518 research outputs found

    Time-varying effective EEG source connectivity: the optimization of model parameters*

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    Adaptive estimation methods based on general Kalman filter are powerful tools to investigate brain networks dynamics given the non-stationary nature of neural signals. These methods rely on two parameters, the model order p and adaptation constant c, which determine the resolution and smoothness of the time-varying multivariate autoregressive estimates. A sub-optimal filtering may present consistent biases in the frequency domain and temporal distortions, leading to fallacious interpretations. Thus, the performance of these methods heavily depends on the accurate choice of these two parameters in the filter design. In this work, we sought to define an objective criterion for the optimal choice of these parameters. Since residual- and information-based criteria are not guaranteed to reach an absolute minimum, we propose to study the partial derivatives of these functions to guide the choice of p and c. To validate the performance of our method, we used a dataset of human visual evoked potentials during face perception where the generation and propagation of information in the brain is well understood and a set of simulated data where the ground truth is available

    Estimating EEG Source Dipole Orientation Based on Singular-value Decomposition for Connectivity Analysis.

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    In the last decade, the use of high-density electrode arrays for EEG recordings combined with the improvements of source reconstruction algorithms has allowed the investigation of brain networks dynamics at a sub-second scale. One powerful tool for investigating large-scale functional brain networks with EEG is time-varying effective connectivity applied to source signals obtained from electric source imaging. Due to computational and interpretation limitations, the brain is usually parcelled into a limited number of regions of interests (ROIs) before computing EEG connectivity. One specific need and still open problem is how to represent the time- and frequency-content carried by hundreds of dipoles with diverging orientation in each ROI with one unique representative time-series. The main aim of this paper is to provide a method to compute a signal that explains most of the variability of the data contained in each ROI before computing, for instance, time-varying connectivity. As the representative time-series for a ROI, we propose to use the first singular vector computed by a singular-value decomposition of all dipoles belonging to the same ROI. We applied this method to two real datasets (visual evoked potentials and epileptic spikes) and evaluated the time-course and the frequency content of the obtained signals. For each ROI, both the time-course and the frequency content of the proposed method reflected the expected time-course and the scalp-EEG frequency content, representing most of the variability of the sources (~ 80%) and improving connectivity results in comparison to other procedures used so far. We also confirm these results in a simulated dataset with a known ground truth

    Improving Access to Mental Health Care and Psychosocial Support within a Fragile Context: A Case Study from Afghanistan

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    As one article in a series on Global Mental Health Practice, Peter Ventevogel and colleagues provide a case study of their efforts to integrate brief, practice-oriented mental health training into the Afghanistan health care system at a time when the system was being rebuilt from scratch

    Large-Scale 3-5 Hz Oscillation Constrains the Expression of Neocortical Fast Ripples in a Mouse Model of Mesial Temporal Lobe Epilepsy.

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    Large-scale slow oscillations allow the integration of neuronal activity across brain regions during sensory or cognitive processing. However, evidence that this form of coding also holds for pathological networks, such as for distributed networks in epileptic disorders, does not yet exist. Here, we show in a mouse model of unilateral hippocampal epilepsy that epileptic fast ripples generated in the neocortex distant from the primary focus occur during transient trains of interictal epileptic discharges. During these epileptic paroxysms, local phase-locking of neuronal firing and a phase-amplitude coupling of the epileptic discharges over a slow oscillation at 3-5 Hz are detected. Furthermore, the buildup of the slow oscillation begins in the bihippocampal network that includes the focus, which synchronizes and drives the activity across the large-scale epileptic network into the frontal cortex. This study provides the first functional description of the emergence of neocortical fast ripples in hippocampal epilepsy and shows that cross-frequency coupling might be a fundamental mechanism underlying the spreading of epileptic activity

    Protein disulfide-isomerase interacts with a substrate protein at all stages along its folding pathway

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    In contrast to molecular chaperones that couple protein folding to ATP hydrolysis, protein disulfide-isomerase (PDI) catalyzes protein folding coupled to formation of disulfide bonds (oxidative folding). However, we do not know how PDI distinguishes folded, partly-folded and unfolded protein substrates. As a model intermediate in an oxidative folding pathway, we prepared a two-disulfide mutant of basic pancreatic trypsin inhibitor (BPTI) and showed by NMR that it is partly-folded and highly dynamic. NMR studies show that it binds to PDI at the same site that binds peptide ligands, with rapid binding and dissociation kinetics; surface plasmon resonance shows its interaction with PDI has a Kd of ca. 10−5 M. For comparison, we characterized the interactions of PDI with native BPTI and fully-unfolded BPTI. Interestingly, PDI does bind native BPTI, but binding is quantitatively weaker than with partly-folded and unfolded BPTI. Hence PDI recognizes and binds substrates via permanently or transiently unfolded regions. This is the first study of PDI's interaction with a partly-folded protein, and the first to analyze this folding catalyst's changing interactions with substrates along an oxidative folding pathway. We have identified key features that make PDI an effective catalyst of oxidative protein folding – differential affinity, rapid ligand exchange and conformational flexibility

    Beyond food for thought : directing sustainability transitions research to address fundamental change in agri-food systems

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    Dominant agricultural and food systems lead to continuous resource depletion and unacceptable environmental and social impacts. While current calls for changing agrifood systems are increasingly framed in the context of sustainability transitions, they rarely make an explicit link to transition studies to address these systemic challenges, nor do transition scholars sufficiently address agri-food systems, despite their global pertinence. From this viewpoint, we illustrate several gaps in the agri-food systems debate that sustainability transition studies could engage in. We propose four avenues for research in the next decade of transition research on agri-food systems: 1) Crossscale dynamics between coupled systems; 2) Social justice, equity and inclusion; 3) Sustainability transitions in low- and middle-income countries; 4) Cross-sectoral governance and system integration. We call for a decade of new transition research that moves beyond single-scale and sector perspectives toward more inclusive and integrated analyses of food system dynamics
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