The Effect of Probabilistic Context on Implicit Temporal Expectations in Down Syndrome

One of the most important sources of predictability that human beings can exploit to create an internal representation of the external environment is the ability to implicitly build up subjective statistics of events\u2019 temporal structure and, consequently, use this knowledge to prepare for future actions. Stimulus expectancy can be subjectively shaped by hierarchically nested sources of prediction, capitalizing on either local or global probabilistic rules. In order to better understand the nature of local-global proactive motor control in Down Syndrome, in the present study a group of participants with Down Syndrome (DS group; n = 28; mean age 29.5 \ub1 13 years; range 10\u201354) and a group of typically developing participants matched by either gender or mental age (TD-MA group; n = 28; 5.6 \ub1 1 years; range 4\u20138) were administered a novel motor preparation task, defined as the Dynamic Temporal Prediction (DTP) task. In the DTP, the temporal preparation to imperative stimuli is implicitly shaped by the local increase of expectancy. This is manipulated trial-by-trial as a function of the preparatory foreperiod interval (Stimulus-Onset Asynchrony or SOA). In addition, temporal preparation can be also implicitly adjusted as a function of global predictive context, so that a block-wise SOA-distribution bias toward a given preparatory interval might determine a high-order source of expectancy, with functional consequences on proactive motor control adjustment. Results showed that in both groups motor preparation was biased by temporal expectancy when this was locally manipulated within-trials. By contrast, only the TD-MA group was sensitive to global rule changes: only in this cohort was behavioral performance overall impacted by the SOA probabilistic distribution manipulated between-blocks. The evidence of a local-global dissociation in DS suggests that the use of flexible cognitive mechanisms to implicitly extract high-order probabilistic rules in order to build-up an internal model of the temporal properties of events is disrupted in this developmental disorder. Moreover, since the content of the information to be processed in the DTP task was neither verbal nor spatial, we suggest that atypical global processing in Down Syndrome is a domain-general rather than specific aspect characterizing the cognitive profile of this population

Attention deficits predict phenotypic outcomes in syndrome-specific and domain-specific ways

Attentional difficulties, both at home and in the classroom, are reported across a number of neurodevelopmental disorders. However, exactly how attention influences early socio-cognitive learning remains unclear. We addressed this question both concurrently and longitudinally in a cross-syndrome design, with respect to the communicative domain of vocabulary and to the cognitive domain of early literacy, and then extended the analysis to social behavior. Participants were young children (aged 4–9 years at Time 1) with either Williams syndrome (WS, N = 26) or Down syndrome (DS, N = 26) and typically developing controls (N = 103). Children with WS displayed significantly greater attentional deficits (as indexed by teacher report of behavior typical of attention deficit hyperactivity disorder (ADHD) than children with DS, but both groups had greater attentional problems than the controls. Despite their attention differences, children with DS and those with WS were equivalent in their cognitive abilities of reading single words, both at Time 1 and 12 months later, at Time 2, although they differed in their early communicative abilities in terms of vocabulary. Greater ADHD-like behaviors predicted poorer subsequent literacy for children with DS, but not for children with WS, pointing to syndrome-specific attentional constraints on specific aspects of early development. Overall, our findings highlight the need to investigate more precisely whether and, if so, how, syndrome-specific profiles of behavioral difficulties constrain learning and socio-cognitive outcomes across different domains

Dynamic sustained attention markers differentiate atypical development: the case of Williams syndrome and Down's syndrome

Impaired sustained attention is considered an important factor in determining poor functional outcomes across multiple cognitive and behavioural disorders. Sustained attention is compromised for both children with Williams syndrome (WS) and Down's syndrome (DS), but specific difficulties remain poorly understood because of limitations in how sustained attention has been assessed thus far. In the current study, we compared the performance of typically developing children (N = 99), children with WS (N = 25), and children with DS (N = 18), on a Continuous Performance Task - a standard tool for measuring sustained attention. In contrast to previous studies, primarily focused on overall differences in mean performance, we estimated the extent to which performance changed over time on task, thus focusing directly on the sustained element of performance. Children with WS and children with DS performed more poorly overall compared to typically developing children. Importantly, measures specific to changes over time differentiated between children with the two syndromes. Children with WS showed a decrement in performance, whereas children with Down's syndrome demonstrated non-specific poor performance. In addition, our measure of change in performance predicted teacher-rated attention deficits symptoms across the full sample. An approach that captures dynamic changes in performance over assessments may be fruitful for investigating similarities and differences in sustained attention for other atypically developing populations. [Abstract copyright: Copyright © 2019. Published by Elsevier Ltd.

Visual attention and autistic behavior in infants with fragile X syndrome

Fragile X syndrome (FXS) is the leading known inherited cause of intellectual disability and the most common known biological cause of autism. Approximately 25% to 50% of males with FXS meet full diagnostic criteria for autism. Despite the high comorbidity between FXS and autism and the ability to diagnose FXS prenatally or at birth, no studies have examined indicators of autism in infants with FXS. The current study focused on indices of visual attention, one of the earliest and most robust behavioral indicators of autism in idiopathic (non-FXS) autism. Analyses revealed lower HR variability, shallower HR decelerations, and prolonged look durations in 12-month old infants with FXS that were correlated with severity of autistic behavior but not mental age

The adolescent HIV executive function and drumming (AHEAD) study, a feasibility trial of a group drumming intervention amongst adolescents with HIV

