People with autism spectrum disorder (ASD) show atypical attention to social stimuli [1] and gaze at faces [2] and complex images [3] in unusual ways. But all studies to date are limited by the experimenter’s selected stimuli, which are generally photographs taken by people without autism. What might participants with ASD show us if they were the ones taking the photos? We gave participants a digital camera and analysed the photos they took: images taken by participants with ASD had unusual features and showed strikingly different ways of photographing other people.
Revealing the world of autism through the lens of a camera
Although tactile reactivity issues are commonly reported in children with autism spectrum disorder (ASD), the underlying mechanisms are poorly understood. Less feed-forward inhibition has been proposed as a potential mechanism for some symptoms of ASD. We tested static and dynamic tactile thresholds as a behavioral proxy of feed-forward inhibition in 42 children (21 children with ASD and 21 typically developing [TD] children). Subthreshold conditioning typically raises the dynamic detection threshold, thus comparison of the dynamic to the static threshold generates a metric that predicts gamma-aminobutyric acid (GABA) mediated feed-forward inhibition. Children with ASD had marginally higher static thresholds and a significantly lower ratio between thresholds as compared with TD children. The lower ratio, only seen in children with ASD, might be indicative of less inhibition. Static thresholds were correlated with autism spectrum quotient scores, indicating the higher the tactile threshold, the more ASD traits. The amount of feed-forward inhibition (ratio between dynamic/static) was negatively correlated with autism diagnostic observation schedule repetitive behavior scores, meaning the less inhibition the more ASD symptoms. In summary, children with ASD showed altered tactile processing compared with TD children; thus measuring static and dynamic thresholds could be a potential biomarker for ASD and might be useful for prediction of treatment response with therapeutics, including those that target the GABAergic system. Autism Res 2016, 9: 616-620. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
Keywords: GABA; autism spectrum disorder; inhibition; tactile processing.
Autism spectrum disorders (ASDs) are common yet complex neurodevelopmental disorders, characterized by social, communication and behavioral deficits. Behavioral interventions have shown favorable results-however, the promise of precision medicine in ASD is hampered by a lack of sensitive, objective neurobiological markers (neurobiomarkers) to identify subgroups of young children likely to respond to specific treatments. Such neurobiomarkers are essential because early childhood provides a sensitive window of opportunity for intervention, while unsuccessful intervention is costly to children, families and society. In young children with ASD, we show that functional magnetic resonance imaging-based stratification neurobiomarkers accurately predict responses to an evidence-based behavioral treatment-pivotal response treatment. Neural predictors were identified in the pretreatment levels of activity in response to biological vs scrambled motion in the neural circuits that support social information processing (superior temporal sulcus, fusiform gyrus, amygdala, inferior parietal cortex and superior parietal lobule) and social motivation/reward (orbitofrontal cortex, insula, putamen, pallidum and ventral striatum). The predictive value of our findings for individual children with ASD was supported by a multivariate pattern analysis with cross validation. Predicting who will respond to a particular treatment for ASD, we believe the current findings mark the very first evidence of prediction/stratification biomarkers in young children with ASD. The implications of the findings are far reaching and should greatly accelerate progress toward more precise and effective treatments for core deficits in ASD.
Background: Individuals with autism spectrum disorder (ASD) show atypical brain activity, perhaps due to delayed maturation. Previous studies examining the maturation of auditory electrophysiological activity have been limited due to their use of cross-sectional designs. The present study took a first step in examining magnetoencephalography (MEG) evidence of abnormal auditory response maturation in ASD via the use of a longitudinal design.
Methods: Initially recruited for a previous study, 27 children with ASD and nine typically developing (TD) children, aged 6- to 11-years-old, were re-recruited two to five years later. At both timepoints, MEG data were obtained while participants passively listened to sinusoidal pure-tones. Bilateral primary/secondary auditory cortex time domain (100 ms evoked response latency (M100)) and spectrotemporal measures (gamma-band power and inter-trial coherence (ITC)) were examined. MEG measures were also qualitatively examined for five children who exhibited “optimal outcome”, participants who were initially on spectrum, but no longer met diagnostic criteria at follow-up.
Results: M100 latencies were delayed in ASD versus TD at the initial exam (~ 19 ms) and at follow-up (~ 18 ms). At both exams, M100 latencies were associated with clinical ASD severity. In addition, gamma-band evoked power and ITC were reduced in ASD versus TD. M100 latency and gamma-band maturation rates did not differ between ASD and TD. Of note, the cohort of five children that demonstrated “optimal outcome” additionally exhibited M100 latency and gamma-band activity mean values in-between TD and ASD at both timepoints. Though justifying only qualitative interpretation, these “optimal outcome” related data are presented here to motivate future studies.
