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Functional magnetic resonance imaging (fMRI) is widely used in clinical applications to highlight brain areas involved in specific cognitive processes. Brain impairments, such as tumors, suppress the fMRI activation of the anatomical areas they invade and, thus, brain-damaged functional networks present missing links/areas of activation. The identification of the missing circuitry components is of crucial importance to estimate the damage extent. The study of functional networks associated with clinical tasks but performed by healthy individuals becomes, therefore, of paramount concern. These "healthy" networks can, indeed, be used as control networks for clinical studies. In this work we investigate the functional architecture of 20 healthy individuals performing a language task designed for clinical purposes. We unveil a common architecture persistent across all subjects under study, that we call "core" network, which involves Broca's area, Wernicke's area, the premotor area, and the pre-supplementary motor area. We study the connectivity of this circuitry by using the k-core centrality measure, and we find that three of these areas belong to the most robust structure of the functional language network for the specific task under study. Our results provide useful insights on primarily important functional connections. © 2019 Massachusetts Institute of Technology.Late human development is characterized by the maturation of high-level functional processes, which rely on reshaping of white matter connections, as well as synaptic density. However, the relationship between the whole-brain dynamics and the underlying white matter networks in neurodevelopment is largely unknown. In this study, we focused on how the structural connectome shapes the emerging dynamics of cerebral development between the ages of 6 and 33 years, using functional and diffusion magnetic resonance imaging combined into a spatiotemporal connectivity framework. We defined two new measures of brain dynamics, namely the system diversity and the spatiotemporal diversity, which quantify the level of integration/segregation between functional systems and the level of temporal self-similarity of the functional patterns of brain dynamics, respectively. We observed a global increase in system diversity and a global decrease and local refinement in spatiotemporal diversity values with age. In support of these findings, we further found an increase in the usage of long-range and inter-system white matter connectivity and a decrease in the usage of short-range connectivity with age. These findings suggest that dynamic functional patterns in the brain progressively become more integrative and temporally self-similar with age. These functional changes are supported by a greater involvement of long-range and inter-system axonal pathways. © 2019 Massachusetts Institute of Technology.Age-related declines in cognition are associated with widespread structural and functional brain changes, including changes in resting-state functional connectivity and gray and white matter status. Recently we have shown that the elasticity of cerebral arteries also explains some of the variance in cognitive and brain health in aging. Here, we investigated how network segregation, cerebral arterial elasticity (measured with pulse-DOT-the arterial pulse based on diffuse optical tomography) and gray and white matter status jointly account for age-related differences in cognitive performance. We hypothesized that at least some of the variance in brain and cognitive aging is linked to reduced cerebrovascular elasticity, leading to increased cortical atrophy and white matter abnormalities, which, in turn, are linked to reduced network segregation and decreases in cognitive performance. Pairwise comparisons between these variables are consistent with an exploratory hierarchical model linking them, especially when focusing on association network segregation (compared with segregation in sensorimotor networks). These findings suggest that preventing or slowing age-related changes in one or more of these factors may induce a neurophysiological cascade beneficial for preserving cognition in aging. © 2019 Massachusetts Institute of Technology.Whole-brain network analysis is commonly used to investigate the topology of the brain using a variety of neuroimaging modalities. This approach is notable for its applicability to a large number of domains, such as understanding how brain network organization relates to cognition and behavior and examining disrupted brain network organization in disease. Temsirolimus A benefit to this approach is the ability to summarize overall brain network organization with a single metric (e.g., global efficiency). However, important local differences in network structure might exist without any corresponding observable differences in global topology, making a whole-brain analysis strategy unlikely to detect relevant local findings. Conversely, using local network metrics can identify local differences, but are not directly informative of differences in global topology. Here, we propose the network statistic (NS) jackknife framework, a simulated lesioning method that combines the utility of global network analysis strategies with the ability to detect relevant local differences in network structure. We evaluate the NS jackknife framework with a simulation study and an empirical example comparing global efficiency in children with attention-deficit/hyperactivity disorder (ADHD) and typically developing (TD) children. The NS jackknife framework has been implemented in a public, open-source R package, netjack, available at https//cran.r-project.org/package=netjack. © 2019 Massachusetts Institute of Technology.The brain is a complex, multiscale dynamical system composed of many interacting regions. Knowledge of the spatiotemporal organization of these interactions is critical for establishing a solid understanding of the brain's functional architecture and the