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

White matter integrity related to functional working memory networks in traumatic brain injury

Objective: This study explores the functional and structural patterns of connectivity underlying working memory impairment after severe traumatic axonal injury. Methods: We performed an fMRI n-back task and acquired diffusion tensor images (DTI) in a group of 19 chronic-stage patients with severe traumatic brain injury (TBI) and evidence of traumatic axonal injury and 19 matched healthy controls. We performed image analyses with FSL software and fMRI data were analyzed using probabilistic independent component analysis. Fractional anisotropy (FA) maps from DTI images were analyzed with FMRIB's Diffusion Toolbox. Results: We identified working memory and default mode networks. Global FA values correlated with both networks and FA whole-brain analysis revealed correlations in several tracts associated with the functional activation. Furthermore, working memory performance in the patient group correlated with the functional activation patterns and with the FA values of the associative fasciculi. Conclusion: Combining structural and functional neuroimaging data, we were able to describe structural white matter changes related to functional network alterations and to lower performance in working memory in chronic TBI.MAPFRE FoundationPreprintMedicin

Sex differences in brain and cognition in de novo Parkinson's disease

Background and objective: Brain atrophy and cognitive impairment in neurodegenerative diseases are influenced by sex. We aimed to investigate sex differences in brain atrophy and cognition in de novo Parkinson's disease (PD) patients. Methods: Clinical, neuropsychological and T1-weighted MRI data from 205 PD patients (127 males:78 females) and 69 healthy controls (40 males:29 females) were obtained from the PPMI dataset. Results: PD males had a greater motor and rapid eye movement sleep behavior disorder symptomatology than PD females. They also showed cortical thinning in postcentral and precentral regions, greater global cortical and subcortical atrophy and smaller volumes in thalamus, caudate, putamen, pallidum, hippocampus, and brainstem, compared with PD females. Healthy controls only showed reduced hippocampal volume in males compared to females. PD males performed worse than PD females in global cognition, immediate verbal recall, and mental processing speed. In both groups males performed worse than females in semantic verbal fluency and delayed verbal recall; as well as females performed worse than males in visuospatial function. Conclusions: Sex effect in brain and cognition is already evident in de novo PD not explained by age per se, being a relevant factor to consider in clinical and translational research in PD

Brain atrophy pattern in de novo Parkinsons disease with probable RBD associated with cognitive impairment

Rapid eye movement sleep behavior disorder (RBD) is associated with high likelihood of prodromal Parkinson's disease (PD) and is common in de novo PD. It is associated with greater cognitive impairment and brain atrophy. However, the relation between structural brain characteristics and cognition remains poorly understood. We aimed to investigate subcortical and cortical atrophy in de novo PD with probable RBD (PD-pRBD) and to relate it with cognitive impairment. We analyzed volumetry, cortical thickness, and cognitive measures from 79 PD-pRBD patients, 126 PD without probable RBD patients (PD-non pRBD), and 69 controls from the Parkinson's Progression Markers Initiative (PPMI). Regression models of cognition were tested using magnetic resonance imaging measures as predictors. We found lower left thalamus volume in PD-pRBD compared with PD-non pRBD. Compared with controls, PD-pRBD group showed atrophy in the bilateral putamen, left hippocampus, left amygdala, and thinning in the right superior temporal gyrus. Specific deep gray matter nuclei volumes were associated with impairment in global cognition, phonemic fluency, processing speed, and visuospatial function in PD-pRBD. In conclusion, cognitive impairment and gray matter atrophy are already present in de novo PD-pRBD. Thalamus, hippocampus, and putamen volumes were mainly associated with these cognitive deficits

Impaired Structural Connectivity In Parkinson's Disease Patients With Mild Cognitive Impairment: A Study Based On Probabilistic Tractography

