Developmental Perspectives on the Study of Persons with Intellectual Disability.

Developmental approaches provide inclusive, universal, and methodologically rigorous frameworks for studying persons with intellectual disability (ID). This is an exceptionally heterogeneous group with regard to etiology, genotype, and phenotype that simply shares the traditional diagnostic criteria, typically a score of two standard deviations below the population mean of 100 on standardized IQ tests and deficits in adaptive behavior. We trace the foundational, conceptual, and methodological roots of developmental approaches and highlight ways that these and more recent iterations continue to be central to advances in the increasingly nuanced study of persons with ID. This work is premised on the consideration of specific etiological groupings and subgroupings across and between different domains of functioning within the context of familial and complex environments throughout the life span. We highlight the potential contributions of advances in behavioral methodologies, genomics, and neuroscience when considered within universal and hierarchic frameworks based on development.

The science of humanity and the humanity of science: Perspectives on Ed Zigler's contributions to developmental psychopathology and the study of all children.

We present this article as a testament to Ed Zigler's commitment to science in the service of humanity and to policy based on conceptually compelling theory and methodologically rigorous science. In doing so, we highlight ways that Ed's universal and inclusive developmental world view, early training as a behaviorist, exacting scientific standards, concern for others, and appreciation of his own roots and upbringing all transformed the way that many different groups of people of all ages and backgrounds are studied, viewed, and intervened with by researchers, policy makers, and society at large. Ed's narrative of development rather than defect, universality rather than difference, and holistic rather than reductionist continues to compel us in the quest for a kinder, more inclusive, and enabling society. Conversely, Ed's behaviorist training as a graduate student also influenced him throughout his career and was essential to his career-long commitment to systemic action in the service of improving the lives of others. We cite the lessons that we, as his descendants, learned from Ed and apply them to our own areas of research with populations that Ed did not study, but had considerable interest in - persons with autism spectrum disorder and Indigenous youth.

Autism Spectrum Disorders and ADHD: Overlapping Phenomenology, Diagnostic Issues, and Treatment Considerations.

PURPOSE OF REVIEW: Autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) are both increasing in prevalence and commonly co-occur with each other. The goal of this review is to outline what has been published recently on the topics of ASD, ADHD, and the comorbid state (ASD+ADHD) with a particular focus on shared phenomenology, differential diagnosis, and treatment considerations. RECENT FINDINGS: ASD and ADHD have shared genetic heritability and are both associated with shared impairments in social functioning and executive functioning. Quantitative and qualitative differences exist, however, in the phenotypic presentations of the impairments which characterize ASD and ADHD. For ASD interventions to be maximally efficacious, comorbid ADHD needs to be considered (and vice versa). The research on ASD and ADHD suggests some overlap between the two disorders yet enough differences to indicate that these conditions are sufficiently distinct to warrant separate diagnostic categories.

Adults blink more deeply: a comparative study of the attentional blink across different age groups.

The attentional blink (AB) is thought to help the visual system parse and categorize rapidly changing information by segmenting it into temporal chunks, and is elicited using Rapid Serial Visual Presentation. It is reflected in a decrease in accuracy at detecting the second of two targets presented within 200-500 ms of the first, and its development appears to be protracted on tasks that require set-shifting. Here, younger (M = 8.5 years) and older (M = 12.8 years) children and adults (M = 19.13 years) completed a simple AB task with no set-shift requirement in which participants detected two letters in a stream of numbers presented at a rate of 135 ms/item. In addition to assessing the developmental course of the AB on this simple task, we also assessed temporal order errors, or swaps. The AB and its associated characteristics are present in both groups but developmental differences were noted in the depth of the AB, and the presence or absence of lag-1 sparing. These developmental changes were explained by changes in a single parameter, inhibition, using the eTST model, which suggests that the AB is an adaptive function of the visual system.

Developmental changes in feature detection across time: Evidence from the attentional blink.

