Publications by authors named "Bonnie Auyeung"

91 Publications

Developmental Relations Between Internalising Problems and ADHD in Childhood: a Symptom Level Perspective.

Res Child Adolesc Psychopathol 2021 Aug 7. Epub 2021 Aug 7.

Department of Psychology, Univsersity of Edinburgh, Edinburgh, UK.

ADHD and internalising problems commonly co-occur with up to 50% of children diagnosed with ADHD also suffering from anxiety or depression. However, their developmental relations are currently not well understood. Longitudinal symptom level analyses can provide valuable insights into how difficulties in these areas of psychosocial functioning affect each other. Using Gaussian Graphical Models and Graphical Vector Autoregression Models, this study estimated cross-sectional and longitudinal networks of ADHD and internalising symptoms in 1387 children using parent- and teacher-reported Social Behaviour Questionnaires (SBQ) when children were aged 7, 9 and 11. Cross-sectional and longitudinal networks suggested that ADHD shares reciprocal relations with internalising symptoms through a number of potential bridge symptoms that are primarily connected to anxiety symptoms. High scores on child cannot sit still, is restless, or hyperactive were found to be the strongest bridge symptom acting as an antecedent to higher internalising symptoms whereas child is worried was the strongest antecedent for higher ADHD symptoms. Findings of this study highlight several potential bridge symptoms that may serve as key intervention targets and further emphasise the need for clinicians to assess children presenting with ADHD symptoms for internalising problems and vice versa.
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http://dx.doi.org/10.1007/s10802-021-00856-3DOI Listing
August 2021

Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) and associations with attention-deficit/hyperactivity disorder and autism spectrum disorder in children.

Environ Res 2021 Jul 19;202:111692. Epub 2021 Jul 19.

Division of Mental and Physical Health, Norwegian Institute of Public Health, PO Box 222, Skøyen, N-0213, Oslo, Norway.

Background: Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) may be a risk factor for neurodevelopmental deficits and disorders, but evidence is inconsistent.

Objectives: We investigated whether prenatal exposure to PFAS were associated with childhood diagnosis of attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD).

Methods: This study was based on the Norwegian Mother, Father and Child Cohort Study and included n = 821 ADHD cases, n = 400 ASD cases and n = 980 controls. Diagnostic cases were identified by linkage with the Norwegian Patient Registry. In addition, we used data from the Medical Birth Registry of Norway. The study included the following PFAS measured in maternal plasma sampled mid-pregnancy: Perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorohexane sulfonate (PFHxS), perfluoroheptanesulfonic acid (PFHpS), and perfluorooctane sulfonate (PFOS). Relationships between individual PFAS and ADHD or ASD diagnoses were examined using multivariable adjusted logistic regression models. We also tested for possible non-linear exposure-outcome associations. Further, we investigated the PFAS mixture associations with ASD and ADHD diagnoses using a quantile-based g-computation approach.

Results: Odds of ASD was significantly elevated in PFOA quartile 2 [OR = 1.71 (95% CI: 1.20, 2.45)] compared to quartile 1, and PFOA appeared to have a non-linear, inverted U-shaped dose-response relationship with ASD. PFOA was also associated with increased odds of ADHD, mainly in quartile 2 [OR = 1.54 (95% CI: 1.16, 2.04)] compared to quartile 1, and displayed a non-linear relationship in the restricted cubic spline model. Several PFAS (PFUnDA, PFDA, and PFOS) were inversely associated with odds of ADHD and/or ASD. Some of the associations were modified by child sex and maternal education. The overall PFAS mixture was inversely associated with ASD [OR = 0.76 (95% CI: 0.64, 0.90)] as well as the carboxylate mixture [OR = 0.79 (95% CI: 0.68, 0.93)] and the sulfonate mixture [OR = 0.84 (95% CI: 0.73, 0.96)].

Conclusion: Prenatal exposure to PFOA was associated with increased risk of ASD and ADHD in children. For some PFAS, as well as their mixtures, there were inverse associations with ASD and/or ADHD. However, the inverse associations reported herein should not be interpreted as protective effects, but rather that there could be some unresolved confounding for these relationships. The epidemiologic literature linking PFAS exposures with neurodevelopmental outcomes is still inconclusive, suggesting the need for more research to elucidate the neurotoxicological potential of PFAS during early development.
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http://dx.doi.org/10.1016/j.envres.2021.111692DOI Listing
July 2021

The Impact of COVID-19 Restrictions on Psychological Distress in Family Caregivers of Children with Neurodevelopmental Disability in the UK.

J Autism Dev Disord 2021 Jul 20. Epub 2021 Jul 20.

Department of Health and Clinical Psychology, School of Health in Social Science, University of Edinburgh, Edinburgh, Scotland, UK, EH8 9AG.

Caregivers of a child with a neurodevelopmental disability are more vulnerable to mental health difficulties. These difficulties are influenced by the child's challenging behaviours, and the caregiver's coping strategies; factors impacted by the COVID-19 pandemic. An online mixed methods survey was conducted on caregivers of children with neurodevelopmental disabilities (n = 43) and children who are typically developing (n = 67). The results showed that presence of challenging behaviours related to neurodevelopmental disability, and caregiver coping strategies predicted caregiver psychological distress during lockdown. Themes that emerged included 'confusing messages and guidance', 'loss of freedom' and 'unsupported and forgotten'. The results demonstrate the pressing need for the implementation of appropriate support to protect the mental health of caregivers across the UK.
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http://dx.doi.org/10.1007/s10803-021-05132-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294318PMC
July 2021

Prenatal Maternal Infections and Children's Neurodevelopment in the UK Millennium Cohort Study: A Focus on ASD and ADHD.

J Atten Disord 2021 May 19:10870547211015422. Epub 2021 May 19.

University of Edinburgh, UK.

