Abstract
The human cerebral hemispheres show a left–right asymmetrical torque pattern, which has been claimed to be absent in chimpanzees. The functional significance and developmental mechanisms are unknown. Here, we carried out the largest-ever analysis of global brain shape asymmetry in magnetic resonance imaging data. Three population datasets were used, UK Biobank (N = 39 678), Human Connectome Project (N = 1113), and BIL&GIN (N = 453). At the population level, there was an anterior and dorsal skew of the right hemisphere, relative to the left. Both skews were associated independently with handedness, and various regional gray and white matter metrics oppositely in the two hemispheres, as well as other variables related to cognitive functions, sociodemographic factors, and physical and mental health. The two skews showed single nucleotide polymorphisms-based heritabilities of 4–13%, but also substantial polygenicity in causal mixture model analysis, and no individually significant loci were found in genome-wide association studies for either skew. There was evidence for a significant genetic correlation between horizontal brain skew and autism, which requires future replication. These results provide the first large-scale description of population-average brain skews and their inter-individual variations, their replicable associations with handedness, and insights into biological and other factors which associate with human brain asymmetry.
Highlights
A counter-clockwise twist of the whole brain along the anterior– posterior axis, that is, the fronto-occipital torque, has been widely reported in humans since observations in the middle of the 20th century (e.g., Yakovlev and Rakic 1966; LeMay 1976; Weinberger et al 1982; Zilles et al 1996; Watkins et al 2001; Kong et al 2018; see Toga and Thompson 2003, for a review)
The sample sizes were not large in these previous studies (e.g., 37 cases and 44 controls in Maller et al 2017; 231 cases and 68 controls in Fullard et al 2019), and further replication is needed, these results suggest that the global brain asymmetry pattern may reflect an optimal organization of the human brain, and deviation from it might serve as a biomarker of brain dysfunction
Using linkage disequilibrium (LD) score regression with the genome-wide association studies (GWAS) summary statistics for handedness (N > 330 000) from de Kovel and Francks (2019) and the summary statistics from our GWAS for brain skew measures, we found no significant genetic correlations of hand preference with the skews (Ps > 0.10)
Summary
A counter-clockwise twist of the whole brain along the anterior– posterior axis, that is, the fronto-occipital torque, has been widely reported in humans since observations in the middle of the 20th century (e.g., Yakovlev and Rakic 1966; LeMay 1976; Weinberger et al 1982; Zilles et al 1996; Watkins et al 2001; Kong et al 2018; see Toga and Thompson 2003, for a review). An early study reported that the left hemisphere was shifted dorsally relative to the right (Best 1986), but recent work based on magnetic resonance imaging (MRI) analysis of 91 human brains found the opposite pattern, that is, the left hemisphere shifted significantly downward relative to the right (Xiang et al 2019). This pattern was reported to be human specific, in comparison to chimpanzees (Xiang et al 2019). Neither vertical nor horizontal asymmetries have been measured in large-scale population analysis in thousands of people, to assess their averages, variances, or correlations
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
