Global topology of human connectome is insensitive to early life environments - A prospective longitudinal study of the general population.

The widely acknowledged detrimental impact of early adversity on child development has driven efforts to understand the underlying mechanisms that may mediate these effects within the developing brain. Recent efforts have begun to move beyond associating adversity with the morphology of individual brain regions towards determining if and how adversity might shape their interconnectivity. However, whether adversity effects a global shift in the organisation of whole-brain networks remains unclear. In this study, we assessed this possibility using parental questionnaire and diffusion imaging data from The Avon Longitudinal Study of Parents and Children (ALSPAC, N = 913), a prospective longitudinal study spanning more than 20 years. We tested whether a wide range of adversities-including experiences of abuse, domestic violence, physical and emotional cruelty, poverty, neglect, and parental separation-measured by questionnaire within the first seven years of life were significantly associated with the tractography-derived connectome in young adulthood. We tested this across multiple measures of organisation and using a computational model that simulated the wiring economy of the brain. We found no significant relationships between early exposure to any form of adversity and the global organisation of the structural connectome in young adulthood. We did detect local differences in the medial prefrontal cortex, as well as an association between weaker brain wiring constraints and greater externalising behaviour in adolescence. Our results indicate that further efforts are necessary to delimit the magnitude and functional implications of adversity-related differences in connectomic organization. RESEARCH HIGHLIGHTS: Diverse prospective measures of the early-life environment do not predict the organisation of the DTI tractography-derived connectome in young adulthood Wiring economy of the connectome is weakly associated with externalising in adolescence, but not internalising or cognitive ability Further work is needed to establish the scope and significance of global adversity-related differences in the structural connectome.

Mapping neurodevelopmental diversity in executive function.

Executive function, an umbrella term used to describe the goal-directed regulation of thoughts, actions, and emotions, is an important dimension implicated in neurodiversity and established malleable predictor of multiple adult outcomes. Neurodevelopmental differences have been linked to both executive function strengths and weaknesses, but evidence for associations between specific profiles of executive function and specific neurodevelopmental conditions is mixed. In this exploratory study, we adopt an unsupervised machine learning approach (self-organising maps), combined with k-means clustering to identify data-driven profiles of executive function in a transdiagnostic sample of 566 neurodivergent children aged 8-18 years old. We include measures designed to capture two distinct aspects of executive function: performance-based tasks designed to tap the state-like efficiency of cognitive skills under optimal conditions, and behaviour ratings suited to capturing the trait-like application of cognitive control in everyday contexts. Three profiles of executive function were identified: one had consistent difficulties across both types of assessments, while the other two had inconsistent profiles of predominantly rating- or predominantly task-based difficulties. Girls and children without a formal diagnosis were more likely to have an inconsistent profile of primarily task-based difficulties. Children with these different profiles had differences in academic achievement and mental health outcomes and could further be differentiated from a comparison group of children on both shared and profile-unique patterns of neural white matter organisation. Importantly, children's executive function profiles were not directly related to diagnostic categories or to dimensions of neurodiversity associated with specific diagnoses (e.g., hyperactivity, inattention, social communication). These findings support the idea that the two types of executive function assessments provide non-redundant information related to children's neurodevelopmental differences and that they should not be used interchangeably. The findings advance our understanding of executive function profiles and their relationship to behavioural outcomes and neural variation in neurodivergent populations.

Cognitive difficulties following adversity are not related to mental health: Findings from the ABCD study.

Early life adversity is associated with differences in cognition and mental health that can impact on daily functioning. This study uses a hybrid machine-learning approach that combines random forest classification with hierarchical clustering to clarify whether there are cognitive differences between individuals who have experienced moderate-to-severe adversity relative to those have not experienced adversity, to explore whether different forms of adversity are associated with distinct cognitive alterations and whether these such alterations are related to mental health using data from the ABCD study (n = 5,955). Cognitive measures spanning language, reasoning, memory, risk-taking, affective control, and reward processing predicted whether a child had a history of adversity with reasonable accuracy (67%), and with good specificity and sensitivity (>70%). Two subgroups were identified within the adversity group and two within the no-adversity group that were distinguished by cognitive ability (low vs high). There was no evidence for specific associations between the type of adverse exposure and cognitive profile. Worse cognition predicted lower levels of mental health in unexposed children. However, while children who experience adversity had elevated mental health difficulties, their mental health did not differ as a function of cognitive ability, thus providing novel insight into the heterogeneity of psychiatric risk.

