and nonresponders did not differ in their perceived stress level or behavioral performance during the task despite differences in neuroendocrine function. Future research will be able to leverage the MISTiC task for many purposes, including probing associations between individual differences in stress responses with environmental conditions, personality differences, and the development of psychopathology.

Myelination influences brain connectivity during sensitive periods of development by enhancing neural signaling speed and regulating synapse formation to reduce plasticity. However, in vivo studies characterizing the maturational timing of cortical myelination during human development remain scant. Here, we take advantage of recent advances in high-resolution cortical T1w/T2w myelin mapping methods, including principled correction of B1+ transmit field effects, using data from the Human Connectome Project in Development (N=628, ages 8-21) to characterize the maturational timing of myelination from childhood through early adulthood throughout the cerebral neocortex. We apply Bayesian spline models and functional latent clustering analysis to demonstrate graded variation in the rate of cortical T1w/T2w myelin growth in neocortical areas that is strongly correlated with the sensorimotor-association (S-A) axis of cortical organization reported by others. In sensorimotor areas T1w/T2w myelin starts at high levels at early ages, increases at a fast pace, and decelerates at later ages (18-21). In intermediate multimodal areas along the S-A axis, T1w/T2w myelin tends to start at intermediate levels and increase linearly at an intermediate pace. In transmodal/paralimbic association areas high along the S-A axis, T1w/T2w myelin tends to start at low levels and increase linearly at the slowest pace. These data provide evidence for graded variation along the S-A axis in the rate of cortical myelination during adolescence, which could reflect ongoing plasticity underlying the development of complex information processing and psychological functioning.Significance StatementMyelin is a lipid membrane that is essential to healthy brain function. Myelin wraps axons to increase neural signaling speed, enabling complex neuronal functioning underlying learning and cognition. Here we characterize the developmental timing of myelination across the cerebral cortex during adolescence using recent advances in non-invasive myelin mapping. Our results provide new evidence demonstrating graded variation across the cortex in the timing of myelination during adolescence, with rapid myelination in lower-order sensory areas and gradual myelination in higher-order association areas. This spatial pattern of microstructural brain development closely parallels the sensorimotor-to-association axis of cortical organization and plasticity during ontogeny.

The human cerebral cortex undergoes considerable changes during development, with cortical maturation patterns reflecting regional heterogeneity that generally progresses in a posterior-to-anterior fashion. However, the organizing principles that govern cortical development remain unclear. In the current study, we characterized age-related differences in cortical thickness (CT) as a function of sex, pubertal timing, and two dissociable indices of socioeconomic status (i.e., income-to-needs and maternal education) in the context of functional brain network organization, using a cross-sectional sample (n = 789) diverse in race, ethnicity, and socioeconomic status from the Lifespan Human Connectome Project in Development (HCP-D). We found that CT generally followed a linear decline from 5 to 21 years of age, except for three functional networks that displayed nonlinear trajectories. We found no main effect of sex or age by sex interaction for any network. Earlier pubertal timing was associated with reduced mean CT and CT in seven networks. We also found a significant age by maternal education interaction for mean CT across cortex and CT in the dorsal attention network, where higher levels of maternal education were associated with steeper age-related decreases in CT. Taken together, our results suggest that these biological and environmental variations may impact the emerging functional connectome.

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

Exposure to childhood maltreatment (CM) may disrupt typical development of neural systems underlying impulse control and emotion regulation. Yet resilient outcomes are observed in some individuals exposed to CM. Individual differences in adult functioning may result from variation in inhibitory control in the context of emotional distractions, underpinned by cognitive–affective brain circuits. Thirty-eight healthy adults with a history of substantiated CM and 34 nonmaltreated adults from the same longitudinal sample performed a Go/No-Go task in which task-relevant stimuli (letters) were presented at the center of task-irrelevant, negative, or neutral images, while undergoing functional magnetic resonance imaging. The comparison group, but not the maltreated group, made increased inhibitory control errors in the context of negative, but not neutral, distractor images. In addition, the comparison group had greater right inferior frontal gyrus and bilateral frontal pole activation during inhibitory control blocks with negative compared to neutral background images relative to the CM group. Across the full sample, greater adaptive functioning in everyday contexts was associated with superior inhibitory control and greater right frontal pole activation. Results suggest that resilience following early adversity is associated with enhanced attention and behavioral regulation in the context of task-irrelevant negative emotional stimuli in a laboratory setting.