The ability to select targets from an ongoing stream of visual information is critical to the successful management of visual attention. The attentional blink (AB), a phenomenon elicited using rapid serial visual presentation, allows for the assessment of the limits of the temporal visual system, and is reflected in a decrease in accuracy in the detection of the second of two targets when it occurs within 200-500ms of a first target. Evidence regarding the development of the AB is mixed and appears to be dependent on the task demands. Here we present data examining the AB across middle childhood, early adolescence, and adulthood using a feature binding task. Participants were asked to detect and report the identity of two purple letters presented in a stream of black letters at a rate of 135ms/item. On this feature binding task, the depth of the AB was invariant across development but AB recovery occurred earlier with increasing age. Furthermore, the error data suggested important developments in temporal binding that were reflected both in a decrease in the number of swaps (where participants reverse the order of the targets but identify them correctly) and in the spread of temporal binding errors with age. These findings suggest that the characteristics of the AB and its development are task dependent and also suggest that the development of binding abilities in visual search tasks mirrors the time course of multisensory binding effects, perhaps suggesting a common mechanism.

Mosaic epigenetic dysregulation of ectodermal cells in autism spectrum disorder.

DNA mutational events are increasingly being identified in autism spectrum disorder (ASD), but the potential additional role of dysregulation of the epigenome in the pathogenesis of the condition remains unclear. The epigenome is of interest as a possible mediator of environmental effects during development, encoding a cellular memory reflected by altered function of progeny cells. Advanced maternal age (AMA) is associated with an increased risk of having a child with ASD for reasons that are not understood. To explore whether AMA involves covert aneuploidy or epigenetic dysregulation leading to ASD in the offspring, we tested a homogeneous ectodermal cell type from 47 individuals with ASD compared with 48 typically developing (TD) controls born to mothers of ≥35 years, using a quantitative genome-wide DNA methylation assay. We show that DNA methylation patterns are dysregulated in ectodermal cells in these individuals, having accounted for confounding effects due to subject age, sex and ancestral haplotype. We did not find mosaic aneuploidy or copy number variability to occur at differentially-methylated regions in these subjects. Of note, the loci with distinctive DNA methylation were found at genes expressed in the brain and encoding protein products significantly enriched for interactions with those produced by known ASD-causing genes, representing a perturbation by epigenomic dysregulation of the same networks compromised by DNA mutational mechanisms. The results indicate the presence of a mosaic subpopulation of epigenetically-dysregulated, ectodermally-derived cells in subjects with ASD. The epigenetic dysregulation observed in these ASD subjects born to older mothers may be associated with aging parental gametes, environmental influences during embryogenesis or could be the consequence of mutations of the chromatin regulatory genes increasingly implicated in ASD. The results indicate that epigenetic dysregulatory mechanisms may complement and interact with DNA mutations in the pathogenesis of the disorder.

Severe multisensory speech integration deficits in high-functioning school-aged children with Autism Spectrum Disorder (ASD) and their resolution during early adolescence.

Under noisy listening conditions, visualizing a speaker's articulations substantially improves speech intelligibility. This multisensory speech integration ability is crucial to effective communication, and the appropriate development of this capacity greatly impacts a child's ability to successfully navigate educational and social settings. Research shows that multisensory integration abilities continue developing late into childhood. The primary aim here was to track the development of these abilities in children with autism, since multisensory deficits are increasingly recognized as a component of the autism spectrum disorder (ASD) phenotype. The abilities of high-functioning ASD children (n = 84) to integrate seen and heard speech were assessed cross-sectionally, while environmental noise levels were systematically manipulated, comparing them with age-matched neurotypical children (n = 142). Severe integration deficits were uncovered in ASD, which were increasingly pronounced as background noise increased. These deficits were evident in school-aged ASD children (5-12 year olds), but were fully ameliorated in ASD children entering adolescence (13-15 year olds). The severity of multisensory deficits uncovered has important implications for educators and clinicians working in ASD. We consider the observation that the multisensory speech system recovers substantially in adolescence as an indication that it is likely amenable to intervention during earlier childhood, with potentially profound implications for the development of social communication abilities in ASD children.

The development of multisensory integration in high-functioning autism: high-density electrical mapping and psychophysical measures reveal impairments in the processing of audiovisual inputs.

