Gamified Attention Training in the Primary School Classroom: A Cluster-Randomized Controlled Trial.

Objective: This randomized controlled trial evaluated the efficacy of attention training delivered in class on cognitive attention processes, inattention, hyperactivity, working memory, and numeracy in primary school children. Method: Eight classes (n = 98 children; 5-9 years) were cluster randomized to gamified attention training, a placebo program, or a no-contact control condition. Assessments were conducted at baseline, immediately after the 5-week intervention (posttraining), and 6 months later (follow-up). Results: Posttraining, attention training was associated with reduced inattention and hyperactivity within the classroom compared with controls, and reduced hyperactivity at home compared with the no-contact control. At follow-up, reduced hyperactivity within the classroom compared with the no-contact control persisted. No effects of training on cognitive attention processes, working memory, and numeracy were observed posttraining. Conclusion: Classroom-based attention training has select benefits in reducing inattention and hyperactivity, but may not promote gains in cognitive or academic skills in primary school children.

Higher Tablet Use Is Associated With Better Sustained Attention Performance but Poorer Sleep Quality in School-Aged Children.

There are growing concerns that increased screen device usage may have a detrimental impact on classroom behaviour and attentional focus. The consequences of screen use on child cognitive functioning have been relatively under-studied, and results remain largely inconsistent. Screen usage may displace the time usually spent asleep. The aim of this study was to examine associations between screen use, behavioural inattention and sustained attention control, and the potential modifying role of sleep. The relations between screen use, behavioural inattention, sustained attention and sleep were investigated in 162 6- to 8-year-old children, using parent-reported daily screen use, the SWAN ADHD behaviour rating scale, The sustained attention to response task and the children's sleep habits questionnaire. Tablet use was associated with better sustained attention performance but was not associated with classroom behavioural inattention. Shorter sleep duration was associated with poorer behavioural inattention and sustained attention. Sleep quality and duration did not act as mediators between screen usage and behavioural inattention nor sustained attention control. These findings suggest that careful management of the amount of time spent on electronic screen devices could have a beneficial cognitive impact on young children. The results also highlight the critical role of sleep in enhancing both behavioural attention and sustained attention, which are essential for supporting cognitive development and learning.

A child-focused version of the Attention Network Task designed to investigate interactions between the attention networks, including the endogenous orienting network.

A new variation of the Attention Network Task (ANT) was designed to measure the functioning of and interactions between the alerting, exogenous and endogenous visual spatial orienting, and executive control systems in young school children. Previous research has produced mixed results regarding typical functioning of the attention networks in six-year-olds; no ANT has measured the functioning of the endogenous network. This Staged ANT tested the Alerting, Exogenous, and Endogenous orienting networks in separate conditions. Two hundred and forty-seven children (average age 6 years, 103 girls) completed the task. There was no clear benefit of the alerting cue until the spatial orienting cues were introduced into the task, suggesting task complexity was needed before alerting benefits were observed. The validity effect of the exogenous cue was very strong: in contrast, the validity effect of the endogenous cue was very weak. The flanker effect was very strong. A benefit of the alerting cue was shown during both the exogenous and endogenous conditions, while a cost of the alerting cue was shown during the invalid exogenous trials. Neither the alerting nor validity effects interacted with the flanker effect. These results suggest that the alerting cue primes the exogenous and endogenous systems for the upcoming cues. Once the complexity of the task increases with the addition of the flankers, the alerting effect attenuates. The alerting and the two orienting networks interact together but the executive attention network acts independently, in children aged 6 years.

Reduced caudate volume and cognitive slowing in men at risk of fragile X-associated tremor ataxia syndrome.

