Atypical Local and Distal Patterns of Occipito-frontal Functional Connectivity are Related to Symptom Severity in Autism

Autism spectrum disorders (ASDs) are increasingly prevalent neurodevelopmental disorders characterized by sociocommunicative impairments. Growing consensus indicates that neurobehavioral abnormalities require explanation in terms of interconnected networks. Despite theoretical speculations about increased local and reduced distal connectivity, links between local and distal functional connectivity have not been systematically investigated in ASDs. Specifically, it remains open whether hypothesized local overconnectivity may reflect isolated versus overly integrative processing. Resting state functional MRI data from 57 children and adolescents with ASDs and 51 typically developing (TD) participants were included. In regional homogeneity (ReHo) analyses, pericalcarine visual cortex was found be locally overconnected (ASD > TD). Using this region as seed in whole-brain analyses, we observed overconnectivity in distal regions, specifically middle frontal gyri, for an ASD subgroup identified through k-means clustering. While in this subgroup local occipital to distal frontal overconnectivity was associated with greater symptom severity, a second subgroup showed the opposite pattern of connectivity and symptom severity correlations. Our findings suggest that increased local connectivity in ASDs is region-specific and may be partially associated with more integrative long-distance connectivity. Results also highlight the need to test for subtypes, as differential patterns of brain-behavior links were observed in two distinct subgroups of our ASD cohort.

Keywords: autism; frontal cortex; functional connectivity MRI; local connectivity; visual cortex.

Background: The objective of this study was to examine intrinsic whole-brain functional connectivity in autism spectrum disorder (ASD) using the framework of functional segregation and integration. Emphasis was given to potential gender and developmental effects as well as identification of specific networks that may contribute to the global results.

Methods: We leveraged an open data resource (N = 1587) of resting-state functional magnetic resonance imaging data in the Autism Brain Imaging Data Exchange (ABIDE) initiative, combining data from more than 2100 unique cross-sectional datasets in ABIDE I and ABIDE II collected at different sites. Modularity and global efficiency were utilized to assess functional segregation and integration, respectively. A meta-analytic approach for handling site differences was used. The effects of age, gender, and diagnostic category on segregation and integration were assessed using linear regression.

Results: Modularity decreased nonlinearly in the ASD group with age, as evidenced by an increase and then decrease over development. Global efficiency had an opposite relationship with age by first decreasing and then increasing in the ASD group. Both modularity and global efficiency remained largely stable in the typically developing control group during development, representing a significantly different effect than seen in the ASD group. Age effects on modularity were localized to the somatosensory network. Finally, a marginally significant interaction between age, gender, and diagnostic category was found for modularity.

Conclusions: Our results support prior work that suggested a quadratic effect of age on brain development in ASD, while providing new insights about the specific characteristics of developmental and gender effects on intrinsic connectivity in ASD.

Keywords: ABIDE; Age; Autism; Functional connectivity; Functional integration; Gender.

Background: Autism spectrum disorder (ASD) is associated with impaired face processing. The N170 event-related potential (ERP) has been considered a promising neural marker of this impairment. However, no quantitative review to date has integrated the literature to assess whether the N170 response to faces in individuals with ASD differs from that of typically developing (TD) individuals.

Methods: This meta-analysis examined the corpus of literature investigating difference in N170 response to faces in individuals with ASD and without ASD. Data from 23 studies (NASD = 374, NTD = 359) were reviewed. Meta-analysis was used to examine the effect size of the difference in N170 latency and amplitude among individuals with ASD and without ASD. Analyses were also conducted examining hemispheric differences, potential moderators, and publication bias.

Results: On average, N170 latencies to faces were delayed in individuals with ASD, but amplitudes did not differ for individuals with ASD and TD individuals. Moderator analyses revealed that N170 amplitudes were smaller in magnitude in the ASD participants relative to the TD participants in adult samples and in those with higher cognitive ability. However, effects differed as a function of hemisphere of recording. No evidence of publication bias was found.