Early adversity changes the economic conditions of mouse structural brain network organization.

Early adversity can change educational, cognitive, and mental health outcomes. However, the neural processes through which early adversity exerts these effects remain largely unknown. We used generative network modeling of the mouse connectome to test whether unpredictable postnatal stress shifts the constraints that govern the organization of the structural connectome. A model that trades off the wiring cost of long-distance connections with topological homophily (i.e., links between regions with shared neighbors) generated simulations that successfully replicate the rodent connectome. The imposition of early life adversity shifted the best-performing parameter combinations toward zero, heightening the stochastic nature of the generative process. Put simply, unpredictable postnatal stress changes the economic constraints that reproduce rodent connectome organization, introducing greater randomness into the development of the simulations. While this change may constrain the development of cognitive abilities, it could also reflect an adaptive mechanism that facilitates effective responses to future challenges.

Dimensions of internalizing symptoms are stable across early adolescence and predicted by executive functions: Longitudinal findings from the Adolescent Brain and Cognitive Development (ABCD) study.

Early adolescence is characterized by rapid changes in executive function and increased vulnerability to internalizing difficulties. The aim of this study was to explore whether internalizing symptoms are stable across early adolescence and to identify possible links with executive function. Using data from the Adolescent Brain and Cognitive Development Study (ABCD), we identified four dimensions of internalizing symptoms from item-level ratings on the Child Behavior Checklist at ages 10 (n = 10,841) and 12 (n = 5,846), with an invariant factor structure across time. These dimensions corresponded to anxiety, depression, withdrawal, and somatic problems. We then examined associations between these dimensions and three aspects of executive function at age 10 measured by the NIH Toolbox: inhibition, shifting and working memory. Worse shifting and inhibition at age 10 was associated with elevated symptoms of anxiety and withdrawal cross-sectionally, while poor inhibition was also uniquely associated with symptoms of depression. Longitudinal associations were more limited: Worse inhibition at age 10 predicted greater symptoms of withdrawal at age 12, while worse shifting predicted fewer symptoms of anxiety 2 years later. These findings suggest that poor executive function in early adolescence is associated with greater internalizing difficulties and poor inhibition may contribute to later social withdrawal.

A meta-analytic review of the impact of ADHD medications on anxiety and depression in children and adolescents.

Anxiety and depression are listed as common side effects for medications licensed for treating ADHD in children and adolescents. This meta-analytic review of randomised controlled trials aimed to explore the effect of medications on symptoms of anxiety and depression in children and adolescents with ADHD. A meta-analytic review of ADHD drug trials in children and adolescents was conducted. Random effects meta-analyses were conducted on anxiety and depression outcomes measured by validated psychological scales or side effect rating scales. Only 11% of eligible trials in this review reported anxiety and/or depression as an outcome or side effect, limiting the conclusions of the meta-analyses. Relative to placebo control, no significant effect of medication was found for symptoms of anxiety or depression in randomised controlled trials of ADHD medication in children and adolescents. This review highlights the systemic lack of mental health outcome reporting in child and adolescent ADHD drug trials. The importance of widespread implementation of standardised measurement of mental health outcomes in future trials is discussed.

Cognitive segmentation and fluid reasoning in childhood.

The ability to solve novel complex problems predicts success in a wide range of areas. Recent research suggests that the ability to cognitively segment complex problems into smaller parts constrains nonverbal reasoning in adults. This study aimed to test whether cognitively segmenting problems improves nonverbal reasoning performance for children as it does for adults. A total of 115 children aged 6-10 years completed two versions of a modified traditional matrix reasoning task in which demands on working memory, integration, and processing speed were minimised, such that the only significant requirement was to break each problem into its constituent parts. In one version of the task, participants were presented with a traditional 2×2 Matrix and asked to draw the missing matrix item into a response box below. In a second version, the problem was broken down into its component features across three separate cells, reducing the need for participants to segment the problem. As with adults, performance was better in the condition in which the problems were separated into component parts. Children with lower fluid intelligence did not benefit more in the separated condition than children with higher fluid intelligence, and there was no evidence that segmenting problems was more beneficial for younger than older children. This study demonstrates that cognitive segmentation is a critical component of complex problem-solving for children, as it is for adults. By forcing children to focus their attention on separate parts of a complex visual problem, their performance can be dramatically improved.

