Links between the intrauterine theory of gender identity, transsexualism and mind-brain-body identity

The intrauterine view of gender identity and sexual orientation

The intrauterine theory of gender identity proposes that gender identity is encoded in brain during intrauterine development (e.g., Savic et al. 2011; Swab, 2007). The brain is thought to develop in the male ‘direction’ through a surge of testosterone on nerve cells, likely in the bed nucleus of the stria terminalis (BSTc) in the limbic system (Chung et al. 2002; Krujiver et al. 2000; Zhou et al. 1995), whereas in the female ‘direction,’ this surge is absent.

This view of gender identity has been adapted to explain transsexualism: since sexual differentiation of the brain occurs in the second half of pregnancy, and sexual differentiation of the sexual organs occurs in months 1-2 of pregnancy, transsexuality is possible. Thus, the relative masculinization of the brain at birth may not reflect the relative masculinization of the genitals (e.g., Bao & Swab, 2011; Savic et al. 2011; Veale et al. 2010).

The intrauterine theory implies that transsexualism is entirely dependent on a specific and dedicated neuroanatomical brain ‘module’, the BTSc. At a time during the second half of pregnancy, the BSTc comes ‘on-line’, and sexual  – or transsexual  – identity is thereby formed in the individual.

The intrauterine theory as a maturational theory

As a maturational brain theory, the intrauterine theory assumes functional localization of gender identity as an attribute of a specific brain structure or region (i.e., the BSTc) and its patterns of functional connectivity, rather than its patterns of functional connectivity to other structures or regions, to the whole brain and its external environment (van Rysewyk, 2010). Developmentally, a maturational view assumes establishment of intraregional connections, rather than interregional connectivity. It follows that the intrauterine view implies that transsexualism, at the level of the brain, involves a process of organizing intraregional interactions within the BSTc. The bed nucleus of the STc appears to be critically involved.

Extending the maturational aspect of the intrauterine view to gender development also means that we should observe changes in the response properties of the BSTc during pregnancy as regions within the BSTc interact with each other to establish their functional gender roles. Thus, the onset of transsexual identity during intrauterine development will be associated with reliable changes in several regions in the BSTc.

Representation of ST ‘off-line’

Representation of ST ‘on-line’ – onset of transsexual identity

The intrauterine theory and mind-brain identity theory

Philosophically, the intrauterine view is also highly compatible with mind-brain identity theory, a philosophy of mind and consciousness (van Rysewyk, 2013). Mind-brain identity theory claims that mental states are identical to brain states. This implies that a person’s indubitable sense of gender identity as manifested in real-time feelings, sensations, thoughts and reports to others of being a woman or a man are numerically identical to specific brain states, possibly states of a single brain structure or region.

Are the brain states in question states of one brain structure – the BSTc? It appears not, for Chung et al. (2002) found that significant sexual dimorphism in BSTc size and neuron number does not develop in humans until adulthood. However, most male-to-female (MTF) transsexuals self-report that their feelings of gender dysphoria began in early childhood (e.g., Lawrence, 2003).

Clearly, these important findings are not compatible with the maturation of one brain structure or region, but with inter-regional brain development, of which the BSTc may feature as merely one, but significant, contributor. Thus, following the onset of transsexual identity, there is a reorganization of interactions between different brain structures and regions. This reorganization process could change previously existing mappings between brain structures and regions and their functions. It follows that the same phenomenal sense of gender identity in a person (e.g., recurring feelings of gender dysphoria) could be supported by different neural substrates at different ages during development. This possibility doesn’t necessarily exclude a maturational theory of transsexual identity, since the BSTc may be stimulated to reorganize its intrauterine functional connectivity following appropriate stimulation during postnatal development.

Future experimental questions for the function of the BSTc in gender identity and sexual orientation

1. The extent of BSTc localization in gender identity: how diffuse or focal is BSTc activity that results from gender-identity based stimulation?

2. The extent of BSTc specialization in gender identity: How coarsely or finely-tuned is BSTc activity that results from gender-identity based stimulation?

The inter-regional interaction theory of gender identity assumes that as brain tissue becomes more specialized (i.e., finely-tuned), it will become activated by a narrow range of gender-based experiences. With increased specialization, less extensive areas of brain tissue (BSTc?) will identify with gender-based phenomenology.