Fragile X-associated tremor ataxia syndrome is an inherited neurodegenerative disorder caused by premutation expansions (55-200 CGG repeats) of the FMR1 gene. There is accumulating evidence to suggest that early cognitive and brain imaging signs may be observed in some premutation carriers without motor signs of FXTAS, but few studies have examined the relationships between subcortical brain volumes and cognitive performance in this group. This study examined the relationships between caudate volume and select cognitive measures (executive function and information processing speed) in men at risk of developing FXTAS and controls with normal FMR1 alleles (<45 CGG repeats). The results showed that men with premutation alleles performed worse on measures of executive function and information processing speed, and had significantly reduced caudate volume, compared to controls. Smaller caudate volume in the premutation group was associated with slower processing speed. These findings provide preliminary evidence that early reductions in caudate volume may be associated with cognitive slowing in men with the premutation who do not present with cardinal motor signs of FXTAS. If confirmed in future studies with larger PM cohorts, these findings will have important implications for the identification of sensitive measures with potential utility for tracking cognitive decline.

ß-glucuronidase use as a single internal control gene may confound analysis in FMR1 mRNA toxicity studies.

Relationships between Fragile X Mental Retardation 1 (FMR1) mRNA levels in blood and intragenic FMR1 CGG triplet expansions support the pathogenic role of RNA gain of function toxicity in premutation (PM: 55-199 CGGs) related disorders. Real-time PCR (RT-PCR) studies reporting these findings normalised FMR1 mRNA level to a single internal control gene called ß-glucuronidase (GUS). This study evaluated FMR1 mRNA-CGG correlations in 33 PM and 33 age- and IQ-matched control females using three normalisation strategies in peripheral blood mononuclear cells (PBMCs): (i) GUS as a single internal control; (ii) the mean of GUS, Eukaryotic Translation Initiation Factor 4A2 (EIF4A2) and succinate dehydrogenase complex flavoprotein subunit A (SDHA); and (iii) the mean of EIF4A2 and SDHA (with no contribution from GUS). GUS mRNA levels normalised to the mean of EIF4A2 and SDHA mRNA levels and EIF4A2/SDHA ratio were also evaluated. FMR1mRNA level normalised to the mean of EIF4A2 and SDHA mRNA levels, with no contribution from GUS, showed the most significant correlation with CGG size and the greatest difference between PM and control groups (p = 10-11). Only 15% of FMR1 mRNA PM results exceeded the maximum control value when normalised to GUS, compared with over 42% when normalised to the mean of EIF4A2 and SDHA mRNA levels. Neither GUS mRNA level normalised to the mean RNA levels of EIF4A2 and SDHA, nor to the EIF4A2/SDHA ratio were correlated with CGG size. However, greater variability in GUS mRNA levels were observed for both PM and control females across the full range of CGG repeat as compared to the EIF4A2/SDHA ratio. In conclusion, normalisation with multiple control genes, excluding GUS, can improve assessment of the biological significance of FMR1 mRNA-CGG size relationships.

The Association Between Anxiety Symptoms and Sleep in School-Aged Children: A Combined Insight From the Children's Sleep Habits Questionnaire and Actigraphy.

The current study assessed the association between anxiety symptoms and sleep in 90 school-aged children, aged 6-12 years (Mage = 108 months, 52.2% male). The Children's Sleep Habits Questionnaire (CSHQ) and 14 nights of actigraphy were used to assess sleep. Anxiety was assessed using the Spence Children's Anxiety Scale (SCAS). A significant association was found between parent-reported anxiety symptoms and current sleep problems (i.e., CSHQ total scores ≥ 41). An examination of SCAS subscales identified a specific association between generalized anxiety disorder (GAD) symptoms and increased parental sleep concerns, including sleep onset delay, sleep duration, and daytime sleepiness. Regarding actigraphy, whilst anxiety was not associated with average sleep variables, a relationship was identified between anxiety and the night-to-night variability of actigraphy-derived sleep schedules.

Sleep patterns predictive of daytime challenging behavior in individuals with low-functioning autism.

