To Typically Developing Research Articles

Evaluating user interface of a mobile augmented reality coloring application for children with autism: An eye-tracking investigation

Mobile augmented reality (AR) solutions are increasingly being used to facilitate learning and skills training for children with autism spectrum disorder (ASD). Derived from the fact that mobile AR systems can be embedded with multimedia effects, such as 3D animations, sounds or personalized images, with potential benefits for learning and engagement. Many mobile AR-based applications have been developed over the past decade; however, little is known about how children with autism interact with mobile AR application interface elements, which limits the accessible user interface (UI) design of such applications. In this study, we conducted an eye-tracking experiment to examine how children with autism interact differently with the UI of mobile AR coloring apps compared to typically developing (TD) children. Both quantitative and qualitative data suggest that 1) icons and images were more attractive to ASD children and could facilitate their understanding of the task more effectively; 2) a richer interface makes participants with autism focus more on irrelevant elements; and 3) the size and position of icons affected their speed of information processing. We recommend that UI be designed to suit the characteristics of children with autism. For example, visual stimuli such as icons or images should be meaningful; screen elements need to be simple and clear; background distractions should be avoided; and text also needs to be brief and precise. This study is expected to inspire researchers to provide AR apps with accessible UIs in the future and improve the user experience (UX) of children with autism.

A cross-sectional study on the neurocognitive outcomes in vestibularimpaired school-aged children: are they at higher risk for cognitive deficits?

This study aimed to assess if children with a vestibular impairment (VI) are more prone to have neurocognitive deficits compared to typically developing (TD) peers, taking into account important confounding factors with hearing loss being the most important. The neurocognitive performance of fifteen VI children (6-13years old) was compared to that of an age-, handedness- and sex-weighted group of TD peers (n = 60). Secondly, their performance was also compared to matched groups of TD and hearingimpaired (HI) children to evaluate the involvement of HI. The protocol comprises cognitive tests assessing response inhibition, emotion recognition, visuospatial memory, selective and sustained attention, visual memory and visual-motor integration.Based on the results, the VI group had significantly reduced scores on 'social cognition' (p = 0.018), 'executive functions' (p < 0.01), and 'perceptual-motor functioning' (p = 0.020) compared to their TD and HI peers. For the categories 'complex attention' and 'learning and memory' no differences could be observed. Analogous to the findings of previous literature, the symptoms of a VI are often not limited to the primary functions of the system, but also comprise an impact on emotional and cognitive performance. Therefore, more holistic rehabilitation approaches should be encouraged, with a screening and attention for cognitive, emotional and behavioral dysfunctions in the vestibular population. Since this is one of the first studies to investigate the involvement of a VI in a child's cognitive development, these findings support the need for studies further characterizing the impact of a VI, the underlying pathophysiology and the effect of different rehabilitation procedures.

Visuomotor skill learning in young adults with Down syndrome

BackgroundIndividuals with Down syndrome (DS) have impaired general motor skills compared to typically developed (TD) individuals. AimsTo gain knowledge on how young adults with DS learn and retain new motor skills. Methods and ProceduresA DS-group (mean age = 23.9 ± 3 years, N = 11), and an age-matched TD-group (mean age 22.8 ± 1.8, N = 14) were recruited. The participants practiced a visuomotor accuracy tracking task (VATT) in seven blocks (10.6 min). Online and offline effects of practice were assessed based on tests of motor performance at baseline immediate and 7-day retention. Outcomes and ResultsThe TD-group performed better than the DS-group on all blocks (all P < 0.001). Both groups improved VATT-performance online from baseline to immediate retention, (all P < 0.001) with no difference in online effect between groups. A significant between-group difference was observed in the offline effect (∆TD - ∆DS, P = 0.04), as the DS-group’s performance at 7-day retention was equal to their performance at immediate retention (∆DS, P > 0.05), whereas an offline decrease in performance was found in the TD-group (∆TD, P < 0.001). Conclusions and ImplicationsVisuomotor pinch force accuracy is lower for adults with DS compared to TD. However, adults with DS display significant online improvements in performance with motor practice similar to changes observed for TD. Additionally, adults with DS demonstrate offline consolidation following motor learning leading to significant retention effects.

