Diagnosis and management of Cornelia de Lange syndrome: first international consensus statement.

Cornelia de Lange syndrome (CdLS) is an archetypical genetic syndrome that is characterized by intellectual disability, well-defined facial features, upper limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in any one of seven genes, all of which have a structural or regulatory function in the cohesin complex. Although recent advances in next-generation sequencing have improved molecular diagnostics, marked heterogeneity exists in clinical and molecular diagnostic approaches and care practices worldwide. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria, both for classic CdLS and non-classic CdLS phenotypes, molecular investigations, long-term management and care planning.

The Association of Intrapair Birth-Weight Differences With Internalizing and Externalizing Behavior Problems.

Problem behaviors are of increasing public health concern. Twin studies have revealed substantial genetic and environmental influences on children's behavior, and examining birth-weight difference could allow the identification of the specific contribution of multiple non-shared prenatal environmental factors. The Twins and Multiple Births Association Heritability Study, a UK, volunteer-based study, recruited mothers of twins aged 18 months to 5 years; 960 twins (480 pairs) were included in the analysis. Twins' mothers answered questions relative to their pregnancy and their twins' characteristics, and completed the Child Behavior Checklist (CBCL) 1½-5. The association between the absolute birth-weight difference and each CBCL scale's score difference was analyzed by means of multiple linear regressions. Expected mean CBCL score differences were calculated. In monozygotic (MZ) twins, statistically and clinically significant associations were found between intrapair birth-weight difference and difference in total problems, internalizing problems, and emotional reactiveness. No significant results were observed neither in dizygotic (DZ) twins when analyzed as a separate group nor in MZ and DZ twins combined. The results of the present study suggest that with increasing the absolute birth-weight difference, the intrapair difference in total problems, internalizing behaviors and emotionality increases, with smaller twins being at major risk for later behavior problems. Moreover, these results suggest a causal association between birth weight and behavior development.

Variation in serotonin transporter linked polymorphic region (5-HTTLPR) short/long genotype modulates resting frontal electroencephalography asymmetries in children.

Previous studies have documented the serotonin transporter linked polymorphic region (5-HTTLPR) as a genetic susceptibility variant that contributes to variability in outcomes related to affective psychopathology, with the short allele associated with negative affectivity and the long allele associated with positive affectivity. In a separate but related line of research, extensive evidence suggests that frontal electroencephalography (EEG) hemispheric asymmetry in the alpha band is also associated with risk for affective psychopathologies, with leftward asymmetry associated with approach-related behavior patterns and rightward frontal EEG asymmetry associated with withdrawn behavioral tendencies. We examined frontal EEG hemispheric asymmetries in relation to 5-HTTLPR genotyping in 70 children between 4 and 6 years of age. Analyses revealed that frontal EEG lateralization interacted with genotype such that children homozygous for the short allele exhibited rightward frontal EEG asymmetries, children who were homozygous for the long allele consistently exhibited a positive pattern of leftward asymmetry, and heterozygotes exhibited equivalent left and right frontal activity. These findings suggest that the 5-HTTLPR short allele may provide a degree of susceptibility for later affective psychopathology in adolescence and adulthood, through mediation of frontal brain activity that is associated with cognitive-behavioral withdrawal tendencies and negative affectivity.

Associative learning alone is insufficient for the evolution and maintenance of the human mirror neuron system.

Cook et al. argue that mirror neurons originate from associative learning processes, without evolutionary influence from social-cognitive mechanisms. We disagree with this claim and present arguments based upon cross-species comparisons, EEG findings, and developmental neuroscience that the evolution of mirror neurons is most likely driven simultaneously and interactively by evolutionarily adaptive psychological mechanisms and lower-level biological mechanisms that support them.

Neurocognitive Concussion Test Performance for Student Athletes on the Autism Spectrum.

