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Sex is primarily the process of combining male and female genes to form offspring, however over the past billion years complex systems of behaviour (and the motivation and reward circuits that root such behaviours) have evolved around this process and no where is this complexity more elaborately represented than in the human brain. At some point in their life, everyone will engage in sexual behaviour or at least experience sexual desire. Ultimately the brain is the largest sex organ controlling the biological urge, mediating all thoughts, experiences and physiological responses to sex, so 'Where Does Sex Live in the Brain?'.

The article The Brain: Where Does Sex Live in the Brain? From Top to Bottom was published (2009) in the American popular science magazine 'Discover' and provides a brief examination of the neural basis of sex and sexual desire. Written by the general science writer and blogger Carl Zimmer it serves as a brief review of the origins of research into sex and provides a brief summary of modern neuroscience's attempts to pinpoint where sex lives in the brain.

The article begins with the summary of a number of case studies relating to individuals with abnormal manifestations of sexual behaviour related to abnormalities in their brains (e.g spontaneous organisms relating to epilepsy in the temporal lobe and abnormal sexual feelings resulting from brain tumours). Zimmer then moves onto to relay the findings from experimental studies, specifically brain imaging studies (including PET, fMRI and EEG recordings), related to understanding the neural underpinnings of sex.

The article is of interest as it serves to introduce the lay person into the hitherto unexplored neural terrain of sex, and
whilst many people are acutely aware of the more obvious physiological manifestations of sexual desire, few are aware of the neurobiological and neuroanatomical mechanisms that underpin it.

1. Neuroscientific Context

Sexual desire is defined as the behavioural drive that motivates individuals to fantasize about or seek out sexual activity. In contrast, sexual arousal is defined as the autonomic physiological processes that prepare the body for sexual activity (Toledano, Pfaus., 2006). It is important to make clear distinctions between the two definitions as confusion can occur due to, the often simultaneous occurrence of both mechanisms (Pfaus., 2009).

Sexual desire is the culmination of several different neural mechanisms, each is controlled in different areas of the brain and is activated at different times of the sexual experience. The euphoric and pleasurable experience of sex stems primarily from the limbic system. The colloquial term for areas including the amygdala, hippocampus and limbic lobe (dentate and cingulate gyrus). This area is common to all mammals and is considered one of the oldest areas of the brain. It regulates emotion and encourages the avoidance of painful of aversive stimuli and the repetition of pleasurable experiences.

From a physiological perspective sexual arousal is controlled by the parasympathetic portion of the autonomic nervous system and manifests itself as vasodilation in sexual organs along with several other physiological phenomena including an increase in heart rate. An orgasm and in particular male ejaculation is controlled by the sympathetic portion, this is also accompanied by deactivation of many areas in the brain relating to external stimuli in particular fear, allowing the mind to focus on the task at hand.

1.1 Testosterone and Oestrogen

Sexual desire is initially modulated by the release of sex hormones, for males testosterone and for females oestrogen, our levels of these hormones are understood to affect our behaviour. Recent studies how found that male testosterone levels increase by approximately 7.8% in males even though they do no consider her attractive. (van der Meij, 2011)

Testosterone, a member of the androgen family of steroids, is secreted in the testes of males and the ovaries of females as well as small amounts from adrenal glands. Arousal causes the cerebral cortex to signal the hypothalamus to stimulate the production of testosterone, the production is regulated by a complex chain of events known as the hypothalamic-pituitary-gonadal axis; Gonadotropin-releasing hormone (GnRH) is secreted by the hypothalamus, via the hypophyseal portal system, it travels to the anterior pituitary which then releases luteinizing hormone (LH) in order to stimulate the production of testosterone in the testes. Production levels are controlled by negative feedback.

Luteinizing hormones also stimulate the production of oestrogen in the ovaries, some oestrogens are also produced in other tissues such as the liver and adrenal glands. In females, oestrogen synthesis begins in cells in the ovaries by the synthesis of androstenedione, this compound then travels into the surrounding granulosa cells of the basal membrane where it is converted to oestrone or oestradiol, testosterone is also converted to oestradiol at this point.

1.2 Amygdala

Prior to the physical stimulation, comes sexual desire. Largely mediated by emotion through the limbic system, activation of the amygdala can trigger penile erection, sexual feelings,(Georgiadis and Holstege, 2005) sensations of extreme pleasure (Olds and Milner, 1954), memories of sexual intercourse (Gloor, 1986), as well as ovulation, uterine contractions, and orgasm.

The amygdala is sexually differentiated, males on average have a 16% larger cortico-medial area which is the area responsible for steroid uptake, specifically the male and female sex hormones testosterone and oestrogen. These are known to produce sex specific behaviours (Rhawn J, 2004). Males more then females, were found to have greater amygdala activation when presented with a sexually pleasing, visual stimuli (Hamann et al., 2004).