Differences in cardiac vagal modulation and cortisol response in adolescents with and without Autism Spectrum Disorder

BackgroundPrevious research pointed towards a need of enhanced understanding of cardiac vagal modulation during resting and stress conditions in individuals with Autism Spectrum Disorder (ASD). This cross-sectional study addressed the following hypotheses: lower values of cardiac vagal modulation will be found in adolescents with ASD in comparison to typically developing (TD) peers; different levels of cardiac vagal reactivity and recovery will be found in adolescents with ASD. In addition, exploratory analyses examined the possible association between cardiac vagal modulation and psychosocial functioning and baseline cortisol levels. MethodsAge and sex matched groups of adolescents (13–17 year) with ASD (n = 47) and TD peers (n = 47) were included. Heart rate, breathing frequency and cortisol levels were determined during baseline and a standardized stress-provoking assessment. Behavioral data concerning autism and behavioral characteristics were collected prior to the assessment. ResultsAdolescents with ASD displayed lower levels of cardiac vagal modulation during baseline and stress-provocation compared to their TD peers. However, levels of cardiac vagal reactivity and recovery were similar across groups. Exploratory analyses indicated weak to moderate associations between the level of cardiac vagal modulation and self- and parent-reported measures of autism characteristics and psychosocial functioning in adolescents with ASD. No significant associations were found between baseline cortisol levels and cardiac vagal modulation in both groups. ConclusionThese findings suggest a parasympathetic hypo-activity in adolescents with ASD and, although the level of reactivity and recovery was the same as TD peers, this hypo-activity might be related to several aspects of psychosocial functioning.

Pragmatic Deficits in Attention Deficit/Hyperactivity Disorder: Systematic Review and Meta-Analysis

Introduction: While poorer pragmatic language skills have been found in attention-deficit/hyperactivity disorder (ADHD) populations, there has been no conclusive evidence of this. We aimed to conduct a meta-analysis of pragmatic language abilities in ADHD populations to definitively demonstrate the extent of pragmatic language deficits in these populations as compared to typically developing (TD) populations. Methods: Studies were identified using the search terms ((attention deficit) OR (adhd)) AND (pragmatics), and those studies were screened and reviewed for inclusion criteria, descriptive information, and outcome variables in order to conduct a meta-analysis. Results: A total of 14 studies (5,772 participants) met the criteria for quantitative synthesis. Meta-analysis indicated that ADHD populations exhibited significantly poorer pragmatic language skills than TD populations, with a very large overall effect size of −1.55. These results indicate that pragmatic language is significantly impaired in ADHD populations. Conclusion: It is suggested that pragmatic language skills may deserve greater surveillance considering the importance of pragmatic language in socio-emotional development, daily life, and academic success.

Association of adverse childhood experience-related increase in neurite density with sensory over-responsivity in autism spectrum disorder: A neurite orientation dispersion and density imaging study

Sensory over-responsivity (SOR) causes social and daily distress in individuals with autism spectrum disorder (ASD). Compared to typically developed (TD) individuals, ASD individuals are at higher risk of adverse childhood experiences (ACEs), which induce abnormal neuronal development. However, whether or how ACEs are associated with abnormal neural development and SOR in ASD remains to be determined. Forty-five individuals with ASD and 43 TD individuals underwent T1-weighted and neurite orientation dispersion and density imaging; the axonal and dendritic densities were defined as the neurite density index (NDI). Voxel-based analyses were performed to explore the brain regions associated with SOR. The relationships between severity of ACEs and SOR, and NDI in the brain regions were examined. ASD individuals showed a significantly positive association between SOR severity and NDI in the right superior temporal gyrus (STG), which was not found in TD individuals. Severity of ACEs correlated significantly with that of SOR and NDI in the right STG in ASD; ASD individuals having severe SOR showed significantly higher NDI in the right STG than those with mild SOR and TD individuals. In individuals with ASD, NDI in the right STG, but not ACEs, could predict the severity of SOR, which was not shown in TD subjects. Our findings suggest that severe ACEs are involved in excessive neurite density in the right STG in ASD. ACE-associated excessive neurite density in the right STG is critical for SOR in ASD, which may be a therapeutic target in the future.

