FMRI and Bisexuality

Individuals who identify as bisexual have been overlooked in investigations for much of the short time dedicated to examining sexual orientation through neuroimaging. Exploring neural responses in subgroups of the population who are not 'monosexual' is critical to studying a topic that involves examining variations in sexual identities across the population. In one study, men who identified as homosexual, heterosexual, and bisexual were exposed to sexually explicit images and videos of men, women, and same-sex couples. This time, a region of interest analysis was carried out on the ventral striatum, specifically within the nucleus accumbens section.

This region has been identified as one that selects actions based on relative valuations, giving it an association with reward and motivation. In the fMRI study, T2*-weighted images were collected, which are created using MR sequences with gradient echoes. To tailor this specific study to allow for the identification of a bisexual orientation, a voxel-wise calculation of the absolute difference in the data values between the response to male-centric stimuli and female-centric stimuli was required to show a preferential response. As seen in Figure 3, the expected outcome of homosexual and heterosexual men showing greater ventral striatum activity to their preferred stimulus was observed. Bisexual individuals, on the other hand, showed no significant preferential activation pattern (Safron et al., 2017) to male vs. female stimuli. Although this investigation is somewhat more limited in scope compared to analyses focused on homosexual or heterosexual orientations, it does provide empirical evidence of a potential neurological basis for bisexuality, which could potentially guide further exploration.

Sexual Orientation Neural Circuity: A meta-analysis

The potential of modern imaging techniques stretches beyond simply looking for dimorphisms in brain structures between a small number of subjects. From the late 2000s onwards, many researchers exposed participants to a variety of both sexual and non-sexual stimuli in an attempt to better understand sexual orientation. A conglomerate of 17 such studies (with hundreds of participants of varying sexual orientation identities), all of which were either MRI or PET imaging in nature, was created to see the overlap in the structural correlates believed to be involved in sexual orientation (Poeppl et al., 2016). To carry this out, researchers used a version of the Activation Likelihood Estimation (ALE) algorithm used in computational neuroscience to create a co-ordinate based meta-analysis of neuroimaging data (Eickhoff et al., 2012). Essentially, this algorithm is able to identify areas (voxel-wise) with a convergence of activated coordinates across experiments that is higher than expected from a random association in space. The result of this meta-analysis can be seen in Figure 4. Fascinatingly, the results of this meta-analysis identified a neural circuit encoding sexual orientation that is exclusively confined to phylogenetically-old, subcortical structures (with no regions of the neocortex being highlighted by the analysis). Specifically, that analysis identified that sexual preference is controlled by the anterior area of the hypothalamus (which agrees with numerous previous studies), the thalamus (anterior and mediodorsal regions), the septal area, and the dentate gyrus.

Previous studies of these areas help reinforce this finding. Damage to the dentate gyrus and anterior hypothalamus have been seen to distort sexual drive in humans, as well as the acquisition of altered sexual preferences (Baird et al., 2008). Lesion studies have also revealed that the regions of the thalamus highlighted by the meta-analysis may be implicated in mate selection (Müller et al., 1999). As such, the outcome of this synthesized imaging data adds to the thesis outlined that sexual preferences and mate selection (and hence sexual orientation) are strongly anchored in a set, biologically-controlled neural circuit.

Link to Endocrinology and Genetics

By now, it is clear to see that neuroimaging has been paramount in establishing that there is a strong likelihood of a developed neural circuit that can encode for human sexual orientation. Yet, how (and by what mechanism) are the biological measures put in place to result in the acquisition of sexual orientation before sexual maturity and adulthood? Enduring theories point to prenatal or neonatal steroid levels being responsible, with strong reference to fetal androgen levels presumably being lower than 'normal' in homosexual men (Morris et al., 2004). Studies of the sexually dimorphic nucleus (SDN) in sheep, however, have taken this theory further. It was observed that the ovine SDN (oSDN), a cluster of neurons involved in expressing cytochrome P450 aromatase, was over twice as large in rams that were 'female-oriented' in their choice of mate as opposed to 'male-oriented' rams (Roselli et al., 2004). In addition, these male-oriented rams exhibited an oSDN volume closer to that of ewes than their own female-oriented counterparts. As such, a link can be made involving the relationship between the aromatase enzyme, which converts testosterone into estrogens, and neuroanatomy, namely the SDN (which includes the anterior hypothalamus). As this enzyme has been seen to 'masculinize' the brains of rats and cause traditionally 'masculine behavior', it could provide a model for explaining the neural circuitry discovered of a sexual preference (for males) that is seen in heterosexual females (Morris et al., 2004).

Similarly, genetic analyses have sought to understand the phenomenon of male homosexuality as well. Female mice have been seen to lose their typical 'female behavior', such as lactation and maternal aggression, when a gene encoding a neuronal ion channel (TRPC2) has been knocked-out (Dulac et al., 2007). In fact, these females began to exhibit characteristic male sexual and courtship behaviors such as mounting, pelvic thrust, solicitation, and anogenital olfactory investigation. This implies that functional neuronal circuits underlying male-specific sexual behaviors exist in a normal female mouse brain, again being a candidate for an explanation for the dimorphic patterns seen.

Possibilities for Future Study, Limitations and Uses

Biological research related to sexual orientation in humans still seems to be only just gaining momentum, but the evidence already shows that humans have a vast array of neural differences, not only in relation to assigned sex but also sexual orientation. This exploration of findings from advancement in neuroimaging gives rise to the idea of a visible, innate neurobiological circuit appearing to be responsible for sexual orientation for humans. Sexual dimorphism appears to be a key in understanding this – with homosexual men continually showing similarities to heterosexual women in neural structure, function, and (a)symmetry. Comparable patterns can be seen in animals, and investigations into the hormonal and genetic causes of sexual orientation acquisition appear to be tightly linked with the innate neural circuit that has been found. One of the major strengths in neuroimaging studies of sexual orientation – in the fMRI studies presented as well as in post-mortem studies - is that they have been human-specific. These mechanistic studies, however, have only been carried out in animals. It is easy to understand why - generally knock-out experiments are needed, and it is entirely unethical to potentially hijack a healthy human’s sexual development. Moving forward, however, genetic, or hormone/steroid factors must be (safely) investigated further in areas known to display sexual (and sexual orientation) dimorphism to evaluate a potential link in humans. For instance, it could be possible to study androgen concentration in the SDN in humans in relation to sexual identity.

As this investigation (based on current literature) has outlined, the majority of studies are primarily focused on men. Even then, there are mostly inquiries into the differences between strictly heterosexual and strictly homosexual men. As such, there is a vacancy in the literature for understanding female homosexuality and bisexuality to the same extent as male homosexuality. This needs to be filled to come closer to understanding the neural basis for the various complex facets of human sexual identity.

Beyond the societal benefits of eliminating claims of sexuality being “chosen” or not having a biological basis, using fMRI to understand sexual orientation also creates possibilities in the field of neuroimaging beyond understanding its own nature. Psychological and medical studies can show correlations of conditions with those of certain sexual orientations, and understanding overlapping activity patterns could shed new light on these areas. A study in 2018 found that non-heterosexual individuals may have a higher risk of psychiatric morbidity, including increased instances of bipolar disorder in lesbian women (Abé et al., 2018). With mounting evidence for sexual orientation-related brain differences, this raises the concern that sexual orientation may be an important factor to control for in neuroimaging studies of neuropsychiatric disorders.

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