Growing up in Los Angeles in the 1970s, I gradually came to realise that my father was not the stereotypical psychoanalyst. Yes, he had an office with enigmatic modern art on the walls, copies of The New Yorker in the waiting room and the requisite analytical couch. It’s true that said couch had a wedge-shaped pillow designed for the client to assume the supine posture so frequently portrayed in the cartoons from those same issues of The New Yorker. And, during psychoanalytic sessions, my father did indeed perch in a black leather Eames chair, notebook in hand. But beyond those trappings, he had the sceptical and logical mind of a physician (in those days, nearly all psychoanalysts were, like my father, MDs).
Starting when I was a small child and continuing until I left for university, my father and I would eat dinner together at one of several local restaurants every Wednesday night. Over matzoh ball soup at Zucky’s Delicatessen, we’d discuss anything and everything, including the progress of his psychoanalytic clients (with names and identifying details omitted of course). It was an odd way to grow up and I loved it. In our Wednesday night case studies, there would be the expected psychodynamic talk of dream interpretation and early childhood experiences, but it was all tempered by what would come to be known as neuroscience. He would say that, when the talking cure worked (as it did for most of his clients), it did so not in the nebulous realm of id, ego and superego, but rather by changing the cellular and molecular structure of the brain.
In some cases, he dispensed, not just with psychoanalytic theory, but with any form of talking cure. I remember one particular night when I was in middle school when he was delighted to realise that a client’s persistent and unrelenting depression was not rooted in a tormented childhood or conflicted sexuality. Instead, it was a direct consequence of thyroid hormone deficiency and hence best treated with a simple pill. As I grew older, I came to admire his flexibility and breadth of intellect in these matters. He encouraged me to follow in his footsteps and become a doctor, maybe even a psychiatrist, but I knew that would be a poor choice for me.
‘It wouldn’t work. I’m not as empathetic as you, Dad. In fact, sick people kind of annoy me.’
‘Then you could be a pathologist,’ was his reply.
Like my father, I longed to understand human mental life. But, unlike him, I came of age in an era when biological understanding of brain function was beginning to gain some traction. And so, I took a different path towards the same goal and became a neuroscientist, working at the level of molecules and cells in the brain.
Nothing in psychoanalytic theory evoked more scepticism in my father than Sigmund Freud’s conception of sexual sensation and orgasm. Yes, father and son would discuss Freud’s key theory of immature clitoral orgasms transitioning to mature vaginal orgasms in female development. ‘It’s unmitigated bullshit!’ he’d say, his voice rising. ‘No medical evidence exists for this idea at all!’ It’s not surprising that the servers at Zucky’s would give us a wide berth. To make up for it, he tipped well.
Sexual sensation is absolutely central to both our shared human experience and our individual quirks and kinks. It’s exactly the sort of topic that has traditionally had lots of behavioural observation and theorising attached to it (including by psychoanalysts). There’s no question that sexual sensation is sculpted by early life experience. Yet it’s also embedded in a biological matrix, with brain regions and nerve bundles and special molecular machines specialised to transduce pressure on the skin into what is, ultimately, erotic sensation. It’s one of many places where psychology and biology meet.
Stimulation of the female genitals activated the groin and, oddly, an area adjacent to the representation of the toes
Until very recently, biology had rather little to bring to the table, and our understanding of sexual sensation had been shockingly incomplete. We have known for some time that touch sensations from the genital region pass through four different nerves on their way to the spinal cord and, ultimately, the brain. Of these, the pudendal nerve is the most important for sexual sensation, carrying signals from the clitoris in cisgendered women and the penis in cisgendered men. In women, the pelvic nerve conveys touch signals from the labia minora, the vaginal walls, the anus and the rectum. In men, the pudendal nerve carries information from the anus and the scrotum as well as the penis. In women, sensations from the cervix and the uterus can also be conveyed by the hypogastric nerve as well as the vagus nerve, which travels directly to the brain stem, thereby bypassing the spinal cord entirely.
