Brain connectivity dynamics in cisgender and transmen people with gender incongruence before gender affirmative hormone treatment

Large-scale brain network interactions have been described between trans- and cis-gender binary identities. However, a temporal perspective of the brain's spontaneous fuctuations is missing. We investigated the functional connectivity dynamics in transmen with gender incongruence and its relationship with interoceptive awareness. We describe four states in native and meta-state spaces: (i) one state highly prevalent with sparse overall connections; (ii) a second with strong couplings mainly involving components of the salience, default, and executive control networks. Two states with global sparse connectivity but positive couplings (iii) within the sensorimotor network, and (iv) between salience network regions. Transmen had more dynamical fuidity than cismen, while cismen presented less meta-state fuidity and range dynamism than transmen and ciswomen. A positive association between attention regulation and fuidity and meta-state range dynamism was found in transmen. There exist gender diferences in the temporal brain dynamism, characterized by distinct interrelations of the salience network as catalyst interacting with other networks. We ofer a functional explanation from the neurodevelopmental cortical hypothesis of a gendered-self

Brain network interactions in transgender individuals with gender incongruence

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. Restingstate 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

Data for functional MRI connectivity in transgender people with gender incongruence and cisgender individuals

We provide T2*-weighted and T1-weighted images acquired on a 3T MRI scanner obtained from 17 transwomen and 29 transmen with gender incongruence; and 22 ciswomen and 19 cismen that identified themselves to the sex assigned at birth. Data from three different techniques that describe global and regional connectivity differences within functional resting-state networks in transwomen and transmen with early-in-life onset gender incongruence are provided: (1) we obtained spatial maps from data-driven independent component analysis using the melodic tool from FSL software; (2) we provide the functional networks interactions of two functional atlases' seeds from a seed-to-seed approach; (3) and global graph-theoretical metrics such as the smallworld organization, and the segregation and integration properties of the networks. Interpretations of the present dataset can be found in the original article, doi:10.1016/j.neuroimage.2020.116613[1]. The original and processed nifti images are available in Mendeley datasets. In addition, correlation matrices for the seed-to-seed and graph-theory analyses as well as the graph-theoretical measures were made available in Matlab files. Finally, we present supplementary information for the original article

Neuroanatomical and functional correlates of cognitive and affective empathy in young healthy adults

Neural substrates of empathy are mainly investigated through task-related functional MRI. However, the functional neural mechanisms at rest underlying the empathic response have been poorly studied. We aimed to investigate neuroanatomical and functional substrates of cognitive and affective empathy. The self-reported empathy questionnaire Cognitive and Affective Empathy Test (TECA), T1 and T2∗-weighted 3-Tesla MRI were obtained from 22 healthy young females (mean age: 19.6 ± 2.4) and 20 males (mean age: 22.5 ± 4.4). Groups of low and high empathy were established for each scale. FreeSurfer v6.0 was used to estimate cortical thickness and to automatically segment the subcortical structures. FSL v5.0.10 was used to compare resting-state connectivity differences between empathy groups in six defined regions: the orbitofrontal, cingulate, and insular cortices, and the amygdala, hippocampus, and thalamus using a non-parametric permutation approach. The high empathy group in the Perspective Taking subscale (cognitive empathy) had greater thickness in the left orbitofrontal and ventrolateral frontal cortices, bilateral anterior cingulate, superior frontal, and occipital regions. Within the affective empathy scales, subjects with high Empathic Distress had higher thalamic volumes than the low-empathy group. Regarding resting-state connectivity analyses, low-empathy individuals in the Empathic Happiness scale had increased connectivity between the orbitofrontal cortex and the anterior cingulate when compared with the high-empathy group. In conclusion, from a structural point of view, there is a clear dissociation between the brain correlates of affective and cognitive factors of empathy. Neocortical correlates were found for the cognitive empathy dimension, whereas affective empathy is related to lower volumes in subcortical structures. Functionally, affective empathy is linked to connectivity between the orbital and cingulate cortices

