Genetics of path lengths in brain connectivity networks: HARDI-based maps in 457 adults

Brain connectivity analyses are increasingly popular for investigating organization. Many connectivity measures including path lengths are generally defined as the number of nodes traversed to connect a node in a graph to the others. Despite its name, path length is purely topological, and does not take into account the physical length of the connections. The distance of the trajectory may also be highly relevant, but is typically overlooked in connectivity analyses. Here we combined genotyping, anatomical MRI and HARDI to understand how our genes influence the cortical connections, using whole-brain tractography. We defined a new measure, based on Dijkstra's algorithm, to compute path lengths for tracts connecting pairs of cortical regions. We compiled these measures into matrices where elements represent the physical distance traveled along tracts. We then analyzed a large cohort of healthy twins and show that our path length measure is reliable, heritable, and influenced even in young adults by the Alzheimer's risk gene, CLU.

L-dopa modulates functional connectivity in striatal cognitive and motor networks: A double-blind placebo-controlled study

Functional connectivity (FC) analyses of resting-state fMRI data allow for the mapping of large-scale functional networks, and provide a novel means of examining the impact of dopaminergic challenge. Here, using a double-blind, placebo-controlled design, we examined the effect of L-dopa, a dopamine precursor, on striatal resting-state FC in 19 healthy young adults.Weexamined the FC of 6 striatal regions of interest (ROIs) previously shown to elicit networks known to be associated with motivational, cognitive and motor subdivisions of the caudate and putamen (Di Martino et al., 2008). In addition to replicating the previously demonstrated patterns of striatal FC, we observed robust effects of L-dopa. Specifically, L-dopa increased FC in motor pathways connecting the putamen ROIs with the cerebellum and brainstem. Although L-dopa also increased FC between the inferior ventral striatum and ventrolateral prefrontal cortex, it disrupted ventral striatal and dorsal caudate FC with the default mode network. These alterations in FC are consistent with studies that have demonstrated dopaminergic modulation of cognitive and motor striatal networks in healthy participants. Recent studies have demonstrated altered resting state FC in several conditions believed to be characterized by abnormal dopaminergic neurotransmission. Our findings suggest that the application of similar experimental pharmacological manipulations in such populations may further our understanding of the role of dopaminergic neurotransmission in those conditions.

Identifying rate-limiting nodes in large-scale cortical networks for visuospatial processing: An illustration using fMRI

With the advent of functional neuroimaging techniques, in particular functional magnetic resonance imaging (fMRI), we have gained greater insight into the neural correlates of visuospatial function. However, it may not always be easy to identify the cerebral regions most specifically associated with performance on a given task. One approach is to examine the quantitative relationships between regional activation and behavioral performance measures. In the present study, we investigated the functional neuroanatomy of two different visuospatial processing tasks, judgement of line orientation and mental rotation. Twenty-four normal participants were scanned with fMRI using blocked periodic designs for experimental task presentation. Accuracy and reaction time (RT) to each trial of both activation and baseline conditions in each experiment was recorded. Both experiments activated dorsal and ventral visual cortical areas as well as dorsolateral prefrontal cortex. More regionally specific associations with task performance were identified by estimating the association between (sinusoidal) power of functional response and mean RT to the activation condition; a permutation test based on spatial statistics was used for inference. There was significant behavioral-physiological association in right ventral extrastriate cortex for the line orientation task and in bilateral (predominantly right) superior parietal lobule for the mental rotation task. Comparable associations were not found between power of response and RT to the baseline conditions of the tasks. These data suggest that one region in a neurocognitive network may be most strongly associated with behavioral performance and this may be regarded as the computationally least efficient or rate-limiting node of the network.

Multiple stages classification of Alzheimer’s disease based on structural brain networks using generalized low rank approximations (GLRAM)

To classify each stage for a progressing disease such as Alzheimer’s disease is a key issue for the disease prevention and treatment. In this study, we derived structural brain networks from diffusion-weighted MRI using whole-brain tractography since there is growing interest in relating connectivity measures to clinical, cognitive, and genetic data. Relatively little work has usedmachine learning to make inferences about variations in brain networks in the progression of the Alzheimer’s disease. Here we developed a framework to utilize generalized low rank approximations of matrices (GLRAM) and modified linear discrimination analysis for unsupervised feature learning and classification of connectivity matrices. We apply the methods to brain networks derived from DWI scans of 41 people with Alzheimer’s disease, 73 people with EMCI, 38 people with LMCI, 47 elderly healthy controls and 221 young healthy controls. Our results show that this new framework can significantly improve classification accuracy when combining multiple datasets; this suggests the value of using data beyond the classification task at hand to model variations in brain connectivity.

