Switching operation modes in the neocortex via cholinergic neuromodulation

In order to deal with the uncertainty in the world, our brains need to be able to flexibly switch between the exploration of new sensory representations and exploitation of previously acquired ones. This requires forming accurate estimations of what and how much something is expected. While modeling has allowed for the development of several ways to form predictions, how the brain could implement those is still under debate. Here, we recognize acetylcholine as one of the main neuromodulators driving learning based on uncertainty, promoting the exploration of new sensory representations. We identify its interactions with cortical inhibitory interneurons and derive a biophysically grounded computational model able to capture and learn from uncertainty. This model allows us to understand inhibition beyond gain control by suggesting that different interneuron subtypes either encode predictions or estimate their uncertainty, facilitating detection of unexpected cues. Moreover, we show how acetylcholine-like neuromodulation uniquely interacts with global and local sources of inhibition, disrupting perceptual certainty and promoting the rapid acquisition of new perceptual cues. Altogether, our model proposes that cortical acetylcholine favors sensory exploration over exploitation in a cortical microcircuit dedicated to estimating sensory uncertainty

Can frozen sperm samples withstand being sent to space? Considering the creation of a sperm bank outside Earth

The aim of the research is to investigate the effects of microgravity exposure on the motility and vitality of human sperm. The likelihood of human reproduction in space relies heavily on the conditions in which human sperm may act under altered gravity conditions. A first step before longer duration experiments in microgravity conditions are conducted is to model the alterations that frozen human sperm may suffer, and their validation in short-term parabolic flights. It is unknown if microgravity has a negative effect on frozen sperm samples. Our hypothesis is that frozen samples can withstand different gravity conditions without significant alterations. In order to test this hypothesis, 15 sperm samples from healthy donors were divided in two fractions (microgravity vs ground conditions) and frozen and stored in liquid nitrogen until the day of the experiment. A specific container as payload carrying the frozen sperm samples in vapors of liquid nitrogen was located in the aircraft cockpit, with no manual operation during the parabolas. A total of three parabolic flights (5 samples/flight) were completed during 2018-19 with 20 parabolas conducted in each flight. The parabolic flights allowed for 5 to 8 seconds of microgravity periods, using a CAP10B aerobatic plane operated by Barcelona-Sabadell Aeroclub, with UPC BarcelonaTech and Women’s Health Dexeus, a leading center in human assisted reproduction, in charge of the research. The CAP10B aircraft has successfully proven in the last decade to perform optimal parabolas for both education and research purposes. After thawing, sperm motility was evaluated by using a Makler® counting chamber and SCA®CASA System as a computerized semen motility analyzer. Sperm vitality was also evaluated by using Eosin-nigrosin staining. The study was approved by the Ethical Board of Hospital Universitari Dexeus, Barcelona (Spain). Comparing mean values between control group (Earth) and the study group (microgravity) no significant statistical differences were found, in any of the parameters analyzed: motile sperm concentration (106/ml); progressive a+b motility (%), velocity (µm/s), straight line velocity (µm/s), linearity index (%) and vitality (%). Limitations of this parabolic flight are a short period of microgravity and hypergravity peaks before and after the parabolas. In conclusion, these are the first experimental results published while exposing human frozen sperm to microgravity in a controlled parabolic flight experiment. More in-flight short-term and long-term studies are needed to verify the viability of transporting human sperm samples outside Earth, and to continue advancing the possibility of human reproduction in space.Postprint (published version

Association of central obesity with unique cardiac remodelling in young adults born small for gestational age

Being born small for gestational age (SGA, 10% of all births) is associated with increased risk of cardiovascular mortality in adulthood together with lower exercise tolerance, but mechanistic pathways are unclear. Central obesity is known to worsen cardiovascular outcomes, but it is uncertain how it affects the heart in adults born SGA. We aimed to assess whether central obesity makes young adults born SGA more susceptible to cardiac remodelling and dysfunction.A perinatal cohort from a tertiary university hospital in Spain of young adults (30-40 years) randomly selected, 80 born SGA (birth weight below 10th centile) and 75 with normal birth weight (controls) was recruited. We studied the associations between SGA and central obesity (measured via the hip-to-waist ratio and used as a continuous variable) and cardiac regional structure and function, assessed by cardiac magnetic resonance using statistical shape analysis. Both SGA and waist-to-hip were highly associated to cardiac shape (F = 3.94, P < 0.001; F = 5.18, P < 0.001 respectively) with a statistically significant interaction (F = 2.29, P = 0.02). While controls tend to increase left ventricular end-diastolic volumes, mass and stroke volume with increasing waist-to-hip ratio, young adults born SGA showed a unique response with inability to increase cardiac dimensions or mass resulting in reduced stroke volume and exercise capacity.SGA young adults show a unique cardiac adaptation to central obesity. These results support considering SGA as a risk factor that may benefit from preventive strategies to reduce cardiometabolic risk.© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: [email protected]

