Interaction between central and peripheral vision: Influence of distance and spatial frequencies.

Visual scene perception is based on reciprocal interactions between central and peripheral information. Such interactions are commonly investigated through the semantic congruence effect, which usually reveals a congruence effect of central vision on peripheral vision as strong as the reverse. The aim of the present study was to further investigate the mechanisms underlying central-peripheral visual interactions using a central-peripheral congruence paradigm through three behavioral experiments. We presented simultaneously a central and a peripheral stimulus, that could be either semantically congruent or incongruent. To assess the congruence effect of central vision on peripheral vision, participants had to categorize the peripheral target stimulus while ignoring the central distractor stimulus. To assess the congruence effect of the peripheral vision on central vision, they had to categorize the central target stimulus while ignoring the peripheral distractor stimulus. Experiment 1 revealed that the physical distance between central and peripheral stimuli influences central-peripheral visual interactions: Congruence effect of central vision is stronger when the distance between the target and the distractor is the shortest. Experiments 2 and 3 revealed that the spatial frequency content of distractors also influence central-peripheral interactions: Congruence effect of central vision is observed only when the distractor contained high spatial frequencies while congruence effect of peripheral vision is observed only when the distractor contained low spatial frequencies. These results raise the question of how these influences are exerted (bottom-up vs. top-down) and are discussed based on the retinocortical properties of the visual system and the predictive brain hypothesis.

Towards an optimization of functional localizers in non-human primate neuroimaging with (fMRI) frequency-tagging.

Non-human primate (NHP) neuroimaging can provide essential insights into the neural basis of human cognitive functions. While functional magnetic resonance imaging (fMRI) localizers can play an essential role in reaching this objective (Russ et al., 2021), they often differ substantially across species in terms of paradigms, measured signals, and data analysis, biasing the comparisons. Here we introduce a functional frequency-tagging face localizer for NHP imaging, successfully developed in humans and outperforming standard face localizers (Gao et al., 2018). FMRI recordings were performed in two awake macaques. Within a rapid 6 Hz stream of natural non-face objects images, human or monkey face stimuli were presented in bursts every 9 s. We also included control conditions with phase-scrambled versions of all images. As in humans, face-selective activity was objectively identified and quantified at the peak of the face-stimulation frequency (0.111 Hz) and its second harmonic (0.222 Hz) in the Fourier domain. Focal activations with a high signal-to-noise ratio were observed in regions previously described as face-selective, mainly in the STS (clusters PL, ML, MF; also, AL, AF), both for human and monkey faces. Robust face-selective activations were also found in the prefrontal cortex of one monkey (PVL and PO clusters). Face-selective neural activity was highly reliable and excluded all contributions from low-level visual cues contained in the amplitude spectrum of the stimuli. These observations indicate that fMRI frequency-tagging provides a highly valuable approach to objectively compare human and monkey visual recognition systems within the same framework.

Efficient multi-scale representation of visual objects using a biologically plausible spike-latency code and winner-take-all inhibition.

Deep neural networks have surpassed human performance in key visual challenges such as object recognition, but require a large amount of energy, computation, and memory. In contrast, spiking neural networks (SNNs) have the potential to improve both the efficiency and biological plausibility of object recognition systems. Here we present a SNN model that uses spike-latency coding and winner-take-all inhibition (WTA-I) to efficiently represent visual stimuli using multi-scale parallel processing. Mimicking neuronal response properties in early visual cortex, images were preprocessed with three different spatial frequency (SF) channels, before they were fed to a layer of spiking neurons whose synaptic weights were updated using spike-timing-dependent-plasticity. We investigate how the quality of the represented objects changes under different SF bands and WTA-I schemes. We demonstrate that a network of 200 spiking neurons tuned to three SFs can efficiently represent objects with as little as 15 spikes per neuron. Studying how core object recognition may be implemented using biologically plausible learning rules in SNNs may not only further our understanding of the brain, but also lead to novel and efficient artificial vision systems.

Symmetry Processing in the Macaque Visual Cortex.