Increased severity of problematic daytime behavior has been associated with poorer sleep quality in individuals with autism spectrum disorder. In this work, we investigate whether this relationship holds in a real-time setting, such that an individual's prior sleep can be used to predict their subsequent daytime behavior. We analyzed an extensive real-world dataset containing over 20,000 nightly sleep observations matched to subsequent challenging daytime behaviors (aggression, self-injury, tantrums, property destruction and a challenging behavior index) across 67 individuals with low-functioning autism living in two U.S. residential facilities. Using support vector machine classifiers, a statistically significant predictive relationship was found in 81% of individuals studied (P < 0.05). For all five behaviors examined, prediction accuracy increased up to approximately eight nights of prior sleep used to make the prediction, indicating that the behavioral effects of sleep may manifest on extended timescales. Accurate prediction was most strongly driven by sleep variability measures, highlighting the importance of regular sleep patterns. Our findings constitute an initial step towards the development of a real-time monitoring tool to pre-empt behavioral episodes and guide prophylactic treatment for individuals with autism. Autism Res 2018, 11: 391-403. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We analyzed over 20,000 nights of sleep from 67 individuals with autism to investigate whether daytime behaviors can be predicted from prior sleep patterns. Better-than-chance accuracy was obtained for 81% of individuals, with measures of night-to-night variation in sleep timing and duration most relevant for accurate prediction. Our results highlight the importance of regular sleep patterns for better daytime functioning and represent a step toward the development of 'smart sleep technologies' to pre-empt behavior in individuals with autism.

Behaviorally-determined sleep phenotypes are robustly associated with adaptive functioning in individuals with low functioning autism.

Despite sleep disturbance being a common complaint in individuals with autism, specific sleep phenotypes and their relationship to adaptive functioning have yet to be identified. This study used cluster analysis to find distinct sleep patterns and relate them to independent measures of adaptive functioning in individuals with autism. Approximately 50,000 nights of care-giver sleep/wake logs were collected on school-days for 106 individuals with low functioning autism (87 boys, 14.77 ± 3.11 years) for 0.5-6 years (2.2 ± 1.5 years) from two residential schools. Using hierarchical cluster analysis, performed on summary statistics of each individual across their recording duration, two clusters of individuals with clearly distinguishable sleep phenotypes were found. The groups were summarized as 'unstable' sleepers (cluster 1, n = 41) and 'stable' sleepers (cluster 2, n = 65), with the former exhibiting reduced sleep duration, earlier sleep offset, and less stability in sleep timing. The sleep clusters displayed significant differences in properties that were not used for clustering, such as intellectual functioning, communication, and socialization, demonstrating that sleep phenotypes are associated with symptom severity in individuals with autism. This study provides foundational evidence for profiling and targeting sleep as a standard part of therapeutic intervention in individuals with autism.

White matter microstructure, cognition, and molecular markers in fragile X premutation females.

OBJECTIVE: To examine the interrelationships between fragile X mental retardation 1 (FMR1) mRNA and the FMR1 exon 1/intron 1 boundary methylation, white matter microstructure, and executive function, in women with a FMR1 premutation expansion (PM; 55-199 CGG repeats) and controls (CGG < 44). METHODS: Twenty women with PM without fragile X-associated tremor/ataxia syndrome (FXTAS) and 20 control women between 22 and 54 years of age completed this study. FMR1 mRNA and methylation levels for 9 CpG sites within the FMR1 exon 1/intron 1 boundary from peripheral blood samples were analyzed. To measure white matter microstructure, diffusion-weighted imaging was used, from which fractional anisotropy (FA) and mean diffusivity (MD) values from anatomic regions within the corpus callosum and cerebellar peduncles were extracted. Executive function was assessed across a range of tasks. RESULTS: No differences were revealed in white matter microstructure between women with PM and controls. However, we reveal that for women with PM (but not controls), higher FMR1 mRNA correlated with lower MD values within the middle cerebellar peduncle and Paced Auditory Serial Addition Test scores, higher methylation of the FMR1 exon 1/intron 1 boundary correlated with lower MD within the inferior and middle cerebellar peduncles and longer prosaccade latencies, and higher FA values within the corpus callosum and cerebellar peduncle regions corresponded to superior executive function. CONCLUSIONS: We provide evidence linking white matter microstructure to executive dysfunction and elevated FMR1 mRNA and FMR1 exon 1/intron 1 boundary methylation in women with PM without FXTAS. This suggests that the FXTAS phenotype may not be distinct but may form part of a spectrum of PM involvement.