An increased density of enkephalins and opiate receptors can be also found in amydala. When experiencing a craving for pleasure inducing drugs these receptors becomes active. (Childress et al, 1999). This gives the amydala an ability to inducing extreme feelings of pleasure as well as motivating pleasure seeking behaviour.

Several case studies of subjects with lesions or tumors in areas proximal to the amygdala illustrated aggressive tendencies, became sexually preoccupied and experienced hyper religiosity thoughts similar to Kluver Bucy syndrome. (Devinsky, Sacks and Devinsky, 2010).

The amydala projects through three pathways to many areas of the brain, the stria terminalis, the amydalofugal pathway and the anterior commisure.These pathways influence hormonal and somatomotor aspects of behaviour and also emotional states. There is also increasing evidence that the central nucleus of the amygdala is responsible for pheromone detection given a large number of olfactory projections.

The amygdalofugal pathway connects the corticomedian nuclei of the amygdala with the thalamus, median hypothalamus, brain stem and nucleus accumbens. This pathway is thought to be responsible for pleasurable feelings. The stria terminalis has projections to and from the hypthothalamic-pituitary-adrenal axis and is thought to mediate threat monitoring and the stress response. It is thought to be responsible for sympathetic nervous system activation. The anterior commisure serves to connect the left and right amygdala. In a 1992 (Allen and Gorski) study it was thought to correlate to the sexual orientation of an individual as it was posited that male homosexuals had a anterior commisure more similar to a womans however this yet to be adequately supported by evidence.

1.3 Ventral striatum

Input travels from the basolateral nuclei of the amygdala along the amygdalofugal pathway to the ventral striatum, made up of the nucleus accumbens, putamen and parts of the caudate nucleus. The nucleus accumbens plays a role in pleasure and reward due to a large large of dopaminergic neurons from the VTA (ventral tegmental area).
Gert Holstege (2003) using Positron Emission Tomography measured cBF in males during orgasm and found "primary activation was found in the mesodiencephalic transition zone, including the ventral tegmental area......Parallels are drawn between ejaculation and heroin rush."

1.4 Orbitofrontal Cortex

The orbital frontal cortex (OFC) is located on ventrally along the frontal skull and superior to the orbits of the eye. The OFC has a large network of connections that project to a variety of areas in the brain, examples include; all somatosensory modalities, hippocampus, ventral tegmental axis and amygdala. The OFC has structural variability amongst individuals, three sub types have been identified; each sub-types contain different sulci locations (Kringelbach, Rolls., 2004). This is significant as disorders could potentially be linked to genetic factors due to the differences in each subtype.

In contrast to many other cortical regions, the OFC is still poorly understood. Currently it is understood that higher cognitive functions occur in this area, in particular, sensory integration "representing the affective value of reinforcers in expectation" and judgements based on reward and punishment (Kringelbach., 2005)

Orbitofrontal cortex shown in red

In terms of sexual desire, the OFC is thought to mediate reward and punishment and personal assessment, however. This relates to mate selection to whether an individual is perceived as desirable (Spinella., 2007). Evidence through studies into facial attractiveness and those involving males presented with a sexually attractive visual stimuli both support the OFC involvement in this role (O’Doherty et al., 2003, Stoleru.,2003).

Representing the reward value of sensory stimuli, beautiful faces andthe affective value of reinforcers in expectation (Ishai, 2007). The OFC is responsible for the disassociation of rewarding, adaptive value of a face can be disassociated from that of an aesthetically pleasing one. In effect mediating beauty for members of the opposite sex. Other functions of the OFC also include managing expectation, particularly based on memories modulated by projections from the hippocampus. These decisions, emotional states and perceived consequences are then used to modulate sexual desire and its related physiological responses

Patients with non functioning neurons in the medial orbitofrontal cortex were shown in several studies to have an increased sex drive and an inability to control their response to sexual stimuli, in extreme cases leading to hyper sexuality, drug use, gambling and an inability to empathise.

1.5 Vagus Nerve

Barry Komisaruk and Beverly Whipple researched the phenomenon that is the orgasm in women, notably those who suffer from spinal cord injuries, to determine if there is a neural pathway from the genitals to the brain. In studies that included both upper level injuries (i.e. injuries that have affected T10 and above) and lower level injuries (i.e. injuries that have affected below T10) it was shown that it was possible for these women to perceive sensations in response to self stimulation of their genitalia. Along with this evidence, the women also reported discomfort during their menstrual cycle and those who were pregnant perceived uterine contractions. It was proposed that these sensations were taking a path to the brain that does not go via the spinal cord, that is the Vagus nerves.