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

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

The variation in experiences between high and low-socioeconomic status contexts are posited to play a crucial role in shaping the developing brain and may explain differences in child outcomes. Yet, examinations of SES and brain development have largely been limited to distal proxies of these experiences (e.g., income comparisons). The current study sought to disentangle the effects of multiple socioeconomic indices and dimensions of more proximal experiences on resting-state functional connectivity (rsFC) in a sample of 7834 youth (aged 9–10 years) from the Adolescent Brain Cognitive Development (ABCD) study. We applied moderated nonlinear factor analysis (MNLFA) to establish measurement invariance among three latent environmental dimensions of experience (material/economic deprivation, caregiver social support, and psychosocial threat). Results revealed measurement biases as a function of child age, sex, racial group, family income, and parental education, which were statistically adjusted in the final MNLFA scores. Mixed-effects models demonstrated that socioeconomic indices and psychosocial threat differentially predicted variation in frontolimbic networks, and threat statistically moderated the association between income and connectivity between the dorsal and ventral attention networks. Findings illuminate the importance of reducing measurement biases to gain a more socioculturally-valid understanding of the complex and nuanced links between socioeconomic context, children’s experiences, and neurodevelopment., Highlights • Measurement biases were found for several environmental measures in the ABCD study. • MNLFA tests and adjusts for measurement biases to afford socioculturally-valid conclusions. • Parental education and psychosocial threat were uniquely associated with frontolimbic networks. • Associations between INR and DAN-VAN connectivity varied by threat experiences.

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

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

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

The quality of early caregiving may partially shape brain structure and circuits involved in regulating emotions, including the frontal cortex, affecting vulnerability to the development of psychopathology and maladaptation. Given the profound impact of child maltreatment (CM) on psychological and neural development, we tested whether CM alters the pathways linking mother–adolescent relationship, frontal cortex, and adult outcomes. We used structural equation modeling to investigate whether CM history affected the association between mother–child relationship quality during early adolescence, frontal lobe volume in adulthood, and adult internalizing and externalizing symptomatology and competence. Participants from a longitudinal high-risk, low-income sample included 48 adults with a history of CM and 40 adults without such history ( M = 30.0 years). Results showed that greater frontal lobe volume predicted higher levels of adult adaptive functioning and fewer adult internalizing symptoms but showed no relation to adult externalizing symptoms. Frontal lobe volume significantly mediated the effect of adolescent maternal relationship quality on both adult internalizing symptoms and adult adaptive functioning, but only for individuals with no maltreatment history. Given the observed relationship between frontal lobe volume and healthy adult functioning across the full sample, it will be important to identify protective factors in maltreated individuals that foster frontal lobe development.

Background Non-suicidal self-injury (NSSI) is a major, trans-diagnostic mental health problem among adolescents. Alexithymia has been identified as a developmental risk factor for NSSI. Research on how alexithymia relates to the neurobiology of automatic emotion processing is only beginning to emerge. This study evaluates the relationship between alexithymic features and neural responses to automatic processing of emotional content in adolescents with NSSI. Methods 25 female adolescents (ages 13–21) with a history of repeated engagement in NSSI completed the Toronto Alexithymia Scale and the Difficulties with Emotion Regulation Scale and underwent functional magnetic resonance imaging (fMRI) during a task in which participants were exposed to masked emotions. Results One facet of alexithymia, limited internal emotion awareness or externally-oriented thinking (EOT), was related to differential reactivity to masked emotional faces in clusters in the right supramarginal gyrus and right inferior frontal gyrus. Follow-up assessment of regional reactivity revealed that greater EOT is associated with lower activation to masked happy faces but higher activation to masked fearful faces. Other facets of alexithymia did not show relationships with reactivity to masked emotional faces. Limitations This is a cross-sectional and small sample that only includes females, which may attenuate generalizability of findings. Conclusions We report neural correlates of multiple facets of alexithymia in adolescents with NSSI. Among adolescents who self-harm, those with higher levels of EOT may be less alert to subtle positively-valenced emotion cues. For this subset of adolescents with NSSI, interventions designed to enhance mental representation of emotional responses and attention to positive emotions may be appropriate.