The developmental trajectory of parent-report and objective sleep profiles in autism spectrum disorder: Associations with anxiety and bedtime routines.

The present study compared the course of parent-report and actigraphy-derived sleep profiles over a 1-year period, in school-age children with autism spectrum disorder and typically developing children. The Children's Sleep Habits Questionnaire and 14 nights of actigraphy were used to assess sleep profiles. Parents also completed the Spence Children's Anxiety Scale, the Social Worries Questionnaire and the Bedtime Routines Questionnaire. Between-group differences in parent-reported sleep problems were less pronounced at follow-up compared to baseline. The course of objective sleep was comparable between groups, with a significant reduction in sleep duration over time in both groups. Children with autism spectrum disorder were further characterised by significantly more night-to-night variability in sleep quality, across both time points. Reductions over time in parent-reported sleep problems were significantly associated with reduced anxiety. Reductions in actigraphy-derived sleep efficiency were associated with an increased frequency of maladaptive activities in the hour before bedtime, in both children with and without autism spectrum disorder.

Visual attention and academic performance in children with developmental disabilities and behavioural attention deficits.

Despite well-documented attention deficits in children with intellectual and developmental disabilities (IDD), distinctions across types of attention problems and their association with academic attainment has not been fully explored. This study examines visual attention capacities and inattentive/hyperactive behaviours in 77 children aged 4 to 11 years with IDD and elevated behavioural attention difficulties. Children with autism spectrum disorder (ASD; n = 23), Down syndrome (DS; n = 22), and non-specific intellectual disability (NSID; n = 32) completed computerized visual search and vigilance paradigms. In addition, parents and teachers completed rating scales of inattention and hyperactivity. Concurrent associations between attention abilities and early literacy and numeracy skills were also examined. Children completed measures of receptive vocabulary, phonological abilities and cardinality skills. As expected, the results indicated that all groups had relatively comparable levels of inattentive/hyperactive behaviours as rated by parents and teachers. However, the extent of visual attention deficits varied as a result of group; namely children with DS had poorer visual search and vigilance abilities than children with ASD and NSID. Further, significant associations between visual attention difficulties and poorer literacy and numeracy skills were observed, regardless of group. Collectively the findings demonstrate that in children with IDD who present with homogenous behavioural attention difficulties, at the cognitive level, subtle profiles of attentional problems can be delineated.

Computerised attention training for children with intellectual and developmental disabilities: a randomised controlled trial.

BACKGROUND: Children with intellectual and developmental disabilities (IDD) experience heightened attention difficulties which have been linked to poorer cognitive, academic and social outcomes. Although, increasing research has focused on the potential of computerised cognitive training in reducing attention problems, limited studies have assessed whether this intervention could be utilised for those with IDD. This study aimed to assess the efficacy of a computerised attention training programme in children with IDD. METHODS: In a double-blind randomised controlled trial, children (n = 76; IQ < 75) aged 4-11 years were assigned to an adaptive attention training condition or a nonadaptive control condition. Both conditions were completed at home over a 5-week period and consisted of 25 sessions, each of 20-min duration. Outcome measures (baseline, posttraining and 3-month follow-up) assessed core attention skills (selective attention, sustained attention and attentional control) and inattentive/hyperactive behaviour. RESULTS: Children in the attention training condition showed greater improvement in selective attention performance compared to children in the control condition (SMD = 0.24, 95% CI 0.02, 0.45). These improvements were maintained 3 months after training had ceased (SMD = 0.26, 95% CI 0.04, 0.48). The attention training programme was not effective in promoting improvements in sustained attention, attentional control or inattentive/hyperactive behaviours. CONCLUSIONS: The findings suggest that attention training may enhance some aspects of attention (selective attention) in children with IDD, but the small to medium effect sizes indicate that further refinement of the training programme is needed to promote larger, more global improvements.