Background: Probabilistic tractography, in combination with graph theory, has been used to reconstruct the structural whole-brain connectome. Threshold-free network-based statistics (TFNBS) is a useful technique to study structural connectivity in neurodegenerative disorders; however, there are no previous studies using TFNBS in Parkinson's disease (PD) with and without mild cognitive impairment (MCI). Methods: Sixty-two PD patients, 27 of whom classified as PD-MCI, and 51 healthy controls (HC) underwent diffusion-weighted 3T MRI. Probabilistic tractography, using FSL, was used to compute the number of streamlines (NOS) between regions. NOS matrices were used to find group differences with TFNBS, and to calculate global and local measures of network integrity using graph theory. A binominal logistic regression was then used to assess the discrimination between PD with and without MCI using non-overlapping significant tracts. Tract-based spatial statistics (TBSS) were also performed with FSL to study changes in fractional anisotropy (FA) and mean diffusivity (MD). Results: PD-MCI showed 37 white matter (WM) connections with reduced connectivity strength compared to HC, mainly involving temporo-occipital regions. These were able to differentiate PD-MCI from PD without MCI with an area under the curve of 83-85%. PD without MCI showed disrupted connectivity in 18 connections involving fronto-temporal regions. No significant differences were found in graph measures. Only PD-MCI showed reduced FA compared with HC. Discussion: TFNBS based on whole-brain probabilistic tractography can detect structural connectivity alterations in PD with and without MCI. Reduced structural connectivity in fronto-striatal and posterior corticocortical connections is associated with PD-MCI

Mechanisms of Cognitive Impairment in Cerebral Small Vessel Disease: Multimodal MRI Results from the St George's Cognition and Neuroimaging in Stroke (SCANS) Study.

Cerebral small vessel disease (SVD) is a common cause of vascular cognitive impairment. A number of disease features can be assessed on MRI including lacunar infarcts, T2 lesion volume, brain atrophy, and cerebral microbleeds. In addition, diffusion tensor imaging (DTI) is sensitive to disruption of white matter ultrastructure, and recently it has been suggested that additional information on the pattern of damage may be obtained from axial diffusivity, a proposed marker of axonal damage, and radial diffusivity, an indicator of demyelination. We determined the contribution of these whole brain MRI markers to cognitive impairment in SVD. Consecutive patients with lacunar stroke and confluent leukoaraiosis were recruited into the ongoing SCANS study of cognitive impairment in SVD (n = 115), and underwent neuropsychological assessment and multimodal MRI. SVD subjects displayed poor performance on tests of executive function and processing speed. In the SVD group brain volume was lower, white matter hyperintensity volume higher and all diffusion characteristics differed significantly from control subjects (n = 50). On multi-predictor analysis independent predictors of executive function in SVD were lacunar infarct count and diffusivity of normal appearing white matter on DTI. Independent predictors of processing speed were lacunar infarct count and brain atrophy. Radial diffusivity was a stronger DTI predictor than axial diffusivity, suggesting ischaemic demyelination, seen neuropathologically in SVD, may be an important predictor of cognitive impairment in SVD. Our study provides information on the mechanism of cognitive impairment in SVD

Structural brain changes in post-acute COVID-19 patients with persistent olfactory dysfunction

