Coverage, Continuity and Visual Cortical Architecture

The primary visual cortex of many mammals contains a continuous representation of visual space, with a roughly repetitive aperiodic map of orientation preferences superimposed. It was recently found that orientation preference maps (OPMs) obey statistical laws which are apparently invariant among species widely separated in eutherian evolution. Here, we examine whether one of the most prominent models for the optimization of cortical maps, the elastic net (EN) model, can reproduce this common design. The EN model generates representations which optimally trade of stimulus space coverage and map continuity. While this model has been used in numerous studies, no analytical results about the precise layout of the predicted OPMs have been obtained so far. We present a mathematical approach to analytically calculate the cortical representations predicted by the EN model for the joint mapping of stimulus position and orientation. We find that in all previously studied regimes, predicted OPM layouts are perfectly periodic. An unbiased search through the EN parameter space identifies a novel regime of aperiodic OPMs with pinwheel densities lower than found in experiments. In an extreme limit, aperiodic OPMs quantitatively resembling experimental observations emerge. Stabilization of these layouts results from strong nonlocal interactions rather than from a coverage-continuity-compromise. Our results demonstrate that optimization models for stimulus representations dominated by nonlocal suppressive interactions are in principle capable of correctly predicting the common OPM design. They question that visual cortical feature representations can be explained by a coverage-continuity-compromise.Comment: 100 pages, including an Appendix, 21 + 7 figure

Accurate path integration in continuous attractor network models of grid cells

Grid cells in the rat entorhinal cortex display strikingly regular firing responses to the animal's position in 2-D space and have been hypothesized to form the neural substrate for dead-reckoning. However, errors accumulate rapidly when velocity inputs are integrated in existing models of grid cell activity. To produce grid-cell-like responses, these models would require frequent resets triggered by external sensory cues. Such inadequacies, shared by various models, cast doubt on the dead-reckoning potential of the grid cell system. Here we focus on the question of accurate path integration, specifically in continuous attractor models of grid cell activity. We show, in contrast to previous models, that continuous attractor models can generate regular triangular grid responses, based on inputs that encode only the rat's velocity and heading direction. We consider the role of the network boundary in the integration performance of the network and show that both periodic and aperiodic networks are capable of accurate path integration, despite important differences in their attractor manifolds. We quantify the rate at which errors in the velocity integration accumulate as a function of network size and intrinsic noise within the network. With a plausible range of parameters and the inclusion of spike variability, our model networks can accurately integrate velocity inputs over a maximum of ~10–100 meters and ~1–10 minutes. These findings form a proof-of-concept that continuous attractor dynamics may underlie velocity integration in the dorsolateral medial entorhinal cortex. The simulations also generate pertinent upper bounds on the accuracy of integration that may be achieved by continuous attractor dynamics in the grid cell network. We suggest experiments to test the continuous attractor model and differentiate it from models in which single cells establish their responses independently of each other

Predicted contextual modulation varies with distance from pinwheel centers in the orientation preference map

In the primary visual cortex (V1) of some mammals, columns of neurons with the full range of orientation preferences converge at the center of a pinwheel-like arrangement, the ‘pinwheel center' (PWC). Because a neuron receives abundant inputs from nearby neurons, the neuron's position on the cortical map likely has a significant impact on its responses to the layout of orientations inside and outside its classical receptive field (CRF). To understand the positional specificity of responses, we constructed a computational model based on orientation preference maps in monkey V1 and hypothetical neuronal connections. The model simulations showed that neurons near PWCs displayed weaker but detectable orientation selectivity within their CRFs, and strongly reduced contextual modulation from extra-CRF stimuli, than neurons distant from PWCs. We suggest that neurons near PWCs robustly extract local orientation within their CRF embedded in visual scenes, and that contextual information is processed in regions distant from PWCs

Suicide with psychiatric diagnosis and without utilization of psychiatric service

