Contextual coherence increases perceived numerosity independent of semantic content.

Number perception emerges from multiple stages of visual processing. Understanding how systematic biases in number perception occur within a hierarchy of increasingly complex feature representations helps uncover the multistage processing underlying our visual number sense. Recent work demonstrated that reducing coherence of low-level visual attributes, such as color and orientation, systematically reduces perceived number. Here, we ask when in the visual processing hierarchy coherence affects numerosity perception and specifically whether the coherence effect is exclusive to low-level visual features or instead whether it can be driven by contextual or semantic relationships. We tested adults in an ordinal numerical comparison task with contextual coherence mathematically manipulated using a statistical model of visual object co-occurrence. Across several experiments, we found that arrays with high contextual coherence were perceived as numerically larger than arrays with low contextual coherence. This contextual coherence effect was not attenuated even when we reduced objects to texforms (unrecognizable images that preserve midlevel visual features) or removed semantic content from the images through box scrambling and diffeomorphic warping. Together, these results suggest that visual coherence derived from natural statistics of object co-occurrence systematically alters perceived numerosity at low-level visual processing, even before later stages at which items can be explicitly categorized and identified. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A Phone in a Basket Looks Like a Knife in a Cup: Role-Filler Independence in Visual Processing.

When a piece of fruit is in a bowl, and the bowl is on a table, we appreciate not only the individual objects and their features, but also the relations containment and support, which abstract away from the particular objects involved. Independent representation of roles (e.g., containers vs. supporters) and "fillers" of those roles (e.g., bowls vs. cups, tables vs. chairs) is a core principle of language and higher-level reasoning. But does such role-filler independence also arise in automatic visual processing? Here, we show that it does, by exploring a surprising error that such independence can produce. In four experiments, participants saw a stream of images containing different objects arranged in force-dynamic relations-e.g., a phone contained in a basket, a marker resting on a garbage can, or a knife sitting in a cup. Participants had to respond to a single target image (e.g., a phone in a basket) within a stream of distractors presented under time constraints. Surprisingly, even though participants completed this task quickly and accurately, they false-alarmed more often to images matching the target's relational category than to those that did not-even when those images involved completely different objects. In other words, participants searching for a phone in a basket were more likely to mistakenly respond to a knife in a cup than to a marker on a garbage can. Follow-up experiments ruled out strategic responses and also controlled for various confounding image features. We suggest that visual processing represents relations abstractly, in ways that separate roles from fillers.

High-performing neural network models of visual cortex benefit from high latent dimensionality.

Geometric descriptions of deep neural networks (DNNs) have the potential to uncover core representational principles of computational models in neuroscience. Here we examined the geometry of DNN models of visual cortex by quantifying the latent dimensionality of their natural image representations. A popular view holds that optimal DNNs compress their representations onto low-dimensional subspaces to achieve invariance and robustness, which suggests that better models of visual cortex should have lower dimensional geometries. Surprisingly, we found a strong trend in the opposite direction-neural networks with high-dimensional image subspaces tended to have better generalization performance when predicting cortical responses to held-out stimuli in both monkey electrophysiology and human fMRI data. Moreover, we found that high dimensionality was associated with better performance when learning new categories of stimuli, suggesting that higher dimensional representations are better suited to generalize beyond their training domains. These findings suggest a general principle whereby high-dimensional geometry confers computational benefits to DNN models of visual cortex.

Hierarchical organization of social action features along the lateral visual pathway.

Recent theoretical work has argued that in addition to the classical ventral (what) and dorsal (where/how) visual streams, there is a third visual stream on the lateral surface of the brain specialized for processing social information. Like visual representations in the ventral and dorsal streams, representations in the lateral stream are thought to be hierarchically organized. However, no prior studies have comprehensively investigated the organization of naturalistic, social visual content in the lateral stream. To address this question, we curated a naturalistic stimulus set of 250 3-s videos of two people engaged in everyday actions. Each clip was richly annotated for its low-level visual features, mid-level scene and object properties, visual social primitives (including the distance between people and the extent to which they were facing), and high-level information about social interactions and affective content. Using a condition-rich fMRI experiment and a within-subject encoding model approach, we found that low-level visual features are represented in early visual cortex (EVC) and middle temporal (MT) area, mid-level visual social features in extrastriate body area (EBA) and lateral occipital complex (LOC), and high-level social interaction information along the superior temporal sulcus (STS). Communicative interactions, in particular, explained unique variance in regions of the STS after accounting for variance explained by all other labeled features. Taken together, these results provide support for representation of increasingly abstract social visual content-consistent with hierarchical organization-along the lateral visual stream and suggest that recognizing communicative actions may be a key computational goal of the lateral visual pathway.