Symmetry is a highly salient feature of the natural world that is perceived by many species. In humans, the cerebral areas processing symmetry are now well identified from neuroimaging measurements. Macaque could constitute a good animal model to explore the underlying neural mechanisms, but a previous comparative study concluded that functional magnetic resonance imaging responses to mirror symmetry in this species were weaker than those observed in humans. Here, we re-examined symmetry processing in macaques from a broader perspective, using both rotation and reflection symmetry embedded in regular textures. Highly consistent responses to symmetry were found in a large network of areas (notably in areas V3 and V4), in line with what was reported in humans under identical experimental conditions. Our results suggest that the cortical networks that process symmetry in humans and macaques are potentially more similar than previously reported and point toward macaque as a relevant model for understanding symmetry processing.

The T1D-associated lncRNA Lnc13 modulates human pancreatic ß cell inflammation by allele-specific stabilization of STAT1 mRNA.

The vast majority of type 1 diabetes (T1D) genetic association signals lie in noncoding regions of the human genome. Many have been predicted to affect the expression and secondary structure of long noncoding RNAs (lncRNAs), but the contribution of these lncRNAs to the pathogenesis of T1D remains to be clarified. Here, we performed a complete functional characterization of a lncRNA that harbors a single nucleotide polymorphism (SNP) associated with T1D, namely, Lnc13 Human pancreatic islets harboring the T1D-associated SNP risk genotype in Lnc13 (rs917997*CC) showed higher STAT1 expression than islets harboring the heterozygous genotype (rs917997*CT). Up-regulation of Lnc13 in pancreatic ß-cells increased activation of the proinflammatory STAT1 pathway, which correlated with increased production of chemokines in an allele-specific manner. In a mirror image, Lnc13 gene disruption in ß-cells partially counteracts polyinosinic-polycytidylic acid (PIC)-induced STAT1 and proinflammatory chemokine expression. Furthermore, we observed that PIC, a viral mimetic, induces Lnc13 translocation from the nucleus to the cytoplasm promoting the interaction of STAT1 mRNA with (poly[rC] binding protein 2) (PCBP2). Interestingly, Lnc13-PCBP2 interaction regulates the stability of the STAT1 mRNA, sustaining inflammation in ß-cells in an allele-specific manner. Our results show that the T1D-associated Lnc13 may contribute to the pathogenesis of T1D by increasing pancreatic ß-cell inflammation. These findings provide information on the molecular mechanisms by which disease-associated SNPs in lncRNAs influence disease pathogenesis and open the door to the development of diagnostic and therapeutic approaches based on lncRNA targeting.

Human Omental Mesothelial Cells Impart an Immunomodulatory Landscape Impeding B- and T-Cell Activation.

Mesothelial cells form the mesothelium, a simple epithelium lining the walls of serous cavities and the surface of visceral organs. Although mesothelial cells are phenotypically well characterized, their immunoregulatory properties remain largely unknown, with only two studies reporting their capacity to inhibit T cells through TGF-ß and their consumption of L-arginine by arginase-1. Whether human mesothelial cells can suppress other immune cells and possess additional leukosuppressive mechanisms, remain to be addressed to better delineate their therapeutic potential for cell therapy. Herein, we generated secretomes from omental mesothelial cells (OMC) and assess their capacity to inhibit lymphocytes proliferation, suppress activated T and B cells, as well as to modify macrophage activation markers. The secretome from mesenchymal stromal cells (MSC) served as a control of immuno-suppression. Although OMC and MSC were phenotypically divergent, their cytokine secretion patterns as well as expression of inflammatory and immunomodulary genes were similar. As such, OMC- and MSC-derived secretomes (OMC-S and MSC-S) both polarized RAW 264.7 macrophages towards a M2-like anti-inflammatory phenotype and suppressed mouse and human lymphocytes proliferation. OMC-S displayed a strong ability to suppress mouse- and human-activated CD19+/CD25+ B cells as compared to MSC-S. The lymphosuppressive activity of the OMC-S could be significantly counteracted either by SB-431542, an inhibitor of TGFß and activin signaling pathways, or with a monoclonal antibody against the TGFß1, ß2, and ß3 isoforms. A strong blockade of the OMC-S-mediated lymphosuppressive activity was achieved using L-NMMA, a specific inhibitor of nitric oxide synthase (NOS). Taken together, our results suggest that OMC are potent immunomodulators.