Successful integration of auditory and visual inputs is crucial for both basic perceptual functions and for higher-order processes related to social cognition. Autism spectrum disorders (ASD) are characterized by impairments in social cognition and are associated with abnormalities in sensory and perceptual processes. Several groups have reported that individuals with ASD are impaired in their ability to integrate socially relevant audiovisual (AV) information, and it has been suggested that this contributes to the higher-order social and cognitive deficits observed in ASD. However, successful integration of auditory and visual inputs also influences detection and perception of nonsocial stimuli, and integration deficits may impair earlier stages of information processing, with cascading downstream effects. To assess the integrity of basic AV integration, we recorded high-density electrophysiology from a cohort of high-functioning children with ASD (7-16 years) while they performed a simple AV reaction time task. Children with ASD showed considerably less behavioral facilitation to multisensory inputs, deficits that were paralleled by less effective neural integration. Evidence for processing differences relative to typically developing children was seen as early as 100 ms poststimulation, and topographic analysis suggested that children with ASD relied on different cortical networks during this early multisensory processing stage.

Autism and sexual and gender minority identity in college students: Examination of self-reported rates, functional outcomes, and treatment engagement.

LAY ABSTRACT: Autistic individuals and those who identify with a sexual and/or gender minority are both at risk for various mental health concerns and related impairments. However, the connection between autism and sexual and/or gender minorities and mental health and functional outcomes is not clear. Here, we provide evidence of these connections by analyzing data from a large nationally representative dataset from the American College Health Association-National College Health Assessment III. We found that autistic college students who identify with both sexual and gender minorities reported the highest rates of stress, academic, and mental health concerns including suicidality when compared with autistic college students with or without a sexual and/or gender minority. In addition, college students with at least two identities, such as autism and a sexual minority identity or both a sexual and gender minority identity, reported the next highest rates of concern. These findings affirm the need for mental healthcare providers to consider the intersections of a sexual and gender minority identities in non-autistic and, especially, in autistic college students to develop and provide better support and resources.

Brain Signatures of Early and Late Neural Measures of Auditory Habituation and Discrimination in Autism and Their Relationship to Autistic Traits and Sensory Overresponsivity.

Sensory differences are included in the DSM-5 criteria of autism for the first time, yet it is unclear how they relate to neural indicators of perception. We studied early brain signatures of perception and examined their relationship to sensory behaviors and autistic traits. Thirteen autistic children and 13 Typically Developing (TD) children matched on age and nonverbal IQ participated in a passive oddball task, during which P1 habituation and P1 and MMN discrimination were evoked by pure tones. Autistic children had less neural habituation than the TD comparison group, and the MMN, but not P1, mapped on to sensory overresponsivity. Findings highlight the significance of temporal and contextual factors in neural information processing as it relates to autistic traits and sensory behaviors.

Atypical cortical representation of peripheral visual space in children with an autism spectrum disorder.

A key feature of early visual cortical regions is that they contain discretely organized retinotopic maps. Titration of these maps must occur through experience, and the fidelity of their spatial tuning will depend on the consistency and accuracy of the eye movement system. Anomalies in fixation patterns and the ballistics of eye movements are well documented in autism spectrum disorder (ASD), with off-center fixations a hallmark of the phenotype. We hypothesized that these atypicalities might affect the development of visuo-spatial maps and specifically that peripheral inputs might receive altered processing in ASD. Using high-density recordings of visual evoked potentials (VEPs) and a novel system-identification approach known as VESPA (visual evoked spread spectrum analysis), we assessed sensory responses to centrally and peripherally presented stimuli. Additionally, input luminance was varied to bias responsiveness to the magnocellular system, given previous suggestions of magnocellular-specific deficits in ASD. Participants were 22 ASD children (7-17 years of age) and 31 age- and performance-IQ-matched neurotypical controls. Both VEP and VESPA responses to central presentations were indistinguishable between groups. In contrast, peripheral presentations resulted in significantly greater early VEP and VESPA amplitudes in the ASD cohort. We found no evidence that anomalous enhancement was restricted to magnocellular-biased responses. The extent of peripheral response enhancement was related to the severity of stereotyped behaviors and restricted interests, cardinal symptoms of ASD. The current results point to differential visuo-spatial cortical mapping in ASD, shedding light on the consequences of peculiarities in gaze and stereotyped visual behaviors often reported by clinicians working with this population.

