While most measures of working memory (WM) performance have been shown to plateau by mid-adolescence and developmental changes in fronto-parietal regions supporting WM encoding and maintenance have been well characterized, little is known about developmental variation in WM filtering. We investigated the possibility that the neural underpinnings of filtering in WM reach maturity later in life than WM function without filtering. Using a cued WM filtering task (McNab and Klingberg, 2008), we investigated neural activity during WM filtering in a sample of 64 adults and adolescents. Regardless of age, increases in WM activity with load were concentrated in the expected fronto-parietal network. For adults, but not adolescents, recruitment of the basal ganglia during presentation of a filtering cue was associated with neural and behavioral indices of successful filtering, suggesting that WM filtering and related basal ganglia function may still be maturing throughout adolescence and into adulthood.

The prefrontal cortex (PFC) develops from birth through late adolescence. This extended developmental trajectory provides many opportunities for experience to shape the structure and function of the PFC. To date, a few studies have reported links between parental socioeconomic status (SES) and prefrontal function in childhood, raising the possibility that aspects of environment associated with SES impact prefrontal function. Considering that behavioral measures of prefrontal function are associated with learning across multiple domains, this is an important area of investigation. In this study, we used fMRI to replicate previous findings, demonstrating an association between parental SES and PFC function during childhood. In addition, we present two hypothetical mechanisms by which SES could come to affect PFC function of this association: language environment and stress reactivity. We measured language use in the home environment and change in salivary cortisol before and after fMRI scanning. Complexity of family language, but not the child's own language use, was associated with both parental SES and PFC activation. Change in salivary cortisol was also associated with both SES and PFC activation. These observed associations emphasize the importance of both enrichment and adversity-reduction interventions in creating good developmental environments for all children.

Attention-deficit hyperactivity disorder (ADHD) is the most commonly diagnosed psychological disorder of childhood. Medication and cognitive behavioral therapy are effective treatments for many children; however, adherence to medication and therapy regimens is low. Thus, identifying effective adjunct treatments is imperative. Previous studies exploring computerized training programs as supplementary treatments have targeted working memory or attention. However, many lines of research suggest inhibitory control (IC) plays a central role in ADHD pathophysiology, which makes IC a potential intervention target. In this randomized control trial (NCT03363568), we target IC using a modified stop-signal task (SST) training designed by NeuroScouting, LLC in 40 children with ADHD, aged 8 to 11 years. Children were randomly assigned to adaptive treatment (n = 20) or non-adaptive control (n = 20) with identical stimuli and task goals. Children trained at home for at least 5 days a week (about 15m/day) for 4-weeks. Relative to the control group, the treatment group showed decreased relative theta power in resting EEG and trending improvements in parent ratings of attention (i.e. decreases in inattentive behaviors). Both groups showed improved SST performance. There was not evidence for treatment effects on hyperactivity or teacher ratings of symptoms. Results suggest training IC alone has potential to positively impact symptoms of ADHD and provide evidence for neural underpinnings of this impact (change in theta power; change in N200 latency). This shows promising initial results for the use of computerized training of IC in children with ADHD as a potential adjunct treatment option for children with ADHD.

The neural processes that support inhibitory control in the face of stimuli with a history of reward association are not yet well understood. Yet, the ability to flexibly adapt behavior to changing reward-contingency contexts is important for daily functioning and warrants further investigation. This study aimed to characterize neural and behavioral impacts of stimuli with a history of conditioned reward association on motor inhibitory control in healthy young adults by investigating group-level effects as well as individual variation in the ability to inhibit responses to stimuli with a reward history. Participants (N = 41) first completed a reward conditioning phase, during which responses to rewarded stimuli were associated with money and responses to unrewarded stimuli were not. Rewarded and unrewarded stimuli from training were carried forward as No-Go targets in a subsequent go/no-go task to test the effect of reward history on inhibitory control. Participants underwent functional brain imaging during the go/no-go portion of the task. On average, a history of reward conditioning disrupted inhibitory control. Compared to inhibition of responses to stimuli with no reward history, trials that required inhibition of responses to previously rewarded stimuli were associated with greater activity in frontal and striatal regions, including the inferior frontal gyrus, insula, striatum, and thalamus. Activity in the insula and thalamus during false alarms and in the ventromedial prefrontal cortex during correctly withheld trials predicted behavioral performance on the task. Overall, these results suggest that reward history serves to disrupt inhibitory control and provide evidence for diverging roles of the insula and ventromedial prefrontal cortex while inhibiting responses to stimuli with a reward history.