Stereomotion Processing in the Nonhuman Primate Brain.

The cortical areas that process disparity-defined motion-in-depth (i.e., cyclopean stereomotion [CSM]) were characterized with functional magnetic resonance imaging (fMRI) in two awake, behaving macaques. The experimental protocol was similar to previous human neuroimaging studies. We contrasted the responses to dynamic random-dot patterns that continuously changed their binocular disparity over time with those to a control condition that shared the same properties, except that the temporal frames were shuffled. A whole-brain voxel-wise analysis revealed that in all four cortical hemispheres, three areas showed consistent sensitivity to CSM. Two of them were localized respectively in the lower bank of the superior temporal sulcus (CSMSTS) and on the neighboring infero-temporal gyrus (CSMITG). The third area was situated in the posterior parietal cortex (CSMPPC). Additional regions of interest-based analyses within retinotopic areas defined in both animals indicated weaker but significant responses to CSM within the MT cluster (most notably in areas MSTv and FST). Altogether, our results are in agreement with previous findings in both human and macaque and suggest that the cortical areas that process CSM are relatively well preserved between the two primate species.

Nuclear Envelope Integrity in Health and Disease: Consequences on Genome Instability and Inflammation.

The dynamic nature of the nuclear envelope (NE) is often underestimated. The NE protects, regulates, and organizes the eukaryote genome and adapts to epigenetic changes and to its environment. The NE morphology is characterized by a wide range of diversity and abnormality such as invagination and blebbing, and it is a diagnostic factor for pathologies such as cancer. Recently, the micronuclei, a small nucleus that contains a full chromosome or a fragment thereof, has gained much attention. The NE of micronuclei is prone to collapse, leading to DNA release into the cytoplasm with consequences ranging from the activation of the cGAS/STING pathway, an innate immune response, to the creation of chromosomal instability. The discovery of those mechanisms has revolutionized the understanding of some inflammation-related diseases and the origin of complex chromosomal rearrangements, as observed during the initiation of tumorigenesis. Herein, we will highlight the complexity of the NE biology and discuss the clinical symptoms observed in NE-related diseases. The interplay between innate immunity, genomic instability, and nuclear envelope leakage could be a major focus in future years to explain a wide range of diseases and could lead to new classes of therapeutics.

Harnessing the Endogenous Plasticity of Pancreatic Islets: A Feasible Regenerative Medicine Therapy for Diabetes?

Diabetes is a chronic metabolic disease caused by an absolute or relative deficiency in functional pancreatic ß-cells that leads to defective control of blood glucose. Current treatments for diabetes, despite their great beneficial effects on clinical symptoms, are not curative treatments, leading to a chronic dependence on insulin throughout life that does not prevent the secondary complications associated with diabetes. The overwhelming increase in DM incidence has led to a search for novel antidiabetic therapies aiming at the regeneration of the lost functional ß-cells to allow the re-establishment of the endogenous glucose homeostasis. Here we review several aspects that must be considered for the development of novel and successful regenerative therapies for diabetes: first, the need to maintain the heterogeneity of islet ß-cells with several subpopulations of ß-cells characterized by different transcriptomic profiles correlating with differences in functionality and in resistance/behavior under stress conditions; second, the existence of an intrinsic islet plasticity that allows stimulus-mediated transcriptome alterations that trigger the transdifferentiation of islet non-ß-cells into ß-cells; and finally, the possibility of using agents that promote a fully functional/mature ß-cell phenotype to reduce and reverse the process of dedifferentiation of ß-cells during diabetes.

The Effects of Body Position on Trochanteric Soft Tissue Thickness-Implications for Predictions of Impact Force and Hip Fracture Risk During Lateral Falls.

