Analyzing the Quality of Life in Individuals with Fragile X Syndrome in Relation to Sleep and Mental Health.

The purpose of this paper was to examine the physical, emotional, social and school functioning domains of quality of life of individuals with Fragile X Syndrome, in relation to mental health and sleep patterns to gain a better understanding of how these aspects are affected by the disorder. This study included 119 individuals with Fragile X Syndrome who were given different cognitive examinations by a neuropsychologist or by parent-proxy questionnaires. This study focused on the Pediatric Quality of Life Inventory (PedsQoL), the Anxiety, Depression and Mood Scale (ADAMS), the Children's Sleep Habits Questionnaire (CSHQ), but did include other cognitive tests (Vineland Adaptive Behaviour Scales, Nonverbal IQ, Autism Diagnostic Observation Schedule). We identified significant associations between decreases in emotional, social and school domains of PedsQoL and the ADAMS subtests of Generalized Anxiety, Manic/Hyperactivity and Obsessive/Compulsivity, with the subtest of Depressed Mood having associations with lower physical and emotional domains. We also identified a significant impact between CSHQ subtests of Sleep Anxiety, Night Wakings, Daytime Sleepiness, and Parasomnia with the emotional and school domains of PedsQoL. There were associations connecting school functioning with Bedtime Resistance, and additional associations connecting emotional functioning with Sleep Duration and Sleep Onset Delay. Physical functioning was also associated with Sleep Anxiety. Our study shows how mental health and sleep defects impact improper sleep patterns and mental health which leads to decreases in the quality of life for individuals with FXS, and how it is important to screen for these symptoms in order to alleviate issues.

Assessing the Contribution of Measures of Attention and Executive Function to Diagnosis of ADHD or Autism.

Attention and executive function (EF) dysregulation are common in a number of disorders including autism and attention-deficit/hyperactivity disorder (ADHD). Better understanding of the relationship between indirect and direct measures of attention and EF and common neurodevelopmental diagnoses may contribute to more efficient and effective diagnostic assessment in childhood. We obtained cognitive (NIH Toolbox, Little Man Task, Matrix Reasoning Task, and Rey Delayed Recall) and symptom (CBCL, and BPMT) assessment data from the Adolescent Brain and Cognitive Development (ABCD) database for three groups, autistic (N = 110), ADHD (N = 878), and control without autism or ADHD diagnoses (N = 9130) and used ridge regression to determine which attention and EF assessments were most strongly associated with autism or ADHD. More variance was accounted for in the model for the ADHD group (31%) compared to the autism group (2.7%). Finally, we ran odds ratios (using clinical cutoffs where available and 2 standard deviations below the mean when not) for each assessment measure, which generally demonstrated a greater significance within the indirect measures when compared to the direct measures. These results add to the growing literature of symptom variably across diagnostic groups allowing for better understanding of presentations in autism and ADHD and how best to assess diagnosis. It also highlights the increased difficulty in differentiating autism and controls when compared to ADHD and controls and the importance of indirect measures of attention and EF in this differentiation.

The role of stimulant washout status in functional connectivity of default mode and fronto-parietal networks in children with neurodevelopmental conditions.

BACKGROUND: Stimulant medication is the primary pharmacological treatment for attention dysregulation and is commonly prescribed for children with Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism. Neuroimaging studies of these groups commonly use a 24-48-hour washout period to mediate the effects of stimulant medication on functional connectivity (FC) metrics. However, the impact of washout on functional connectivity has received limited study. METHODS: We used fMRI data from participants with diagnosis of Autism and ADHD (and an off stimulant control) from the Adolescent Brain and Cognitive Development (ABCD) and Autism Brain Imaging Data Exchange (ABIDE) databases to explore the effect of simulant washout on FC. Connectivity within and between the default mode (DMN) and fronto-parietal networks (FPN) was examined, as these networks have previously been implicated in attention dysregulation and associated with stimulant medication usage. For each diagnostic group, we assessed effects in interconnectivity between DMN and FPN, intraconnectivity within DMN, and intraconnectivity within FPN. RESULTS: We found no significant effect of medication status in intra- and inter-connectivity of the DMN and the FPN in either diagnostic group. IMPLICATIONS: Our findings suggest that more information is needed about the effect of stimulant medication, and washout, on the FC of attention networks in clinical populations.