Objective: No clear answer has yet been attained as to the influence of prenatal exposure to infection on autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), either alone or as co-occurring issues. The current study examined links between hospital-recorded and maternal-reported prenatal infections and ASD, ADHD, and co-occurring ASD and ADHD.

Methods: Participants were n = 15,462 children and mother pairs from the Millennium Cohort Study (MCS), a population-representative UK sample.

Results: Findings show associations between maternal-reported infections and ASD, and some evidence of links with ADHD and co-occurring ASD and ADHD. Hospital-recorded infections were not found to be associated with ASD, ADHD, or their co-occurrence. Agreement between hospital-recorded and maternal-reported infections was low, which may explain the discrepant findings.

Conclusion: Prenatal maternal infections may be associated with increased odds of ASD and ADHD. Findings point to the importance of drawing on multiple sources of information when ascertaining prenatal infection status.
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http://dx.doi.org/10.1177/10870547211015422DOI Listing
May 2021

Imbalanced social-communicative and restricted repetitive behavior subtypes of autism spectrum disorder exhibit different neural circuitry.

Commun Biol 2021 05 14;4(1):574. Epub 2021 May 14.

Roche Pharma Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases, Roche Innovation Center Basel, Basel, Switzerland.

Social-communication (SC) and restricted repetitive behaviors (RRB) are autism diagnostic symptom domains. SC and RRB severity can markedly differ within and between individuals and may be underpinned by different neural circuitry and genetic mechanisms. Modeling SC-RRB balance could help identify how neural circuitry and genetic mechanisms map onto such phenotypic heterogeneity. Here, we developed a phenotypic stratification model that makes highly accurate (97-99%) out-of-sample SC = RRB, SC > RRB, and RRB > SC subtype predictions. Applying this model to resting state fMRI data from the EU-AIMS LEAP dataset (n = 509), we find that while the phenotypic subtypes share many commonalities in terms of intrinsic functional connectivity, they also show replicable differences within some networks compared to a typically-developing group (TD). Specifically, the somatomotor network is hypoconnected with perisylvian circuitry in SC > RRB and visual association circuitry in SC = RRB. The SC = RRB subtype show hyperconnectivity between medial motor and anterior salience circuitry. Genes that are highly expressed within these networks show a differential enrichment pattern with known autism-associated genes, indicating that such circuits are affected by differing autism-associated genomic mechanisms. These results suggest that SC-RRB imbalance subtypes share many commonalities, but also express subtle differences in functional neural circuitry and the genomic underpinnings behind such circuitry.
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http://dx.doi.org/10.1038/s42003-021-02015-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121854PMC
May 2021

Alexithymia and Autistic Traits as Contributing Factors to Empathy Difficulties in Preadolescent Children.

J Autism Dev Disord 2021 Mar 31. Epub 2021 Mar 31.

Psychology Department, The University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK.

Recent evidence suggests that, contrary to traditional views, empathy difficulties may not be a core feature of autism; but are rather due to co-occurring alexithymia. Empathy, alexithymia and autistic traits have yet to be examined concurrently in children. Therefore, we examined the co-occurrence of empathy difficulties and alexithymia in 59 typically developing and 5 autistic children. Multiple measures (self-report, parent-report and a behavioural task) were used to evaluate empathy and to assess differences in self- and parent-reports using multiple regressions. Alexithymia was found to predict empathy significantly better than autistic traits, providing support for the alexithymia hypothesis. From a therapeutic perspective, results suggest autistic children who screen positive for elevated alexithymic traits may benefit from additional support targeting emotion identification.
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http://dx.doi.org/10.1007/s10803-021-04986-xDOI Listing
March 2021

IQ and Internalising Symptoms in Adolescents with ASD.

J Autism Dev Disord 2021 Nov 30;51(11):3887-3907. Epub 2020 Dec 30.

University of Edinburgh, School of Philosophy, Psychology and Language Sciences, Room S30, Psychology Building, 7 George Square, Edinburgh, EH8 9JZ, Scotland, UK.

Intelligence quotient (IQ), has been found to relate to the presence of internalising symptoms in autism spectrum disorder (ASD). This meta-analysis sought to clarify the direction of the relationship between IQ and two prevalent internalising symptoms, anxiety and depression, in adolescents with ASD. Secondly, this study aimed to highlight methodological factors contributing to inconsistent findings in existing research. Self-reported anxiety was found to be significantly higher in youth with a lower IQ, while depression was positively associated with IQ. Consequently, parents, schools and clinicians should be cautious of underestimating anxiety in youth with a lower IQ. However, care should also be taken to ensure adolescents with ASD without intellectual disabilities are not overlooked with regards to social and emotional support.
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http://dx.doi.org/10.1007/s10803-020-04810-yDOI Listing
November 2021

Links between perinatal risk factors and maternal psychological distress: A network analysis.

Acta Obstet Gynecol Scand 2021 05 5;100(5):917-926. Epub 2021 Jan 5.

Department of Psychology, University of Edinburgh, Edinburgh, UK.

Introduction: This paper explores a range of perinatal risk factors that may increase maternal vulnerability to postnatal psychological distress in a sample of 17 531 women participating in the Millennium Cohort Study, a diverse British, longitudinal birth cohort study.

Material And Methods: Using a graphical network modeling framework, this study models the links between postnatal psychological distress and perinatal risk factors, while controlling for sociodemographic factors and history of depression and anxiety. Postnatal psychological distress was assessed at 9 months postpartum using the Rutter Malaise Inventory.

