Making Connections: Neurodevelopmental Changes in Brain Connectivity After Adverse Experiences in Early Adolescence.

Adverse childhood experiences have been linked to detrimental mental health outcomes in adulthood. This study investigates a potential neurodevelopmental pathway between adversity and mental health outcomes: brain connectivity. We used data from the prospective, longitudinal Adolescent Brain Cognitive Development (ABCD) study (N ≍ 12.000, participants aged 9-13 years, male and female) and assessed structural brain connectivity using fractional anisotropy (FA) of white matter tracts. The adverse experiences modeled included family conflict and traumatic experiences. K-means clustering and latent basis growth models were used to determine subgroups based on total levels and trajectories of brain connectivity. Multinomial regression was used to determine associations between cluster membership and adverse experiences. The results showed that higher family conflict was associated with higher FA levels across brain tracts (e.g., t (3) = -3.81, ß = -0.09, p bonf = 0.003) and within the corpus callosum (CC), fornix, and anterior thalamic radiations (ATR). A decreasing FA trajectory across two brain imaging timepoints was linked to lower socioeconomic status and neighborhood safety. Socioeconomic status was related to FA across brain tracts (e.g., t (3) = 3.44, ß = 0.10, p bonf = 0.01), the CC and the ATR. Neighborhood safety was associated with FA in the Fornix and ATR (e.g., t (1) = 3.48, ß = 0.09, p bonf = 0.01). There is a complex and multifaceted relationship between adverse experiences and brain development, where adverse experiences during early adolescence are related to brain connectivity. These findings underscore the importance of studying adverse experiences beyond early childhood to understand lifespan developmental outcomes.

A Hierarchical Watershed Model of Fluid Intelligence in Childhood and Adolescence.

Fluid intelligence is the capacity to solve novel problems in the absence of task-specific knowledge and is highly predictive of outcomes like educational attainment and psychopathology. Here, we modeled the neurocognitive architecture of fluid intelligence in two cohorts: the Centre for Attention, Leaning and Memory sample (CALM) (N = 551, aged 5-17 years) and the Enhanced Nathan Kline Institute-Rockland Sample (NKI-RS) (N = 335, aged 6-17 years). We used multivariate structural equation modeling to test a preregistered watershed model of fluid intelligence. This model predicts that white matter contributes to intermediate cognitive phenotypes, like working memory and processing speed, which, in turn, contribute to fluid intelligence. We found that this model performed well for both samples and explained large amounts of variance in fluid intelligence (R2CALM = 51.2%, R2NKI-RS = 78.3%). The relationship between cognitive abilities and white matter differed with age, showing a dip in strength around ages 7-12 years. This age effect may reflect a reorganization of the neurocognitive architecture around pre- and early puberty. Overall, these findings highlight that intelligence is part of a complex hierarchical system of partially independent effects.

Multimodal Integration and Vividness in the Angular Gyrus During Episodic Encoding and Retrieval.

Much evidence suggests that the angular gyrus (AnG) is involved in episodic memory, but its precise role has yet to be determined. We examined two possible accounts within the same experimental paradigm: the "cortical binding of relational activity" (CoBRA) account (Shimamura, 2011), which suggests that the AnG acts as a convergence zone that binds multimodal episodic features, and the subjectivity account (Yazar et al., 2012), which implicates AnG involvement in subjective mnemonic experience (such as vividness or confidence). fMRI was used during both encoding and retrieval of paired associates. During study, female and male human participants memorized picture-pairs of common objects (in the unimodal task) or of an object-picture and an environmental sound (in the crossmodal task). At test, they performed a cued-recall task and further indicated the vividness of their memory. During retrieval, BOLD activation in the AnG was greatest for vividly remembered associates, consistent with the subjectivity account. During encoding, the same effect of vividness was found, but this was further modulated by task: greater activations were associated with subsequent recall in the crossmodal than the unimodal task. Therefore, encoding data suggest an additional role to the AnG in crossmodal integration, consistent with its role at retrieval proposed by CoBRA. These results resolve some of the puzzles in the literature and indicate that the AnG can play different roles during encoding and retrieval as determined by the cognitive demands posed by different mnemonic tasks.SIGNIFICANCE STATEMENT We offer new insights into the multiplicity of processes that are associated with angular gyrus (AnG) activation during encoding and retrieval of newly formed memories. We used fMRI while human participants learned and subsequently recalled pairs of objects presented to the same sensory modality or to different modalities. We were able to show that the AnG is involved when vivid memories are created and retrieved, as well as when encoded information is integrated across different sensory modalities. These findings provide novel evidence for the contribution of the AnG to our subjective experience of remembering alongside its role in integrative processes that promote subsequent memory.