Executive functioning, ADHD symptoms and resting state functional connectivity in children with perinatal stroke.

Perinatal stroke describes a group of focal, vascular brain injuries that occur early in development, often resulting in lifelong disability. Two types of perinatal stroke predominate, arterial ischemic stroke (AIS) and periventricular venous infarction (PVI). Though perinatal stroke is typically considered a motor disorder, other comorbidities commonly exist including attention-deficit hyperactivity disorder (ADHD) and deficits in executive function. Rates of ADHD symptoms are higher in children with perinatal stroke and deficits in executive function may also occur but underlying mechanisms are not known. We measured resting state functional connectivity in children with perinatal stroke using previously established dorsal attention, frontoparietal, and default mode network seeds. Associations with parental ratings of executive function and ADHD symptoms were examined. A total of 120 participants aged 6-19 years [AIS N = 31; PVI N = 30; Controls N = 59] were recruited. In comparison to typically developing peers, both the AIS and PVI groups showed lower intra- and inter-hemispheric functional connectivity values in the networks investigated. Group differences in between-network connectivity were also demonstrated, showing weaker anticorrelations between task-positive (frontoparietal and dorsal attention) and task-negative (default mode) networks in stroke groups compared to controls. Both within-network and between-network functional connectivity values were highly associated with parental reports of executive function and ADHD symptoms. These results suggest that differences in functional connectivity exist both within and between networks after perinatal stroke, the degree of which is associated with ADHD symptoms and executive function.

The Relationship Between Cortical Thickness and Executive Function Measures in Children With and Without ADHD.

OBJECTIVE: Attention Deficit Hyperactivity Disorder (ADHD) is characterized by inattention, hyperactivity, and impulsivity; however, other executive function dysregulation is common, including inhibition and working memory. This study aims to identify CT differences based on executive function performance in individuals with and without ADHD. METHODS: Data for this study was acquired from the Adolescent Brain and Cognitive Development (ABCD) database (61 ADHD, and 61 age and sex matched controls). General linear models were used to assess relationships between measures, CT, and diagnosis. RESULTS: We found a significant relation between CT and working memory scores in the right precentral area. Additionally, we found significant interactions between CT, diagnosis, and measure outcome in the Flanker assessment (in the left fusiform area) and the attention score of the CBCL (in the right precentral region). CONCLUSION: This suggests that there may be different relationships that exist between CT and executive function in children with ADHD.

Atypical Tactile Perception in Early Childhood Autism.

We assessed different aspects of tactile perception in young children (3-6 years) with autism. Autistic and neurotypical children completed vibrotactile tasks assessing reaction time, amplitude discrimination (sequential and simultaneous) and temporal discrimination (temporal order judgment and duration discrimination). Autistic children had elevated and more variable reaction times, suggesting slower perceptual-motor processing speed and/or greater distractibility. Children with autism also showed higher amplitude discrimination and temporal order judgement thresholds compared to neurotypical children. Tactile perceptual metrics did not associate with social or tactile sensitivities measured by parent-reports. Altered tactile behavioral responses appear in early childhood, can be quantified but appear dissociated from sensitivity. This implies these measures are complementary, but not necessarily related, phenomena of atypical tactile perception in autism.

The transition to adult income supports for youth that received special education in British Columbia, Canada: A cohort study.