OBJECTIVE: To examine baseline neurocognitive functioning among adolescent athletes on the autism spectrum based on self-reported level of academic performance. METHOD: Participants in this cross-sectional, observational study were 6,441 adolescent athletes with a self-reported diagnosis of autism who completed pre-season neurocognitive testing using Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT); 4,742 reported a co-occurring learning disorder (LD), and 6,612 individuals without autism or LD were included as a control group. The majority (57%) self-reported Average Academic Performance, 39% Above Average, and 4% Below Average performance. RESULTS: Athletes with self-reported autism (with or without LD; 12.2%) were 2.74x (95% CI: 2.17-2.82) more likely to fall below cutoffs for ImPACT Embedded Invalidity Indicators (EVIs), with a significant interaction between self-reported Diagnosis and Academic Performance; individuals with co-occurring autism and LD who reported Below Average Academic Performance had the greatest likelihood of scoring below cutoffs (22%), followed by ASD without LD (14.8%) and Controls (14.6%) with Below Average Academic Performance. Analyses of variance (ANOVAs) revealed main effects of Diagnosis and Academic Performance on neurocognitive performance, with interactions on all ImPACT Composite Scores except Processing Speed. CONCLUSION: Athletes with self-reported ASD are more likely to fall below ImPACT EVIs and score worse on ImPACT, with greater likelihood/worse performance related to level of academic functioning. Academic performance should be considered when interpreting neurocognitive testing data, to best index neuropsychological functioning associated with concussion in this population. The current findings highlight the importance of individual participant baseline neuropsychological testing for individuals on the autism spectrum.

A delayed intervention start randomized controlled trial of high- and low-tech communication training approaches for school-age autistic children with co-occurring intellectual disability.

The researchers designed a delayed intervention start randomized controlled trial to compare improvements in functional communication following augmentative and alternative communication (AAC) interventions. The study compared outcomes from function-based applied behavior analytic (ABA) and eclectic non-ABA forms of classroom-based communication strategies (waitlist control) as well as from high- and low-tech forms of AAC. High-tech AAC consisted of tablet-based communication, and low-tech AAC used an exchange of picture cards. The community-based sample consisted of 29 autistic children with a co-occurring intellectual disability. Participants were randomized to groups (AAC, waitlist control), and each group received approximately 3 months of communication intervention. Multilevel modeling of learner outcomes indicated that the function-based approach produced greater improvements than the eclectic alternative, but significant differences were not observed between outcomes of high- and low-tech forms of function-based AAC. These results are consistent with earlier investigations and provide supporting evidence that both high- and low-tech forms of function-based intervention are effective for use with autistic children with accompanying intellectual disability. Additional discussion is provided regarding further research into how technology is applied and incorporated into behavior analytic programming.

Sex differences in social and emotional insight in youth with and without autism.

Autism was formally recognized by the medical community in the first half of the twentieth century. Almost 100 years later, a small but growing literature has reported sex differences in the behavioral expression of autism. Recent research has also begun to explore the internal experiences of individuals with autism, including social and emotional insight. The current study examines sex differences in language-based markers of social and emotional insight in girls and boys with autism and non-autistic peers during semi-structured clinical interviews. Sixty-four participants aged 5 to 17 years were individually matched on chronological age and full-scale IQ to form four groups: autistic girls, autistic boys, non-autistic girls, and non-autistic boys. Transcribed interviews were scored using four scales that index aspects of social and emotional insight. Results revealed the main effects of diagnosis, such that youth with autism exhibited lower insight than non-autistic youth on scales indexing social cognition and object relations, emotional investment, and social causality. With regards to sex differences, across diagnoses, girls were rated higher than boys on the social cognition and object relations, emotional investment, and social causality scales. Examined within each diagnosis separately, clear sex differences emerged: both autistic and non-autistic girls demonstrated better social cognition and understanding of social causality than boys in their respective diagnostic groups. No within-diagnosis sex differences were found on the emotional insight scales, however. These results suggest that relatively enhanced social cognition and understanding of social causality in girls may be a population-level sex difference that is preserved in autism, despite the core social challenges that characterize this condition. The current findings reveal critical new information about insight into social and emotional thinking and relationships in autistic girls versus boys that have important implications for improving identification and designing effective interventions.

The neural and cognitive time course of theory of mind.

Neuroimaging and neuropsychological studies implicate both frontal and temporoparietal cortices when humans reason about the mental states of others. Here, we report an event-related potentials study of the time course of one such "theory of mind" ability: visual perspective taking. The findings suggest that posterior cortex, perhaps the temporoparietal cortex, calculates and represents the perspective of self versus other, and then, later, the right frontal cortex resolves conflict between perspectives during response selection.

Neural correlates of verbal and nonverbal semantic integration in children with autism spectrum disorders.