Age differences in the prosocial influence effect.

Social influence occurs when an individual's thoughts or behaviours are affected by other people. There are significant age effects on susceptibility to social influence, typically a decline from childhood to adulthood. Most research has focused on negative aspects of social influence, such as peer influence on risky behaviour, particularly in adolescence. The current study investigated the impact of social influence on the reporting of prosocial behaviour (any act intended to help another person). In this study, 755 participants aged 8-59 completed a computerized task in which they rated how likely they would be to engage in a prosocial behaviour. Afterwards, they were told the average rating (in fact fictitious) that other participants had given to the same question, and then were asked to rate the same behaviour again. We found that participants' age affected the extent to which they were influenced by other people: children (8-11 years), young adolescents (12-14 years) and mid-adolescents (15-18 years) all significantly changed their ratings, while young adults (19-25 years) and adults (26-59 years) did not. Across the three youngest age groups, children showed the most susceptibility to prosocial influence, changing their reporting of prosocial behaviour the most. The study provides evidence that younger people's increased susceptibility to social influence can have positive outcomes.

A Window of Opportunity for Cognitive Training in Adolescence.

In the current study, we investigated windows for enhanced learning of cognitive skills during adolescence. Six hundred thirty-three participants (11-33 years old) were divided into four age groups, and each participant was randomly allocated to one of three training groups. Each training group completed up to 20 days of online training in numerosity discrimination (i.e., discriminating small from large numbers of objects), relational reasoning (i.e., detecting abstract relationships between groups of items), or face perception (i.e., identifying differences in faces). Training yielded some improvement in performance on the numerosity-discrimination task, but only in older adolescents or adults. In contrast, training in relational reasoning improved performance on that task in all age groups, but training benefits were greater for people in late adolescence and adulthood than for people earlier in adolescence. Training did not increase performance on the face-perception task for any age group. Our findings suggest that for certain cognitive skills, training during late adolescence and adulthood yields greater improvement than training earlier in adolescence, which highlights the relevance of this late developmental stage for education.

Identifying characteristics of adolescents with persistent loneliness during COVID-19: A multi-country eight-wave longitudinal study.

Background: Elevated loneliness experiences characterise young people. While loneliness at this developmental juncture may emerge from age-typical upheaval in social relationships, there is little data on the extent to which young people experience high and persistent levels of loneliness, and importantly, who is most vulnerable to these experiences. Using the widespread social restrictions associated with the COVID-19 pandemic, which precipitated loneliness in many, we aimed to examine adolescents' loneliness profiles across time and the demographic predictors (age, sex, and country) of more severe trajectories. Methods: Participants aged 12-18 years, recruited into a multi-wave study (N = 1039) across three sites (UK, Israel, and India) completed a 3-item loneliness measure fortnightly across 8 timepoints during the pandemic. Results: Latent class growth analysis suggested 5 distinct trajectories: (1) low stable (33%), (2) low increasing (19%), (3) moderate decreasing (17%), (4) moderate stable (23%), and (5) high increasing (8%). Females and older adolescents were more likely to experience persistently high loneliness. Conclusions: These findings indicate a need for interventions to reduce loneliness in adolescents as we emerge from the pandemic, particularly for those groups identified as being at highest risk.

Networks of Adversity in Childhood and Adolescence and Their Relationship to Adult Mental Health.

