Higher brain function relies upon the ability to flexibly integrate information across specialized communities of brain regions; however, it is unclear how this mechanism manifests over time. In this ...study, we used time-resolved network analysis of fMRI data to demonstrate that the human brain traverses between functional states that maximize either segregation into tight-knit communities or integration across otherwise disparate neural regions. Integrated states enable faster and more accurate performance on a cognitive task, and are associated with dilations in pupil diameter, suggesting that ascending neuromodulatory systems may govern the transition between these alternative modes of brain function. Together, our results confirm a direct link between cognitive performance and the dynamic reorganization of the network structure of the brain.
•The human brain network traverses segregated and integrated states over time•Integrated states enable fast, effective performance on an N-back task•Integrated states track with fluctuations in pupil diameter•Cognitive performance relates to the dynamic reorganization of brain architecture
Shine et al. use dynamic analyses of fMRI data to demonstrate that the network architecture of the human brain fluctuates between states of high and low global integration that track with effective task performance and may relate to fluctuations in arousal.
•Neural systems converge within the architecture of the basal ganglia and thalamus.•Emerging data suggests that basal ganglia and thalamus act as network hubs.•Basal ganglia and thalamus form a core ...circuit supporting large-scale integration.•Opportunities and challenges of subcortical-inclusive connectomic mapping.
Higher brain function requires integration of distributed neuronal activity across large-scale brain networks. Recent scientific advances at the interface of subcortical brain anatomy and network science have highlighted the possible contribution of subcortical structures to large-scale network communication. We begin our review by examining neuroanatomical literature suggesting that diverse neural systems converge within the architecture of the basal ganglia and thalamus. These findings dovetail with those of recent network analyses that have demonstrated that the basal ganglia and thalamus belong to an ensemble of highly interconnected network hubs. A synthesis of these findings suggests a new view of the subcortex, in which the basal ganglia and thalamus form part of a core circuit that supports large-scale integration of functionally diverse neural signals. Finally, we close with an overview of some of the major opportunities and challenges facing subcortical-inclusive descriptions of large-scale network communication in the human brain.
Non-steroidal anti-inflammatory drugs (NSAIDs) are a common cause of adverse drug events (ADEs), but renal risks of NSAIDs are less well quantified than gastrointestinal and cardiac risks. This paper ...reports a systematic review of published population-based observational studies examining the risk of acute kidney injury (AKI) associated with NSAIDs in community-dwelling adults and those with pre-existing chronic kidney disease (CKD).
MEDLINE and EMBASE databases were searched until June 2016, and 3789 papers screened. Ten studies reporting NSAID risk of AKI in the general population were included in random effects meta-analysis, of which five additionally reported NSAID risk in people with CKD.
In the general population, the pooled odds ratio (OR) of AKI for current NSAID exposure was 1.73 (95%CI 1.44 to 2.07), with somewhat higher risk observed in older people (OR 2.51, 95%CI 1.52 to 2.68). In people with CKD, individual study OR of AKI due to current NSAID exposure ranged from 1.12 to 5.25, with pooled estimate OR 1.63 (95% CI 1.22 to 2.19).
No study reported baseline risk of AKI in different populations meaning absolute risks could not be estimated, but baseline risk and therefore the absolute risk of NSAID exposure is likely to be higher in people with CKD and older people. Large population based studies measuring AKI using current definitions and estimating the absolute risk of harm are needed in order to better inform clinical decision making.
Functional connectivity provides an informative and powerful framework for exploring brain organization. Despite this, few statistical methods are available for the accurate estimation of dynamic ...changes in functional network architecture. To date, the majority of existing statistical techniques have assumed that connectivity structure is stationary, which is in direct contrast to emerging data that suggests that the strength of connectivity between regions is variable over time. Therefore, the development of statistical methods that enable exploration of dynamic changes in functional connectivity is currently of great importance to the neuroscience community. In this paper, we introduce the ‘Multiplication of Temporal Derivatives’ (MTD) and then demonstrate the utility of this metric to: (i) detect dynamic changes in connectivity using data from a novel state-switching simulation; (ii) accurately estimate graph structure in a previously-described ‘ground-truth’ simulated dataset; and (iii) identify task-driven alterations in functional connectivity. We show that the MTD is more sensitive than existing sliding-window methods in detecting dynamic alterations in connectivity structure across a range of correlation strengths and window lengths in simulated data. In addition to the temporal precision offered by MTD, we demonstrate that the metric is also able to accurately estimate stationary network structure in both simulated and real task-based data, suggesting that the method may be used to identify dynamic changes in network structure as they evolve through time.