<p>Abstract</p> <p>Background</p> <p>Considerable attention has been focused on the study of suicides among those who have received help from healthcare providers. However, little is known about the profiles of suicide deceased who had psychiatric illnesses but made no contact with psychiatric services prior to their death. Behavioural model of health service use is applied to identify factors associated with the utilization of psychiatric service among the suicide deceased.</p> <p>Methods</p> <p>With respect to completed suicide cases, who were diagnosed with a mental disorder, a comparison study was made between those who had (contact group; n = 52; 43.7%) and those who had not made any contact (non-contact group; n = 67; 56.3%) with a psychiatrist during the final six months prior to death. A <it>sample </it>of 119 deceased cases aged between 15 and 59 with at least one psychiatric diagnosis assessed by the Structured Clinical Interview for DSM-IV-TR (SCID I) were selected from a psychological autopsy study in Hong Kong.</p> <p>Results</p> <p>The contact and non-contact group could be well distinguished from each other by "<it>predisposing</it>" variables: age group & gender, and most of the "<it>enabling"</it>, and "<it>need" </it>variables tested in this study. Multiple logistic regression analysis has found four factors are statistically significantly associated with non-contact suicide deceased: (i) having non-psychotic disorders (OR = 13.5, 95% CI:2.9-62.9), (ii) unmanageable debts (OR = 10.5, CI:2.4-45.3), (iii) being full/partially/self employed at the time of death (OR = 10.0, CI:1.6-64.1) and (iv) having higher levels of social problem-solving ability (SPSI) (OR = 2.0, CI:1.1-3.6).</p> <p>Conclusion</p> <p>The non-contact group was clearly different from the contact group and actually comprised a larger proportion of the suicide population that they could hardly be reached by usual individual-based suicide prevention efforts. For this reason, both universal and strategic suicide prevention measures need to be developed specifically in non-medical settings to reach out to this non-contact group in order to achieve better suicide prevention results.</p

Neural network model of the primary visual cortex: From functional architecture to lateral connectivity and back

The role of intrinsic cortical dynamics is a debatable issue. A recent optical imaging study (Kenet et al., 2003) found that activity patterns similar to orientation maps (OMs), emerge in the primary visual cortex (V1) even in the absence of sensory input, suggesting an intrinsic mechanism of OM activation. To better understand these results and shed light on the intrinsic V1 processing, we suggest a neural network model in which OMs are encoded by the intrinsic lateral connections. The proposed connectivity pattern depends on the preferred orientation and, unlike previous models, on the degree of orientation selectivity of the interconnected neurons. We prove that the network has a ring attractor composed of an approximated version of the OMs. Consequently, OMs emerge spontaneously when the network is presented with an unstructured noisy input. Simulations show that the model can be applied to experimental data and generate realistic OMs. We study a variation of the model with spatially restricted connections, and show that it gives rise to states composed of several OMs. We hypothesize that these states can represent local properties of the visual scene

Setting priorities for land management to mitigate climate change

<p>Abstract</p> <p>Background</p> <p>No consensus has been reached how to measure the effectiveness of climate change mitigation in the land-use sector and how to prioritize land use accordingly. We used the long-term cumulative and average sectorial C stocks in biomass, soil and products, C stock changes, the substitution of fossil energy and of energy-intensive products, and net present value (NPV) as evaluation criteria for the effectiveness of a hectare of productive land to mitigate climate change and produce economic returns. We evaluated land management options using real-life data of Thuringia, a region representative for central-western European conditions, and input from life cycle assessment, with a carbon-tracking model. We focused on solid biomass use for energy production.</p> <p>Results</p> <p>In forestry, the traditional timber production was most economically viable and most climate-friendly due to an assumed recycling rate of 80% of wood products for bioenergy. Intensification towards "pure bioenergy production" would reduce the average sectorial C stocks and the C substitution and would turn NPV negative. In the forest conservation (non-use) option, the sectorial C stocks increased by 52% against timber production, which was not compensated by foregone wood products and C substitution. Among the cropland options wheat for food with straw use for energy, whole cereals for energy, and short rotation coppice for bioenergy the latter was most climate-friendly. However, specific subsidies or incentives for perennials would be needed to favour this option.</p> <p>Conclusions</p> <p>When using the harvested products as materials prior to energy use there is no climate argument to support intensification by switching from sawn-wood timber production towards energy-wood in forestry systems. A legal framework would be needed to ensure that harvested products are first used for raw materials prior to energy use. Only an effective recycling of biomaterials frees land for long-term sustained C sequestration by conservation. Reuse cascades avoid additional emissions from shifting production or intensification.</p