Scene context is predictive of unconstrained object similarity judgments.

What makes objects alike in the human mind? Computational approaches for characterizing object similarity have largely focused on the visual forms of objects or their linguistic associations. However, intuitive notions of object similarity may depend heavily on contextual reasoning-that is, objects may be grouped together in the mind if they occur in the context of similar scenes or events. Using large-scale analyses of natural scene statistics and human behavior, we found that a computational model of the associations between objects and their scene contexts is strongly predictive of how humans spontaneously group objects by similarity. Specifically, we learned contextual prototypes for a diverse set of object categories by taking the average response of a convolutional neural network (CNN) to the scene contexts in which the objects typically occurred. In behavioral experiments, we found that contextual prototypes were strongly predictive of human similarity judgments for a large set of objects and rivaled the performance of models based on CNN representations of the objects themselves or word embeddings for their names. Together, our findings reveal the remarkable degree to which the natural statistics of context predict commonsense notions of object similarity.

Perceived Distance Alters Memory for Scene Boundaries.

Memory often fills in what is not there. A striking example of this is boundary extension, whereby observers mistakenly recall a view that extends beyond what was seen. However, not all visual memories extend in this way, which suggests that this process depends on specific scene properties. What factors determine when visual memories will include details that go beyond perceptual experience? Here, seven experiments (N = 1,100 adults) explored whether spatial scale-specifically, perceived viewing distance-drives boundary extension. We created fake miniatures by exploiting tilt shift, a photographic effect that selectively reduces perceived distance while preserving other scene properties (e.g., making a distant railway appear like a model train). Fake miniaturization increased boundary extension for otherwise identical scenes: Participants who performed a scene-memory task misremembered fake-miniaturized views as farther away than they actually were. This effect went beyond low-level image changes and generalized to a completely different distance manipulation. Thus, visual memory is modulated by the spatial scale at which the environment is viewed.

Scene memories are biased toward high-probability views.

Visual scenes are often remembered as if they were observed from a different viewpoint. Some scenes are remembered as farther than they appeared, and others as closer. These memory distortions-also known as boundary extension and contraction-are strikingly consistent for a given scene, but their cause remains unknown. We tested whether these distortions can be explained by an inferential process that adjusts scene memories toward high-probability views, using viewing depth as a test case. We first carried out a large-scale analysis of depth maps of natural indoor scenes to quantify the statistical probability of views in depth. We then assessed human observers' memory for these scenes at various depths and found that viewpoint judgments were consistently biased toward the modal depth, even when just a few seconds elapsed between viewing and reporting. Thus, scenes closer than the modal depth showed a boundary-extension bias (remembered as farther-away), and scenes farther than the modal depth showed a boundary-contraction bias (remembered as closer). By contrast, scenes at the modal depth did not elicit a consistent bias in either direction. This same pattern of results was observed in a follow-up experiment using tightly controlled stimuli from virtual environments. Together, these findings show that scene memories are biased toward statistically probable views, which may serve to increase the accuracy of noisy or incomplete scene representations. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Early Electrophysiological Markers of Navigational Affordances in Scenes.

Scene perception and spatial navigation are interdependent cognitive functions, and there is increasing evidence that cortical areas that process perceptual scene properties also carry information about the potential for navigation in the environment (navigational affordances). However, the temporal stages by which visual information is transformed into navigationally relevant information are not yet known. We hypothesized that navigational affordances are encoded during perceptual processing and therefore should modulate early visually evoked ERPs, especially the scene-selective P2 component. To test this idea, we recorded ERPs from participants while they passively viewed computer-generated room scenes matched in visual complexity. By simply changing the number of doors (0 doors, 1 door, 2 doors, 3 doors), we were able to systematically vary the number of pathways that afford movement in the local environment, while keeping the overall size and shape of the environment constant. We found that rooms with 0 doors evoked a higher P2 response than rooms with three doors, consistent with prior research reporting higher P2 amplitude to closed relative to open scenes. Moreover, we found P2 amplitude scaled linearly with the number of doors in the scenes. Navigability effects on the ERP waveform were also observed in a multivariate analysis, which showed significant decoding of the number of doors and their location at earlier time windows. Together, our results suggest that navigational affordances are represented in the early stages of scene perception. This complements research showing that the occipital place area automatically encodes the structure of navigable space and strengthens the link between scene perception and navigation.

