Abstract

BackgroundNeuroimaging studies can shed light on the neurobiological underpinnings of autism spectrum disorders (ASD). Studies of the resting brain have shown both altered baseline metabolism from PET/SPECT and altered functional connectivity (FC) of intrinsic brain networks based on resting-state fMRI. To date, however, no study has investigated these two physiological parameters of resting brain function jointly, or explored the relationship between these measures and ASD symptom severity.MethodsHere, we used pseudo-continuous arterial spin labeling with 3D background-suppressed GRASE to assess resting cerebral blood flow (CBF) and FC in 17 youth with ASD and 22 matched typically developing (TD) children.ResultsA pattern of altered resting perfusion was found in ASD versus TD children including frontotemporal hyperperfusion and hypoperfusion in the dorsal anterior cingulate cortex. We found increased local FC in the anterior module of the default mode network (DMN) accompanied by decreased CBF in the same area. In our cohort, both alterations were associated with greater social impairments as assessed with the Social Responsiveness Scale (SRS-total T scores). While FC was correlated with CBF in TD children, this association between FC and baseline perfusion was disrupted in children with ASD. Furthermore, there was reduced long-range FC between anterior and posterior modules of the DMN in children with ASD.ConclusionTaken together, the findings of this study – the first to jointly assess resting CBF and FC in ASD – highlight new avenues for identifying novel imaging markers of ASD symptomatology.

Highlights

  • Autism spectrum disorders (ASD) are characterized by impairments in social communication, the presence of restricted interests and repetitive behaviors and/or sensory over-responsivity (American Psychiatric Association, 2013)

  • We identified two components representing the anterior and posterior part of the default mode network (DMN), suggesting that perfusion based functional connectivity (FC) analysis is able to identify the DMN similar to the networks known from blood oxygenation level dependent (BOLD) resting-state functional MRI (rs-fMRI)

  • While PET/SPECT imaging is typically used to assess cerebral metabolic rate of glucose (CMRglu) or cerebral blood flow (CBF) and BOLD rs-fMRI to estimate FC, here we capitalized on the ability of the latest pseudocontinuous ASL (pCASL) with 3D BS GRASE to provide robust CBF measurements and adequate temporal resolution and signal-to-noise ratio (SNR) for FC analysis (Jann et al 2015a)

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Summary

Introduction

Autism spectrum disorders (ASD) are characterized by impairments in social communication, the presence of restricted interests and repetitive behaviors and/or sensory over-responsivity (American Psychiatric Association, 2013). In addition to altered activation patterns during tasks, changes in functional connectivity (FC) of several key resting brain networks (Assaf et al 2010; Rudie et al 2012a,b; Lynch et al 2013; Hernandez et al 2014; Maximo et al 2014; Washington et al 2014) have been identified, leading to the hypothesis that ASD might be caused by increased (hyper-) or decreased (hypo-). We found increased local FC in the anterior module of the default mode network (DMN) accompanied by decreased CBF in the same area In our cohort, both alterations were associated with greater social impairments as assessed with the Social Responsiveness Scale (SRS-total T scores). Conclusion: Taken together, the findings of this study – the first to jointly assess resting CBF and FC in ASD – highlight new avenues for identifying novel imaging markers of ASD symptomatology

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