Touch signals from the pelvis ultimately arrive at the outer rind of the brain, a region called the neocortex, where they are represented in a distorted and fragmented body map in the primary somatosensory region. You’ve probably seen drawings of these body maps with giant hands and feet and relatively small torsos, corresponding to the density of certain types of touch sensor in the skin. In one study, women with their heads in a brain scanner were given a handheld dildo and asked to self-stimulate various genital regions – the external clitoris, the vagina and the cervix.
Stimulation of the female genitals activated two completely different spots in the neocortical body map: one just where you might expect, at the groin; and another, a bit oddly, adjacent to the representation of the toes. It turns out that men also have this dual mapping of the genitals. More generally, it raises the issue of whether this particular toe-adjacent bit of the primary somatosensory cortex (called the mesial surface of the postcentral gyrus) has a special role in sexual touch. Some people have even speculated that this particular toe/genital adjacency in the brain somehow underlies foot fetish sexual behaviour (I’m not convinced).
Disappointingly, if you were to examine a microscope slide prepared from postmortem tissue of this area of the brain, you’d find nothing unusual about it. The individual neurons and their overall layered structure look almost the same as those in regions processing touch information from less erotic parts of the body. So, despite some tantalising hints, the biology of what makes touch on some parts of the skin feel sexy while other parts not has remained a mystery. Only now, with a recent publication from David Ginty’s and Stephen Liberles’s groups at Harvard Medical School, are some real answers emerging.
If you ask around or do a few spicy internet searches, you will find that there are people who feel a sexual sensation from being touched on nearly any part of the body. Still, while recognising the solid supporting roles of ears and feet and so on, the genitals are clearly the star of this show. In the right context, almost everyone – no matter their sex assigned at birth, their gender identity, their sexual orientation or the particulars of the early life experiences they might recount to a psychoanalyst – finds stimulation of the clitoris or the glans (head) of the penis to be sexually exciting. But how, through the course of evolution, have these body parts become sexual ground zero? Is there something special about the structure of the nerve endings in the penis and the clitoris and the way they ultimately convey electrical messages to the brain?
The story of the search for the biological basis of sexual sensation begins, even before Freud’s time, in Göttingen, Germany in 1860 when the anatomist Wilhelm Krause, using thin slices of cadaver tissue and a microscope, described a new type of structure in the skin consisting of the long, thin, information-sending portion of a neuron, called the axon, sometimes coiled up in a messy ball, surrounded by a capsule of non-neuronal cells, forming an oval or cylindrical shape. These tiny structures have come to be called Krause corpuscles and they were observed in the hairless skin of the penis and the clitoris as well as the lips, nipples and anus.
Perhaps the clitoris and the penile glans play such an important role in sexual sensation because they have a high density of this type of nerve ending. In fact, the clitoris has the highest density of Krause corpuscles of any tissue, while they are absent from the skin that forms the lining of the vagina. This distribution corresponds well with the relative contribution of these two regions to sexual sensation and potentially argues against Freudian notions of a purely vaginal orgasm in mature women. Similarly, within the glans penis, the greatest density of Krause corpuscles is found at the corona (the ridge that forms the edge of the glans) and the frenulum (the bit of elastic tissue on the underside of the glans). These are the locations on the penis that are often reported to be the most sensitive for sexual stimulation.
The clitoral Krause corpuscles showed greater sensitivity than the penile neurons
This anatomical distribution of Krause corpuscles has suggested that they are the cellular basis of sexual sensation, but this idea remained unproven for more than 160 years. One complication is that, while the genitals, lips, anus and nipples are all sexy locations, Krause corpuscles have also been found in less erotically charged body parts like the surface of the eyeball (the conjunctivum) and the lining of the finger joints (the synovium) which rarely figure in even the most obscure sexual kinks. Even more importantly, until just now, it has not been known what type of sensations the Krause corpuscles detect. Some nerve endings in the skin are specialised for responding to heat or cold or inflammation. Others are tuned to detect painful or itchy stimuli, while yet another group respond to various mechanical forces acting on the skin, like indentation, stretching or vibration. If the Krause corpuscles were truly involved in sexual sensation, then one would expect that they would be a part of this last group, called mechanoreceptors.
