Sex beyond the genitalia: The human brain mosaic

Edited by Bruce S. McEwen, The Rockefeller University, New York, NY, and approved October 23, 2015 (received for review June 4, 2015)
November 30, 2015
112 (50) 15468-15473
Letter
Joel et al.'s method systematically fails to detect large, consistent sex differences
Marco Del Giudice, Richard A. Lippa [...] David P. Schmitt
Letter
Multivariate revisit to “sex beyond the genitalia”
Jonathan D. Rosenblatt
Letter
Patterns in the human brain mosaic discriminate males from females
Adam M. Chekroud, Emily J. Ward [...] Avram J. Holmes

Significance

Sex/gender differences in the brain are of high social interest because their presence is typically assumed to prove that humans belong to two distinct categories not only in terms of their genitalia, and thus justify differential treatment of males and females. Here we show that, although there are sex/gender differences in brain and behavior, humans and human brains are comprised of unique “mosaics” of features, some more common in females compared with males, some more common in males compared with females, and some common in both females and males. Our results demonstrate that regardless of the cause of observed sex/gender differences in brain and behavior (nature or nurture), human brains cannot be categorized into two distinct classes: male brain/female brain.

Abstract

Whereas a categorical difference in the genitals has always been acknowledged, the question of how far these categories extend into human biology is still not resolved. Documented sex/gender differences in the brain are often taken as support of a sexually dimorphic view of human brains (“female brain” or “male brain”). However, such a distinction would be possible only if sex/gender differences in brain features were highly dimorphic (i.e., little overlap between the forms of these features in males and females) and internally consistent (i.e., a brain has only “male” or only “female” features). Here, analysis of MRIs of more than 1,400 human brains from four datasets reveals extensive overlap between the distributions of females and males for all gray matter, white matter, and connections assessed. Moreover, analyses of internal consistency reveal that brains with features that are consistently at one end of the “maleness-femaleness” continuum are rare. Rather, most brains are comprised of unique “mosaics” of features, some more common in females compared with males, some more common in males compared with females, and some common in both females and males. Our findings are robust across sample, age, type of MRI, and method of analysis. These findings are corroborated by a similar analysis of personality traits, attitudes, interests, and behaviors of more than 5,500 individuals, which reveals that internal consistency is extremely rare. Our study demonstrates that, although there are sex/gender differences in the brain, human brains do not belong to one of two distinct categories: male brain/female brain.

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Data Availability

Data deposition: Our anonymized raw neuroimaging data and accompanying metadata have been deposited at psy-neuro-nassy.uzh.ch and are accessible with a username and password that can be obtained from the authors by email ([email protected] or [email protected]).

Acknowledgments

We thank Dr. Bobbi Carothers (Washington University in St. Louis) and Prof. Harry Reis (University of Rochester) for allowing us to use their data and Prof. Reis for stimulating discussions of the mosaic hypothesis. This research used the Maryland Adolescent Development In Context Study of Adolescent Development in Multiple Contexts, 1991–1998 (Log 1066) dataset (made accessible in 2000, numeric data files). These data were collected by Jacqueline S. Eccles (Producer) and are available through the Henry A. Murray Research Archive of the Institute for Quantitative Social Science at Harvard University (Distributor). Special acknowledgment is due to Ronald R. Rindfuss and Barbara Entwisle for assistance in the original design. This research used data from Add Health, a program project directed by Kathleen Mullan Harris and designed by J. Richard Udry, Peter S. Bearman, and Kathleen Mullan Harris at the University of North Carolina at Chapel Hill and funded by Eunice Kennedy Shriver National Institute of Child Health and Human Development Grant P01-HD31921, with cooperative funding from 23 other federal agencies and foundations. Information on how to obtain the Add Health data files is available on the National Longitudinal study of Adolescent Health (Add Health) website (www.cpc.unc.edu/addhealth). No direct support was received from Grant P01-HD31921 for this analysis. This work was supported by Swiss National Science Foundation Grants 320030-120661, 320030B-138668, 20030B-138668, and 4-62341-05 and European Union Future and Emerging Technologies Integrated Project Presence: Research Encompassing Sensory Enhancement, Neuroscience, Cerebral-Computer Interfaces and Application (PRESENCCIA) Grant 27731 (to L.J.).

Supporting Information

Supporting Information (PDF)
Supporting Information

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Information & Authors

Information

Published in

Go to Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences
Vol. 112 | No. 50
December 15, 2015
PubMed: 26621705

Classifications

Data Availability

Data deposition: Our anonymized raw neuroimaging data and accompanying metadata have been deposited at psy-neuro-nassy.uzh.ch and are accessible with a username and password that can be obtained from the authors by email ([email protected] or [email protected]).