•We introduce the Multiplication of Temporal Derivatives (MTD) tool for estimating time-varying functional connectivity.•We show via simulations that the MTD provides superior temporal sensitivity to changes in connectivity.•We show that the average MTD score can accurately estimate stationary functional connectivity.•We apply the MTD to a working memory task to demonstrate inter-modular connectivity during task data.
The conservation of marine benthic biodiversity is a recognised goal of a number of national and international programs such as the United Nations Convention on Biodiversity (CBD). In order to attain ...this goal, information is needed about the distribution of life in the ocean so that spatial conservation measures such as marine protected areas (MPAs) can be designed to maximise protection within boundaries of acceptable dimensions. Ideally, a map would be produced that showed the distribution of benthic biodiversity to enable the efficient design of MPAs. The dilemma is that such maps do not exist for most areas and it is not possible at present to predict the spatial distribution of all marine life using the sparse biological information currently available. Knowledge of the geomorphology and biogeography of the seafloor has improved markedly over the past 10 years. Using multibeam sonar, the benthic ecology of submarine features such as fjords, sand banks, coral reefs, seamounts, canyons, mud volcanoes and spreading ridges has been revealed in unprecedented detail. This book provides a synthesis of seabed geomorphology and benthic habitats based on the most recent, up-to-date information. Introductory chapters explain the drivers that underpin the need for benthic habitat maps, including threats to ocean health, the habitat mapping approach based on principles of biogeography and benthic ecology and seabed (geomorphic) classification schemes. Case studies from around the world are then presented. They represent a range of seabed features where detailed bathymetric maps have been combined with seabed video and sampling to yield an integrated picture of the benthic communities that are associated with different types of benthic habitat. The final chapter examines critical knowledge gaps and future directions for benthic habitat mapping research.
Reviews and compares the different methodologies currently being used Includes global case studiesProvides geological expertise into what has traditionally been a biological discipline
Impairments in motor automaticity cause patients with Parkinson's disease to rely on attentional resources during gait, resulting in greater motor variability and a higher risk of falls. Although ...dopaminergic circuitry is known to play an important role in motor automaticity, little evidence exists on the neural mechanisms underlying the breakdown of locomotor automaticity in Parkinson's disease. This impedes clinical management and is in great part due to mobility restrictions that accompany the neuroimaging of gait. This study therefore utilized a virtual reality gait paradigm in conjunction with functional MRI to investigate the role of dopaminergic medication on lower limb motor automaticity in 23 patients with Parkinson's disease that were measured both on and off dopaminergic medication. Participants either operated foot pedals to navigate a corridor (‘walk’ condition) or watched the screen while a researcher operated the paradigm from outside the scanner (‘watch’ condition), a setting that controlled for the non-motor aspects of the task. Step time variability during walk was used as a surrogate measure for motor automaticity (where higher variability equates to reduced automaticity), and patients demonstrated a predicted increase in step time variability during the dopaminergic “off” state. During the “off” state, subjects showed an increased blood oxygen level-dependent response in the bilateral orbitofrontal cortices (walk>watch). To estimate step time variability, a parametric modulator was designed that allowed for the examination of brain regions associated with periods of decreased automaticity. This analysis showed that patients on dopaminergic medication recruited the cerebellum during periods of increasing variability, whereas patients off medication instead relied upon cortical regions implicated in cognitive control. Finally, a task-based functional connectivity analysis was conducted to examine the manner in which dopamine modulates large-scale network interactions during gait. A main effect of medication was found for functional connectivity within an attentional motor network and a significant condition by medication interaction for functional connectivity was found within the striatum. Furthermore, functional connectivity within the striatum correlated strongly with increasing step time variability during walk in the off state (r=0.616, p=0.002), but not in the on state (r=−0.233, p=0.284). Post-hoc analyses revealed that functional connectivity in the dopamine depleted state within an orbitofrontal-striatal limbic circuit was correlated with worse step time variability (r=0.653, p<0.001). Overall, this study demonstrates that dopamine ameliorates gait automaticity in Parkinson's disease by altering striatal, limbic and cerebellar processing, thereby informing future therapeutic avenues for gait and falls prevention.
•Parkinson's disease patients performed a virtual reality gait task during fMRI.•The role of dopamine on gait automaticity impairments was investigated.•Limbic interference and poor striatal and cerebellar processing impair automaticity.•Dopamine ameliorates gait automaticity impairments in Parkinson's disease.
