Attention and motor profiles in children with developmental coordination disorder: A neuropsychological and neuroimaging investigation

AIM: This study aimed to (1) quantify attention and executive functioning in children with developmental coordination disorder (DCD), (2) assess whether some children with DCD are more likely to show attention difficulties, and (3) characterize brain correlates of motor and attention deficits. METHOD: Fifty-three children (36 with DCD and 17 without) aged 8 to 10 years underwent T1-weighted and diffusion-weighted magnetic resonance imaging, and standardized attention and motor assessments. Parents completed questionnaires of executive functioning and symptoms of inattention and hyperactivity. We assessed regional cortical thickness and surface area, and cerebellar, callosal, and primary motor tract structure. RESULTS: Analyses of covariance and one-sample t-tests identified impaired attention, non-motor processing speed, and executive functioning in children with DCD, yet partial Spearman's rank correlation coefficients revealed these were unrelated to one another or the type or severity of the motor deficit. Robust regression analyses revealed that cortical morphology in the posterior cingulate was associated with both gross motor skills and inattentive symptoms in children with DCD, while gross motor skills were also associated with left corticospinal tract (CST) morphology. INTERPRETATION: Children with DCD may benefit from routine attention and hyperactivity assessments. Alterations in the posterior cingulate and CST may be linked to impaired forward modelling during movements in children with DCD. Overall, alterations in these regions may explain the high rate of non-motor impairments in children with DCD

The genetic and molecular basis of developmental language disorder: A review

Language disorders are highly heritable and are influenced by complex interactions between genetic and environmental factors. Despite more than twenty years of research, we still lack critical understanding of the biological underpinnings of language. This review provides an overview of the genetic landscape of developmental language disorders (DLD), with an emphasis on the importance of defining the specific features (the phenotype) of DLD to inform gene discovery. We review the specific phenotype of DLD in the genetic literature, and the influence of historic variation in diagnostic inclusion criteria on researchers’ ability to compare and replicate genotype-phenotype studies. This review provides an overview of the recently identified gene pathways in populations with DLD and explores current state-of-the-art approaches to genetic analysis based on the hypothesized architecture of DLD. We will show how recent global efforts to unify diagnostic criteria have vastly increased sample size and allow for large multi-cohort metanalyses, leading the identification of a growing number of contributory loci. We emphasize the important role of estimating the genetic architecture of DLD to decipher underlying genetic associations. Finally, we explore the potential for epigenetics and environmental interactions to further unravel the biological basis of language disorders.

Phylogeny of the Australian Solanum dioicum group using seven nuclear genes: Testing Symon’s fruit and seed dispersal hypotheses.

The dioecious and andromonoecious Solanum taxa (the “S. dioicum group”) of the Australian Monsoon Tropics have been the subject of phylogenetic and taxonomic study for decades, yet much of their basic biology is still unknown. This is especially true for plant-animal interactions, including the influence of fruit form and calyx morphology on seed dispersal. We combine field/greenhouse observations and specimen-based study with phylogenetic analysis of seven nuclear regions obtained via a microfluidic PCR-based enrichment strategy and high-throughput sequencing, and present the first species-tree hypothesis for the S. dioicum group. Our results suggest that epizoochorous trample burr seed dispersal (strongly linked to calyx accrescence) is far more common among Australian Solanum than previously thought and support the hypothesis that the combination of large fleshy fruits and endozoochorous dispersal represents a reversal in this study group. The general lack of direct evidence related to biotic dispersal (epizoochorous or endozoochorous) may be a function of declines and/or extinctions of vertebrate dispersers. Because of this, some taxa might now rely on secondary dispersal mechanisms (e.g. shakers, tumbleweeds, rafting) as a means to maintain current populations and establish new ones

Corticobulbar Tract Injury, Oromotor Impairment and Language Plasticity in Adolescents Born Preterm

Children born preterm are at risk of impairments in oromotor control, with implications for early feeding and speech development. In this study, we aimed to identify (a) neuroanatomical markers of persistent oromotor deficits using diffusion-weighted imaging (DWI) tractography and (b) evidence of compensatory neuroplasticity using functional MRI (fMRI) during a language production task. In a cross-sectional study of 36 adolescents born very preterm (<33 weeks’ gestation) we identified persistent difficulties in oromotor control in 31% of cases, but no clinical diagnoses of speech-sound disorder (e.g., dysarthria, dyspraxia). We used DWI-tractography to examine the microstructure (fractional anisotropy, FA) of the corticospinal and corticobulbar tracts. Compared to the unimpaired group, the oromotor-impaired group showed (i) reduced FA within the dorsal portion of the left corticobulbar tract (containing fibres associated with movements of the lips, tongue, and larynx) and (ii) greater recruitment of right hemisphere language regions on fMRI. We conclude that, despite the development of apparently normal everyday speech, early injury to the corticobulbar tract leads to persistent subclinical problems with voluntary control of the face, lips, jaw, and tongue. Furthermore, we speculate that early speech problems may be ameliorated by cerebral plasticity – in particular, recruitment of right hemisphere language areas