Results: Results of the graphical network models indicate that lower levels of happiness about the pregnancy (Edge weight [w] = 0.084, 95% CI = 0.069-0.100, b = 0.095), smoking during pregnancy (w = 0.026, 95% CI = -0.009-0.060, b = 0.029), infection during pregnancy (w = 0.071, 95% CI = 0.024-0.118, b = 0.090), hyperemesis gravidarum (w = 0.068, 95% CI = 0.013-0.123, b = 0.083), baby in special care (w = 0.048, 95% CI = -0.004-0.099, b = 0.062), not being white (w = 0.101, 95% CI = 0.062-0.140, b = 0.118), being from a more deprived area (w = -0.028, 95% CI = -0.051 to -0.005, b = -0.039), lower income (w = -0.025, 95% CI = -0.055-0.005, b = -0.036), and history of depression or anxiety (w = 0.574, 95% CI = 0.545-0.603, b = 0.764) were associated with increased psychological distress.

Conclusions: Some perinatal risk factors may be directly associated with postnatal psychological distress, but many risk factors appear to be primarily associated with demographic factors. This emphasizes the importance of taking a holistic approach when evaluating an individual's risk of developing postnatal psychological distress.
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http://dx.doi.org/10.1111/aogs.14056DOI Listing
May 2021

Longitudinal effects of breast feeding on parent-reported child behaviour.

Arch Dis Child 2021 04 9;106(4):355-360. Epub 2020 Nov 9.

School of Philosophy, Psychology and Language Sciences, The University of Edinburgh, Edinburgh, UK.

Objective: Shorter breastfeeding duration has been linked to a range of difficulties in children. However, evidence linking shorter breastfeeding duration to child behavioural problems has been inconclusive. Owing to an almost exclusive focus on early childhood in previous research, little is known about breastfeeding effects on behaviour throughout childhood and adolescence. This study examines the longitudinal effect of breast feeding on parent-reported behaviour in children aged 3-14.

Design: Data come from the Millennium Cohort Study, a large, prospective, UK birth cohort study.

Participants: 11 148 children, their parents and teachers.

Methods: This study maps the effect of breastfeeding duration on parent-reported child behaviour longitudinally, using latent growth curve modelling and on teacher-reported child behaviour using multiple regression analyses. Breastfeeding duration was assessed through parent interviews when the child was 9 months old. Children's behavioural development was measured using parent-reported Strengths and Difficulties Questionnaires (SDQ) at 3, 5, 7, 11 and 14 years and teacher-reported SDQs at 7 and 11 years.

Results: Breast feeding was associated with fewer parent-reported behavioural difficulties at all ages even after adjusting for potential confounders (<2 months: =-0.22, 95% CI -0.39 to -0.04; 2-4 months: =-0.53, 95% CI -0.75 to -0.32; 4-6 months: =-1.07, 95% CI -1.33 to -0.81; >6 months: =-1.24, 95% CI -1.44 to -1.04; =adjusted mean difference of raw SDQ scores at age 3, reference: never breast fed).

Conclusion: This study provides further evidence supporting links between breastfeeding duration and children's socioemotional behavioural development. Potential implications include intervention strategies encouraging breast feeding.
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http://dx.doi.org/10.1136/archdischild-2020-319038DOI Listing
April 2021

Prenatal maternal infections and children's socioemotional development: findings from the UK Millennium Cohort Study.

Eur Child Adolesc Psychiatry 2021 Oct 19;30(10):1641-1650. Epub 2020 Sep 19.

Department of Psychology, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK.

Previous research suggests that prenatal maternal infections may be associated with increased odds of children having a neurodevelopmental disorder. However, little evidence exists on associations with broader child outcomes, especially subclinical symptoms. Participants were the N = 14,021 members of the population-representative UK Millennium Cohort Study. We examined associations between prenatal maternal infections, both maternal-reported and hospital-recorded, and children's socioemotional development, using the Strengths and Difficulties Questionnaire (SDQ) at age three. Maternal-reported prenatal infections were associated with increased emotional symptoms, after adjusting for several potential confounds and covariates. Hospital-recorded prenatal infections were not associated with children's socioemotional outcomes, after adjusting for potential confounding and covarying factors. Findings suggest that prenatal maternal infections, particularly those which the mothers remember months later, may be associated with increased emotional problems in early childhood. This emphasises the need for screening for and preventing infections during pregnancy. Further, the occurrence of prenatal infection indicates the potential need for early intervention for children's emotional difficulties.
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http://dx.doi.org/10.1007/s00787-020-01644-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505323PMC
October 2021

The association between analgesic drug use in pregnancy and neurodevelopmental disorders: protocol for an umbrella review.

Syst Rev 2020 09 2;9(1):202. Epub 2020 Sep 2.

Department of Psychology, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK.

Background: Maternal prenatal health has been shown to be an important influence on children's developmental outcomes, which has led to an increased emphasis on providing more information to support clinical decisions in pregnancy. Several systematic reviews suggest that analgesic drug use during pregnancy may have neurodisruptive properties. However, no firm conclusions have yet been drawn on the associations between prenatal analgesic drug use and children's long-term development of neurodevelopmental disorders such as autism spectrum disorder (ASD) or attention deficit hyperactivity disorder (ADHD). Therefore, an umbrella review is proposed for the purpose of examining the associations between maternal analgesic drug use during pregnancy and diagnoses of neurodevelopmental disorders.

Methods: Included systematic reviews will consist of studies examining the effect of maternal prenatal analgesic drug use, specifically ibuprofen, acetaminophen, aspirin, naproxen, diclofenac, and ketoprofen, on children's neurodevelopmental disorder status. Examined drugs were restricted to those readily accessible and frequently used by pregnant women, and with characteristics that allow them to cross the placenta and directly affect fetal development. Outcomes will be restricted to formal clinical diagnoses of ASD and/or ADHD. Two reviewers will independently identify eligible reviews from six databases (e.g., PubMed, EMBASE, PsychINFO) from inception dates of databases to the date of data extraction, and conduct manual searches of reference lists, consultation with field experts, and scan of pre-print archives. Extracted data will also include short qualitative summaries by both reviewers. As part of quality assessment, a standardized measurement tool to assess systematic reviews (AMSTAR 2) will be used. A narrative synthesis is proposed to integrate findings from different, potentially methodologically heterogeneous, studies.