AHEAD feasibility trial assessed the feasibility and acceptability of an 8-session group drummingprogramme aiming to improve executive function, depression and anxiety symptoms, andperceived social support in adolescents living with HIV in a rural low-income South Africansetting. Sixty-eight 12- to 19-year-old adolescents participated. They were individuallyrandomised. The intervention arm (n= 34) received weekly hour-long group drumming sessions.Controls (n= 34) received no intervention. Feasibility and acceptability were assessed usingrates of: enrolment; retention; attendance; logistical problems; adolescent-reportedacceptability. Secondary measures included:five Oxford Cognitive Screen-Executive Function(OCS-EF) tasks; two Rapid Assessment of Cognitive and Emotional Regulation (RACER) tasks; theSelf-Reporting Questionnaire-20 (SRQ-20) measuring depression and anxiety symptoms; theMultidimensional Scale of Perceived Social Support (MSPSS). All feasibility criteria were withingreen progression limits. Enrolment, retention, and acceptability were high. There was a positive effect on adolescent depressed mood with a signal for a working memory effect. There were no significant effects on executive function or socio-emotional scales. Qualitative findings suggested socio-emotional benefits including group belonging; decreased internalised stigma; improved mood; and decreased anxiety. Group drumming is a feasible and acceptable intervention among adolescents living with HIV in rural South Africa. A full-scale trial is recommendedAfrica-Oxford Initiative (AfiOx-32), the Society for Education, Music and Psychology Research (SEMPRE) Gerry Farrell scholarship, the Murray Speight grant, the Rhodes Trust, and the Medical Research Council United Kingdom.https://www.tandfonline.com/loi/caic20Musi

Metabolite profiles of medulloblastoma for rapid and non-invasive detection of molecular disease groups

BackgroundThe malignant childhood brain tumour, medulloblastoma, is classified clinically into molecular groups which guide therapy. DNA-methylation profiling is the current classification ‘gold-standard’, typically delivered 3–4 weeks post-surgery. Pre-surgery non-invasive diagnostics thus offer significant potential to improve early diagnosis and clinical management. Here, we determine tumour metabolite profiles of the four medulloblastoma groups, assess their diagnostic utility using tumour tissue and potential for non-invasive diagnosis using in vivo magnetic resonance spectroscopy (MRS).MethodsMetabolite profiles were acquired by high-resolution magic-angle spinning NMR spectroscopy (MAS) from 86 medulloblastomas (from 59 male and 27 female patients), previously classified by DNA-methylation array (WNT (n = 9), SHH (n = 22), Group3 (n = 21), Group4 (n = 34)); RNA-seq data was available for sixty. Unsupervised class-discovery was performed and a support vector machine (SVM) constructed to assess diagnostic performance. The SVM classifier was adapted to use only metabolites (n = 10) routinely quantified from in vivo MRS data, and re-tested. Glutamate was assessed as a predictor of overall survival.FindingsGroup-specific metabolite profiles were identified; tumours clustered with good concordance to their reference molecular group (93%). GABA was only detected in WNT, taurine was low in SHH and lipids were high in Group3. The tissue-based metabolite SVM classifier had a cross-validated accuracy of 89% (100% for WNT) and, adapted to use metabolites routinely quantified in vivo, gave a combined classification accuracy of 90% for SHH, Group3 and Group4. Glutamate predicted survival after incorporating known risk-factors (HR = 3.39, 95% CI 1.4–8.1, p = 0.025).InterpretationTissue metabolite profiles characterise medulloblastoma molecular groups. Their combination with machine learning can aid rapid diagnosis from tissue and potentially in vivo. Specific metabolites provide important information; GABA identifying WNT and glutamate conferring poor prognosis

Shorter spontaneous fixation durations in infants with later emerging autism

Little is known about how spontaneous attentional deployment differs on a millisecond-level scale in the early development of autism spectrum disorders (ASD). We measured fine-grained eye movement patterns in 6-to 9-month-old infants at high or low familial risk (HR/LR) of ASD while they viewed static images. We observed shorter fixation durations (i.e. the time interval between saccades) in HR than LR infants. Preliminary analyses indicate that these results were replicated in a second cohort of infants. Fixation durations were shortest in those infants who went on to receive an ASD diagnosis at 36 months. While these findings demonstrate early-developing atypicality in fine-grained measures of attentional deployment early in the etiology of ASD, the specificity of these effects to ASD remains to be determined

Genetic modifiers in rare disorders: the case of fragile X syndrome.

Methods employed in genome-wide association studies are not feasible ways to explore genotype-phenotype associations in rare disorders due to limited statistical power. An alternative approach is to examine relationships among specific single nucleotide polymorphisms (SNPs), selected a priori, and behavioural characteristics. Here, we adopt this strategy to examine relationships between three SNPs (5-HTTLPR, MAOA, COMT) and specific clinically-relevant behaviours that are phenotypic of fragile X syndrome (FXS) but vary in severity and frequency across individuals. Sixty-four males with FXS participated in the current study. Data from standardised informant measures of challenging behaviour (defined as physical aggression, property destruction, stereotyped behaviour, and self-injury), autism symptomatology, attention-deficit-hyperactivity-disorder characteristics, repetitive behaviour and mood/interest and pleasure were compared between each SNP genotype. No association was observed between behavioural characteristics and either 5-HTTLPR (serotonin) or MAOA (monoamine oxidase) genotypes. However, compared to the COMT (dopamine) AG and GG genotypes, the AA genotype was associated with greater interest and pleasure in the environment, and with reduced risk for property destruction, stereotyped behaviour and compulsive behaviour. The results suggest that common genetic variation in the COMT genotype affecting dopamine levels in the brain may contribute to the variability of challenging and repetitive behaviours and interest and pleasure in this population. This study identifies a role for additional genetic risk in understanding the neural and genetic mechanisms contributing to phenotypic variability in neurodevelopmental disorders, and highlights the merit of investigating SNPs that are selected a priori on a theoretical basis in rare populations