Conclusions: Atypicality of N170-particularly latency-to faces appears to be a specific biomarker of social-communicative dysfunction in ASD and may relate to differential developmental experiences and use of compensatory cognitive mechanisms. Future research should examine phenotypic differences that contribute to N170 heterogeneity, as well as specificity of N170 differences in ASD versus non-ASD clinical populations, and N170 malleability with treatment.

Keywords: Autism spectrum disorder (ASD); Electroencephalography (EEG); Event-related potential (ERP); Face processing; Meta-analysis; N170.

The parts of the body that are used to produce and perceive signed languages (the hands, face, and visual system) differ from those used to produce and perceive spoken languages (the vocal tract and auditory system). In this paper we address two factors that have important consequences for sign language acquisition. First, there are three types of lexical signs: one-handed, two-handed symmetrical, and two-handed asymmetrical. Natural variation in hand dominance in the population leads to varied input to children learning sign. Children must learn that signs are not specified for the right or left hand but for dominant and non-dominant. Second, we posit that children have at least four imitation strategies available for imitating signs: anatomical (Activate the same muscles as the sign model), which could lead learners to inappropriately use their non-dominant hand; mirroring (Produce a mirror image of the modeled sign), which could lead learners to produce lateral movement reversal errors or to use the non-dominant hand; visual matching (Reproduce what you see from your perspective), which could lead learners to produce inward-outward movement and palm orientation reversals; and reversing (Reproduce what the sign model would see from his/her perspective). This last strategy is the only one that always yields correct phonological forms in signed languages. To test our hypotheses, we turn to evidence from typical and atypical hearing and deaf children as well as from typical adults; the data come from studies of both sign acquisition and gesture imitation. Specifically, we posit that all children initially use a visual matching strategy but typical children switch to a mirroring strategy sometime in the second year of life; typical adults tend to use a mirroring strategy in learning signs and imitating gestures. By contrast, children and adults with autism spectrum disorder (ASD) appear to use the visual matching strategy well into childhood or even adulthood. Finally, we present evidence that sign language exposure changes how adults imitate gestures, switching from a mirroring strategy to the correct reversal strategy. These four strategies for imitation do not exist in speech and as such constitute a unique problem for research in language acquisition.

Keywords: American Sign Language (ASL); Autism Spectrum Disorders (ASD); imitation; language acquisition; sign language; visual perspective-taking.

Electroenchephalography (EEG) recordings collected with developmental populations present particular challenges from a data processing perspective. These EEGs have a high degree of artifact contamination and often short recording lengths. As both sample sizes and EEG channel densities increase, traditional processing approaches like manual data rejection are becoming unsustainable. Moreover, such subjective approaches preclude standardized metrics of data quality, despite the heightened importance of such measures for EEGs with high rates of initial artifact contamination. There is presently a paucity of automated resources for processing these EEG data and no consistent reporting of data quality measures. To address these challenges, we propose the Harvard Automated Processing Pipeline for EEG (HAPPE) as a standardized, automated pipeline compatible with EEG recordings of variable lengths and artifact contamination levels, including high-artifact and short EEG recordings from young children or those with neurodevelopmental disorders. HAPPE processes event-related and resting-state EEG data from raw files through a series of filtering, artifact rejection, and re-referencing steps to processed EEG suitable for time-frequency-domain analyses. HAPPE also includes a post-processing report of data quality metrics to facilitate the evaluation and reporting of data quality in a standardized manner. Here, we describe each processing step in HAPPE, perform an example analysis with EEG files we have made freely available, and show that HAPPE outperforms seven alternative, widely-used processing approaches. HAPPE removes more artifact than all alternative approaches while simultaneously preserving greater or equivalent amounts of EEG signal in almost all instances. We also provide distributions of HAPPE’s data quality metrics in an 867 file dataset as a reference distribution and in support of HAPPE’s performance across EEG data with variable artifact contamination and recording lengths. HAPPE software is freely available under the terms of the GNU General Public License at https://github.com/lcnhappe/happe.

Keywords: EEG; EEG processing; artifact removal; automated; data quality; development; electroencephalography; pipeline.