A cross-syndrome evaluation of a new attention rating scale: The Scale of Attention in Intellectual Disability.

Whilst neuropsychological research has enhanced our understanding of inattentive and hyperactive behaviours among children with intellectual disability (ID), the absence of rating scales developed for this group continues to be a gap in knowledge. This study examined these behaviours in 176 children with autism spectrum disorder (ASD), Down Syndrome (DS), or idiopathic ID using a newly developed teacher rating scale, the Scale of Attention in Intellectual Disability. Findings suggested that children with ASD had a significantly greater breadth of hyperactive/impulsive behaviours than those with DS or idiopathic ID. These findings support existing research suggesting differing profiles of attention and activity across groups. Understanding disorder-specific profiles has implications for developing strategies to support students with ID in the classroom.

Executive Dysfunction in Female FMR1 Premutation Carriers.

There is now growing evidence of cognitive weakness in female premutation carriers (between 55 and 199 CGG repeats) of the fragile X mental retardation gene, including impairments associated with executive function. While an age-related decline in assessments of executive function has been found for male premutation carriers, few studies have explored whether female carriers show a similar trajectory with age. A total of 20 female premutation carriers and 21 age- and IQ-matched healthy controls completed a battery of tasks assessing executive function tasks, including the behavioural dyscontrol scale (BDS), symbol digit modalities test (SDMT), paced auditory serial addition test (PASAT), Haylings sentence completion test and the digit span task (forward and backward). Performance was compared between premutation carriers and healthy controls, and the association between task performance and age was also ascertained. Compared to controls, female premutation carriers had significant impairment on the BDS, SDMT, PASAT, and Haylings sentence completion task, all of which rely on quick, or timed, responses. Further analyses revealed no significant association between age and task performance for either premutation carriers or controls. This study demonstrates that a cohort of female premutation carriers have deficits on a range of tasks of executive function that require the rapid temporal resolution of responses. We propose that the understanding of the phenotype of premutation carriers will be advanced through use of such measures.

Novel methylation markers of the dysexecutive-psychiatric phenotype in FMR1 premutation women.

OBJECTIVE: To examine the epigenetic basis of psychiatric symptoms and dysexecutive impairments in FMR1 premutation (PM: 55 to 199 CGG repeats) women. METHODS: A total of 35 FMR1 PM women aged between 22 and 55 years and 35 age- and IQ-matched women controls (CGG <45) participated in this study. All participants completed a range of executive function tests and self-reported symptoms of psychiatric disorders. The molecular measures included DNA methylation of the FMR1 CpG island in blood, presented as FMR1 activation ratio (AR), and 9 CpG sites located at the FMR1 exon1/intron 1 boundary, CGG size, and FMR1 mRNA levels. RESULTS: We show that FMR1 intron 1 methylation levels could be used to dichotomize PM women into greater and lower risk categories (p = 0.006 to 0.037; odds ratio = 14-24.8), with only FMR1 intron 1 methylation, and to a lesser extent AR, being significantly correlated with the likelihood of probable dysexecutive or psychiatric symptoms (p < 0.05). Furthermore, the significant relationships between methylation and social anxiety were found to be mediated by executive function performance, but only in PM women. FMR1 exon 1 methylation, CGG size, and FMR1 mRNA could not predict probable dysexecutive/psychiatric disorders in PM women. CONCLUSIONS: This is the first study supporting presence of specific epigenetic etiology associated with increased risk of developing comorbid dysexecutive and social anxiety symptoms in PM women. These findings could have implications for early intervention and risk estimate recommendations aimed at improving the outcomes for PM women and their families.

Development of a New Attention Rating Scale for Children With Intellectual Disability: The Scale of Attention in Intellectual Disability (SAID).