Objective: This research aims to study structural brain changes in patients with persistent olfactory dysfunctions after coronavirus disease 2019 (COVID-19). Methods: COVID-19 patients were evaluated using T1-weighted and diffusion tensor imaging (DTI) on a 3T MRI scanner, 9.94 ± 3.83 months after COVID-19 diagnosis. Gray matter (GM) voxel-based morphometry was performed using FSL-VBM. Voxelwise statistical analysis of the fractional anisotropy, mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity was carried out with the tract-based spatial statistics in the olfactory system. The smell identification test (UPSIT) was used to classify patients as normal olfaction or olfactory dysfunction groups. Intergroup comparisons between GM and DTI measures were computed, as well as correlations with the UPSIT scores. Results: Forty-eight COVID-19 patients were included in the study. Twenty-three were classified as olfactory dysfunction, and 25 as normal olfaction. The olfactory dysfunction group had lower GM volume in a cluster involving the left amygdala, insular cortex, parahippocampal gyrus, frontal superior and inferior orbital gyri, gyrus rectus, olfactory cortex, caudate, and putamen. This group also showed higher MD values in the genu of the corpus callosum, the orbitofrontal area, the anterior thalamic radiation, and the forceps minor; and higher RD values in the anterior corona radiata, the genu of the corpus callosum, and uncinate fasciculus compared with the normal olfaction group. The UPSIT scores for the whole sample were negatively associated with both MD and RD values (p-value ≤0.05 FWE-corrected). Interpretation: There is decreased GM volume and increased MD in olfactory-related regions explaining prolonged olfactory deficits in post-acute COVID-19 patients

Sex differences in brain atrophy and cognitive impairment in Parkinson's disease patients with and without probable rapid eye movement sleep behavior disorder

Background: The presence of rapid eye movement sleep behavior disorder (RBD) contributes to increase cognitive impairment and brain atrophy in Parkinson's disease (PD), but the impact of sex is unclear. We aimed to investigate sex differences in cognition and brain atrophy in PD patients with and without probable RBD (pRBD). Methods: Magnetic resonance imaging and cognition data were obtained for 274 participants from the Parkinson's Progression Marker Initiative database: 79 PD with pRBD (PD-pRBD; male/female, 54/25), 126 PD without pRBD (PD-non pRBD; male/female, 73/53), and 69 healthy controls (male/female, 40/29). FreeSurfer was used to obtain volumetric and cortical thickness data. Results: Males showed greater global cortical and subcortical gray matter atrophy than females in the PD-pRBD group. Significant group-by-sex interactions were found in the pallidum. Structures showing a within-group sex effect in the deep gray matter differed, with significant volume reductions for males in one structure in in PD-non pRBD (brainstem), and three in PD-pRBD (caudate, pallidum and brainstem). Significant group-by-sex interactions were found in Montreal Cognitive Assessment (MoCA) and Symbol Digits Modalities Test (SDMT). Males performed worse than females in MoCA, phonemic fluency and SDMT in the PD-pRBD group. Conclusion: Male sex is related to increased cognitive impairment and subcortical atrophy in de novo PD-pRBD. Accordingly, we suggest that sex differences are relevant and should be considered in future clinical and translational research

Parameters from site classification to harmonize MRI clinical studies: Application to a multi-site Parkinson's disease dataset

Multi-site MRI datasets are crucial for big data research. However, neuroimaging studies must face the batch effect. Here, we propose an approach that uses the predictive probabilities provided by Gaussian processes (GPs) to harmonize clinical-based studies. A multi-site dataset of 216 Parkinson's disease (PD) patients and 87 healthy subjects (HS) was used. We performed a site GP classification using MRI data. The outcomes estimated from this classification, redefined like Weighted HARMonization PArameters (WHARMPA), were used as regressors in two different clinical studies: A PD versus HS machine learning classification using GP, and a VBM comparison (FWE-p < .05, k = 100). Same studies were also conducted using conventional Boolean site covariates, and without information about site belonging. The results from site GP classification provided high scores, balanced accuracy (BAC) was 98.39% for grey matter images. PD versus HS classification performed better when the WHARMPA were used to harmonize (BAC = 78.60%; AUC = 0.90) than when using the Boolean site information (BAC = 56.31%; AUC = 0.71) and without it (BAC = 57.22%; AUC = 0.73). The VBM analysis harmonized using WHARMPA provided larger and more statistically robust clusters in regions previously reported in PD than when the Boolean site covariates or no corrections were added to the model. In conclusion, WHARMPA might encode global site-effects quantitatively and allow the harmonization of data. This method is user-friendly and provides a powerful solution, without complex implementations, to clean the analyses by removing variability associated with the differences between sites