Screening for new autism treatments using cells in a dish
Sensory symptoms, including auditory processing deficits, are common in autism spectrum disorder (ASD). Processing of temporal aspects of auditory input is understudied; yet, deficits in this domain could contribute to language-related impairments. In children with ASD and well-matched controls, this study examined electrophysiological response to silent gaps in auditory stimuli. Results revealed attenuated amplitude of the P2 event-related potential (ERP) component in ASD. The P2 amplitude reduction was also associated with sensory, language, and diagnostic features. These results suggest that neural response during auditory gap detection is a promising ASD biomarker that could be useful for stratifying subgroups and evaluating treatment response.
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.
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.