Conclusions: Children with ASD showed perturbed auditory cortex neural activity, as evidenced by M100 latency delays as well as reduced transient gamma-band activity. Despite evidence for maturation of these responses in ASD, the neural abnormalities in ASD persisted across time. Of note, data from the five children whom demonstrated “optimal outcome” qualitatively suggest that such clinical improvements may be associated with auditory brain responses intermediate between TD and ASD. These “optimal outcome” related results are not statistically significant though, likely due to the low sample size of this cohort, and to be expected as a result of the relatively low proportion of “optimal outcome” in the ASD population. Thus, further investigations with larger cohorts are needed to determine if the above auditory response phenotypes have prognostic utility, predictive of clinical outcome.
Keywords: ASD; Gamma; M100; MEG; Maturation.
he phenotypic complexity of Autism Spectrum Disorder motivates the application of
modern computational methods to large collections of observational data, both for improved clinical diagnosis and for better scientific understanding. We have begun to create a
corpus of annotated language samples relevant to this research, and we plan to join with
other researchers in pooling and publishing
such resources on a large scale. The goal of
this paper is to present some initial explorations to illustrate the opportunities that such
datasets will afford
Two populations have been found to exhibit delays in theory of mind (ToM): deaf children of hearing parents and children with autism spectrum disorder (ASD). Deaf children exposed to sign from birth by their deaf parents, however, show no such delay, suggesting that early language exposure is key to ToM development. Sign languages also present frequent opportunities with visual perspective-taking (VPT), leading to the question of whether sign exposure could benefit children with ASD. We present the first study of children with ASD exposed to sign from birth by their deaf parents. Seventeen native-signing children with a confirmed ASD diagnosis and a chronological- and mental age-matched control group of 18 typically developing (TD) native-signing deaf children were tested on American Sign Language (ASL) comprehension, two minimally verbal social cognition tasks (ToM and VPT), and one spatial cognition task (mental rotation). The TD children outperformed the children with ASD on ASL comprehension (p < 0.0001), ToM (p = 0.02), and VPT (p < 0.01), but not mental rotation (p = 0.12). Language strongly correlated with ToM (p < 0.01) and VPT (p < 0.001), but not mental rotation (p = ns). Native exposure to sign is thus insufficient to overcome the language and social impairments implicated in ASD. Contrary to the hypothesis that sign could provide a scaffold for ToM skills, we find that signing children with ASD are unable to access language so as to gain any potential benefit sign might confer. Our results support a strong link between the development of social cognition and language, regardless of modality, for TD and ASD children. Autism Res 2016, 9: 1304-1315. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Keywords: cognitive neuroscience; developmental psychology; social cognition; theory of mind.
Background: Autism spectrum disorder (ASD) encompasses a complex manifestation of symptoms that include deficits in social interaction and repetitive or stereotyped interests and behaviors. In keeping with the increasing recognition of the dimensional characteristics of ASD symptoms and the categorical nature of a diagnosis, we sought to delineate the neural mechanisms of ASD symptoms based on the functional connectivity of four known neural networks (i.e., default mode network, dorsal attention network, salience network, and executive control network).
Methods: We leveraged an open data resource (Autism Brain Imaging Data Exchange) providing resting-state functional magnetic resonance imaging data sets from 90 boys with ASD and 95 typically developing boys. This data set also included the Social Responsiveness Scale as a dimensional measure of ASD traits. Seed-based functional connectivity was paired with linear regression to identify functional connectivity abnormalities associated with categorical effects of ASD diagnosis, dimensional effects of ASD-like behaviors, and their interaction.
Results: Our results revealed the existence of dimensional mechanisms of ASD uniquely affecting each network based on the presence of connectivity-behavioral relationships; these were independent of diagnostic category. However, we also found evidence of categorical differences (i.e., diagnostic group differences) in connectivity strength for each network as well as categorical differences in connectivity-behavioral relationships (i.e., diagnosis-by-behavior interactions), supporting the coexistence of categorical mechanisms of ASD.
Conclusions: Our findings support a hybrid model for ASD characterization that includes a combination of categorical and dimensional brain mechanisms and provide a novel understanding of the neural underpinnings of ASD.
