Autism: The first firm finding = underconnectivity?

doi:10.1016/j.yebeh.2007.03.010

Epilepsy & Behavior

Volume 11, Issue 1, August 2007, Pages 20-24

https://doi.org/10.1016/j.yebeh.2007.03.010 Get rights and content

Abstract

In January 2005, J.R. Hughes and M. Melyn published an electroencephalographic study on autistic children and found 46% with seizures and also a relatively high prevalence of 20% with epileptiform discharges but without any clinical seizures (Clin EEG Neurosci 2005;36:15–20). Because the discharges have always been viewed as focal events and the clinical seizures as requiring spread, the conclusion from these data was that children with autism may have a deficiency of corticocortical fibers. Since that time many MRI and functional MRI studies have been published confirming that one of the first findings in this devastating condition is underconnectivity. Specific findings are the thinning of the corpus callosum and the reduced connectivity, especially with the frontal areas and also the fusiform face area. Other studies involving positron emission tomography scans, magnetoencephalography, and perception have added to the evidence of underconnectivity. One final point is the initial overgrowth of white matter in the first 2 years of life in autistic children, followed later by arrested growth, resulting in aberrant connectivity; myelination of white matter will likely be significant in the etiology of autism.

Introduction

In January 2005, J.R. Hughes and M. Melyn [1] published an EEG study on autism, reporting seizures in 46%, as well as a relatively high prevalence of epileptiform discharges (20%) in others who did not have a history of clinical seizures. Although 20% may not seem high, this value was significantly different from that of the control group of matched children without autism. Because discharges are usually regarded as an exquisitely focal finding and the seizures require some spread from the focus, the final conclusion from these data was that a clue to one problem in autistic children may be a deficiency of corticocortical fibers to account for this presumed lack of spread from a focus. After that study, 19 studies—mainly MRI and functional MRI (fMRI) studies—have been published on autism and autistic spectrum disorders that are consistent with the original conclusions from the EEG study. The evidence is now clear that one major finding in autism is the underconnectivity within the brain. This finding is consistent with the behavior of these children, who tend to concentrate on some object, rather than on any person, but without any significant relationship to other sensory modalities, as may be expected from disconnected cerebral circuits.

Section snippets

Other theories

Some general conclusions relevant to autism are that growth dysregulation [2] is likely involved and also that mechanical factors from cortical folding influencing the lamina [3] may also be implicated. A separate and different view of this disorder is that females are better than males as “empathizers,” dealing with people, and males are better “systemizers,” dealing with the rules governing the behavior of things[4]. Autism is then viewed as an “extreme male brain” [5]. Another theory relates

Corpus callosum

The first group of studies discussed here used MRI to determine underconnectivity. One of the most common findings in autism has been the decrease in the size of the corpus callosum. As early as 1993, Courchesne et al. [15] reported the thinning of the corpus callosum as part of white matter volume loss, in addition to the loss in the parietal lobes. Also, the cortical volume loss in the same parietal lobes was found to extend into the adjacent superior frontal and occipital lobes. The cortical

Emphasis on facial area

One of the major clinical findings in the autistic spectrum is the lack of apparent recognition of faces, as these children tend to concentrate on things and not people. A number of studies have provided evidence to account for this phenomenon. In 2003, Frith [41] reported that autistic children failed to activate the fusiform face area during face perception tests, also demonstrating weak activation of medial frontal cortex and the superior temporal gyrus. The conclusion was that this finding

Increase in white matter

With considerable evidence indicating a decrease in the networks involving various areas, it may be somewhat surprising that an increase in white matter could be found. The earliest evidence came from Frith’s study [41] showing an increase in total brain volume during the first few years as a marker of abnormal connectivity from lack of pruning. In the next year (2004), Courchesne [43] was more specific by pointing out that the overgrowth occurred during the first 2 years of life, followed by

Myelination

As white matter myelination generally reflects the progression of functional brain maturation [48], it is reasonable to explore the process of myelination as a putative etiology of autism. The time when this disorder usually reveals itself clinically is between 2 and 3 years of age [43], and, therefore, it is this same time interval that may lead us to discover the etiology of autism. The onset of myelination, as indicated by the expression of myelin basic protein, is usually at 1 year of age,

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Autism: The first firm finding = underconnectivity?

Abstract

Introduction

Section snippets

Other theories

Corpus callosum

Emphasis on facial area

Increase in white matter

Myelination

Magn Reson Imaging

NeuroImage

Biol Psychiatry

NeuroImage

NeuroImage

Curr Opin Neurobiol

NeuroImage

Brain Res

Psychiatry Res

NeuroImage

NeuroImage

NeuroImage

EEG and seizures in autistic children and adolescents: further findings with therapeutic implications

Clin EEG Neurosci

The neurobiological basis of autism from a developmental perspective

Dev Psychopathol

Role of mechanical factors in the morphology of the primate cerebral cortex

PloS Comput Biol

Autism: a window onto the development of the social and the analytic brain

Annu Rev Neurosci

Sex differences in the brain: implications for explaining autism

Science

EEG evidence for the presence of an action observation–execution matching system in children

Eur J Neurosci

A resilient, low-frequency, small-world human brain functional network with highly connected association cortical hubs

Neuroscience

Functional connectivity as revealed by spatial independent component analysis of fMRI measurements during rest

Hum Brain Mapp

Functional connectivity in the resting brain: a network analysis of the default mode hypothesis

Proc Natl Acad Sci USA

Conceptual processing during the conscious resting state: a functional MRI study

J Cogn Neurosci

Modulation of functional connectivity during the resting state and the motor task

Hum Brain Mapp

Effect of prior cognitive state on resting state networks measured with functional connectivity

Hum Brain Mapp

Functional connectivity of the fusiform gyrus during a face-matching task in subjects with mild cognitive impairment

Brain

Parietal lobe abnormalities with MR in patients with infantile autism

Am J Roentgenol