Sex differences in the structural connectome of the human brain

Madhura Ingalhalikar; Alex Smith; Drew Parker; Theodore D. Satterthwaite; Mark A. Elliott; Kosha Ruparel; Hakon Hakonarson; Raquel E. Gur; Ruben C. Gur; Ragini Verma

doi:10.1073/pnas.1316909110

New Research In

Edited by Charles Gross, Princeton University, Princeton, NJ, and approved November 1, 2013 (received for review September 9, 2013)

Significance

Sex differences are of high scientific and societal interest because of their prominence in behavior of humans and nonhuman species. This work is highly significant because it studies a very large population of 949 youths (8–22 y, 428 males and 521 females) using the diffusion-based structural connectome of the brain, identifying novel sex differences. The results establish that male brains are optimized for intrahemispheric and female brains for interhemispheric communication. The developmental trajectories of males and females separate at a young age, demonstrating wide differences during adolescence and adulthood. The observations suggest that male brains are structured to facilitate connectivity between perception and coordinated action, whereas female brains are designed to facilitate communication between analytical and intuitive processing modes.

Abstract

Sex differences in human behavior show adaptive complementarity: Males have better motor and spatial abilities, whereas females have superior memory and social cognition skills. Studies also show sex differences in human brains but do not explain this complementarity. In this work, we modeled the structural connectome using diffusion tensor imaging in a sample of 949 youths (aged 8–22 y, 428 males and 521 females) and discovered unique sex differences in brain connectivity during the course of development. Connection-wise statistical analysis, as well as analysis of regional and global network measures, presented a comprehensive description of network characteristics. In all supratentorial regions, males had greater within-hemispheric connectivity, as well as enhanced modularity and transitivity, whereas between-hemispheric connectivity and cross-module participation predominated in females. However, this effect was reversed in the cerebellar connections. Analysis of these changes developmentally demonstrated differences in trajectory between males and females mainly in adolescence and in adulthood. Overall, the results suggest that male brains are structured to facilitate connectivity between perception and coordinated action, whereas female brains are designed to facilitate communication between analytical and intuitive processing modes.

Footnotes

↵¹M.I. and A.S. contributed equally to this work.
↵²To whom correspondence should be addressed. E-mail: ragini.verma{at}uphs.upenn.edu.

Author contributions: M.I., T.D.S., H.H., R.E.G., R.C.G., and R.V. designed research; A.S., M.A.E., K.R., and H.H. performed research; A.S. and D.P. analyzed data; and M.I., R.E.G., R.C.G., and R.V. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
See Commentary on page 577.
Data deposition: The data reported in this paper have been deposited in the dbGaP database, www.ncbi.nlm.nih.gov/gap (accession no. phs000607.v1.p1).

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