Grey-matter texture abnormalities and reduced hippocampal volume are distinguishing features of schizophrenia

Neurodevelopmental processes are widely believed to underlie schizophrenia. Analysis of brain texture from conventional magnetic resonance imaging (MRI) can detect disturbance in brain cytoarchitecture. We tested the hypothesis that patients with schizophrenia manifest quantitative differences in brain texture that, alongside discrete volumetric changes, may serve as an endophenotypic biomarker. Texture analysis (TA) of grey matter distribution and voxel-based morphometry (VBM) of regional brain volumes were applied to MRI scans of 27 patients with schizophrenia and 24 controls. Texture parameters (uniformity and entropy) were also used as covariates in VBM analyses to test for correspondence with regional brain volume. Linear discriminant analysis tested if texture and volumetric data predicted diagnostic group membership (schizophrenia or control). We found that uniformity and entropy of grey matter differed significantly between individuals with schizophrenia and controls at the fine spatial scale (filter width below 2 mm). Within the schizophrenia group, these texture parameters correlated with volumes of the left hippocampus, right amygdala and cerebellum. The best predictor of diagnostic group membership was the combination of fine texture heterogeneity and left hippocampal size. This study highlights the presence of distributed grey-matter abnormalities in schizophrenia, and their relation to focal structural abnormality of the hippocampus. The conjunction of these features has potential as a neuroimaging endophenotype of schizophrenia

Sex Differences and Autism: Brain Function during Verbal Fluency and Mental Rotation

Autism spectrum conditions (ASC) affect more males than females. This suggests that the neurobiology of autism: 1) may overlap with mechanisms underlying typical sex-differentiation or 2) alternately reflect sex-specificity in how autism is expressed in males and females. Here we used functional magnetic resonance imaging (fMRI) to test these alternate hypotheses. Fifteen men and fourteen women with Asperger syndrome (AS), and sixteen typically developing men and sixteen typically developing women underwent fMRI during performance of mental rotation and verbal fluency tasks. All groups performed the tasks equally well. On the verbal fluency task, despite equivalent task-performance, both males and females with AS showed enhanced activation of left occipitoparietal and inferior prefrontal activity compared to controls. During mental rotation, there was a significant diagnosis-by-sex interaction across occipital, temporal, parietal, middle frontal regions, with greater activation in AS males and typical females compared to AS females and typical males. These findings suggest a complex relationship between autism and sex that is differentially expressed in verbal and visuospatial domains

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

Transcriptional Stochasticity as a Key Aspect of HIV-1 Latency

This review summarizes current advances in the role of transcriptional stochasticity in HIV-1 latency, which were possible in a large part due to the development of single-cell approaches. HIV-1 transcription proceeds in bursts of RNA production, which stem from the stochastic switching of the viral promoter between ON and OFF states. This switching is caused by random binding dynamics of transcription factors and nucleosomes to the viral promoter and occurs at several time scales from minutes to hours. Transcriptional bursts are mainly controlled by the core transcription factors TBP, SP1 and NF-κb, the chromatin status of the viral promoter and RNA polymerase II pausing. In particular, spontaneous variability in the promoter chromatin creates heterogeneity in the response to activators such as TNF-α, which is then amplified by the Tat feedback loop to generate high and low viral transcriptional states. This phenomenon is likely at the basis of the partial and stochastic response of latent T cells from HIV-1 patients to latency-reversing agents, which is a barrier for the development of shock-and-kill strategies of viral eradication. A detailed understanding of the transcriptional stochasticity of HIV-1 and the possibility to precisely model this phenomenon will be important assets to develop more effective therapeutic strategies

A 3D lighting system for fMRI rendering fidelity experiments

Summarization: Although improvements in basic computer graphics rendering hardware and lighting algorithms have produced some remarkable results, it is still computationally demanding to render a highly realistic Virtual Environment (VE) in real-time. This paper presents a real-time synthetic lighting system incorporating sophisticated global illumination algorithms aiming to induce similar subjective lighting impressions as in the real world. The lighting system proposed is designed to render an interactive VE on an fMRI display, enabling the conduct of formal neuroscientific experiments and investigating the effects of visual fidelity as well as varied lighting configurations on feelings of presence, ‘reality’ and comfort. Ultimately, the goal is to use this system to explore the effect of lighting variations (daylight vs. forms of artificial light) on subjective impressions of a group of patients suffering from the ‘depersonalization’ syndrome. The system was developed in close collaboration with the Brighton and Sussex Medical School in the UK. It was a challenge to develop an interactive lighting system to be utilized for fMRI experimentation due to infrastructural and technical demands. Such demands were based on acquiring user input when immersed in the constrained environment of an fMRI scanner while the system reacts to it in real-time. fMRI experiments usually employ simple display material, for example using photographs, video clips or simple computerized stimuli. Employing VEs in fMRI has the advantage that it is possible to involve participants in interactive animated environments which more realistically reflect social and emotional situations.Παρουσιάστηκε στο: International Journal of Interactive World

Selective updating of working memory content modulates meso-cortico-striatal activity

Accumulating evidence from non-human primates and computational modeling suggests that dopaminergic signals arising from the midbrain (substantia nigra/ventral tegmental area) mediate striatal gating of the prefrontal cortex during the selective updating of working memory. Using event-related functional magnetic resonance imaging, we explored the neural mechanisms underlying the selective updating of information stored in working memory. Participants were scanned during a novel working memory task that parses the neurophysiology underlying working memory maintenance, overwriting, and selective updating. Analyses revealed a functionally coupled network consisting of a midbrain region encompassing the substantia nigra/ventral tegmental area, caudate, and dorsolateral prefrontal cortex that was selectively engaged during working memory updating compared to the overwriting and maintenance of working memory content. Further analysis revealed differential midbrain-dorsolateral prefrontal interactions during selective updating between low-performing and high-performing individuals. These findings highlight the role of this meso-cortico-striatal circuitry during the selective updating of working memory in humans, which complements previous research in behavioral neuroscience and computational modelin

Exploring behavioural fidelity of synthetic stimuli while immersed in fMRI displays

Summarization: The goal of the proposed experiments is to assess the fidelity of a simulation as well as develop synthetic imaging systems which will result in controlled functional Magnetic Resonance Imaging (fMRI) experiments involving the normal population as well as patients. The ultimate goal of the experiments planned is to explore whether natural and artificial scenes of varied fidelity for training or for therapeutic purposes engage common perceptual or neuroscientific mechanisms. Such input is non-obtrusive and is derived at the same time as the experience occurs. The first experiment briefly summarized is exploring brain empathic responses of users participating in an interactive economic game developed to be displayed in a fMRI scanner. The second experiment presents an interactive lighting system also to be displayed in an fMRI scanner. Its scope is to enable the monitoring of neural activation patterns in response to lighting manipulations ranging from daylight and artificial light of the normal population initially and potentially of groups of patients suffering from the depersonalization syndrome. A broader aim of this work is to assess whether such powerful social-psychological studies could be usefully carried out within Virtual Environments advancing both cognitive neuroscience and computer graphics research.Παρουσιάστηκε στο: Third International Conference on Games and Virtual Worlds for Serious Applications (VS-GAMES

Goodness-of-fit measures of CIBERSORT deconvolution of pseudobulk RNA-Seq data (i.e., correlation coefficients and Root Mean Square Error- RMSE) show a better performance for a model based on brain scRNA-Seq signature- Velmeshev 2019 (higher correlation coefficients and lower RMSE).

The algorithm fails though to estimate microglia and endothelia. (TIF)</p