Transdiagnostic profiles of behaviour and communication relate to academic and socioemotional functioning and neural white matter organisation.

BACKGROUND: Behavioural and language difficulties co-occur in multiple neurodevelopmental conditions. Our understanding of these problems has arguably been slowed by an overreliance on study designs that compare diagnostic groups and fail to capture the overlap across different neurodevelopmental disorders and the heterogeneity within them. METHODS: We recruited a large transdiagnostic cohort of children with complex needs (N = 805) to identify distinct subgroups of children with common profiles of behavioural and language strengths and difficulties. We then investigated whether and how these data-driven groupings could be distinguished from a comparison sample (N = 158) on measures of academic and socioemotional functioning and patterns of global and local white matter connectome organisation. Academic skills were assessed via standardised measures of reading and maths. Socioemotional functioning was captured by the parent-rated version of the Strengths and Difficulties Questionnaire. RESULTS: We identified three distinct subgroups of children, each with different levels of difficulties in structural language, pragmatic communication, and hot and cool executive functions. All three subgroups struggled with academic and socioemotional skills relative to the comparison sample, potentially representing three alternative but related developmental pathways to difficulties in these areas. The children with the weakest language skills had the most widespread difficulties with learning, whereas those with more pronounced difficulties with hot executive skills experienced the most severe difficulties in the socioemotional domain. Each data-driven subgroup could be distinguished from the comparison sample based on both shared and subgroup-unique patterns of neural white matter organisation. Children with the most pronounced deficits in language, cool executive, or hot executive function were differentiated from the comparison sample by altered connectivity in predominantly thalamocortical, temporal-parietal-occipital, and frontostriatal circuits, respectively. CONCLUSIONS: These findings advance our understanding of commonly co-morbid behavioural and language problems and their relationship to behavioural outcomes and neurobiological substrates.

Testing Deprivation and Threat: A Preregistered Network Analysis of the Dimensions of Early Adversity.

Despite abundant evidence of the detrimental effects of childhood adversity, its nature and underlying mechanisms remain contested. One influential theory, the dimensional model of adversity and psychopathology, proposes deprivation and threat as distinct dimensions of early experience. In this preregistered analysis of data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we used a network and clustering approach to assess the dimensionality of relationships between childhood adversity and adolescent cognition and emotional functioning, and we used recursive partitioning to identify timing effects. We found evidence that deprivation and threat are separate dimensions of adversity and that early experiences of deprivation cluster with later measures of cognition and emotional functioning. This cluster varies by age of exposure; it includes fewer forms of deprivation as children grow from infancy to middle childhood. Our measures did not form a specific cluster linking threat to emotional functioning.

Cognitive and Academic Skills in Two Developmental Cohorts of Different Ability Level: A Mutualistic Network Perspective.

Mutualistic theories assume that the mastering of a skill, either cognitive or academic, supports and amplifies the development of other such abilities. The current study uses network science to model cross-sectional associations between cognitive and academic performance in two age-matched developmental cohorts. One cohort was a community sample drawn from the general school population, while the other included struggling learners. The community sample outperformed the struggling learners across all measures. Network models suggested that although the tasks were similarly interrelated across cohorts, there were some notable differences in association strength: Academic skills were more closely coupled in the community sample, while maths was more strongly related to cognitive skills in the struggling learners. We demonstrate the utility of network models as an analytic framework that is consistent with contemporary theories of learning difficulties and the nature of the relationship between cognitive and learning skills more broadly.

Inconsistencies between Subjective Reports of Cognitive Difficulties and Performance on Cognitive Tests are Associated with Elevated Internalising and Externalising Symptoms in Children with Learning-related Problems.