Keywords: Autism spectrum disorder; Default mode network; Dimensional measures; Functional connectivity; Resting-state fMRI; Social cognition.
Objective: The objectives of this review are to highlight the impact of the first decade of high-risk (HR) infant sibling work in autism spectrum disorder (ASD) and to identify potential areas of translational focus for the next decade of research.
Method: A group of clinicians and researchers in ASD working both inside and outside of the HR design met on a regular basis to review the infant sibling research, and came to an agreement on areas that had changed clinical practice and areas that had the potential to change practice with further research. The group then outlined several methodological and translational challenges that must be addressed in the next decade of research if the field is to reach its potential.
Results: The review concluded that the HR design has yielded an understanding that ASD often, but not always, begins to emerge between 6 and 18 months, with early signs affecting social communication. Research using the HR design has also allowed a better understanding of the sibling recurrence risk (between 10% and 20%). Emerging areas of interest include the developmental trajectories of social communications skills in the early years, the expression of a milder phenotype in siblings not affected with ASD, and the possibility that early intervention with infant siblings may improve outcomes for those with ASD. Important challenges for the future include linking screening to intervention, collecting large sample sizes while ensuring cross-site reliability, and building in capacity for replication.
Conclusion: Although there are significant methodological and translational challenges for high-risk infant sibling research, the potential of this design to improve long-term outcomes of all children with ASD is substantial.
Keywords: autism; development; longitudinal; opportunities; sibling.
Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects more than 1 % of the population and close to 20 % of prospectively studied infants with an older sibling with ASD. Although significant progress has been made in characterizing the emergence of behavioral symptoms of ASD, far less is known about the underlying disruptions to early learning. Recent models suggest that core aspects of the causal path to ASD may only be apparent in early infancy. Here, we investigated social attention in 6- and 12-month-old infants who did and did not meet criteria for ASD at 24 months using both cognitive and electrophysiological methods. We hypothesized that a reduction in attention engagement to faces would be associated with later ASD.
Methods: In a prospective longitudinal design, we used measures of both visual attention (habituation) and brain function (event-related potentials to faces and objects) at 6 and 12 months and investigated the relationship to ASD outcome at 24 months.
Results: High-risk infants who met criteria for ASD at 24 months showed shorter epochs of visual attention, faster but less prolonged neural activation to faces, and delayed sensitization responses (increases in looking) to faces at 6 months; these differences were less apparent at 12 months. These findings are consistent with disrupted engagement of sustained attention to social stimuli.
Conclusions: These findings suggest that there may be fundamental early disruptions to attention engagement that may have cascading consequences for later social functioning.
Keywords: ASD; Event-related potential; Habituation; Social attention; Social information processing.
Little is known about the social behavior of children with and without autism spectrum disorder during recess. This study documented the naturally occurring recess engagement and peer interaction behaviors of children with and without autism spectrum disorder in inclusive school settings. Participants included 51 children with autism spectrum disorder and 51 classmates without autism spectrum disorder who served as peer models matched on gender, classroom, grade, age, and ethnicity. Using a timed-interval behavior-coding system, children with autism spectrum disorder spent approximately 30% of their recess time engaged in solitary activities, whereas their classmates only spent approximately 9% of recess unengaged. In addition, children with autism spectrum disorder spent about 40% of the recess period jointly engaged with peers in a reciprocal activity, conversation, or game as compared to 70% for matched classmates. These findings provide a context for which to interpret intervention outcomes and gains for children with autism spectrum disorder in inclusive settings.
Keywords: autism spectrum disorder; peers; playground engagement; social communication.
Although children with autism spectrum disorder are frequently included in mainstream classrooms, it is not known how their social networks change compared to typically developing children and whether the factors predictive of this change may be unique. This study identified and compared predictors of social connectivity of children with and without autism spectrum disorder using a social network analysis. Participants included 182 children with autism spectrum disorder and 152 children without autism spectrum disorder, aged 5-12 years in 152 general education K-5 classrooms. General linear models were used to compare how age, classroom size, gender, baseline connectivity, diagnosis, and intelligence quotient predicted changes in social connectivity (closeness). Gender and classroom size had a unique interaction in predicting final social connectivity and the change in connectivity for children with autism spectrum disorder; boys who were placed in larger classrooms showed increased social network fragmentation. This increased fragmentation for boys when placed in larger classrooms was not seen in typically developing boys. These results have implications regarding placement, intervention objectives, and ongoing school support that aimed to increase the social success of children with autism spectrum disorder in public schools.