The Vagus nerve is known to lead to the Nucleus Tractus Solitarii (NTS) in the Medulla Oblongata. Using Functional Magnetic Resonance Imaging (fMRI) Komisaruk and Whipple implemented a prior experiment (a sweet-salty-sour-bitter taste test) to stimulate the NTS to show its activation pattern. It was hypothesised that with self stimulation the NTS would activate, thus showing that the Vagus nerves are the path taken to the brain, bypassing the spinal cord (Whipple, 2008). Following this stimulation of the brain via the vagus nerve during orgasm there was a difference in activity between preorgasm and orgasm. Areas of activation during and after orgasm include the hypothalamic paraventricular nucleus (PVN), midbrain central gray, amygdala, hippocampus, anterior cingulate, frontal, parietal, temporal and insular cortices, anterior basal ganglia, and cerebellum (Whipple, 2008). Although this may be the explanation for female orgasms, there is no evidence to suggest that this is the case for males.

1.6 Disorders

Sexual disorders involve a change in sexual desire, sexual orientation and/or ability to orgasm due to damage related to respective neural areas. The two main disorders relating to sexual desire are hyposexual desire disorder (HSDD) and hypersexuality.
Sexual disorders can occur in isolation or can occur alongside a change in general behaviours (Baird et al., 2007). The causes of sexual desire disorders vary, but some may include a decrease in the production of oestrogen in woman or testosterone in both men and women, while others are related to physical damage to neuroanatomical structures.

Hypoactive Sexual Disorder (HSDD) is characterised in an individual by low to zero levels in desire for sexual activity or sexual fantasy without cause from drug abuse or medical conditions (with the exception of sexual dysfunction (Beck., 1995) Abnormality in either the medial orbitofrontal cortex (Stoleru et al., 2003) or damage to particular limbic structures can cause HSDD to occur (Baird et al., 2007). In males, greater activation of the gyrus rectus within the medial orbitofrontal cortex while observing sexually visual pictures have been been strongly linked to HSDD (Stoleru et al., 2003). Other causes of HSSD usually involve bilateral damage of hypothalamus or bilateral damage of the temporal lobes, including the amygdala (Baird et al.,2007).

Hypersexuality can be considered to be the opposite to hypoactive sexual disorder, however this is insufficient for a definition (Kaplan., 2010). What constitutes as too much sex? This question is difficult to answer, however a definition can be constructed based on what is characterised as hypersexuality, according to the DSM-V manual. Hypersexuality can be defined as; an increased desire for sex that creates a negative impact in meeting social commitments and or personal development in the suffering individual (Kafka., 2009).

Evidence has been found that hypersexuality occurs more often in those that suffer lesions in the right hemisphere of the brain as opposed to the left hemisphere (Suffren et al., 2011), even though these particular hypersexuality cases are rare. The lesions are located in the temporal lobe. It has to be noted that this hypersexual activity was not exhibited by any of the patients prestroke and this condition is not gender specific (Monga et al., 1986), however there are far more cases in males than in females. Dopaminergic agonists that are used to treat diseases such as Parkinson's Disease have also been known to cause hypersexual characteristics in about 4% of patients. This could be due to the increased interaction between dopamine and dopaminergic receptors increasing the activity (Park and Stacy, 2011).

Dean Hamer a scientist at the cancer institute published a book titled the science of desire exploring correlations between genetic factors and people's sexual preferences. Controversially he found genetic predictors of homosexuality, increased "risk taking" behaviour related to dopamine genes and high levels of sexual desire due to the anxious form of the serotonin trantroporter gene.

2. Analysis of Quality

The article was published in the general science magazine 'Discover' magazine and the prevalence of simplified concepts, condensed findings and accessible language suggests thats its target readership is the general public. Although it lacks the technical detail and subject expertise of a journal article, it does accomplish in providing a context and conveying many nuanced neuroscience concepts in understandable terms without over simplifying them. This allows a non-proffesional reader to engage in the article without having to have any prior knowledge. The title 'Where does sex live in the brain? From top to bottom' is perhaps a slight sensationalism (there is nothing in the article that comes close to a coherent answer as to where sex 'lives' in the brain), however the body of the article is not as ambitious as the title, and tends to remain objective. Hence the neuroscientific quality of Zimmer article is very much reliant on the merit of the studies which he refers to. The studies he refers to are all well substantiated and reputable, however he has selected a rather narrow range of studies and failed to include a large body of work in his article. This is failure of acknowledgment is perhaps due to practical constraints (i.e. not having enough time or space to adequately summarise the entire body of neuroscientific inquiry into sex and sexual desire).