BACKGROUND: Autism is a pervasive developmental disorder characterized by deficits in social-emotional, social-communicative, and language skills. Behavioral and neuroimaging studies have found that children with autism spectrum disorders (ASD) evidence abnormalities in semantic processing, with particular difficulties in verbal comprehension. However, it is not known whether these semantic deficits are confined to the verbal domain or represent a more general problem with semantic processing. The focus of the current study was to investigate verbal and meaningful nonverbal semantic processing in high-functioning children with autism (mean age = 5.8 years) using event-related potentials (ERPs). METHOD: ERPs were recorded while children attended to semantically matching and mismatching picture-word and picture-environmental sound pairs. RESULTS: ERPs of typically developing children exhibited evidence of semantic incongruency detection in both the word and environmental sound conditions, as indexed by elicitation of an N400 effect. In contrast, children with ASD showed an N400 effect in the environmental sound condition but not in the word condition. CONCLUSIONS: These results provide evidence for a deficiency in the automatic activation of semantic representations in children with ASD, and suggest that this deficit is somewhat more selective to, or more severe in, the verbal than the nonverbal domain.

Safety and Feasibility of an Immersive Virtual Reality Intervention Program for Teaching Police Interaction Skills to Adolescents and Adults with Autism.

Low-cost, wireless immersive virtual reality (VR) holds significant promise as a flexible and scalable intervention tool to help individuals with autism spectrum disorder (ASD) learn and develop critical practical life skills, including interacting safely and effectively with police officers. Previous research suggests that VR is a motivating intervention platform, but many individuals with ASD also exhibit anxiety and sensory sensitivities which might make it difficult to tolerate VR experiences. Here, we describe the results of a relatively large-scale, National Institutes of Health-funded systematic examination of the safety, feasibility, and usability of an immersive VR training program in adolescents and adults with ASD, aged 12 and older. Sixty verbally fluent individuals with no personal or immediate family history of seizures or migraines participated in either one (n = 30) or three 45-min (n = 30) VR sessions using a lightweight wireless headset, and were monitored for side effects. Participants also reported on system usability, enjoyment, and willingness to engage in further VR sessions. Results confirm that immersive VR is safe, feasible, and highly usable for verbally fluent adolescents and adults with ASD. LAY SUMMARY: Immersive virtual reality (VR) holds promise as a means to provide social skills interventions for individuals with autism spectrum disorder (ASD), but it is unclear whether associated anxiety and sensory symptoms might limit feasibility. Here, we report data that indicate that immersive VR is both safe and feasible for use in verbally fluent adolescents and adults with ASD, for up to three 45-min sessions. Autism Res 2020, 13: 1418-1424. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.

A Lifespan Approach to Patient-Reported Outcomes and Quality of Life for People on the Autism Spectrum.

Autistic self-advocates, family members, and community organizations have called for greater emphasis on enhancing quality of life (QoL) for people with autism. Doing this is critical to understand how QoL unfolds across the life course and to clarify whether gender affects QoL, health, and functioning for people with autism. The purpose of this study was to curate and test a lifespan QoL measurement tool using freely available and well-constructed National Institutes of Health Parent-Reported Outcomes Measurement Information System (PROMIS). To develop the PROMIS Autism Battery-Lifespan (PAB-L), we identified PROMIS scales relevant for autism, reviewed each item, consulted with a panel of autism experts, and elicited feedback from autistic people and family members. This battery provides a comprehensive portrait of QoL for children ages 5-13 (through parent proxy), teens 14-17 (parent proxy and self-report), and adults 18-65 (self-report) with autism compared to the general population. Participants and parent informants (N = 912) recruited through a children's hospital and nationwide U.S. autism research registry completed the PAB-L online. Results indicate that compared to general population norms, people with autism of all ages (or their proxies) reported less desirable outcomes and lower QoL across all domains. Women and girls experienced greater challenges in some areas compared to men and boys with autism. The PAB-L appears to be a feasible and acceptable method for assessing patient-reported outcomes and QoL for autistic people across the life course. Autism Res 2020, 13: 970-987. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We developed a survey to measure the quality of life of children, teens, and adults with autism using free National Institutes of Health PROMIS questionnaires. People with autism and family members rated the PROMIS Autism Battery-Lifespan as useful and important. Some reported a good quality of life, while many reported that their lives were not going as well as they wanted. Women and girls reported more challenges in some areas of life than men and boys.

Effects of gestational length, gender, postnatal age, and birth order on visual contrast sensitivity in infants.

