Network organization is globally atypical in autism: A graph theory study of intrinsic functional connectivity.

BACKGROUND: Despite abundant evidence of brain network anomalies in autism spectrum disorder (ASD), findings have varied from broad functional underconnectivity to broad overconnectivity. Rather than pursuing overly simplifying general hypotheses ('under' vs. 'over'), we tested the hypothesis of atypical network distribution in ASD (i.e., participation of unusual loci in distributed functional networks). METHODS: We used a selective high-quality data subset from the ABIDE datashare (including 111 ASD and 174 typically developing [TD] participants) and several graph theory metrics. Resting state functional MRI data were preprocessed and analyzed for detection of low-frequency intrinsic signal correlations. Groups were tightly matched for available demographics and head motion. RESULTS: As hypothesized, the Rand Index (reflecting how similar network organization was to a normative set of networks) was significantly lower in ASD than TD participants. This was accounted for by globally reduced cohesion and density, but increased dispersion of networks. While differences in hub architecture did not survive correction, rich club connectivity (among the hubs) was increased in the ASD group. CONCLUSIONS: Our findings support the model of reduced network integration (connectivity with networks) and differentiation (or segregation; based on connectivity outside network boundaries) in ASD. While the findings applied at the global level, they were not equally robust across all networks and in one case (greater cohesion within ventral attention network in ASD) even reversed.

Sensory Symptoms and Processing of Nonverbal Auditory and Visual Stimuli in Children with Autism Spectrum Disorder.

Atypical sensory responses are common in autism spectrum disorder (ASD). While evidence suggests impaired auditory-visual integration for verbal information, findings for nonverbal stimuli are inconsistent. We tested for sensory symptoms in children with ASD (using the Adolescent/Adult Sensory Profile) and examined unisensory and bisensory processing with a nonverbal auditory-visual paradigm, for which neurotypical adults show bisensory facilitation. ASD participants reported more atypical sensory symptoms overall, most prominently in the auditory modality. On the experimental task, reduced response times for bisensory compared to unisensory trials were seen in both ASD and control groups, but neither group showed significant race model violation (evidence of intermodal integration). Findings do not support impaired bisensory processing for simple nonverbal stimuli in high-functioning children with ASD.

Regional specificity of aberrant thalamocortical connectivity in autism.

Preliminary evidence suggests aberrant (mostly reduced) thalamocortical (TC) connectivity in autism spectrum disorder (ASD), but despite the crucial role of thalamus in sensorimotor functions and its extensive connectivity with cerebral cortex, relevant evidence remains limited. We performed a comprehensive investigation of region-specific TC connectivity in ASD. Resting-state functional MRI and diffusion tensor imaging (DTI) data were acquired for 60 children and adolescents with ASD (ages 7-17 years) and 45 age, sex, and IQ-matched typically developing (TD) participants. We examined intrinsic functional connectivity (iFC) and anatomical connectivity (probabilistic tractography) with thalamus, using 68 unilateral cerebral cortical regions of interest (ROIs). For frontal and parietal lobes, iFC was atypically reduced in the ASD group for supramodal association cortices, but was increased for cingulate gyri and motor cortex. Temporal iFC was characterized by overconnectivity for auditory cortices, but underconnectivity for amygdalae. Occipital iFC was broadly reduced in the ASD group. DTI indices (such as increased radial diffusion) for regions with group differences in iFC further indicated compromised anatomical connectivity, especially for frontal ROIs, in the ASD group. Our findings highlight the regional specificity of aberrant TC connectivity in ASD. Their overall pattern can be largely accounted for by functional overconnectivity with limbic and sensorimotor regions, but underconnectivity with supramodal association cortices. This could be related to comparatively early maturation of limbic and sensorimotor regions in the context of early overgrowth in ASD, at the expense of TC connectivity with later maturing cortical regions.

Diagnostic classification of intrinsic functional connectivity highlights somatosensory, default mode, and visual regions in autism.

Despite consensus on the neurological nature of autism spectrum disorders (ASD), brain biomarkers remain unknown and diagnosis continues to be based on behavioral criteria. Growing evidence suggests that brain abnormalities in ASD occur at the level of interconnected networks; however, previous attempts using functional connectivity data for diagnostic classification have reached only moderate accuracy. We selected 252 low-motion resting-state functional MRI (rs-fMRI) scans from the Autism Brain Imaging Data Exchange (ABIDE) including typically developing (TD) and ASD participants (n = 126 each), matched for age, non-verbal IQ, and head motion. A matrix of functional connectivities between 220 functionally defined regions of interest was used for diagnostic classification, implementing several machine learning tools. While support vector machines in combination with particle swarm optimization and recursive feature elimination performed modestly (with accuracies for validation datasets <70%), diagnostic classification reached a high accuracy of 91% with random forest (RF), a nonparametric ensemble learning method. Among the 100 most informative features (connectivities), for which this peak accuracy was achieved, participation of somatosensory, default mode, visual, and subcortical regions stood out. Whereas some of these findings were expected, given previous findings of default mode abnormalities and atypical visual functioning in ASD, the prominent role of somatosensory regions was remarkable. The finding of peak accuracy for 100 interregional functional connectivities further suggests that brain biomarkers of ASD may be regionally complex and distributed, rather than localized.