The characteristics and reproducibility of motor speech functional neuroimaging in healthy controls

IntroductionFunctional magnetic resonance imaging (fMRI) can improve our understanding of neural processes subserving motor speech function. Yet its reproducibility remains unclear. This study aimed to evaluate the reproducibility of fMRI using a word repetition task across two time points.MethodsImaging data from 14 healthy controls were analysed using a multi-level general linear model.ResultsSignificant activation was observed during the task in the right hemispheric cerebellar lobules IV-V, right putamen, and bilateral sensorimotor cortices. Activation between timepoints was found to be moderately reproducible across time in the cerebellum but not in other brain regions.DiscussionPreliminary findings highlight the involvement of the cerebellum and connected cerebral regions during a motor speech task. More work is needed to determine the degree of reproducibility of speech fMRI before this could be used as a reliable marker of changes in brain activity

A Cross-Sectional Survey of Potential Factors, Motivations, and Barriers Influencing Research Participation and Retention among People Who Use Drugs in the Rural USA

BACKGROUND: Despite high morbidity and mortality among people who use drugs (PWUD) in rural America, most research is conducted within urban areas. Our objective was to describe influencing factors, motivations, and barriers to research participation and retention among rural PWUD. METHODS: We recruited 255 eligible participants from community outreach and community-based, epidemiologic research cohorts from April to July 2019 to participate in a cross-sectional survey. Eligible participants reported opioid or injection drug use to get high within 30 days and resided in high-needs rural counties in Oregon, Kentucky, and Ohio. We aggregated response rankings to identify salient influences, motivations, and barriers. We estimated prevalence ratios to assess for gender, preferred drug use, and geographic differences using log-binomial models. RESULTS: Most participants were male (55%) and preferred methamphetamine (36%) over heroin (35%). Participants reported confidentiality, amount of financial compensation, and time required as primary influential factors for research participation. Primary motivations for participation include financial compensation, free HIV/HCV testing, and contribution to research. Changed or false participant contact information and transportation are principal barriers to retention. Respondents who prefer methamphetamines over heroin reported being influenced by the purpose and use of their information (PR = 1.12; 95% CI: 1.00, 1.26). Females and Oregonians (versus Appalachians) reported knowing and wanting to help the research team as participation motivation (PR = 1.57; 95% CI: 1.09, 2.26 and PR = 2.12; 95% CI: 1.51, 2.99). CONCLUSIONS: Beyond financial compensation, researchers should emphasize confidentiality, offer testing and linkage with care, use several contact methods, aid transportation, and accommodate demographic differences to improve research participation and retention among rural PWUD

Perisylvian and Hippocampal Anomalies in Individuals With Pathogenic GRIN2A Variants

BACKGROUND AND OBJECTIVES: Pathogenic variants in GRIN2A are associated with a spectrum of epilepsy-aphasia syndromes (EASs). Seizures as well as speech and language disorders occur frequently but vary widely in severity, both between individuals and across the life span. The link between this phenotypic spectrum and brain characteristics is unknown. Specifically, altered brain networks at the root of speech and language deficits remain to be identified. Patients with pathogenic variants in GRIN2A offer an opportunity to interrogate the impact of glutamate receptor dysfunction on brain development. METHODS: We characterized brain anomalies in individuals with pathogenic GRIN2A variants and EASs, hypothesizing alterations in perisylvian speech-language regions and the striatum. We compared structural MRI data from 10 individuals (3 children and 7 adults, 3 female) with pathogenic GRIN2A variants with data from age-matched controls (N = 51 and N = 203 in a secondary analysis). We examined cortical thickness and volume in 4 a priori hypothesized speech and language regions (inferior frontal, precentral, supramarginal, and superior temporal) and across the whole brain. Subcortical structures (hippocampus, basal ganglia, thalamus) and the corpus callosum were also compared. RESULTS: Individuals with pathogenic GRIN2A variants showed increased thickness and volume in the posterior part of Broca's area (inferior frontal gyrus, pars opercularis). For thickness, the effects were bilateral but more pronounced in the left (large effect size, η2 = 0.37) than the right (η2 = 0.12) hemisphere. Both volume and thickness were also higher in the bilateral superior temporal region while the supramarginal region showed increased thickness only. Whole-brain analyses confirmed left-sided thickness increases in Broca's area, with additional increases in the occipital and superior frontal cortices bilaterally. Hippocampal volume was reduced in the left hemisphere. There were no age-dependent effects or corpus callosum group differences. DISCUSSION: Anomalies in perisylvian regions, with largest differences in Broca's area, suggest an altered development of classical speech-language networks in GRIN2A-related EAS. Left hippocampal reduction suggests a role for this structure in early speech and language development and is consistent with GRIN2A gene expression in that region. Overall, elucidating the neural correlates of EAS provides insights into the impact of GRIN2A dysfunction, opening avenues for targeted intervention in developmental syndromes with compromised speech-language development