Investigating the Structure of the CESD-R and DASS-21 Across Adults with Low and High Levels of Autistic Traits.

The current study examined factorial invariance of the Center for Epidemiologic Studies Depression Scale-Revised (CESD-R) and the Depression Anxiety Stress Scales-21 (DASS-21) using a convenience sample of 434 adults surveyed though Amazon Mechanical Turk. Participants were sorted into two groups based on their score on the Autism-Spectrum Quotient. Results indicated that the CESD-R did not demonstrate configural invariance. The DASS-21 demonstrated evidence of scalar invariance, indicating cross-group equality in factor loadings and factor intercepts. Findings suggest that the DASS-21 measures symptoms of depression, anxiety, and stress consistently across individuals with high and low levels of ASD-related traits, whereas the CESD-R may not be valid when assessing symptoms of depression in those with a high level of ASD-related traits.

Brief Report: Sensory Features Associated with Autism After Controlling for ADHD Symptoms.

BACKGROUND: Sensory processing differences are reported both in children with ADHD and in children with autism. Given the substantial overlap between autism and ADHD, the current study examined which sensory features were uniquely predictive of autistic traits after controlling for ADHD symptoms, age, IQ, and sex in a sample of children and adolescents with autism aged 6-17 years. METHODS: The sample included 61 children and adolescents with autism. The Sensory Profile was used to examine Dunn's quadrant model (seeking, sensitivity, avoiding, registration), ADHD symptoms were measured using hyperactivity and attention problems BASC-2 T-scores, and autistic traits were measured using the AQ. RESULTS: After controlling for age, IQ, sex, and ADHD symptoms, Dunn's sensitivity quadrant predicted autistic traits. CONCLUSIONS: Findings provide insight into the phenotype of autism and ADHD. Sensory sensitivity may be unique to autism over and above elevated ADHD symptoms that are commonly seen in this population.

Barriers to an Autistic Identity: How RRBs may Contribute to the Underdiagnosis of Females.

Background: Autistic females are frequently underdiagnosed, misdiagnosed, and/or diagnosed later in life. Restricted and Repetitive Behaviors (RRBs) are increasingly critical for diagnosis and yet are commonly rated lower in females. Whether this reflects genuinely lower levels of these traits, or if female-typical RRBs have a different phenotypic presentation that may not register on current quantitative measurement tools is unclear. Methods: Twenty-one autistic females and 21 autistic males matched on chronological age and FSIQ completed the AQ, ADOS-2, and ADI-R. Items from the ADOS-2 and ADI-R were selected that were relevant to the four areas of restricted and repetitive behavior in the DSM-5 diagnostic criteria of autism. Using a mixed-methods analytical approach, scores and comments on these measures were compared between sexes to better characterize RRBs in autistic females. Results: There were no sex differences on the AQ, which broadly assesses autistic traits. When analyzed by the four DSM-5 RRB criteria, there were no sex differences on the ADI-R when using traditional algorithm scoring that narrows questions down to those that are more sensitive and specific in capturing autism in research samples with a high proportion of males. When incorporating additional items relevant to the DSM-5 to identify sex changes in a broader pool of items, females scored higher on stereotyped movements and speech. Females also engaged in more sensory behaviors during the ADOS-2. Qualitative analyses indicated that females were more likely to engage in stereotyped body rocking and spinning, stereotyped behaviors when anxious, to show major reactions to changes, repetitive language including listing and counting, and sensory behaviors, especially in the tactile domain. Conclusion: Exploratory findings highlight sex differences in RRBs that may help enhance diagnostic clarity for females. Higher tactile sensory behaviors in females suggests there may be increased diagnostic sensitivity for females with the updated DSM-5 that now includes sensory components as part of the diagnostic criteria.

