Introduction

The goal of this assignment was to collect four peer reviewed scientific articles on the same topic in order to write an annotated bibliography. This article included a list of the four articles as well as their abstracts, an annotated bibliography chart in order to organize the readings and pick the most relevant aspects from them, and a final draft which portrayed the significance of each of the sources in the overall scientific community as well as in the forthcoming Literature Review assignment.

Annotated Bibliography Articles

Articles for Annotated Bibliography and Literature Review

1. Structural Connectivity Network of Transgender People

Abstract: Although previous investigations of transsexual people have focused on regional brain alterations, evaluations on a network level, especially those structural in nature, are largely missing. Therefore, we investigated the structural connectome of 23 female-to-male (FtM) and 21 male-to-female (MtF) transgender patients before hormone therapy as compared with 25 female and 25 male healthy controls. Graph theoretical analysis of whole-brain probabilistic tractography networks (adjusted for differences in intracranial volume) showed decreased hemispheric connectivity ratios of subcortical/limbic areas for both transgender groups. Subsequent analysis revealed that this finding was driven by increased interhemispheric lobar connectivity weights (LCWs) in MtF transsexuals and decreased interhemispheric LCWs in FtM patients. This was further reflected on a regional level, where the MtF group showed mostly increased local efficiencies and FtM patients decreased values. Importantly, these parameters separated each patient group from the remaining subjects for the majority of significant findings. This work complements previously established regional alterations with important findings of structural connectivity. Specifically, our data suggest that network parameters may reflect unique characteristics of transgender patients, whereas local physiological aspects have been shown to represent the transition from the biological sex to the actual gender identity.

2. Brain network interactions in transgender individuals with gender incongruence

Abstract:Functional brain organization in transgender persons remains unclear. Our aims were to investigate global and regional connectivity differences within functional networks in transwomen and transmen with early-in-life onset gender incongruence; and to test the consistency of two available hypotheses that attempted to explain gender variants: (i) a neurodevelopmental cortical hypothesis that suggests the existence of different brain phenotypes based on structural MRI data and genes polymorphisms of sex hormone receptors; (ii) a functional-based hypothesis in relation to regions involved in the own body perception. T2*-weighted images in a 3-T MRI were obtained from 29 transmen and 17 transwomen as well as 22 cisgender women and 19 cisgender men. Resting-state independent component analysis, seed-to-seed functional network and graph theory analyses were performed. Transmen, transwomen, and cisgender women had decreased connectivity compared with cisgender men in superior parietal regions, as part of the salience (SN) and the executive control (ECN) networks. Transmen also had weaker connectivity compared with cisgender men between intra-SN regions and weaker inter-network connectivity between regions of the SN, the default mode network (DMN), the ECN and the sensorimotor network. Transwomen had lower small-worldness, modularity and clustering coefficient than cisgender men. There were no differences among transmen, transwomen, and ciswomen. Together these results underline the importance of the SN interacting with DMN, ECN, and sensorimotor networks in transmen, involving regions of the entire brain with a frontal predominance. Reduced global connectivity graph-theoretical measures were a characteristic of transwomen. It is proposed that the interaction between networks is a keystone in building a gendered self. Finally, our findings suggest that both proposed hypotheses are complementary in explaining brain differences between gender variants.

3. Testosterone effects on the brains of transgender men

Abstract: Transgender individuals experience incongruence between their gender identity and birth-assigned sex. The resulting gender dysphoria (GD), which some gender-incongruent individuals experience, is theorized to be a consequence of atypical cerebral sexual differentiation, but support for this assertion is inconsistent. We recently found that GD is associated with disconnected networks involved in self-referential thinking and own body perception. Here, we investigate how these networks in trans men (assigned female at birth with male gender identity) are affected by testosterone. In 22 trans men, we obtained T₁-weighted, diffusion-weighted, and resting-state functional magnetic resonance imaging scans before and after testosterone treatment, measuring cortical thickness (Cth), subcortical volumes, fractional anisotropy (FA), and functional connectivity. Nineteen cisgender controls (male and female) were also scanned twice. The medial prefrontal cortex (mPFC) was thicker in trans men than controls pretreatment, and remained unchanged posttreatment. Testosterone treatment resulted in increased Cth in the insular cortex, changes in cortico-cortical thickness covariation between mPFC and occipital cortex, increased FA in the fronto-occipital tract connecting these regions, and increased functional connectivity between mPFC and temporo-parietal junction, compared with controls. Concluding, in trans men testosterone treatment resulted in functional and structural changes in self-referential and own body perception areas.