Difficulties with attention, impulsivity, and hyperactivity are thought to be as common among children with intellectual disability (ID) as they are in children without ID. Despite this, there is a lack of scales to specifically assess ADHD symptomatology in children and adolescents with ID. This article describes the development and evaluation of a teacher-completed measure; the Scale of Attention in Intellectual Disability (SAID). A community survey of 176 teachers of children 5-13 years of age, with ID at all levels of impairment indicated that the T-SAID is a reliable and valid measure. Integrating this scale with neuropsychological and clinical research holds exciting promise for enhancing our understanding of the nature of attention difficulties within populations with ID.

Delineation of the working memory profile in female FMR1 premutation carriers: the effect of cognitive load on ocular motor responses.

Fragile X mental retardation 1 (FMR1) premutation carriers (PM-carriers) are characterised as having mid-sized expansions of between 55 and 200 CGG repeats in the 5' untranslated region of the FMR1 gene. While there is evidence of executive dysfunction in PM-carriers, few studies have explicitly explored working memory capabilities in female PM-carriers. 14 female PM-carriers and 13 age- and IQ-matched healthy controls completed an ocular motor n-back working memory paradigm. This task examined working memory ability and the effect of measured increases in cognitive load. Female PM-carriers were found to have attenuated working memory capabilities. Increasing the cognitive load did not elicit the expected reciprocal increase in the task errors for female PM-carriers, as it did in controls. However female PM-carriers took longer to respond than controls, regardless of the cognitive load. Further, FMR1 mRNA levels were found to significantly predict PM-carrier response time. Although preliminary, these findings provide further evidence of executive dysfunction, specifically disruption to working memory processes, which were found to be associated with increases in FMR1 mRNA expression in female PM-carriers. With future validation, ocular motor paradigms such as the n-back paradigm will be critical to the development of behavioural biomarkers for identification of PM-carrier cognitive-affective phenotypes.

Evidence linking FMR1 mRNA and attentional demands of stepping and postural control in women with the premutation.

Recent studies in young adult females with the fragile X mental retardation 1 (FMR1) gene premutation (PM) have shown subtle but significant impairments in executive control and postural stability. Less is known about the influence of age and FMR1 gene expression on executive control and postural stability in females with the PM. Here, we examined the attentional demands of reactive stepping using a well-validated measure of choice stepping reaction time under dual-task interference. We explored the interrelationships between step initiation times during a concurrent verbal fluency task and specific impairments in executive control previously reported in females with the PM. Our results showed increased dual-task interference on step initiation times and variability in female PM compared with control subjects. In addition, we observed greater choice stepping reaction time dual-task costs above the breakpoint of 81 CGG repeats relative to below this CGG range. Dual-task interference on both reaction time and movement time were significantly predicted by low working memory capacity in female PM carriers. Importantly, we revealed that FMR1 messenger RNA level is the most significant predictor accounting for dual-task stepping variability in both reaction time and movement time in PM females. These findings for the first time provide evidence linking elevated FMR1 messenger RNA levels that have been previously associated with FMR1 RNA toxicity and deficits in cerebellar motor and cognitive networks in a subgroup of at-risk PM women.

The relationship between sleep and behavior in autism spectrum disorder (ASD): a review.

Although there is evidence that significant sleep problems are common in children with autism spectrum disorder (ASD) and that poor sleep exacerbates problematic daytime behavior, such relationships have received very little attention in both research and clinical practice. Treatment guidelines to help manage challenging behaviors in ASD fail to mention sleep at all, or they present a very limited account. Moreover, limited attention is given to children with low-functioning autism, those individuals who often experience the most severe sleep disruption and behavioral problems. This paper describes the nature of sleep difficulties in ASD and highlights the complexities of sleep disruption in individuals with low-functioning autism. It is proposed that profiling ASD children based on the nature of their sleep disruption might help to understand symptom and behavioral profiles (or vice versa) and therefore lead to better-targeted interventions. This paper concludes with a discussion of the limitations of current knowledge and proposes areas that are important for future research. Treating disordered sleep in ASD has great potential to improve daytime behavior and family functioning in this vulnerable population.