Mapping Cortical Brain Asymmetry in 17,141 Healthy Individuals Worldwide via the ENIGMA Consortium

Abstract

Hemispheric asymmetry is a cardinal feature of human brain organization. Altered brain asymmetry has also been linked to some cognitive and neuropsychiatric disorders. Here the ENIGMA consortium presents the largest ever analysis of cerebral cortical asymmetry and its variability across individuals. Cortical thickness and surface area were assessed in MRI scans of 17,141 healthy individuals from 99 datasets worldwide. Results revealed widespread asymmetries at both hemispheric and regional levels, with a generally thicker cortex but smaller surface area in the left hemisphere relative to the right. Regionally, asymmetries of cortical thickness and/or surface area were found in the inferior frontal gyrus, transverse temporal gyrus, parahippocampal gyrus, and entorhinal cortex. These regions are involved in lateralized functions, including language and visuospatial processing. In addition to population-level asymmetries, variability in brain asymmetry was related to sex, age, and brain size (indexed by intracranial volume). Interestingly, we did not find significant associations between asymmetries and handedness. Finally, with two independent pedigree datasets (N = 1,443 and 1,113, respectively), we found several asymmetries showing modest but highly reliable heritability. The structural asymmetries identified, and their variabilities and heritability provide a reference resource for future studies on the genetic basis of brain asymmetry and altered laterality in cognitive, neurological, and psychiatric disorders.Significance StatementLeft-right asymmetry is a key feature of the human brain's structure and function. It remains unclear which cortical regions are asymmetrical on average in the population, and how biological factors such as age, sex and genetic variation affect these asymmetries. Here we describe by far the largest ever study of cerebral cortical brain asymmetry, based on data from 17,141 participants. We found a global anterior-posterior 'torque' pattern in cortical thickness, together with various regional asymmetries at the population level, which have not been previously described, as well as effects of age, sex, and heritability estimates. From these data, we have created an on-line resource that will serve future studies of human brain anatomy in health and disease.

Evidence for a genetic effect in altered cortical surface area but not in cortical thinning in siblings of patients with mesial temporal lobe epilepsy

“…Both these relatives had values above the median of the relative group for the reduced surface area in the anteromedial temporal cortex, further strengthening the possibility that these subtle morphological changes are inherited . Limitations of this study include the small number of subjects studied and that they side‐flipped the images to increase power to detect differences, thus treating both hemispheres as if they were equal, which is not the case, as shown recently by Kong et al The study by Alhusaini et al showed that the alterations of cortical morphology found in anteromedial regions of unaffected siblings of subjects with left MTLE‐HS (more in the left entorhinal cortex and parahippocampal gyrus) differed from those found in unaffected siblings of subjects with right MTLE‐HS (more in the right entorhinal cortex and temporal pole).…”

“…Effect sizes of cortical thickness and surface area were independent, and the asymmetry was generally more prominent for surface area compared with that of cortical thickness . Most regions showed significant asymmetry in surface area, although with no clear directional pattern affecting neighboring regions, or along the anterior‐posterior axis, as they observed for cortical thickness …”

“…A recent study that mapped cortical brain asymmetry in 17 141 healthy individuals showed regions with different asymmetrical patterns in cortical thickness and surface area and a significant heritability of these asymmetry characteristics . Effect sizes of cortical thickness and surface area were independent, and the asymmetry was generally more prominent for surface area compared with that of cortical thickness . Most regions showed significant asymmetry in surface area, although with no clear directional pattern affecting neighboring regions, or along the anterior‐posterior axis, as they observed for cortical thickness …”

“…These results suggest some independence of these two surface‐based measures, and potentially, their asymmetry patterns. A recent study that mapped cortical brain asymmetry in 17 141 healthy individuals showed regions with different asymmetrical patterns in cortical thickness and surface area and a significant heritability of these asymmetry characteristics . Effect sizes of cortical thickness and surface area were independent, and the asymmetry was generally more prominent for surface area compared with that of cortical thickness .…”

Default Mode Network in Temporal Lobe epilepsy: interactions with memory performance

“…Specifically, in MTLE associated with HS 17 , side of hippocampal atrophy plays a key role in cognitive performance. It has been consistently accepted that side matters 18 being the left hippocampus more related to verbal memory, while right hippocampus associates with nonverbal memory 19 ,20 . Hence, it is expected that left-HS patients present more verbal deficits while right-HS patients normally present more nonverbal deficits.…”