RNA precursors give rise to mRNA after splicing of intronic sequences traditionally thought to occur in the nucleus. Here, we show that intron sequences are retained in a number of ...dendritically-targeted mRNAs, by using microarray and Illumina sequencing of isolated dendritic mRNA as well as in situ hybridization. Many of the retained introns contain ID elements, a class of SINE retrotransposon. A portion of these SINEs confers dendritic targeting to exogenous and endogenous transcripts showing the necessity of ID-mediated mechanisms for the targeting of different transcripts to dendrites. ID elements are capable of selectively altering the distribution of endogenous proteins, providing a link between intronic SINEs and protein function. As such, the ID element represents a common dendritic targeting element found across multiple RNAs. Retention of intronic sequence is a more general phenomenon than previously thought and plays a functional role in the biology of the neuron, partly mediated by co-opted repetitive sequences.
► A varied population of dendritic localized mRNAs selectively retain intron sequences ► SINE ID elements within these introns can drive dendritic transport of transcripts ► Dendritic protein distribution is altered when ID-mediated localization is disrupted ► Intron SINEs provide a possible mechanistic link to viral mediated neural diseases
Using a dynamic graph theoretical approach, Shine et al. show that individuals with Parkinson's disease demonstrate heightened network-level integration during the 'Off' state that is inversely ...correlated with motor symptom severity. Network-level integration relates to two measures of neurocognitive reserve, suggesting a protective function for 'Off' state integration.
Abstract
Parkinson's disease is primarily characterized by diminished dopaminergic function; however, the impact of these impairments on large-scale brain dynamics remains unclear. It has been difficult to disentangle the direct effects of Parkinson's disease from compensatory changes that reconfigure the functional signature of the whole brain network. To examine the causal role of dopamine depletion in network-level topology, we investigated time-varying network structure in 37 individuals with idiopathic Parkinson's disease, both ON and OFF dopamine replacement therapy, along with 50 age-matched, healthy control subjects using resting state functional MRI. By tracking dynamic network-level topology, we found that the Parkinson's disease OFF state was associated with greater network-level integration than in the ON state. The extent of integration in the OFF state inversely correlated with motor symptom severity, suggesting that a shift toward a more integrated network topology may be a compensatory mechanism associated with preserved motor function in the dopamine depleted OFF state. Furthermore, we were able to demonstrate that measures of both cognitive and brain reserve (i.e. premorbid intelligence and whole brain grey matter volume) had a positive relationship with the relative increase in network integration observed in the dopaminergic OFF state. This suggests that each of these factors plays an important role in promoting network integration in the dopaminergic OFF state. Our findings provide a mechanistic basis for understanding the Parkinson's disease OFF state and provide a further conceptual link with network-level reconfiguration. Together, our results highlight the mechanisms responsible for pathological and compensatory change in Parkinson's disease.
Background Acute kidney injury (AKI) is common and associated with adverse outcomes as well as important healthcare costs. However, evidence examining the epidemiology of acute kidney disease ...(AKD)--recently defined as AKI persisting between 7 and 90 days--remains limited. The aims of this study were to establish the rates of early AKI recovery, progression to AKD and non-recovery; examine risk factors associated with non-recovery and investigate the association between recovery timing and adverse outcomes, in a population-based cohort. Methods All adult residents of Tayside & Fife, Scotland, UK, with at least one episode of community or hospital-managed AKI using KDIGO creatinine-based definition during the period 1 January 2010 to 31 December 2018 were identified. Logistic regression was used to examine factors associated with non-recovery, and Cox modelling was used to establish associations between AKI recovery timing and risks of mortality and development of de novo CKD. Results Over 9 years, 56,906 patients with at least one AKI episode were identified with 18,773 (33%) of these progressing to AKD. Of those progressing to AKD, 5059 (27%) had still not recovered at day 90 post AKI diagnosis. Risk factors for AKD included: increasing AKI severity, pre-existing cancer or chronic heart failure and recent use of loop diuretics. Compared with early AKI recovery, progression to AKD was associated with increased hazard of 1-year mortality and de novo CKD (HR = 1.20, 95% CI 1.13 to 1.26 and HR = 2.21, 95% CI 1.91 to 2.57 respectively). Conclusions These findings highlight the importance of early AKI recognition and management to avoid progression to AKD and long-term adverse outcomes. Keywords: Acute kidney injury, Acute kidney disease, Chronic kidney disease, Recovery, Epidemiology
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