Neural Network of Body Representation Differs between Transsexuals and Cissexuals

<div><p>Body image is the internal representation of an individual’s own physical appearance. Individuals with gender identity disorder (GID), commonly referred to as transsexuals (TXs), are unable to form a satisfactory body image due to the dissonance between their biological sex and gender identity. We reasoned that changes in the resting-state functional connectivity (rsFC) network would neurologically reflect such experiential incongruence in TXs. Using graph theory-based network analysis, we investigated the regional changes of the degree centrality of the rsFC network. The degree centrality is an index of the functional importance of a node in a neural network. We hypothesized that three key regions of the body representation network, i.e., the primary somatosensory cortex, the superior parietal lobule and the insula, would show a higher degree centrality in TXs. Twenty-three pre-treatment TXs (11 male-to-female and 12 female-to-male TXs) as one psychosocial group and 23 age-matched healthy cissexual control subjects (CISs, 11 males and 12 females) were recruited. Resting-state functional magnetic resonance imaging was performed, and binarized rsFC networks were constructed. The TXs demonstrated a significantly higher degree centrality in the bilateral superior parietal lobule and the primary somatosensory cortex. In addition, the connectivity between the right insula and the bilateral primary somatosensory cortices was negatively correlated with the selfness rating of their desired genders. These data indicate that the key components of body representation manifest in TXs as critical function hubs in the rsFC network. The negative association may imply a coping mechanism that dissociates bodily emotion from body image. The changes in the functional connectome may serve as representational markers for the dysphoric bodily self of TXs.</p></div

Inclusion and exclusion criteria for the TX group and the CON group.

<p>*Subjects who were in the period ranging from less than 11 days (follicular phase) or more than 17 days after the beginning of their last menses were included. Follow-up phone calls were made to verify the date of the beginning of the next menses. This selection criterion was used on the basis that sudden surges in LH (luteinizing hormone) and FSH (follicle stimulating hormone) at mid-menstrual cycle could affect brain activation patterns.</p

Inclusion and exclusion criteria for the TX and the CIS groups.

<p>Subjects who were in the period ranging from less than 11 days (follicular phase) or more than 17 days after the beginning of their last menses were included. Follow-up phone calls were made to verify the date of the beginning of the next menses. This selection criterion was used on the basis that sudden surges in LH (luteinizing hormone) and FSH (follicle stimulating hormone) at mid-menstrual cycle could affect brain activation patterns.</p

Connectional pattern of the node of interests (NOIs).

<p>The nodes with stronger connections (i.e., group connectivity >10%) within each of the NOIs are displayed for the TX and the CIS groups. The nodal size and edge color denote the strength of the group connectivity between a node and the NOI. Stronger group connectivity indicates that a larger number of participants shared the same edge in their binary networks.</p

Behavioral and neuroimaging data.

<p><i>Panel Ia. Arousal score</i>. Both TXs and CONs were highly aroused when watching the E-films. <i>Panel Ib. Selfness score</i>. Both TXs and CONs demonstrated high selfness ratings for their desired genders as opposed to the un-desired genders while watching the E-films. TXs, compared to CONs, rated higher <i>selfness</i> scores (P<0.001) for their desired genders when watching the E-films. Notably, TXs also reported high selfness ratings even while watching the N-films. In contrast, the CONs did not show such significant differences compared to the TXs and featured much lower <i>selfness</i> scores for their desireed genders when watching the N-films (P<0.001). <i>Panel IIa. Arousal score</i>. Both hormone-treated (H⁺/TXs) and untreated (H⁻/TXs) subgroups rated significantly higher levels of <i>arousal</i> when watching the E-films vs. N-films. <i>Panel IIb. Selfness score</i>. Both hormone-treated (H⁺/TXs) and untreated (H⁻/TXs) subgroups rated significantly higher <i>selfness</i> scores for the desired gender compared to the un-desired gender when watching the E-films and N-films. <i>Panel IIIa</i> and <i>Panel IIIb</i>. The imaging subgroups (H⁻/TXs and fc/CONs) showed similar rating patterns as those of their original groups (TXs and CONs, respectively). The two-tailed Wilcoxon signed-rank test was used for within-group comparisons. The asterisks indicate the level of significance. ** P<0.01, *** P<0.001.</p

Demographic data and the results of psychological assessments.

<p><b><i>Behavioral study.</i></b> Demographic data and the scores of psychological assessments were compared between TXs and CONs (total participants) and between hormone-treated (H⁺/TXs) and untreated (H⁻/TXs) subjects.</p><p><b><i>Neuroimaging study.</i></b> Demographic data and the scores of psychological assessments were compared between H⁻/TXs and fc/CONs for subjects participating in the neuroimaging experiment. Age and education are presented as the mean ± standard deviation in years. The percentage denotes the proportion of participants with a particular status within the group. Only sub-categories of the DSQ that reached statistical significance are listed.</p>a<p>The two-tailed Mann-Whitney <i>U</i>-test was used for between-group comparisons of continuous variables.</p>b<p>Fisher's exact test was used for between-group categorical variables. The asterisks indicate the level of significance.</p><p>*P<0.05;</p><p>**P<0.01;</p><p>***P<0.001.</p

The between-group difference in the degree centrality of the node of interests (NOIs).

<p>All NOIs showed an increased degree centrality (one-tailed two-sample t-test, TX>CIS) across a range of network densities (1–12%). An asterisk denotes p<0.05.</p

Abbreviations for the anatomical regions defined by the Harvard-Oxford cortical and subcortical atlases.

<p>Formerly termed the Supplementary Motor Cortex.</p

A priori voxel-based and ROI-based correlation analyses.

<p><i>Panel a. Intragroup comparison</i>. Voxel-based correlation analysis was performed by anchoring the VTA as the seed region (defined as a sphere with a 3-mm radius centered at the MNI coordinates [4, −18, −12]) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070808#pone.0070808-Georgiadis1" target="_blank">[11]</a>. The a priori ROIs specifically relate to the processing of social exclusion <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070808#pone.0070808-Eisenberger1" target="_blank">[13]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070808#pone.0070808-Slavich1" target="_blank">[14]</a>, emotional conflict in interpersonal relationships <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070808#pone.0070808-Ruz1" target="_blank">[15]</a> and behavioral adjustments in response to punishment <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070808#pone.0070808-Wrase1" target="_blank">[16]</a>. VTA-seeded ROI (radius  = 10 mm)-based analysis with a small-volume correction(SVC, controlled for the family-wise error, P = 0.05) was performed based on the connectivity map for H⁻/TXs and fc/CONs. <i>Panel b. Intergroup comparison</i>. The same VTA-seeded ROI-based analysis was performed using the contrast map (H⁻/TXs >fc/CONs) with and without a SVC. [X] indicates the cited reference.</p