Motor Function and Physiology in Youth With Neurofibromatosis Type 1

BackgroundNeurofibromatosis type 1 (NF1) is a genetic neurocutaneous disorder commonly associated with motor and cognitive symptoms that greatly impact quality of life. Transcranial magnetic stimulation (TMS) can quantify motor cortex physiology, reflecting the basis for impaired motor function as well as, possibly, clues for mechanisms of effective treatment. We hypothesized that children with NF1 have impaired motor function and altered motor cortex physiology compared to typically developing (TD) control children and children with attention-deficit/hyperactivity disorder (ADHD). MethodsChildren aged 8-17 years with NF1 (n = 21) were compared to children aged 8-12 years with ADHD (n = 59) and TD controls (n = 88). Motor development was assessed using the Physical and Neurological Examination for Subtle Signs (PANESS) scale. The balance of inhibition and excitation in motor cortex was assessed using the TMS measures short-interval cortical inhibition (SICI) and intracortical facilitation (ICF). Measures were compared by diagnosis and tested using bivariate correlations and regression for association with clinical characteristics. ResultsIn NF1, ADHD severity scores were intermediate between the ADHD and TD cohorts, but total PANESS scores were markedly elevated (worse) compared to both (P < 0.001). Motor cortex ICF (excitatory) was significantly lower in NF1 than in TD and ADHD (P < 0.001), but SICI (inhibitory) did not differ. However, in NF1, better PANESS scores correlated with lower SICI ratios (more inhibition; ρ = 0.62, P = 0.003) and lower ICF ratios (less excitation; ρ = 0.38, P = 0.06). ConclusionsTMS-evoked SICI and ICF may reflect processes underlying abnormal motor function in children with NF1.

Resting-state gamma oscillations in adult Autism spectrum disorder: A High-Density EEG study

IntroductionAutism is neurodevelopmental disorder with a heterogeneous presentation of symptoms, which include disturbances in sensory, motor and cognitive processes, among which social cognitive impairments and social interaction difficulties play prominent role. Despite the fact that these impairments can lead to lifelong disability and difficulties in everyday functioning, their neurobiological basis remains largely unknown. Neural oscillations in the gamma band have been shown to be an important candidate neurobiological marker of higher order cognitive processes and social interactions. Yet, alterations of gamma oscillations in ASD have received little attention in the literature.ObjectivesThe aim of the current study was to investigate resting state gamma oscillations in the EEG in order to delineate alterations in ASD as compared to typically developing (TD) subjects in the intrinsic activity of the neural networks that have been linked to social cognitive functioning.MethodsResting-state EEGs were obtained in an ongoing study investigating ASD (N=19) and TD subjects (N=15), based on eyes closed condition. EEGs were recorded using a 128-channel BioSemi system. EEG absolute power was investigated in the gamma 30-48Hz frequency band.ResultsGamma activity was significantly (p&lt;0.05) diminished in multiple brain regions in ASD as compared TD subjects. The diminished gamma activity had a distinctive topographical distribution, which included the left and right inferior temporal gyrus, the right superior temporal gyrus, the TPJ and the right extrastriate areas. Additionally, we found a hemispheric asymmetry in the occipital brain areas with a decrease of gamma activity on the right and an increase in the left hemisphere as compared to TD.ConclusionsDiminished gamma activity in the above brain areas may represent a cortical dysfunction which can be present due to a reduced capacity to process socially relevant information and a decreased capacity to omit irrelevant stimuli.Funding: Hungarian Brain Research program,#NAP2022-I-4/2022Disclosure of InterestNone Declared

Interpretation of Misarticulated Words by Children With and Without Speech Sound Disorders.

Children with speech sound disorders (SSDs) often struggle with forming early representations for phonemes and words, which could impact their speech production as well as their lexical access. This difficulty may limit their ability to accurately identify nonexemplar productions of words, such as developmental misarticulations produced by peers. The purpose of this study was to examine word interpretation of misarticulated words by children with SSD. Seventeen monolingual English-speaking preschoolers were assessed for language, phonological processing, and articulation skills. Participants heard three types of words: accurate productions (e.g., "leaf"), common misarticulated productions (e.g., "weaf"), uncommon misarticulated productions (e.g., "yeaf"), and unrelated nonwords (e.g., "gim"). Children were presented with these words aurally and asked to select the picture that matched what they heard-either a real object or a blank square. The proportion of real object picture selections was calculated for each word type and compared within subjects. The findings indicate that children with SSD reliably associated common misarticulated words with pictured objects more frequently than they did in the uncommon misarticulation condition. These results were compared between subjects to typically developing (TD) peers' responses using a one-way analysis of variance. The results indicate that children with SSD identified common substitutions as real object pictures more often than TD peers. The results of this study suggest that children with SSD are sensitive to the commonness of misarticulations; however, they accept common substitutions as real object pictures significantly more often than TD peers.