Adverse experiences before the age of eighteen are common and include diverse events ranging from sexual abuse to parental divorce. These stressful experiences have been linked to physical and mental health issues. Previous research has focused mainly on childhood adversity, such as experiences in the family environment. Little consideration has been given to adversities that may be particularly harmful in adolescence. To understand adolescents' adverse experiences, this project used data from the Avon Longitudinal Study of Parents and Children (ALSPAC, total N = 14,901, N ≈ 1,200 - 10,000 per measure). We modelled interrelations of adversities in childhood (1-11 years) and adolescence (11-23 years) and examined adversity clusters using network analysis. We found two similar clusters in the childhood and adolescence networks: (1) direct abuse and (2) adverse family factors. We identified a third cluster of (3) educational and social adversities for adolescence. For both age groups, emotional abuse in the family environment was closely linked to mental health in early adulthood and most adversities were linked with depression in early adulthood. In adolescence, housing and academic issues and abuse by a romantic partner were particularly central to the network of adversities. Thus, we found commonalities and differences in the relevance of adverse experiences at different developmental stages. These findings highlight the need to develop age-dependent frameworks for adversity research and policymaking.

Longitudinal development of language and fine motor skills is correlated, but not coupled, in a childhood atypical cohort.

LAY ABSTRACT: More and more members of the autistic community and the research field are moving away from the idea that there will be a single biological or cognitive explanation for autistic characteristics. However, little is known about the complex dynamic processes that could explain why early difficulties in the language and motor domain often go hand-in-hand. We here study how language and motor skills develop simultaneously in the British Autism Study of Infant Siblings cohort of infants, and compare the way they are linked between children with and without developmental delays. Our results suggest that improvements in one domain go hand-in-hand with improvements in the other in both groups and show no compelling evidence for group differences in how motor skills relate to language and vice versa. We did observe a larger diversity in motor and language skills at 6 months, and because we found the motor and language development to be tightly linked, this suggests that even very small early impairments can result in larger developmental delays in later childhood. Greater variability at baseline, combined with very strong correlations between the slopes, suggests that dynamic processes may amplify small differences between individuals at 6months to result into large individual differences in autism symptomatology at 36 months.

Trajectories of adolescent life satisfaction.

Increasing global policy interest in measuring and improving population wellbeing has prompted academic investigations into the dynamics of lifespan life satisfaction. Yet little research has assessed the complete adolescent age range, although it harbours developmental changes that could affect wellbeing far into adulthood. This study investigates how life satisfaction develops throughout the whole of adolescence, and compares this development to that in adulthood, by applying exploratory and confirmatory latent growth curve modelling to UK and German data, respectively (37 076 participants, 10-24 years). We find a near universal decrease in life satisfaction during adolescence. This decrease is steeper than at any other point across adulthood. Further, our findings suggest that adolescent girls' life satisfaction is lower than boys', but that this difference does not extend into adulthood. The study highlights the importance of studying adolescent subjective wellbeing trajectories to inform research, policy and practice.

Using large, publicly available data sets to study adolescent development: opportunities and challenges.

Adolescence is a period of rapid change, with cognitive, mental wellbeing, environmental biological factors interacting to shape lifelong outcomes. Large, longitudinal phenotypically rich data sets available for reuse (secondary data) have revolutionized the way we study adolescence, allowing the field to examine these unfolding processes across hundreds or even thousands of individuals. Here, we outline the opportunities and challenges associated with such secondary data sets, provide an overview of particularly valuable resources available to the field, and recommend best practices to improve the rigor and transparency of analyses conducted on large, secondary data sets.

The effects of age on resting-state BOLD signal variability is explained by cardiovascular and cerebrovascular factors.

Accurate identification of brain function is necessary to understand neurocognitive aging, and thereby promote health and well-being. Many studies of neurocognitive aging have investigated brain function with the blood-oxygen level-dependent (BOLD) signal measured by functional magnetic resonance imaging. However, the BOLD signal is a composite of neural and vascular signals, which are differentially affected by aging. It is, therefore, essential to distinguish the age effects on vascular versus neural function. The BOLD signal variability at rest (known as resting state fluctuation amplitude, RSFA), is a safe, scalable, and robust means to calibrate vascular responsivity, as an alternative to breath-holding and hypercapnia. However, the use of RSFA for normalization of BOLD imaging assumes that age differences in RSFA reflecting only vascular factors, rather than age-related differences in neural function (activity) or neuronal loss (atrophy). Previous studies indicate that two vascular factors, cardiovascular health (CVH) and cerebrovascular function, are insufficient when used alone to fully explain age-related differences in RSFA. It remains possible that their joint consideration is required to fully capture age differences in RSFA. We tested the hypothesis that RSFA no longer varies with age after adjusting for a combination of cardiovascular and cerebrovascular measures. We also tested the hypothesis that RSFA variation with age is not associated with atrophy. We used data from the population-based, lifespan Cam-CAN cohort. After controlling for cardiovascular and cerebrovascular estimates alone, the residual variance in RSFA across individuals was significantly associated with age. However, when controlling for both cardiovascular and cerebrovascular estimates, the variance in RSFA was no longer associated with age. Grey matter volumes did not explain age differences in RSFA, after controlling for CVH. The results were consistent between voxel-level analysis and independent component analysis. Our findings indicate that cardiovascular and cerebrovascular signals are together sufficient predictors of age differences in RSFA. We suggest that RSFA can be used to separate vascular from neuronal factors, to characterize neurocognitive aging. We discuss the implications and make recommendations for the use of RSFA in the research of aging.

