Twenty-four-month effortful control predicts emerging autism characteristics.

Longitudinal research can assess how diverging development of multiple cognitive skills during infancy, as well as familial background, are related to the emergence of neurodevelopmental conditions. Sensorimotor and effortful control difficulties are seen in infants later diagnosed with autism; this study explored the relationships between these skills and autism characteristics in 340 infants (240 with elevated familial autism likelihood) assessed at 4-7, 8-10, 12-15, 24, and 36 months. We tested: (1) the relationship between parent-reported effortful control (Rothbart's temperament questionnaires) and sensorimotor skills (Mullen Scales of Early Learning), using random intercept cross-lagged panel modelling; (2) whether household income and maternal education predicted stable individual differences in cognition; (3) sensorimotor and effortful control skills as individual and interactive predictors of parent-reported autism characteristics (Social Responsiveness Scale) at 3 years, using multiple regression; and (4) moderation of interactions by familial likelihood. Sensorimotor skills were longitudinally associated with effortful control at the subsequent measurement point from 12-15 months. Socioeconomic status indicators did not predict stable between-infant differences in sensorimotor or effortful control skills. Effortful control skills were longitudinally related to 3-year autism characteristics from the first year of life, with evidence for an interaction with sensorimotor skills at 24 months. Effects of effortful control increased with age and were particularly important for infants with family histories of autism. Results are discussed in relation to different theoretical frameworks: Developmental Cascades and Anterior Modifiers in the Emergence of Neurodevelopmental Disorders. We suggest a role for 24-month effortful control in explaining the emergent autism phenotype. RESEARCH HIGHLIGHTS: Sensorimotor skills longitudinally predicted effortful control from 12-15 months onward but effortful control did not longitudinally predict sensorimotor skills during infancy. Measures of effortful control skills taken before the age of 1 predicted continuous variation in autism characteristics at 36 months, with associations increasing in strength with age. Effortful control (measured at 12-15 and 24 months) was a stronger predictor of 36-month autism characteristics in infants with elevated familial likelihood for autism. The relationship between 24-month sensorimotor skills and 36-month autism characteristics was stronger in infants with weaker effortful control skills.

Air pollution, traffic noise, mental health, and cognitive development: A multi-exposure longitudinal study of London adolescents in the SCAMP cohort.

BACKGROUND: There is increasing evidence that air pollution and noise may have detrimental psychological impacts, but there are few studies evaluating adolescents, ground-level ozone exposure, multi-exposure models, or metrics beyond outdoor residential exposure. This study aimed to address these gaps. METHODS: Annual air pollution and traffic noise exposure at home and school were modelled for adolescents in the Greater London SCAMP cohort (N=7555). Indoor, outdoor and hybrid environments were modelled for air pollution. Cognitive and mental health measures were self-completed at two timepoints (baseline aged 11-12 and follow-up aged 13-15). Associations were modelled using multi-level multivariate linear or ordinal logistic regression. RESULTS: This is the first study to investigate ground-level ozone exposure in relation to adolescent executive functioning, finding that a 1 interquartile range increase in outdoor ozone corresponded to -0.06 (p < 0.001) z-score between baseline and follow-up, 38 % less improvement than average (median development + 0.16). Exposure to nitrogen dioxide (NO2), 24-hour traffic noise, and particulate matter < 10 µg/m3 (PM10) were also significantly associated with slower executive functioning development when adjusting for ozone. In two-pollutant models, particulate matter and ozone were associated with increased externalising problems. Daytime and evening noise were associated with higher anxiety symptoms, and 24-hour noise with worse speech-in-noise perception (auditory processing). Adjusting for air pollutants, 24-hour noise was also associated with higher anxiety symptoms and slower fluid intelligence development. CONCLUSIONS: Ozone's potentially detrimental effects on adolescent cognition have been overlooked in the literature. Our findings also suggest harmful impacts of other air pollutants and noise on mental health. Further research should attempt to replicate these findings and use mechanistic enquiry to enhance causal inference. Policy makers should carefully consider how to manage the public health impacts of ozone, as efforts to reduce other air pollutants such as NO2 can increase ozone levels, as will the progression of climate change.