This study investigated whether brain-derived neurotrophic factor (BDNF) genotype moderated inhibitory control during an emotionally valenced task in a sample of internationally adopted adolescents ( N = 109, ages 12-13 years) who spent their early years in institutional care. Participants were genotyped for the Val66Met polymorphism of the BDNF gene. Inhibitory control in different emotional contexts was assessed via a Go-NoGo task where letters appeared at the center of positive, negative, neutral, or scrambled images. Carriers of one or more methionine (Met) alleles demonstrated a significant association between poorer performance and increased adversity, indexed by age at adoption, while valine/valine (Val/Val) carriers did not. Thus, Val/Val genotype was associated with resilience to increased impulsivity with more prolonged deprivation. These results do not converge with research suggesting differential susceptibility effects for this polymorphism, but more closely reflect a diathesis-stress model for the impact of BDNF genotype on a behavioral measure of impulsivity during emotional distraction.

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

A controversy exists about the effects of violent video game play, with some studies showing “positive” effects on spatial attention, others showing “negative” effects on aggression, and others suggesting that there are no important effects. The present study examined neural recruitment during violent videogame play among 13 late adolescent gamers, half of whom habitually played violent games and half of whom habitually played nonviolent games. Participants played a video game in violent and nonviolent modes while undergoing functional MRI scanning. Nonviolent gamers had an increase in emotional response regions when playing the violent game; violent gamers demonstrated an active suppression of these same regions. In addition, nonviolent gamers showed increases in spatial attention, navigation, and cognitive control regions, whereas experienced violent gamers showed no change from baseline. These results provide neurological support for both aggression desensitization and improvements in spatial attention, but not for the hypothesis that violent games have no appreciable effect.

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

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

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

Objective Pregnancies complicated by diabetes mellitus impair offspring memory functions during infancy and early childhood. The purpose of this study was to investigate the long-term consequences of such pregnancies on memory and memory-related brain regions in 10-year-old children. Methods Nineteen children of diabetic mothers (CDMs) and 35 children of nondiabetic mothers participated in this 10-year follow-up study. Memory performance was assessed using a continuous recognition memory task during which children made old/new judgments in response to pictures of concrete and abstract objects presented after different lags or delays. In addition, the volume of the hippocampal formation (HF) was measured using high-resolution structural images. Results At 10 years of age, recognition memory performance of CDMs did not differ from children of nondiabetic mothers. Similarly, the volume of the HF did not differ between groups. However, the size of the HF in CDMs predicted the time those children needed to provide accurate responses in the continuous recognition memory task. Conclusions CDMs do not show memory impairments by 10 years of age, despite evidence for such impairments early in life. However, subtle differences in underlying neural processes may still be present. These results have important implications for long-term cognitive development of CDMs.

Borderline personality disorder (BPD) is a serious condition involving emotion dysregulation. Past research has identified BPD-associated differences within fronto-limbic circuitry during conditions of processing negative emotion. Functional magnetic resonance imaging (fMRI) paradigms that incorporate overt and covert (masked) presentations of emotional stimuli can provide complementary information about neural systems underlying emotion processing (e.g., both slow [overt] and fast [covert; automatic] processing pathways). This study examined brain activation during processing of overt and covert presentations of emotional faces in 12 women with BPD and 12 age-matched healthy controls. To assess a range of emotional valence and arousal, we examined responses to fear, happy and neutral expressions. All participants underwent an fMRI scanning session in which participants passively viewed emotional faces. Scanning sessions consisted of 5 runs including: (1) Overt Fear (OF) versus Neutral (N), (2) Covert Fear (CF) versus Covert Neutral (CN), (3) Overt Happy (OH) versus N, (4) Covert Happy (CH) versus CN, and (5) N versus fixation. We compared whole-brain activation between groups for each run. In response to overt fear, BPD patients showed greater activation both in left amygdala and in several frontal cortical regions. There were no significant differences in brain activation in response to overt happy faces. In response to covert fear and covert happy stimuli, the BPD group also showed greater activation than controls in several regions including frontal and temporal cortical regions, as well as cerebellum and thalamus. These findings add to prior reports suggesting increased amygdala activation in BPD, but we found this only in the overt fear versus fixation condition. In this sample, BPD patients showed hyper-activation, rather than hypo-activation, of cortical regulatory regions during overt fear. Enhanced cortical recruitment in response to covert fear and happy faces in BPD could reflect a more extended response system in which stimuli that typically only activate automatic pathways are additionally tapping into cortical regulatory systems. The observation of this pattern both in response to fear and in response to happy presentations suggests that the effect of arousal may be as or more impactful than the effect of emotional valence.