Discussion: This umbrella review of associations between maternal prenatal use of analgesic drugs and children's neurodevelopmental disorders could allow for firmer conclusions to be drawn through the synthesis of all relevant published research. The synthesis of findings using high-quality evidence could provide more accurate healthcare information on the long-term effects of analgesic drugs on neurodevelopment, to better guide future clinical decisions during pregnancy. This review will also allow gaps and methodological differences in the literature to be identified, informing recommendations for future research.

Systematic Review Registration: PROSPERO CRD42020179216 .
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http://dx.doi.org/10.1186/s13643-020-01465-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469356PMC
September 2020

External rewards and positive stimuli promote different cognitive control engagement strategies in children.

Dev Cogn Neurosci 2020 08 21;44:100806. Epub 2020 Jun 21.

Department of Psychology, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK.

In everyday life, children often need to engage control in emotionally or motivationally relevant contexts. This study disentangled and directly compared the respective influences of external rewards and positive stimuli on childhood cognitive control. We expected external rewards to promote proactive cognitive control and positive stimuli to impair proactive control, especially in younger age. EEG data were recorded while children (5-6 years old and 9-10 years old) and adults completed a cued task-switching paradigm in three conditions: positive-stimulus, external-reward and control conditions. Provision of reward resulted in more accurate but slower responses, and more pronounced cue-locked posterior positivity, potentially suggesting general proactive mobilisation of attention (i.e., readiness). Despite no effects on behaviour, the presentation of positive stimuli was unexpectedly associated with a greater cue-locked extended slow-wave when task cues were presented ahead of targets (i.e. proactive-control possible) in younger children, suggesting greater proactive cue preparation. In contrast to our hypothesis, both external rewards and positive stimuli seem to promote different types of proactive approaches in children.
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http://dx.doi.org/10.1016/j.dcn.2020.100806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327410PMC
August 2020

Consistent use of proactive control and relation with academic achievement in childhood.

Cognition 2020 10 8;203:104329. Epub 2020 Jun 8.

Department of Psychology, University of Edinburgh, 7 George Square, EH8 9JZ Edinburgh, United Kingdom. Electronic address:

As children become older, they better maintain task-relevant information in preparation of upcoming cognitive demands. This is referred to as proactive control, which is a key component of cognitive control development. However, it is still uncertain whether children engage in proactive control consistently across different contexts and how proactive control relates to academic abilities. This study used two common tasks-the AX Continuous Performance Task (AX-CPT) and the Cued Task-Switching Paradigm (CTS)-to examine whether proactive control engagement in 102 children (age range: 6.91-10.91 years) converges between the two tasks and predicts academic abilities. Proactive control indices modestly correlated between tasks in higher but not lower working-memory children, suggesting that consistency in proactive control engagement across contexts is relatively low during childhood but increases with working memory capacity. Further, working memory (but not verbal speed) predicted proactive control engagement in both tasks. While proactive control as measured by each task predicted math and reading performance, only proactive control measured by CTS additionally predicted reasoning, suggesting that proactive control can be used as a proxy for academic achievements.
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http://dx.doi.org/10.1016/j.cognition.2020.104329DOI Listing
October 2020

Social cognition in adults with autism spectrum disorders: Validation of the Edinburgh Social Cognition Test (ESCoT).

Clin Neuropsychol 2021 10 19;35(7):1275-1293. Epub 2020 Mar 19.

Human Cognitive Neuroscience, School of Philosophy, Psychology, and Language Sciences, University of Edinburgh, Edinburgh, UK.

Objective: Many existing tests of social cognition are not appropriate for clinical use, due to their length, complexity or uncertainty in what they are assessing. The Edinburgh Social Cognition Test (ESCoT) is a new test of social cognition that assesses affective and cognitive Theory of Mind as well as inter- and intrapersonal understanding of social norms using animated interactions.

Method: To support the development of the ESCoT as a clinical tool, we derived cut-off scores from a neurotypical population ( = 236) and sought to validate the ESCoT in a sample of Autism Spectrum Disorder (ASD;  = 19) adults and neurotypical controls (NC;  38) matched on age and education. The ESCoT was administered alongside established tests and questionnaire measures of ASD, empathy, systemizing traits and intelligence.

Results: Performance on the subtests of the ESCoT and ESCoT total scores correlated with performance on traditional tests, demonstrating convergent validity. ASD adults performed poorer on all measures of social cognition. Unlike the ESCoT, performance on the established tests was predicted by verbal comprehension abilities. Using a ROC curve analysis, we showed that the ESCoT was more effective than existing tests at differentiating ASD adults from NC. Furthermore, a total of 42.11% of ASD adults were impaired on the ESCoT compared to 0% of NC adults.

Conclusions: Overall these results demonstrate that the ESCoT is a useful test for clinical assessment and can aid in the detection of potential difficulties in ToM and social norm understanding.
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http://dx.doi.org/10.1080/13854046.2020.1737236DOI Listing
October 2021

Effects of oxytocin administration on salivary sex hormone levels in autistic and neurotypical women.

Mol Autism 2020 03 18;11(1):20. Epub 2020 Mar 18.

Autism Research Centre, Department of Psychiatry, University of Cambridge, 18b Trumpington Road, Cambridge, CB2 8AH, UK.

Background: Oxytocin administration, which may be of therapeutic value for individuals with social difficulties, is likely to affect endogenous levels of other socially relevant hormones. However, to date, the effects of oxytocin administration on endogenous hormones have only been examined in neurotypical individuals. The need to consider multi-hormone interactions is particularly warranted in oxytocin trials for autism due to evidence of irregularities in both oxytocin and sex steroid systems.

Methods: In this double-blind cross-over study, saliva samples were collected from 16 autistic and 29 neurotypical women before and after intranasal administration of 24 IU oxytocin or placebo. Oestradiol, testosterone, and oxytocin levels were quantified in saliva samples. Participants also completed the Autism-Spectrum Quotient (AQ) and Empathy Quotient (EQ) questionnaires.