Sex-specific behavioural deficits in adulthood following acute activation of the GABAA receptor in the neonatal mouse.

INTRODUCTION: Sex differences exist in the prevalence of neurodevelopmental disorders (NDDs). Part of the aetiology of NDDs has been proposed to be alterations in the balance between excitatory and inhibitory neurotransmission, leading to the question of whether males and females respond differently to altered neurotransmitter balance. We investigated whether pharmacological alteration of GABAA signalling in early development results in sex-dependent changes in adult behaviours associated with NDDs. METHODS: Male and female C57BL/6J mice received intraperitoneal injections of 0.5mg/kg muscimol or saline on postnatal days (P) 3-5 and were subjected to behavioural testing, specifically open field, light dark box, marble burying, sucralose preference, social interaction and olfactory habituation/dishabituation tests between P60-90. RESULTS: Early postnatal administration of muscimol resulted in reduced anxiety in the light dark box test in both male and female adult mice. Muscimol reduced sucralose preference in males, but not females, whereas female mice showed reduced social behaviours. Regional alterations in cortical thickness were observed in the weeks following GABAA receptor activation, pointing to an evolving structural difference in the brain underlying adult behaviour. CONCLUSIONS: We conclude that activation of the GABAA receptor in the first week of life resulted in long-lasting changes in a range of behaviours in adulthood following altered neurodevelopment. Sex of the individual affected the nature and severity of these abnormalities, explaining part of the varied pathophysiology and neurodevelopmental diagnosis that derive from excitatory/inhibitory imbalance.

Cross-sectional and longitudinal assessment of cognitive development in Williams syndrome.

Williams syndrome (WS) is a rare genetic syndrome. As with all rare syndromes, obtaining adequately powered sample sizes is a challenge. Here we present legacy data from seven UK labs, enabling the characterisation of cross-sectional and longitudinal developmental trajectories of verbal and non-verbal development in the largest sample of individuals with WS to-date. In Study 1, we report cross-sectional data between N = 102 and N = 209 children and adults with WS on measures of verbal and non-verbal ability. In Study 2, we report longitudinal data from N = 17 to N = 54 children and adults with WS who had been tested on at least three timepoints on these measures. Data support the WS characteristic cognitive profile of stronger verbal than non-verbal ability, and shallow developmental progression for both domains. Both cross-sectional and longitudinal data demonstrate steeper rates of development in the child participants than the adolescent and adults in our sample. Cross-sectional data indicate steeper development in verbal than non-verbal ability, and that individual differences in the discrepancy between verbal and non-verbal ability are largely accounted for by level of intellectual functioning. A diverging developmental discrepancy between verbal and non-verbal ability, whilst marginal, is not mirrored statistically in the longitudinal data. Cross-sectional and longitudinal data are discussed with reference to validating cross-sectional developmental patterns using longitudinal data and the importance of individual differences in understanding developmental progression.

Dose imbalance of DYRK1A kinase causes systemic progeroid status in Down syndrome by increasing the un-repaired DNA damage and reducing LaminB1 levels.

