Conceived and designed the experiments: HS JP HB OJ HM. Performed the experiments: JP SW. Analyzed the data: HS JP SK OG. Contributed reagents/materials/analysis tools: JP SW OJ HM OG. Wrote the paper: HS JP HB SK.
The authors have declared that no competing interests exist.
Is sexual orientation associated with structural differences in the brain? To address this question, 80 homosexual and heterosexual men and women (16 homosexual men and 15 homosexual women) underwent structural MRI. We used voxel-based morphometry to test for differences in grey matter concentration associated with gender and sexual orientation. Compared with heterosexual women, homosexual women displayed less grey matter bilaterally in the temporo-basal cortex, ventral cerebellum, and left ventral premotor cortex. The relative decrease in grey matter was most prominent in the left perirhinal cortex. The left perirhinal area also showed less grey matter in heterosexual men than in heterosexual women. Thus, in homosexual women, the perirhinal cortex grey matter displayed a more male-like structural pattern. This is in accordance with previous research that revealed signs of sex-atypical prenatal androgenization in homosexual women, but not in homosexual men. The relevance of the perirhinal area for high order multimodal (olfactory and visual) object, social, and sexual processing is discussed.
In humans, structural brain differences between men and women are well known. Total brain size, as well as grey matter (GM) and white matter (WM) size were found to be bigger in men than in women
Sexual dimorphism of the human brain has been related to effects of prenatal androgenization
In an effort to investigate differences in brain morphology between heterosexual and homosexual men and women, we performed a VBM study. We first calculated gender related whole brain effects on GM, WM and cerebrospinal fluid (CSF) to check the comparability of our sample. Since gender effects were found to be pronounced when GM images were calculated with unmodulated brain images, we used unmodulated images to test for differences in the regional probability to belong to GM (concentration)
Twenty-five heterosexual women (mean age: 24.9±3.3 ys.), 24 heterosexual men (mean age: 25.3±3.2 ys.), 16 homosexual men (mean age: 27.3±3.7 ys.), and 15 homosexual women (mean age: 24.9±5.8 ys.) participated in the study. A subset had been involved in a previous functional MRI study
MRI scanning was performed on a 1.5-Tesla Philips Intera scanner using a quadrature head coil. A structural MRI was acquired on each participant using a 3D T1 weighted sequence (TR 7.9, TE 3.7 ms, flip angle 8°, FOV 220×132×178 mm3, 256×256 matrix, 1.2 mm slice-thickness) yielding 110 sagittal slices.
Data pre-processing and statistical analysis was performed using SPM2 software (
In brief, VBM comprises first, spatial normalization of all images to a standardized anatomical space to allow spatial averaging, second, segmentation of images into the three major tissue compartments (GM, WM, and CSF) and third, comparison of local GM concentration across the whole brain
Global effects of gender were tested on each tissue type with mean voxel values as dependent variable using two-way ANOVAs (with gender and sexual orientation as grouping factors). In addition, post hoc t-test within gender comparisons were performed for exploratory purpose. Regional GM concentration was compared using a two sample t-tests, while controlling for global GM mean voxel values to remove variance due to differences in brain tissue size. In this way we performed comparisons between male and female brains, and within-gender comparisons, i.e. homosexual men vs. heterosexual men and homosexual women vs. heterosexual women (one-sided in both directions). Absolute threshold mask was set to 10% limiting the analysis to voxels with more than 10% probability of containing GM. Resulting statistical parametric maps were corrected for multiple comparisons in the entire volume using the false discovery rate (FDR) method (p<0.05)
Male brains were larger than female brains. Two-way ANOVAs (with gender and sexual orientation as grouping factors) revealed higher mean tissue voxel values of males compared to females in GM (F1,76 = 24.8; p<0.001), WM (F1,76 = 20; p<0.001) and cerebrospinal fluid (CSF) (F1,76 = 23.9; p<0.001). No main effect for sexual orientation and no interaction of the two grouping factors were detected in any tissue type. By means of post hoc t-tests for independent samples mean voxel tissue values were compared between heterosexual and homosexual subjects within each gender group. No differences were found expect for a higher degree of CSF in homosexual men compared to heterosexual men (t(38) = −2.14; p = 0.04; two-sided) (
GM | WM | CSF | n | ||
Men | 858±59 | 568±43 | 387±30 | 40 | |
heterosexual | 856±68 | 565±47 | 377±24 | 24 | |
homosexual | 863±45 | 572±37 | 398±33 | 16 | |
Women | 795±52 | 515±58 | 345±47 | 40 | |
heterosexual | 796±53 | 523±59 | 346±51 | 25 | |
homosexual | 794±53 | 518±60 | 341±41 | 15 | |
Total | heterosexual | 825±67 | 538±59 | 362±43 | 49 |
homosexual | 829±59 | 546±56 | 370±47 | 31 | |
Total | 826±64 | 541±57 | 365±44 | 80 |
Mean volume values as delivered by SPM segmentation algorithm.
GM = grey matter, WM = white matter, CSF = cerebrospinal fluid.