Unveiling functions of the visual cortex using task-specific deep neural networks.

The human visual cortex enables visual perception through a cascade of hierarchical computations in cortical regions with distinct functionalities. Here, we introduce an AI-driven approach to discover the functional mapping of the visual cortex. We related human brain responses to scene images measured with functional MRI (fMRI) systematically to a diverse set of deep neural networks (DNNs) optimized to perform different scene perception tasks. We found a structured mapping between DNN tasks and brain regions along the ventral and dorsal visual streams. Low-level visual tasks mapped onto early brain regions, 3-dimensional scene perception tasks mapped onto the dorsal stream, and semantic tasks mapped onto the ventral stream. This mapping was of high fidelity, with more than 60% of the explainable variance in nine key regions being explained. Together, our results provide a novel functional mapping of the human visual cortex and demonstrate the power of the computational approach.

Object representations in the human brain reflect the co-occurrence statistics of vision and language.

A central regularity of visual perception is the co-occurrence of objects in the natural environment. Here we use machine learning and fMRI to test the hypothesis that object co-occurrence statistics are encoded in the human visual system and elicited by the perception of individual objects. We identified low-dimensional representations that capture the latent statistical structure of object co-occurrence in real-world scenes, and we mapped these statistical representations onto voxel-wise fMRI responses during object viewing. We found that cortical responses to single objects were predicted by the statistical ensembles in which they typically occur, and that this link between objects and their visual contexts was made most strongly in parahippocampal cortex, overlapping with the anterior portion of scene-selective parahippocampal place area. In contrast, a language-based statistical model of the co-occurrence of object names in written text predicted responses in neighboring regions of object-selective visual cortex. Together, these findings show that the sensory coding of objects in the human brain reflects the latent statistics of object context in visual and linguistic experience.

An Optimized Model of Hypertrophic Preconditioning Confers Cardioprotection in the Mouse.

BACKGROUND: Conventional models of hypertrophic preconditioning (C-HP) can be established surgically through transverse aortic constriction (TAC) → deconstriction (De-TAC) → reconstriction (Re-TAC) characterized by dynamic afterload while it exerts technical difficulty on operators and poses high mortality during perioperative period in mice. We aimed to introduce an optimized method for obtaining a hypertrophic preconditioning (O-HP) model for further study on cardiac hypertrophy. METHODS: Ninety mice were divided into four groups: sham, TAC, C-HP, and O-HP. The sham group was exerted on three-time thoracotomies. The TAC group experienced twice thoracotomies and one TAC operation. C-HP and O-HP groups were given TAC, De-TAC, and Re-TAC operation at day 0, day 3, and day 7 in conventional and optimized method, respectively. We optimized the operating procedure in O-HP mice compared with the C-HP group by (1) leaving a ∼3-cm suture fixed in the subcutaneous layer after aortic constriction in TAC surgery (2) using two small forceps to untie the constriction knot instead of cutting it in the De-TAC operation. Ultrasound biomicroscopy was used for hemodynamics and cardiac function detection. Four weeks after the third surgery, all mice were sacrificed and pathology was analyzed among four groups. RESULTS: Four weeks after Re-TAC, the survival of O-HP mice was 63.3% while that of C-HP was 26.7%. Ultrasound biomicroscopy showed a successful establishment of HP models. C-HP and O-HP mice had improved cardiac structure and function indicated by left ventricular end-systolic diameter, left ventricular end-systolic posterior wall thickness, left ventricular ejection fraction, and left ventricular fractional shortening than the TAC group. Pathological analysis showed O-HP as well as C-HP had less hypertrophy than the TAC mice. CONCLUSIONS: Our results provide a rapid, safe, efficient, and reproducible method for optimized establishment of the HP model, which will facilitate studies for early intervention and prevention of left ventricular hypertrophy and heart failure.

