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 (Enhancing NeuroImaging Genetics through Meta-Analysis) 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 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 significant, replicable 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.

Keywords: brain asymmetry; cortical thickness; lateralization; meta-analysis; surface area.

Fig. 1.

The age ranges and sizes of each dataset. Each line covers the age range of an individual dataset, with different colors indicating the sample sizes (see color key). The position of the gray/black dot on each line indicates the median age of that dataset. Black dots indicate datasets with handedness information available. For more details, see Dataset S1.

Fig. 2.

Forest plot of asymmetry score per dataset, for the overall asymmetry in cortical thickness. Asymmetry score indicates the effect size of the interhemispheric difference. The size of a square is proportional to the weights assigned in meta-analysis. The confidence intervals are shown, as well as a dashed vertical line to indicate the point of an asymmetry score of zero.

Fig. 3.

Forest plot of asymmetry score per dataset, for the overall asymmetry in surface area. Asymmetry score indicates the effect size of the interhemispheric difference. The size of a square is proportional to the weights assigned in meta-analysis. The confidence intervals are shown, as well as a dashed vertical line to indicate the point of an asymmetry score of zero.

Fig. 4.

Average regional asymmetries in cortical thickness reveal a fronto-occipital pattern. Positive asymmetry (A, left side; red in B) indicates leftward asymmetry, while negative asymmetry (A, right side; blue in B) indicates rightward asymmetry. Asymmetry score indicates the effect size of the interhemispheric difference. Error bars indicate SEM. L, left; R, right.

Fig. 5.

Average asymmetry pattern in surface area. Positive asymmetry (A, left side; red in B) indicates leftward asymmetry, while negative asymmetry (A, right side; blue in B) indicates rightward asymmetry. Asymmetry score indicates the effect size of the interhemispheric difference. Error bars indicate SEM. L, left; R, right.

Fig. 6.

Meta-analysis results for effects of sex, age, ICV, and handedness on regional asymmetry indexes in cortical thickness and surface area. Red–yellow indicates an increased asymmetry index (AI) in males/with age and ICV; blue–light blue indicates a decreased AI in males/with age and ICV. AI was defined as (L − R)/((L + R)/2). A Z threshold of 3.18 (P = 0.05, Bonferroni corrected) was used. For more details, see Datasets S3–S6.