Neurobehaviour between birth and 40 weeks’ gestation in infants born <30 weeks’ gestation and parental psychological wellbeing: predictors of brain development and child outcomes

BACKGROUND: Infants born <30 weeks’ gestation are at increased risk of long term neurodevelopmental problems compared with term born peers. The predictive value of neurobehavioural examinations at term equivalent age in very preterm infants has been reported for subsequent impairment. Yet there is little knowledge surrounding earlier neurobehavioural development in preterm infants prior to term equivalent age, and how it relates to perinatal factors, cerebral structure, and later developmental outcomes. In addition, maternal psychological wellbeing has been associated with child development. Given the high rate of psychological distress reported by parents of preterm children, it is vital we understand maternal and paternal wellbeing in the early weeks and months after preterm birth and how this influences the parent–child relationship and children’s outcomes. Therefore this study aims to examine how 1) early neurobehaviour and 2) parental mental health relate to developmental outcomes for infants born preterm compared with infants born at term. METHODS/DESIGN: This prospective cohort study will describe the neurobehaviour of 150 infants born at <30 weeks’ gestational age from birth to term equivalent age, and explore how early neurobehavioural deficits relate to brain growth or injury determined by magnetic resonance imaging, perinatal factors, parental mental health and later developmental outcomes measured using standardised assessment tools at term, one and two years’ corrected age. A control group of 150 healthy term-born infants will also be recruited for comparison of outcomes. To examine the effects of parental mental health on developmental outcomes, both parents of preterm and term-born infants will complete standardised questionnaires related to symptoms of anxiety, depression and post-traumatic stress at regular intervals from the first week of their child’s birth until their child’s second birthday. The parent–child relationship will be assessed at one and two years’ corrected age. DISCUSSION: Detailing the trajectory of infant neurobehaviour and parental psychological distress following very preterm birth is important not only to identify infants most at risk, further understand the parental experience and highlight potential times for intervention for the infant and/or parent, but also to gain insight into the effect this has on parent–child interaction and child development

GNB1 and obesity:Evidence for a correlation between haploinsufficiency and syndromic obesity

Most patients with GNB1 encephalopathy have developmental delay and/or intellectual disability, brain anomalies and seizures. Recently, two cases with GNB1 encephalopathy caused by haploinsufficiency have been reported that also show a Prader–Willi-like phenotype of childhood hypotonia and severe obesity. Here we present three new cases from our expert centre for genetic obesity in which GNB1 truncating and splice variants, probably leading to haploinsufficiency, were identified. They all have obesity, hyperphagia and intellectual deficit. The clinical cases and their weight courses are presented, together with a review of all 68 published cases with GNB1 encephalopathy. Information on weight was not mentioned in most of these articles, so we contacted authors for additional clinical information on weight status and hyperphagia. Of the 42 patients whose weight status we could determine, obesity was present in 8 patients (19%). Obesity is significantly over-represented in the group with truncating and splicing variants. In this group, we see an obesity prevalence of 75%. Since GNB1 has been linked to several key genes in the hypothalamic leptin-melanocortin pathway, which regulates satiety and energy expenditure, our data support the potential association between GNB1 haploinsufficiency and genetic obesity. We also suggest GNB1 is a candidate gene for the known obesity phenotype of the 1p36 microdeletion syndrome given this chromosomal region includes the GNB1 gene. Knowledge of an additional obesity phenotype is important for prognosis, early interventions against obesity and awareness when prescribing weight-inducing medication.</p