brainlife.io: a decentralized and open-source cloud platform to support neuroscience research.

Neuroscience is advancing standardization and tool development to support rigor and transparency. Consequently, data pipeline complexity has increased, hindering FAIR (findable, accessible, interoperable and reusable) access. brainlife.io was developed to democratize neuroimaging research. The platform provides data standardization, management, visualization and processing and automatically tracks the provenance history of thousands of data objects. Here, brainlife.io is described and evaluated for validity, reliability, reproducibility, replicability and scientific utility using four data modalities and 3,200 participants.

Integrating data science and neuroscience in developmental psychopathology: Formative examples and future directions.

This commentary discusses opportunities for advancing the field of developmental psychopathology through the integration of data science and neuroscience approaches. We first review elements of our research program investigating how early life adversity shapes neurodevelopment and may convey risk for psychopathology. We then illustrate three ways that data science techniques (e.g., machine learning) can support developmental psychopathology research, such as by distinguishing between common and diverse developmental outcomes after stress exposure. Finally, we discuss logistical and conceptual refinements that may aid the field moving forward. Throughout the piece, we underscore the profound impact of Dr Dante Cicchetti, reflecting on how his work influenced our own, and gave rise to the field of developmental psychopathology.

Pathways to adolescent social anxiety: Testing interactions between neural social reward function and perceived social threat in daily life.

Recent theories suggest that for youth highly sensitive to incentives, perceiving more social threat may contribute to social anxiety (SA) symptoms. In 129 girls (ages 11-13) oversampled for shy/fearful temperament, we thus examined how interactions between neural responses to social reward (vs. neutral) cues (measured during anticipation of peer feedback) and perceived social threat in daily peer interactions (measured using ecological momentary assessment) predict SA symptoms two years later. No significant interactions emerged when neural reward function was modeled as a latent factor. Secondary analyses showed that higher perceived social threat was associated with more severe SA symptoms two years later only for girls with higher basolateral amygdala (BLA) activation to social reward cues at baseline. Interaction effects were specific to BLA activation to social reward (not threat) cues, though a main effect of BLA activation to social threat (vs. neutral) cues on SA emerged. Unexpectedly, interactions between social threat and BLA activation to social reward cues also predicted generalized anxiety and depression symptoms two years later, suggesting possible transdiagnostic risk pathways. Perceiving high social threat may be particularly detrimental for youth highly sensitive to reward incentives, potentially due to mediating reward learning processes, though this remains to be tested.

Probing multiple algorithms to calculate brain age: Examining reliability, relations with demographics, and predictive power.

The calculation of so-called "brain age" from structural MRIs has been an emerging biomarker in aging research. Data suggests that discrepancies between chronological age and the predicted age of the brain may be predictive of mortality and morbidity (for review, see Cole, Marioni, Harris, & Deary, 2019). However, with these promising results come technical complexities of how to calculate brain age. Various groups have deployed methods leveraging different statistical approaches, often crafting novel algorithms for assessing this biomarker derived from structural MRIs. There remain many open questions about the reliability, collinearity, and predictive power of different algorithms. Here, we complete a rigorous systematic comparison of three commonly used, previously published brain age algorithms (XGBoost, brainageR, and DeepBrainNet) to serve as a foundation for future applied research. First, using multiple datasets with repeated structural MRI scans, we calculated two metrics of reliability (intraclass correlations and Bland-Altman bias). We then considered correlations between brain age variables, chronological age, biological sex, and image quality. We also calculated the magnitude of collinearity between approaches. Finally, we used machine learning approaches to identify significant predictors across brain age algorithms related to clinical diagnoses of cognitive impairment. Using a large sample (N = 2557), we find all three commonly used brain age algorithms demonstrate excellent reliability (r > .9). We also note that brainageR and DeepBrainNet are reasonably correlated with one another, and that the XGBoost brain age is strongly related to image quality. Finally, and notably, we find that XGBoost brain age calculations were more sensitive to the detection of clinical diagnoses of cognitive impairment. We close this work with recommendations for future research studies focused on brain age.

Trajectories of cortical structures associated with stress across adolescence: a bivariate latent change score approach.

