The impact of distractor congruency on stimulus processing in retinotopic visual cortex

The brain is frequently confronted with sensory information that elicits conflicting response choices. While much research has addressed the top down control mechanisms associated with detection and resolution of response competition, the effects of response competition on sensory processing in the primary visual cortex remain unclear. To address this question we modified a typical 'flanker task' (Eriksen and Eriksen, 1974) so that the effects of response competition on human early retinotopic visual cortex could be assessed. Healthy human participants were scanned using fMRI while making a speeded choice response that classified a target object image into one of two categories (e.g. fruits, animals). An irrelevant distractor image that was either congruent (same image as target), incongruent (image from opposite category as target), or neutral (image from task-irrelevant category, e.g. household items) was also present on each trial, but in a different quadrant of the visual field relative to the target. Retinotopic V1 areas responding to the target stimuli showed increased response to targets in the presence of response-incongruent (compared to response-neutral) distractors. A negative correlation with behavioral response competition effects indicated that an increased primary visual cortical response to targets in the incongruent (vs. neutral) trials is associated with a reduced response competition effect on behavior. These results suggest a novel conflict resolution mechanism in the primary visual cortex

Attention induced neural response trade-off in retinotopic cortex under load

The effects of perceptual load on visual cortex response to distractors are well established and various phenomena of ‘inattentional blindness’ associated with elimination of visual cortex response to unattended distractors, have been documented in tasks of high load. Here we tested an account for these effects in terms of a load-induced trade-off between target and distractor processing in retinotopic visual cortex. Participants were scanned using fMRI while performing a visual-search task and ignoring distractor checkerboards in the periphery. Retinotopic responses to target and distractors were assessed as a function of search load (comparing search set-sizes two, three and five). We found that increased load not only increased activity in frontoparietal network, but also had opposite effects on retinotopic responses to target and distractors. Target-related signals in areas V2–V3 linearly increased, while distractor response linearly decreased, with increased load. Critically, the slopes were equivalent for both load functions, thus demonstrating resource trade-off. Load effects were also found in displays with the same item number in the distractor hemisphere across different set sizes, thus ruling out local intrahemispheric interactions as the cause. Our findings provide new evidence for load theory proposals of attention resource sharing between target and distractor leading to inattentional blindness

Working Memory Load Modulates Distractor Competition in Primary Visual Cortex

When stimuli compete for sensory processing and response selection, coherent goal-guided behavior requires cognitive control so that task-relevant "targets" rather than irrelevant distractors are selected. It has been shown that reduced cognitive control under high working memory load increases distractor competition for selection. It remains unknown, though, whether cognitive control by working memory has an effect on the earliest levels of sensory processing in primary visual cortex. The present study addressed this question by having subjects perform a selective attention task involving classification of meaningful target objects while also ignoring congruent and incongruent distractor images. The level of cognitive control over distractor competition was varied through a concurrent working memory task of either low (1 digit) or high (6 digits) load. Functional magnetic resonance imaging revealed greater distractor competition effects not only on behavior but also on the sensory correlates in primary visual cortex (areas V1-V2) in conditions of high (vs. low) working memory load. In addition, high working memory load resulted in increased congruency-related functional connectivity between anterior cingulate cortex and V1. These results are the first to establish the neural correlates of distractor competition effects in primary visual cortex and the critical role of working memory in their cognitive control

Locally Reducing KCC2 Activity in the Hippocampus is Sufficient to Induce Temporal Lobe Epilepsy

Mesial temporal lobe epilepsy (mTLE) is the most common form of epilepsy, believed to arise in part from compromised GABAergic inhibition. The neuronal specific K+/Cl− co-transporter 2 (KCC2) is a critical determinant of the efficacy of GABAergic inhibition and deficits in its activity are observed in mTLE patients and animal models of epilepsy. To test if reductions of KCC2 activity directly contribute to the pathophysiology of mTLE, we locally ablated KCC2 expression in a subset of principal neurons within the adult hippocampus. Deletion of KCC2 resulted in compromised GABAergic inhibition and the development of spontaneous, recurrent generalized seizures. Moreover, local ablation of KCC2 activity resulted in hippocampal sclerosis, a key pathological change seen in mTLE. Collectively, our results demonstrate that local deficits in KCC2 activity within the hippocampus are sufficient to precipitate mTLE