Neurocognitive reorganization between crystallized intelligence, fluid intelligence and white matter microstructure in two age-heterogeneous developmental cohorts.

Despite the reliability of intelligence measures in predicting important life outcomes such as educational achievement and mortality, the exact configuration and neural correlates of cognitive abilities remain poorly understood, especially in childhood and adolescence. Therefore, we sought to elucidate the factorial structure and neural substrates of child and adolescent intelligence using two cross-sectional, developmental samples (CALM: N = 551 (N = 165 imaging), age range: 5-18 years, NKI-Rockland: N = 337 (N = 65 imaging), age range: 6-18 years). In a preregistered analysis, we used structural equation modelling (SEM) to examine the neurocognitive architecture of individual differences in childhood and adolescent cognitive ability. In both samples, we found that cognitive ability in lower and typical-ability cohorts is best understood as two separable constructs, crystallized and fluid intelligence, which became more distinct across development, in line with the age differentiation hypothesis. Further analyses revealed that white matter microstructure, most prominently the superior longitudinal fasciculus, was strongly associated with crystallized (gc) and fluid (gf) abilities. Finally, we used SEM trees to demonstrate evidence for developmental reorganization of gc and gf and their white matter substrates such that the relationships among these factors dropped between 7-8 years before increasing around age 10. Together, our results suggest that shortly before puberty marks a pivotal phase of change in the neurocognitive architecture of intelligence.

Social exclusion affects working memory performance in young adolescent girls.

Adolescence has been proposed to be a sensitive period of social development, during which the social environment has a heightened effect on brain and behaviour. As such, negative social experiences, such as social exclusion, may have particularly detrimental effects on psychological well-being. However, little is known about how social exclusion affects cognitive performance during this time of life. Here, we compared the effects of exclusion between adolescence and adulthood. We recruited 98 females in three age groups: young adolescents (N = 36, aged 10.1-14.0), mid-adolescents (N = 35, aged 14.3-17.9) and adults (N = 27, aged 18.3-38.1). All age groups showed reductions in mood after exclusion, compared to inclusion, in a virtual ball-tossing game. Young adolescents also showed reduced verbal working memory accuracy following exclusion. There was no effect of exclusion on visuo-spatial working memory in any age group. These results suggest young adolescent girls' verbal working memory accuracy was affected by a short, virtual social exclusion experience. This highlights the importance of the social environment in adolescence and underlines the need to consider age differences in response to exclusion in the design and timing of social exclusion interventions in schools.

The neurocognitive correlates of academic diligence in adolescent girls.

Academic diligence is the ability to regulate behavior in the service of goals, and a predictor of educational attainment. Here we combined behavioral, structural MRI, functional MRI and connectivity data to investigate the neurocognitive correlates of diligence. We assessed whether individual differences in diligence are related to the interplay between frontal control and striatal reward systems, as predicted by the dual-systems hypothesis of adolescent development. We obtained behavioral measures of diligence from 40 adolescent girls (aged 14-15 years) using the Academic Diligence Task. We collected structural imaging data for each participant, as well as functional imaging data during an emotional go-no-go self-control task. As predicted by the dual-systems hypothesis, we found that inferior frontal activation and gyrification correlated with academic diligence. However, neither striatal activation nor structure, nor fronto-striatal connectivity, showed clear associations with diligence. Instead, we found prominent activation of temporal areas during the go-no-go task. This suggests that academic diligence is associated with an extended network of brain regions.

Strong and specific associations between cardiovascular risk factors and white matter micro- and macrostructure in healthy aging.