BACKGROUND: Stress exposure in childhood and adolescence has been linked to reductions in cortical structures and cognitive functioning. However, to date, most of these studies have been cross-sectional, limiting the ability to make long-term inferences, given that most cortical structures continue to develop through adolescence. METHODS: Here, we used a subset of the IMAGEN population cohort sample (N = 502; assessment ages: 14, 19, and 22 years; mean age: 21.945 years; SD = 0.610) to understand longitudinally the long-term interrelations between stress, cortical development, and cognitive functioning. To these ends, we first used a latent change score model to examine four bivariate relations - assessing individual differences in change in the relations between adolescent stress exposure and volume, surface area, and cortical thickness of cortical structures, as well as cognitive outcomes. Second, we probed for indirect neurocognitive effects linking stress to cortical brain structures and cognitive functions using rich longitudinal mediation modeling. RESULTS: Latent change score modeling showed that greater baseline adolescence stress at age 14 predicted a small reduction in the right anterior cingulate volume (Std. ß = -.327, p = .042, 95% CI [-0.643, -0.012]) and right anterior cingulate surface area (Std. ß = -.274, p = .038, 95% CI [-0.533, -0.015]) across ages 14-22. These effects were very modest in nature and became nonsignificant after correcting for multiple comparisons. Our longitudinal analyses found no evidence of indirect effects in the two neurocognitive pathways linking adolescent stress to brain and cognitive outcomes. CONCLUSION: Findings shed light on the impact of stress on brain reductions, particularly in the prefrontal cortex that have consistently been implicated in the previous cross-sectional studies. However, the magnitude of effects observed in our study is smaller than that has been reported in past cross-sectional work. This suggests that the potential impact of stress during adolescence on brain structures may likely be more modest than previously noted.

Femoral artery aneurysm with large hematoma from Pasteurella: case report and literature review.

BACKGROUND: Pasteurella multocida is a well-known gram-negative facultative anaerobe well known for its ability to cause soft tissue infections following animal bite or scratch. Here we present a case with mycotic aneurysm of the superficial femoral artery due to P. multocida infection. CASE PRESENTATION: A 62 year old male patient presented with worsening right leg pain and swelling. On examination, he was found to have profound swelling and erythema of the right medial thigh and tenderness to palpation. Computerized tomography showed findings suggestive of right femoral pseudoaneurysm with a large right medial thigh hematoma. Blood cultures grew P. multocida. Patient underwent emergent open resection of the mycotic aneurysm and vascular bypass surgery. Intraoperatively, the site was noted to be grossly infected with multiple pockets of pus which were drained and pus cultures grew P. multocida. The diagnosis of P. multocida bacteremia with right femoral mycotic aneurysm and thigh abscess was made. Patient received 6 weeks of intravenous ceftriaxone and recovered. CONCLUSION: Our case is the first report on infection of peripheral vessel with Pasteurella and highlights the importance of prompt surgical intervention and effective antibiotic treatment.

Developmental connections between socioeconomic status, self-regulation, and adult externalizing problems.

Children from low socioeconomic status (SES) backgrounds are at particularly heightened risk for developing later externalizing problems. A large body of research has suggested an important role for self-regulation in this developmental linkage. Self-regulation has been conceptualized as a mediator as well as a moderator of these connections. Using data from the Child Development Project (CDP, N = 585), we probe these contrasting (mediating/moderating) conceptualizations, using both Frequentist and Bayesian statistical approaches, in the linkage between early SES and later externalizing problems in a multi-decade longitudinal study. Connecting early SES, physiology (i.e., heart rate reactivity) and inhibitory control (a Stroop task) in adolescence, and externalizing symptomatology in early adulthood, we found the relation between SES and externalizing problems was moderated by multiple facets of self-regulation. Participants from lower early SES backgrounds, who also had high heart rate reactivity and lower inhibitory control, had elevated levels of externalizing problems in adulthood relative to those with low heart rate reactivity and better inhibitory control. Such patterns persisted after controlling for externalizing problems earlier in life. The present results may aid in understanding the combinations of factors that contribute to the development of externalizing psychopathology in economically marginalized youth.

