Understanding the evolution of negative symptoms in first-episode psychosis (FEP) requires long-term longitudinal study designs that capture the progression of this condition and the associated brain ...changes.
To explore the factors underlying negative symptoms and their association with long-term abnormal brain trajectories.
We followed up 357 people with FEP over a 10-year period. Factor analyses were conducted to explore negative symptom dimensionality. Latent growth mixture modelling (LGMM) was used to identify the latent classes. Analysis of variance (ANOVA) was conducted to investigate developmental trajectories of cortical thickness. Finally, the resulting ANOVA maps were correlated with a wide set of regional molecular profiles derived from public databases.
Three trajectories (stable, decreasing and increasing) were found in each of the three factors (expressivity, experiential and attention) identified by the factor analyses. Patients with an increasing trajectory in the expressivity factor showed cortical thinning in caudal middle frontal, pars triangularis, rostral middle frontal and superior frontal regions from the third to the tenth year after the onset of the psychotic disorder. The
-statistic map of cortical thickness expressivity differences was associated with a receptor density map derived from positron emission tomography data.
Stable and decreasing were the most common trajectories. Additionally, cortical thickness abnormalities found at relatively late stages of FEP onset could be exploited as a biomarker of poor symptom outcome in the expressivity dimension. Finally, the brain areas with less density of receptors spatially overlap areas that discriminate the trajectories of the expressivity dimension.
Macroscopic cortical networks are important for cognitive function, but it remains challenging to construct anatomically plausible individual structural connectomes from human neuroimaging. We ...introduce a new technique for cortical network mapping based on inter-regional similarity of multiple morphometric parameters measured using multimodal MRI. In three cohorts (two human, one macaque), we find that the resulting morphometric similarity networks (MSNs) have a complex topological organization comprising modules and high-degree hubs. Human MSN modules recapitulate known cortical cytoarchitectonic divisions, and greater inter-regional morphometric similarity was associated with stronger inter-regional co-expression of genes enriched for neuronal terms. Comparing macaque MSNs with tract-tracing data confirmed that morphometric similarity was related to axonal connectivity. Finally, variation in the degree of human MSN nodes accounted for about 40% of between-subject variability in IQ. Morphometric similarity mapping provides a novel, robust, and biologically plausible approach to understanding how human cortical networks underpin individual differences in psychological functions.
•Morphometric similarity networks (MSNs) are connectomes generated from structural MRI•MSN topology captures known cortical cytoarchitecture and related gene expression•Macaque MSNs map onto gold-standard connectivity derived from axonal tract tracing•Human IQ is linked to variation in MSN degree of relevant anatomical regions
Morphometric similarity mapping is a robust new method to examine the structural organization of individual brains in vivo. It provides morphometric similarity networks (MSNs) that capture cellular, molecular, and functional features of the brain and predict inter-individual differences in cognition.
•Use of flor yeast in sparkling wine production for the first time.•The effect of CO2 on twenty-six variables and fifty-three volatiles is studied.•CO2 pressure affects six and nine chemical families ...in the middle and at the end of second fermentation, respectively.•Aroma profiles based on Odorant series show differences due to CO2 effect.•A Principal Component Analysis highlights differences in several volatile metabolites by the CO2.
Saccharomyces cerevisiae flor yeast is used for the first time in sparkling wine-making. Twenty-six oenological variables and fifty-three volatile metabolites are quantified in the middle (P = 3 bar) and at the end (P = 6 bar) of the second fermentation, carried out in open and closed bottles. A heat-map of volatiles and the fingerprints obtained for ten chemical families and ten odorant series visualize the changes for each condition. Terpenes, fatty acids and volatile phenols increased their contents by pressure effect at the end of the study by 25.0, 7.8 and 2.2%, respectively. The remaining families decrease between 17.4% and 30.1% for furanic compounds and esters in the same stage. A Principal Component Analysis established that nine volatiles are mainly affected by pressure and five by fermentation stage. The use of ethanol-tolerant flor yeasts constitutes an innovative procedure for the enhancement of the sparkling wines diversification.