A growing number of studies have examined alterations in white matter organization in people with posttraumatic stress disorder (PTSD) using diffusion MRI (dMRI), but the results have been mixed which may be partially due to relatively small sample sizes among studies. Altered structural connectivity may be both a neurobiological vulnerability for, and a result of, PTSD. In an effort to find reliable effects, we present a multi-cohort analysis of dMRI metrics across 3047 individuals from 28 cohorts currently participating in the PGC-ENIGMA PTSD working group (a joint partnership between the Psychiatric Genomics Consortium and the Enhancing NeuroImaging Genetics through Meta-Analysis consortium). Comparing regional white matter metrics across the full brain in 1426 individuals with PTSD and 1621 controls (2174 males/873 females) between ages 18-83, 92% of whom were trauma-exposed, we report associations between PTSD and disrupted white matter organization measured by lower fractional anisotropy (FA) in the tapetum region of the corpus callosum (Cohen's d = -0.11, p = 0.0055). The tapetum connects the left and right hippocampus, for which structure and function have been consistently implicated in PTSD. Results were consistent even after accounting for the effects of multiple potentially confounding variables: childhood trauma exposure, comorbid depression, history of traumatic brain injury, current alcohol abuse or dependence, and current use of psychotropic medications. Our results show that PTSD may be associated with alterations in the broader hippocampal network.

The interactions of brain regions with other regions at the network level likely provide the infrastructure necessary for cognitive processes to develop. Specifically, it has been theorized that in infancy brain networks become more modular, or segregated, to support early cognitive specialization, before integration across networks increases to support the emergence of higher-order cognition. The present study examined the maturation of structural covariance networks (SCNs) derived from longitudinal cortical thickness data collected between infancy and childhood (0-6 years). We assessed modularity as a measure of network segregation and global efficiency as a measure of network integration. At the group level, we observed trajectories of increasing modularity and decreasing global efficiency between early infancy and six years. We further examined subject-based maturational coupling networks (sbMCNs) in a subset of this cohort with cognitive outcome data at 8-10 years, which allowed us to relate the network organization of longitudinal cortical thickness maturation to cognitive outcomes in middle childhood. We found that lower global efficiency of sbMCNs throughout early development (across the first year) related to greater motor learning at 8-10 years. Together, these results provide novel evidence characterizing the maturation of brain network segregation and integration across the first six years of life, and suggest that specific trajectories of brain network maturation contribute to later cognitive outcomes.

The dimensional model of adversity proposes that experiences of threat and deprivation have distinct neurodevelopmental consequences. We examined these dimensions, separately and jointly, with brain structure in a sample of 149 youth aged 8-17-half recruited based on exposure to threat-related experiences. We predicted that greater threat would be uniquely associated with reduced cortical thickness and surface area in brain regions associated with salience processing including ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC), and insula, and that deprivation experiences would be uniquely associated with reductions in cortical thickness and surface area in frontoparietal areas associated with cognitive control. As predicted, greater threat was associated with thinner cortex in a network including areas involved in salience processing (anterior insula, vmPFC), and smaller amygdala volume (particularly in younger participants), after controlling for deprivation. Contrary to our hypotheses, threat was also associated with thinning in the frontoparietal control network. However, these associations were reduced following control for deprivation. No associations were found between deprivation and brain structure. This examination of deprivation and threat concurrently in the same sample provided further evidence that threat-related experiences influence the structure of the developing brain independent of deprivation.