There was a significant effect of gender on GM. Brains of (heterosexual and homosexual) women showed areas of increased GM concentration, relatively symmetrically and widespread through the entire cortical mantle, in the cerebellum bilateral and subcortical bilateral in the amygdala, caudate, thalamus, and right hippocampus. Major cortical areas of increased GM concentration could be found in the midline of both hemispheres, spanning from cuneus and posterior cingulate to prefrontal superior gyrus and anterior cingulate as well as bilaterally in the superior parietal lobule. Cohens ‘d effect size of the voxel showing maximum difference between gender (x, y, z = 26, −26, 66) was 1.27.
With regard to within-gender comparison, there were no GM differences between heterosexual and homosexual men, but heterosexual women showed clusters of increased GM concentration in comparison to homosexual women bilaterally in the temporo-basal cortex, ventral cerebellum, and left ventral premotor cortex. Higher GM concentrations were most prominent in the left perirhinal cortex, resembling the larges cluster of increased GM concentration spanning ventrally from the collateral sulcus, to the rhinal sulcus at the ventral border of the entorhinal cortex and extending to the ventral margin of the amygdala (
Coronal sections from y = 8 to y = −6 (p<0.05; FDR corrected). Left brain side is to the left.
Area | Side | Cluster extent | Peak difference | ||||
P | T-value | Coordinates | |||||
Perirhinal cortex | L | 1209 | 0.011 | 6.20 | −32 | 1 | −35 |
Ventral premotor cortex | L | 101 | 0.015 | 5.37 | −63 | 3 | 36 |
Cerebellum | L | 744 | 0.015 | 5.37 | −10 | −40 | −55 |
Cerebellum | R | 303 | 0.031 | 4.74 | 26 | −50 | −59 |
Perirhinal cortex | R | 240 | 0.036 | 4.61 | 34 | 3 | −36 |
Regional differences in GM concentration are characterized by the cluster extent, stereotactic MNI coordinates and T-value of the voxel showing the peak difference. P-values were corrected by the False Discovery Rate. R = right; L = left.
Finally, we tested for common areas of decreased GM in homosexual women and heterosexual males (both relative to heterosexual women). Therefore the contrast
Areas of decreased GM concentration in heterosexual men are shown in blue and areas of decreased GM concentration in homosexual women are shown in yellow (p<0.05; FDR corrected, sagittal section at x = −29). Reduced GM concentration of homosexual women (relative to heterosexual women) is located within a sex dimorphic brain area.
The novel finding of the present study is that homosexual women have less GM in the temporo-basal cortex, ventral cerebellum and left ventral premotor cortex compared with heterosexual women. No difference in GM was found between male homo- and heterosexuals. Finally, we were able to replicate previous findings regarding the influence of gender on regional grey matter in the adult human brain. Most of these differences are not influenced by sexual orientation.
The main morphometric difference between heterosexual and homosexual women was found in the left perirhinal cortex with a relative reduction in GM in homosexual women. This area was also found to be sex-dimorphic, showing a relative reduction in GM in males. This raises the question whether female homosexuality is associated with a sex atypical differentiation of this brain area. The perirhinal cortex is located close to entorhinal cortex, hippocampus, parahippocampal gyrus and amygdala, and is known to be involved in a variety of functions like olfactory processing, memory encoding and spatial processing. These functions are related to the processing of sexual stimuli as well.
Sex differences of the olfactory system are known at a behavioural level
Though we show that the perirhinal cortex is morphologically different in women dependent on their sexual orientation, the functional correlates of the difference in GM concentration remains to be explored. Several questions are raised by our finding and may stimulate future directions of research: First, the contribution of the area around the rhinal sulcus to sexual odour processing, sexual behaviour and pair-bonding in humans remains unknown. Second, it is unknown whether homosexual and heterosexual women show behavioural differences in odour perception. Third, the mechanisms leading to the GM differences in the perirhinal cortex remain to be determined.
In addition to the temporo-basal cortex, the ventral cerebellum and left ventral premotor cortex showed less GM compared to heterosexual women. The detected differences in the cerebellum and premotor cortex are difficult to interpret in the context of this exploratory investigation, as these areas were not sex-dimorphic. The functional significance of this morphometric difference needs to be clarified in future studies.
In the male group, sexual orientation was not associated with regional differences in GM. This indicates that at least at the macroscopic level, the cortex of homosexual men shows no male-to-female shift in GM concentration. Conversely, homosexual women showed in some areas, mostly in the temporo-basal cortex, less GM concentration than heterosexual women, depicting a trend towards a male-like GM pattern. This is of particular interest, because the temporobasal cluster showing a male-like decrease in GM concentration was found in an area that also showed changes related to gender. These findings – a “male-like” GM pattern in homosexual women but no “female-like” pattern in homosexual men - suggest that male and female homosexuality is not analogously manifested at a structural level in the human brain. Accordingly, there was no overall effect of sexual orientation on regional GM when considering women and man together.
The discrepant morphometric changes parallel other findings of sex-dimorphic features that were more male-like in homosexual women, but not female-like in homosexual men, such as the 2D∶4D finger ratio, otoacoustic emissions, and body build
In agreement with numerous studies