This study examined how androgens modulate neural networks involved in empathy in female-to-male transsexuals. Brain responses in the mPFC and pSTS to emotional cues decreased during hormonal treatment. Before treatment, functional connections within frontal regions and between frontal, temporal, and striatal structures were stronger; after treatment, connections within the limbic system were stronger, similar to patterns in healthy males. The study assessed changes in brain activity and network connectivity before and during hormonal treatment in 8 transsexuals using fMRI to understand how hormones influence neural mechanisms underlying empathy.

1. Androgens Modulate Neural Networks of Empathetic
Processes in Female-to-Male Transsexuals
Z. Ye1, R. Kopyciok1, B. Mohammadi1,2, U. M. Krämer1, C. Brunnlieb1, M. Heldmann1, A. Samii2, T. F. Münte1
1University of Lübeck, Germany 2International Neuroscience Institute, Germany
Univariate Analysis
Performed with SPM8 on the basis of general linear model (p < 0.05
corrected at cluster level).
• Brain responses to emotional cues in the medial prefrontal cortex
(mPFC) and posterior superior temporal sulcus (pSTS) decreased
during hormonal treatment.
Network Analysis
Performed with the Brain Connectivity Toolbox on the basis of graph
theory
• Each cerebral hemisphere was segmented into 45 regions according to
the Automated Anatomical Labeling.
• Correlations were computed for every possible pair of regions to
construct the connectivity matrix.
• The connectivity matrix was systematically threshold to generate 99
undirected binary matrix with costs from 0.01 to 0.99 at 0.01 intervals.
• A small world network has both high global efficiency and high local
efficiency. The brain network behaved like the small world network
when cost = 0.12~0.23 (small-world regime).
• Statistics were performed in the samll-world regime. Alpha levels were
controlled with permutation (p < 0.05 corrected).
• Left and right middle cingulate cortex (LMC/RMC), left middle
temporal gyrus (LMT) and right superior temporal gyrus (RST) were
regional hubs of which centrality did not change when androgen level
changed.
Acknowledgments
Deutsche Forschungsgemeinschaft
• DFG, SFB 779, TP A5 to TFM
• KR 3691/1-1 to UMK
German Federal Department of
Research BMBF (to TFM).
More info: Thomas.muente@neuro.uni-luebeck.de (Prof. Dr. T. F. Münte)
Methods
Transsexuals and hormonal treatment
• Female-to-male transsexuals (n = 8, mean 28 years): Each was scanned
twice, once before (pre-test) and once during hormonal therapy (post-
test; 12months after the treatment began).
• Hormone administration route and schedules were heterogeneous, as
defined by the attending endocrinologist.
Healthy controls: Females (n = 31, mean 24 years) and Males (n = 30,
mean 27 years)
Research Questions
Women usually show higher sensitivity than men to emotional and social
cues and are therefore better in showing empathy with others and in
the deciphering of other’s intentions and mental states. These sex
differences have been linked to hormonal levels. However, it remains
unclear how hormones modulate neural mechanisms underlying
empathic processes. Here we assess effects of chronic hormonal
treatment in a group of female-to-male transsexuals before and during
androgen therapy with functional magnetic resonance imaging (fMRI).
We ask two questions.
Q1: How is brain activity in response to emotional and/or social cues
modulated during hormonal treatment in transsexuals (pre- vs. post-
test)? ( Univariate analysis)
Q2: How are neural networks of empathic processes modulated during
hormonal treatment in transsexuals? Do same differences show up in
healthy females vs. males? ( Graph theoretical analysis)
Stimuli and task
• Black-and-white drawings
depicting emotionally
negative or neural (Emot
vs. Neut) social situations
involving one or two
persons (One vs. Two)
• Participants watched the
pictures during three
sessions and completed a
recognition after each
session.
Data acquisition
• Collected on 3T Siemens scanner using EPI sequence, with 2000-ms
TR, 30-ms TE and 80°flip angle.
• 32 transversal slices; 192 mm*192 mm field of view; 3-mm thickness,
0.75-mm gap; 3 mm*3 mm in-plane resolution.
• MPFC and pSTS responses to social cues also decreased during
hormonal treatment.
• Functional connections within frontal regions, those between frontal
and temporal lobes, and those between frontal and striatal structures
were stronger when androgen level was low (transsexuals before
hormonal treatment and healthy females).
• Functional connections within limbic system was stronger when
androgen level was high (transsexuals after hormonal treatment and
healthy males).