Although there is evidence that family violence increased in the United States during the COVID-19 pandemic, few studies have characterized longitudinal trends in family violence across the course of initial stay-at-home orders.

The MGH-USC CONNECTOM MRI scanner housed at the Massachusetts General Hospital (MGH) is a major hardware innovation of the Human Connectome Project (HCP). The 3T CONNECTOM scanner is capable of producing a magnetic field gradient of up to 300 mT/m strength for in vivo human brain imaging, which greatly shortens the time spent on diffusion encoding, and decreases the signal loss due to T2 decay. To demonstrate the capability of the novel gradient system, data of healthy adult participants were acquired for this MGH-USC Adult Diffusion Dataset (N=35), minimally preprocessed, and shared through the Laboratory of Neuro Imaging Image Data Archive (LONI IDA) and the WU-Minn Connectome Database (ConnectomeDB). Another purpose of sharing the data is to facilitate methodological studies of diffusion MRI (dMRI) analyses utilizing high diffusion contrast, which perhaps is not easily feasible with standard MR gradient system. In addition, acquisition of the MGH-Harvard-USC Lifespan Dataset is currently underway to include 120 healthy participants ranging from 8 to 90 years old, which will also be shared through LONI IDA and ConnectomeDB. Here we describe the efforts of the MGH-USC HCP consortium in acquiring and sharing the ultra-high b-value diffusion MRI data and provide a report on data preprocessing and access. We conclude with a demonstration of the example data, along with results of standard diffusion analyses, including q-ball Orientation Distribution Function (ODF) reconstruction and tractography.

During adolescence, rapid development and reorganization of the dopaminergic system supports increasingly sophisticated reward learning and the ability to exert behavioral control. Disruptions in the ability to exert control over previously rewarded behavior may underlie some forms of adolescent psychopathology. Specifically, symptoms of externalizing psychopathology may be associated with difficulties in flexibly adapting behavior in the context of reward. However, the direct interaction of cognitive control and reward learning in adolescent psychopathology symptoms has not yet been investigated. The present study used a Research Domain Criteria framework to investigate whether behavioral and neuronal indices of inhibition to previously rewarded stimuli underlie individual differences in externalizing symptoms in N = 61 typically developing adolescents. Using a task that integrates the Monetary Incentive Delay and Go-No-Go paradigms, we observed a positive association between externalizing symptoms and activation of the left middle frontal gyrus during response inhibition to cues with a history of reward. These associations were robust to controls for internalizing symptoms and neural recruitment during inhibition of cues with no reward history. Our findings suggest that inhibitory control over stimuli with a history of reward may be a useful marker for future inquiry into the development of externalizing psychopathology in adolescence.

Growing evidence suggests that childhood socioeconomic status (SES) influences neural development, which may contribute to the well-documented SES-related disparities in academic achievement. However, the particular aspects of SES that impact neural structure and function are not well understood. Here, we investigate associations of childhood SES and a potential mechanism-degree of cognitive stimulation in the home environment-with cortical structure, white matter microstructure, and neural function during a working memory (WM) task across development. Analyses included 53 youths (age 6-19 years). Higher SES as reflected in the income-to-needs ratio was associated with higher parent-reported achievement, WM performance, and cognitive stimulation in the home environment. Although SES was not significantly associated with cortical thickness, children raised in more cognitively stimulating environments had thicker cortex in the frontoparietal network and cognitive stimulation mediated the assocation between SES and cortical thickness in the frontoparietal network. Higher family SES was associated with white matter microstructure and neural activation in the frontoparietal network during a WM task, including greater fractional anisotropy (FA) in the right and left superior longitudinal fasciculi (SLF), and greater BOLD activation in multiple regions of the prefrontal cortex during WM encoding and maintenance. Greater FA and activation in these regions was associated higher parent-reported achievement. Together, cognitive stimulation, WM performance, FA in the SLF, and prefrontal activation during WM encoding and maintenance significantly mediated the association between SES and parent-reported achievement. These findings highlight potential neural, cognitive, and environmental mechanisms linking SES with academic achievement and suggest that enhancing cognitive stimulation in the home environment might be one effective strategy for reducing SES-related disparities in academic outcomes.