BACKGROUND: People with Down syndrome (DS) show clinical signs of accelerated ageing. Causative mechanisms remain unknown and hypotheses range from the (essentially untreatable) amplified-chromosomal-instability explanation, to potential actions of individual supernumerary chromosome-21 genes. The latter explanation could open a route to therapeutic amelioration if the specific over-acting genes could be identified and their action toned-down. METHODS: Biological age was estimated through patterns of sugar molecules attached to plasma immunoglobulin-G (IgG-glycans, an established "biological-ageing-clock") in n = 246 individuals with DS from three European populations, clinically characterised for the presence of co-morbidities, and compared to n = 256 age-, sex- and demography-matched healthy controls. Isogenic human induced pluripotent stem cell (hiPSCs) models of full and partial trisomy-21 with CRISPR-Cas9 gene editing and two kinase inhibitors were studied prior and after differentiation to cerebral organoids. FINDINGS: Biological age in adults with DS is (on average) 18.4-19.1 years older than in chronological-age-matched controls independent of co-morbidities, and this shift remains constant throughout lifespan. Changes are detectable from early childhood, and do not require a supernumerary chromosome, but are seen in segmental duplication of only 31 genes, along with increased DNA damage and decreased levels of LaminB1 in nucleated blood cells. We demonstrate that these cell-autonomous phenotypes can be gene-dose-modelled and pharmacologically corrected in hiPSCs and derived cerebral organoids. Using isogenic hiPSC models we show that chromosome-21 gene DYRK1A overdose is sufficient and necessary to cause excess unrepaired DNA damage. INTERPRETATION: Explanation of hitherto observed accelerated ageing in DS as a developmental progeroid syndrome driven by DYRK1A overdose provides a target for early pharmacological preventative intervention strategies. FUNDING: Main funding came from the "Research Cooperability" Program of the Croatian Science Foundation funded by the European Union from the European Social Fund under the Operational Programme Efficient Human Resources 2014-2020, Project PZS-2019-02-4277, and the Wellcome Trust Grants 098330/Z/12/Z and 217199/Z/19/Z (UK). All other funding is described in details in the "Acknowledgements".

Complex cognition and individual variability: a mixed methods study of the relationship between creativity and executive control.

One of the methodological challenges of educational neuroscience is understanding real world cognition in the multifaceted environment of the classroom. Complex cognition does not simplify to processes (which might be satisfactorily measured in the lab) but to sets of activities, likely to vary between individuals, which involve the iterative use of multiple processes, as well as the environment, over an extended period of time. As such, studying complex cognition requires methodological flexibility; any single method is unlikely to provide complete answers. We illustrate this idea with our research exploring the relationship between executive control (EC) and creativity in primary school age children; in it, we used both qualitative and quantitative tools and a novel approach to bringing both sets of findings together. Quantitative findings helped inform 'how much' a participant could deploy EC or creative thinking, while qualitative findings told us more about 'how' they deployed EC in their creativity. Through triangulating findings, we gained insights which would have remained obscure using either approach alone; namely, first, that wide variation in how children deploy EC in creativity means that the same creative results can be achieved with very different levels of EC involvement, and second, that high levels of EC can limit creativity. We argue that, beyond the specific findings of this study, there might be useful broader methodological lessons for educational neuroscience. We also attempt to demystify mixed methods by showing that a multi-pronged approach is more feasible than many assume; for example, by using existing, familiar tools in novel ways. In our work, we redeployed well-established quantitative tests used in creativity research as stimuli for qualitative investigation. For educational neuroscience to evolve its understanding of complex cognition, we suggest it might benefit from being innovative, open-minded and ambitious in how it exploits the diversity of methodological tools available.

A systematic review of cognitive interventions for adult patients with brain tumours.

BACKGROUND: Neurocognitive impairments are common in patients with current or previously treated brain tumours, and such impairments can negatively affect patient outcomes including quality of life and survival. This systematic review aimed to identify and describe interventions used to ameliorate (improve) or prevent cognitive impairments in adults with brain tumours. METHODS: We performed a literature search of the Ovid MEDLINE, PsychINFO and PsycTESTS databases from commencement until September 2021. RESULTS: In total, 9998 articles were identified by the search strategy; an additional 14 articles were identified through other sources. Of these, 35 randomised and nonrandomised studies were deemed to meet the inclusion/exclusion criteria of our review and were subsequently included for evaluation. A range of interventions were associated with positive effects on cognition, including pharmacological agents such as memantine, donepezil, methylphenidate, modafinil, ginkgo biloba and shenqi fuzheng, and nonpharmacological interventions such as general and cognitive rehabilitation, working memory training, Goal Management Training, aerobic exercise, virtual reality training combined with computer-assisted cognitive rehabilitation, hyperbaric oxygen therapy and semantic strategy training. However, most identified studies had a number of methodological limitations and were judged to be at moderate-to-high risk of bias. In addition, it remains unclear whether and to what extent the identified interventions lead to durable cognitive benefits after cessation of the intervention. CONCLUSION: The 35 studies identified in this systematic review have indicated potential cognitive benefits for a number of pharmacological and nonpharmacological interventions in patients with brain tumours. Study limitations were identified and further studies should focus on improved study reporting, methods to reduce bias and minimise participant drop-out and withdrawal where possible, and consider standardisation of methods and interventions across studies. Greater collaboration between centres could result in larger studies with standardised methods and outcome measures, and should be a focus of future research in the field.