Youth in special education have complex needs that are supported across multiple systems. Our research investigates the use of adult income assistance, as one structure that supports youth as they transition to adulthood. We created a cohort of youth (5-22 years old) using linked administrative data from British Columbia government ministries from 1996 to 2018. Youth were grouped by their special education funding (most to least; Level 1, Level 2, Level 3, Unfunded, and no special education). We investigated (1) youth characteristics and service use patterns, (2) which youth used income supports after the child-to-adult transition (19-22 years old), and what youth characteristics and service use patterns were associated with use, and (3) how much income support they used (CAD$). Of 174,527 youth, 254 (0.1%) were Level 1, 6020 (3.4%) were Level 2, 4409 (2.5%) were Level 3, 21,232 (12.2%) were Unfunded, and 142,612 (81.7%) were not in special education. Youth assigned higher funding levels, compared to lower levels, generally had increased service use, and in the transition to adult services were more likely to use income supports, and received more income support. An important exception was youth with serious behavioural/mental health special education funding (Level 3), who had increased service use for their level of funding, but received less income support due to a reliance on Temporary versus Disability Assistance. Youth that received an accredited diploma were less likely to use income supports. Factors related to the use of income supports are further described. This study highlights differences in access to income support when youth transition to adult services and considerations around equitable access to support.

Autism interest intensity in early childhood associates with executive functioning but not reward sensitivity or anxiety symptoms.

LAY ABSTRACT: Personal interests in autism are a source of joy, pride, and assist with the formation of social relationships. However, highly intense engagement can also interfere with other activities including activities of daily living. Theories have suggested that intense interests relate to executive functioning, reward sensitivity, and anxiety symptoms; but none of these theories have been tested in early childhood. Understanding which behavioral traits relate to intense interests in early childhood could help understand how intense interests may emerge, while also providing clues for how to manage interest intensity and best promote the many benefits of personal interests. We recruited families with autistic and non-autistic children aged 3-6 years. Parents completed questionnaires to assess children's interest diversity and intensity, executive functioning, reward sensitivity, and anxiety symptoms. We found that for autistic and non-autistic children, greater difficulty shifting attention between activities related to more intense interests. In autistic children only, difficulty with inhibitory control of attention also related to more intense interests. However, reward sensitivity and anxiety symptoms did not relate to interest intensity. Based on these observations, assisting young children with developing executive functioning skills could help with mediating the interference of interests in daily life to ultimately promote the many benefits of personal interests.

Frontal interhemispheric structural connectivity, attention, and executive function in children with perinatal stroke.

Perinatal stroke affects ∼1 in 1000 births and concomitant cognitive impairments are common but poorly understood. Rates of Attention Deficit/Hyperactivity Disorder (ADHD) are increased 5-10× and executive dysfunction can be disabling. We used diffusion imaging to investigate whether stroke-related differences in frontal white matter (WM) relate to cognitive impairments. Anterior forceps were isolated using tractography and sampled along the tract. Resulting metrics quantified frontal WM microstructure. Associations between WM metrics and parent ratings of ADHD symptoms (ADHD-5 rating scale) and executive functioning (Behavior Rating Inventory of Executive Function (BRIEF)) were explored. Eighty-three children were recruited (arterial ischemic stroke [AIS] n = 26; periventricular venous infarction [PVI] n = 26; controls n = 31). WM metrics were altered for stroke groups compared to controls. Along-tract analyses showed differences in WM metrics in areas approximating the lesion as well as more remote differences at midline and in the nonlesioned hemisphere. WM metrics correlated with parental ratings of ADHD and executive function such that higher diffusivity values were associated with poorer function. These findings suggest that underlying microstructure of frontal white matter quantified via tractography may provide a relevant biomarker associated with cognition and behavior in children with perinatal stroke.

Cross-ministry data on service use and limitations faced by children in special education.

BACKGROUND: Children with disabilities often face limitations that cross support sectors. OBJECTIVE: Our aim was to measure cross-ministry service use, outcomes, and functional limitations faced by children who qualified for special education. METHODS: We used longitudinal British Columbia ministry data linked to children (0-18y) registered in K-12 education. Children were grouped by special education funding (most to least; Level 1, Level 2, Level 3, Unfunded, and no special education), and related to 1) service use patterns, 2) the age they first used disability services, and 3) functional limitations reported in health visits. We also reported how length of special education use related to disability service use. RESULTS: Of 111,274 children, 154(0.1%) were Level 1, 4427(4.0%) Level 2, 2897(2.6%) Level 3, 13472(12.1%) Unfunded, and 90324(81.2%) not in special education. Children with higher funding levels, compared to lower levels of funding, generally were more likely to experience poorer outcomes, have functional limitations, have service needs, and receive early support. One exception was children with serious behavioral/mental health special education coding, which had poorer outcomes for their level of funding. Children received child disability supports early (about half of users started by 4y), but use was mostly limited to those with many years (9+years) of funded special education (70.7% of the all users) and biased to certain special education codes (i.e., Level 1, severe intellectual disability, and autism). CONCLUSIONS: This study provides evidence of the long-term, diverse needs of children in special education and may be used to inform decisions surrounding their support.