To investigate effects of visual experience versus preprogrammed mechanisms on visual development, we used multiple regression analysis to determine the extent to which a variety of variables (that differ in the extent to which they are tied to visual experience) predict luminance and chromatic (red/green) contrast sensitivity (CS), which are mediated by the magnocellular (M) and parvocellular (P) subcortical pathways, respectively. Our variables included gestational length (GL), birth weight (BW), gender, postnatal age (PNA), and birth order (BO). Two-month-olds (n = 60) and 6-month-olds (n = 122) were tested. Results revealed that (1) at 2 months, infants with longer GL have higher luminance CS; (2) at both ages, CS significantly increases over a approximately 21-day range of PNA, but this effect is stronger in 2- than 6-month-olds and stronger for chromatic than luminance CS; (3) at 2 months, boys have higher luminance CS than girls; and (4) at 2 months, firstborn infants have higher CS, while at 6 months, non-firstborn infants have higher CS. The results for PNA/GL are consistent with the possibility that P pathway development is more influenced by variables tied to visual experience (PNA), while M pathway development is more influenced by variables unrelated to visual experience (GL). Other variables, including prenatal environment, are also discussed.

Maternal pre-pregnancy weight and twins' temperament.

Maternal pre-pregnancy weight has been related with young singletons' cognitive and behavioral development, but it is not clear if it has an effect on temperament. We used a twin cohort to evaluate the association between maternal pre-pregnancy body mass index (BMI) and infants' temperament. The mothers of 834 twins answered questions regarding their pre-pregnancy BMI and their 0- to 18-month-old children's temperament using the Revised Infant Behavior Questionnaire. Three temperamental dimensions were examined: activity level, distress to limitation and duration of orienting. The relationship between maternal pre-pregnancy BMI and each temperamental component was investigated by means of multilevel mixed-effects linear regression analysis. We found no clear evidence of an association of maternal pre-pregnancy BMI with twins' temperament. The development of temperament is influenced by a large number of factors, probably different from those influencing children's emotional and behavioral development.

What's in a name? A preliminary event-related potential study of response to name in preschool children with and without autism spectrum disorder.

The ability to selectively respond to one's own name is important for social and language development, and is disrupted in atypically developing populations (e.g., autism spectrum disorder). Research with typically developing samples using event-related potentials (ERPs) has demonstrated that the subject's own name (SON) is differentiated from other stimuli at both early sensory and later cognitive stages of auditory processing. While neural indices of response to name have been researched extensively in adults, no such studies have been conducted with typically developing preschool children or children with autism spectrum disorder (ASD). The present study investigated ERP response to name in a sample of typically developing (TD) preschoolers (n = 19; mean age = 4.3 years) as well as a small, exploratory comparison group of preschoolers with ASD (n = 13; mean age = 4.4 years). TD preschoolers exhibited significantly greater negativity to SON over frontal regions than to an unfamiliar nonsense name, consistent with the adult SON negativity component. This component was present whether the name was spoken by a parent or an unfamiliar adult, suggesting that it reflects SON-specific processing rather than broad self-relevant information processing. Comparing preschoolers with ASD to the TD children revealed a significant SON negativity component across both groups. The amplitude of the SON negativity response was significantly correlated with social variables in the ASD group, though these correlations did not survive correction for multiple comparisons. This study is the first to demonstrate the presence of the SON component in preschool children with and without ASD.

The roles of visual expertise and visual input in the face inversion effect: behavioral and neurocomputational evidence.

Research has shown that inverting faces significantly disrupts the processing of configural information, leading to a face inversion effect. We recently used a contextual priming technique to show that the presence or absence of the face inversion effect can be determined via the top-down activation of face versus non-face processing systems [Ge, L., Wang, Z., McCleery, J., & Lee, K. (2006). Activation of face expertise and the inversion effect. Psychological Science, 17(1), 12-16]. In the current study, we replicate these findings using the same technique but under different conditions. We then extend these findings through the application of a neural network model of face and Chinese character expertise systems. Results provide support for the hypothesis that a specialized face expertise system develops through extensive training of the visual system with upright faces, and that top-down mechanisms are capable of influencing when this face expertise system is engaged.

Do Children with Autism Spectrum Disorder Benefit from Structural Alignment When Constructing Categories?

