Abstract
Background
Although widespread structural brain abnormalities have been consistently reported in schizophrenia, their relation to the heterogeneous clinical manifestations is not well ...understood. Multivariate methods are needed to uncover covariance patterns between multiple symptom dimensions and system-wide brain imaging data.
Methods
This cross-sectional study used structural magnetic resonance imaging and neuropsychological data from 133 patients with chronic schizophrenia (48 female, 34.8±13.2 years) from the Northwestern University Schizophrenia Data and Software Tool (NUSDAST). We estimate disease-related voxel-wise tissue volume loss using deformation-based morphometry (DBM) of T1 weighted images. In patients with schizophrenia, multiple clinical dimensions including positive/negative symptoms and cognitive deficits, demographic data as well as individual tissue volume loss (DBM) were included in the multivariate model. Clinical-anatomical phenotypes were identified using partial least squares analysis.
Results
Multivariate analysis revealed three distinct clinical-anatomical phenotypes accounting for 27.5%, 15%, and 13% of the shared covariance between clinical-behavioural data and tissue volume loss (total of 55.5%). The first clinical-anatomical phenotype encompassed cognitive impairments, severity of negative symptoms and tissue volume loss within the default mode network and visual network. The second clinical-anatomical phenotype was associated with additional cognitive impairments and tissue volume loss within the frontoparietal and ventral attention network, while the third clinical-anatomical phenotype encompassed a mixed positive and negative symptoms phenotype and tissue volume loss within the dorsal attention network. Critically, the pattern of volume loss within the first most prevalent clinical-anatomical phenotype mediated (a*b) the effect of socioeconomic status on clinical outcome (cognitive performance and negative symptoms) (a*b=-0.033(0.008); P<1.0×〖10〗^(-4); 95% CI -0.049, -0.018). Finally, we partly replicated the first clinical-anatomical phenotype in an independent sample of patients with schizophrenia (n=108).
Discussion
The heterogeneous clinical manifestation of schizophrenia can be significantly explained by three clinical-anatomical phenotypes. Despite their distributed topography, each phenotype is centered on a specific, well-defined set of intrinsic networks.
Abstract
Socioeconomic status (SES) anchors individuals in their social network layers. Our embedding in the societal fabric resonates with habitus, world view, opportunity, and health disparity. It ...remains obscure how distinct facets of SES are reflected in the architecture of the central nervous system. Here, we capitalized on multivariate multi-output learning algorithms to explore possible imprints of SES in gray and white matter structure in the wider population (n ≈ 10,000 UK Biobank participants). Individuals with higher SES, compared with those with lower SES, showed a pattern of increased region volumes in the left brain and decreased region volumes in the right brain. The analogous lateralization pattern emerged for the fiber structure of anatomical white matter tracts. Our multimodal findings suggest hemispheric asymmetry as an SES-related brain signature, which was consistent across six different indicators of SES: degree, education, income, job, neighborhood and vehicle count. Hence, hemispheric specialization may have evolved in human primates in a way that reveals crucial links to SES.
Abstract
Brain atrophy has been reported in the early stages of Parkinson’s disease, but there have been few longitudinal studies. How intrinsic properties of the brain, such as anatomical ...connectivity, local cell-type distribution and gene expression combine to determine the pattern of disease progression also remains unknown. One hypothesis proposes that the disease stems from prion-like propagation of misfolded alpha-synuclein via the connectome that might cause varying degrees of tissue damage based on local properties. Here, we used MRI data from the Parkinson Progression Markers Initiative to map the progression of brain atrophy over 1, 2 and 4 years compared with baseline. We derived atrophy maps for four time points using deformation-based morphometry applied to T1-weighted MRI from 120 de novo Parkinson’s disease patients, 74 of whom had imaging at all four time points (50 Men: 24 Women) and 157 healthy control participants (115 Men: 42 Women). In order to determine factors that may influence neurodegeneration, we related atrophy progression to brain structural and functional connectivity, cell-type expression and gene ontology enrichment analyses. After regressing out the expected age and sex effects associated with normal ageing, we found that atrophy significantly progressed over 2 and 4 years in the caudate, nucleus accumbens, hippocampus and posterior cortical regions. This progression was shaped by both structural and functional brain connectivity. Also, the progression of atrophy was more pronounced in regions with a higher expression of genes related to synapses and was inversely related to the prevalence of oligodendrocytes and endothelial cells. In sum, we demonstrate that the progression of atrophy in Parkinson’s disease is in line with the prion-like propagation hypothesis of alpha-synuclein and provide evidence that synapses may be especially vulnerable to synucleinopathy. In addition to identifying vulnerable brain regions, this study reveals different factors that may be implicated in the neurotoxic mechanisms leading to progression in Parkinson’s disease. All brain maps generated here are available on request.
Tremblay et al. report a specific pattern of atrophy progression over four years in the brain of patients with de novo Parkinson’s disease and related it to brain structural and functional connectivity, cell-type expression and genes associated with synaptic activity.
Graphical Abstract
Graphical Abstract
Abstract
In mammals, many sperm that reach the oviduct are held in a reservoir by binding to epithelium. To leave the reservoir, sperm detach from the epithelium; however, they may bind and detach ...again as they ascend into the ampulla toward oocytes. In order to elucidate the nature of binding interactions along the oviduct, we compared the effects of bursts of strong fluid flow (as would be caused by oviductal contractions), heparin, and hyperactivation on detachment of bovine sperm bound in vitro to epithelium on intact folds of isthmic and ampullar mucosa. Intact folds of oviductal mucosa were used to represent the strong attachments of epithelial cells to each other and to underlying connective tissue that exist in vivo. Effects of heparin on binding were tested because heparin binds to the Binder of SPerm (BSP) proteins that attach sperm to oviductal epithelium. Sperm bound by their heads to beating cilia on both isthmic and ampullar epithelia and could not be detached by strong bursts of fluid flow. Addition of heparin immediately detached sperm from isthmic epithelium but not ampullar epithelium. Addition of 4-aminopyridine immediately stimulated hyperactivation of sperm but did not detach them from isthmic or ampullar epithelium unless added with heparin. These observations indicate that the nature of binding of sperm to ampullar epithelium differs from that of binding to isthmic epithelium; specifically, sperm bound to isthmic epithelium can be detached by heparin alone, while sperm bound to ampullar epithelium requires both heparin and hyperactivation to detach from the epithelium.
PDF
