Biology subjects

Carvalho, J.

Publications and source records attributed to Carvalho, J..

25 records · Page 2Linked to original sources

bioRxiv2020

Bayesian Connective Field Modeling: a Markov Chain Monte Carlo approach.

The majority of neurons in the human brain process signals from neurons elsewhere in the brain. Connective Field (CF) modeling is a biologically-grounded method to describe this essential aspect of the brains circuitry. It allows characterizing the response of a population of neurons in terms of the activity in another part of the brain. CF modeling translates the concept of the receptive field (RF) into the domain of connectivity by assessing the spatial dependency between signals in distinct cortical visual field areas. Standard CF model estimation has some intrinsic limitations in that it cannot estimate the uncertainty associated with each of its parameters. Obtaining the uncertainty will allow identification of model biases, e.g. related to an over- or under-fitting or a co-dependence of parameters, thereby improving the CF prediction. To enable this, here we present a Bayesian framework for the CF model. Using a Markov Chain Monte Carlo (MCMC) approach, we estimate the underlying posterior distribution of the CF parameters and consequently, quantify the uncertainty associated with each estimate. We applied the method and its new Bayesian features to characterize the cortical circuitry of the early human visual cortex of 12 healthy participants that were assessed using 3T fMRI. In addition, we show how the MCMC approach enables the use of effect size (beta) as a data-driven parameter to retain relevant voxels for further analysis. Finally, we demonstrate how our new method can be used to compare different CF models. Our results show that single Gaussian models are favoured over differences of Gaussians (i.e. center-surround) models, suggesting that the cortico-cortical connections of the early visual system do not possess center-surround organisation. We conclude that our new Bayesian CF framework provides a comprehensive tool to improve our fundamental understanding of the human cortical circuitry in health and disease. Highlights{square} We present and validate a Bayesian CF framework based on a MCMC approach. {square}The MCMC CF approach quantifies the model uncertainty associated with each CF parameter. {square}We show how to use effect size beta as a data-driven threshold to retain relevant voxels. {square}The cortical connective fields of the human early visual system are best described by a single, circular symmetric, Gaussian.

neuroscience↗

bioRxiv2020

Visual field reconstruction using fMRI-based techniques

PurposeTo evaluate the accuracy and reliability of functional magnetic resonance imaging (fMRI)-based techniques to assess the integrity of the visual field (VF). MethodsWe combined fMRI and neurocomputational models, i.e conventional population receptive field (pRF) mapping and a new advanced pRF framework "micro-probing" (MP), to reconstruct the visual field representations of different cortical areas. To demonstrate their scope, both approaches were applied in healthy participants with simulated scotomas (SS) and participants with glaucoma. For the latter group we compared the VFs obtained with standard automated perimetry (SAP) and via fMRI. ResultsUsing SS, we found that the fMRI-based techniques can detect absolute defects in VFs that are larger than 3 deg, in single participants, and based on 12 minutes of fMRI scan time. Moreover, we found that MP results in a less biased estimation of the preserved VF. In participants with glaucoma, we found that fMRI-based VF reconstruction detected VF defects with a correspondence to SAP that was decent, reflected by the positive correlation between fMRI-based sampling density and SAP-based contrast sensitivity loss (SAP) r2=0.44, p=0.0002.This correlation was higher for our new approach (MP) compared to that for the conventional pRF analysis. ConclusionsfMRI-based reconstruction of the VF enables the evaluation of vision loss and provides useful details on the properties of the visual cortex. Translational RelevancefMRI-based VF reconstruction provides an objective alternative to detect VF defects. It may either complement SAP, or could provide VF information in patients unable to perform SAP.

neuroscience↗

bioRxiv2020

Predicting range shifts of African apes under global change scenarios

AimModelling African great ape distribution has until now focused on current or past conditions, whilst future scenarios remain scarcely explored. Using an ensemble forecasting approach, we predicted changes in taxon-specific distribution under future scenarios of climate, land-use and human population changes. LocationSub-Saharan Africa MethodsWe compiled occurrence data on African ape populations from the IUCN A.P.E.S. database and extracted relevant human-, climate- and habitat-related predictors representing current and future (2050) conditions to predict taxon-specific distribution under a best- and a worst-case scenario, using ensemble forecasting. Given the large effect on model predictions, we further tested algorithm sensitivity by considering default and non-default modelling options. The latter included interactions between predictors and polynomial terms in correlative algorithms. ResultsThe future distributions of gorilla and bonobo populations are likely to be directly determined by climate-related variables. In contrast, future chimpanzee distribution is influenced mostly by anthropogenic variables. Both our modelling approaches produced similar model accuracy, although a slight difference in the magnitude of range change was found for Gorilla beringei beringei, G. gorilla diehli, and Pan troglodytes schweinfurthii. On average, a decline of 50% of the geographic range (non-default; or 55% default) is expected under the best scenario if no dispersal occurs (57% non-default or 58% default in worst scenario). However, new areas of suitable habitat are predicted to become available for most taxa if dispersal occurs (81% or 103% best, 93% or 91% worst, non-default and default, respectively), except for G. b. beringei. Main ConclusionsDespite the uncertainty in predicting the precise proportion of suitable habitat by 2050, both modelling approaches predict large range losses for all African apes. Thus, conservation planners urgently need to integrate land-use planning and simultaneously support conservation and climate change mitigation measures at all decision-making levels both in range countries and abroad.

ecology↗

bioRxiv2020

Foveal pRF properties in the visual cortex depend on the extent of stimulated visual field