To reveal the location and function of Krause corpuscles, Lijun Qi, Michael Iskols, Jia Yin Xiao and Annie Handler of the Ginty lab and Rachel Greenberg of the Liberles lab used laboratory mice. By applying fluorescent antibodies directed against proteins in the nerve cell axons and some of the non-neuronal cells that form the Krause corpuscle’s capsule, they were able to count all of these structures within sections of genital tissue using a microscope. They found that male and female mice have almost the same total number of Krause corpuscles in the genitals but, since the clitoris is so much smaller than the penis, that the former achieved a 15-fold higher density of these nerve endings. In addition, the shape of Krause corpuscles in the clitoris was somewhat more complex and lobulated compared with those in the penis (some say they look like mulberries).
The lab investigators discovered that neurons terminating in the Krause corpuscles expressed two particular genes celled ret and TrkB. This realisation allowed them to identify the Krause corpuscle neurons and, using clever genetic tricks combined with sophisticated imaging techniques, to record their electrical signals in lightly anesthetised mice. When they gently stimulated the penis or clitoris using a paintbrush or a custom-made indenting tool, the Krause corpuscle neurons were electrically activated, with the clitoral Krause corpuscles showing greater sensitivity (they were activated with less pressure applied to the indenting tool compared with those from the penis). When a vibrating probe was used, both the clitoral and penile neurons were activated with even smaller forces. Interestingly, the optimal vibration frequency for activating these neurons was 40-80 Hz, which is almost exactly the range used in vibrating sex toys intended for people – a triumph of human factors engineering.
The findings showed that Krause corpuscles in the genitals are indeed mechanoreceptors. (If you want to hit on horny nerds at parties, you can tell them that these are a particular type, called A-fiber low-threshold rapidly adapting mechanoreceptors.) However, this still doesn’t prove that they are responsible for sexual sensation. To do that, the investigators employed further genetic and optical manipulations to directly activate Krause corpuscle neurons of the genitals without touching them (this involves causing the Krause corpuscle neurons to express a foreign protein that produces electrical activation when illuminated with blue light).
They found that activating neurons in the penis of male mice with said blue light produced an erection similar to that evoked by stimulation with a paintbrush or vibrator. Conversely, when Krause corpuscle neurons (in particular the TrkB-expressing subtype) were ablated or removed using a different genetic trick, male mice seemed similarly motivated to mate with unablated females, as measured by sniffing and exploring behaviours – but they showed impaired penetration, thrusting and ejaculation.
When the situation was reversed, and ablated females (in the fertile, typically receptive phase of their oestrus cycle) were paired with intact males, the females appeared less receptive to male sexual advances, allowing fewer and shorter bouts of penetration and thrusting. And when female Krause corpuscle neurons were activated optically, vaginal contraction was evoked, which is presumed to be a correlate of sexual arousal.
These results suggest that Krause corpuscles in the penis and clitoris convey sensations to the spinal cord, and ultimately to the brain, where they are perceived as sexual. Unfortunately, we can’t simply lie back on the pillow and ask the mice how it felt when their genital Krause corpuscles were artificially activated or ablated. And so, we still don’t know for sure what the subjective sensation entailed.
If we are to locate the actual centre for sexual sensation in the brain, we can start by tracking the neural circuit, starting with termination of the genital Krause corpuscles in the spinal cord (called the dorsomedial region of the sacral cord). When the genital Krause corpuscles terminate in the spinal cord, they activate spinal sexual reflexes (like vaginal lubrication, and penile erection and ejaculation). The next neurons in the sensory chain project up the spinal cord and into the brain. We know that, in both mice and humans, stimulation of the genitals activates a particular set of brain regions including, critically, a pleasure/reward centre called the nucleus accumbens. It will be interesting to see whether the electrical messages from the genital Krause corpuscles ultimately reach these same brain areas and produce a similar pattern of activation in mice.
There are some important caveats to the present findings. The first is that, of course, mice are not people, and so we cannot assume that sexual perception will be exactly the same in both species. The second is that, due to certain technical details, the investigators were unable to ablate absolutely all of the Krause corpuscle neurons – a tiny fraction remained. Perhaps, if they had been able to destroy all of them, the attenuation of mating behaviour that they observed would have been complete rather than partial. As it is, the possibility remains that there are other sensors and neural pathways for genital sexual sensation that do not involve Krause corpuscles.
