A neural circuit encoding sexual preference in humans

Highlights

• Identification of a core neural circuit using meta-analytic remodeling.

• Sexual preference is encoded by phylogenetically old, subcortical brain structures.

• Hypothalamus, thalamus, septal area, and para-/hippocampus control sexual preference.

• Substantia innominata regulates sexual non-preference.

Abstract

Sexual preference determines mate choice for reproduction and hence guarantees conservation of species in mammals. Despite this fundamental role in human behavior, current knowledge on its target-specific neurofunctional substrate is based on lesion studies and therefore limited. We used meta-analytic remodeling of neuroimaging data from 364 human subjects with diverse sexual interests during sexual stimulation to quantify neural regions associated with sexual preference manipulations. We found that sexual preference is encoded by four phylogenetically old, subcortical brain structures. More specifically, sexual preference is controlled by the anterior and preoptic area of the hypothalamus, the anterior and mediodorsal thalamus, the septal area, and the perirhinal parahippocampus including the dentate gyrus. In contrast, sexual non-preference is regulated by the substantia innominata. We anticipate the identification of a core neural circuit for sexual preferences to be a starting point for further sophisticated investigations into the neural principles of sexual behavior and particularly of its aberrations.

Introduction

Sexuality is a central component of human behavior. In both animals and humans, ⿿nature displays an interesting range of sexual behaviors, some of which may offend some of us⿿ (Gross, 2014). These behaviors are significantly affected by individual sexual preferences. In humans, sexual preferences refer to the favored way of reaching orgasm and to corresponding preferred sexual activities or preferred types of sexual partners (Langevin, 1983, Quinsey, 2003). These preferences hence reflect the ultimate choice of a sexual activity/partner over another that one would make (Bailey, 2009). Albeit often conflated, researchers make efforts to distinguish between sexual preference and sexual orientation. While sexual orientation is considered a ⿿stable and enduring internal preference for same- versus opposite-sex sexual interactions and partnering⿿, sexual preference is assumed to represent ⿿the manifestation of behavioral choices rather than a stable internal predisposition⿿ (Bailey and Zuk, 2009). Yet, the nomenclatural shift from sexual preference to sexual orientation has also been challenged. Particularly, it has been noted that it may overemphasize biological determination while neglecting psychological and sociocultural dimensions, but on the other hand also disregard that ⿿choices are seldom if ever entirely volitional⿿ (De Cecco and Parker, 1995). The debate on definitions seems heated at times, and it has been noted that a consistent definition of sexual orientation is still lacking (Moser, 2016). Nobody may disagree that hetero- and homosexuality represent sexual orientations (Moser, 2016). However, the notion of, for instance, asexuality (Bogaert, 2015) and pedophilia (Seto, 2012) as sexual orientations or the consideration of absence of sexual orientation in women (Bailey, 2009) are highly controversial. This mini-review is not limited to same-sex and opposite-sex preferences (i.e., sexual orientation) but includes also sexual preferences relating to other variables such as age (i.e., disorders of sexual preference). Therefore, it employs the term and refers to sexual preference as the preferred way of reaching orgasm concerning particular sexual activities or types of partners (Langevin, 1983, Quinsey, 2003).

Evidence for influence of epi-/genetic mechanisms but also of emotional maternal bond have fueled the controversial debate over the origin of sexual preferences, which has centered on the nature vs. nurture dichotomy (Hamer et al., 1993, Kendrick et al., 1998, Liu et al., 2011, Majerus et al., 1982, Ngun and Vilain, 2014). A quasi intermediate model between the ⿿nature⿿ and ⿿nurture⿿ view on the basis of genetic, hormone, and birth order studies proposes that sexual preference in humans may be stipulated in neural circuitry during early fetal development (Rahman, 2005). It has therefore been advocated for a future focus on elucidating ⿿the fundamental neural architecture underlying the target-specific direction of human sexual orientation⿿ (Rahman, 2005). A postmortem study had reported that the interstitial nuclei of the anterior hypothalamus (group 3; INAH 3) were twice as large in heterosexual men as not only in heterosexual women but also in homosexual men (LeVay, 1991). The inferred thesis of neuroanatomical sexual dimorphism being a biological substrate for sexual preference was further tested using modern neuroimaging techniques. Positron emission tomography (PET) and magnetic resonance imaging (MRI) showed sex-atypical (i.e., opposite-sex-like) cerebral asymmetry and functional connections (of the amygdala) in homosexual subjects (Savic and Lindström, 2008). The findings of these pioneering experiments seem plausible, given that homosexual subjects⿿ sexual preference is similar to that of their opposite sex. The results however leave open whether these sexually dimorphic structures are significantly involved in the functional brain response to sexual stimuli that is specific to one⿿s sexual preference, i.e., the neural basis underlying its target-specific direction.

Notably, the only MRI study that explicitly aimed at unraveling the functional neural correlates of sexual orientation in humans found stronger neuronal response to preferred as compared to non-preferred visual sexual stimuli in the reward and motor system (including ventral striatum, centromedian thalamus, and ventral premotor cortex) but not in the suggested candidate regions (Ponseti et al., 2006). The data currently available regarding consistently recruited areas mediating sexual preferences hence seems contradictory and the initial question remains unresolved. When however reviewing the rich corpus of studies investigating human brain response to sexual stimuli, we noticed that a considerable proportion implicitly also assessed brain activations related to sexual preference by comparing preferred with relatively non-preferred sexual stimuli, which were used as control stimuli, in various subject groups. In other words, we became aware of the existence of an extensive data pool that seemed ideally suited for identifying neural regions associated with sexual preference manipulations when recapitulated and re-analyzed in this context.

This meta-analytic mini-review reassesses if sexual preference-related brain activity is actually found in regions where previous neuroanatomical studies located sexual preference-related changes in brain anatomy. The overlap and link between brain structure and function might serve as evidence that the candidate regions are indeed functionally involved in encoding sexual preference and related neuroanatomical variations not merely epiphenomena. Such spatial localization could provide further hints at the temporal manifestation of sexual preferences and confine the spectrum of neurotransmitters and receptors that regulate this aspect of personality (LeVay, 1991).