Secondary infections due to transmission via the duodenoscope have been reported in up to 3% of endoscopic retrograde cholangiopancreatographies. The use of single-use duodenoscopes has been ...suggested. We investigate the cost-effectiveness of these duodenoscopes use in cholangiopancreatography.
A cost-effectiveness analysis was implemented to compare the performance of cholangiopancreatographies with reusable duodenoscopes versus single-use duodenoscopes. Effectiveness was analyzed by calculating quality-adjusted life years (QALY) from the perspective of the National Health System. Possibility of crossover from single-use to reusable duodenoscopes was considered. A willingness-to-pay of €25,000/QALY was set, the incremental cost-effectiveness ratio (ICER) was calculated, and deterministic and probabilistic sensitivity analyses were performed.
Considering cholangiopancreatographies with single-use and reusable duodenoscopes at a cost of €2900 and €1333, respectively, and a 10% rate of single-use duodenoscopes, ICER was greater than €3,000,000/QALY. A lower single-use duodenoscope cost of €1211 resulted in an ICER of €23,583/QALY. When the unit cost of the single-use duodenoscope was €1211, a crossover rate of more than 9.5% made the use of the single-use duodenoscope inefficient.
Single-use duodenoscopes are cost-effective in a proportion of cholangiopancreatographies if its cost is reduced. Increased crossover rate makes single-use duodenoscope use not cost-effective.
Autism spectrum disorder (ASD) is a highly complex neurodevelopmental condition that is accompanied by neuroanatomical differences on the macroscopic and microscopic level. Findings from ...histological, genetic, and more recently in vivo neuroimaging studies converge in suggesting that neuroanatomical abnormalities, specifically around the gray‐white matter (GWM) boundary, represent a crucial feature of ASD. However, no research has yet characterized the GWM boundary in ASD based on measures of diffusion. Here, we registered diffusion tensor imaging data to the structural T1‐weighted images of 92 adults with ASD and 92 matched neurotypical controls in order to examine between‐group differences and group‐by‐sex interactions in fractional anisotropy and mean diffusivity sampled at the GWM boundary, and at different sampling depths within the superficial white and into the gray matter. As hypothesized, we observed atypical diffusion at and around the GWM boundary in ASD, with between‐group differences and group‐by‐sex interactions depending on tissue class and sampling depth. Furthermore, we identified that altered diffusion at the GWM boundary partially (i.e., ~50%) overlapped with atypical gray‐white matter tissue contrast in ASD. Our study thus replicates and extends previous work highlighting the GWM boundary as a crucial target of neuropathology in ASD, and guides future work elucidating etiological mechanisms.
The present study observed atypical diffusion at and around the gray‐white matter (GWM) boundary in individuals with autism spectrum disorder (ASD) relative to neurotypical controls, with between‐group differences and group‐by‐sex interactions depending on tissue class and sampling depth. Altered diffusion at the GWM boundary was further identified to partially (i.e., ~50%) and nonrandomly overlap with atypical gray‐white matter tissue contrast in ASD. The study thus replicates and extends previous work highlighting the GWM boundary as a crucial target of neuropathology in ASD, and guides future work elucidating etiological mechanisms.
Abstract
Motivated by prior data on local cortical shrinkage and intracortical myelination, we predicted age-related changes in topological organization of cortical structural networks during ...adolescence. We estimated structural correlation from magnetic resonance imaging measures of cortical thickness at 308 regions in a sample of N = 297 healthy participants, aged 14-24 years. We used a novel sliding-window analysis to measure age-related changes in network attributes globally, locally and in the context of several community partitions of the network. We found that the strength of structural correlation generally decreased as a function of age. Association cortical regions demonstrated a sharp decrease in nodal degree (hubness) from 14 years, reaching a minimum at approximately 19 years, and then levelling off or even slightly increasing until 24 years. Greater and more prolonged age-related changes in degree of cortical regions within the brain network were associated with faster rates of adolescent cortical myelination and shrinkage. The brain regions that demonstrated the greatest age-related changes were concentrated within prefrontal modules. We conclude that human adolescence is associated with biologically plausible changes in structural imaging markers of brain network organization, consistent with the concept of tuning or consolidating anatomical connectivity between frontal cortex and the rest of the connectome.