Interest in monitoring long-term neurodevelopmental outcomes of children born moderate-to-late preterm (32-36 weeks gestation) is increasing. Moderate-to-late preterm birth has a negative impact on academic achievement, which may relate to differential development of executive function (EF). Prior studies reporting deficits in EF in preterm children have almost exclusively assessed EF in affectively neutral contexts in high-risk preterm children (< 32 weeks gestation). Disrupted function in motivational or emotionally charged contexts (hot EF) following preterm birth remains uninvestigated, despite evidence that preterm children show differential development of neural circuitry subserving hot EF, including reduced orbitofrontal cortex volume. The present study is the first to examine whether low-risk, healthy children born moderate-to-late preterm exhibit impairments in the development of hot EF. Preterm children at age 4.5 years were less likely to choose larger, delayed rewards across all levels of reward magnitude on a delay discounting task using tangible rewards, but performed more similarly to their full-term peers on a delay aversion task involving abstract rewards and on measures of cool EF. The relationship between gestational age at birth and selection of delayed rewards extended across the entire gestational age range of the sample (32-42 weeks), and remained significant after controlling for intelligence and processing speed. Results imply that there is not a finite cut-off point at which children are spared from potential long-term neurodevelopmental effects of PT birth. Further investigation of reward processing and hot EF in individuals with a history of PT birth is warranted given the susceptibility of prefrontal cortex development to early environmental variations.

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

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

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

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

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

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

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

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

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

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

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

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

Chronic parental maltreatment has been associated with lower levels of interpersonal trust, and depriving environments have been shown to predict shortsighted, risk-averse decision-making. The present study examined whether a circumscribed period of adverse care occurring only early in life was associated with biases in trust behavior. Fifty-three post-institutionalized (PI) youth, adopted internationally on average by one year of age, and 33 never-institutionalized, non-adopted youth (M age = 12.9 years) played a trust game. Participants decided whether or not to share coins with a different anonymous peer in each trial with the potential to receive a larger number of coins in return. Trials were presented in blocks that varied in the degree to which the peers behaved in a trustworthy (reciprocal) or untrustworthy (non-reciprocal) manner. A comparison condition consisted of a computerized lottery with the same choices and probabilistic risk as the peer trials. Non-adopted comparison youth showed a tendency to share more with peers than to invest in the lottery and tended to maintain their level of sharing across trials despite experiencing trials in which peers failed to reciprocate. In contrast, PI children, particularly those who were adopted over a year of age, shared less with peers than they invested in the lottery and quickly adapted their sharing behavior to peers' responses. These results suggest that PI youth were more mistrusting, more sensitive to both defection and reciprocation, and potentially more accurate in their trusting decisions than comparison youth. Results support the presence of a sensitive period for the development of trust in others, whereby conditions early in life may set long-term biases in decision-making.

Adverse early care is associated with attention regulatory problems, but not all so exposed develop attention problems. In a sample of 612 youth (girls = 432, M = 11.82 years, SD = 1.5) adopted from institutions (e.g., orphanages) in 25 countries, we examined whether the Val66Met polymorphism of the brain-derived neurotrophic factor gene moderates attention problems associated with the duration of institutional care. Parent-reported attention problem symptoms were collected using the MacArthur Health and Behavior Questionnaire. DNA was genotyped for the brain-derived neurotrophic factor Val66Met (rs6265) single nucleotide polymorphism. Among youth from Southeast (SE) Asia, the predominant genotype was valine/methionine (Val/Met), whereas among youth from Russia/Europe and Caribbean/South America, the predominant genotype was Val/Val. For analysis, youth were grouped as carrying Val/Val or Met/Met alleles. Being female, being from SE Asia, and being younger when adopted were associated with fewer attention regulatory problem symptoms. Youth carrying at least one copy of the Met allele were more sensitive to the duration of deprivation, yielding an interaction that followed a differential susceptibility pattern. Thus, youth with Val/Met or Met/Met genotypes exhibited fewer symptoms than Val/Val genotypes when adoption was very early and more symptoms when adoption occurred later in development. Similar patterns were observed when SE Asian youth and youth from other parts of the world were analyzed separately.