Tactile cortical responses and association with tactile reactivity in young children on the autism spectrum.

BACKGROUND: Unusual behavioral reactions to sensory stimuli are frequently reported in individuals on the autism spectrum (AS). Despite the early emergence of sensory features (< age 3) and their potential impact on development and quality of life, little is known about the neural mechanisms underlying sensory reactivity in early childhood autism. METHODS: Here, we used electroencephalography (EEG) to investigate tactile cortical processing in young children aged 3-6 years with autism and in neurotypical (NT) children. Scalp EEG was recorded from 33 children with autism, including those with low cognitive and/or verbal abilities, and 45 age- and sex-matched NT children during passive tactile fingertip stimulation. We compared properties of early and later somatosensory-evoked potentials (SEPs) and their adaptation with repetitive stimulation between autistic and NT children and assessed whether these neural measures are linked to "real-world" parent-reported tactile reactivity. RESULTS: As expected, we found elevated tactile reactivity in children on the autism spectrum. Our findings indicated no differences in amplitude or latency of early and mid-latency somatosensory-evoked potentials (P50, N80, P100), nor adaptation between autistic and NT children. However, latency of later processing of tactile information (N140) was shorter in young children with autism compared to NT children, suggesting faster processing speed in young autistic children. Further, correlational analyses and exploratory analyses using tactile reactivity as a grouping variable found that enhanced early neural responses were associated with greater tactile reactivity in autism. LIMITATIONS: The relatively small sample size and the inclusion of a broad range of autistic children (e.g., with low cognitive and/or verbal abilities) may have limited our power to detect subtle group differences and associations. Hence, replications are needed to verify these results. CONCLUSIONS: Our findings suggest that electrophysiological somatosensory cortex processing measures may be indices of "real-world" tactile reactivity in early childhood autism. Together, these findings advance our understanding of the neurophysiological mechanisms underlying tactile reactivity in early childhood autism and, in the clinical context, may have therapeutic implications.

Description of neurodevelopmental phenotypes associated with 10 genetic neurodevelopmental disorders: A scoping review.

Neurodevelopmental disorders (NDDs) are a heterogeneous group of conditions including intellectual disability, global developmental delay, autism spectrum disorder, and attention deficit hyperactivity disorder. Advances in genetic diagnostic technology have led to the identification of a number of NDD-associated genes, but reports of cognitive and developmental outcomes in affected individuals have been variable. The objective of this scoping review is to synthesize available information pertaining to the developmental outcomes of individuals with pathogenic variants in ten emerging recurrent NDD-associated genes identified from large scale sequencing studies; ADNP, ANKRD11, ARID1B, CHD2, CHD8, CTNNB1, DDX3X, DYRK1A, SCN2A, and SYNGAP1. After a comprehensive search, 260 articles were selected that reported on neurodevelopmental measures or diagnoses. We identify the spectrum of developmental outcomes for each genetic NDD, including prevalence of intellectual disability, frequency of co-morbid NDDs such as ADHD and autism, and commonly reported medical issues that can help inform diagnosis and treatment. There are significant gaps in our understanding of the natural history of these conditions. Future research focusing on barriers to assessment, the development of modified assessment tools appropriate for long-term outcomes in genetic NDD, and collection of longitudinal data will increase understanding of prognosis in these conditions and inform evaluations of treatment.

The Emergence of Cognitive Maps for Spatial Navigation in 7- to 10-Year-Old Children.

