Biological Basis of Human Sexual Orientation

The desire to study the biological basis of human sexual orientation in the scientific community is relatively recent phenomenon. To this day, sexual orientation acquisition remains one of the most prominent biological mechanisms unknown to science. It has become clear, however, that human sexual arousal, which is usually triggered by external stimuli or endogenous factors, is a multidimensional experience comprising cognitive, emotional, motivational, and physiological components (Hu et al, 2008). With this in mind, from as early as the 1990s, studies have attempted to uncover a neurological basis to account for the differences in sexual orientation in humans, with particular focus being placed upon differences in neural structures between homosexual and heterosexual individuals.

With the turn of the millennium came further study into such differences using functional imaging techniques, namely functional Magnetic Resonance Imaging (fMRI) studies, as well as endocrinology investigations and genetic knock-out experiments (such as Dulac et al, 2007) to identify potential neural circuits.

The progression from using post-mortem and lesion studies to modern in vivo imaging has continued to shed light on dimorphic features in the brain in individuals of differing sexual orientations, allowing us to form hypotheses on development and function . In this investigation, I will review and analyse the progression of major research endeavours into studying this highly complex topic, with particular focus on neuroanatomical correlations and imaging techniques to attempt to ascertain a theory on the neural basis of human sexuality. In looking at this, I will then briefly consider the limitations of the procedures highlighted as well as the possibilities in this field of research for the future, such as the applications of understanding the neural basis in human sexuality in other aspects of neuroscience.

Basis for Research – Sexual Dimorphism in the Brain via Post-Mortem Studies Prior to the end of the twentieth century, sexual orientation – an individual’s sexual and/or romantic attraction to their preferred gender(s) – was studied mostly at the level of psychology, ethics or anthropology. Modern inquiries into the scientific study of the neural basis of sexual orientation, however, is based upon sexual dimorphism in the brain – the idea that areas of the brain vary between those assigned male and female at birth.

One of the most prominent studies of this was seen in 1991. This was before the widespread use of fMRI, and as such the ‘imaging’/study method used was a post-mortem study, conducted using the brains of deceased homosexual men that had died from complications due to AIDS, during the United States AIDS epidemic. From classic lesion studies, the anterior hypothalamus had been identified to be important in traditional male sexual behaviour in monkeys (Slimp et al, 1978). Knowing this, particular nuclei of the hypothalamus from homosexual men and heterosexual individuals (both male and female) were compared. The INAH 3 interstitial nucleus of the anterior hypothalamus was observed to be more than twice as large in heterosexual men than in heterosexual women, showing a clear instance of sexual dimorphism.

Crucially, however, the size of INAH 3 was also seen to be more than twice as large in heterosexual men than in homosexual men, as seen in Figure 1 (LeVay, 1991). This was one of the first instances of an indication that a neural structure was dimorphic with sexual orientation, as such suggesting that sexual orientation has a biological substrate. It indeed backed up other dimorphic claims on the issue, with studies in the literature noting some other structural differences between the brains of deceased individuals of differing sexual orientation, such as the finding of a greater suprachiasmatic nucleus volume in homosexual men compared to heterosexual men (Swaab and Hofman, 1990). The INAH 3 nucleus would later be seen to be involved in a structure of the brain that researchers have named the ‘sexually dimorphic nucleus’ (SDN), with itself and its homologs found to be widely conserved in mammals (Vasey et al, 2005).

Another prominent finding in the post-mortem study of sexual orientation was seen in the anterior commissure. In particular, the midsagittal area of this structure is larger in women than in men. However, brains taken from deceased homosexual men showed that their midsagittal anterior commissure was 18% larger than that of heterosexual woman, and 34% larger than that of heterosexual men (Allen and Gorski, 1992). Although the significance of this is still entirely unknown, it is noteworthy of a sexual dimorphism with sexual orientation patterns that has no role in reproduction. Sexual orientation in the age of fMRI (and PET) Although post-mortem studies resulted in some of the first primary findings into the neural correlates of sexual orientation, these studies are limited in their ability to understand a phenomenon such as this, that is hypothesised to involve complex neural systems and connections.