Associations between Socioeconomic Status, Cognition, and Brain Structure: Evaluating Potential Causal Pathways Through Mechanistic Models of Development.

Differences in socioeconomic status (SES) correlate both with differences in cognitive development and in brain structure. Associations between SES and brain measures such as cortical surface area and cortical thickness mediate differences in cognitive skills such as executive function and language. However, causal accounts that link SES, brain, and behavior are challenging because SES is a multidimensional construct: correlated environmental factors, such as family income and parental education, are only distal markers for proximal causal pathways. Moreover, the causal accounts themselves must span multiple levels of description, employ a developmental perspective, and integrate genetic effects on individual differences. Nevertheless, causal accounts have the potential to inform policy and guide interventions to reduce gaps in developmental outcomes. In this article, we review the range of empirical data to be integrated in causal accounts of developmental effects on the brain and cognition associated with variation in SES. We take the specific example of language development and evaluate the potential of a multiscale computational model of development, based on an artificial neural network, to support the construction of causal accounts. We show how, with bridging assumptions that link properties of network structure to magnetic resonance imaging (MRI) measures of brain structure, different sets of empirical data on SES effects can be connected. We use the model to contrast two possible causal pathways for environmental influences that are associated with SES: differences in prenatal brain development and differences in postnatal cognitive stimulation. We then use the model to explore the implications of each pathway for the potential to intervene to reduce gaps in developmental outcomes. The model points to the cumulative effects of social disadvantage on multiple pathways as the source of the poorest response to interventions. Overall, we highlight the importance of implemented models to test competing accounts of environmental influences on individual differences.

Modulatory effects of SES and multilinguistic experience on cognitive development: a longitudinal data analysis of multilingual and monolingual adolescents from the SCAMP cohort.

Previous research has shown that cognitive development is sensitive to socio-economic status (SES) and multilinguistic experiences. However, these effects are difficult to disentangle and SES may modulate the effects of multilingualism. The present study used data from a large cohort of pupils who took part in the Study of Cognition, Adolescents and Mobile Phones (SCAMP) at ages 11-12 (T1) and 13-15 years old (T2). Cognitive measures were derived from tasks of cognitive flexibility, verbal, spatial and visuo-spatial working memory, speech processing and non-verbal reasoning. Using SES information collected through questionnaires (school type, level of deprivation, parental education and occupation), the sample was clustered into high/medium/low SES groups. Comparisons focused on 517 monolingual and 329 multilingual pupils in the high/low SES groups. Having controlled for multiple comparisons, the results indicated a significant beneficial effect of bilingualism in measures of working memory, visuo-spatial processing and non-verbal reasoning. These effects were present in both high and low SES individuals and sustained at both times of development, with a particularly significant improvement of working memory abilities in low SES bilinguals at T2 as compared to monolingual peers. Theoretical and practical implications of these findings are considered and guidance for educators is discussed.

Influences on cognitive outcomes in adult patients with gliomas: A systematic review.