Patterns of cortical thinning in nondemented Parkinson's disease patients

Background: Clinical variability in the Parkinson's disease phenotype suggests the existence of disease subtypes. We investigated whether distinct anatomical patterns of atrophy can be identified in Parkinson's disease using a hypothesis-free, datadriven approach based on cortical thickness data. Methods: T1-weighted 3-tesla MRI and a comprehensive neuropsychological assessment were performed in a sample of 88 nondemented Parkinson's disease patients and 31 healthy controls. We performed a hierarchical cluster analysis of imaging data using Ward's linkage method. A general linear model with cortical thickness data was used to compare clustering groups. Results: We observed 3 patterns of cortical thinning in patients when compared with healthy controls. Pattern 1 (n530, 34.09%) consisted of cortical atrophy in bilateral precentral gyrus, inferior and superior parietal lobules, cuneus, posterior cingulate, and parahippocampal gyrus. These patients showed worse cognitive performance when compared with controls and the other 2 patterns. Pattern 2 (n529, 32.95%) consisted of cortical atrophy involving occipital and frontal as well as superior parietal areas and included patients with younger age at onset. Finally, in pattern 3 (n529, 32.95%), there was no detectable cortical thinning. Patients in the 3 patterns did not differ in disease duration, motor severity, dopaminergic medication doses, or presence of mild cognitive impairment. Conclusions: Three cortical atrophy subtypes were identified in nondemented Parkinson's disease patients: (1) parieto-temporal pattern of atrophy with worse cognitive performance, (2) occipital and frontal cortical atrophy and younger disease onset, and (3) patients without detectable cortical atrophy. These findings may help identify prognosis markers in Parkinson's disease. VC 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Societ

The Effects of Testosterone on the Brain of Transgender Men

Transgender men (TM) experience an incongruence between the female sex assigned when they were born and their self-perceived male identity. Some TM seek for a gender affirming hormone treatment (GAHT) to induce a somatic transition from female to male through continuous administration of testosterone. GAHT seems to be relatively safe. However, testosterone produces structural changes in the brain as detected by quantitative magnetic resonance imaging. Mainly, it induces an increase in cortical volume and thickness and subcortical structural volume probably due to the anabolic effects. Animal models, specifically developed to test the anabolic hypothesis, suggest that testosterone and estradiol, its aromatized metabolite, participate in the control of astrocyte water trafficking, thereby controlling brain volume

Disrupted functional connectivity in PD with probable RBD and its cognitive correlates

Recent studies associated rapid eye movement sleep behavior disorder (RBD) in Parkinson's disease (PD) with severe cognitive impairment and brain atrophy. However, whole-brain functional connectivity has never been explored in this group of PD patients. In this study, whole-brain network-based statistics and graph-theoretical approaches were used to characterize resting-state interregional functional connectivity in PD with probable RBD (PD-pRBD) and its relationship with cognition. Our sample consisted of 30 healthy controls, 32 PD without probable RBD (PD-non pRBD), and 27 PD-pRBD. The PD-pRBD group showed reduced functional connectivity compared with controls mainly involving cingulate areas with temporal, frontal, insular, and thalamic regions (p < 0.001). Also, the PD-pRBD group showed reduced functional connectivity between right ventral posterior cingulate and left medial precuneus compared with PD-non pRBD (p < 0.05). We found increased normalized characteristic path length in PD-pRBD compared with PD-non pRBD. In the PD-pRBD group, mean connectivity strength from reduced connections correlated with visuoperceptual task and normalized characteristic path length correlated with processing speed and verbal memory tasks. This work demonstrates the existence of disrupted functional connectivity in PD-pRBD, together with abnormal network integrity, that supports its consideration as a severe PD subtype

Comparing the accuracy and neuroanatomical correlates of the UPSIT-40 and the Sniffin' Sticks test in REM sleep behavior disorder