4. A structural magnetic resonance imaging study in transgender persons on cross-sex hormone therapy

Abstract: Background: To date, research findings are inconsistent about whether the neuroanatomy in transgender persons resembles that of their natal sex or their gender identity. Moreover, few studies have examined the effects of longterm cross-sex hormonal treatment on neuroanatomy in this cohort. The purpose of the present study was to examine neuroanatomical differences in transgender persons after prolonged cross-sex hormone therapy. Methods: Eighteen transgender men (female-to-male), 17 transgender women (male-to-female), 30 nontransgender men (natal men), and 27 nontransgender women (natal women) completed a high-resolution structural magnetic resonance imaging scan at 3 T. Eligibility criteria for transgender persons were gender-affirming surgery and at least 2 years of cross-sex hormone therapy. Exclusion criteria for nontransgender persons were the presence of psychiatric or neurological disorders. Results: The mean neuroanatomical volume for the amygdala, putamen, and corpus callosum differed between transgender women and natal women but not between transgender women and natal men. Differences between transgender men and natal men were found in several brain structures, including the medial temporal lobe structures and cerebellum. Differences between transgender men and natal women were found in the medial temporal lobe, nucleus accumbens, and 3rd ventricle. Sexual dimorphism between nontransgender men and women included larger cerebellar volumes and smaller anterior corpus callosum in natal men than in natal women. The results remained stable after correcting for additional factors including age, total intracranial volume, anxiety, and depressive symptoms. Conclusions: Neuroanatomical differences were region-specific between transgender persons and their natal sex as well as their gender identity, raising the possibility of a localized influence of sex hormones on neuroanatomy.

Annotated Bibliography Chart

Annotated Bibliography/Literature Review Chart of 4 Articles

Title/Authors	Research Question	Methods	Results	Discussion/Conclusions
Structural Connectivity Networks of Transgender People by Hahn Andreas, Kranz George S., Küblböck Martin, Kaufmann  Ulrike, Ganger Sebastian, Hummer Allan, Sieger Rene, Winkler Dietmar, Kasper  Siegfried, Windischberger Christian, Swaab Dick F., Lazenberger Rupert.	How are the structural connectomes arranged in the brain of transgender individuals compared to cisgendered individuals?	– 94 subjects total (23 FTM, 21 MTF, 25 healthy females, 21 healthy men) -Patients were diagnosed with having Gender Dysphoria by a licensed psychiatrist before testing-Patients went through normal doctor visit testing (pregnancy test, blood test, etc.-Patients underwent MRI testing in order to get weighted images of parts of the brain	-Most of the physiological aspects of the brain undergo a biological transition to the gender identity, while the aspects on a network level experience the stress that accompanies gender incongruence	-Differences in hemispheric and lobar connectivity were observed-Findings add valuable information to previous research regarding the whole brain
Brain network interactions in transgender individuals with gender incongruence by Carme Uribe, Carme Junque, Esther Gomez Gil, Alexandra Abos, Sven C. Mueller, Antonio Guillamon	Do different brain phenotypes exist for different genders?	-87 participants (29 transmen, 17 transwomen, 22 cisgender women, 19 cisgender men)-Brains were evaluated in a resting state-Interactions between functional networks in the frontal lobe were evaluated using MRI-Graph theory analyses was used to evaluate the MRI’s	-different brain phenotypes related to different variants of gender rather than just two for the common genders	-connectivity in the attentional brain network is relevant for both transmen and women-interrelations involve cortical and subcortical nodes over the whole-brain, but with a frontal predominance
Testosterone Effects on the Brain in Transgender Men by Sarah M Burke, Amir H Manzouri, Cecilia Dhejne, Karin Bergstrom, Stefan Arver, Jamie D Feusner, Ivanka Savic- Berglund	How are the disconnected brain networks in trans men affected by testosterone?	-The MRI of 22 trans men were taken-The diffusion of the brain was weighted, resting-state functional magnetic resonance imaging scans before and after testosterone treatment were taken, cortical thickness (Cth) was measured, subcortical volumes were taken, fractional anisotropy (FA) was measured as well as functional connectivity-19 cisgender men were also scanned twice	– treatment resulted in increased Cth in the insular cortex, changes in cortico-cortical thickness covariation between mPFC and occipital cortex, increased FA in the frontal-occipital tract connecting these regions, and increased functional connectivity between mPFC and temporoparietal junction, compared with controls	-Treatment resulted in both functional and structural changes in the self-referential portions of the brain
A Structural Magnetic Resonance Imaging Study in Transgender Persons on Cross-Hormone Sex Therapy by Sven C Mueller, Lionel Landre, Katrien Wiercks, Guy T’Sjoen	What are the neuroanatomical differences in transgender persons after prolonged cross-sex hormone therapy?	-18 trans men, 17 trans females, 30 cis men, and 27 cis women were in this study-Each subject underwent an MRI scan at 3T-Eligibility criteria was gender-affirming surgery and at least two years on T	-Difference between TM and NM in medial temporal lobe and cerebellum-Difference between TM and NW in the medial temporal lobe, nucleus acumens, and 3rd ventricle	-There might be a localized influence of sex hormones on neuroanatomy because neuroanatomical differences were region-specific