relationship between neural dynamics and cognition in health and disease. The possibility of studying these dynamics through careful analysis of neuroimaging data has catalyzed substantial interest in methods that estimate time-resolved fluctuations in functional connectivity (often referred to as "dynamic" or time-varying functional connectivity; TVFC). At the same time, debates have emerged regarding the application of TVFC analyses to resting fMRI data, and about the statistical validity, physiological origins, and cognitive and behavioral relevance of resting TVFC. These and other unresolved issues complicate interpretation of resting TVFC findings and limit the insights that can be gained from this promising new research area. This article brings together scientists with a variety of perspectives on resting TVFC to review the current literature in light of these issues. We introduce core concepts, define key terms, summarize controversies and open questions, and present a forward-looking perspective on how resting TVFC analyses can be rigorously and productively applied to investigate a wide range of questions in cognitive and systems neuroscience. © 2019 Massachusetts Institute of Technology.The discovery of a stable, whole-brain functional connectivity organization that is largely independent of external events has drastically extended our view of human brain function. However, this discovery has been primarily based on functional magnetic resonance imaging (fMRI). The role of this whole-brain organization in fast oscillation-based connectivity as measured, for example, by electroencephalography (EEG) and magnetoencephalography (MEG) is only beginning to emerge. Here, we review studies of intrinsic connectivity and its whole-brain organization in EEG, MEG, and intracranial electrophysiology with a particular focus on direct comparisons to connectome studies in fMRI. Synthesizing this literature, we conclude that irrespective of temporal scale over four orders of magnitude, intrinsic neurophysiological connectivity shows spatial similarity to the connectivity organization commonly observed in fMRI. A shared structural connectivity basis and cross-frequency coupling are possible mechanisms contributing to this similarity. Acknowledging that a stable whole-brain organization governs long-range coupling across all timescales of neural processing motivates researchers to take "baseline" intrinsic connectivity into account when investigating brain-behavior associations, and further encourages more widespread exploration of functional connectomics approaches beyond fMRI by using EEG and MEG modalities. © 2019 Massachusetts Institute of Technology.Sleep is a universal phenomenon occurring in all species studied thus far. Sleep loss results in adverse physiological effects at both the organismal and cellular levels suggesting an adaptive role for sleep in the maintenance of overall health. This review examines the bidirectional relationship between sleep and cellular stress. Cellular stress in this review refers to a shift in cellular homeostasis in response to an external stressor. Studies that illustrate the fact that sleep loss induces cellular stress and those that provide evidence that cellular stress in turn promotes sleep will be discussed.Introduction To develop effective therapies and identify novel early biomarkers for chronic kidney disease, an understanding of the molecular mechanisms orchestrating it is essential. We here set out to understand how differences in chronic kidney disease (CKD) origin are reflected in gene expression. To this end, we integrated publicly available human glomerular microarray gene expression data for 9 kidney disease entities that account for most of CKD worldwide. Our primary goal was to demonstrate the possibilities and potential on data analysis and integration to the nephrology community. Methods We integrated data from 5 publicly available studies and compared glomerular gene expression profiles of disease with that of controls from nontumor parts of kidney cancer nephrectomy tissues. A major challenge was the integration of the data from different sources, platforms, and conditions that we mitigated with a bespoke stringent procedure. Results We performed a global transcriptome-based delineation of differe specific molecular mechanisms underlying different kidney disease entities that can pave the way to identify biomarkers and potential therapeutic targets. To facilitate further use, we provide our results as a free interactive Web application https//saezlab.shinyapps.io/ckd_landscape/. However, because of the limitations of the data and the difficulties in its integration, any specific result should be considered with caution. Indeed, we consider this study rather an illustration of the value of functional genomics and integration of existing data. © 2019 International Society of Nephrology. Published by Elsevier Inc.Introduction Although chronic kidney disease (CKD) is associated with increased risk for coronary artery disease (CAD), the underlying mechanisms are not completely defined. In the present study, we tested the hypothesis that flux of cholesterol from macrophage foam cells to liver is impaired in subjects with CKD. Methods Consecutive healthy patients, patients with at least 1 CAD risk factor, patients with established CAD, and patients with CKD stages G3 to G5 (n ≥ 15/group) were recruited prospectively. The ability of total patient serum without any modifications to (i) facilitate efflux of cholesterol from human THP1-macrophage foam cells under physiological conditions (cholesterol efflux capacity [CEC]) and (ii) to deliver this effluxed cholesterol to primary hepatocytes with physiological expression of high-density lipoprotein (HDL) receptor SR-BI (capacity to deliver cholesterol to hepatocytes [CDCH]) was evaluated. Results Although healthy patients, patients with at least 1 CAD risk factor, and patients with established CAD all showed similar CEC, patients with CKD showed significantly higher CEC.