References

Bao, A. M., & Swaab, D. F. (2011). Sexual differentiation of the human brain: relation to gender identity, sexual orientation and neuropsychiatric disorders.Frontiers in neuroendocrinology, 32(2), 214-226.

Chung, W. C., De Vries, G. J., & Swaab, D. F. (2002). Sexual differentiation of the bed nucleus of the stria terminalis in humans may extend into adulthood. Journal of Neuroscience, 22, 1027-1033.

Kruijver, F. P., Zhou, J. N., Pool, C. W., Hofman, M. A., Gooren, L. J., & Swaab, D. F. (2000). Male-to-female transsexuals have female neuron numbers in a limbic nucleus. Journal of Clinical Endocrinology and Metabolism, 85, 2034-2041.

Lawrence, A. A. (2003). Factors associated with satisfaction or regret following male-to-female sex reassignment surgery. Archives of Sexual Behavior, 32, 299-315.

Savic, I., Garcia-Falgueras, A., & Swaab, D. F. (2010). Sexual differentiation of the human brain in relation to gender identity and sexual orientation. Progress in Brain Research, 186, 41-65.

Swaab, D. F. (2007). Sexual differentiation of the brain and behavior. Best Practice & Research Clinical Endocrinology & Metabolism, 21(3), 431-444.

van Rysewyk, S. (2010). Towards the the developmental pathway of face perception abilities in the human brain. In: A. Freitas-Magalhães (Ed.), ‘Emotional Expression: The Brain and the Face’ (V. II, Second Series), University of Fernando Pessoa Press, Oporto: pp. 111-131.

van Rysewyk, S. (2013). Pain is Mechanism. PhD Dissertation, University of Tasmania.

Veale, J. F., Clarke, D. E., & Lomax, T. C. (2010). Biological and psychosocial correlates of adult gender-variant identities: a review. Personality and Individual Differences, 48(4), 357-366.

Zhou, J. N., Hofman, M. A., Gooren, L. J., & Swaab, D. F. (1995). A sex difference in the human brain and its relation to transsexuality. Nature, 378, 68-70.

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mind-brain identity theory, ‘brain-sex’ theory of transsexualism and the dimorphic brain

Introduction

According to an influential neuroscientific theory, gender identity is encoded in the brain during intrauterine development. The brain is thought to develop in the male ‘direction’ through a surge of testosterone on nerve cells; in the female ‘direction’, this surge is thought to be absent (e.g., Savic et al. 2011; Swab, 2007). Call this the ‘standard view of gender identity’.

The standard view of gender identity offers an explanation of transsexualism. Since sexual differentiation of the brain occurs in the second half of pregnancy, and sexual differentiation of the sexual organs occurs in months 1-2 of pregnancy, trans-sexuality may occur. The relative masculinization of the brain at birth may not reflect the relative masculinization of the genitals (e.g., Bao & Swab, 2011; Savic et al. 2011; Veale et al. 2010). According to the standard view, transsexualism is entirely dependent on, and thereby reduces to, specific neurophysiological changes that occur during intrauterine growth in two interconnected organ types (i.e., brain and genitals).

The reductive nature of the standard view of gender identity is compatible with  mind-brain identity theory in philosophy of mind and consciousness. Mind-brain identity theory claims that mental states are identical to brain states. Concerning gender identity, mind-brain identity theory claims that a person’s gender identity is identical to neurophysiological mechanism. A strong and profound implication of this view, if it is correct, is that a person’s indubitable sense of being a ‘female’ or a ‘male’ is nothing more than the operations of neurophysiology encoded during intrauterine growth. Mind-brain identity theory contrasts with philosophies of mind which propose that minds are dependent but still somehow ‘more than’ the body on which they depend.

Brain-Sex Theory of Transsexualism and Mind-Brain Identity

According to the strong version of ‘brain-sex’ theory of transsexualism,  transsexualism is nothing more than (one and the same as) a specific neuranatomical (i.e., structural) intersex type, in which one or more sexually dimorphic brain areas are incompatible with bological sex. The theory therefore assumes that the relationship between transsexualism and neurophysiology is one of identity. Gender identity reduces to neurophysiology. Thus, there is a specific neuroanatomical type for female gender identity in male-to-female (MTF) transsexuals, and a specific neuroanatomical type for male gender identity in female-to-male (FTM) transsexuals. The most compelling neuroscientific evidence in support of an identity view of transsexualism comes from Kruijver et al. (2000) and Zhou et al. (1995).