Cumulative early childhood adversity and later antisocial behavior: The mediating role of passive avoidance.

Twenty-six percent of children experience a traumatic event by the age of 4. Negative events during childhood have deleterious correlates later in life, including antisocial behavior. However, the mechanisms that play into this relation are unclear. We explored deficits in neurocognitive functioning, specifically problems in passive avoidance, a construct with elements of inhibitory control and learning as a potential acquired mediator for the pathway between cumulative early childhood adversity from birth to age 7 and later antisocial behavior through age 18, using prospective longitudinal data from 585 participants. Path analyses showed that cumulative early childhood adversity predicted impaired passive avoidance during adolescence and increased antisocial behavior during late adolescence. Furthermore, poor neurocognition, namely, passive avoidance, predicted later antisocial behavior and significantly mediated the relation between cumulative early childhood adversity and later antisocial behavior. This research has implications for understanding the development of later antisocial behavior and points to a potential target for neurocognitive intervention within the pathway from cumulative early childhood adversity to later antisocial behavior.

Improved overall survival of melanoma of the head and neck treated with Mohs micrographic surgery versus wide local excision.

BACKGROUND: Optimal surgical management for melanoma of the head and neck remains controversial. OBJECTIVE: Assess outcomes for melanomas of the head and neck treated with Mohs micrographic surgery (MMS) versus wide local excision (WLE) from the National Cancer Database. METHODS: Head and neck melanoma data from the National Cancer Database from years 2004-2015 were analyzed. RESULTS: In total, 50,397 cases of head and neck melanoma were reviewed; 3510 (7%) were treated with MMS and 46,887 (93%) with WLE. After controlling for potential confounding variables, patients treated with MMS were more likely than patients treated with WLE to survive after 5 years (hazard ratio [HR] 1.181, 95% confidence interval [CI] 1.083-1.288; P < .001). Factors associated with a statistically significant survival disadvantage included male sex (HR 1.287, 95% CI 1.242-1.357; P = 0), tumor ulceration (HR 1.687, 95% CI 1.616-1.760; P = 0), and positive surgical margins (HR 1.395, 95% CI 1.306-1.490; P = 0). Patient survival was inversely proportional to tumor Breslow depth. LIMITATIONS: Database study, limited number of MMS treated melanomas. CONCLUSION: MMS is a valid treatment option for melanoma of the head and neck; National Cancer Database data suggests that MMS might confer a survival benefit over WLE.

Individual differences in executive function partially explain the socioeconomic gradient in middle-school academic achievement.

Children from families with low socioeconomic status (SES) earn lower grades, perform worse on achievement tests, and attain less education on average than their peers from higher-SES families. We evaluated neurocognitive mediators of SES disparities in achievement in a diverse sample of youth whose data were linked to administrative records of performance on school-administered tests of 7th grade reading and math proficiency (N = 203). We used structural equation modeling to evaluate whether associations between SES (measured at ages 8-9) and achievement (measured at age 13) are mediated by verbal ability and executive function (measured at age 10), a suite of top-down mental processes that facilitate control of thinking and behavior. Children from relatively higher-SES families performed better than their lower-SES peers on all neurocognitive and achievement measures, and SES disparities in both reading and math achievement were partially mediated by variation in executive function, but not verbal ability. SES disparities in executive function explained approximately 37% of the SES gap in math achievement and 17% of the SES gap in reading achievement. Exploratory modeling suggests that SES-related variation in working memory may play a particularly prominent role in mediation. We discuss potential implications of these findings for research, intervention programming, and classroom practice.

Retrospectively reported childhood physical abuse, systemic inflammation, and resting corticolimbic connectivity in midlife adults.