Like all good science, this report suggests many questions for future investigators. Why do Krause corpuscle neurons from the penis and clitoris produce strong sexual sensations, and those from the lips, nipples and anus typically produce weaker sexual sensations, while those from the finger joints and the eyeball appear to produce none at all? Is it because of how genital Krause corpuscle signals are processed in the lower lumbar spinal cord and the particular locations where their signals ultimately arrive in the brain? One hypothesis is that electrical signals from Krause corpuscles in the finger joints don’t evoke a sexual sensation in part because they don’t ultimately reach the brain’s reward centres (like the aforementioned nucleus accumbens).
In both women and men, the density of all types of touch sensors in the skin seems to decrease steadily after age 20
Are the pathways to the brain from Krause corpuscles in the clitoris and the penis the same, or do they diverge in important ways that might contribute to differences in sexual sensation and the experience of orgasm? Does the mulberry shape of Krause corpuscles in the clitoris confer some optimal pattern for sexual stimulation that’s different from that of the Krause corpuscles of the penis? When women and men describe their orgasms in qualitative terms (omitting anatomical words like penis or clitoris) and these descriptions are evaluated by readers blind to the sex of the author, there are no discernible differences. Likewise, brain scans cannot reliably distinguish male from female orgasms (to my knowledge, there are no published studies on this topic including trans or non-binary folks). That said, on average, female orgasms tend to be somewhat longer than male orgasms (about 25 versus 15 seconds, as measured by the rectal contractions that accompany orgasm) and have a much shorter refractory period before the next can occur. While these differences might be related to Krause corpuscle function, I’m betting on subtle brain function differences in this case (at a level that cannot be resolved by today’s brain-scanning machines).
Of particular interest to this 62-year-old neuroscientist is the question of whether the density of genital Krause corpuscles decreases with age and, if so, does this decrease underlie age-related changes in sexual sensation and propensity for orgasm? It’s a cultural and comedic trope that young men reach orgasm quickly (in either partnered or solo sex) while older men last longer. One cultural explanation for this difference has been that sexual experience earlier in life is novel and this novelty is somehow more intrinsically sexually exciting. That may well be true, but it’s probably not the whole story. Generally speaking, in both women and men, the density of all types of touch sensors in the skin seems to decrease steadily after about age 20. The mechanosensors in the fingertips that subserve fine discriminative touch (like those used to read Braille dots) are slowly lost with age in a way that parallels a gradual loss of fine touch sensation.
Likewise, with ageing, nerve endings in the skin that transduce painful stimuli are reduced all over the body. This loss may help explain why bedridden elderly people often do not readily complain about pain from their bedsores. It’s likely that, like other touch sensors, Krause corpuscle density gradually decreases in adulthood and that this decrease may contribute to attenuated sexual sensation and success in achieving orgasm. It will be interesting to test this hypothesis (with analysis of cadaver tissue) and to determine if Krause corpuscle loss proceeds similarly in the clitoris and the penis. Within the clitoris, it will be instructive to compare Krause corpuscle density in the external clitoris, which appears to be the main site for sexual sensation, and the clitoral bulbs, which lie adjacent to the anterior wall of the vagina and might be the basis of the much debated ‘G-spot’ sensation.
My father died in 2006 at the age of 82, having lived a full and rewarding life. Of course, I wish he were still here today. I cannot help but feel that he would have loved to hear about these findings. In his psychoanalytic world, individual variation in preferred sexual acts or propensity to achieve orgasm is mostly thought to reflect one’s social and embodied experience in the world, particularly experience in early life. That idea is almost certainly true. Our brains are built to be modified by experience (not just social experience) and in particular to lay down memories both conscious and subconscious.
The general psychoanalytic idea that we are moulded by our experiences and that we are the most susceptible to these influences in early life is broadly consistent with contemporary neuroscientific thought about critical periods for experience-dependent brain-wiring in early life. Our emerging molecular and cellular understanding of such brain plasticity does not provide an immediate challenge to these psychodynamic notions. Early experiences encoded by the plastic brain are, of course, central to the particulars of sexual sensation in adulthood, but the lowly nerve endings of the skin, and their person-to-person variation, are also likely to have an important role in creating our sexual individuality.