Correction: da Costa et al. Establishment of a Temperature-Sensitive Model of Oncogene-Induced Senescence in Angiosarcoma Cells. Cancers 2020, 12, 395.

The authors wish to make the following corrections to this paper [...].

Endophilin A2 deficiency protects rodents from autoimmune arthritis by modulating T cell activation.

The introduction of the CTLA-4 recombinant fusion protein has demonstrated therapeutic effects by selectively modulating T-cell activation in rheumatoid arthritis. Here we show, using a forward genetic approach, that a mutation in the SH3gl1 gene encoding the endocytic protein Endophilin A2 is associated with the development of arthritis in rodents. Defective expression of SH3gl1 affects T cell effector functions and alters the activation threshold of autoreactive T cells, thereby leading to complete protection from chronic autoimmune inflammatory disease in both mice and rats. We further show that SH3GL1 regulates human T cell signaling and T cell receptor internalization, and its expression is upregulated in rheumatoid arthritis patients. Collectively our data identify SH3GL1 as a key regulator of T cell activation, and as a potential target for treatment of autoimmune diseases.

Glycan Activation of Clec4b Induces Reactive Oxygen Species Protecting against Neutrophilia and Arthritis.

Animal models for complex diseases are needed to position and analyze the function of interacting genes. Previous positional cloning identified Ncf1 and Clec4b to be major regulators of arthritis models in rats. Here, we investigate epistasis between Ncf1 and Clec4b, two major regulators of arthritis in rats. We find that Clec4b and Ncf1 exert an additive effect on arthritis given by their joint ability to regulate neutrophils. Both genes are highly expressed in neutrophils, together regulating neutrophil availability and their capacity to generate reactive oxygen species. Using a glycan array, we identify key ligands of Clec4b and demonstrate that Clec4b-specific stimulation triggers neutrophils into oxidative burst. Our observations highlight Clec4b as an important regulator of neutrophils and demonstrate how epistatic interactions affect the susceptibility to, and severity of, autoimmune arthritis.

Similarly oriented objects appear more numerous.

Several non-numerical factors influence the numerical estimation of visual arrays, including the spacing of items and whether they are arranged randomly or symmetrically. Here we report a novel numerosity illusion we term the coherence illusion. When items in an array have a coherent orientation (all pointing in the same direction) they seem to be more numerous than when items are oriented randomly. Participants show parametric effects of orientation coherence in three distinct numerical judgment tasks. These findings are not predicted by any current model of numerical estimation. We discuss array entropy as a possible framework for explaining both the coherence illusion and the previously reported regular-random illusion.

Establishment of a Temperature-Sensitive Model of Oncogene-Induced Senescence in Angiosarcoma Cells.

: Lesions with driver mutations, including atypical nevi and seborrheic keratoses, are very common in dermatology, and are prone to senescence. The molecular events that prevent senescent lesions from becoming malignant are not well understood. We have developed a model of vascular proliferation using a temperaturesensitive, large T antigen and oncogenic HRas. By elevating the temperature to 39 °C, we can turn off large T antigen and study the molecular events in cells with the Ras driver mutation. To assess the signaling events associated with the switch from a proliferative to a nonproliferative state in the constant presence of a driver oncogene, SVR cells were cultivated for 24 and 48 hours and compared with SVR cells at 37 °C. Cells were evaluated by Western Blot (WB) gene chip microarray (GC) and quantitative reverse transcription polymerase chain reaction (RT-qPCR). Upon evaluation, a novel phenotype was observed in endothelial cells after switching off the large T antigen. This phenotype was characterized by Notch activation, downregulation of p38 phosphorylation, downregulation of the master immune switch IRF7, and downregulation of hnRNP A0 . Switching off proliferative signaling may result in immune privilege and Notch activation, which may account, in part, for the survival of common skin lesions.

Tris DBA palladium is an orally available inhibitor of GNAQ mutant uveal melanoma in vivo.