Exploring the unmet needs of adults with cerebral palsy living in urban South Africa

Purpose The investigators aimed to understand the unmet needs of adults with cerebral palsy (CP) living in urban South Africa and to ascertain similarities or differences to typically developing (TD) adults in the same community. Materials and methods Participants were interviewed with an adapted version of the Southampton Needs Assessment Questionnaire (SNAQ). Non-parametric statistical analysis was utilised for quantitative data and qualitative data were analysed using free coding to identify themes. Results Thirty adults with CP (median age 34.8 years; GMFCS levels I/II/III/IV/V: n = 6/6/5/7/6; socio-economic status (SES) low/average/high: n = 8/17/5) were matched for gender, age, and SES. Adults with CP reported a higher unemployment rate and lower level of satisfaction with access to health services than TD peers. Core themes identified by the participants with CP that made community participation more difficult were physical capacity, poor access to accommodation, transport and health services, lack of socialising opportunities, poor universal design, and lack of financial independence. Conclusions Adults with CP reported experiencing many challenges in their communities. Improved access to health care services and transport, and the universal design of housing and community buildings to accommodate individuals with a disability should be made a priority. Implications for rehabilitation Adults with cerebral palsy (CP) reported that their disability had an impact on their social life, home life, and work life. Accessibility issues have been identified as a major factor affecting adults with CP in a variety of areas, including access to and use of health services, housing, transportation, and community buildings. Adults with CP reported the need for support during the transition to adulthood, especially with developing life skills that will promote living independently in the community as adults with disabilities.

The role of single trial variability in event related potentials in children with attention deficit hyperactivity disorder

ObjectiveChildren with attention deficit hyperactivity disorder (ADHD) show attenuated mean P3 component amplitudes compared to typically developing (TD) children. This finding may be the result of individual differences in P3 amplitudes, P3 latencies, and/or greater single trial variability (STV) in amplitude or latency, suggesting neural “noise.” MethodsEvent related potentials (ERPs) from 75 children with ADHD and 29 TD children were recorded with electroencephalography (EEG). Caregivers provided ratings on child ADHD symptoms. Single-trial ERP amplitudes and latencies were extracted from the P3 component time window during a visual oddball task. Additionally, we computed individual-centered and trial-centered P3 amplitudes to account for inter-individual and inter-trial variability in the timing of the P3 peak. ResultsIn line with prior research, greater ADHD symptom severity was associated with reduced mean P3 amplitude. This correlation was no longer significant after correcting for inter-trial differences in P3 latency. In contrast, greater ADHD symptom severity was associated with reduced STV in P3 amplitude. ConclusionsOur results suggest that attenuated average P3 amplitude in ADHD samples is due to a consistent reduction in strength of the neurophysiological signal at the single trial level, as well as increased inter-trial variability in the timing of P3 peak amplitudes. The traditional method of extracting P3 amplitudes based on a single time window for all trials may not adequately capture variability in P3 latencies associated with ADHD. SignificanceInter- and intra-individual differences in brain signatures should be considered in models of neurobiological differences in neurodevelopmental samples.

The influence of wearing an ultrasound device on gait in children with cerebral palsy and typically developing children