Anatomic registration based on medial axis parametrizations

El corregistro de imagines ha sido durante muchos años el método estándar para poner dos imágenes en correspondencia. Se ha usado de manera generalizada en el campo de la imagen médica, para poner imágenes de dos pacientes diferentes en una misma posición de solapamiento en el espacio. Sin embargo, el corregistro de estas imágenes es un proceso iterativo y lento de muchas variables y con tendencia a caer en mínimos de energía local. Un sistema de coordenadas que parametrizase el interior de los órganos es una herramienta muy potente para la identificación y marcado de tejido dañado o enfermo. Si las mismas coordenadas se asignan a lugares específicos anatómicos, la parametrización asegura la integración de datos a lo largo de diferentes modalidades de imagen. Los mapas armónicos se han usado para producir mallados paramétricos sobre la superficie de formas anatómicas, dadas sus capacidades para establecer valores en posiciones determinadas como condiciones de frontera. Sin embargo la mayoría de las implementaciones aplicadas a imagen médica se limitan a bien la superficie del órgano o bien se proporciona una coordenada de profundidad en lugares discretos y de diversidad limitada. La superficie medial de una forma se puede usar para proporcionar una base continua para la definición de una coordenada de profundidad. Debido a la gran variedad de métodos disponibles para la generación de estas estructuras, y que cada uno de ellos, genera estructuras diferentes, no todos los métodos son adecuados para ser el origen de coordenadas de profundidad. Sería deseable que se generasen superficies mediales que fuesen suaves y robustas al ruido en la frontera del objeto, con un número reducido de ramas en su superficie. En esta tesis presentamos método para el cálculo de superficies mediales suaves y las aplicamos a la generación de parametrizaciones anatómicas volumétricas, que extienden las parametrizaciones armónicas actuales al interior de la anatomía, usando información proporcionada por la superficie medial. Este sistema de referencia establece una base sólida para la creación de modelos del órgano o forma anatómicas y permite la comparación de diversos pacientes en un marco de referencia comúnImage registration has been for many years the gold standard method to bring two images into correspondence. It has been used extensively in the field of medical imaging in order to put images of different patients into a common overlapping spatial position. However, medical image registration is a slow, iterative optimization process, where many variables and prone to fall into the pit traps local minima. A coordinate system parameterizing the interior of organs is a powerful tool for a systematic localization of injured tissue. If the same coordinate values are assigned to specific anatomical sites, parameterizations ensure integration of data across different medical image modalities. Harmonic mappings have been used to produce parametric meshes over the surface of anatomical shapes, given their ability to set values at specific locations through boundary conditions. However, most of the existing implementations in medical imaging restrict to either anatomical surfaces, or the depth coordinate with boundary conditions is given at discrete sites of limited geometric diversity. The medial surface of the shape can be used to provide a continuous basis for the definition of a depth coordinate. However, given that different methods for generation of medial surfaces generate different manifolds, not all of them are equally suited to be the basis of radial coordinate for a parameterization. It would be desirable that the medial surface will be smooth, and robust to surface shape noise, with low number of spurious branches or surfaces. In this thesis we present methods for computation of smooth medial manifolds and apply them to the generation of for anatomical volumetric parameterization that extends current harmonic parameterizations to the interior anatomy using information provided by the volume medial surface. This reference system sets a solid base for creating anatomical models of the anatomical shapes, and allows comparing several patients in a common framework of reference

MSClique: Multiple structure discovery through the maximum weighted clique problem

We present a novel approach for feature correspondence and multiple structure discovery in computer vision. In contrast to existing methods, we exploit the fact that point-sets on the same structure usually lie close to each other, thus forming clusters in the image. Given a pair of input images, we initially extract points of interest and extract hierarchical representations by agglomerative clustering. We use the maximum weighted clique problem to find the set of corresponding clusters with maximum number of inliers representing the multiple structures at the correct scales. Our method is parameter-free and only needs two sets of points along with their tentative correspondences, thus being extremely easy to use. We demonstrate the effectiveness of our method in multiple-structure fitting experiments in both publicly available and in-house datasets. As shown in the experiments, our approach finds a higher number of structures containing fewer outliers compared to state-of-the-art methods.Peer ReviewedPostprint (published version

Bronchial Infection and Temporal Evolution of Bronchiectasis in Patients With Chronic Obstructive Pulmonary Disease