“Invisible” stimulus paradigms provide a method for investigating basic affective processing in clinical and non-clinical populations. Neuroimaging studies utilizing continuous flash suppression (CFS) have shown increased amygdala response to invisible fearful versus neutral faces. The current study used CFS in conjunction with functional MRI to test for differences in brain reactivity to visible and invisible emotional faces in relation to two distinct trait dimensions relevant to psychopathology: negative affectivity (NA) and fearfulness. Subjects consisted of college students (N = 31) assessed for fear/fearlessness along with dispositional NA. The main brain regions of interest included the fusiform face area (FFA), superior temporal sulcus (STS), and amygdala. Higher NA, but not trait fear, was associated with enhanced response to fearful versus neutral faces in STS and right amygdala (but not FFA), within the invisible condition specifically. The finding that NA rather than fearfulness predicted degree of amygdala reactivity to suppressed faces implicates the input subdivision of the amygdala in the observed effects. Given the central role of NA in anxiety and mood disorders, the current data also support use of the CFS methodology for investigating the neurobiology of these disorders.

The medial temporal lobes (MTL) support declarative memory and mature structurally and functionally during the postnatal years in humans. Although recent work has addressed the development of declarative memory in early childhood, less is known about continued development beyond this period of time. The purpose of this investigation was to explore MTL-dependent memory across middle childhood. Children (6 – 10 years old) and adults completed two computerized tasks, place learning (PL) and transitive inference (TI), that each examined relational memory, as well as the flexible use of relational learning. Findings suggest that the development of relational memory precedes the development of the ability to use relational knowledge flexibly in novel situations. Implications for the development of underlying brain areas and ideas for future neuroimaging investigations are discussed.

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

Early adversity, for example poor caregiving, can have profound effects on emotional development. Orphanage rearing, even in the best circumstances, lies outside of the bounds of a species-typical caregiving environment. The long-term effects of this early adversity on the neurobiological development associated with socio-emotional behaviors are not well understood. Seventy-eight children, who include those who have experienced orphanage care and a comparison group, were assessed. Magnetic resonance imaging (MRI) was used to measure volumes of whole brain and limbic structures (e.g. amygdala, hippocampus). Emotion regulation was assessed with an emotional go-nogo paradigm, and anxiety and internalizing behaviors were assessed using the Screen for Child Anxiety Related Emotional Disorders, the Child Behavior Checklist, and a structured clinical interview. Late adoption was associated with larger corrected amygdala volumes, poorer emotion regulation, and increased anxiety. Although more than 50% of the children who experienced orphanage rearing met criteria for a psychiatric disorder, with a third having an anxiety disorder, the group differences observed in amygdala volume were not driven by the presence of an anxiety disorder. The findings are consistent with previous reports describing negative effects of prolonged orphanage care on emotional behavior and with animal models that show long-term changes in the amygdala and emotional behavior following early postnatal stress. These changes in limbic circuitry may underlie residual emotional and social problems experienced by children who have been internationally adopted.

There has been a dramatic rise in geneenvironment studies of human behavior over the past decade that have moved the field beyond simple nature versus nurture de- bates. These studies offer promise in accounting for more variability in behavioral and biological phenotypes than stud- ies that focus on genetic or experiential factors alone. They also provide clues into mechanisms of modifying genetic risk or resilience in neurodevelopmental disorders. Yet, it is rare that these studies consider how these interactions change over the course of development. In this paper, we describe research that focuses on the impact of a polymorphism in a brain-derived neurotrophic factor (BDNF) gene, known to be involved in learning and development. Specifically we present findings that assess the effects of genotypic and environmental loadings on neuroanatomic and behavioral phenotypes across development. The findings illustrate the use of a genetic mouse model that mimics the human poly- morphism, to constrain the interpretation of gene-environ- ment interactions across development in humans. © 2009

Structural and functional magnetic resonance imaging (MRI) are increasingly common research methods among investigators interested in typically and atypically developing populations. However, the effective use of these tools requires an understanding of the basis of the magnetic resonance signal, as well as some of the additional experimental complications that arise when collecting MRI data from developmental populations. This primer provides a foundation for investigators who wish to utilize MRI methods in their research and whose primary interest involves typically and atypically developing populations. The basic concepts of MRI physics are introduced, as well as the typical MRI scanner components and their role in MRI data acquisition. In addition, a variety of scan types (structural, functional, diffusion tensor) are discussed, along with a number of important experimental design factors that can impact the quality and utility of the data collected. Special consideration is given to working with pediatric and special populations.