The network structure of cancer ecosystems, bioRxiv, 2017-12-30

Ever since Paget’s seed-and-soil and Ewing’s connectivity hypotheses to explain tumor metastasis (1,2), it has become clear that cancer progression can be envisaged as an ecological phenomenon. This connection has flourished during the past two decades (3–7), giving rise to important insights into the ecology and evolution of cancer progression, with therapeutic implications (8–10). Here, we take a metapopulation view of metastasis (i.e. the migration to and colonization of, habitat patches) and represent it as a bipartite network, distinguishing source patches, or organs that host a primary tumor, and acceptor patches, or organs colonized ultimately from the source through metastasis. Using 20,326, biomedical records obtained from literature, we show that (i) the network structure of cancer ecosystems is non-random, exhibiting a nested subset pattern as has been found both in the distribution of species across islands and island-like habitats (11–13), and in the distribution of among species interactions across different ecological networks (14–16); (ii) similar to ecological networks, there is a heterogeneous distribution of degree (i.e., number of connections associated with a source or acceptor organ); (iii) there is a significant correlation between metastatic incidence (or the frequency with which tumor cells from a source organ colonize an acceptor one) and arterial blood supply, suggesting that more irrigated organs have a higher probability of developing metastasis or being invaded; (iv) there is a positive correlation between metastatic incidence and acceptor organ degree (or number of different tumor-bearing source organs that generate metastasis in a given acceptor organ), and a negative one between acceptor organ degree and number of stem cell divisions, implying that there are preferred sink organs for metastasis and that this could be related to average acceptor organ cell longevity; (v) there is a negative association between organ cell turnover and source organ degree, implying that organs with rapid cell turnovers tend to generate more metastasis, a process akin to the phenomenon of propagule pressure in ecology (17); and (vi) the cancer ecosystem network exhibits a modular structure in both source and acceptor patches, suggesting that some of them share more connections among themselves than with the rest of the network. We show that both niche-related processes occurring at the organ level as well as spatial connectivity and propagule pressure contribute to metastaticspread and result in a non-random cancer network, which exhibits a truncated power law degree distribution, clustering and a nested subset structure. The similarity between the cancer network and ecological networks highlights the importance of ecological approaches in increasing our understanding of patterns in cancer incidence and dynamics, which may lead to new strategies to control tumor spread within the human ecosystem.

biorxiv ecology 0-100-users 2017

Confidence modulates exploration and exploitation in value-based learning, bioRxiv, 2017-12-29

AbstractUncertainty is ubiquitous in cognitive processing, which is why agents require a precise handle on how to deal with the noise inherent in their mental operations. Previous research suggests that people possess a remarkable ability to track and report uncertainty, often in the form of confidence judgments. Here, we argue that humans use uncertainty inherent in their representations of value beliefs to arbitrate between exploration and exploitation. Such uncertainty is reflected in explicit confidence judgments. Using a novel variant of a multi-armed bandit paradigm, we studied how beliefs were formed and how uncertainty in the encoding of these value beliefs (belief confidence) evolved over time. We found that people used uncertainty to arbitrate between exploration and exploitation, reflected in a higher tendency towards exploration when their confidence in their value representations was low. We furthermore found that value uncertainty can be linked to frameworks of metacognition in decision making in two ways. First, belief confidence drives decision confidence—that is people’s evaluation of their own choices. Second, individuals with higher metacognitive insight into their choices were also better at tracing the uncertainty in their environment. Together, these findings argue that such uncertainty representations play a key role in the context of cognitive control.

biorxiv neuroscience 100-200-users 2017

Deep image reconstruction from human brain activity, bioRxiv, 2017-12-29

Machine learning-based analysis of human functional magnetic resonance imaging (fMRI) patterns has enabled the visualization of perceptual content. However, it has been limited to the reconstruction with low-level image bases or to the matching to exemplars. Recent work showed that visual cortical activity can be decoded (translated) into hierarchical features of a deep neural network (DNN) for the same input image, providing a way to make use of the information from hierarchical visual features. Here, we present a novel image reconstruction method, in which the pixel values of an image are optimized to make its DNN features similar to those decoded from human brain activity at multiple layers. We found that the generated images resembled the stimulus images (both natural images and artificial shapes) and the subjective visual content during imagery. While our model was solely trained with natural images, our method successfully generalized the reconstruction to artificial shapes, indicating that our model indeed reconstructs or generates images from brain activity, not simply matches to exemplars. A natural image prior introduced by another deep neural network effectively rendered semantically meaningful details to reconstructions by constraining reconstructed images to be similar to natural images. Furthermore, human judgment of reconstructions suggests the effectiveness of combining multiple DNN layers to enhance visual quality of generated images. The results suggest that hierarchical visual information in the brain can be effectively combined to reconstruct perceptual and subjective images.

biorxiv neuroscience 500+-users 2017

 

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