Uveal melanoma is a rare but often lethal malignancy and is the leading cause of death due to an ophthalmic condition. Uveal melanoma is often diagnosed at a late stage and has a strong propensity to hepatic metastasis. Recently, the most common driver mutations in uveal melanoma have been identified, predominantly in the G-proteins GNAQ. This pattern differs from that of cutaneous melanoma in which Braf and Nras predominate. There are no current clinically used agents that target GNAQ mutations, unlike the use of Braf inhibitors in cutaneous melanoma. We tested the novel agent Tris DBA palladium and found that it was markedly more effective against GNAQ mutant melanomas than wild type uveal melanomas. Given that ARF6 has recently been discovered as a node in GNAQ mutations, we evaluated the efficacy of Tris DBA palladium on ARF6 signaling and found that it was effective in inhibiting ARF6 activation. Finally, Tris DBA palladium was orally effective against GNAQ mutant melanoma in vivo. Tris DBA Palladium deserves further evaluation as a systemic agent for uveal melanoma.

Adipose-derived mesenchymal stromal/stem cells in systemic sclerosis: Alterations in function and beneficial effect on lung fibrosis are regulated by caveolin-1.

The potential value of mesenchymal stromal/stem cell therapy in treating skin fibrosis in scleroderma (systemic sclerosis) and of the caveolin-1 scaffolding domain peptide in treating lung, skin, and heart fibrosis is known. To understand how these observations may relate to differences between mesenchymal stromal/stem cells from healthy subjects and subjects with fibrosis, we have characterized the fibrogenic and adipogenic potential of adipose-derived mesenchymal stromal/stem cells from systemic sclerosis patients, from mice with fibrotic lung and skin disease induced by systemic bleomycin treatment, and from healthy controls. Early passage systemic sclerosis adipose-derived mesenchymal stromal/stem cells have a profibrotic/anti-adipogenic phenotype compared to healthy adipose-derived mesenchymal stromal/stem cells (low caveolin-1, high α-smooth muscle actin, high HSP47, low pAKT, low capacity for adipogenic differentiation). This phenotype is mimicked by treating healthy adipose-derived mesenchymal stromal/stem cells with transforming growth factor beta or caveolin-1 small interfering RNA and is reversed in systemic sclerosis adipose-derived mesenchymal stromal/stem cells by treatment with caveolin-1 scaffolding domain peptide, but not scrambled caveolin-1 scaffolding domain peptide. Similar results were obtained with adipose-derived mesenchymal stromal/stem cells from systemic sclerosis patients and from bleomycin-treated mice, indicating the central role of caveolin-1 in mesenchymal stromal/stem cell differentiation in fibrotic disease.

Selenium unmasks protective iron armor: A possible defense against cutaneous inflammation and cancer.

BACKGROUND: A link between selenium deficiency and inflammatory skin diseases have been noted by many, but this link is still not well understood. We have previously studied the efficacy of ceramide analogs, based on the fire ant venom Solenopsin A, against our psoriasis animal model. Treatment of animals with solenopsin analogs resulted in significantly improved skin as well as in a coordinate downregulation of selenoproteins, namely Glutathione Peroxidase 4 (GPX4). We thus hypothesize that ferroptosis may be a physiologic process that may protect the skin from both inflammatory and neoplastic processes. METHODS: We analyze and compare gene expression profiles in the GEO database from clinical skin samples taken from healthy patients and psoriasis patients (both involved and noninvolved skin lesions). We validated the gene expression results against a second, independent, cohort from the GEO database. RESULTS: Significant reduction in gene expression of GPX4, elevated expression of Nrf2 downstream targets, and expression profiles mirroring erastin-inhibition of Cystine/Glutamate Antiporter-System XC activity in psoriatic skin lesions, compared to both noninvolved skin and healthy patient samples, suggest an innately inducible mechanism of ferroptosis. CONCLUSIONS: We present data that may indicate selenoproteins, particularly GPX4, in resolving inflammation and skin cancer, including the novel hypothesis that the human organism may downregulate GPX4 and reactive oxygen (REDOX) regulating proteins in the skin as a way of resolving psoriasis and nonmelanoma skin cancer through increased reactive oxygen species. Further studies are needed to investigate ferroptosis as a possible physiologic mechanism for eliminating inflammatory and malignant tissues. GENERAL SIGNIFICANCE: This study provides a fresh framework for understanding the seemingly contradictory effects of selenium supplementation. In addition, it offers a novel explanation of how physiologic upregulation of ferroptosis and downregulation of selenoprotein synthesis may mediate resolution of inflammation and carcinogenesis. This is of therapeutic significance.