Pivotal Response Treatment (PRT) is an evidence-based treatment for individuals with ASD that targets social communication skills, most notably social motivation. The aim of the current study was to map microanalytic changes in social communication during dyadic child-therapist interactions following a 16-week trial of PRT. We proposed that a microanalytic approach would allow us to meticulously outline the dynamics of the “building blocks” of children’s discourse, stressing certain aspect that might go unnoticed in global methods of coding. We hypothesized that PRT would improve measures of linguistic social communication in children.

We utilized continuous microanalysis of behavior to explore changes in social communication during PRT sessions in 20 high-functioning children with ASD (ages 4–7 years). For each child, two videotaped PRT sessions – at the beginning and end of these 16 weeks – were coded for vocalizations and verbalizations. This allowed us to compare the amount, fluency, adequacy and reciprocity of social communication between child and therapist at the early versus final stages of PRT.

Results

Compared to baseline, at endpoint, children increased their overall use of vocalizations as well as the congruency of their responses to those of the therapist. The amount of non-congruent responses also dropped significantly. Additionally, children improved in measures of conversational fluency and use of self-referential pronouns.

Conclusions

These results provide a mapping of microanalytic changes in social and linguistic communication that occur during PRT and point to children’s improvement in social communication behavior leading to greater social reciprocity and conversational synchrony following treatment.

Keywords

Autism Spectrum Disorders (ASD)
Pivotal Response Treatment (PRT)
Microanalysis
Social communication
Vocalizations
Verbalizations

Problem solving between parents and teachers is critical to maximizing student outcomes. The current study examined the associations among the different components of problem solving, as well as the relationship between various characteristics and problem solving in parents and teachers of children with autism spectrum disorder (ASD). Participants were 18 teachers and 39 parents of children with ASD. Parents and teachers completed a demographic survey, phone interview, and dyad observation. Results indicated that parent and teacher problem solving strategies were correlated with each other. Lower-income parents and parents interacting with White teachers displayed less problem solving. Findings suggest that school-based service delivery models to improve problem solving should consider both skill development, as well as the sociodemographic characteristics that parents and teachers bring to their interactions.

Keywords: autism spectrum disorder; communication; family involvement; parent–teacher relationships; problem solving.

Little research examines the best ways to improve communication between parents and teachers of children with Autism Spectrum Disorder (ASD) and its effect on child outcomes. The present study tests an innovative parent-teacher consultation model, entitled Partners in School. The goal of Partners in School is to improve parent-teacher communication aboutevidence-based practices (EBPs), and subsequently, outcomes for children with ASD. Participants were 26 teachers and 49 parents of children with ASD from a large urban public school district. Parents and teachers completed measures of their communication and child outcomes prior to and after receiving consultation through Partners in School. Results indicated that parents and teachers perceived improvements in child outcomes after participation inPartners in School. Changes in parent-teacher communication also were associated with changes in some child outcomes. Discussionhighlights the important role of communication inconsultations targeting family-school partnerships for children with ASD.

Keywords: autism; autism spectrum disorder; consultation; family-school partnerships; parent-teacher communication; parent-teacher relationships.

Little research examines the best ways to improve communication between parents and teachers of children with Autism Spectrum Disorder (ASD) and its effect on child outcomes. The present study tests an innovative parent-teacher consultation model, entitled Partners in School. The goal of Partners in School is to improve parent-teacher communication aboutevidence-based practices (EBPs), and subsequently, outcomes for children with ASD. Participants were 26 teachers and 49 parents of children with ASD from a large urban public school district. Parents and teachers completed measures of their communication and child outcomes prior to and after receiving consultation through Partners in School. Results indicated that parents and teachers perceived improvements in child outcomes after participation inPartners in School. Changes in parent-teacher communication also were associated with changes in some child outcomes. Discussionhighlights the important role of communication inconsultations targeting family-school partnerships for children with ASD.

Keywords: autism; autism spectrum disorder; consultation; family-school partnerships; parent-teacher communication; parent-teacher relationships.

