Developing Automated Algorithms to Assess Linguistic Variation in Individuals with Autism
Importance: Converging evidence indicates that brain abnormalities in autism spectrum disorder (ASD) involve atypical network connectivity, but it is unclear whether altered connectivity is especially prominent in brain networks that participate in social cognition.
Objective: To investigate whether adolescents with ASD show altered functional connectivity in 2 brain networks putatively impaired in ASD and involved in social processing, theory of mind (ToM) and mirror neuron system (MNS).
Design, setting, and participants: Cross-sectional study using resting-state functional magnetic resonance imaging involving 25 adolescents with ASD between the ages of 11 and 18 years and 25 typically developing adolescents matched for age, handedness, and nonverbal IQ.
Main outcomes and measures: Statistical parametric maps testing the degree of whole-brain functional connectivity and social functioning measures.
Results: Relative to typically developing controls, participants with ASD showed a mixed pattern of both over- and underconnectivity in the ToM network, which was associated with greater social impairment. Increased connectivity in the ASD group was detected primarily between the regions of the MNS and ToM, and was correlated with sociocommunicative measures, suggesting that excessive ToM-MNS cross talk might be associated with social impairment. In a secondary analysis comparing a subset of the 15 participants with ASD with the most severe symptomology and a tightly matched subset of 15 typically developing controls, participants with ASD showed exclusive overconnectivity effects in both ToM and MNS networks, which were also associated with greater social dysfunction.
Conclusions and relevance: Adolescents with ASD showed atypically increased functional connectivity involving the mentalizing and mirror neuron systems, largely reflecting greater cross talk between the 2. This finding is consistent with emerging evidence of reduced network segregation in ASD and challenges the prevailing theory of general long-distance underconnectivity in ASD. This excess ToM-MNS connectivity may reflect immature or aberrant developmental processes in 2 brain networks involved in understanding of others, a domain of impairment in ASD. Further, robust links with sociocommunicative symptoms of ASD implicate atypically increased ToM-MNS connectivity in social deficits observed in ASD.
Objective: Converging evidence indicates that brain abnormalities in autism spectrum disorder (ASD) involve atypical network connectivity, but few studies have integrated functional with structural connectivity measures. This multimodal investigation examined functional and structural connectivity of the imitation network in children and adolescents with ASD, and its links with clinical symptoms.
Methods: Resting state functional magnetic resonance imaging and diffusion-weighted imaging were performed in 35 participants with ASD and 35 typically developing controls, aged 8 to 17 years, matched for age, gender, intelligence quotient, and head motion.
Results: Within-network analyses revealed overall reduced functional connectivity (FC) between distributed imitation regions in the ASD group. Whole brain analyses showed that underconnectivity in ASD occurred exclusively in regions belonging to the imitation network, whereas overconnectivity was observed between imitation nodes and extraneous regions. Structurally, reduced fractional anisotropy and increased mean diffusivity were found in white matter tracts directly connecting key imitation regions with atypical FC in ASD. These differences in microstructural organization of white matter correlated with weaker FC and greater ASD symptomatology.
Interpretation: Findings demonstrate atypical connectivity of the brain network supporting imitation in ASD, characterized by a highly specific pattern. This pattern of underconnectivity within, but overconnectivity outside the functional network is in contrast with typical development and suggests reduced network integration and differentiation in ASD. Our findings also indicate that atypical connectivity of the imitation network may contribute to ASD clinical symptoms, highlighting the role of this fundamental social cognition ability in the pathophysiology of ASD.
The intraparietal sulcus (IPS), a region in the dorsal attention network (DAN), has been implicated in multi-sensory attention and working memory. Working memory and attention develop across childhood; changes in functional connectivity within the DAN may relate to this maturation. Previous findings regarding fronto-parietal intrinsic functional connectivity age-effects were mixed. Our study aimed to circumvent limitations of previous work using a large cross-sectional sample, 183 typically developing participants 6.5-20 years, from the Autism Brain Imaging Data Exchange, and seed regions along the anterior-to-posterior axis of the IPS. These seeds, IPS0-4, were entered into functional connectivity models. Group-level models investigated differential connectivity along the IPS and relationships with age. Anterior IPS3/4 exhibited greater connectivity with sensorimotor/pre-motor regions. Posterior IPS0/1 demonstrated greater connectivity with dorsal and ventral visual regions. Positive age-effects were found between IPS3-4 and visual regions. Negative age-effects were found between IPS and superior parietal and medial orbitofrontal cortices. Follow-up region of interest analyses were used to estimate age-effects for DAN and anticorrelated default mode network regions. Results suggest age-effects on IPS functional connectivity are relatively modest, and may differ pre- and across-adolescence. Studying typical age-related connectivity variability within this network may help to understand neurodevelopmental disorders marked by impaired attention.
Keywords: Attention; Functional connectivity; IPS; Resting-state fMRI; Visual-spatial; Visuotopic.