People with autism have left and right brain areas more symmetrical

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The left and right halves of our brains develop differently, as each hemisphere ‘specialises’ in certain functions.

For example, for most people the left hemisphere–controlling the right hand–is dominant for language.

But brain asymmetry is sometimes affected in people with developmental or psychiatric disorders like autism, which is characterised by impaired social cognition, repetitive behaviour and restricted interests.

PhD student Merel Postema explains: “Previous studies have suggested that people with autism spectrum disorder are less likely to have the typical asymmetries for language dominance or hand preference.

However, it has not been clear whether asymmetry of the brain’s anatomy is affected in autism, because different studies have reported different findings.”

Do people with autism have a more symmetrical brain?

To settle this question, scientists from the international ENIGMA consortium of brain researchers decided to do a large-scale study, based on brain scans that were collected in different countries over more than 20 years.

This is by far the largest ever study of this question, using brain scan data from 1,774 people with autism and 1,809 healthy controls.

The team found that the left and right cerebral hemispheres of the brain are indeed more similar in people with autism.

In other words, people with ASD had less brain asymmetry.

The reduced asymmetry was mostly found for cortical thickness, at various locations across the brain’s surface.

In the healthy brain, the thickness of the cerebral cortex (the thin layer of gray matter that covers the brain) differs between the left and right hemispheres. Importantly, the anatomical differences did not depend on age, sex, IQ, the severity of symptoms, or medication use.

This shows the brain symmetry via brain scans

Altered asymmetry of cerebral cortex thickness in autism spectrum disorder. The stars show the affected brain regions. The image is credited to Clyde Francks, MPI Nijmegen.

“The very small average differences in brain asymmetry between affected people and controls mean that changes of brain asymmetry will not be useful in terms of clinical prediction”, says study leader Clyde Francks.

“But the findings might inform our understanding of the neurobiology of autism spectrum disorder”.

As the bulk of the data were from children, the findings suggest that altered development of the brain’s left-right axis is involved in autism, affecting widespread brain regions with diverse functions.

For example, many of the affected brain regions overlap with the default mode network, which is a network of inter-connected brain regions that is particularly active during passive rest and mind-wandering, rather than when doing a specific task. Why this might relate to ASD may be a topic of future research.


Social deficits are a defining feature of autism spectrum disorder (ASD), but also frequently affect children with attention-deficit/ hyperactivity disorder (ADHD)1, and can occur in obsessive-compulsive disorder (OCD) as well25. Increasingly, recognition of the overlapping and related nature of both the symptoms and the biology of different neurodevelopmental disorders68 has led to a call for research that spans diagnostic boundaries, and focuses instead on dimensions of psychopathology9.

Decades of neuroimaging research have begun to delineate the neural substrates of sociality. Different theoretical models of the social brain have been put forward from meta-analyses10,11 and reviews of the literature1214 (summarized in Supplementary Table 1). Across models, three functional/structural groups emerge.

Brain regions hypothesized to be involved in mentalization and empathy (group 1), cluster along the midline and lateral aspects of the brain, including the temporal–parietal junction (TPJ), superior temporal gyrus/sulcus (STS/STG), dorsal medial prefrontal cortex, temporal poles, and the posterior cingulate.

Anterior and prefrontal regions (group 2), including the anterior and dorsal cingulate, orbital frontal cortex, and the dorsal and ventral lateral prefrontal cortices, may contribute to executive function and cognitive control over affective and social processes. Deeper cortical and subcortical structures (group 3), including the insula, amygdala, hippocampus, and the dorsal and ventral striatum, are more central to affective responding, memory, and social reward processing (Supplementary Table 1).

Structural neuroanatomical differences in many of these regions have been detected in individuals with OCD, ASD, and ADHD compared to controls8,1521. For example, recent meta-analyses suggest increased frontal lobe thickness in ASD20, thinner temporal/parietal thickness in ASD and OCD20,22, and smaller subcortical volumes in ASD and ADHD20,23. The extent to which social deficits may differentially localize to specific brain regions/networks in different disorders is unclear, however24.

In ASD, social deficits have been associated with both larger2529 and smaller27,30,31 cortical measurements, particularly in frontal and temporal–parietal regions.

In ADHD, social deficits were associated with greater overall cortical gray matter volume32 and smaller left caudate volumes33.

Cortical gray matter volume is a product of cortical thickness and surface area. Recent work has provided evidence that cortical thickness and cortical surface area measurements are under distinct genetic influences34, and follow unique developmental timelines35,36, necessitating that they be studied independently.

Cortical thickness measurements on magnetic resonance imaging (MRI) are thought to reflect the underlying cortical microstructure, involving the number and organization of cortical neurons, neuronal dendritic arborization, the number and size of glial cells, and to some extent the maturation of the adjacent white matter37.

Cortical thickness, including the timing and rate of cortical thinning, has been a major area of study across neurodevelopmental disorders, particularly in ASD24.

The association between brain (i.e., cortical thickness/subcortical volume) and behavior (i.e., social deficits) was the focus of the following study, in efforts to identify and compare the neural substrates of sociality across disorders.

Given that the specific behavioral dimensions that contribute social impairments may vary across neurodevelopmental disorders (e.g., impaired mentalization in ASD38, executive function in ADHD39, and reward processing in OCD40), one hypothesis is that the neutral substrates of sociality will also differ by diagnosis (e.g., primarily lateral mentalization regions in ASD, frontal cognitive regions in ADHD, and subcortical regions OCD).

An alternative hypothesis is that the brain regions associated with social deficits will span diagnostic boundaries. In children with ASD, ADHD, and OCD, for example, white matter fractional anisotropy correlated with adaptive functioning abilities, irrespective of diagnosis8.

Neuroimaging analyses comparing the structural neuroanatomical correlates of social deficits across children with ASD, ADHD, or OCD have not yet been performed.

To address this knowledge gap, we first compared cortical thickness/subcortical volume measurements in social brain regions across a group of children with ASD, ADHD, OCD, or controls. Next, we examined how cortical thickness/subcortical volume corresponded with social deficits across disorders. We hypothesized that social deficits would correlate with structural anatomy, irrespective of diagnosis.


Source:
Max Planck Institute
Media Contacts:
Marjolein Scherphuis – Max Planck Institute
Image Source:
The image is credited to Clyde Francks, MPI Nijmegen.

Original Research: Open access
“Altered structural brain asymmetry in autism spectrum disorder in a study of 54 datasets”. Postema, M.C., Van Rooij, D., Anagnostou, E., Arango, C., Auzias, G., Behrmann, M., … Francks, C..
Nature Communications doi:10.1038/s41467-019-13005-8.

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