Examining the Latent Structure and Correlates of Sensory Reactivity in Autism: A Multi-site Integrative Data Analysis by the Autism Sensory Research Consortium.

Background Differences in responding to sensory stimuli, including sensory hyperreactivity (HYPER), hyporeactivity (HYPO), and sensory seeking (SEEK) have been observed in autistic individuals across sensory modalities, but few studies have examined the structure of these "supra-modal" traits in the autistic population. Methods Leveraging a combined sample of 3,868 autistic youth drawn from 12 distinct data sources (ages 3-18 years and representing the full range of cognitive ability), the current study used modern psychometric and meta-analytic techniques to interrogate the latent structure and correlates of caregiver-reported HYPER, HYPO, and SEEK within and across sensory modalities. Bifactor statistical indices were used to both evaluate the strength of a "general response pattern" factor for each supra-modal construct and determine the added value of "modality-specific response pattern" scores (e.g., Visual HYPER). Bayesian random-effects integrative data analysis models were used to examine the clinical and demographic correlates of all interpretable HYPER, HYPO and SEEK (sub)constructs. Results All modality-specific HYPER subconstructs could be reliably and validly measured, whereas certain modality-specific HYPO and SEEK subconstructs were psychometrically inadequate when measured using existing items. Bifactor analyses unambiguously supported the validity of a supra-modal HYPER construct (ω H = .800), whereas a coherent supra-modal HYPO construct was not supported (ω H = .611), and supra-modal SEEK models suggested a more limited version of the construct that excluded some sensory modalities (ω H = .799; 4/7 modalities). Within each sensory construct, modality-specific subscales demonstrated substantial added value beyond the supra-modal score. Meta-analytic correlations varied by construct, although sensory features tended to correlate most strongly with other domains of core autism features and co-occurring psychiatric symptoms. Certain subconstructs within the HYPO and SEEK domains were also associated with lower adaptive behavior scores. Limitations: Conclusions may not be generalizable beyond the specific pool of items used in the current study, which was limited to parent-report of observable behaviors and excluded multisensory items that reflect many "real-world" sensory experiences. Conclusion Psychometric issues may limit the degree to which some measures of supra-modal HYPO/SEEK can be interpreted. Depending on the research question at hand, modality-specific response pattern scores may represent a valid alternative method of characterizing sensory reactivity in autism.

Examining the latent structure and correlates of sensory reactivity in autism: a multi-site integrative data analysis by the autism sensory research consortium.

BACKGROUND: Differences in responding to sensory stimuli, including sensory hyperreactivity (HYPER), hyporeactivity (HYPO), and sensory seeking (SEEK) have been observed in autistic individuals across sensory modalities, but few studies have examined the structure of these "supra-modal" traits in the autistic population. METHODS: Leveraging a combined sample of 3868 autistic youth drawn from 12 distinct data sources (ages 3-18 years and representing the full range of cognitive ability), the current study used modern psychometric and meta-analytic techniques to interrogate the latent structure and correlates of caregiver-reported HYPER, HYPO, and SEEK within and across sensory modalities. Bifactor statistical indices were used to both evaluate the strength of a "general response pattern" factor for each supra-modal construct and determine the added value of "modality-specific response pattern" scores (e.g., Visual HYPER). Bayesian random-effects integrative data analysis models were used to examine the clinical and demographic correlates of all interpretable HYPER, HYPO, and SEEK (sub)constructs. RESULTS: All modality-specific HYPER subconstructs could be reliably and validly measured, whereas certain modality-specific HYPO and SEEK subconstructs were psychometrically inadequate when measured using existing items. Bifactor analyses supported the validity of a supra-modal HYPER construct (ωH = .800) but not a supra-modal HYPO construct (ωH = .653), and supra-modal SEEK models suggested a more limited version of the construct that excluded some sensory modalities (ωH = .800; 4/7 modalities). Modality-specific subscales demonstrated significant added value for all response patterns. Meta-analytic correlations varied by construct, although sensory features tended to correlate most with other domains of core autism features and co-occurring psychiatric symptoms (with general HYPER and speech HYPO demonstrating the largest numbers of practically significant correlations). LIMITATIONS: Conclusions may not be generalizable beyond the specific pool of items used in the current study, which was limited to caregiver report of observable behaviors and excluded multisensory items that reflect many "real-world" sensory experiences. CONCLUSION: Of the three sensory response patterns, only HYPER demonstrated sufficient evidence for valid interpretation at the supra-modal level, whereas supra-modal HYPO/SEEK constructs demonstrated substantial psychometric limitations. For clinicians and researchers seeking to characterize sensory reactivity in autism, modality-specific response pattern scores may represent viable alternatives that overcome many of these limitations.