Trochanteric soft tissue thickness (TSTT) is a protective factor against fall-related hip fractures. This study's objectives were to determine: (1) the influence of body posture on TSTT and (2) the downstream effects of TSTT on biomechanical model predictions of fall-related impact force (Ffemur) and hip fracture factor of risk. Ultrasound was used to measure TSTT in 45 community-dwelling older adults in standing, supine, and side-lying positions with hip rotation angles of -25°, 0°, and 25°. Supine TSTT (mean [SD] = 5.57 [2.8] cm) was 29% and 69% greater than in standing and side-lying positions, respectively. The Ffemur based on supine TSTT (3380 [2017] N) was 19% lower than the standing position (4173 [1764] N) and 31% lower than the side-lying position (4908 [1524] N). As factor of risk was directly influenced by Ffemur, the relative effects on fracture risk were similar. While less pronounced (<10%), the effects of hip rotation angle were consistent across TSTT, Ffemur, and factor of risk. Based on the sensitivity of impact models to TSTT, these results highlight the need for a standardized TSTT measurement approach. In addition, the consistent influence of hip rotation on TSTT (and downstream model predictions) support its importance as a factor that may influence fall-related hip fracture risk.

Emergence of Binocular Disparity Selectivity through Hebbian Learning.

Neural selectivity in the early visual cortex strongly reflects the statistics of our environment (Barlow, 2001; Geisler, 2008). Although this has been described extensively in literature through various encoding hypotheses (Barlow and Földiák, 1989; Atick and Redlich, 1992; Olshausen and Field, 1996), an explanation as to how the cortex might develop the computational architecture to support these encoding schemes remains elusive. Here, using the more realistic example of binocular vision as opposed to monocular luminance-field images, we show how a simple Hebbian coincidence-detector is capable of accounting for the emergence of binocular, disparity selective, receptive fields. We propose a model based on spike timing-dependent plasticity, which not only converges to realistic single-cell and population characteristics, but also demonstrates how known biases in natural statistics may influence population encoding and downstream correlates of behavior. Furthermore, we show that the receptive fields we obtain are closer in structure to electrophysiological data reported in macaques than those predicted by normative encoding schemes (Ringach, 2002). We also demonstrate the robustness of our model to the input dataset, noise at various processing stages, and internal parameter variation. Together, our modeling results suggest that Hebbian coincidence detection is an important computational principle and could provide a biologically plausible mechanism for the emergence of selectivity to natural statistics in the early sensory cortex.SIGNIFICANCE STATEMENT Neural selectivity in the early visual cortex is often explained through encoding schemes that postulate that the computational aim of early sensory processing is to use the least possible resources (neurons, energy) to code the most informative features of the stimulus (information efficiency). In this article, using stereo images of natural scenes, we demonstrate how a simple Hebbian rule can lead to the emergence of a disparity-selective neural population that not only shows realistic single-cell and population tunings, but also demonstrates how known biases in natural statistics may influence population encoding and downstream correlates of behavior. Our approach allows us to view early neural selectivity, not as an optimization problem, but as an emergent property driven by biological rules of plasticity.

Asymmetry of pictorial space: A cultural phenomenon.

Art experts have argued that the mirror reversal of pictorial artworks produces an alteration of their spatial content. However, this putative asymmetry of the pictorial space remains to be empirically proved and causally explained. Here, we address these issues with the "corridor illusion," a size illusion triggered by the pictorial space of a receding corridor. We show that mirror-reversed corridors-receding respectively leftward and rightward-induce markedly different illusion strengths and thus convey distinct pictorial spaces. Remarkably, the illusion is stronger with the rightward corridor among native left-to-right readers (French participants, n = 40 males) but conversely stronger with the leftward corridor among native right-to-left readers (Syrian participants, n = 40 males). Together, these results demonstrate an asymmetry of the pictorial space and point to our reading/writing habits as a major cause of this phenomenon.

