Abnormal lateralization of functional connectivity between language and default mode regions in autism

Jared A Nielsen,Brandon A Zielinski,Jeffrey S Anderson,Erin D Bigler,Janet E Lainhart,P Thomas Fletcher,Nicholas Lange,Andrew L Alexander

doi:10.1186/2040-2392-5-8

Abstract

BackgroundLateralization of brain structure and function occurs in typical development, and abnormal lateralization is present in various neuropsychiatric disorders. Autism is characterized by a lack of left lateralization in structure and function of regions involved in language, such as Broca and Wernicke areas.MethodsUsing functional connectivity magnetic resonance imaging from a large publicly available sample (n = 964), we tested whether abnormal functional lateralization in autism exists preferentially in language regions or in a more diffuse pattern across networks of lateralized brain regions.ResultsThe autism group exhibited significantly reduced left lateralization in a few connections involving language regions and regions from the default mode network, but results were not significant throughout left- and right-lateralized networks. There is a trend that suggests the lack of left lateralization in a connection involving Wernicke area and the posterior cingulate cortex associates with more severe autism.ConclusionsAbnormal language lateralization in autism may be due to abnormal language development rather than to a deficit in hemispheric specialization of the entire brain.

Highlights

Lateralization of brain structure and function occurs in typical development, and abnormal lateralization is present in various neuropsychiatric disorders
We studied whether the lateralization of brain function differs between autism and typical development in a diffuse, network-wide manner or within isolated language-related brain regions
The majority of the analyses were done on 964 (517 typically developing subjects and 447 subjects with autism from 16 sites and datasets because three sites had multiple datasets) of the 1,112 Autism Brain Imaging Data Exchange (ABIDE) subjects who met the following inclusion criteria: 1) successful normalization to Montreal Neurological Institute (MNI) space of magnetization-prepared rapid acquisition with gradient echo (MPRAGE) verified by manual visual inspection, 2) co-registration of blood-oxygen-level dependent (BOLD) and MPRAGE images, 3) segmentation of MPRAGE image, 4) full brain coverage from MNI z > −35 to z

Summary

Introduction

Lateralization of brain structure and function occurs in typical development, and abnormal lateralization is present in various neuropsychiatric disorders. Abnormal brain lateralization in autism has been measured by multiple techniques, including magnetic resonance imaging (MRI) [10,17,18], functional MRI [11,19,20], diffusion imaging [14,15,21], positron emission tomography [22,23,24], and electroencephalography [25,26,27] It has been reported throughout the lifespan in infancy and childhood [20,24,25,26,27,28,29], adolescence [20], and adulthood [22,23]. Lateralization of brain function correlates with language ability in individuals with autism [25]

Methods

Results

Discussion

Conclusion