Generalized models for estimating cerebral lateralisation of young children using functional transcranial Doppler ultrasound.

Thompson et al., 2023 (Generalized models for quantifying laterality using functional transcranial Doppler ultrasound. Human Brain Mapping, 44(1), 35-48) introduced generalised model-based analysis methods for determining cerebral lateralisation from functional transcranial Doppler ultrasound (fTCD) data which substantially decreased the uncertainty of individual lateralisation estimates across several large adult samples. We aimed to assess the suitability of these methods for increasing precision in lateralisation estimates for child fTCD data. We applied these methods to adult fTCD data to establish the validity of two child-friendly language and visuospatial tasks. We also applied the methods to fTCD data from 4- to 7-year-old children. For both samples, the laterality estimates from the complex generalised additive model (GAM) approach correlated strongly with the traditional methods while also decreasing individual standard errors compared to the popular period-of-interest averaging method. We recommend future research using fTCD with young children consider using GAMs to reduce the noise in their LI estimates.

Generalized models for quantifying laterality using functional transcranial Doppler ultrasound.

We consider how analysis of brain lateralization using functional transcranial Doppler ultrasound (fTCD) data can be brought in line with modern statistical methods typically used in functional magnetic resonance imaging (fMRI). Conventionally, a laterality index is computed in fTCD from the difference between the averages of each hemisphere's signal within a period of interest (POI) over a series of trials. We demonstrate use of generalized linear models (GLMs) and generalized additive models (GAM) to analyze data from individual participants in three published studies (N = 154, 73 and 31), and compare this with results from the conventional POI averaging approach, and with laterality assessed using fMRI (N = 31). The GLM approach was based on classic fMRI analysis that includes a hemodynamic response function as a predictor; the GAM approach estimated the response function from the data, including a term for time relative to epoch start (simple GAM), plus a categorical index corresponding to individual epochs (complex GAM). Individual estimates of the fTCD laterality index are similar across all methods, but error of measurement is lowest using complex GAM. Reliable identification of cases of bilateral language appears to be more accurate with complex GAM. We also show that the GAM-based approach can be used to efficiently analyze more complex designs that incorporate interactions between tasks.

Mapping and identifying service models for community-based services for children with intellectual disabilities and behaviours that challenge in England.

BACKGROUND: One in five children with an intellectual disability in the UK display behaviours that challenge. Despite associated impacts on the children themselves, their families, and services, little research has been published about how best to design, organise, and deliver health and care services to these children. The purpose of this study was to describe how services are structured and organised ("service models") in England for community-based health and care services for children with intellectual disability who display behaviours that challenge. METHODS: Survey data about services were collected from 161 eligible community-based services in England. Staff from 60 of these services were also interviewed. A combination of latent class and descriptive analysis, coupled with consultation with family carers and professionals was used to identify and describe groupings of similar services (i.e., "service models"). RESULTS: The latent class analysis, completed as a first step in the process, supported a distinction between specialist services and non-specialist services for children who display behaviours that challenge. Planned descriptive analyses incorporating additional study variables were undertaken to further refine the service models. Five service models were identified: Child and Adolescent Mental Health Services (CAMHS) (n = 69 services), Intellectual Disability CAMHS (n = 28 services), Children and Young People Disability services (n = 25 services), Specialist services for children who display behaviours that challenge (n = 27 services), and broader age range services for children and/or adolescents and adults (n= 12 services). CONCLUSIONS: Our analysis led to a typology of five service models for community health and care services for children with intellectual disabilities and behaviours that challenge in England. Identification of a typology of service models is a first step in building evidence about the best provision of services for children with intellectual disabilities who display behaviours that challenge. The methods used in the current study may be useful in research developing service typologies in other specialist fields of health and care. STUDY REGISTRATION: Trial Registration: Current Controlled Trials ISRCTN88920546, Date assigned 05/07/2022.

Psychiatric inpatient admissions and discharges of people with intellectual disabilities: A time series analysis of English national data.

BACKGROUND: We examined whether a series of variables were related to the number of psychiatric inpatients using publicly available data about English psychiatric bed utilisation and NHS workforce. METHOD: Using linear regression, with auto-regressive errors, we examined relationships between variables over time using data from December 2013 to March 2021. RESULTS: Over time, the number of inpatients reduced by either 6.58 or 8.07 per month depending upon the dataset utilised, and the number of community nurses and community nursing support staff reduced by 7.43 and 2.14 nurses per month, respectively. Increasing numbers of consultant psychiatrists were associated with fewer inpatients over time. More care and treatment reviews (CTRs) were associated with more admissions over time, while more post-admission CTRs were associated with increased discharges over time. CONCLUSIONS: Future studies should examine whether psychiatric bed utilisation elsewhere within the NHS by people with intellectual disabilities has increased.

Functional organisation for verb generation in children with developmental language disorder.