Molecular Modelling of Islet ß-Cell Adaptation to Inflammation in Pregnancy and Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM), a metabolic disease that develops with the increase in insulin resistance during late pregnancy, is currently one of the most common complications affecting pregnancy. The polygenic nature of GDM, together with the interplay between different genetic variants with nutritional and environmental factors has hindered the full understanding of the etiology of this disease. However, an important genetic overlap has been found with type 2 diabetes mellitus (T2DM) and, as in the case of T2DM, most of the identified loci are associated with ß-cell function. Early detection of GDM and adequate interventions to control the maternal glycemia are necessary to avoid the adverse outcomes for both the mother and the offspring. The in utero exposure to the diabetic milieu predispose these children for future diseases, among them T2DM, originating a vicious circle implicated in the increased prevalence of both GDM and T2DM. The involvement of inflammatory processes in the development of GDM highlights the importance of pancreatic ß-cell factors able to favor the adaptation processes required during gestation, concomitantly with the protection of the islets from an inflammatory milieu. In this regard, two members of the Pax family of transcription factors, PAX4 and PAX8, together with the chromatin remodeler factor HMG20A, have gained great relevance due to their involvement in ß-cell mass adaptation together with their anti-inflammatory properties. Mutations in these factors have been associated with GDM, highlighting these as novel candidates for genetic screening analysis in the identification of women at risk of developing GDM.

Dynamics of perceptual decisions about symmetry in visual cortex.

Neuroimaging studies have identified multiple extra-striate visual areas that are sensitive to symmetry in planar images (Kohler et al., 2016; Sasaki et al., 2005). Here, we investigated which of these areas are directly involved in perceptual decisions about symmetry, by recording high-density EEG in participants (n = 25) who made rapid judgments about whether an exemplar image contained rotation symmetry or not. Stimulus-locked sensor-level analysis revealed symmetry-specific activity that increased with increasing order of rotation symmetry. Response-locked analysis identified activity occurring between 600 and 200 ms before the button-press, that was directly related to perceptual decision making. We then used fMRI-informed EEG source imaging to characterize the dynamics of symmetry-specific activity within an extended network of areas in visual cortex. The most consistent cortical source of the stimulus-locked activity was VO1, a topographically organized area in ventral visual cortex, that was highly sensitive to symmetry in a previous study (Kohler et al., 2016). Importantly, VO1 activity also contained a strong decision-related component, suggesting that this area plays a crucial role in perceptual decisions about symmetry. Other candidate areas, such as lateral occipital cortex, had weak stimulus-locked symmetry responses and no evidence of correlation with response timing.

Processing of Egomotion-Consistent Optic Flow in the Rhesus Macaque Cortex.

The cortical network that processes visual cues to self-motion was characterized with functional magnetic resonance imaging in 3 awake behaving macaques. The experimental protocol was similar to previous human studies in which the responses to a single large optic flow patch were contrasted with responses to an array of 9 similar flow patches. This distinguishes cortical regions where neurons respond to flow in their receptive fields regardless of surrounding motion from those that are sensitive to whether the overall image arises from self-motion. In all 3 animals, significant selectivity for egomotion-consistent flow was found in several areas previously associated with optic flow processing, and notably dorsal middle superior temporal area, ventral intra-parietal area, and VPS. It was also seen in areas 7a (Opt), STPm, FEFsem, FEFsac and in a region of the cingulate sulcus that may be homologous with human area CSv. Selectivity for egomotion-compatible flow was never total but was particularly strong in VPS and putative macaque CSv. Direct comparison of results with the equivalent human studies reveals several commonalities but also some differences.

PAX4 preserves endoplasmic reticulum integrity preventing beta cell degeneration in a mouse model of type 1 diabetes mellitus.