Final Draft of Annotated Bibliography

Brain Makeup of Transgender Individuals: An Annotated Bibliography

Hahn Andreas, Kranz George S., Küblböck Martin, Kaufmann Ulrike, Ganger Sebastian, Hummer Allan, Sieger Rene, Winkler Dietmar, Kasper Siegfried, Windischberger Christian, Swaab Dick F., Lazenberger Rupert. Structural Connectivity Networks of Transgender People. National Center for Biotechnology Information. [accessed 2020 April 27th]; 25(10): 3527–3534. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4585501/

This study focuses on network connectivity in different parts of the brain and how those network connections can impact gender identity and gender expression. There were a total of 94 people in this study. 50 of the subjects were men and women that did not go through hormone therapy. 23 of the subjects were female-to-male transgender patients while the other 21 were male-to-female transgender patients. The transgender patients were tested before hormone therapy. Statistical analysis was done on all of the brain imaging data. It was found that most of the psychological aspects of the brain undergo a biological transition to the gender identity, while the aspects on a network level experience the stress that accompanies gender incongruence.

Andreas Hahn and the rest of the authors are respected Oxford researchers who have all had their work cited many times before. They are neuroscientists who have been doing research into the network of the brain for decades. This particular study is one of the only ones that has ever focused on the network of transgender individuals. The results suggest that not only are the gender expression of transgender individuals similar to their brain function but they also experience stress in the brain because of gender incongruence.

Uribe Carme, Junque Carme, Gomez-Gil Esther, Abos Alexandra, Mueller Sven C, Antonio Guillamon. 2019. Brain network interactions in transgender individuals with gender incongruence. Elsevier. [accessed 2020 April 27th]; https://reader.elsevier.com/reader/sd/pii/S1053811920301002?token=DC7841D6BF1CAE0CAE4260965656F00039D820D6342C21FEB456F2ACDD4F42F90F1DF6F73EC06857E35D7F7CF709B54A

There were 87 participants in this study. 29 transmen, 17 transwomen, 22 cisgender women, and 19 cisgender men. The brains of these individuals were evaluated in a resting state, the interactions between the functional networks were studied, and graph theory analyses were performed. The study suggested that there are different brain phenotypes related to different variants of gender.

The authors of this article have written articles concerning this topic before. This article was done in order to investigate further research suggestions from a previous article. The focus of this study is the network connectivity of the brain overall. This study approached the brain as an entire organ, allowing for a more complete look at all of the temporal interactions. This article will be important for my review because it shows the difference in the lobes of the brain for both transgender and cisgender individuals.

Burke Sarah M, Manzouri Amir H, Dhejne Cecilia, Bergström Karin, Arver Stefan, Feusner Jamie D, Savic-Berglund Ivanka. 2018. Testosterone Effects on the Brain in Transgender Men. [accessed 2020 April 27th]; 28(5): 1582–1596. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6248653/

This study focused on 22 trans men before and after testosterone treatments, as well as 19 cisgender individuals as a control group. The study focused on the size of the prefrontal cortex as well as functional connectivity. It was found that in trans men the testosterone treatment resulted in both functional and structural changes in the self-referential portions of the brain.

The authors of this article (except for Jamie D Fausner who is a respected doctor in California) are renowned members of the scientific community in Sweden. The study found that testosterone treatment altered the brains of transgender individuals and brought them closer to their gender expression. This will be important for my literature review because this study shows how testosterone changes parts of the brain, it supports the idea of the plasticity of the brain.

Mueller Sven C, Landre Lionel, Wierckx Katrien, T’Sjoen Guy. 2016. A Structural Magnetic Resonance Imaging Study in Transgender Persons on Cross-Hormone Sex Therapy. Neuroendocrinology. [ accessed 2020 April 27th]; 105:123-130. https://www.karger.com/Article/PDF/448787

The goal of this study was to investigate the long term effect of cross-sex hormone therapy in the brain. 18 transgender men, 17 transgender women, 30 cis-gendered men, and 27 cis-gendered women were involved in this study. Transgender individuals could only be included in the study if they had been on treatment for at least two years. This study found that neuroanatomical differences were specific between natal and gender identity, meaning that sex therapy might have a localized influence on the brain.

The authors of this article are well known in their fields and have conducted similar research in the past. The finding of the article that the hormone might focus on specific parts of the brain is novel research. It will be important for my literature review because it presents a whole new take on the influence of drugs on the brains of transgender individuals.