Results: Distinct patterns of change in testosterone and oestradiol levels pre- to-post-administration were observed in autistic relative to neurotypical women (ANCOVA, p < 0.05 main effect of Group), controlling for sample collection time. The mean percent change oestradiol was + 8.8% for the autism group and - 13.0% for the neurotypical group (t = 1.81, p = 0.08), while the mean percent change testosterone was + 1.1% in the autism group and - 12.6% in the neurotypical group (t = 1.26, p = 0.22). In the oxytocin condition, the mean percent change oestradiol was + 12.6% in the autism group and - 6.9% in the neurotypical group (t = 1.78, p = 0.08), while the mean percent change testosterone was + 14.4% in the autism group and - 15.2% in the neurotypical group (t = 3.00, p = 0.006). Robust regression confirmed that group differences in percent change hormone levels were not driven by a small number of influential individuals. Baseline hormone levels did not differ between groups when considered individually. However, baseline testosterone relative to oestradiol (T:E2 ratio) was higher in autistic women (p = 0.023, Cohen's d = 0.63), and this ratio correlated positively and negatively with AQ and EQ scores, respectively, in the combined sample.

Limitations: Further studies with larger and more diverse autistic sample are warranted to confirm these effects.

Conclusions: This study provides the first evidence that oxytocin influences endogenous testosterone levels in autistic individuals, with autistic women showing increases similar to previous reports of neurotypical men. These findings highlight the need to consider sex steroid hormones as a variable in future oxytocin trials.
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http://dx.doi.org/10.1186/s13229-020-00326-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079504PMC
March 2020

Reciprocal Developmental Relations Between ADHD and Anxiety in Adolescence: A Within-Person Longitudinal Analysis of Commonly Co-Occurring Symptoms.

J Atten Disord 2020 Mar 14:1087054720908333. Epub 2020 Mar 14.

University of Cambridge, UK.

Significant anxiety often occurs in the presence of ADHD symptoms; however, the reasons are not well understood. We aimed to establish whether the relations between ADHD symptons and anxiety are bidirectional or unidirectional.

Method: Weexamined the developmental relations between ADHD and anxiety symptoms across adolescence (ages 13, 15, and 17) in a community-ascertained, normative longitudinal sample of 1,483 youth (52% male). We used an autoregressive latent trajectory model with structured residuals (ALT-SR) to examine within-person developmental relations between ADHD and anxiety symptoms to determine whether it is ADHD symptoms that lead to anxiety symptoms and/or the reverse.

Results: Results suggested that there are reciprocal within-person developmental relations between ADHD and anxiety symptoms.

Conclusions: Our findings support the recommendation that targeting ADHD symptoms can be fruitful for addressing anxiety symptoms; however, they suggest that targeting anxiety symptoms may also benefit ADHD symptoms. Results also underline the importance of careful assessment for underlying ADHD symptoms among adolescents presenting with anxiety.
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http://dx.doi.org/10.1177/1087054720908333DOI Listing
March 2020

Foetal oestrogens and autism.

Mol Psychiatry 2020 11 29;25(11):2970-2978. Epub 2019 Jul 29.

Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK.

Elevated latent prenatal steroidogenic activity has been found in the amniotic fluid of autistic boys, based on measuring prenatal androgens and other steroid hormones. To date, it is unclear if other prenatal steroids also contribute to autism likelihood. Prenatal oestrogens need to be investigated, as they play a key role in synaptogenesis and corticogenesis during prenatal development, in both males and females. Here we test whether levels of prenatal oestriol, oestradiol, oestrone and oestrone sulphate in amniotic fluid are associated with autism, in the same Danish Historic Birth Cohort, in which prenatal androgens were measured, using univariate logistic regression (n = 98 cases, n = 177 controls). We also make a like-to-like comparison between the prenatal oestrogens and androgens. Oestradiol, oestrone, oestriol and progesterone each related to autism in univariate analyses after correction with false discovery rate. A comparison of standardised odds ratios showed that oestradiol, oestrone and progesterone had the largest effects on autism likelihood. These results for the first time show that prenatal oestrogens contribute to autism likelihood, extending the finding of elevated prenatal steroidogenic activity in autism. This likely affects sexual differentiation, brain development and function.
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http://dx.doi.org/10.1038/s41380-019-0454-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577840PMC
November 2020

Age-related differentiation in verbal and visuospatial working memory processing in childhood.

Psychol Res 2020 Nov 12;84(8):2354-2360. Epub 2019 Jul 12.

Center for Research on Individual Development and Adaptive Education of Children at Risk (IDeA), Frankfurt, Germany.

Working memory (WM), a key feature of the cognitive system, allows for maintaining and processing information simultaneously and in a controlled manner. WM processing continuously develops across childhood, with significant increases both in verbal and visuospatial WM. Verbal and visuospatial WM may show different developmental trajectories, as verbal (but not visuospatial) WM relies on internal verbal rehearsal, which is less developed in younger children. We examined complex VWM and VSWM performance in 125 younger (age 4-6 years) and 101 older (age 8-10 years) children. Latent multi-group modeling showed that (1) older children performed better on both verbal and visuospatial WM span tasks than younger children, (2) both age groups performed better on verbal than visuospatial WM, and (3) a model with two factors representing verbal and visuospatial WM fit the data better than a one-factor model. Importantly, the correlation between the two factors was significantly higher in younger than in older children, suggesting an age-related differentiation of verbal and spatial WM processing in middle childhood. Age-related differentiation is an important characteristic of cognitive functioning and thus the findings contribute to our general understanding of WM processing.
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http://dx.doi.org/10.1007/s00426-019-01219-wDOI Listing
November 2020

10Kin1day: A Bottom-Up Neuroimaging Initiative.

