Sensory-Tactile Functional Mapping and Use-Associated Structural Variation of the Human Female Genital Representation Field

Sensory-Tactile Functional Mapping and Use-Associated Structural Variation of the Human Female Genital Representation Field. Andrea J. J. Knop, Stephanie Spengler, Carsten Bogler, Carina Forster, Michael Brecht, John-Dylan Haynes and Christine Heim. Journal of Neuroscience, February 9 2022, 42 (6) 1131-1140; https://doi.org/10.1523/JNEUROSCI.1081-21.2021

Abstract: The precise location of the human female genital representation field in the primary somatosensory cortex (S1) is controversial and its capacity for use-associated structural variation as a function of sexual behavior remains unknown. We used a functional magnetic resonance imaging (fMRI)-compatible sensory-tactile stimulation paradigm to functionally map the location of the female genital representation field in 20 adult women. Neural response to tactile stimulation of the clitoral region (vs right hand) identified individually-diverse focal bilateral activations in dorsolateral areas of S1 (BA1–BA3) in alignment with anatomic location. We next used cortical surface analyses to assess structural thickness across the 10 individually most activated vertices per hemisphere for each woman. We show that frequency of sexual intercourse within 12 months is correlated with structural thickness of the individually-mapped left genital field. Our results provide a precise functional localization of the female genital field and provide support for use-associated structural variation of the human genital cortex.

SIGNIFICANCE STATEMENT We provide a precise location of the human female genital field in the somatosensory cortex and, for the first time, provide evidence in support of structural variation of the human genital field in association with frequency of genital contact. Our study represents a significant methodological advance by individually mapping genital fields for structural analyses. On a secondary level, our results suggest that any study investigating changes in the human genital field must map the field individually to achieve sufficient precision. Our results pave the way for future research into the plasticity of the human genital cortex as a function of normal or adverse experience as well as changes in pathologic conditions, i.e., sexual dysfunction, sexual deviation, or sexual risk-taking behavior.

Keywords: functional mappinggenital fieldindividual variabilityplasticitysexual behaviorsomatosensory cortex

Discussion

We present novel evidence on the precise location of the female genital representation field and its capacity for use-associated structural variation. Using functional mapping during sensory-tactile stimulation of the clitoral region, we show focal bilateral neural activations within the dorsolateral postcentral gyrus in S1. We show that the individual location of peak neural activations in response to clitoral stimulation varies considerably between women. We applied cortical surface analysis to the individually-mapped ROI to compute structural thickness of the genital field. Correlating the individually-mapped morphologic data with behavioral data on sexual contact, we provide first evidence that thickness of the genital field varies as a function of frequency of genital intercourse in the past 12 months and lifetime, in line with use-associated plasticity.

Our results are noteworthy in several ways. To localize the female genital field, we measured neural response in a tactile-sensory stimulation paradigm that delivers a physiologically valid stimulus as opposed to a previous study using electrical stimulation of the clitoris (Michels et al., 2010). Furthermore, our tactile-sensory stimulation paradigm did not involve touching of body parts adjacent to the clitoris nor did it induce marked sexual arousal as opposed to previous studies using self-delivered or partner-delivered stimulation (Georgiadis et al., 2006, 2009, 2010; Komisaruk et al., 2011). The sole other study that used a sensory-tactile nonarousing stimulation paradigm to localize the genital field was limited to males (Kell et al., 2005). Our stimulation paradigm induced focal targeted neural activations, without inducing neural activation in other brain regions, at comparatively (Kell et al., 2005; Michels et al., 2010) high levels of statistical significance without using somatosensory template masks. Therefore, our data provide unequivocal information about the location of the female genital field and represent a significant methodological advance compared with previous studies that yielded conflicting results (Georgiadis et al., 2006, 2009; Michels et al., 2010; Komisaruk et al., 2011), likely because of confounding factors inherent to stimulation paradigms used in these studies (Pratt et al., 1980; Forss et al., 1994). On a group level, the mean location of the female genital field in the dorsolateral postcentral gyrus, identified in our study, corresponds with the location reported in two of the previous studies in females using electrical (Michels et al., 2010) or partner-delivered manual stimulation (Georgiadis et al., 2006) as well as with the location reported for males in the above-referenced study using sensory-tactile stimulation in males (Kell et al., 2005). Our results confirm a somatotopically-ordered representation of the female clitoris, adjacent to the representation of the hips and upper legs and commensurate with anatomic location, and disprove displaced location in the mesial wall of the precentral lobe. Our results provide independent confirmation for the revision (Kell et al., 2005) of the original homunculus (Penfield and Rasmussen, 1950) and extend the validity of the revised homunculus to women. Our results confirm a bilateral somatosensory representation of the anatomically centered clitoris, in line with histologic mapping data on the localization and bilateral representation of the rat genital cortex (Lenschow et al., 2016; Lauer et al., 2017; Lenschow and Brecht, 2018).

Our results suggest profound variability of the individual location of the genital field within the dorsolateral part of S1 with individual peak activations clearly deviating from the group mean. This means that any study looking at structural variation of the genital field as a function of certain conditions, such as sexual behavior, sexual abuse or sexual dysfunction, must necessarily implement individual mapping of the genital field and compute data, i.e., cortical thickness, on an individual level. Clearly, only by using individually-mapped ROIs, such studies yield precise reliable surface-based parameters for association with specific conditions.