Individuals with ASD seem to construct categories via processes different to typically developing individuals. We examined whether individuals with ASD engage in structural alignment of exemplars when constructing categories. We taught children with ASD and typically developing children novel nouns for either single or multiple exemplars, and then examined their extensions of the learned nouns to objects that were either a perceptual or conceptual match to the original exemplar(s). Results indicated that, unlike typically developing participants, those with ASD gained no benefit from seeing multiple exemplars of the category and, thus, did not appear to engage in structural alignment in their formation of categories. However, they demonstrated superior performance compared to typically developing children when presented with a single exemplar.

A pilot community-based randomized comparison of speech generating devices and the picture exchange communication system for children diagnosed with autism spectrum disorder.

A pilot community-based randomized controlled trial was conducted to compare the effects of the Picture Exchange Communication System (PECS) to a teaching sequence using a high-tech Speech Generating Device (SGD) to teach social communication behaviors. The two approaches were compared to evaluate the effectiveness of the newer, more high-tech intervention using technology to improve social and communicative behavior of children diagnosed with Autism Spectrum Disorder. A total of 35 school-age children were randomized to either a high-tech (SGD device) or low-tech (PECS cards) form of Augmentative and Alternative Communication (AAC). Study participants received 4 months of communication training delivered in their classrooms, and the primary outcome measures of the trial were several functional communication skills emphasized in the PECS teaching sequence. Results indicated that both high-tech and low-tech AAC approaches resulted in significant improvements in communication, and that these improvements did not differ significantly between the two approaches. These findings support the use of high-tech AAC, and highlight the need for evidence-based guidelines for its use as well as evaluation with individuals with a range impairments and disabilities. Autism Research 2018, 11: 1701-1711. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This study compared the effectiveness of a free and open-source app for teaching social and communicative behavior to children with autism spectrum disorder (ASD) to traditional picture card approaches. Thirty-five children with ASD were randomized to a picture card or app-based intervention and both treatment approaches resulted in significant improvements in social and communicative behavior. These data indicated that both "high-tech" and "low-tech" interventions were effective for improving behavior and that there was not a significant difference between the two approaches.

Effects of maternal depression in the Still-Face Paradigm: A meta-analysis.

The Still-Face Paradigm (SFP) enables researchers to examine the quality of mother-infant interactions. In typical infants, a classic still-face effect (SFE) has been confirmed whereby infants demonstrate reduced positive affect (PA), reduced gaze (GA), and increased negative affect (NA). Recently, the SFP has been used to examine the effect of maternal depression upon infant behaviour. However, the nature and consistency of the behavioural responses of infants of depressed mothers during the SFP remains unclear. In the current meta-analysis, we examined whether or not infants of depressed mothers demonstrate the classic SFE, as well as whether or not these infants display the same levels of PA, NA, and GA as their counterparts with non-depressed mothers. Results revealed that infants of depressed mothers display the classic SFE like infants of their non-depressed counterparts. However, infants of depressed mothers also demonstrated significantly higher levels of PA during the still-face episode. One potential interpretation of this finding is that infants prior experience of similar, depressed interactions with their mothers, encourages them to amplify their positive attachment signals in order to engage maternal attention and response. Alternatively, or additionally, infants of depressed mothers could be using PA in order to regulate their own NA.

Abnormal magnocellular pathway visual processing in infants at risk for autism.

BACKGROUND: A wealth of data has documented impairments in face processing in individuals with autism spectrum disorders (ASD). Recently, the suggestion has been made that these impairments may arise from abnormal development of a subcortical system involved in face processing that originates in the magnocellular pathway of the primate visual system. METHODS: To test this developmental hypothesis, we obtained visual perceptual data from 6-month-old infants who were at risk for ASD because they had an older sibling diagnosed with the disorder ("high-risk infants"). To measure sensitivity of the magnocellular (M) pathway and, for comparison, of the parvocellular (P) visual pathway, we employed visual stimuli designed to selectively stimulate the two. Sensitivity data from high-risk infants (n = 13) were compared with data from matched control infants (i.e., "low-risk" infants with no family history of ASD, n = 26). RESULTS: On the P pathway stimulus, high-risk infants exhibited sensitivities that were identical to those of control infants. By contrast, on the M pathway stimulus, high-risk infants exhibited sensitivities nearly twofold greater than those of control infants. CONCLUSIONS: Given that ASD and its symptoms are known to run in families, these preliminary results suggest that ASD may be associated with abnormal M pathway function early in infancy, which may aid in early diagnosis of the disorder.