Neuroscientific Evidence for Brain-Sex Theory of Transsexualism

Zhou et al. (1995)

Zhou et al. (1995) observed that a group of neurons in the hypothalamus, the central subdivision of the bed nucleus of the stria terminalis (BSTc), was sexually dimorphic in humans. Zhou et al. found that the average volume of the BSTc in postmortem males was roughly 44% larger than in females. However, in 6 male-to-female (MTF) transsexuals who had feminizing hormone treatment, the average volume of the BSTc was within the typical female range. The authors found that the 6 transsexuals they investigated varied in their sexual orientations and inferred that there was no relationship between BSTc size and the sexual orientation of transsexuals. I assume that this assertion implies that transsexual sexual orientation and BSTc size are not type identical; that is, they are not the same type. Finally, further postmortem investigations conducted in a small number of nontranssexual patients with abnormal hormone levels, led Zhou et al. to reason that the small volume of the BSTc in MTF transsexuals cannot be explained by adult sex hormone levels (p. 70). Thus, there appears to be a relationship of identity between transsexualism and small BSTc volume. They are one and the same.

Kruijver et al. (2000)

Kruijver et al. (2000) conducted a follow-up study in which they investigated the number of neurons in the BSTc rather than its volume. The authors examined tissue from the same 6 MTF transsexuals studied by Zhou et al. (1995). They also studied nerve tissue from one female-to-male (FTM) transsexual and from an 84-yr-old man who ‘had very strong cross-gender identity feelings but was never . . . sex-reassigned or treated . . . with estrogens’ (p. 2039). The authors found that BSTc neuron number was even more sexually dimorphic than BSTc volume; namely, the average BSTc neuron number in males was 71% higher than in females. Once again, the 6 MTF transsexuals showed a sex-reversed identity pattern, with an average BSTc neuron number in the female range. BSTc neuron number was also in the female range in the untreated gender dysphoric male and was in the male range in the FtM transsexual. Again, the putative sexual orientation of the MTF transsexuals appeared to make no difference. In contrast to the claims of the standard view of gender identity, data from the few non-transsexual patients with abnormal hormone levels led Kruijver et al. (2000) to conclude that ‘hormonal changes in adulthood did not show any clear relationship with the BSTc . . . neuron number’ (p. 2039).

Neuroscientific Objections to Brain-Sex Theory of Transsexualism

Chung et al. (2002)

Brain-sex theory of transsexualism faces several neuroscientific challenges. Chung et al. (2002) found that significant sexual dimorphism in BSTc size and neuron number does not develop in humans until adulthood. However, most MTF transsexuals self-report that their feelings of gender dysphoria began in early childhood (e.g., Lawrence, 2003). Since MTF transsexuals have not yet become sexually dimorphic by the time cross-gender feelings have become obvious, it is unlikely that BSTc volume and neuron number can be a neuroanatomical signature identifiable with gender identity. However, Chung et al. (2002) speculate that foetal or neonatal hormone levels could influence gender identity and could also produce changes in BSTc synaptic density, neuronal activity, or neurochemicals that may not affect BSTc volume or neuron number immediately, but may do so during adulthood. I am not aware of any evidence in support of this hypothesis. In any event, mind-brain identity theory can agree with Chung’s et al. (2002) speculation. Mind-brain identity theory is neutral on whether ‘brain characteristics’ will be macro or micro, or both, or what their specific developmental effects will be. Gender identity might be a state of the entire brain, synapses, or multiple, interacting physiological systems. Macro/microreductionism is optional, not required. Finally, Chung et al. (2002) speculate that inconsistency between an individual’s gender identity and biological sex might likely affect adult BSTc size and neuron number by some yet unknown mechanism or mechanisms. Given that neuroscience is in a very early stage of understanding gender identity, the implication that more time is needed to understand transsexualism appears prudent.