Children with learning difficulties are commonly assumed to have underlying cognitive deficits by health and educational professionals. However, not all children referred for psycho-educational assessment will be found to have deficits when their abilities are measured by performance on cognitive tasks. The primary aim of this study was to estimate the prevalence of this inconsistent cognitive profile (ICP) in a transdiagnostic sample of children referred by health and education service providers for problems related to attention, learning and memory (N = 715). A second aim was to explore whether elevated mental health problems were associated with ICPs. Findings suggest that approximately half of this sample could be characterised as having an ICP. Cognitive difficulties, whether identified by parent ratings or task performance, were associated with elevated internalising and externalising difficulties. Crucially, a larger discrepancy between a parent's actual ratings of a child's cognitive difficulties and the ratings that would be predicted based on the child's performance on cognitive tasks was associated greater internalising and externalising difficulties for measures of working memory, and greater externalising difficulties for measures of attention. These findings suggest that subjective cognitive difficulties occurring in the absence of any task-based performance deficits may be a functional problem arising from mental health problems.

Dimensions of cognition, behaviour, and mental health in struggling learners: A spotlight on girls.

Background: Fewer girls than boys are identified as struggling at school for suspected problems in attention, learning and/or memory. The objectives of this study were to: i) identify dimensions of cognition, behaviour and mental health in a unique transdiagnostic sample of struggling learners; ii) test whether these constructs were equivalent for boys and girls, and; iii) compare their performance across the dimensions. Methods: 805 school-aged children, identified by practitioners as experiencing problems in cognition and learning, completed cognitive assessments, and parents/carers rated their behaviour and mental health problems. Results: Three cognitive [Executive, Speed, Phonological], three behavioural [Cognitive Control, Emotion Regulation, Behaviour Regulation], and two mental health [Internalising, Externalising] dimensions distinguished the sample. Dimensions were structurally comparable between boys and girls, but differences in severity were present: girls had greater impairments on performance-based measures of cognition; boys were rated as having more severe externalising problems. Conclusions: Gender biases to stereotypically male behaviours are prevalent among practitioners, even when the focus is on identifying cognitive and learning difficulties. This underscores the need to include cognitive and female-representative criteria in diagnostic systems to identify girls whose difficulties could go easily undetected.

Annual Research Review: The transdiagnostic revolution in neurodevelopmental disorders.

Practitioners frequently use diagnostic criteria to identify children with neurodevelopmental disorders and to guide intervention decisions. These criteria also provide the organising framework for much of the research focussing on these disorders. Study design, recruitment, analysis and theory are largely built on the assumption that diagnostic criteria reflect an underlying reality. However, there is growing concern that this assumption may not be a valid and that an alternative transdiagnostic approach may better serve our understanding of this large heterogeneous population of young people. This review draws on important developments over the past decade that have set the stage for much-needed breakthroughs in understanding neurodevelopmental disorders. We evaluate contemporary approaches to study design and recruitment, review the use of data-driven methods to characterise cognition, behaviour and neurobiology, and consider what alternative transdiagnostic models could mean for children and families. This review concludes that an overreliance on ill-fitting diagnostic criteria is impeding progress towards identifying the barriers that children encounter, understanding underpinning mechanisms and finding the best route to supporting them.

Higher-order dimensions of psychopathology in a neurodevelopmental transdiagnostic sample.

Hierarchical dimensional models of psychopathology derived for adult and child community populations offer more informative and efficient methods for assessing and treating symptoms of mental ill health than traditional diagnostic approaches. It is not yet clear how many dimensions should be included in models for youth with neurodevelopmental conditions. The aim of this study was to delineate the hierarchical dimensional structure of psychopathology in a transdiagnostic sample of children and adolescents with learning-related problems, and to test the concurrent predictive value of the model for clinically, socially, and educationally relevant outcomes. A sample of N = 403 participants from the Centre for Attention Learning and Memory (CALM) cohort were included. Hierarchical factor analysis delineated dimensions of psychopathology from ratings on the Conner's Parent Rating Short Form, the Revised Children's Anxiety and Depression Scale, and the Strengths and Difficulties Questionnaire. A hierarchical structure with a general p factor at the apex, broad internalizing and broad externalizing spectra below, and three more specific factors (specific internalizing, social maladjustment, and neurodevelopmental) emerged. The p factor predicted all concurrently measured social, clinical, and educational outcomes, but the other dimensions provided incremental predictive value. The neurodevelopmental dimension, which captured symptoms of inattention, hyperactivity, and executive function and emerged from the higher-order externalizing factor, was the strongest predictor of learning. This suggests that in struggling learners, cognitive and affective behaviors may interact to influence learning outcomes. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

A classroom intervention targeting working memory, attention and language skills: a cluster randomised feasibility trial.