Although much is known about adults' ability to orient by means of cognitive maps (mental representations of the environment), it is less clear when this important ability emerges in development. In the present study, 97 seven- to 10-year-olds and 26 adults played a video game designed to investigate the ability to orient using cognitive maps. The game required participants to reach target locations as quickly as possible, necessitating the identification and use of novel shortcuts. Seven- and 8-year-olds were less effective than older children and adults in using shortcuts. These findings provide clear evidence of a distinct developmental change around 9 years of age when children begin to proficiently orient and navigate using cognitive maps.

Development of spatial orientation skills: an fMRI study.

The ability to orient and navigate in spatial surroundings is a cognitive process that undergoes a prolonged maturation with progression of skills, strategies and proficiency over much of childhood. In the present study, we used functional Magnetic Resonance Imaging (fMRI) to investigate the neurological mechanisms underlying the ability to orient in a virtual interior environment in children aged 10 to 12 years of age, a developmental stage in which children start using effective spatial orientation strategies in large-scale surroundings. We found that, in comparison to young adults, children were not as proficient at the spatial orientation task, and revealed increased neural activity in areas of the brain associated with visuospatial processing and navigation (left cuneus and mid occipital area, left inferior parietal region and precuneus, right inferior parietal cortex, right precentral gyrus, cerebellar vermis and bilateral medial cerebellar lobes). When functional connectivity analyses of resting state fMRI data were performed, using seed areas that were associated with performance, increased connectivity was seen in the adults from the right hippocampal/parahippocampal gyrus to the contralateral caudate, the insular cortex, and the posterior supramarginal gyrus; children had increased connectivity from the right paracentral lobule to the right superior frontal gyrus as compared to adults. These findings support the hypothesis that, as children are maturing in their navigation abilities, they are refining and increasing the proficiency of visuospatial skills with a complimentary increase in connectivity of longer-range distributed networks allowing for flexible use of efficient and effective spatial orientation strategies.

Spatial Orientation and Navigation in Children With Perinatal Stroke.

As a focal injury in an otherwise healthy child, perinatal stroke provides a clinical model of developmental brain plasticity. In this study, we report evidence that children with perinatal periventricular venous infarcts perform as well as control children on a video game that tests navigation abilities. In addition, children with a history of perinatal arterial strokes overcame initial deficits in navigation performance after additional practice. These findings lend support to the hypothesis that a complex cognitive skill dependent on a distributed neural network with prolonged maturation, such as navigation, may demonstrate resilience after early brain injury.

Systematic review of MRI findings in children with developmental delay or cognitive impairment.

AIM: To summarize the reported rates of magnetic resonance imaging (MRI) abnormalities in children with isolated global developmental delay (GDD) or intellectual disability (ID). METHOD: A literature search was conducted using electronic databases for studies reporting the rate of MRI abnormalities in children with clinically diagnosed ID or GDD and no other neurological signs, symptoms, or previously determined aetiology. All investigations with participants from birth to 18years were considered. Study quality was evaluated using the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (MAStARI) critical appraisal checklist items. RESULTS: Eighteen cross sectional, and 11 case-controlled studies adhered to inclusion criteria. Reported rates of abnormalities ranged from 0% to 98%. When all subjects with developmental delay from all papers were considered (n=2299) the total percentage found to have abnormalities was 38%. Abnormalities led to an etiological diagnosis for delay in 7.9% of cases. INTERPRETATION: Definitions of abnormalities varied widely between studies, and drastically different rates of abnormalities are reported. Currently available evidence is not of sufficient quality to make firm recommendations on the use of neuroimaging in ID or GDD but MRI should be considered for children that do not have a diagnosis after thorough clinical evaluation.

A review of cognitive outcomes in children following perinatal stroke.

Perinatal stroke is a significant cause of congenital neurological disability. Although motor deficits and epilepsy are relatively easy to identify, developmental and behavioral co-morbidities are more complex and challenging to define. We provide an overview of perinatal stroke syndromes and theories relating injury in the developing brain to long-term outcomes. We present a comprehensive overview of the effects on intelligence and other specific cognitive domains, as well as investigations relating clinical features and neuroimaging to deficits. Better understanding of the impact of early stroke has potential to elucidate processes of brain development, in addition to providing guidance for prognosis and rehabilitation.