A novel histological index for evaluation of environmental enteric dysfunction identifies geographic-specific features of enteropathy among children with suboptimal growth

Background: A major limitation to understanding the etiopathogenesis of environmental enteric dysfunction (EED) is the lack of a comprehensive, reproducible histologic framework for characterizing the small bowel lesions. We hypothesized that the development of such a system will identify unique histology features for EED, and that some features might correlate with clinical severity.Methods: Duodenal endoscopic biopsies from two cohorts where EED is prevalent (Pakistan, Zambia) and North American children with and without gluten sensitive enteropathy (GSE) were processed for routine hematoxylin & eosin (H&E) staining, and scanned to produce whole slide images (WSIs) which we shared among study pathologists via a secure web browser-based platform. A semi-quantitative scoring index composed of 11 parameters encompassing tissue injury and response patterns commonly observed in routine clinical practice was constructed by three gastrointestinal pathologists, with input from EED experts. The pathologists then read the WSIs using the EED histology index, and inter-observer reliability was assessed. The histology index was further used to identify within- and between-child variations as well as features common across and unique to each cohort, and those that correlated with host phenotype.Results: Eight of the 11 histologic scoring parameters showed useful degrees of variation. The overall concordance across all parameters was 96% weighted agreement, kappa 0.70, and Gwet\u27s AC 0.93. Zambian and Pakistani tissues shared some histologic features with GSE, but most features were distinct, particularly abundance of intraepithelial lymphocytes in the Pakistani cohort, and marked villous destruction and loss of secretory cell lineages in the Zambian cohort.Conclusions: We propose the first EED histology index for interpreting duodenal biopsies. This index should be useful in future clinical and translational studies of this widespread, poorly understood, and highly consequential disorder, which might be caused by multiple contributing processes, in different regions of the world

Equivalence of switching linear systems by bisimulation

A general notion of hybrid bisimulation is proposed for the class of switching linear systems. Connections between the notions of bisimulation-based equivalence, state-space equivalence, algebraic and input–output equivalence are investigated. An algebraic characterization of hybrid bisimulation and an algorithmic procedure converging in a finite number of steps to the maximal hybrid bisimulation are derived. Hybrid state space reduction is performed by hybrid bisimulation between the hybrid system and itself. By specializing the results obtained on bisimulation, also characterizations of simulation and abstraction are derived. Connections between observability, bisimulation-based reduction and simulation-based abstraction are studied.\ud \u

A mathematical model for the onset of avascular tumor growth in response to the loss of p53 function

We present a mathematical model for the formation of an avascular tumor based on the loss by gene mutation of the tumor suppressor function of p53. The wild type p53 protein regulates apoptosis, cell expression of growth factor and matrix metalloproteinase, which are regulatory functions that many mutant p53 proteins do not possess. The focus is on a description of cell movement as the transport of cell population density rather than as the movement of individual cells. In contrast to earlier works on solid tumor growth, a model is proposed for the initiation of tumor growth. The central idea, taken from the mathematical theory of dynamical systems, is to view the loss of p53 function in a few cells as a small instability in a rest state for an appropriate system of differential equations describing cell movement. This instability is shown (numerically) to lead to a second, spatially inhomogeneous, solution that can be thought of as a solid tumor whose growth is nutrient diffusion limited. In this formulation, one is led to a system of nine partial differential equations. We show computationally that there can be tumor states that coexist with benign states and that are highly unstable in the sense that a slight increase in tumor size results in the tumor occupying the sample region while a slight decrease in tumor size results in its ultimate disappearance