[Background]: Bronchiectasis (BE) impact the clinical course and prognosis of patients with chronic obstructive pulmonary disease (COPD). Yet, the temporal evolution of BE in these patients is unknown. This study seeks to assess the temporal evolution of BE in persons with COPD.[Methods]: 201 moderate-to-severe patients were recruited between 2004 and 2007 and followed up at least every 6 monts (median of 102 months). To investigate the temporal evolution of BE, in 2015 a second high-resolution computed tomography scan (HRCT) was obtained in survivors and compared with the one obtained at recruitment.[Results]: 99 (49.3%) died during follow-up. The second HRCT could be obtained in 77 patients and showed that (1) in 27.3% of patients BE never developed, in 36.4% they remained stable, in 16.9% they increased in size and/or extension, and in 19.5% new BE emerged; and that (2) the presence of chronic purulent sputum (hazard ratio [HR], 2.8 [95% confidence interval {CI}, 1.3–5.8]), number of hospitalizations due to exacerbatons (HR, 1.2 [95% CI, 1.1–1.5]), and number of pathogenic microorganism (PPM) isolations (HR, 1.1 [95% CI, 1.02–1.3]) were independent risk factors for the progression or development of BE.[Conclusions]: The presence of chronic purulent sputum production, number of PPMs isolated in sputum, and number of hospitalizations due to exacerbations of COPD are independent risk factors of BE progression in patients with COPD

Automated Analysis of Basal Ganglia Intensity Distribution in Multisequence MRI of the Brain - Application to Creutzfeldt-Jakob Disease

We present a method for the analysis of basal ganglia (including the thalamus) for accurate detection of human spongiform encephalopathy in multisequence MRI of the brain. One common feature of most forms of prion protein infections is the appearance of hyperintensities in the deep grey matter area of the brain in T2-weighted MR images. We employ T1, T2 and Flair-T2 MR sequences for the detection of intensity deviations in the internal nuclei. First, the MR data is registered to a probabilistic atlas and normalised in intensity. Then smoothing is applied with edge enhancement. The segmentation of hyperintensities is performed using a model of the human visual system. For more accurate results, a priori anatomical data from a segmented atlas is employed to refine the registration and remove false positives. The results are robust over the patient data and in accordance to the clinical ground truth. Our method further allows the quantification of intensity distributions in basal ganglia. The caudate nuclei are highlighted as main areas of diagnosis of sporadic Creutzfeldt-Jakob Disease (CJD), in agreement with the histological data. The algorithm permitted to classify the intensities of abnormal signals in sporadic CJD patient FLAIR images with a more significant hypersignal in caudate nuclei (10/10) and putamen (6/10) than in thalami. Using normalised measures of the intensity relations between the internal grey nuclei of patients, we robustly differentiate sporadic CJD and new-variant CJD patients, as a first attempt towards an automatic classification tool of human spongiform encephalopathies

Identification of Myocardial Insulin Resistance by Using Liver Tests: A Simple Approach for Clinical Practice

Cardiovascular risk; Myocardial insulin resistance; Non-alcoholic fatty liver diseaseRiesgo cardiovascular; Resistencia a la insulina del miocardio; Enfermedad del higado graso no alcoholicoRisc cardiovascular; Resistència a la insulina del miocardi; Malaltia del fetge gras no alcohòlicBackground: We report that myocardial insulin resistance (mIR) occurs in around 60% of patients with type 2 diabetes (T2D) and was associated with higher cardiovascular risk in comparison with patients with insulin-sensitive myocardium (mIS). These two phenotypes (mIR vs. mIS) can only be assessed using time-consuming and expensive methods. The aim of the present study is to search a simple and reliable surrogate to identify both phenotypes. Methods: Forty-seven patients with T2D underwent myocardial [18F]FDG PET/CT at baseline and after a hyperinsulinemic–euglycemic clamp (HEC) to determine mIR were prospectively recruited. Biochemical assessments were performed before and after the HEC. Baseline hepatic steatosis index and index of hepatic fibrosis (FIB-4) were calculated. Furthermore, liver stiffness measurement was performed using transient elastography. Results: The best model to predict the presence of mIR was the combination of transaminases, protein levels, FIB-4 score and HOMA (AUC = 0.95; sensibility: 0.81; specificity: 0.95). We observed significantly higher levels of fibrosis in patients with mIR than in those with mIS (p = 0.034). In addition, we found that patients with mIR presented a reduced glucose uptake by the liver in comparison with patients with mIS. Conclusions: The combination of HOMA, protein, transaminases and FIB-4 is a simple and reliable tool for identifying mIR in patients with T2D. This information will be useful to improve the stratification of cardiovascular risk in T2D.This work was supported by the Carlos III Health Institute and the European Regional Development Fund (PI16/02064, PI20/01588) and the Agency for Management of University and Research Grants (AGAUR) of Catalonia (2017SGR1303)