Childhood abuse confers risk for psychopathology and pathophysiology in midlife through intermediate pathways that remain unclear. Systemic inflammation was tested in the present study as one pathway that may link physical abuse in childhood to the adult functioning of corticolimbic brain circuits broadly implicated in risk for poor mental and physical health. Midlife adults (N = 303; 30-51 years of age; 149 women) without psychiatric, immune, or cardiovascular diagnoses provided retrospective reports of childhood physical abuse. Functional connectivity between corticolimbic brain areas (amygdala, hippocampus, ventromedial prefrontal cortex [vmPFC], anterior cingulate cortex [ACC]) was measured at rest using functional magnetic resonance imaging. Circulating levels of interleukin(IL)-6, a pro-inflammatory cytokine previously linked to childhood abuse and corticolimbic functionality, were measured via blood draw. Consistent with prior studies, retrospectively reported childhood physical abuse was associated positively with circulating IL-6, and negatively with connectivity between the amygdala and vmPFC. IL-6 was also associated negatively with several corticolimbic functional connections, including amygdala-vmPFC connectivity. Moreover, path analyses revealed an indirect effect of IL-6 that partially explained the association between childhood physical abuse and adult amygdala-vmPFC connectivity. Consistent with recent neurobiological models of early life influences on disease risk across the lifespan, associations between childhood physical abuse and adulthood corticolimbic circuit functionality may be partially explained by inflammatory processes.

Poverty and self-regulation: Connecting psychosocial processes, neurobiology, and the risk for psychopathology.

In the United States, over 40% of youth under the age of 18 live at or near the federal poverty line. Several decades of research have established clear links between exposure to child poverty and the development of psychopathology, yet the mechanisms that convey this risk remain unclear. We review research in developmental science and other allied disciplines that identify self-regulation as a critical factor that may influence the development of psychopathology after exposure to poverty. We then connect this work with neurobiological research in an effort to further inform these associations. We propose a starting framework focused on the neural correlates of self-regulation, and discuss recent work relating poverty to alterations in brain regions related to self-regulation. We close this review by highlighting important considerations for future research on poverty/socioeconomic status, neurobiology, self-regulation, and the risks related to the development of negative mental health outcomes.

A Family Focused Intervention Influences Hippocampal-Prefrontal Connectivity Through Gains in Self-Regulation.

The stressors associated with poverty increase the risks for externalizing psychopathology; however, specific patterns of neurobiology and higher self-regulation may buffer against these effects. This study leveraged a randomized control trial, aimed at increasing self-regulation at ~11 years of age. As adults, these same individuals completed functional MRI scanning (Mage  = 24.88 years; intervention n = 44; control n = 49). Functional connectivity between the hippocampus and ventromedial prefrontal cortex was examined in relation to the intervention, gains in self-regulation, and present-day externalizing symptoms. Increased connectivity between these brain areas was noted in the intervention group compared to controls. Furthermore, individual gains in self-regulation, instilled by the intervention, statistically explained this brain difference. These results begin to connect neurobiological and psychosocial markers of risk and resiliency.

Resting state coupling between the amygdala and ventromedial prefrontal cortex is related to household income in childhood and indexes future psychological vulnerability to stress.

While child poverty is a significant risk factor for poor mental health, the developmental pathways involved with these associations are poorly understood. To advance knowledge about these important linkages, the present study examined the developmental sequelae of childhood exposure to poverty in a multiyear longitudinal study. Here, we focused on exposure to poverty, neurobiological circuitry connected to emotion dysregulation, later exposure to stressful life events, and symptoms of psychopathology. We grounded our work in a biopsychosocial perspective, with a specific interest in "stress sensitization" and emotion dysregulation. Motivated by past work, we first tested whether exposure to poverty was related to changes in the resting-state coupling between two brain structures centrally involved with emotion processing and regulation (the amygdala and the ventromedial prefrontal cortex; vmPFC). As predicted, we found lower household income at age 10 was related to lower resting-state coupling between these areas at age 15. We then tested if variations in amygdala-vmPFC connectivity interacted with more contemporaneous stressors to predict challenges with mental health at age 16. In line with past reports showing risk for poor mental health is greatest in those exposed to early and then later, more contemporaneous stress, we predicted and found that lower vmPFC-amygdala coupling in the context of greater contemporaneous stress was related to higher levels of internalizing and externalizing symptoms. We believe these important interactions between neurobiology and life history are an additional vantage point for understanding risk and resiliency, and suggest avenues for prediction of psychopathology related to early life challenge.

Heightened connectivity between the ventral striatum and medial prefrontal cortex as a biomarker for stress-related psychopathology: understanding interactive effects of early and more recent stress.