BackgroundUltrasonography with motion analysis enables dynamic imaging of medial gastrocnemius (MG) muscles and tendons during gait. This revealed pathological muscle-tendon dynamics in children with spastic cerebral palsy (CP) compared to typically developing (TD) children. However, wearing an ultrasound probe on the lower leg could interfere with gait and bias muscle length changes observed with ultrasound. Research questionDoes wearing an ultrasound probe on the MG influence gait in children with CP and TD children? MethodsEighteen children with spastic CP and 16 age-matched TD children walked at comfortable walking speed on an instrumented treadmill. One baseline gait condition (BASE) and two conditions with an ultrasound probe and custom-made probe holder were measured: on the mid-muscle fascicles (FAS) and on the muscle-tendon junction (MTJ). The effect of condition and group on spatiotemporal parameters, hip, knee and ankle kinematics, ankle moment, ankle power, and modeled MG muscle-tendon unit (MTU) length was assessed using two-way repeated measures ANOVA’s. Statistical non-parametric mapping was applied for time-series. Post-hoc paired-samples t-tests were conducted, and the root mean square difference was calculated for significant parts. ResultsChildren took wider steps during FAS (CP, TD) and MTJ (TD) compared to BASE, and during FAS compared to MTJ (CP). Hip extension was lower (2.7°) during terminal stance for MTJ compared to FAS for TD only. There was less swing knee flexion (FAS 4.9°; MTJ 4.0°) and ankle plantarflexion around toe-off (FAS 3.0°; MTJ 2.4°) for both ultrasound placements, with no group effect. Power absorption during loading response was slightly increased for both ultrasound placements (0.12 W/kg), with no group effect. MTU shortened less in swing for both ultrasound placements (FAS 3.6 mm; MTJ 3.7 mm), with no group effect. SignificanceWearing an ultrasound probe causes minimal lower-limb gait alterations and MTU length changes that are mostly similar in CP and TD.

Examination of common and unique brain regions for atypical reading and math: a meta-analysis.

The purpose of this study is to identify consistencies across functional neuroimaging studies regarding common and unique brain regions/networks for individuals with reading difficulties (RD) and math difficulties (MD) compared to typically developing (TD) individuals. A systematic search of the literature, utilizing multiple databases, yielded 116 functional magnetic resonance imaging and positron emission tomography studies that met the criteria. Coordinates that directly compared TD with either RD or MD were entered into GingerALE (Brainmap.org). An activation likelihood estimate (ALE) meta-analysis was conducted to examine common and unique brain regions for RD and MD. Overall, more studies examined RD (n = 96) than MD (n = 20). Across studies, overactivation for reading and math occurred in the right insula and inferior frontal gyrus for atypically developing (AD) > TD comparisons, albeit in slightly different areas of these regions; however, inherent threshold variability across imaging studies could diminish overlying regions. For TD > AD comparisons, there were no similar or overlapping brain regions. Results indicate there were domain-specific differences for RD and MD; however, there were some similarities in the ancillary recruitment of executive functioning skills. Theoretical and practical implications for researchers and educators are discussed.

Age differences and brain maturation provide insight into heterogeneous results in autism spectrum disorder.

Studies comparing individuals with autism spectrum disorder (ASD) to typically developing (TD) individuals have yielded inconsistent results. These inconsistencies reflect, in part, atypical trajectories of development in children and young adults with ASD compared to TD peers. These different trajectories alter group differences between children with and without ASD as they age. This paper first summarizes the disparate trajectories evident in our studies and, upon further investigation, laboratories using the same recruiting source. These studies indicated that cognition improves into adulthood typically, and is associated with the maturation of striatal, frontal, and temporal lobes, but these age-related improvements did not emerge in the young adults with ASD. This pattern - of improvement into adulthood in the TD group but not in the group with ASD - occurred in both social and non-social tasks. However, the difference between TD and ASD trajectories was most robust on a social task, face recognition. While tempting to ascribe this uneven deficit to the social differences in ASD, it may also reflect the prolonged typical development of social cognitive tasks such as face recognition into adulthood. This paper then reviews the evidence on age-related and developmental changes from other studies on ASD. The broader literature also suggests that individuals with ASD do not exhibit the typical improvements during adolescence on skills important for navigating the transition to adulthood. These skills include execution function, social cognition and communication, and emotional recognition and self-awareness. Relatedly, neuroimaging studies indicate arrested or atypical brain maturation in striatal, frontal, and temporal regions during adolescence in ASD. This review not only highlights the importance of a developmental framework and explicit consideration of age and/or stage when studying ASD, but also the potential importance of adolescence on outcomes in ASD.