BACKGROUND: International debate around the best models of speech and language therapy provision for children with language disorders has highlighted the need for research into classroom-based approaches and intervention dosage. Working memory (WM) is a cognitive skill linked to attention and language. 'Recall to Enhance Children's Attention, Language and Learning' (RECALL) is a novel, 6-week, classroom-based intervention delivered by health professionals (HPs) and teachers. It is designed to target WM and enhance attention and language skills in 4-5 year olds. METHODS: A cluster randomised feasibility trial was conducted to investigate aspects of the feasibility of a definitive trial to evaluate RECALL: (i) recruitment and sampling procedures; (ii) compliance and fidelity; (iii) the acceptability of RECALL to HPs and teachers; (iv) the appropriateness of the outcome measures. Six classes of 4-5 year olds participated: two received RECALL, two received an existing intervention targeting attention skills (not underpinned by WM theory), and two received education as usual (no intervention). Ten children in each class (n = 60) were sampled to assess the appropriateness of the outcome measures. Classroom observations were conducted to measure fidelity and semi-structured interviews with HPs, and teachers explored the acceptability of RECALL. RESULTS: The recruitment targets were met, and all six schools completed the trial, but the sampling procedures require modification. Compliance was good (95% of RECALL sessions were delivered), but fidelity to the intervention protocol varied between 76% and 45% across the two schools. This was influenced by large class sizes, child factors, and facilitator factors, e.g., their understanding of the theory underpinning the intervention. The lack of fidelity reduced the dose (number of practice items) accessed by individual children, particularly those most at risk. There were mixed findings regarding the acceptability of RECALL and the appropriateness of the outcome measures. CONCLUSIONS: The trial protocol could be easily scaled-up in a future definitive trial, with an amended sampling procedure. RECALL should be repackaged as a small group intervention to enhance the fidelity of its delivery and its acceptability to HPs and teachers. This study highlights the need for thorough training for professionals who deliver classroom-based interventions for children with language disorders. TRIAL REGISTRATION: ISRCTN13633886 . Registered on 7 September 2018.

Cognitive Dimensions of Learning in Children With Problems in Attention, Learning, and Memory.

A data-driven, transdiagnostic approach was used to identify the cognitive dimensions linked with learning in a mixed group of 805 children aged 5 to 18 years recognised as having problems in attention, learning and memory by a health or education practitioner. Assessments included phonological processing, information processing speed, short-term and working memory, and executive functions, and attainments in word reading, spelling, and maths. Data reduction methods identified three dimensions of phonological processing, processing speed and executive function for the sample as a whole. This model was comparable for children with and without ADHD. The severity of learning difficulties in literacy was linked with phonological processing skills, and in maths with executive control. Associations between cognition and learning were similar across younger and older children and individuals with and without ADHD, although stronger links between learning-related problems and both executive skills and processing speed were observed in children with ADHD. The results establish clear domain-specific cognitive pathways to learning that distinguish individuals in the heterogeneous population of children struggling to learn.

Age-related differences in adults' ability to follow spoken instructions.

A growing body of research illustrates that working memory capacity is a crucial limiting factor in our ability to follow spoken instructions. Despite the ubiquitous nature of instruction following throughout the lifespan, how the natural ageing process affects the ability to do so is not yet fully understood. In this study, we investigated the consequences of action at encoding and recall on the ability to follow spoken instructions. Younger (< 30 y/o) and older (> 65 y/o) adults recalled sequences of spoken action commands under presentation and recall conditions that either did or did not involve their physical performance. Both groups showed an enacted-recall advantage, with superior recall by physical performance than oral repetition. When both encoding and recall were purely verbal, older adults' recall accuracy was comparable to that of their younger counterparts. When action was involved at either encoding or recall, however, the difference in performance between the two age groups became pronounced: enactment-based encoding significantly improved younger adults' ability to follow spoken instructions; there was no such advantage for older adults. These data show that spatial-motoric representations disproportionately benefit younger adults' memory performance. We discuss the practical implications of these findings in the context of lifelong learning.