Submission history

Published online: November 30, 2015
Published in issue: December 15, 2015

Keywords

  1. gender differences
  2. sex differences
  3. brain structure
  4. brain connectivity
  5. behavior

Acknowledgments

We thank Dr. Bobbi Carothers (Washington University in St. Louis) and Prof. Harry Reis (University of Rochester) for allowing us to use their data and Prof. Reis for stimulating discussions of the mosaic hypothesis. This research used the Maryland Adolescent Development In Context Study of Adolescent Development in Multiple Contexts, 1991–1998 (Log 1066) dataset (made accessible in 2000, numeric data files). These data were collected by Jacqueline S. Eccles (Producer) and are available through the Henry A. Murray Research Archive of the Institute for Quantitative Social Science at Harvard University (Distributor). Special acknowledgment is due to Ronald R. Rindfuss and Barbara Entwisle for assistance in the original design. This research used data from Add Health, a program project directed by Kathleen Mullan Harris and designed by J. Richard Udry, Peter S. Bearman, and Kathleen Mullan Harris at the University of North Carolina at Chapel Hill and funded by Eunice Kennedy Shriver National Institute of Child Health and Human Development Grant P01-HD31921, with cooperative funding from 23 other federal agencies and foundations. Information on how to obtain the Add Health data files is available on the National Longitudinal study of Adolescent Health (Add Health) website (www.cpc.unc.edu/addhealth). No direct support was received from Grant P01-HD31921 for this analysis. This work was supported by Swiss National Science Foundation Grants 320030-120661, 320030B-138668, 20030B-138668, and 4-62341-05 and European Union Future and Emerging Technologies Integrated Project Presence: Research Encompassing Sensory Enhancement, Neuroscience, Cerebral-Computer Interfaces and Application (PRESENCCIA) Grant 27731 (to L.J.).

Notes

*We use the term sex/gender to indicate that studies typically assess subjects’ sex (i.e., whether one is male or female) but observed differences may reflect the effects of both sex and gender (that is, the social construction of sex). We ignore here the important issue of the probable effects of gender on observed differences between females and males in brain and behavior, because we want to emphasize that regardless of the cause of these differences (sex, gender, or their interactions), they do not add up to create two distinct categories, one typical of males and the other typical of females.
This article is a PNAS Direct Submission.

Authors

Affiliations

School of Psychological Sciences, Tel-Aviv University, Ramat Aviv, Tel-Aviv 6997801, Israel;
Sagol School of Neuoroscience, Tel-Aviv University, Ramat Aviv, Tel-Aviv 6997801, Israel;
Zohar Berman
Sagol School of Neuoroscience, Tel-Aviv University, Ramat Aviv, Tel-Aviv 6997801, Israel;
Ido Tavor
Department of Neurobiology, Faculty of Life Sciences, Tel-Aviv University, Ramat Aviv, Tel-Aviv 6997801, Israel;
Nadav Wexler
School of Mathematical Sciences, Tel-Aviv University, Ramat Aviv, Tel-Aviv 6997801, Israel;
Olga Gaber
School of Psychological Sciences, Tel-Aviv University, Ramat Aviv, Tel-Aviv 6997801, Israel;
Yaniv Stein
School of Mathematical Sciences, Tel-Aviv University, Ramat Aviv, Tel-Aviv 6997801, Israel;
Nisan Shefi
School of Psychological Sciences, Tel-Aviv University, Ramat Aviv, Tel-Aviv 6997801, Israel;
Sagol School of Neuoroscience, Tel-Aviv University, Ramat Aviv, Tel-Aviv 6997801, Israel;
Jared Pool
Max Planck Research Group for Neuroanatomy & Connectivity, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany;
Sebastian Urchs
Max Planck Research Group for Neuroanatomy & Connectivity, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany;
Daniel S. Margulies
Max Planck Research Group for Neuroanatomy & Connectivity, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany;
Franziskus Liem
Max Planck Research Group for Neuroanatomy & Connectivity, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany;
Division Neuropsychology, Department of Psychology, University of Zurich, 8050 Zurich, Switzerland
Jürgen Hänggi
Division Neuropsychology, Department of Psychology, University of Zurich, 8050 Zurich, Switzerland
Lutz Jäncke
Division Neuropsychology, Department of Psychology, University of Zurich, 8050 Zurich, Switzerland
Yaniv Assaf
Sagol School of Neuoroscience, Tel-Aviv University, Ramat Aviv, Tel-Aviv 6997801, Israel;
Department of Neurobiology, Faculty of Life Sciences, Tel-Aviv University, Ramat Aviv, Tel-Aviv 6997801, Israel;

Notes

1
To whom correspondence should be addressed. Email: [email protected].
Author contributions: D.J. designed research; D.J., Z.B., S.U., F.L., J.H., and L.J. performed research; D.J. and Y.A. contributed new analytic tools; D.J., Z.B., I.T., N.W., O.G., Y.S., N.S., J.P., S.U., F.L., and J.H. analyzed data; and D.J. and D.S.M. wrote the paper.

Competing Interests

The authors declare no conflict of interest.

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    Sex beyond the genitalia: The human brain mosaic
    Proceedings of the National Academy of Sciences
    • Vol. 112
    • No. 50
    • pp. 15257-E7033

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