Short report: Self-compassion and satisfaction with life in Danish adolescents with Developmental Language Disorder (DLD): `We are all in the same boat´

BackgroundAdolescents with Developmental Language Disorder (DLD) are at risk of emotional health problems and low self-esteem. However, little is known about their self-compassion (SC) and satisfaction with life (SWL). The present study compared self-compassion and satisfaction with life reported by Danish adolescents with DLD compared to typically developing (TD) peers, and whether severity of language difficulty is associated with SC and SWL. MethodsResults were obtained from 10 Danish adolescents with DLD compared with 14 age-matched TD adolescents and 132 TD peers, aged 15 years. ResultsFor SC and SWL results showed that adolescents with DLD reported more positive feelings compared to the TD adolescents. Interestingly for SC, the negative, but not the positive, domain differentiated the two groups, as adolescents with DLD reported less symptoms on self-judgment, isolation and overidentification. SC and SWL was strongly correlated with language abilities for the DLD group, but not for the TD group. ConclusionsResults from our pilot study showed that Danish adolescents with DLD reported being less harsh on themselves. Language abilities were associated with self-compassion for the DLD, but not for the TD group. Whether these group differences are due to environmental factors such as the specific Danish school setting of the DLD group or internal factors are discussed and requires further research.

Assessment of Feeding Behaviors and Parents' Frustrations of Children with Autism Spectrum Disorder in Lebanon: A Case-Control Study.

Children with autism spectrum disorder (ASD) exhibit restrictive and repetitive behaviors that affect their eating habits. The purpose of this study is to identify the behavioral feeding problems and eating habits among ASD children compared to typically developed (TD) children age/gender-matched controls, along with their parents'/caregivers' strategies for dealing with them. It included 43 ASD children and 43 TD children aged two to eleven years. The analysis was performed based on two valid questionnaires: the Behavior Pediatrics Feeding Assessment Scale (BPFA) and "My Child Eating Habits" (MCEH). The BPFA and MCEH scores conceded three manifestations that fall into food selectivity and problematic mealtime behavior in both groups of children. Compared to TD children, children with ASD exhibited higher BPFA scores, which indicated food-related behavioral and skill-based problems (p = 0.004). Children with ASD were less likely to consume fruits, vegetables, and milk than TD children, which may lead to nutritional deficiencies (p = 0.003, p = 0.003, and p = 0.010, respectively). Parents of ASD children were concerned about their behavioral problems and expressed their intention of an early intervention. These findings highlight the importance of nutritional clinical routines that incorporate the evaluation of the nutritional status and feeding behaviors of ASD children.

Functional connectivity changes during working memory in autism spectrum disorder: A two-year longitudinal MEG study

Working memory impairments have been reported in adults with autism spectrum disorder (ASD) and associated with functional outcomes and social difficulties. However, little is known about the developmental trajectory of working memory in youth with ASD. The current magnetoencephalography (MEG) study is the first to examine the longitudinal development over two years of working memory networks in youth with ASD. We analysed MEG data from 32 children and adolescents with and without ASD (64 datasets; 7–14 years), all tested twice at a two-year interval, during a visual n-back task, with two loads (1- and 2-back). We performed a whole-brain functional connectivity analysis to examine the networks during the successful recognition of visual stimuli. We demonstrate that youth with ASD show decreased connectivity in the theta frequency (4–7 Hz) in the higher memory load (2-back) condition compared to typically developing (TD) controls. This hypo-connected theta network was anchored in primary visual areas with connections to frontal, parietal and limbic regions. These network differences were found despite similar task performance between ASD and TD groups. Within the TD group, we found an increase in alpha (8–14 Hz) connectivity at Time 2 compared to Time 1 in both the 1- and 2-back conditions. These findings demonstrate the continued development of working memory mechanisms over middle childhood, which were not apparent in youth with ASD. Together, our findings support a network-based approach to understanding atypical neural functioning in ASD and the developmental trajectories of working memory processes over middle childhood.

In individuals with Williams syndrome, dysregulation of methylation in non-coding regions of neuronal and oligodendrocyte DNA is associated with pathology and cortical development.