We computed data on structural thickness of the genital field in individually-mapped ROIs, based on the 10 most activated vertices per hemisphere for each woman. We show that individual thickness of the left genital field associates with frequency of sexual intercourse. The association was stronger for genital intercourse within the past 12 months. While less pronounced, the association was significant for lifetime genital contact. Frequency of genital intercourse was not associated with thickness of the representation field of the right hand nor with thickness of the entire cortical mantle, confirming a specific association between genital touch and genital field thickness. This is compatible with the idea that the female genital field has capacity for structural plasticity depending on its use, commensurate with the general “use-it-or-lose-it” principle of experience-dependent plasticity (Hebb, 1947; Elbert and Rockstroh, 2004; Draganski and May, 2008). While injury-dependent or use-dependent plasticity in the human somatosensory cortex has been reported (Elbert et al., 1994, 1995; Flor et al., 1995; Foell et al., 2014), our results are the first to document structural variation of genital field thickness associated with more or less frequent normative use. Our results are in line with findings from animal studies showing that genital brushing during puberty resulted in lateral expansion of the rat and mouse genital cortex (Lenschow et al., 2017; Sigl-Glöckner et al., 2019). Cortical plasticity serves to enhance the efficiency of processing of behaviorally-relevant inputs and represents an adaptive response (Trachtenberg et al., 2002; Markham and Greenough, 2004; Feldman and Brecht, 2005; May, 2011). In an earlier study, we observed decreased thickness of the genital cortex after exposure to childhood sexual abuse, suggesting that highly aversive and developmentally inappropriate sexual stimulation may limit somatosensory representation to decrease processing of detrimental input (Heim et al., 2013).

Several mechanisms might contribute to dynamic use-associated structural plasticity of the genital field. Structural thickening of the mature cortex as a function of use most likely reflects formation of new synapses by axonal sprouting, dendritic arborization, and dendritic spine growth rather than induction of new neurons through neurogenesis (Markham and Greenough, 2004; Feldman and Brecht, 2005; Feldman, 2009; May, 2011). There is substantial evidence on the central role of glutamatergic synapses in mediating plasticity, reflecting rapid components of NMDA receptor-dependent long-term potentiation (LTP) and long-term depression (LTD; Buonomano and Merzenich, 1998; Feldman, 2009). Another mechanism contributing to use-associated structural plasticity may involve alterations in glial-cell mediated myelination (Timmler and Simons, 2019). While oligodendrogenesis is rare (Yeung et al., 2019), the presence of large numbers of premyelinating oligodendrocytes in the human cortex may enable adaptive myelination to adapt conduction velocity to functional demand (Gibson et al., 2014). Future studies in humans should use novel imaging tools that allow for assessing cortical myelin density (Amunts and Zilles, 2015) to study genital field plasticity. Further, neural activation in response to somatosensory stimulation depends on axonal input from the thalamus (Feldman, 2009). When removing afferent somatosensory input from the thalamus, dendritic spine numbers of somatosensory cortical neurons attenuate (Lendvai et al., 2000). When exposing rats to genital touch or sexual contact during puberty, invading thalamo-cortical afferents promote the expansion of the female genital cortex (Lenschow et al., 2016). Future studies on genital field plasticity should therefore include assessments of thalamo-cortical connectivity and myelination.

It must be noted that use-associated variation of structural thickness of the female genital field in our study was limited to the left hemisphere. This lateralized effect is puzzling given that the neural representation of the clitoris is bilateral. Left-hemispheric dominance of neural plasticity has been reported for learning-dependent structural change after coordination and motor skill training (Draganski et al., 2004; Taubert et al., 2010; Rogge et al., 2018). Such lateralized plasticity may reflect hemispheric specialization (Serrien et al., 2006). In the above referenced study (Heim et al., 2013), thinning of the genital field after sexual abuse was limited to the left hemisphere. While we cannot comprehensively explain these findings, one plausible mechanism may involve lateralized limbic-cortical modulation of sensory afferent inputs into the genital field, leading to unilateral associations of sexual behavior with genital field morphology.

While our localization of the female genital field was experimental in nature, our investigation of the capacity of the genital field for structural variation as a function of genital contact was cross-sectional and relied on retrospective self-report of genital intercourse. Our results align with the general principle of an association between frequency of genital intercourse and structural variation, albeit the direction of effect is a matter of discussion. It is conceivable that thickness of the genital field may drive frequency of sexual intercourse. Results from animal models provide causal that clitoral stimulation drives genital field thickness (Lenschow et al., 2016; Lenschow and Brecht, 2018). Future prospective studies or studies exploiting quasi-experimental conditions, such as induction of behavior change during sexual therapy, are needed to establish causality.

In conclusion, we provide an unequivocal localization of the female genital field in S1 and support for use-associated plasticity of the human genital field. On a secondary level, our findings support the notion that studies investigating change of the human genital field must map the field individually. Our results pave the way for future research into the plasticity of the human genital field as a function of normal or adverse experience as well as genital field structure, function and plasticity in pathologic conditions, such sexual dysfunction, sexual deviation, or sexual risk-taking behavior.