The study of autism as a distributed disorder

Abstract

Past autism research has often been dedicated to tracing the causes of the disorder to a localized neurological abnormality, a single functional network, or a single cognitive-behavioral domain. In this review, I argue that autism is a "distributed disorder" on various levels of study (genetic, neuroanatomical, neurofunctional, behavioral). "Localizing" models are therefore not promising. The large array of potential genetic risk factors suggests that multiple (or all) emerging functional brain networks are affected during early development. This is supported by widespread growth abnormalities throughout the brain. Interactions during development between affected functional networks and atypical experiential effects (associated with atypical behavior) in children with autism further complicate the neurological bases of the disorder, resulting in an "exponentially distributed" profile. Promising approaches to a better characterization of neural endophenotypes in autism are provided by techniques investigating white matter and connectivity, such as MR spectroscopy, diffusion-tensor imaging (DTI), and functional connectivity MRI. According to a recent hypothesis, the autistic brain is generally characterized by "underconnectivity." However, not all findings are consistent with this view. The concepts and methodology of functional connectivity need to be refined and results need to be corroborated by anatomical studies (such as DTI tractography) before definitive conclusions can be drawn.

Copyright 2007 Wiley-Liss, Inc.

Figures

Fig. 1

Activation effects for sentence comprehension in autism group (A) and control group (B), showing overall reduced effects in the former. (C) Correlation of mean time series between diverse cortical regions of interest (ROIs) shows generally reduced functional connectivity in the autism group. Abbreviations: L = left; R = right; CALC = calcarine fissure; DLPFC = dorsolateral prefrontal cortex; FEF = frontal eye field; IES = inferior extrastriate cortex; IFG = inferior frontal gyrus; IPL = inferior parietal lobe; IPS = intraparietal sulcus; IT = inferior temporal gyrus; TRIA = pars triangularis; OP = occipital pole; SMFP = superior medial frontal paracingulate gyrus. From Just et al. (2004).

Fig. 2

Activation patterns for repetitive index finger movement in three men with autism and three gender and age-matched control participants. All participants show activation clusters in the vicinity of the central sulcus contralateral to the side of movement (indicated by the green line). However, in individuals with autism activity tends to be widely scattered across fronto-parietal regions, whereas in control participants additional activity is largely limited to supplementary motor cortex in the medial frontal lobe and a few sites in ipsilateral motor and premotor cortex. Adapted from Müller et al. (2001).

Fig. 3

Effects of functional connectivity (correlation of BOLD time series) with primary visual cortex (A, B) and thalamus (C). Overlays are color-coded showing results of direct statistical group comparisons. Connectivity with V1 is reduced for a group of 8 men with autism (compared to age-matched neurotypical men) in bilateral inferior frontal area 44 (arrows). In the same sets of participants, functional connectivity between thalamus and several cerebral cortical regions in frontal and parietal lobes is, however, increased, in particular in insular and perirolandic regions. Adapted from Villalobos et al., 2005 (A, B) and Mizuno et al., 2006 (C).