Hypotheses concerning the biologic embedding of early adversity via developmental neuroplasticity mechanisms have been proposed on the basis of experimental studies in animals. However, no studies have demonstrated a causal link between early adversity and neural development in humans. Here, we present evidence from a randomized controlled trial linking psychosocial deprivation in early childhood to changes in cortical development from childhood to adolescence using longitudinal data from the Bucharest Early Intervention Project. Changes in cortical structure due to randomization to foster care were most pronounced in the lateral and medial prefrontal cortex and in white matter tracts connecting the prefrontal and parietal cortex. Demonstrating the causal impact of exposure to deprivation on the development of neural structure highlights the importance of early placement into family-based care to mitigate lasting neurodevelopmental consequences associated with early-life deprivation.

Identifying brain alterations associated with suicidal thoughts and behaviors (STBs) in young people is critical to understanding their development and improving early intervention and prevention. The ENIGMA Suicidal Thoughts and Behaviours (ENIGMA-STB) consortium analyzed neuroimaging data harmonized across sites to examine brain morphology associated with STBs in youth. We performed analyses in three separate stages, in samples ranging from most to least homogeneous in terms of suicide assessment instrument and mental disorder. First, in a sample of 577 young people with mood disorders, in which STBs were assessed with the Columbia Suicide Severity Rating Scale (C-SSRS). Second, in a sample of young people with mood disorders, in which STB were assessed using different instruments, MRI metrics were compared among healthy controls without STBs (HC; N = 519), clinical controls with a mood disorder but without STBs (CC; N = 246) and young people with current suicidal ideation (N = 223). In separate analyses, MRI metrics were compared among HCs (N = 253), CCs (N = 217), and suicide attempters (N = 64). Third, in a larger transdiagnostic sample with various assessment instruments (HC = 606; CC = 419; Ideation = 289; HC = 253; CC = 432; Attempt=91). In the homogeneous C-SSRS sample, surface area of the frontal pole was lower in young people with mood disorders and a history of actual suicide attempts (N = 163) than those without a lifetime suicide attempt (N = 323; FDR-p = 0.035, Cohen's d = 0.34). No associations with suicidal ideation were found. When examining more heterogeneous samples, we did not observe significant associations. Lower frontal pole surface area may represent a vulnerability for a (non-interrupted and non-aborted) suicide attempt; however, more research is needed to understand the nature of its relationship to suicide risk.

Many studies report smaller hippocampal and amygdala volumes in posttraumatic stress disorder (PTSD), but findings have not always been consistent. Here, we present the results of a large-scale neuroimaging consortium study on PTSD conducted by the Psychiatric Genomics Consortium (PGC)-Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) PTSD Working Group.

Adolescence is the peak age for both victimization and mental disorder onset. Previous research has reported associations between victimization exposure and many psychiatric conditions. However, causality remains controversial. Within the Environmental Risk Longitudinal Twin Study, we tested whether seven types of adolescent victimization increased risk of multiple psychiatric conditions and approached causal inference by systematically ruling out noncausal explanations. Longitudinal within-individual analyses showed that victimization was followed by increased mental health problems over a childhood baseline of emotional/behavioral problems. Discordant-twin analyses showed that victimization increased risk of mental health problems independent of family background and genetic risk. Both childhood and adolescent victimization made unique contributions to risk. Victimization predicted heightened generalized liability (the "p factor") to multiple psychiatric spectra, including internalizing, externalizing, and thought disorders. Results recommend violence reduction and identification and treatment of adolescent victims to reduce psychiatric burden.