People with brain tumors, including those previously treated, are commonly affected by a range of neurocognitive impairments involving executive function, memory, attention, and social/emotional functioning. Several factors are postulated to underlie this relationship, but evidence relating to many of these factors is conflicting and does not fully explain the variation in cognitive outcomes seen in the literature and in clinical practice. To address this, we performed a systematic literature review to identify and describe the range of factors that can influence cognitive outcomes in adult patients with gliomas. A literature search was performed of Ovid MEDLINE, PsychINFO, and PsycTESTS from commencement until September 2021. Of 9,998 articles identified through the search strategy, and an additional 39 articles identified through other sources, 142 were included in our review. The results confirmed that multiple factors influence cognitive outcomes in patients with gliomas. The effects of tumor characteristics (including location) and treatments administered are some of the most studied variables but the evidence for these is conflicting, which may be the result of methodological and study population differences. Tumor location and laterality overall appear to influence cognitive outcomes, and detection of such an effect is contingent upon administration of appropriate cognitive tests. Surgery appears to have an overall initial deleterious effect on cognition with a recovery in most cases over several months. A large body of evidence supports the adverse effects of radiotherapy on cognition, but the role of chemotherapy is less clear. To contrast, baseline cognitive status appears to be a consistent factor that influences cognitive outcomes, with worse baseline cognition at diagnosis/pre-treatment correlated with worse long-term outcomes. Similarly, much evidence indicates that anti-epileptic drugs have a negative effect on cognition and genetics also appear to have a role. Evidence regarding the effect of age on cognitive outcomes in glioma patients is conflicting, and there is insufficient evidence for gender and fatigue. Cognitive reserve, brain reserve, socioeconomic status, and several other variables discussed in this review, and their influence on cognition and recovery, have not been well-studied in the context of gliomas and are areas for focus in future research. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42017072976.

Bidirectional associations between sleep problems and behavioural difficulties and health-related quality of life in adolescents: Evidence from the SCAMP longitudinal cohort study.

Background: Sleep problems show associations with negative outcomes in both physical and mental health in adolescents, but the associations may be reciprocal. We aimed to assess bidirectional associations between sleep problems and mental health symptoms including behavioural difficulties (internalising and externalising difficulties) and low health-related quality of life (HRQoL). Methods: A total of 6616 adolescents (52.4% females) across Greater London completed baseline assessments when they were aged 11-12 years, and 3803 of them (57.2% females) completed follow-up assessments at aged 13-15 years. Weekday and weekend sleep duration were derived from self-reported bedtime, sleep onset latency and wake time. Sleep disturbance was assessed using a standardized sleep disturbance scale. Internalising and externalising difficulties were assessed using subscales of the Strength and Difficulties Questionnaire. HRQoL was assessed using the KIDSCREEN-10 questionnaire. Cross-lagged structural equation modelling was used with multiple imputation to examine bidirectional associations between sleep problems and mental health symptoms. Results: Females had greater internalising difficulties, worse HRQoL and more sleep disturbance than males. Persistent insufficient weekday and weekend sleep, and sleep disturbance (i.e., at both baseline and follow-up) were associated with internalising and externalising difficulties and low HRQoL at follow-up (ORs ranged from 1.53 to 3.63). Persistent externalising difficulties and low HRQoL were also associated with insufficient weekend sleep and sleep disturbance at follow-up (ORs ranged from 1.68 to 4.25). Using continuous variables, we found bidirectional associations between weekday sleep duration and HRQoL, weekend sleep duration and externalising score, sleep quality and internalising score, and sleep quality and HRQoL. The association magnitudes were mostly similar in the two directions. Conclusions: Our study showed bidirectional associations between sleep problems and mental health symptoms during adolescence, indicating that early intervention and treatment on the first-occurring symptom may prevent the development of subsequent problems.

Stress and Learning in Pupils: Neuroscience Evidence and its Relevance for Teachers.