Williams syndrome (WS) is a neurodevelopmental disorder caused by a heterozygous micro-deletion in the WS critical region (WSCR) and is characterized by hyper-sociability and neurocognitive abnormalities. Nonetheless, whether and to what extent WSCR deletion leads to epigenetic modifications in the brain and induces pathological outcomes remains largely unknown. By examining DNA methylation in frontal cortex, we revealed genome-wide disruption in the methylome of individuals with WS, as compared to typically developed (TD) controls. Surprisingly, differentially methylated sites were predominantly annotated as introns and intergenic loci and were found to be highly enriched around binding sites for transcription factors that regulate neuronal development, plasticity and cognition. Moreover, by utilizing enhancer-promoter interactome data, we confirmed that most of these loci function as active enhancers in the human brain or as target genes of transcriptional networks associated with myelination, oligodendrocyte (OL) differentiation, cognition and social behavior. Cell type-specific methylation analysis revealed aberrant patterns in the methylation of active enhancers in neurons and OLs, and important neuron-glia interactions that might be impaired in individuals with WS. Finally, comparison of methylation profiles from blood samples of individuals with WS and healthy controls, along with other data collected in this study, identified putative targets of endophenotypes associated with WS, which can be used to define brain-risk loci for WS outside the WSCR locus, as well as for other associated pathologies. In conclusion, our study illuminates the brain methylome landscape of individuals with WS and sheds light on how these aberrations might be involved in social behavior and physiological abnormalities. By extension, these results may lead to better diagnostics and more refined therapeutic targets for WS.

Autism spectrum disorder symptom expression in individuals with 3q29 deletion syndrome

BackgroundThe 1.6 Mb 3q29 deletion is associated with neurodevelopmental and neuropsychiatric phenotypes, including a 19-fold increased risk for autism spectrum disorder (ASD). Previous work by our team identified elevated social disability in this population via parent-report questionnaires. However, clinical features of ASD in this population have not been explored in detail.MethodsThirty-one individuals with 3q29 deletion syndrome (3q29del, 61.3% male) were evaluated using two gold-standard clinical ASD evaluations: the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2), and the Autism Diagnostic Interview, Revised (ADI-R). Four matched comparators for each subject were ascertained from the National Database for Autism Research. Item-level scores on the ADOS-2 and ADI-R were compared between subjects with 3q29del and matched comparators.ResultsSubjects with 3q29del and no ASD (3q29del-ASD) had greater evidence of social disability compared to typically developing (TD) comparison subjects across the ADOS-2. Subjects with 3q29del and ASD (3q29del + ASD) were largely indistinguishable from non-syndromic ASD (nsASD) subjects on the ADOS-2. 3q29del + ASD performed significantly better on social communication on the ADI-R than nsASD (3q29 + ASD mean = 11.36; nsASD mean = 15.70; p = 0.01), and this was driven by reduced deficits in nonverbal communication (3q29 + ASD mean = 1.73; nsASD mean = 3.63; p = 0.03). 3q29del + ASD reported significantly later age at the first two-word phrase compared to nsASD (3q29del + ASD mean = 43.89 months; nsASD mean = 37.86 months; p = 0.01). However, speech delay was not related to improved nonverbal communication in 3q29del + ASD.LimitationsThere were not enough TD comparators with ADI-R data in NDAR to include in the present analysis. Additionally, our relatively small sample size made it difficult to assess race and ethnicity effects.Conclusions3q29del is associated with significant social disability, irrespective of ASD diagnosis. 3q29del + ASD have similar levels of social disability to nsASD, while 3q29del-ASD have significantly increased social disability compared to TD individuals. However, social communication is reasonably well preserved in 3q29del + ASD relative to nsASD. It is critical that verbal ability and social disability be examined separately in this population to ensure equal access to ASD and social skills evaluations and services.

Resting state electroencephalography microstates in autism spectrum disorder: A mini-review.

Atypical spatial organization and temporal characteristics, found via resting state electroencephalography (EEG) microstate analysis, have been associated with psychiatric disorders but these temporal and spatial parameters are less known in autism spectrum disorder (ASD). EEG microstates reflect a short time period of stable scalp potential topography. These canonical microstates (i.e., A, B, C, and D) and more are identified by their unique topographic map, mean duration, fraction of time covered, frequency of occurrence and global explained variance percentage; a measure of how well topographical maps represent EEG data. We reviewed the current literature for resting state microstate analysis in ASD and identified eight publications. This current review indicates there is significant alterations in microstate parameters in ASD populations as compared to typically developing (TD) populations. Microstate parameters were also found to change in relation to specific cognitive processes. However, as microstate parameters are found to be changed by cognitive states, the differently acquired data (e.g., eyes closed or open) resting state EEG are likely to produce disparate results. We also review the current understanding of EEG sources of microstates and the underlying brain networks.