Harlalka, V. | bioRxiv Science

bioRxiv2018

Atypical flexibility in dynamic functional connectivity quantifies the severity in autism spectrum disorder

Resting-state functional connectivity (FC) analyses have shown atypical connectivity in autism spectrum disorder (ASD) as compared to typically developing (TD). However, this view emerges from investigating static FC overlooking the age, disease phenotype and their interaction in the whole brain transient connectivity patterns. Contrasting with most extant literature in the present study, we investigated precisely how age and disease phenotypes factors into dynamic changes in functional connectivity of TD and ASD using resting-state functional magnetic resonance imaging (rs-fMRI) data stratified into three cohorts: children (7-11 years) and adolescents (12-17 years), and adults (18+) for the analysis. The dynamic variability in the connection strength and the modular organization in terms of measures: flexibility, cohesion strength and disjointness were explored for each subject to characterize the differences between ASD and TD.\n\nIn ASD, we observed significantly higher inter-subject dynamic variability in connection strength as compared to TD. This hypervariability relates to the symptom severity in ASD. We found that whole-brain flexibility correlates with static modularity only in TD. Further, we observed a core-periphery organization in the resting-state, with Sensorimotor and Visual regions in the rigid core; and DMN and attention areas in the flexible periphery. TD also develops a more cohesive organization of sensorimotor areas. However, in ASD we found a strong positive correlation of symptom severity with the flexibility of rigid areas and with disjointness of sensorimotor areas. The regions of the brain showing the high predictive power of symptom severity were distributed across the cortex, with stronger bearings in the frontal, motor and occipital cortices. Our study demonstrates that the dynamic framework best characterizes the variability in ASD.

neuroscience↗

bioRxiv2018

Integration and segregation in Autism Spectrum Disorders modulated by age, disease, and interaction: A graph-theoretic study of intrinsic functional connectivity

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1 in 50 children between the ages of 6 and 17 years. Brain connectivity and graph theoretic methods have been particularly very useful in shedding light on the differences between high functioning autistic children compared to typically developing (TD) ones. However, very recent developments in network measures raise a cautionary note by highlighting gross under- and over-connectivity in ASD may be an oversimplified hypothesis. Thus the primary aim of our study is to investigate these notions in functional connectomics of ASD versus TD by subjecting the data to reproducibility experiments using two independent datasets.\n\nFurther, we tested the hypothesis of alteration in network segregation and integration in the ASD subjects. We have analyzed the resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) data from the University of California Los Angeles (UCLA) multimodal connectivity database (n=42 ASD, n=37 TD) and rs-fMRI data from the Autism Brain Imaging Data Exchange (ABIDE) (n=187 ASD, n=176 TD) dataset. We assessed the differences in connection strength between TD and ASD subjects. We also performed graph theoretical analysis to analyze the effect of disease on various network measures. Further, using the larger ABIDE dataset, we performed two-factor ANOVA test, to study the effect of age, disease and their interaction by classifying the TD and ASD participants into two cohorts: children (9-12 years, n=73 TD and n=87 ASD) and adolescents (13-16 years, n=103 TD and n=100 ASD). In ASD, we show the existence of atypical connectivity within and between functional networks as compared to TD. We also found in ASD both hypo-and hyper-connectivity within functional networks such as the default mode network (DMN). Further, graph theoretic analysis showed that there is significant effect of age and disease on modularity, clustering coefficient, and local efficiency. We also identified specific areas within the DMN, sensorimotor, visual and attention networks that are affected by age, disease and their interaction. Overall, our findings suggest that maturation, disease and their interaction are critical for unraveling the biological basis and developmental trajectory in ASD and other neuropsychiatric disorders.

neuroscience↗