Our understanding of how stress affects primary school children's attention and learning has developed rapidly. We know that children experience differing levels of stressors (factors that cause stress) in their environments, and that this can influence how they respond to new stressors when they occur in educational contexts. Here, we review evidence showing that stress can increase children's attention and learning capacities in some circumstances but hinder them in others. We show how children differ in their attention and learning styles, dependent on stress levels: for example, more highly stressed children may be more distracted by superficial features and may find it harder to engage in planning and voluntary control. We review intervention research on stress management techniques in children, concentrating on psychological techniques (such as mindfulness and stress reappraisal), physiological techniques (such as breathing exercises) and environmental factors (such as reducing noise). At the current time, raising teachers' awareness of pupils' differing stress responses will be an important step in accommodating the differing needs of children in their classrooms.

The developmental trajectories of spatial skills in middle childhood.

The multidimensional structure of spatial ability remains a debated issue. However, the developmental trajectories of spatial skills have yet to be investigated as a source of evidence within this debate. We tested the intrinsic versus extrinsic and static versus dynamic dimensions of the Uttal et al. (2013, Psychol. Bull., 139, 352) typology in relation to spatial development. Participants (N = 184) aged 6-11 completed spatial tasks chosen to measure these spatial dimensions. The results indicated that the developmental trajectories of intrinsic versus extrinsic skills differed significantly. Intrinsic skills improved more between 6 and 8 years, and 7 and 8 years, than extrinsic skills. Extrinsic skills increased more between 8 and 10 years than intrinsic skills. The trajectories of static versus dynamic skills did not differ significantly. The findings support the intrinsic versus extrinsic, but not the static versus dynamic dimension, of the Uttal et al. (2013, Psychol. Bull., 139, 352) typology.

The role of context in verbal humor processing in autism.

Difficulties in processing humor have been associated with individuals with autism. The current study investigated whether humor comprehension and appreciation could be augmented in children with autism by providing contextual support suggesting that humor was to be expected. A verbally presented riddle task was used in which participants were assessed for their subjective ratings and comprehension of the materials. They were also filmed to record any smiling or laughing. Both riddles and control stimuli were presented with supporting verbal context and also without it. The results showed that (a) the greater subjective appreciation of riddles than of control stimuli was dependent on the provision of context for the participants with autism and that (b) context statistically equated these ratings of riddles between participants with autism and matched typically developing controls. However, context had no effect on comprehension or affective response. The results of the current study demonstrate that children with autism are, even in the most conservative interpretation, able to use verbal context to recognize verbal humor. This lays the foundation of possible interventions based on training sensitivity to context.

Understanding differing outcomes from semantic and phonological interventions with children with word-finding difficulties: A group and case series study.

Developmental Language Disorder occurs in up to 10% of children and many of these children have difficulty retrieving words in their receptive vocabulary. Such word-finding difficulties (WFD) can impact social development and educational outcomes. This research aims to develop the evidence-base for supporting children with WFD and inform the design and analysis of intervention studies. We included 20 children (age 6 to 8) with WFD each of whom participated in two interventions one targeting semantic attributes and the other phonological attributes of target words. The interventions, employing word-webs, were carefully constructed to facilitate direct comparison of outcome which was analysed at both group and case-series level. The study used a robust crossover design with pre-intervention baseline, between-intervention wash-out and post-intervention follow-up testing. We incorporated: matching of item sets on individual performance at baseline, independent randomisation of order of intervention and items to condition, blinding of assessor, evaluation of fidelity and control items. The interventions were clinically feasible, with weekly sessions over six weeks. Intervention improved children's word-finding abilities with statistically significant change only during treatment phases of the study and not over baseline, wash-out or follow-up phases. For the group the semantic intervention resulted in a gain of almost twice as many items as the phonological intervention, a significant difference. However, children differed in their response to intervention. Importantly, case-series analysis revealed outcomes predictable on the basis of children's theoretically driven language profiles. Taking account of individual profiles in determining choice of intervention would enable more children to benefit. The study provides new evidence to inform and refine clinical practice with this population. Future studies should be designed such that results can be analysed at both group and case series levels to extend theoretical understanding and optimise use of appropriate interventions.

Differential Associations of Apolipoprotein E ε4 Genotype With Attentional Abilities Across the Life Span of Individuals With Down Syndrome.