AIMS/HYPOTHESIS: A strategy to enhance pancreatic islet functional beta cell mass (BCM) while restraining inflammation, through the manipulation of molecular and cellular targets, would provide a means to counteract the deteriorating glycaemic control associated with diabetes mellitus. The aims of the current study were to investigate the therapeutic potential of such a target, the islet-enriched and diabetes-linked transcription factor paired box 4 (PAX4), to restrain experimental autoimmune diabetes (EAD) in the RIP-B7.1 mouse model background and to characterise putative cellular mechanisms associated with preserved BCM. METHODS: Two groups of RIP-B7.1 mice were genetically engineered to: (1) conditionally express either PAX4 (BPTL) or its diabetes-linked mutant variant R129W (mutBPTL) using doxycycline (DOX); and (2) constitutively express luciferase in beta cells through the use of RIP. Mice were treated or not with DOX, and EAD was induced by immunisation with a murine preproinsulin II cDNA expression plasmid. The development of hyperglycaemia was monitored for up to 4 weeks following immunisation and alterations in the BCM were assessed weekly by non-invasive in vivo bioluminescence intensity (BLI). In parallel, BCM, islet cell proliferation and apoptosis were evaluated by immunocytochemistry. Alterations in PAX4- and PAX4R129W-mediated islet gene expression were investigated by microarray profiling. PAX4 preservation of endoplasmic reticulum (ER) homeostasis was assessed using thapsigargin, electron microscopy and intracellular calcium measurements. RESULTS: PAX4 overexpression blunted EAD, whereas the diabetes-linked mutant variant PAX4R129W did not convey protection. PAX4-expressing islets exhibited reduced insulitis and decreased beta cell apoptosis, correlating with diminished DNA damage and increased islet cell proliferation. Microarray profiling revealed that PAX4 but not PAX4R129W targeted expression of genes implicated in cell cycle and ER homeostasis. Consistent with the latter, islets overexpressing PAX4 were protected against thapsigargin-mediated ER-stress-related apoptosis. Luminal swelling associated with ER stress induced by thapsigargin was rescued in PAX4-overexpressing beta cells, correlating with preserved cytosolic calcium oscillations in response to glucose. In contrast, RNA interference mediated repression of PAX4-sensitised MIN6 cells to thapsigargin cell death. CONCLUSIONS/INTERPRETATION: The coordinated regulation of distinct cellular pathways particularly related to ER homeostasis by PAX4 not achieved by the mutant variant PAX4R129W alleviates beta cell degeneration and protects against diabetes mellitus. The raw data for the RNA microarray described herein are accessible in the Gene Expression Omnibus database under accession number GSE62846.

On the Analytical Solution of Firing Time for SpikeProp.

Error backpropagation in networks of spiking neurons (SpikeProp) shows promise for the supervised learning of temporal patterns. However, its widespread use is hindered by its computational load and occasional convergence failures. In this letter, we show that the neuronal firing time equation at the core of SpikeProp can be solved analytically using the Lambert W function, offering a marked reduction in execution time over the step-based method used in the literature. Applying this analytical method to SpikeProp, we find that training time per epoch can be reduced by 12% to 56% under different experimental conditions. Finally, this work opens the way for further investigations of SpikeProp's convergence behavior.

The steady-state visual evoked potential in vision research: A review.

Periodic visual stimulation and analysis of the resulting steady-state visual evoked potentials were first introduced over 80 years ago as a means to study visual sensation and perception. From the first single-channel recording of responses to modulated light to the present use of sophisticated digital displays composed of complex visual stimuli and high-density recording arrays, steady-state methods have been applied in a broad range of scientific and applied settings.The purpose of this article is to describe the fundamental stimulation paradigms for steady-state visual evoked potentials and to illustrate these principles through research findings across a range of applications in vision science.

Effects of cognitive stimulation with a self-modeling video on time to exhaustion while running at maximal aerobic velocity: a pilot study.

This study assessed whether video self-modeling improves running performance and influences the rate of perceived exertion and heart rate response. Twelve men (M age=26.8 yr., SD=6; M body mass index=22.1 kg.m(-2), SD=1) performed a time to exhaustion running test at 100 percent maximal aerobic velocity while focusing on a video self-modeling loop to synchronize their stride. Compared to the control condition, there was a significant increase of time to exhaustion. Perceived exertion was lower also, but there was no significant change in mean heart rate. In conclusion, the video self-modeling used as a pacer apparently increased endurance by decreasing perceived exertion without affecting the heart rate.