Editorial: From sex differences in neuroscience to a neuroscience of sex differences: new directions and perspectives

摘要

While we are looking back at a century of behavioral research on sex differences in cognition and emotion, sex differences have for a long time been disregarded as a confound in neuroscience.Several researchers still argue that sex differences in cognition are overall small and negligible (Hyde and Linn, 1988 , 2006 ; Hyde, 2005 , 2006 ). Indeed the data so far are by no means consistent. These inconsistencies are to a large part attributable to small sample sizes and low power on the one hand and a large variation in methodologies on the other hand. This is even more true for studies on menstrual cycle and hormonal contraceptive dependent effects on the brain, as will be pointed out in this Research Topic (Pletzer and Kerschbaum, 2014 ; Sundstr?m Poromaa and Gingnell, 2014 ).However, another reason that these inconsistencies still exist may also be that neuroscience, looking at the topic from the angle of political correctness, has refrained from studying sex differences in the brain in more detail. One major goal of this Research Topic is to change this view and look at the topic from a different angle:Women don't have to be like men to be treated as equal. Women have a right to be women and if that includes being different from men, women have a right to be different from men and—importantly—also vice versa. After all, innovation stems from diversity (e.g., Hewlett et al., 2013 ). Furthermore, women have a right to understand these differences as well as the hormonal changes that not only their body, but also their brain, goes through during their lifetime. So it's important that neuroscience starts paying more attention!The aim of this Research Topic is to point out directions and perspectives on how to resolve inconsistencies in sex difference research. The idea is to move from scattered findings on sex differences in the brain to a neuroscience of sex differences that will help researchers to understand and predict sex differences in their findings and integrate them into their theories.From the beginning of sex difference research, it has been hypothesized that sex differences in behavior are at least in part driven by hormonal influences on the brain either during development (organizational) or later in life (activational) (e.g., Kelly et al., 1999 ). Of course, not all sex differences can be attributable to sex hormones, but genetic, epigenetic, and chromosomal effects also play an important role, as pointed out by Ivanka Savic' contribution to this topic (Savic, 2014 ). However, sex hormone influences have been hypothesized to explain that variation in performance is higher in women than in men (e.g., Hausmann and Güntürkün, 1999 ). Therefore, sex hormones are of special interest to this topic as one important factor that might explain inconsistencies between sex difference studies.Accordingly, the idea for this Research Topic was born during a study on sex differences in number processing. In a number bisection task, we found for two behavioral effect that sex differences in brain activation patterns were present during one cycle phase (follicular or luteal), but not during the other (Pletzer et al., 2011 ). In a follow-up study using the same task we furthermore recognized that women using hormonal contraceptives differed from naturally cycling women in the same way as men (Pletzer et al., 2014 ). These findings have important methodological implications for research on sex differences.First, I propose here, that sex differences should always be investigated by comparing men to naturally cycling women, i.e., naturally occurring sex differences. The question of hormonal contraceptive dependent influences on brain and behavior is related, but separate.Given that in developed countries about half of all women below the age of 45 rely on some method of hormonal contraception (Guttmacher Institute, 2015 ), hormonal contraception may represent a major confound in the study of sex differences. Only a handful of researchers have so far investigated hormonal contraceptive dependent effects on cognition, brain structure or brain function and only few consistencies arise. Within this topic, these findings are reviewed, potential mechanisms of action of hormonal contraceptives on brain and behavior are discussed and perspectives for research on hormonal contraceptive dependent effects are suggested (Pletzer and Kerschbaum, 2014 ).Second, I argue that differences between men and naturally cycling women cannot be investigated without taking menstrual cycle phase into account. Despite an early interest in menstrual cycle dependent influences on mood (Frank, 1931 ), menstrual cycle dependent changes in cognitive functions have only been investigated for about 25 years now, starting with a pioneer study by Hampson ( 1990a , b ). Only few studies have however investigated menstrual cycle dependent changes using neuroimaging methods. In this topic, menstrual cycle dependent changes in brain and behavior were car