For a commentary to this article, and counter-response by the authors, please scroll down to see updates. Biological explanations of differences in behavior between women and men or girls and boys are everywhere, from scientific articles to bestselling self-help books to parenting guides to diversity and inclusion workshops to Hollywood movies. The difference is often described as if it were binary — females are like this and males are like that — and a natural and inevitable consequence of being female or male, assumed implicitly or otherwise to be inscribed in our genes. Then, the biological difference is suggested to underlie a behavioral or psychological difference between females and males. But researching, understanding, and interpreting sex differences in brain and behavior is surprisingly complicated, and particularly so when humans are involved.

eLife digest


Introduction
As part of an initiative to improve rigor and reproducibility in biomedical research, the U. National Institutes of Health now requires the consideration of sex as a biological variable in preclinical studies. This new policy has been interpreted by some as a call to compare males and females with each other. Researchers testing for sex differences may not be trained to do so, however, increasing risk for misinterpretation of results. Using a list of recently published articles curated by Woitowich et al. Sex differences were claimed in the majority of the articles we analyzed; however, statistical evidence supporting those differences was often missing. For example, when a sex-specific effect of a manipulation was claimed, authors usually had not tested statistically whether females and males responded differently.
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Sex differences in the human brain are of interest for many reasons: for example, there are sex differences in the observed prevalence of psychiatric disorders and in some psychological traits that brain differences might help to explain. We report the largest single-sample study of structural and functional sex differences in the human brain female, male participants; mean age Males had higher raw volumes, raw surface areas, and white matter fractional anisotropy; females had higher raw cortical thickness and higher white matter tract complexity. There was considerable distributional overlap between the sexes. Subregional differences were not fully attributable to differences in total volume, total surface area, mean cortical thickness, or height. There was generally greater male variance across the raw structural measures. Functional connectome organization showed stronger connectivity for males in unimodal sensorimotor cortices, and stronger connectivity for females in the default mode network. This large-scale study provides a foundation for attempts to understand the causes and consequences of sex differences in adult brain structure and function. Sex differences have been of enduring biological interest Darwin , but our knowledge about their relevance to the human brain is surprisingly sparse. It has been noted by several researchers that the potential influences of sex are under-explored in neuroscientific research Beery and Zucker ; Cahill , ; Karp et al.
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