Importance: Risk of Alzheimer disease (AD) is particularly high for individuals with Down syndrome (DS). The ε4 allele of the apolipoprotein E gene (APOE ε4) is associated with an additional risk for AD. In typical development, there is evidence that the APOE ε4 genotype is associated with an early cognitive advantage. Here we investigate associations of APOE ε4 with attention across the life span of individuals with DS. Objective: To investigate associations between APOE ε4 and attentional abilities in young children and in adults with DS. Design, Settings, and Participants: In this cross-sectional study, data were collected from 80 young children with DS (8-62 months of age) and 240 adults with DS (16-71 years of age) during the period from 2013 to 2018 at a research center to examine the association between APOE status (ε4 carrier vs ε4 noncarrier) and attentional abilities. Exposure: APOE status (ε4 carrier vs ε4 noncarrier). Main Outcomes and Measures: For the children, attentional ability was assessed using an eye-tracking paradigm, the gap-overlap task; the size of the gap effect was the primary outcome. For the adults, attentional ability was assessed using the CANTAB simple reaction time task; the standard deviation of response time latencies was the primary outcome. Cross-sectional developmental trajectories were constructed linking attentional ability with age in ε4 carriers and ε4 noncarriers for children and adults separately. Results: The child sample comprised 23 ε4 carriers and 57 ε4 noncarriers. The adult sample comprised 61 ε4 carriers and 179 ε4 noncarriers. For the children, a significant difference between trajectory intercepts (ηp2 = 0.14) indicated that ε4 carriers (B = 100.24 [95% CI, 18.52-181.96]) exhibited an attentional advantage over ε4 noncarriers (B = 314.78 [95% CI, 252.17-377.39]). There was an interaction between APOE status and age (ηp2 = 0.10); while the gap effect decreased with age for ε4 noncarriers (B = -4.58 [95% CI, -6.67 to -2.48]), reflecting the development of the attention system, there was no change across age in ε4 carriers (B = 0.77 [95% CI, -1.57 to 3.12]). For the adults, there was no main effect of ε4 carrier status, but there was an interaction between APOE status and age (B = 0.02 [95% CI, 0.004-0.07]), so that ε4 carriers had poorer attentional ability than ε4 noncarriers at older ages. Conclusions and Relevance: APOE ε4 is associated with an attentional advantage early in development and a disadvantage later in life for individuals with DS, similar to the pattern reported in typical development. Understanding the differential role of APOE across the life span is an important step toward future interventions.

Domain-Specific Inhibitory Control Training to Improve Children's Learning of Counterintuitive Concepts in Mathematics and Science.

Evidence from cognitive neuroscience suggests that learning counterintuitive concepts in mathematics and science requires inhibitory control (IC). This prevents interference from misleading perceptual cues and naïve theories children have built from their experiences of the world. Here, we (1) investigate associations between IC, counterintuitive reasoning, and academic achievement and (2) evaluate a classroom-based computerised intervention, called Stop & Think, designed to embed IC training within the learning domain (i.e. mathematics and science content from the school curricula). Cross-sectional analyses of data from 627 children in Years 3 and 5 (7- to 10-year-olds) demonstrated that IC, measured on a Stroop-like task, was associated with counterintuitive reasoning and mathematics and science achievement. A subsample (n = 456) participated either in Stop & Think as a whole-class activity (teacher-led, STT) or using individual computers (pupil-led, STP), or had teaching as usual (TAU). For Year 3 children (but not Year 5), Stop & Think led to better counterintuitive reasoning (i.e. near transfer) in STT (p < .001, ηp 2 = .067) and STP (p < .01, ηp 2 = .041) compared to TAU. Achievement data was not available for Year 3 STP or Year 5 STT. For Year 3, STT led to better science achievement (i.e. far transfer) compared to TAU (p < .05, ηp 2 = .077). There was no transfer to the Stroop-like measure of IC. Overall, these findings support the idea that IC may contribute to counterintuitive reasoning and mathematics and science achievement. Further, we provide preliminary evidence of a domain-specific IC intervention with transferable benefits to academic achievement for Year 3 children.