Tuning the resonance properties of 2D carbon nanotube networks towards a mechanical resonator

The capabilities of the mechanical resonator-based nanosensors in detecting ultra-small mass or force shifts have driven a continuing exploration of the palette of nanomaterials for such application purposes. Based on large-scale molecular dynamics simulations, we have assessed the applicability of a new class of carbon nanomaterials for nanoresonator usage, i.e. the single-wall carbon nanotube (SWNT) network. It is found that SWNT networks inherit excellent mechanical properties from the constituent SWNTs, possessing a high natural frequency. However, although a high quality factor is suggested from the simulation results, it is hard to obtain an unambiguous Q-factor due to the existence of vibration modes in addition to the dominant mode. The nonlinearities resulting from these extra vibration modes are found to exist uniformly under various testing conditions including different initial actuations and temperatures. Further testing shows that these modes can be effectively suppressed through the introduction of axial strain, leading to an extremely high quality factor in the order of 109 estimated from the SWNT network with 2% tensile strain. Additional studies indicate that the carbon rings connecting the SWNTs can also be used to alter the vibrational properties of the resulting network. This study suggests that the SWNT network can be a good candidate for applications as nanoresonators.

A social licence to operate: Corporate social responsibility, local communities and the constitution of global production networks

This article contributes to the theorization of the role of informal regulation (undertaken by leading firms) in the ongoing organization of global production networks. It does so through a qualitative case study of BHP Billiton's Ravensthorpe Nickel Operation (RNO) in the rural Shire of Ravensthorpe in Western Australia. This less tangible, and to date under-researched, dimension of global production networks is foregrounded through a focus on the corporate social responsibility strategy implemented by RNO in the service of achieving and/or demonstrating a broader ‘social licence to operate’. This ‘licence’ functions – beyond the corporation – as a legitimated and legitimating multi-scalar mechanism through which to gain and maintain access to mineral resources and thus to establish viable and ongoing global production networks. Further, this informal regulation is shown to shape social relations and qualities of place conducive to competitive global mineral extraction and to facilitate the positioning of local communities and places in mineral global production networks.

On food security and alternative food networks: Understanding and performing food security in the context of urban bias

This paper offers one explanation for the institutional basis of food insecurity in Australia, and argues that while alternative food networks and the food sovereignty movement perform a valuable function in building forms of social solidarity between urban consumers and rural producers, they currently make only a minor contribution to Australia’s food and nutrition security. The paper begins by identifying two key drivers of food security: household incomes (on the demand side) and nutrition-sensitive, ‘fair food’ agriculture (on the supply side). We focus on this second driver and argue that healthy populations require an agricultural sector that delivers dietary diversity via a fair and sustainable food system. In order to understand why nutrition-sensitive, fair food agriculture is not flourishing in Australia we introduce the development economics theory of urban bias. According to this theory, governments support capital intensive rather than labour intensive agriculture in order to deliver cheap food alongside the transfer of public revenues gained from rural agriculture to urban infrastructure, where the majority of the voting public resides. We chart the unfolding of the Urban Bias across the twentieth century and its consolidation through neo-liberal orthodoxy, and argue that agricultural policies do little to sustain, let alone revitalize, rural and regional Australia. We conclude that by observing food system dynamics through a re-spatialized lens, Urban Bias Theory is valuable in highlighting rural–urban socio-economic and political economy tensions, particularly regarding food system sustainability. It also sheds light on the cultural economy tensions for alternative food networks as they move beyond niche markets to simultaneously support urban food security and sustainable rural livelihoods.

Becoming-topologies of education: Deformations, networks and the database effect

This article uses topological approaches to suggest that education is becoming-topological. Analyses presented in a recent double-issue of Theory, Culture & Society are used to demonstrate the utility of topology for education. In particular, the article explains education's topological character through examining the global convergence of education policy, testing and the discursive ranking of systems, schools and individuals in the promise of reforming education through the proliferation of regimes of testing at local and global levels that constitute a new form of governance through data. In this conceptualisation of global education policy changes in the form and nature of testing combine with it the emergence of global policy network to change the nature of the local (national, regional, school and classroom) forces that operate through the ‘system’. While these forces change, they work through a discursivity that produces disciplinary effects, but in a different way. This new–old disciplinarity, or ‘database effect’, is here represented through a topological approach because of its utility for conceiving education in an increasingly networked world.

Second language social networks and communication-related acculturative stress: The role of interconnectedness

Although a substantial amount of cross-cultural psychology research has investigated acculturative stress in general, little attention has been devoted specifically to communication-related acculturative stress (CRAS). In line with the view that cross-cultural adaptation and second language (L2) learning are social and interpersonal phenomena, the present study examines the hypothesis that migrants’ L2 social network size and interconnectedness predict CRAS. The main idea underlying this hypothesis is that L2 social networks play an important role in fostering social and cultural aspects of communicative competence. Specifically, higher interconnectedness may reflect greater access to unmodified natural cultural representations and L2 communication practices, thus fostering communicative competence through observational learning. As such, structural aspects of migrants’ L2 social networks may be protective against acculturative stress arising from chronic communication difficulties. Results from a study of first generation migrant students (N = 100) support this idea by showing that both inclusiveness and density of the participants’ L2 network account for unique variance in CRAS but not in general acculturative stress. These results support the idea that research on cross-cultural adaptation would benefit from disentangling the various facets of acculturative stress and that the structure of migrants’ L2 network matters for language related outcomes. Finally, this study contributes to an emerging body of work that attempts to integrate cultural/cross-cultural research on acculturation and research on intercultural communication and second language learning.