As such, research into sexual orientation was revolutionised with the advent of functional imaging studies. The inferred thesis given above of neuroanatomical sexual dimorphism being a biological substrate for sexual preference needed to be tested using modern neuroimaging techniques. The process of using functional imaging for this particular field of study is relatively simple, and often varies slightly between studies. Whilst post-mortem studies often used causes of death (such as complications due to AIDS) and previous sexual history, modern imaging studies require patients to self-report their own sexual identity on a ‘Kinsey Scale’, first conceived by psychologist Alfred Kinsey. Scoring between 0 and 6, a score of 0 equates to ‘maximally heterosexual’ and 6 ‘maximally homosexual’. To ensure proper selection into correct categorical groupings, participant interviews are also often conducted (Swaab, 2008).

Division into four distinct subject groups based on these scores – heterosexual men (HeM), homosexual men (HoM), heterosexual women (HeW) and homosexual women (HoW) – are common features in most modern studies, and is paramount in discerning patterns of activity related to sexual orientation. While a category dedicated to bisexuality and other sexual identities can be included, these other sub-division of human sexuality are often omitted, and this continues to be a limitation in the study of sexual orientation. Based on groupings, subjects are then exposed to stimuli based on the sexual preference in their grouping.

Generally, the stimulus is of a sexually explicit or arousing nature, which is of course effective in creating the desired sexual response. In some studies, even putative pheromones were utilised (Savic et al, 2005). Early imaging experiments used functional MRI scans to acquire images from volumes of interest (VOIs) using T1-weighted scans, in which shorter repetition times (TR) and time to echo (TE) are used to produce the 3-D T1-weighted images (Savic and Lindström, 2008). Statistical values, such as paired t-tests and linear regression models are also generally applied to calculate and adjust value variability (and thus comparability) of the voxels showing activation. The result of this process is clear, generally high-resolution images that can show distinct activation patterns in brain regions in relation to the sexual stimuli presented. This would allow for comparisons within the same areas across multiple participants of differing sexual orientations. Positron Emission Tomography (PET) was also utilized in earlier imaging studies. In these studies, relative cerebral blood flow (rCBF) was measured using a [15O]H2O blood tracer (Kilpatrick at al, 2006). Normalized CBF could then be compared within the VOIs to visualize activation patterns and dimorphisms, with a prominent example from Kilpatrick et al using PET to examine cerebral asymmetry in the amygdala in HoW compared to HeW and HeM.

Cerebral Sex Dimorphism Imaging As stated, fMRI paved the way for in vivo imaging of the neural correlates of sexual orientation. As such, it was now possible to image whether certain sexually dimorphic features in the brain may differ between individuals of the same sex but different sexual orientation. Firstly, a clear target for this was simply to look at hemispheric symmetry. In a study of 90 subjects, with 25 HeM and HeW, and 20 HoM and HoW, magnetic resonance volumetry was used to analyze the hemispheres in a whole-brain analysis. Fifty also engaged in PET cerebral blood flow study. The stimuli in both cases were sexually explicit images and videos tailored to the preferences of the subject group. HeM and HoW showed a ‘rightward’ cerebral asymmetry, whereas volumes of the cerebral hemispheres were generally symmetrical in HoM and HeW.

Homosexual subjects also displayed sex-atypical amygdala connections. In HoM, as well as in in HeW, the connections were more widespread from the left amygdala; in HoW and HeM, on the other hand, from the right amygdala (Savic and Lindström, 2008). The results of these are illustrated in Figure 2. The same relation of activity can be seen in the hypothalamus upon the exposure to certain pheromones; sex-differentiated activation of the anterior hypothalamus in HeM and HeW and a sex-atypical, reversed, pattern of activation in HoM and HoW (Savic et al, 2006). These findings added in vivo evidence and connectivity for a neurological basis of sexual orientation. This further gives rise to a dimorphism that is applicable for sexual orientation that isn’t related to reproduction or sexual function.

Despite being useful in theorizing neural development according to encoded preferred sexual stimuli (with HeW and HoM showing synonymous patterns), it doesn’t necessarily provide a visible ‘circuit’ for sexual orientation. Regardless, it is now becoming clear that there is a key difference in the way that heterosexual and homosexual individuals of the same assigned sex process (for example, visual) sexual stimuli, showing that one’s sexual orientation (however it may be acquired) likely has a profound effect on neural development and processing.

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