Education, the science of learning, and the COVID-19 crisis.

In the COVID-19 crisis, the science of learning has two different responsibilities: first, to offer guidance about how best to deal with the impact of the current situation, including lockdown and home-schooling; and second, to consider bigger questions about what this large-scale educational experiment might mean for the future. The first part of this Viewpoint summarises advice for parents on mental health, and on becoming stand-in-teachers. The second part, taking the longer view, considers the potential negative impact of the COVID-19 crisis in increasing inequality in education; but also the potential positive impact of driving innovations in technology use for educating children.

A multi-level developmental approach to exploring individual differences in Down syndrome: genes, brain, behaviour, and environment.

In this article, we focus on the causes of individual differences in Down syndrome (DS), exemplifying the multi-level, multi-method, lifespan developmental approach advocated by Karmiloff-Smith (1998, 2009, 2012, 2016). We evaluate the possibility of linking variations in infant and child development with variations in the (elevated) risk for Alzheimer's disease (AD) in adults with DS. We review the theoretical basis for this argument, considering genetics, epigenetics, brain, behaviour and environment. In studies 1 and 2, we focus on variation in language development. We utilise data from the MacArthur-Bates Communicative Development Inventories (CDI; Fenson et al., 2007), and Mullen Scales of Early Learning (MSEL) receptive and productive language subscales (Mullen, 1995) from 84 infants and children with DS (mean age 2;3, range 0;7 to 5;3). As expected, there was developmental delay in both receptive and expressive vocabulary and wide individual differences. Study 1 examined the influence of an environmental measure (socio-economic status as measured by parental occupation) on the observed variability. SES did not predict a reliable amount of the variation. Study 2 examined the predictive power of a specific genetic measure (apolipoprotein APOE genotype) which modulates risk for AD in adulthood. There was no reliable effect of APOE genotype, though weak evidence that development was faster for the genotype conferring greater AD risk (ε4 carriers), consistent with recent observations in infant attention (D'Souza, Mason et al., 2020). Study 3 considered the concerted effect of the DS genotype on early brain development. We describe new magnetic resonance imaging methods for measuring prenatal and neonatal brain structure in DS (e.g., volumes of supratentorial brain, cortex, cerebellar volume; Patkee et al., 2019). We establish the methodological viability of linking differences in early brain structure to measures of infant cognitive development, measured by the MSEL, as a potential early marker of clinical relevance. Five case studies are presented as proof of concept, but these are as yet too few to discern a pattern.

Visuo-attentional correlates of Autism Spectrum Disorder (ASD) in children with Down syndrome: A comparative study with children with idiopathic ASD.

BACKGROUND: Children with Down syndrome (DS) are at increased likelihood of Autism Spectrum Disorder (ASD) relative to the general population. To better understand the nature of this comorbidity, we examined the visuo-attentional processes associated with autistic trait expression in children with DS, focusing specifically on attentional disengagement and visual search performance. METHOD: We collected eye-tracking data from children with DS (n = 15) and children with idiopathic ASD (iASD, n = 16) matched according to chronological age. Seven children with DS had a formal clinical diagnosis of ASD (DS+ASD). RESULTS: In children with iASD, but not DS, higher autistic trait levels were associated with decreased temporal facilitation on a gap-overlap task, implying increased visuospatial orienting efficiency. In all cases, higher autistic trait levels were associated with improved visual search performance according to decreased target detection latency. On a visual search task, children with DS+ASD outperformed their peers with DS-ASD, mirroring the phenotypic advantage associated with iASD. We found no evidence of a relationship between attentional disengagement and visual search performance, providing preliminary evidence of a differentiation in terms of underlying visuo-attentional mechanism. CONCLUSION: We illustrate the value of progressing beyond insensitive behavioural measures of phenotypic description to examine, in a more fine-grained way, the attentional features associated with ASD comorbidity in children with DS.