Developments of the total entropy utility function for the dual purpose of model discrimination and parameter estimation in Bayesian design

The total entropy utility function is considered for the dual purpose of Bayesian design for model discrimination and parameter estimation. A sequential design setting is proposed where it is shown how to efficiently estimate the total entropy utility for a wide variety of data types. Utility estimation relies on forming particle approximations to a number of intractable integrals which is afforded by the use of the sequential Monte Carlo algorithm for Bayesian inference. A number of motivating examples are considered for demonstrating the performance of total entropy in comparison to utilities for model discrimination and parameter estimation. The results suggest that the total entropy utility selects designs which are efficient under both experimental goals with little compromise in achieving either goal. As such, the total entropy utility is advocated as a general utility for Bayesian design in the presence of model uncertainty.

Bayesian parametric bootstrap for models with intractable likelihoods

In this paper it is demonstrated how the Bayesian parametric bootstrap can be adapted to models with intractable likelihoods. The approach is most appealing when the semi-automatic approximate Bayesian computation (ABC) summary statistics are selected. After a pilot run of ABC, the likelihood-free parametric bootstrap approach requires very few model simulations to produce an approximate posterior, which can be a useful approximation in its own right. An alternative is to use this approximation as a proposal distribution in ABC algorithms to make them more efficient. In this paper, the parametric bootstrap approximation is used to form the initial importance distribution for the sequential Monte Carlo and the ABC importance and rejection sampling algorithms. The new approach is illustrated through a simulation study of the univariate g-and- k quantile distribution, and is used to infer parameter values of a stochastic model describing expanding melanoma cell colonies.

Scalable Bayesian Computation for intractable likelihoods in image analysis

The inverse temperature hyperparameter of the hidden Potts model governs the strength of spatial cohesion and therefore has a substantial influence over the resulting model fit. The difficulty arises from the dependence of an intractable normalising constant on the value of the inverse temperature, thus there is no closed form solution for sampling from the distribution directly. We review three computational approaches for addressing this issue, namely pseudolikelihood, path sampling, and the approximate exchange algorithm. We compare the accuracy and scalability of these methods using a simulation study.

Improving deep convultional neural networks with unsupervised feature learning

The latest generation of Deep Convolutional Neural Networks (DCNN) have dramatically advanced challenging computer vision tasks, especially in object detection and object classification, achieving state-of-the-art performance in several computer vision tasks including text recognition, sign recognition, face recognition and scene understanding. The depth of these supervised networks has enabled learning deeper and hierarchical representation of features. In parallel, unsupervised deep learning such as Convolutional Deep Belief Network (CDBN) has also achieved state-of-the-art in many computer vision tasks. However, there is very limited research on jointly exploiting the strength of these two approaches. In this paper, we investigate the learning capability of both methods. We compare the output of individual layers and show that many learnt filters and outputs of the corresponding level layer are almost similar for both approaches. Stacking the DCNN on top of unsupervised layers or replacing layers in the DCNN with the corresponding learnt layers in the CDBN can improve the recognition/classification accuracy and training computational expense. We demonstrate the validity of the proposal on ImageNet dataset.

Bayesian refinement of association signals for 14 loci in 3 common diseases

To further investigate susceptibility loci identified by genome-wide association studies, we genotyped 5,500 SNPs across 14 associated regions in 8,000 samples from a control group and 3 diseases: type 2 diabetes (T2D), coronary artery disease (CAD) and Graves' disease. We defined, using Bayes theorem, credible sets of SNPs that were 95% likely, based on posterior probability, to contain the causal disease-associated SNPs. In 3 of the 14 regions, TCF7L2 (T2D), CTLA4 (Graves' disease) and CDKN2A-CDKN2B (T2D), much of the posterior probability rested on a single SNP, and, in 4 other regions (CDKN2A-CDKN2B (CAD) and CDKAL1, FTO and HHEX (T2D)), the 95% sets were small, thereby excluding most SNPs as potentially causal. Very few SNPs in our credible sets had annotated functions, illustrating the limitations in understanding the mechanisms underlying susceptibility to common diseases. Our results also show the value of more detailed mapping to target sequences for functional studies. © 2012 Nature America, Inc. All rights reserved.

Multimodal imaging of the collagen and elastic fibre networks in the bovine intervertebral disc

INTRODUCTION. The intervertebral disc is the largest avascular structure in the human body, withstanding transient loads of up to nine times body weight during rigorous physical activity. The key structural elements of the disc are a gel-like nucleus pulposus surrounded by concentric lamellar rings containing criss-crossed collagen fibres. The disc also contains an elastic fiber network which has been suggested to play a structural role, but to date the relationship between the collagen and elastic fiber networks is unclear. CONCLUSION. The multimodal transmitted and reflected polarized light microscopy technique developed here allows clear differentiation between the collagen and elastic fiber networks of the intervertebral disc. The ability to image unstained specimens avoids concerns with uneven stain penetration or specificity of staining. In bovine tail discs, the elastic fiber network is intimately associated with the collagen network.