Previous studies demonstrated that alterations in functional MRI derived receptive field (pRF) properties in cortical projection zones of retinal lesions can erroneously be mistaken for cortical large-scale reorganization in response to visual system pathologies. We tested, whether such confounds are also evident in the normal cortical projection zone of the fovea for simulated peripheral visual field defects. We applied fMRI-based visual field mapping of the central visual field at 3 Tesla in eight controls to compare the pRF properties of the central visual field of a reference condition (stimulus radius: 14{degrees}) and two conditions with simulated peripheral visual field defect, i.e., with a peripheral gray mask, stimulating only the central 7{degrees} or 4{degrees} radius. We quantified, for the cortical representation of the actually stimulated visual field, the changes in the position and size of the pRFs associated with reduced peripheral stimulation using conventional and advanced pRF modeling. We found foveal pRF-positions ([≤]3{degrees}) to be significantly shifted towards the periphery (p<0.05, corrected). These pRF-shifts were largest for the 4{degrees} condition [visual area (mean eccentricity shift): V1 (0.9{degrees}), V2 (0.9{degrees}), V3 (1.0{degrees})], but also evident for the 7{degrees} condition [V1 (0.5{degrees}), V2 (0.5{degrees}), V3 (0.9{degrees})]. Further, an overall enlargement of pRF-sizes was observed. These findings indicate the dependence of foveal pRF parameters on the spatial extent of the stimulated visual field. Consequently, our results imply that, previously reported similar findings in patients with actual peripheral scotomas need to be interpreted with caution and indicate the need for adequate control conditions in investigations of visual cortex reorganization. HighlightsO_LIFoveal pRF properties change in controls with restricted peripheral stimulation C_LIO_LIpRFs shift in position and enlarge in size for reduced stimulation extent C_LIO_LIAlterations in pRF characteristics in patients should be interpreted with caution C_LIO_LIAdequate control conditions needed in investigations of visual cortex plasticity C_LI

neuroscience↗

bioRxiv2019

A novel antibody targeting ICOS increases intratumoural cytotoxic to regulatory T cell ratio and induces tumour regression.

The immunosuppressive tumour microenvironment constitutes a significant hurdle to the response to immune checkpoint inhibitors. Both soluble factors and specialised immune cells such as regulatory T cells (TReg) are key components of active intratumoural immunosuppression. Previous studies have shown that Inducible Co-Stimulatory receptor (ICOS) is highly expressed in the tumour microenvironment, especially on TReg, suggesting that it represents a relevant target for preferential depletion of these cells. Here, we used immune profiling of samples from tumour bearing mice and cancer patients to characterise the expression of ICOS in different tissues and solid tumours. By immunizing an Icos knockout transgenic mouse line expressing antibodies with human variable domains, we selected a fully human IgG1 antibody called KY1044 that binds ICOS from different species. Using KY1044, we demonstrated that we can exploit the differential expression of ICOS on T cell subtypes to modify the tumour microenvironment and thereby improve the anti-tumour immune response. We showed that KY1044 induces sustained depletion of ICOShigh TReg cells in mouse tumours and depletion of ICOShigh T cells in the blood of non-human primates, but was also associated with secretion of pro-inflammatory cytokines from ICOSlow TEFF cells. Altogether, KY1044 improved the intratumoural TEFF:TReg ratio and increased activation of TEFF cells, resulting in monotherapy efficacy or in synergistic combinatorial efficacy when administered with the immune checkpoint blocker anti-PD-L1. In summary, our data demonstrate that targeting ICOS with KY1044 can favourably alter the intratumoural immune contexture, promoting an anti-tumour response.

cancer biology↗

bioRxiv2019

Predictive masking is associated with a system-wide reconfiguration of neural populations in the human visual cortex

The human visual system masks the perceptual consequences of retinal or cortical lesion-induced scotomas by predicting what is missing from nearby regions of the visual field. To reveal the neural mechanisms underlying this remarkable capacity, known as predictive masking, we used fMRI and neural modeling to track changes in cortical population receptive fields (pRFs) and connectivity in response to the introduction of an artificial scotoma (AS). Consistent with predictive masking, we found that extrastriate areas increased their sampling of the V1 region outside the AS projection zone. Moreover, throughout the visual field and hierarchy, pRFs shifted their preferred position towards the AS border. A gain field model, centered at this border, accounted for these shifts, especially for extrastriate areas. This suggests that a system-wide reconfiguration of neural populations in response to a change in visual input is guided by extrastriate signals and underlies the predictive masking of scotomas.

neuroscience↗

bioRxiv2019

Micro-probing enables high-resolution mapping of neuronal subpopulations using fMRI

The characterization of receptive field (RF) properties is fundamental to understanding the neural basis of sensory and cognitive behaviour. The combination of non-invasive imaging, such as fMRI, with biologically inspired neural modeling has enabled the estimation of population RFs directly in humans. However, current approaches require making numerous a priori assumptions, so these cannot reveal unpredicted properties, such as fragmented RFs or subpopulations. This is a critical limitation in studies on adaptation, pathology or reorganization. Here, we introduce micro-probing (MP), a technique for fine-grained and assumption free characterisation of subpopulation RFs. Without specific stimuli or adapted models, MP mapped the bilateral RFs characteristic of observers with a congenital pathway disorder. Moreover, in healthy observers, MP revealed voxels that capture the activity of multiple neuronal subpopulations. Thus, MP provides a versatile framework to visualize, analyze and model, without restrictions, the diverse RFs of cortical subpopulations in health and disease.

neuroscience↗