Background: Olfactory impairment increases the risk of developing neurodegenerative diseases in patients with idiopathic REM sleep behavior disorder (IRBD). Knowing the test properties of distinct olfactory measures could contribute to their selection for clinical or research purposes. Objective: To compare the accuracy in distinguishing IRBD patients from controls with the University of Pennsylvania Smell Identification Test (UPSIT-40) and Sniffin' Sticks Extended test, and to assess the gray-matter volume correlates of these tests. Method: Twenty-one patients with IRBD and 27 healthy controls were assessed using both olfactory tests. Independent logistic regressions were computed with diagnosis as a dependent variable and olfactory measures as predictive variables. Receiver operating characteristic curves were computed for each olfactory subtest. Diagnostic accuracy for IRBD was calculated according to the resulting optimal cut-off score. Structural MRI data, acquired with a 3T scanner, were analyzed with voxel-based morphometry. Results: Patients differed from controls in all olfactory measures. The Sniffin-Identification correctly classified 89.1% of cases; the UPSIT-40, 85.4%; the Sniffin-Discrimination, 82.6%; the Sniffin-Total, 81.8%; and the Sniffin-Threshold, 77.3%. Respective AUROC, optimal cut-off, sensitivity, and specificity for each test were: 0.902, ≤26, 85.7%, and 85.2% for the UPSIT-40; 0.884, ≤29, 89.5%, and 76.0% for the Sniffin-Total; 0.922, ≤11, 90.5%, and 88.0% for the Sniffin-Identification; 0.739, ≤4, 73.7%, and 76.0% for the Sniffin-Threshold; and 0.838, ≤11, 85.7%, and 76.0% for the Sniffin-Discrimination. UPSIT-40 scores correlated with gray-matter volumes in orbitofrontal regions in anosmic patients. Conclusions: UPSIT-40 and Sniffin' Identification showed similar discrimination accuracy, but only the UPSIT-40 showed structural correlates (p ≤ .05 FDR-corrected)

Disruption of posterior brain functional connectivity and its relation to cognitive impairment in idiopathic REM sleep behavior disorder

Background: Resting-state functional MRI has been proposed as a new biomarker of prodromal neurodegenerative disorders, but it has been poorly investigated in the idiopathic form of rapid-eye-movement sleep behavior disorder (IRBD), a clinical harbinger of subsequent synucleinopathy. Particularly, a complex-network approach has not been tested to study brain functional connectivity in IRBD patients. Objectives: The aim of the current work is to characterize resting-state functional connectivity in IRBD patients using a complex-network approach and to determine its possible relation to cognitive impairment. Method: Twenty patients with IRBD and 27 matched healthy controls (HC) underwent resting-state functional MRI with a 3T scanner and a comprehensive neuropsychological battery. The functional connectome was studied using threshold-free network-based statistics. Global and local network parameters were calculated based on graph theory and compared between groups. Head motion, age and sex were introduced as covariates in all analyses. Results: IRBD patients showed reduced cortico-cortical functional connectivity strength in comparison with HC in edges located in posterior regions (p <0.05, FWE corrected). This regional pattern was also shown in an independent analysis comprising posterior areas where a decreased connectivity in 51 edges was found, whereas no significant results were detected when an anterior network was considered (p <0.05, FWE corrected). In the posterior network, the left superior parietal lobule had reduced centrality in IRBD. Functional connectivity strength between left inferior temporal lobe and right superior parietal lobule positively correlated with mental processing speed in IRBD (r=.633; p=.003). No significant correlations were found in the HC group. Conclusion: : Our findings support the presence of disrupted posterior functional brain connectivity of IRBD patients similar to that found in synucleinopathies. Moreover, connectivity reductions in IRBD were associated with lower performance in mental processing speed domain

Differentiation of multiple system atrophy from Parkinson's disease by structural connectivity derived from probabilistic tractography

Recent studies combining difusion tensor-derived metrics and machine learning have shown promising results in the discrimination of multiple system atrophy (MSA) and Parkinson's disease (PD) patients. This approach has not been tested using more complex methodologies such as probabilistic tractography. The aim of this work is assessing whether the strength of structural connectivity between subcortical structures, measured as the number of streamlines (NOS) derived from tractography, can be used to classify MSA and PD patients at the single-patient level. The classifcation performance of subcortical FA and MD was also evaluated to compare the discriminant ability between difusion tensor-derived metrics and NOS. Using difusion-weighted images acquired in a 3T MRI scanner and probabilistic tractography, we reconstructed the white matter tracts between 18 subcortical structures from a sample of 54 healthy controls, 31 MSA patients and 65 PD patients. NOS between subcortical structures were compared between groups and entered as features into a machine learning algorithm. Reduced NOS in MSA compared with controls and PD were found in connections between the putamen, pallidum, ventral diencephalon, thalamus, and cerebellum, in both right and left hemispheres. The classifcation procedure achieved an overall accuracy of 78%, with 71% of the MSA subjects and 86% of the PD patients correctly classifed. NOS features outperformed the discrimination performance obtained with FA and MD. Our fndings suggest that structural connectivity derived from tractography has the potential to correctly distinguish between MSA and PD patients. Furthermore, NOS measures obtained from tractography might be more useful than difusion tensor-derived metrics for the detection of MSA