BACKGROUND: The experience of childhood maltreatment is a significant risk factor for the development of depression. This risk is particularly heightened after exposure to additional, more contemporaneous stress. While behavioral evidence exists for this relation, little is known about biological correlates of these stress interactions. Identifying such correlates may provide biomarkers of risk for later depression. METHODS: Here, we leverage behavioral, experiential, and neuroimaging data from the Duke Neurogenetics Study to identify potential biomarkers of stress exposure. Based on the past research, we were specifically interested in reward-related connectivity and the interaction of early and more recent stress. We examined psychophysiological interactions between the ventral striatum and other brain regions in relation to these stress variables, as well as measures of internalizing symptomatology (n = 926, participant age range = 18-22 years of age). RESULTS: We found relatively increased reward-related functional connectivity between the left ventral striatum and the medial prefrontal cortex in individuals exposed to greater levels of childhood maltreatment who also experienced greater levels of recent life stress (ß = 0.199, p < 0.005). This pattern of functional connectivity was further associated with elevated symptoms of depression (ß = 0.089, p = 0.006). Furthermore, using a moderated mediation framework, we demonstrate that this functional connectivity provides a biological link between cumulative stress exposure and internalizing symptomatology. CONCLUSIONS: These findings suggest a novel biomarker linking cumulative stress exposure with the later experience of depressive symptoms. Our results are discussed in the context of past research examining stress exposure in relation to depression.

Instrumental learning and cognitive flexibility processes are impaired in children exposed to early life stress.

Children who experience severe early life stress show persistent deficits in many aspects of cognitive and social adaptation. Early stress might be associated with these broad changes in functioning because it impairs general learning mechanisms. To explore this possibility, we examined whether individuals who experienced abusive caregiving in childhood had difficulties with instrumental learning and/or cognitive flexibility as adolescents. Fifty-three 14-17-year-old adolescents (31 exposed to high levels of childhood stress, 22 control) completed an fMRI task that required them to first learn associations in the environment and then update those pairings. Adolescents with histories of early life stress eventually learned to pair stimuli with both positive and negative outcomes, but did so more slowly than their peers. Furthermore, these stress-exposed adolescents showed markedly impaired cognitive flexibility; they were less able than their peers to update those pairings when the contingencies changed. These learning problems were reflected in abnormal activity in learning- and attention-related brain circuitry. Both altered patterns of learning and neural activation were associated with the severity of lifetime stress that the adolescents had experienced. Taken together, the results of this experiment suggest that basic learning processes are impaired in adolescents exposed to early life stress. These general learning mechanisms may help explain the emergence of social problems observed in these individuals.

Early adversity and learning: implications for typical and atypical behavioral development.

BACKGROUND: Children who experience early adversity often develop emotion regulatory problems, but little is known about the mechanisms that mediate this relation. We tested whether general associative learning processes contribute to associations between adversity, in the form of child maltreatment, and negative behavioral outcomes. METHODS: Eighty-one participants between 12 and 17 years of age were recruited for this study and completed a probabilistic learning Task. Forty-one of these participants had been exposed to physical abuse, a form of early adversity. Forty additional participants without any known history of maltreatment served as a comparison group. All participants (and their parents) also completed portions of the Youth Life Stress Interview to understand adolescent's behavior. We calculated measures of associative learning, and also constructed mathematical models of learning. RESULTS: We found that adolescents exposed to high levels of adversity early in their lives had lower levels of associative learning than comparison adolescents. In addition, we found that impaired associative learning partially explained the higher levels of behavioral problems among youth who suffered early adversity. Using mathematical models, we also found that two components of learning were specifically affected in children exposed to adversity: choice variability and biases in their beliefs about the likelihood of rewards in the environment. CONCLUSIONS: Participants who had been exposed to early adversity were less able than their peers to correctly learn which stimuli were likely to result in reward, even after repeated feedback. These individuals also used information about known rewards in their environments less often. In addition, individuals exposed to adversity made decisions early in the learning process as if rewards were less consistent and occurred more at random. These data suggest one mechanism through which early life experience shapes behavioral development.