Abstract

Studies in animal models of autism spectrum disorders (ASD) suggest atypical early neural activity is a core vulnerability mechanism which alters functional connectivity and predisposes to dysmaturation of neural circuits. However, underlying biological changes associated to ASD in humans remain unclear. Results from functional connectivity studies of individuals diagnosed with ASD are highly heterogeneous, in part because of complex life-long secondary and/or compensatory events. To minimize these confounds and examine primary vulnerability mechanisms, we need to investigate very early brain development. Here, we tested the hypothesis that brain functional connectivity is altered in neonates who are vulnerable to this condition due to a family history of ASD. We acquired high temporal resolution multiband resting state functional magnetic resonance imaging (fMRI) in newborn infants with and without a first-degree relative with ASD. Differences in local functional connectivity were quantified using regional homogeneity (ReHo) analysis and long-range connectivity was assessed using distance correlation analysis. Neonates who have a first-degree relative with ASD had significantly higher ReHo within multiple resting state networks in comparison to age matched controls; there were no differences in long range connectivity. Atypical local functional activity may constitute a biomarker of vulnerability, that might precede disruptions in long range connectivity reported in older individuals diagnosed with ASD.

Highlights

  • Autism spectrum disorders (ASD) are increasingly common, with current prevalence estimated to be 1 in 59 children[1]

  • We observed no significant differences between groups for the median regional homogeneity (ReHo) values

  • ReHo median values in the somatosensory/ motor network were significantly higher than any other network, with the greatest difference observed in comparison to the default mode network (DMN) (d = 2.1, corrected p < 0.01)

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Summary

Introduction

Autism spectrum disorders (ASD) are increasingly common, with current prevalence estimated to be 1 in 59 children[1]. Evidence from small rodent models suggests that the pathophysiological consequences of genetic (and/or environmental) risks for ASD are present from very early in development and include atypical synaptic mechanisms and altered neural activity[10,11,12,13,14]. These preclinical studies consistently report an increase in spontaneous synchronous activity in the brain of rodents carrying risk genes for ASD around what would be the equivalent time of birth in humans[15].

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