Front Neurol 2019 9;10:425. Epub 2019 May 9.

Department of Psychiatry, Stellenbosch University, Cape Town, South Africa.

We organized 10Kin1day, a pop-up scientific event with the goal to bring together neuroimaging groups from around the world to jointly analyze 10,000+ existing MRI connectivity datasets during a 3-day workshop. In this report, we describe the motivation and principles of 10Kin1day, together with a public release of 8,000+ MRI connectome maps of the human brain.
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http://dx.doi.org/10.3389/fneur.2019.00425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524614PMC
May 2019

Differentiation in prefrontal cortex recruitment during childhood: Evidence from cognitive control demands and social contexts.

Dev Cogn Neurosci 2019 04 19;36:100629. Epub 2019 Mar 19.

Department of Psychology, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK.

Emerging cognitive control during childhood is largely supported by the development of distributed neural networks in which the prefrontal cortex (PFC) is central. The present study used fNIRS to examine how PFC is recruited to support cognitive control in 5-6 and 8-9-year-old children, by (a) progressively increasing cognitive control demands within the same task, and (b) manipulating the social context in which the task was performed (neutral, cooperative, or competitive), a factor that has been shown to influence cognitive control. Activation increased more in left than right PFC with cognitive control demands, a pattern which was more pronounced in older than younger children. In addition, activation was higher in left PFC in competitive than cooperative contexts, and higher in right PFC in cooperative and neutral than competitive contexts. These findings suggest that increasingly efficient cognitive control during childhood is supported by more differentiated recruitment of PFC as a function of cognitive control demands with age.
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http://dx.doi.org/10.1016/j.dcn.2019.100629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969260PMC
April 2019

Autism prevalence in China is comparable to Western prevalence.

Mol Autism 2019 28;10. Epub 2019 Feb 28.

1Cambridge Institute of Public Health, Department of Public Health and Primary Care, University of Cambridge, Forvie Site, Robinson Way, Cambridge, CB2 0SR UK.

Background: Autism prevalence in the West is approximately 1% of school age children. Autism prevalence in China has been reported to be lower than in the West. This is likely due to at least two reasons: (1) most studies in China only included the special school population, overlooking the mainstream school population; and (2) most studies in China have not used contemporary screening and diagnostic methods. To address this, we tested total autism prevalence (mainstream and special schools) in Jilin City, and mainstream school autism prevalence in Jiamusi and Shenzhen cities.

Methods: The study included a three-step process: (1) screening; (2) clinical assessment of 'screen positives' plus controls; and (3) research diagnostic assessment of those meeting clinical threshold for concerns at step 2. Prevalence estimates per 10,000 children aged 6-10 years old were weighted for study design using diagnostic criteria applied at the research assessment stage.

Results: In Jilin City, 77 cases of autism were identified from a total population of 7258, equating to a prevalence of 108 per 10,000 (95% confidence interval (CI) 89, 130). In Shenzhen City: 21,420 children were screened and 35 cases of autism were identified, resulting in a mainstream prevalence of 42 per 10,000 (95% CI 20-89). In Jiamusi City, 16,358 children were screened, with 10 autism cases being identified, with a mainstream prevalence of 19 per 10,000 (95% CI 10-38).

Conclusions: Results from Jilin City, where both mainstream and special school data were available, revealed a similar prevalence of autism in China to the West, at around 1%. Results from Shenzhen and Jiamusi cities, where only mainstream data were available, prevalence is also in line with Western estimates. In all three cities, new cases of autism were identified by the study in mainstream schools, reflecting current under-diagnosis. Non-significant variation across different cities is seen indicating the need to explore potential variation of autism across diverse Chinese regions with large sample sizes to achieve a fully robust national picture.
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http://dx.doi.org/10.1186/s13229-018-0246-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394100PMC
April 2019

Introducing the Joint EEG-Development Inference (JEDI) Model: A Multi-Way, Data Fusion Approach for Estimating Paediatric Developmental Scores via EEG.

IEEE Trans Neural Syst Rehabil Eng 2019 03 10;27(3):348-357. Epub 2019 Jan 10.

Accounting for developmental changes in children is a key consideration for adapting neurorehabilitation technologies to paediatric populations. Using well-established clinical tests and questionnaires can be resource and time intensive. With many data-driven rehabilitation approaches relying on EEG data, a means to rapidly assess and infer developmental status of children directly from these recordings could be critical. This paper proposes a new model for estimating classic developmental diagnostic scores by exploiting data fusion in a joint tensor-matrix decomposition of the EEG and score data. We have designated this model the joint EEG-development inference (JEDI) model. The proposed model is illustrated using a common EEG task (button press) via publicly available paediatric data from pre-adolescent children. Using three distinct recording blocks for training, validation, and testing and a ten-fold cross-validation scheme, a robust experimental design was used to evaluate the JEDI model under various conditions. Results indicate that the JEDI model can estimate the developmental scores of children while maintaining a high degree of similarity at a population level. These results highlight the JEDI model as a potential evolving tool for rapidly assessing child's development. Clinically, the proposed model could provide useful developmental information in a convenient and low resource manner.
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http://dx.doi.org/10.1109/TNSRE.2019.2891827DOI Listing
March 2019

Psychometric properties of the chinese version of autism spectrum quotient-children's version: A sex-specific analysis.

Autism Res 2019 02 28;12(2):303-315. Epub 2018 Dec 28.

Department of Maternal and Child Health, School of Public Health, Sun Yat-Sen University, Guangzhou, China.