Joel (2011)

Joel (2011) challenges an implicit assumption in the standard view of gender identity; namely, human brains are one of two types –  ‘male’ or ‘female’ – and that the differences between these two types subserve subtype differences between men and women in gender identity and transsexualism. According to Joel (2011), this assumption is true only if there is robust correspondence (i.e., high statistical correlation) between the ‘male’/’female’ type of all of the brain characteristics in a single brain. It turns out there isn’t. As Joel points out, concerning most documented sex brain differences, there is overlap between the distributions of the two sexes (e.g., Juraska, 1991; Koscik et al. 2009). Neuroanatomical data also reveal that sex interacts with other factors during the intrauterine period and throughout life to determine brain structure (e.g., prenatal exposure to psychoactive drugs, early handling, rearing conditions, maternal separation, acute and chronic postnatal stress). Human brains therefore are a dynamic heterogeneous mosaic of ‘male’ and ‘female’ brain characteristics that cannot be type identified on a simple continuum between a ‘male type brain’ and a ‘female type brain’ (Joel, 2011). Thus, brains are not type sexed, but type intersexed; sexually multi-morphic rather than dimorphic.

Joel’s theory is compatible with brain-sex theory of transsexualism since both theories claim that transsexualism is intersexual, but incompatible because it denies what brain-sex theory asserts; namely, in transsexualism, one or more sexually dimorphic brain areas are incompatible with bological sex. Thus, Joel’s view rejects the stronger claim that gender is type identical with the sexually dimorphic brain. Accordingly, we cannot predict the specific properties of ‘male/female’ brain characteristics of an individual based on her/his sex.

However, Joel’s view implies the weaker consequence that, on average, we can predict that females will have more brain characteristics with the ‘female’ type than with the ‘male’ type (vice versa for FTM transsexuals), and males will have more brain characteristics with the ‘male’ type than with the ‘female’ type (vice versa for MTF transsexuals). Whether two individuals are similar or not is dependent on the similarity in the details of their brain mosaic; not on the quantity of ‘male’ and ‘female’ characteristics. This means that two similar individuals share characteristics of the same ‘brain mosiac’ type – they have the same type. Brains of the same type must possess the characteristics and properties typical of the type, but that does not imply that they all be exactly similar to one another. This implication is compatible with mind-brain identity theory.

References

Bao, A. M., & Swaab, D. F. (2011). Sexual differentiation of the human brain: relation to gender identity, sexual orientation and neuropsychiatric disorders. Frontiers in neuroendocrinology, 32(2), 214-226.

Chung, W. C., De Vries, G. J., & Swaab, D. F. (2002). Sexual differentiation of the bed nucleus of the stria terminalis in humans may extend into adulthood. Journal of Neuroscience, 22, 1027-1033.

Hines M. (2004). Brain Gender. Oxford: Oxford University Press.

Koscik, T., O’Leary, D., Moser, D. J., Andreasen, N. C., & Nopoulos, P. (2009). Sex differences in parietal lobe morphology: relationship to mental rotation performance. Brain Cognition, 69, 451–459.

Kruijver, F. P., Zhou, J. N., Pool, C. W., Hofman, M. A., Gooren, L. J., & Swaab, D. F. (2000). Male-to-female transsexuals have female neuron numbers in a limbic nucleus. Journal of Clinical Endocrinology and Metabolism, 85, 2034-2041.

Joel, D. (2011). Male or female? Brains are intersex. Frontiers in integrative neuroscience, 5, 57.

Juraska J. M. (1991). Sex differences in “cognitive” regions of the rat brain. Psychoneuroendocrinology 16, 105–109. doi: 10.1016/0306-4530(91)90073-3.

Lawrence, A. A. (2003). Factors associated with satisfaction or regret following male-to-female sex reassignment surgery. Archives of Sexual Behavior, 32, 299-315.

Savic, I., Garcia-Falgueras, A., & Swaab, D. F. (2010). 4 Sexual differentiation of the human brain in relation to gender identity and sexual orientation. Progress in Brain Research, 186, 41-65.

Swaab, D. F. (2007). Sexual differentiation of the brain and behavior. Best Practice & Research Clinical Endocrinology & Metabolism, 21(3), 431-444.

Veale, J. F., Clarke, D. E., & Lomax, T. C. (2010). Biological and psychosocial correlates of adult gender-variant identities: a review. Personality and Individual Differences, 48(4), 357-366.

Zhou, J. N., Hofman, M. A., Gooren, L. J., & Swaab, D. F. (1995). A sex difference in the human brain and its relation to transsexuality. Nature, 378, 68-70.