Subtly altered topological asymmetry of brain structural covariance networks in autism spectrum disorder across 43 datasets from the ENIGMA consortium.

Small average differences in the left-right asymmetry of cerebral cortical thickness have been reported in individuals with autism spectrum disorder (ASD) compared to typically developing controls, affecting widespread cortical regions. The possible impacts of these regional alterations in terms of structural network effects have not previously been characterized. Inter-regional morphological covariance analysis can capture network connectivity between different cortical areas at the macroscale level. Here, we used cortical thickness data from 1455 individuals with ASD and 1560 controls, across 43 independent datasets of the ENIGMA consortium's ASD Working Group, to assess hemispheric asymmetries of intra-individual structural covariance networks, using graph theory-based topological metrics. Compared with typical features of small-world architecture in controls, the ASD sample showed significantly altered average asymmetry of networks involving the fusiform, rostral middle frontal, and medial orbitofrontal cortex, involving higher randomization of the corresponding right-hemispheric networks in ASD. A network involving the superior frontal cortex showed decreased right-hemisphere randomization. Based on comparisons with meta-analyzed functional neuroimaging data, the altered connectivity asymmetry particularly affected networks that subserve executive functions, language-related and sensorimotor processes. These findings provide a network-level characterization of altered left-right brain asymmetry in ASD, based on a large combined sample. Altered asymmetrical brain development in ASD may be partly propagated among spatially distant regions through structural connectivity.

Reduced Gray Matter Volume of the Thalamus and Hippocampal Region in Elderly Healthy Adults with no Impact of APOE ɛ4: A Longitudinal Voxel-Based Morphometry Study.

BACKGROUND: Many cross-sectional voxel-based morphometry (VBM) investigations have shown significant inverse correlations between chronological age and gray matter (GM) volume in several brain regions in healthy humans. However, few VBM studies have documented GM decrements in the healthy elderly with repeated MRI measurements obtained in the same subjects. Also, the extent to which the APOE ɛ4 allele influences longitudinal findings of GM reduction in the healthy elderly is unclear. OBJECTIVE: Verify whether regional GM changes are associated with significant decrements in cognitive performance taking in account the presence of the APOE ɛ4 allele. METHODS: Using structural MRI datasets acquired in 55 cognitively intact elderly subjects at two time-points separated by approximately three years, we searched for voxels showing significant GM reductions taking into account differences in APOE genotype. RESULTS: We found global GM reductions as well as regional GM decrements in the right thalamus and left parahippocampal gyrus (p < 0.05, family-wise error corrected for multiple comparisons over the whole brain). These findings were not affected by APOE ɛ4. CONCLUSIONS: Irrespective of APOE ɛ4, longitudinal VBM analyses show that the hippocampal region and thalamus are critical sites where GM shrinkage is greater than the degree of global volume reduction in healthy elderly subjects.

Grey and white matter volumes either in treatment-naïve or hormone-treated transgender women: a voxel-based morphometry study.

Many previous magnetic resonance imaging (MRI) studies have documented sex differences in brain morphology, but the patterns of sexual brain differences in transgender women - male sex assigned at birth - with a diagnosis of gender dysphoria (TW) have been rarely investigated to date. We acquired T1-weighted MRI data for the following four (n = 80) groups: treatment-naïve TW (TNTW), TW treated with cross-sex hormones for at least one year (TTW), cisgender men, and cisgender women (cisgender individuals as controls). Differences in whole-brain and regional white matter volume and grey matter volume (GMV) were assessed using voxel-based morphometry. We found lower global brain volumes and regional GMVs in a large portion of the posterior-superior frontal cortex in the cisgender women group than in the TTW and cisgender men groups. Additionally, both transgender groups exhibited lower bilateral insular GMVs than the cisgender women group. Our results highlight differences in the insula in both transgender groups; such differences may be characteristic of TW. Furthermore, these alterations in the insula could be related to the neural network of body perception and reflect the distress that accompanies gender dysphoria.

Cortical and Subcortical Brain Morphometry Differences Between Patients With Autism Spectrum Disorder and Healthy Individuals Across the Lifespan: Results From the ENIGMA ASD Working Group.

OBJECTIVE: Neuroimaging studies show structural differences in both cortical and subcortical brain regions in children and adults with autism spectrum disorder (ASD) compared with healthy subjects. Findings are inconsistent, however, and it is unclear how differences develop across the lifespan. The authors investigated brain morphometry differences between individuals with ASD and healthy subjects, cross-sectionally across the lifespan, in a large multinational sample from the Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) ASD working group. METHOD: The sample comprised 1,571 patients with ASD and 1,651 healthy control subjects (age range, 2-64 years) from 49 participating sites. MRI scans were preprocessed at individual sites with a harmonized protocol based on a validated automated-segmentation software program. Mega-analyses were used to test for case-control differences in subcortical volumes, cortical thickness, and surface area. Development of brain morphometry over the lifespan was modeled using a fractional polynomial approach. RESULTS: The case-control mega-analysis demonstrated that ASD was associated with smaller subcortical volumes of the pallidum, putamen, amygdala, and nucleus accumbens (effect sizes [Cohen's d], 0.13 to -0.13), as well as increased cortical thickness in the frontal cortex and decreased thickness in the temporal cortex (effect sizes, -0.21 to 0.20). Analyses of age effects indicate that the development of cortical thickness is altered in ASD, with the largest differences occurring around adolescence. No age-by-ASD interactions were observed in the subcortical partitions. CONCLUSIONS: The ENIGMA ASD working group provides the largest study of brain morphometry differences in ASD to date, using a well-established, validated, publicly available analysis pipeline. ASD patients showed altered morphometry in the cognitive and affective parts of the striatum, frontal cortex, and temporal cortex. Complex developmental trajectories were observed for the different regions, with a developmental peak around adolescence. These findings suggest an interplay in the abnormal development of the striatal, frontal, and temporal regions in ASD across the lifespan.

Gray matter volumes in patients with bipolar disorder and their first-degree relatives.

Bipolar disorder (BD) is highly heritable. First-degree relatives of BD patient have an increased risk to develop the disease. We investigated abnormalities in gray matter (GM) volumes in healthy first-degree relatives of BD patients to identify possible brain structural endophenotypes for the disorder. 3D T1-weighted magnetic resonance images were obtained from 25 DSM-IV BD type I patients, 23 unaffected relatives, and 27 healthy controls (HC). A voxel-based morphometry protocol was used to compare differences in GM volumes between groups. BD patients presented reduced GM volumes bilaterally in the thalamus compared with HC. Relatives presented no global or regional GM differences compared with HC. Our negative results do not support the role of GM volume abnormalities as endophenotypes for BD. Thalamic volume abnormalities may be associated the pathophysiology of the disease.