Little is known about how childhood adversity influences the development of learning and memory and underlying neural circuits. We examined whether violence exposure in childhood influenced hippocampus-dependent associative learning and whether differences: a) were broad or specific to threat cues, and b) exhibited developmental variation. Children (n = 59; 8-19 years, 24 violence-exposed) completed an associative learning task with angry, happy, and neutral faces paired with objects during fMRI scanning. Outside the scanner, participants completed an associative memory test for face-object pairings. Violence-exposed children exhibited broad associative memory difficulties that became more pronounced with age, along with reduced recruitment of the hippocampus and atypical recruitment of fronto-parietal regions during encoding. Violence-exposed children also showed selective disruption of associative memory for threat cues regardless of age, along with reduced recruitment of the intraparietal sulcus (IPS) during encoding in the presence of threat. Broad associative learning difficulties may be a functional consequence of the toxic effects of early-life stress on hippocampal and fronto-parietal cortical development. Difficulties in the presence of threat cues may result from enhanced threat processing that disrupts encoding and short-term storage of associative information in the IPS. These associative learning difficulties may contribute to poor life outcomes following childhood violence exposure.

Despite calls to incorporate population science into neuroimaging research, most studies recruit small, non-representative samples. Here, we examine whether sample composition influences age-related variation in global measurements of gray matter volume, thickness, and surface area. We apply sample weights to structural brain imaging data from a community-based sample of children aged 3-18 (N = 1162) to create a "weighted sample" that approximates the distribution of socioeconomic status, race/ethnicity, and sex in the U.S. Census. We compare associations between age and brain structure in this weighted sample to estimates from the original sample with no sample weights applied (i.e., unweighted). Compared to the unweighted sample, we observe earlier maturation of cortical and sub-cortical structures, and patterns of brain maturation that better reflect known developmental trajectories in the weighted sample. Our empirical demonstration of bias introduced by non-representative sampling in this neuroimaging cohort suggests that sample composition may influence understanding of fundamental neural processes.The influence of sample composition on human neuroimaging results is unknown. Here, the authors weight a large, community-based sample to better reflect the US population and describe how applying these sample weights changes conclusions about age-related variation in brain structure.

Children exposed to early-life psychosocial deprivation associated with institutional rearing are at markedly elevated risk of developing attention-deficit/hyperactivity disorder (ADHD). Neurodevelopmental mechanisms that explain the high prevalence of ADHD in children exposed to institutionalization are unknown. We examined whether abnormalities in cortical thickness and subcortical volume were mechanisms explaining elevations in ADHD among children raised in institutional settings.

Across development children show marked improvement in their executive functions (EFs), including the ability to hold information in working memory and to deploy cognitive control, allowing them to ignore prepotent responses in favor of newly learned behaviors. How does the brain support these age-related improvements? Age-related cortical gray-matter thinning, thought to result from selective pruning of inefficient synaptic connections and increases in myelination, may support age-related improvements in EFs. Here we used structural MRI to measure cortical thickness. We investigate the association between cortical thickness in three cortical regions of interest (ROIs), and age-related changes in cognitive control and working memory in 5-10 year old children. We found significant associations between reductions in cortical thickness and age-related improvements in performance on both working memory and cognitive control tasks. Moreover, we observed a dissociation between ROIs typically thought to underlie changes in cognitive control (right Inferior Frontal gyrus and Anterior Cingulate cortex) and age-related improvements in cognitive control, and ROIs for working memory (superior parietal cortex), and age-related changes in a working memory task. These data add to our growing understanding of how structural maturation of the brain supports vast behavioral changes in executive functions observed across childhood.

Adolescence is a period of increased vulnerability for internalizing problems, particularly following stressful life events. We examined how emotion regulation and brain structure and function were associated with internalizing problems during the COVID-19 pandemic and moderated the association between pandemic-related stressors and internalizing problems.