The author does not present any information as his own but instead tends to simply relay the findings from published neuroscientific studies. As with many emerging fields within neuroscience there is much uncertainity and the author does well not purvey a false sense of absolutism or certainty, instead he hedges his language with caution (e.g. 'may indicate', 'perhaps means', 'suspects that') and is careful to disclaim any data or conclusions as conclusive (e.g. 'we still have a lot to learn about sex', 'many details of how it unfolds still quite obscure'). Furthermore, the eclectic structure of Zimmer's article does well to emphasise that the research on this topic is coming from different perspectives and from different labs, and that perhaps contrary to public belief scientific progress is a rather steady and fragmented process. Zimmer fails to draw any 'unified' conclusions about 'where sex is in the brain', however perhaps this incoherence is ultimately a reflection on the state of the neuroscience in relation to sexual desire, rather than on the quality of his authorship.

3. Appendix

3.1 Search strategy

From the general readings of members of the group, several interesting articles that had been recently read were initially debated and subsequently discarded before settling upon one discussing the neurological benefits of running.

On the date of article submission, several members of the group felt a more entertaining topic for further study could be found. After searching through several respected journals and blogs looking for articles related to oxytocin it was decided that the neuroscience of sex would be both unusual, interesting and the prevalence of articles discussing it would allow for a solid choice.

Ultimately the article was chosen for several reasons, the respectability of the Discover magazine, the obvious neuroscience references and the curiosity that it piqued among members.

The search for background validation of the article focused on peer reviewed journals, as peer reviewed journals are generally the most reliable and objective source of evidence driven information. However on occasion pop articles were consulted that referenced cutting edge work being done as in the case of Holstege fMRI of couples having sex.

4. References

Allen L and Gorski R. (1992) Sexual Orientation and the size of the anterior commissure in the human brain. National Academy of Science USA 89(15) 7199-7202.

Baird, A.D., Wilson, S.J., Bladin, P.F, Saling, M.M., Reutens, D.C., (2007) Neurological control of sexual behaviour: insights from lesion studies. Journal of Neurology, Neurosurgery & Psychiatry, 78, 1042-1049

Beck, G.J.,(1995) Hypoactive Sexual Desire Disorder: An Overview, Journal of Consulting and Clinical Psychology,63, 919-927

Devinsky J, Sacks O, Devinsky O. (2010) Kluver Bucy Syndrome, hypersexuality, and the law. Neurocase, 16(2) 140-145

Discovery channel "The Science of Lust"

Georgiadis J, Holstege G. (2005) Human Brain activation during stimulation of the Penis. Journal of Comparative Neurology. 493:33-38

Gloor P. (1986) Consciousness as a neurological concept in epileptology: a critical review. Epilepsia 27:s14-26.

Hamann S, Herman R, Nolan C, Wallen K. (2004) Men and Women differ in amygdala response to visual sexual stimuli. Nature Nueroscience. 7(4). 325:6

Holstege G, Georgiadis J, Paans A, Meiners L, van der Graaf F, Reinders S. (2003) Brain activation during Human Male Ejaculation. The Journal of Neuroscience, 23(27):9185-9193

Ishai A. (2007) Sex, Beauty and the Orbitofrontal Cortex. International Journal of Psychophysiology. 63 181-195

Kringelbach, M.L., (2005). Review of The human orbitofrontal cortex: Link reward to hedonic experience. Nature, 6, 691-702

Kringelbach, M.L., Rolls, E.T., (2004). The functional neuroanatomy of the human orbitofrontal cortex: Evidence from neuroimaging and neuropsychology, Progress in Neurobiology, 72 , 341–372

O’Doherty, J., Winston, J., Critchley, H., Perrett, D., Burt, D.M., Dolan, R.J., (2003). Beauty in a smile: the role of medial orbitofrontal cortex in facial attractiveness. Neuropsychologia , 41, 147–155.

Olds, J., Milner, P. 1954. Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain.J.Comp. Physiolo. Psycholo. 47, 419–427
Pfaus, J.G., (2009) Review of Pathways of Sexual Desire. The Journal of Sexual Medicine, 6, 1506-1533

Rhawn J (2000) Amygdala. Neuropsychiatry, Neuropsychology, Clinical Neuroscience
(Academic Press, New York)

Spinella, M., (2007). The role of prefrontal systems in sexual behaviour. International Journal of Neuroscience, 117,369–385

Toledano, R., Pfaus J., (2006) The Second Arousal and Desire Inventory (SADI): A Multidimensional Scale to Assess Subjective Sexual Arousal and Desire. The Journal of Sexual Medicine, 3, 853-877

Van der Meij L, Almela M, Buunk A, Fawcett T, Salvador A. (2011) Men with elevated testosterone levels show more affiliative behaviours during interactions with women. Proceedings of the Royal Society of Biological Sciences.

Whipple. B. (2008) Functional Magnetic Resonance Imaging (FMRI) during Orgasm in Women. Sexologies.

Zimmer, Carl. (2009) The Brain: Where Does Sex Live in the Brain? From Top to Bottom. Discover Magazine, October 2009 Issue.