Low level constraints on dynamic contour path integration

Contour integration is a fundamental visual process. The constraints on integrating discrete contour elements and the associated neural mechanisms have typically been investigated using static contour paths. However, in our dynamic natural environment objects and scenes vary over space and time. With the aim of investigating the parameters affecting spatiotemporal contour path integration, we measured human contrast detection performance of a briefly presented foveal target embedded in dynamic collinear stimulus sequences (comprising five short 'predictor' bars appearing consecutively towards the fovea, followed by the 'target' bar) in four experiments. The data showed that participants' target detection performance was relatively unchanged when individual contour elements were separated by up to 2° spatial gap or 200ms temporal gap. Randomising the luminance contrast or colour of the predictors, on the other hand, had similar detrimental effect on grouping dynamic contour path and subsequent target detection performance. Randomising the orientation of the predictors reduced target detection performance greater than introducing misalignment relative to the contour path. The results suggest that the visual system integrates dynamic path elements to bias target detection even when the continuity of path is disrupted in terms of spatial (2°), temporal (200ms), colour (over 10 colours) and luminance (-25% to 25%) information. We discuss how the findings can be largely reconciled within the functioning of V1 horizontal connections

Integrating Diverse Datasets Improves Developmental Enhancer Prediction

Gene-regulatory enhancers have been identified using various approaches, including evolutionary conservation, regulatory protein binding, chromatin modifications, and DNA sequence motifs. To integrate these different approaches, we developed EnhancerFinder, a two-step method for distinguishing developmental enhancers from the genomic background and then predicting their tissue specificity. EnhancerFinder uses a multiple kernel learning approach to integrate DNA sequence motifs, evolutionary patterns, and diverse functional genomics datasets from a variety of cell types. In contrast with prediction approaches that define enhancers based on histone marks or p300 sites from a single cell line, we trained EnhancerFinder on hundreds of experimentally verified human developmental enhancers from the VISTA Enhancer Browser. We comprehensively evaluated EnhancerFinder using cross validation and found that our integrative method improves the identification of enhancers over approaches that consider a single type of data, such as sequence motifs, evolutionary conservation, or the binding of enhancer-associated proteins. We find that VISTA enhancers active in embryonic heart are easier to identify than enhancers active in several other embryonic tissues, likely due to their uniquely high GC content. We applied EnhancerFinder to the entire human genome and predicted 84,301 developmental enhancers and their tissue specificity. These predictions provide specific functional annotations for large amounts of human non-coding DNA, and are significantly enriched near genes with annotated roles in their predicted tissues and lead SNPs from genome-wide association studies. We demonstrate the utility of EnhancerFinder predictions through in vivo validation of novel embryonic gene regulatory enhancers from three developmental transcription factor loci. Our genome-wide developmental enhancer predictions are freely available as a UCSC Genome Browser track, which we hope will enable researchers to further investigate questions in developmental biology. © 2014 Erwin et al

On the Origin of the Functional Architecture of the Cortex

The basic structure of receptive fields and functional maps in primary visual cortex is established without exposure to normal sensory experience and before the onset of the critical period. How the brain wires these circuits in the early stages of development remains unknown. Possible explanations include activity-dependent mechanisms driven by spontaneous activity in the retina and thalamus, and molecular guidance orchestrating thalamo-cortical connections on a fine spatial scale. Here I propose an alternative hypothesis: the blueprint for receptive fields, feature maps, and their inter-relationships may reside in the layout of the retinal ganglion cell mosaics along with a simple statistical connectivity scheme dictating the wiring between thalamus and cortex. The model is shown to account for a number of experimental findings, including the relationship between retinotopy, orientation maps, spatial frequency maps and cytochrome oxidase patches. The theory's simplicity, explanatory and predictive power makes it a serious candidate for the origin of the functional architecture of primary visual cortex

Bidirectional transcription initiation marks accessible chromatin and is not specific to enhancers

Abstract Background Enhancers are modular regulatory elements that are central to the spatial and temporal regulation of gene expression. Bidirectional transcription initiating at enhancers has been proposed to mark active enhancers and as such has been utilized to experimentally identify active enhancers de novo. Results Here, we show that bidirectional transcription initiation is a pervasive feature of accessible chromatin, including at enhancers, promoters, and other DNase hypersensitive regions not marked with canonical histone modification profiles. Transcription is less predictive for enhancer activity than epigenetic modifications such as H3K4me1 or the accessibility of DNA when measured both in enhancer assays and at endogenous loci. The stability of enhancer initiated transcripts does not influence measures of enhancer activity and we cannot detect evidence of purifying selection on the resulting enhancer RNAs within the human population. Conclusions Our results indicate that bidirectional transcription initiation from accessible chromatin is not sufficient for, nor specific to, enhancer activity. Transcription initiating at enhancers may be a frequent by-product of promiscuous RNA polymerase initiation at accessible chromatin and is unlikely to generally play a functional role in enhancer activity