Locked-in Intact Functional Networks in Children with Autism Spectrum Disorder: A Case-Control Study.

Andrew R Pines,Patrick J Mccarty,Varina L Boerwinkle,Raymond Bunch,Richard E Frye,Sarah N Wyckoff,Bethany Sussman

doi:10.3390/jpm11090854

Abstract

Resting-state functional magnetic resonance imaging (rs-fMRI) has the potential to investigate abnormalities in brain network structure and connectivity on an individual level in neurodevelopmental disorders, such as autism spectrum disorder (ASD), paving the way toward using this technology for a personalized, precision medicine approach to diagnosis and treatment. Using a case-control design, we compared five patients with severe regressive-type ASD to five patients with temporal lobe epilepsy (TLE) to examine the association between brain network characteristics and diagnosis. All children with ASD and TLE demonstrated intact motor, language, and frontoparietal (FP) networks. However, aberrant networks not usually seen in the typical brain were also found. These aberrant networks were located in the motor (40%), language (80%), and FP (100%) regions in children with ASD, while children with TLE only presented with aberrant networks in the motor (40%) and language (20%) regions, in addition to identified seizure onset zones. Fisher’s exact test indicated a significant relationship between aberrant FP networks and diagnosis (p = 0.008), with ASD and atypical FP networks co-occurring more frequently than expected by chance. Despite severe cognitive delays, children with regressive-type ASD may demonstrate intact typical cortical network activation despite an inability to use these cognitive facilities. The functions of these intact cognitive networks may not be fully expressed, potentially because aberrant networks interfere with their long-range signaling, thus creating a unique “locked-in network” syndrome.

Highlights

At the time of Resting-state functional magnetic resonance imaging (rs-fMRI), he was diagnosed with autism spectrum disorder (ASD), cognitive delay, severe language impairment (LI), and developmental coordination disorder (DCD)
At the time of rs-fMRI, she was diagnosed with ASD, borderline intellectual disability (ID), severe LI, and delayed visual-motor skills
We propose that analyzing individual patients may provide evidence that ASD symptoms may correlate with aberrant networks that interfere with the maturation of typical resting-state networks (RSNs), effectively creating a locked-in network syndrome

Summary

Introduction

Autism spectrum disorder (ASD) has a prevalence of 1 in 54 children in the United. States and is characterized by deficits in social communication and interaction, and restricted and repetitive behaviors [1]. The neurological basis of ASD remains elusive in this highly heterogenous population. Resting-state functional magnetic resonance imaging (rs-fMRI) is a promising tool that has been used to analyze neural networks in patients with neurodevelopmental and neurological disorders. A review of prior group-level rs-fMRI investigations suggests hypo-, hyper-, and mixed-connectivity patterns among individuals with ASD, with contradictory findings attributed to differences in age, sex, comorbidities, and/or variations in the rs-fMRI scanning and analysis procedures [2].

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Conclusion