Early electrophysiological indices of illusory contour processing within the lateral occipital complex are virtually impervious to manipulations of illusion strength.

The visual system can automatically interpolate or "fill-in" the boundaries of objects when inputs are fragmented or incomplete. A canonical class of visual stimuli known as illusory-contour (IC) stimuli has been extensively used to study this contour interpolation process. Visual evoked potential (VEP) studies have identified a neural signature of these boundary completion processes, the so-called IC-effect, which typically onsets at 90-110 ms and is generated within the lateral occipital complex (LOC). Here we set out to determine the delimiting factors of automatic boundary completion with the use of illusory contour stimuli and high-density scalp recordings of brain activity. Retinal eccentricity, ratio of real to illusory contours (i.e. support ratio), and inducer diameter were each varied parametrically, and any resulting effects on the amplitude and latency of the IC-effect were examined. Somewhat surprisingly, the amplitude of the IC-effect was found to be impervious to all changes in these stimulus parameters, manipulations that are known to impact perceived illusion strength. Thus, this automatic stage of object processing appears to be a binary process in which, so-long as minimal conditions are met, contours are automatically completed. At the same time, the latency of the IC-effect was found to vary inversely with support ratio, likely reflecting the additional time necessary to interpolate across the relatively longer induced boundaries of the implied object. These data are interpreted in the context of a two stage object-recognition model that parses processing into an early automatic perceptual stage that is followed by a more effortful conceptual processing stage.

The development of audiovisual multisensory integration across childhood and early adolescence: a high-density electrical mapping study.

The integration of multisensory information is essential to forming meaningful representations of the environment. Adults benefit from related multisensory stimuli but the extent to which the ability to optimally integrate multisensory inputs for functional purposes is present in children has not been extensively examined. Using a cross-sectional approach, high-density electrical mapping of event-related potentials (ERPs) was combined with behavioral measures to characterize neurodevelopmental changes in basic audiovisual (AV) integration from middle childhood through early adulthood. The data indicated a gradual fine-tuning of multisensory facilitation of performance on an AV simple reaction time task (as indexed by race model violation), which reaches mature levels by about 14 years of age. They also revealed a systematic relationship between age and the brain processes underlying multisensory integration (MSI) in the time frame of the auditory N1 ERP component (∼ 120 ms). A significant positive correlation between behavioral and neurophysiological measures of MSI suggested that the underlying brain processes contributed to the fine-tuning of multisensory facilitation of behavior that was observed over middle childhood. These findings are consistent with protracted plasticity in a dynamic system and provide a starting point from which future studies can begin to examine the developmental course of multisensory processing in clinical populations.

A Preliminary Study Characterizing Subcortical and Cortical Auditory Processing and Their Relation to Autistic Traits and Sensory Features.

This study characterizes the subcortical auditory brainstem response (speech-ABR) and cortical auditory processing (P1 and Mismatch Negativity; MMN) to speech sounds and their relationship to autistic traits and sensory features within the same group of autistic children (n = 10) matched on age and non-verbal IQ to their typically developing (TD) peers (n = 21). No speech-ABR differences were noted, but autistic individuals had larger P1 and faster MMN responses. Correlations revealed that larger P1 amplitudes and MMN responses were associated with greater autistic traits and more sensory features. These findings highlight the complexity of the auditory system and its relationships to behaviours in autism, while also emphasizing the importance of measurement and developmental matching.