Developmental language disorder (DLD) is characterised by difficulties in learning one's native language for no apparent reason. These language difficulties occur in 7% of children and are known to limit future academic and social achievement. Our understanding of the brain abnormalities associated with DLD is limited. Here, we used a simple four-minute verb generation task (children saw a picture of an object and were instructed to say an action that goes with that object) to test children between the ages of 10-15 years (DLD N = 50, typically developing N = 67). We also tested 26 children with poor language ability who did not meet our criteria for DLD. Contrary to our registered predictions, we found that children with DLD did not have (i) reduced activity in language relevant regions such as the left inferior frontal cortex; (ii) dysfunctional striatal activity during overt production; or (iii) a reduction in left-lateralised activity in frontal cortex. Indeed, performance of this simple language task evoked activity in children with DLD in the same regions and to a similar level as in typically developing children. Consistent with previous reports, we found sub-threshold group differences in the left inferior frontal gyrus and caudate nuclei, but only when analysis was limited to a subsample of the DLD group (N = 14) who had the poorest performance on the task. Additionally, we used a two-factor model to capture variation in all children studied (N = 143) on a range of neuropsychological tests and found that these language and verbal memory factors correlated with activity in different brain regions. Our findings indicate a lack of support for some neurological models of atypical language learning, such as the procedural deficit hypothesis or the atypical lateralization hypothesis, at least when using simple language tasks that children can perform. These results also emphasise the importance of controlling for and monitoring task performance.

Profile of language abilities in a sample of adults with developmental disorders.

This study investigated the profile of language abilities in a sample of high-achieving English speaking adults with developmental disorders. Ninety-seven adult participants were recruited: 49 with a dyslexia diagnosis (dyslexic group), 16 with a diagnosis of a different developmental disorder including dyspraxia, autism and SpLD (non-dyslexic developmental disorder group) and 32 with no diagnosis (non-disordered group). Dyslexic and non-dyslexic developmental disorder groups demonstrated similar impairments across measures of word reading, working memory, processing speed and oral language. Dyslexic participants showed the usual pattern of impaired phonological skills but spared non-verbal intelligence and vocabulary. There were also some suggestions of impaired structural oral language skills in this group. A data-driven clustering analysis found that diagnosis was not a reliable predictor of similarity between cases, with diagnostic categories split between data-driven clusters. Overall, the findings indicate that high-achieving adults with developmental disorders do demonstrate impairments that are likely to affect success in higher education, but that support needs should be assessed on a case-by-case basis, rather than according to diagnostic label.

Assessing the reliability of an online behavioural laterality battery: A pre-registered study.

Studies of cerebral lateralization often involve participants completing a series of perceptual tasks under laboratory conditions. This has constrained the number of participants recruited in such studies. Online testing can allow for much larger sample sizes but limits the amount of experimental control that is feasible. Here we considered whether online testing could give valid and reliable results on four tasks: a rhyme decision visual half-field task, a dichotic listening task, a chimeric faces task, and a finger tapping task. We recruited 392 participants, oversampling left-handers, who completed the battery twice. Three of the tasks showed evidence of both validity and reliability, insofar as they showed hemispheric advantages in the expected direction and test-retest reliability of at least r = .75. The reliability of the rhyme decision task was less satisfactory (r = .62). We also confirmed a prediction that extreme left-handers were more likely to depart from typical lateralization. Lateralization across the two language tasks (dichotic listening and rhyme judgement) was weakly correlated, but unrelated to lateralization on the chimeric faces task. We conclude that three of the tasks, dichotic listening, chimeric faces and finger tapping, show considerable promise for online evaluation of cerebral lateralization.

Copy number variation burden does not predict severity of neurodevelopmental phenotype in children with a sex chromosome trisomy.

Sex chromosome trisomies (SCTs) (XXX, XXY, and XYY karyotypes) are associated with an elevated risk of neurodevelopmental disorders. The range of severity of the phenotype is substantial. We considered whether this variable outcome was related to the presence of copy number variants (CNVs)-stretches of duplicated or deleted DNA. A sample of 125 children with an SCT were compared with 181 children of normal karyotype who had been given the same assessments. First, we compared the groups on measures of overall CNV burden: number of CNVs, total span of CNVs, and likely functional impact (probability of loss-of-function intolerance, pLI, summed over CNVs). Differences between groups were small relative to within-group variance and not statistically significant on overall test. Next, we considered whether a measure of general neurodevelopmental impairment was predicted by pLI summed score, SCT versus comparison group, or the interaction between them. There was a substantial effect of SCT/comparison status but the pLI score was not predictive of outcomes in either group. We conclude that variable presence of CNVs is not a likely explanation for the wide phenotypic variation in children with SCTs. We discuss methodological challenges of testing whether CNVs are implicated in causing neurodevelopmental problems.

Investigation into inconsistent lateralisation of language functions as a potential risk factor for language impairment.

Disruption to language lateralisation has been proposed as a cause of developmental language impairments. In this study, we tested the idea that consistency of lateralisation across different language functions is associated with language ability. A large sample of adults with variable language abilities (N = 67 with a developmental disorder affecting language and N = 37 controls) were recruited. Lateralisation was measured using functional transcranial Doppler sonography (fTCD) for three language tasks that engage different language subprocesses (phonological decision, semantic decision and sentence generation). The whole sample was divided into those with consistent versus inconsistent lateralisation across the three tasks. Language ability (using a battery of standardised tests) was compared between the consistent and inconsistent groups. The results did not show a significant effect of lateralisation consistency on language skills. However, of the 31 individuals showing inconsistent lateralisation, the vast majority (84%) were in the disorder group with only five controls showing such a pattern, a difference that was higher than would be expected by chance. The developmental disorder group also demonstrated weaker correlations between laterality indices across pairs of tasks. In summary, although the data did not support the hypothesis that inconsistent language lateralisation is a major cause of poor language skills, the results suggested that some subtypes of language disorder are associated with inefficient distribution of language functions between hemispheres. Inconsistent lateralisation could be a causal factor in the aetiology of language disorder or may arise in some cases as the consequence of developmental disorder, possibly reflective of compensatory reorganisation.