Several interventions have demonstrated efficacy in improving social outcomes for children with autism; however, few have been successfully implemented in schools. This study compared two implementation strategies to improve the use of a social engagement intervention for children with autism in public schools. In total, 31 children with autism in grades K-5 and 28 school personnel participated in a randomized controlled trial. Schools were randomized to (1) training in Remaking Recess, a social engagement intervention, or (2) training in Remaking Recess with implementation support. Linear regression with random effects was used to test the intervention effects on implementation fidelity and social outcomes (peer engagement, social network inclusion, and friendship nominations). In both groups, implementation fidelity improved after training but remained low. Children in the Remaking Recess with implementation support condition had significantly higher social network inclusion and received more friendship nominations than children in the Remaking Recess-only condition (p = 0.03). Children in both groups experienced reduced solitary engagement (p < 0.001) and increased joint engagement (p < 0.001). The results suggest that implementation supports may have an effect on outcomes above and beyond the intervention, and that further research is needed into the active intervention mechanisms.

Keywords: autism spectrum disorder; implementation; school; social engagement intervention.

Keywords: Autism spectrum disorder; Oxytocin; Reward; fMRI.

Symptoms of autism spectrum disorder may influence alliance in psychotherapy. This study examined therapeutic alliance and its relationship with child characteristics and anxiety treatment outcomes in youth with autism spectrum disorder. Youth ( N = 64) with autism spectrum disorder and co-occurring anxiety (7-16 years, IQ > 70) received 16 sessions of modular cognitive-behavioral therapy. Post-treatment therapist, youth and parent ratings of alliance as well as pre- and post-treatment ratings of child behavior were gathered. Ratings of alliance were commensurate to ratings seen in children without autism spectrum disorder. Measures of treatment outcome, but not pretreatment characteristics, were significantly associated with therapist ratings of alliance strength. Data suggest that therapeutic alliance may not be impaired in anxious youth with autism spectrum disorder and may be associated with treatment outcome.

Keywords: anxiety; autism spectrum disorder; cognitive-behavioral therapy; therapeutic alliance.

Background: The male predominance in the prevalence of autism spectrum disorder (ASD) has motivated research on sex differentiation in ASD. Multiple sources of evidence have suggested a neurophenotypic convergence of ASD-related characteristics and typical sex differences. Two existing, albeit competing, models provide predictions on such neurophenotypic convergence. These two models are testable with neuroimaging. Specifically, the Extreme Male Brain (EMB) model predicts that ASD is associated with enhanced brain maleness in both males and females with ASD (i.e., a shift-towards-maleness). In contrast, the Gender Incoherence (GI) model predicts a shift-towards-maleness in females, yet a shift-towards-femaleness in males with ASD.

Methods: To clarify whether either model applies to the intrinsic functional properties of the brain in males with ASD, we measured the statistical overlap between typical sex differences and ASD-related atypicalities in resting-state fMRI (R-fMRI) datasets largely available in males. Main analyses focused on two large-scale R-fMRI samples: 357 neurotypical (NT) males and 471 NT females from the 1000 Functional Connectome Project and 360 males with ASD and 403 NT males from the Autism Brain Imaging Data Exchange.

Results: Across all R-fMRI metrics, results revealed coexisting, but network-specific, shift-towards-maleness and shift-towards-femaleness in males with ASD. A shift-towards-maleness mostly involved the default network, while a shift-towards-femaleness mostly occurred in the somatomotor network. Explorations of the associated cognitive processes using available cognitive ontology maps indicated that higher-order social cognitive functions corresponded to the shift-towards-maleness, while lower-order sensory motor processes corresponded to the shift-towards-femaleness.

Conclusions: The present findings suggest that atypical intrinsic brain properties in males with ASD partly reflect mechanisms involved in sexual differentiation. A model based on network-dependent atypical sex mosaicism can synthesize prior competing theories on factors involved in sex differentiation in ASD.

Keywords: Autism spectrum disorder; Extreme Male Brain; Gender Incoherence; Resting-state fMRI; Sex differentiation; Sex mosaicism.