A Simplified Chinese translation of the Autism Spectrum Quotient-Children's Version (AQ-C) is needed for research in mainland China. Autism Spectrum Disorder (ASD) is a condition that differs in presentation and prevalence by sex. Thus, evaluating the psychometric validity of the AQ-C in males and females is an important step in its validation. The present study aims to develop a Chinese translation of the parent-report AQ-C, and test its psychometric properties among Mandarin Chinese speaking boys and girls. A total of 1,020 non-clinical children and 134 children with ASD were assessed. Factor analyses were performed for the whole sample, as well as for girls and boys separately. A 30-item, 5-factor model (the Chinese AQ-C) showed adequate goodness of fit (root mean square error of approximation [RMSEA] = 0.037; comparative fit index [CFI] = 0.907; Tucker-Lewis index [TLI] = 0.901) for the whole sample. According to parents' reports, non-clinical boys had significantly higher scores than non-clinical girls on the Chinese AQ-C. Sex-specific factor structures were identified resulting in a 4-factor model with 32 items for girls (the Chinese AQ-Girls), and a 4-factor model with 34 items for boys (the Chinese AQ-Boys). The cut-off scores of the Chinese AQ-C, AQ-Girls, and AQ-Boys were 44.5, 42.5, and 46.5, respectively. These three Chinese versions of the AQ-C all showed satisfactory internal consistency (α = 0.786-0.840) and concurrent validity with the Social Responsiveness Scale (r = 0.789-0.814) for the total scale. Differences have been found in the sex-specific factor structures of the AQ-C which would be more reliable to use for future research when measuring autistic traits in the general population. Autism Res 2019, 12: 303-315 © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This study developed Chinese versions of the Autism Spectrum Quotient-Children's Version (AQ-C) in Chinese boys and girls together and separately. The AQ-C showed good psychometric properties in boys and girls together and separately. There were differences in sex-specific factor structures of the AQ-C. These results suggest that the sex-specific Chinese versions of the AQ-C provide reliable and valid measurement of autistic traits.
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http://dx.doi.org/10.1002/aur.2053DOI Listing
February 2019

A cross-cultural study of autistic traits across India, Japan and the UK.

Mol Autism 2018 5;9:52. Epub 2018 Nov 5.

1Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Background: There is a global need for brief screening instruments that can identify key indicators for autism to support frontline professionals in their referral decision-making. Although a universal set of conditions, there may be subtle differences in expression, identification and reporting of autistic traits across cultures. In order to assess the potential for any measure for cross-cultural screening use, it is important to understand the relative performance of such measures in different cultures. Our study aimed to identify the items on the Autism Spectrum Quotient (AQ)-Child that are most predictive of an autism diagnosis among children aged 4-9 years across samples from India, Japan and the UK.

Methods: We analysed parent-reported AQ-Child data from India (73 children with an autism diagnosis and 81 neurotypical children), Japan (116 children with autism and 190 neurotypical children) and the UK (488 children with autism and 532 neurotypical children). None of the children had a reported existing diagnosis of intellectual disability. Discrimination indices (DI) and positive predictive values (PPV) were used to identify the most predictive items in each country.

Results: Sixteen items in the Indian sample, 15 items in the Japanese sample and 28 items in the UK sample demonstrated excellent discriminatory power (DI ≥ 0.5 and PPV ≥ 0.7), suggesting these items represent the strongest indicators for predicting an autism diagnosis within these countries. Across cultures, good performing items were largely overlapping, with five key indicator items appearing across all three countries (can easily keep track of several different people's conversations, enjoys social chit-chat, knows how to tell if someone listening to him/her is getting bored, good at social chit-chat, finds it difficult to work out people's intentions). Four items indicated potential cultural differences. One item was highly discriminative in Japan but poorly discriminative (DI < 0.3) in the UK and India, and a further item had excellent discrimination properties in the UK but poorly discriminated in the Indian and Japanese samples. Two additional items were highly discriminative in two cultures but poor in the third.

Conclusions: Cross-cultural overlap in the items most predictive of an autism diagnosis supports the general notion of universality in autistic traits whilst also highlighting that there can be cultural differences associated with certain autistic traits. These findings have the potential to inform the development of a brief global screening tool for autism. Further development and evaluation work is needed.
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http://dx.doi.org/10.1186/s13229-018-0235-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6217788PMC
December 2018

Neural self-representation in autistic women and association with 'compensatory camouflaging'.

Autism 2019 07 24;23(5):1210-1223. Epub 2018 Oct 24.

2 University of Cambridge, UK.

Prior work has revealed sex/gender-dependent autistic characteristics across behavioural and neural/biological domains. It remains unclear whether and how neural sex/gender differences are related to behavioural sex/gender differences in autism. Here, we examined whether atypical neural responses during mentalizing and self-representation are sex/gender-dependent in autistic adults and explored whether 'camouflaging' (acting as if behaviourally neurotypical) is associated with sex/gender-dependent neural responses. In total,  = 119 adults (33 typically developing males, 29 autistic males, 29 typically developing females and 28 autistic females) participated in a task-related functional magnetic resonance imaging paradigm to assess neural activation within right temporo-parietal junction and ventromedial prefrontal cortex during mentalizing and self-representation. Camouflaging in autism was quantified as the discrepancy between extrinsic behaviour in social-interpersonal contexts and intrinsic status. While autistic men showed hypoactive right temporo-parietal junction mentalizing and ventromedial prefrontal cortex self-representation responses compared to typically developing men, such neural responses in autistic women were not different from typically developing women. In autistic women only, increasing camouflaging was associated with heightened ventromedial prefrontal cortex self-representation response. There is a lack of impaired neural self-representation and mentalizing in autistic women compared to typically developing women. Camouflaging is heightened in autistic women and may relate to neural self-representation response. These results reveal brain-behaviour relations that help explain sex/gender-heterogeneity in social brain function in autism.
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http://dx.doi.org/10.1177/1362361318807159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589917PMC
July 2019

Sex differences in ADHD trajectories across childhood and adolescence.

Dev Sci 2019 01 29;22(1):e12721. Epub 2018 Aug 29.

Jacob's Center for Productive Youth Development, University of Zurich, Zurich, Switzerland.