Cardiovascular health declines with age, increasing the risk of hypertension and elevated heart rate in middle and old age. Here, we used multivariate techniques to investigate the associations between cardiovascular health (diastolic blood pressure, systolic blood pressure, and heart rate) and white matter macrostructure (lesion volume and number) and microstructure (as measured by diffusion-weighted imaging) in the cross-sectional, population-based Cam-CAN cohort (N = 667, aged 18-88). We found that cardiovascular health and age made approximately similar contributions to white matter health and explained up to 56% of variance therein. Lower diastolic blood pressure, higher systolic blood pressure, and higher heart rate were each strongly, and independently, associated with white matter abnormalities on all indices. Body mass and exercise were associated with white matter health, both directly and indirectly via cardiovascular health. These results highlight the importance of cardiovascular risk factors for white matter health across the adult lifespan and suggest that systolic blood pressure, diastolic blood pressure, and heart rate affect white matter health via separate mechanisms.

The matrix reasoning item bank (MaRs-IB): novel, open-access abstract reasoning items for adolescents and adults.

Existing non-verbal ability tests are typically protected by copyright, preventing them from being freely adapted or computerized. Working towards an open science framework, we provide 80 novel, open-access abstract reasoning items, an online implementation and item-level data from 659 participants aged between 11 and 33 years: the matrix reasoning item bank (MaRs-IB). Each MaRs-IB item consists of an incomplete matrix containing abstract shapes. Participants complete the matrices by identifying relationships between the shapes. Our data demonstrate age differences in non-verbal reasoning accuracy, which increased during adolescence and stabilized in early adulthood. There was a slight linear increase in response times with age, resulting in a peak in efficiency (i.e. a measure combining speed and accuracy) in late adolescence. Overall, the data suggest that the MaRs-IB is sensitive to developmental differences in reasoning accuracy. Further psychometric validation is recommended.

The neural determinants of age-related changes in fluid intelligence: a pre-registered, longitudinal analysis in UK Biobank.

Background: Fluid intelligence declines with advancing age, starting in early adulthood. Within-subject declines in fluid intelligence are highly correlated with contemporaneous declines in the ability to live and function independently. To support healthy aging, the mechanisms underlying these declines need to be better understood. Methods: In this pre-registered analysis, we applied latent growth curve modelling to investigate the neural determinants of longitudinal changes in fluid intelligence across three time points in 185,317 individuals (N=9,719 two waves, N=870 three waves) from the UK Biobank (age range: 39-73 years). Results: We found a weak but significant effect of cross-sectional age on the mean fluid intelligence score, such that older individuals scored slightly lower. However, the mean longitudinal slope was positive, rather than negative, suggesting improvement across testing occasions. Despite the considerable sample size, the slope variance was non-significant, suggesting no reliable individual differences in change over time. This null-result is likely due to the nature of the cognitive test used. In a subset of individuals, we found that white matter microstructure (N=8839, as indexed by fractional anisotropy) and grey-matter volume (N=9931) in pre-defined regions-of-interest accounted for complementary and unique variance in mean fluid intelligence scores. The strongest effects were such that higher grey matter volume in the frontal pole and greater white matter microstructure in the posterior thalamic radiations were associated with higher fluid intelligence scores. Conclusions: In a large preregistered analysis, we demonstrate a weak but significant negative association between age and fluid intelligence. However, we did not observe plausible longitudinal patterns, instead observing a weak increase across testing occasions, and no significant individual differences in rates of change, likely due to the suboptimal task design. Finally, we find support for our preregistered expectation that white- and grey matter make separate contributions to individual differences in fluid intelligence beyond age.

Adolescence as a Sensitive Period of Brain Development.

Most research on sensitive periods has focussed on early sensory, motor, and language development, but it has recently been suggested that adolescence might represent a second 'window of opportunity' in brain development. Here, we explore three candidate areas of development that are proposed to undergo sensitive periods in adolescence: memory, the effects of social stress, and drug use. We describe rodent studies, neuroimaging, and large-scale behavioural studies in humans that have yielded data that are consistent with heightened neuroplasticity in adolescence. Critically however, concrete evidence for sensitive periods in adolescence is mostly lacking. To provide conclusive evidence, experimental studies are needed that directly manipulate environmental input and compare effects in child, adolescent, and adult groups.