The Strengths and Difficulties Questionnaire Predicts Concurrent Mental Health Difficulties in a Transdiagnostic Sample of Struggling Learners.

Children and adolescents with developmental problems are at increased risk of experiencing mental health problems. The Strengths and Difficulties Questionnaire (SDQ) is widely used as a screener for detecting mental health difficulties in these populations, but its use thus far has been restricted to groups of children with diagnosed disorders (e.g., ADHD). Transdiagnostic approaches, which focus on symptoms and soften or remove the boundaries between traditional categorical disorders, are increasingly adopted in research and practice. The aim of this study was to assess the potential of the SDQ to detect concurrent mental health problems in a transdiagnostic sample of children. The sample were referred by health and educational professionals for difficulties related to learning (N = 389). Some had one diagnosis, others had multiple, but many had no diagnoses. Parent-rated SDQ scores were significantly positively correlated with parent ratings of mental health difficulties on the Revised Child Anxiety and Depression Scale (RCADS). Ratings on the SDQ Emotion subscale significantly predicted the likelihood of having concurrent clinical anxiety and depression scores. Ratings on the Hyperactivity subscale predicted concurrent anxiety levels. These findings suggest the SDQ could be a valuable screening tool for identifying existing mental health difficulties in children recognized as struggling, as it can be in typically developing children and those with specific diagnoses.

The effects of transcranial direct current stimulation on within- and cross-paradigm transfer following multi-session backward recall training.

Transcranial direct current stimulation (tDCS) has been shown to enhance the efficacy and generalisation of working memory (WM) training, but there has been little systematic investigation into how coupling task-specific WM training with stimulation impacts more specifically on transfer to untrained tasks. This randomised controlled trial investigated the boundary conditions to transfer by testing firstly whether the benefits of training on backward digit recall (BDR) extend to untrained backward recall tasks and n-back tasks with different materials, and secondly which, if any, form of transfer is enhanced by tDCS. Forty-eight participants were allocated to one of three conditions: BDR training with anodal (10 min, 1 mA) or sham tDCS, or visual search training with sham tDCS, applied over the left dorsolateral prefrontal cortex. Transfer was assessed on within- (backward recall with digits, letters, and spatial locations) and cross-paradigm (n-back with digits and letters) transfer tests following three sessions of training and stimulation. On-task training gains were found, with transfer to other backward span but not n-back tasks. There was little evidence that tDCS enhanced on-task training or transfer. These findings indicate that training enhances paradigm-specific processes within WM, but that tDCS does not enhance these gains.

Transdiagnostic Brain Mapping in Developmental Disorders.

Childhood learning difficulties and developmental disorders are common, but progress toward understanding their underlying brain mechanisms has been slow. Structural neuroimaging, cognitive, and learning data were collected from 479 children (299 boys, ranging in age from 62 to 223 months), 337 of whom had been referred to the study on the basis of learning-related cognitive problems. Machine learning identified different cognitive profiles within the sample, and hold-out cross-validation showed that these profiles were significantly associated with children's learning ability. The same machine learning approach was applied to cortical morphology data to identify different brain profiles. Hold-out cross-validation demonstrated that these were significantly associated with children's cognitive profiles. Crucially, these mappings were not one-to-one. The same neural profile could be associated with different cognitive impairments across different children. One possibility is that the organization of some children's brains is less susceptible to local deficits. This was tested by using diffusion-weighted imaging (DWI) to construct whole-brain white-matter connectomes. A simulated attack on each child's connectome revealed that some brain networks were strongly organized around highly connected hubs. Children with these networks had only selective cognitive impairments or no cognitive impairments at all. By contrast, the same attacks had a significantly different impact on some children's networks, because their brain efficiency was less critically dependent on hubs. These children had the most widespread and severe cognitive impairments. On this basis, we propose a new framework in which the nature and mechanisms of brain-to-cognition relationships are moderated by the organizational context of the overall network.