Previous studies have hinted at sex differences in developmental trajectories in ADHD symptoms; however, little is known about the nature or cause of these differences and their implications for clinical practice. We used growth mixture modelling in a community-ascertained cohort of n = 1,571 participants to study sex differences in ADHD symptom developmental trajectories across the elementary and secondary school years. Participants were measured at ages 7, 8, 9, 10, 11, 12, 13, and 15. We found that females were more likely to show large symptom increases in early adolescence while males were more likely to show elevated symptoms from childhood. For both males and females, early adolescence represented a period of vulnerability characterized by relatively sudden symptom increases. Females affected by hyperactivity/impulsivity may be more likely to be excluded from diagnosis due to current age of onset criteria. More attention should be paid to early adolescence as a period of risk for hyperactivity/impulsivity symptom onset or worsening.
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http://dx.doi.org/10.1111/desc.12721DOI Listing
January 2019

Outcomes of ADHD Symptoms in Late Adolescence: Are Developmental Subtypes Important?

J Atten Disord 2020 01 22;24(1):113-125. Epub 2018 Aug 22.

University of Cambridge, UK.

Substantial individual variation exists in the age of onset and course of ADHD symptoms over development. We evaluated whether, within this variation, meaningful developmental subtypes can be defined. Using growth mixture modeling in a community-based sample ( = 1,571), we analyzed ADHD symptom trajectories based on measures taken at ages 7, 8, 9, 10, 11, 13, and 15 years. We evaluated whether those showing developmental trajectories characterized by later onsets versus early onsets differed in terms of mental health and behavioral outcomes in late adolescence (age 17 years). The late onset category was best conceptualized as a milder subtype than early onset. The former was, however, more similar in outcomes to the latter than to the unaffected category, suggesting that later onsets are still associated with impairment. Considering diagnoses for those affected by ADHD symptoms but who do not meet current age of onset criteria may be important for ensuring that they receive appropriate support.
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http://dx.doi.org/10.1177/1087054718790588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611469PMC
January 2020

Sex-specific impact of prenatal androgens on social brain default mode subsystems.

Mol Psychiatry 2020 09 13;25(9):2175-2188. Epub 2018 Aug 13.

Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.

Early-onset neurodevelopmental conditions (e.g., autism) affect males more frequently than females. Androgens may play a role in this male-bias by sex-differentially impacting early prenatal brain development, particularly neural circuits that later develop specialized roles in social cognition. Here, we find that increasing prenatal testosterone in humans is associated with later reduction of functional connectivity between social brain default mode (DMN) subsystems in adolescent males, but has no effect in females. Since testosterone can work directly via the androgen receptor (AR) or indirectly via the estrogen receptor through aromatase conversion to estradiol, we further examined how a potent non-aromatizable androgen, dihydrotestosterone (DHT), acts via the AR to influence gene expression in human neural stem cells (hNSC)-particularly for genes of high-relevance for DMN circuitry. DHT dysregulates a number of genes enriched for syndromic causes of autism and intellectual disability and for genes that in later development are expressed in anatomical patterns that highly correspond to the cortical midline DMN subsystem. DMN-related and DHT-affected genes (e.g., MEF2C) are involved in a number of synaptic processes, many of which impact excitation-inhibition balance. Androgens have male-specific prenatal influence over social brain circuitry in humans and may be relevant towards explaining some component of male-bias in early-onset neurodevelopmental conditions.
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http://dx.doi.org/10.1038/s41380-018-0198-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473837PMC
September 2020

Sex Differences in the Adult Human Brain: Evidence from 5216 UK Biobank Participants.

Cereb Cortex 2018 08;28(8):2959-2975

Department of Psychology, The University of Edinburgh, Edinburgh, UK.

Sex differences in the human brain are of interest for many reasons: for example, there are sex differences in the observed prevalence of psychiatric disorders and in some psychological traits that brain differences might help to explain. We report the largest single-sample study of structural and functional sex differences in the human brain (2750 female, 2466 male participants; mean age 61.7 years, range 44-77 years). Males had higher raw volumes, raw surface areas, and white matter fractional anisotropy; females had higher raw cortical thickness and higher white matter tract complexity. There was considerable distributional overlap between the sexes. Subregional differences were not fully attributable to differences in total volume, total surface area, mean cortical thickness, or height. There was generally greater male variance across the raw structural measures. Functional connectome organization showed stronger connectivity for males in unimodal sensorimotor cortices, and stronger connectivity for females in the default mode network. This large-scale study provides a foundation for attempts to understand the causes and consequences of sex differences in adult brain structure and function.
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http://dx.doi.org/10.1093/cercor/bhy109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6041980PMC
August 2018

The effects of verbal and spatial memory load on children's processing speed.

Ann N Y Acad Sci 2018 07 30;1424(1):161-174. Epub 2018 Apr 30.

Department of Psychology, University of Edinburgh, Edinburgh, Scotland, United Kingdom.

Examining the impact of maintenance on processing speed allows us to test whether storage and processing resources are shared. Comparing these relationships in children of different ages allows further insight into whether one or multiple resources for these operations must be assumed and whether remembering is proactive throughout childhood. We tested 185 4- to 6- and 8- to 10-year-old children using adaptive complex span tasks, in which simple judgments were interleaved between to-be-remembered items. The adaptiveness of our tasks ensured that all participants frequently correctly recalled the items. If storage and processing require a single resource, and if participants serially reactivate the memoranda between processing episodes, processing response times should increase with serial position of the processing judgment within lists. We observed different within-list dynamics for each age group. Older children's processing judgments slowed gradually when more than two memory items were maintained. By contrast, younger children showed no evidence of slower processing with increasing memory load. Our results support models of working memory that assume that some common resource is responsible for verbal and spatial storage and processing. They also support the notion that remembering becomes more proactive as children mature.
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http://dx.doi.org/10.1111/nyas.13653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849596PMC
July 2018
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