Neurodevelopmental disorders have a heritable component and are associated with region specific alterations in brain anatomy. However, it is unclear how genetic risks for neurodevelopmental disorders ...are translated into spatially patterned brain vulnerabilities. Here, we integrated cortical neuroimaging data from patients with neurodevelopmental disorders caused by genomic copy number variations (CNVs) and gene expression data from healthy subjects. For each of the six investigated disorders, we show that spatial patterns of cortical anatomy changes in youth are correlated with cortical spatial expression of CNV genes in neurotypical adults. By transforming normative bulk-tissue cortical expression data into cell-type expression maps, we link anatomical change maps in each analysed disorder to specific cell classes as well as the CNV-region genes they express. Our findings reveal organizing principles that regulate the mapping of genetic risks onto regional brain changes in neurogenetic disorders. Our findings will enable screening for candidate molecular mechanisms from readily available neuroimaging data.
Adolescent changes in human brain function are not entirely understood. Here, we used multiecho functional MRI (fMRI) to measure developmental change in functional connectivity (FC) of resting-state ...oscillations between pairs of 330 cortical regions and 16 subcortical regions in 298 healthy adolescents scanned 520 times. Participants were aged 14 to 26 y and were scanned on 1 to 3 occasions at least 6 mo apart. We found 2 distinct modes of age-related change in FC: “conservative” and “disruptive.” Conservative development was characteristic of primary cortex, which was strongly connected at 14 y and became even more connected in the period from 14 to 26 y. Disruptive development was characteristic of association cortex and subcortical regions, where connectivity was remodeled: connections that were weak at 14 y became stronger during adolescence, and connections that were strong at 14 y became weaker. These modes of development were quantified using the maturational index (MI), estimated as Spearman’s correlation between edgewise baseline FC (at 14 y, FC14) and adolescent change in FC (ΔFC14−26), at each region. Disruptive systems (with negative MI) were activated by social cognition and autobiographical memory tasks in prior fMRI data and significantly colocated with prior maps of aerobic glycolysis (AG), AG-related gene expression, postnatal cortical surface expansion, and adolescent shrinkage of cortical thickness. The presence of these 2 modes of development was robust to numerous sensitivity analyses. We conclude that human brain organization is disrupted during adolescence by remodeling of FC between association cortical and subcortical areas.
Adolescent development of human brain structural and functional networks is increasingly recognized as fundamental to emergence of typical and atypical adult cognitive and emotional processes. We ...analysed multimodal magnetic resonance imaging (MRI) data collected from N ∼ 300 healthy adolescents (51%; female; 14 to 26 y) each scanned repeatedly in an accelerated longitudinal design, to provide an analyzable dataset of 469 structural scans and 448 functional MRI scans. We estimated the morphometric similarity between each possible pair of 358 cortical areas on a feature vector comprising six macro- and microstructural MRI metrics, resulting in a morphometric similarity network (MSN) for each scan. Over the course of adolescence, we found that morphometric similarity increased in paralimbic cortical areas, e.g., insula and cingulate cortex, but generally decreased in neocortical areas, and these results were replicated in an independent developmental MRI cohort (N ∼ 304). Increasing hubness of paralimbic nodes in MSNs was associated with increased strength of coupling between their morphometric similarity and functional connectivity. Decreasing hubness of neocortical nodes in MSNs was associated with reduced strength of structure–function coupling and increasingly diverse functional connections in the corresponding fMRI networks. Neocortical areas became more structurally differentiated and more functionally integrative in a metabolically expensive process linked to cortical thinning and myelination, whereas paralimbic areas specialized for affective and interoceptive functions became less differentiated, as hypothetically predicted by a developmental transition from periallocortical to proisocortical organization of the cortex. Cytoarchitectonically distinct zones of the human cortex undergo distinct neurodevelopmental programs during typical adolescence.
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