The regional variation of laminar thickness in the human isocortex is related to cortical hierarchy and interregional connectivity.

The human isocortex consists of tangentially organized layers with unique cytoarchitectural properties. These layers show spatial variations in thickness and cytoarchitecture across the neocortex, which is thought to support function through enabling targeted corticocortical connections. Here, leveraging maps of the 6 cortical layers based on 3D human brain histology, we aimed to quantitatively characterize the systematic covariation of laminar structure in the cortex and its functional consequences. After correcting for the effect of cortical curvature, we identified a spatial pattern of changes in laminar thickness covariance from lateral frontal to posterior occipital regions, which differentiated the dominance of infra- versus supragranular layer thickness. Corresponding to the laminar regularities of cortical connections along cortical hierarchy, the infragranular-dominant pattern of laminar thickness was associated with higher hierarchical positions of regions, mapped based on resting-state effective connectivity in humans and tract-tracing of structural connections in macaques. Moreover, we show that regions with similar laminar thickness patterns have a higher likelihood of structural connections and strength of functional connections. In sum, here we characterize the organization of laminar thickness in the human isocortex and its association with cortico-cortical connectivity, illustrating how laminar organization may provide a foundational principle of cortical function.

Hippocampal metabolic subregions and networks: Behavioral, molecular, and pathological aging profiles.

INTRODUCTION: Hippocampal local and network dysfunction is the hallmark of Alzheimer's disease (AD). METHODS: We characterized the spatial patterns of hippocampus differentiation based on brain co-metabolism in healthy elderly participants and demonstrated their relevance to study local metabolic changes and associated dysfunction in pathological aging. RESULTS: The hippocampus can be differentiated into anterior/posterior and dorsal cornu ammonis (CA)/ventral (subiculum) subregions. While anterior/posterior CA show co-metabolism with different regions of the subcortical limbic networks, the anterior/posterior subiculum are parts of cortical networks supporting object-centered memory and higher cognitive demands, respectively. Both networks show relationships with the spatial patterns of gene expression pertaining to cell energy metabolism and AD's process. Finally, while local metabolism is generally lower in posterior regions, the anterior-posterior imbalance is maximal in late mild cognitive impairment with the anterior subiculum being relatively preserved. DISCUSSION: Future studies should consider bidimensional hippocampal differentiation and in particular the posterior subicular region to better understand pathological aging.

ENIGMA-Sleep: Challenges, opportunities, and the road map.

Neuroimaging and genetics studies have advanced our understanding of the neurobiology of sleep and its disorders. However, individual studies usually have limitations to identifying consistent and reproducible effects, including modest sample sizes, heterogeneous clinical characteristics and varied methodologies. These issues call for a large-scale multi-centre effort in sleep research, in order to increase the number of samples, and harmonize the methods of data collection, preprocessing and analysis using pre-registered well-established protocols. The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium provides a powerful collaborative framework for combining datasets across individual sites. Recently, we have launched the ENIGMA-Sleep working group with the collaboration of several institutes from 15 countries to perform large-scale worldwide neuroimaging and genetics studies for better understanding the neurobiology of impaired sleep quality in population-based healthy individuals, the neural consequences of sleep deprivation, pathophysiology of sleep disorders, as well as neural correlates of sleep disturbances across various neuropsychiatric disorders. In this introductory review, we describe the details of our currently available datasets and our ongoing projects in the ENIGMA-Sleep group, and discuss both the potential challenges and opportunities of a collaborative initiative in sleep medicine.

Predictive value of red blood cell distribution width for mortality in patients with acute pancreatitis: A systematic review and meta-analysis.

Background: Red blood cell distribution width (RDW) is a quantitative measure of variability in the size of circulating erythrocytes. It has been recently identified as a prognostic marker in several diseases including acute pancreatitis (AP). In this systematic review the prognostic value of RDW in predicting mortality of AP patients will be assessed. Methods: PubMed, Scopus, EMBASE, and ISI databases were searched until September 2016 using the following search strategy: (pancreatitis OR pancreatitides) AND (RDW OR "red cell distribution width" OR "red blood cell distribution width" OR anisocytosis). Four authors independently reviewed the retrieved articles. Studies were included if they had evaluated the association between RDW value and mortality of acute pancreatitis patients. Case reports, comments, letters to the editor, reviews, study protocols, and experimental studies were not included. Data abstraction and quality assessment for the included studies was independently performed by two authors. Quality of studies was assessed using Oxford Center for Evidence-Based Medicine checklist for prognostic studies. Data were synthesized qualitatively, and a meta-analysis was performed on the diagnostic performance of RDW to predict mortality in AP patients. Results: Seven studies (976 patients) were included in the systematic review. Six studies reported a statistically significant association between RDW value and mortality. Meta-analysis was performed on four studies (487 patients) using a bivariate model and a summary receiver operating characteristic (sROC) curve was plotted with an area under the curve (AUC) of 0.757. The pooled diagnostic odds ratio (DOR), sensitivity and specificity was 19.51 (95% CI: 5.26-72.30), 67% (95% CI: 51%-80%) and 90% (95% CI: 73%-96%), respectively. Conclusion: RDW is an easy to use and an inexpensive marker with a moderate prognostic value to predict death in AP patients. Clinicians should be more alert when a patient with AP has an increased RDW. Investigation of possible combinations of other prognostic markers with RDW is recommended.

The interplay between insomnia symptoms and Alzheimer's Disease across three main brain networks.

STUDY OBJECTIVES: Insomnia symptoms are prevalent along the trajectory of Alzheimer's disease (AD), but the neurobiological underpinning of their interaction is poorly understood. Here, we assessed structural and functional brain measures within and between the default mode network (DMN), salience network (SN), and central executive network (CEN). METHODS: We selected 320 subjects from the ADNI database and divided by their diagnosis: cognitively normal (CN), Mild Cognitive Impairment (MCI), and AD, with and without self-reported insomnia symptoms. We measured the gray matter volume (GMV), structural covariance (SC), degrees centrality (DC), and functional connectivity (FC), testing the effect and interaction of insomnia symptoms and diagnosis on each index. Subsequently, we performed a within-group linear regression across each network and ROI. Finally, we correlated observed abnormalities with changes in cognitive and affective scores. RESULTS: Insomnia symptoms were associated with FC alterations across all groups. The AD group also demonstrated an interaction between insomnia and diagnosis. Within-group analyses revealed that in CN and MCI, insomnia symptoms were characterised by within-network hyperconnectivity, while in AD, within- and between-network hypoconnectivity was ubiquitous. SC and GMV alterations were non-significant in the presence of insomnia symptoms, and DC indices only showed network-level alterations in the CEN of AD individuals. Abnormal FC within and between DMN and CEN hubs was additionally associated with reduced cognitive function across all groups, and increased depressive symptoms in AD. CONCLUSIONS: We conclude that patients with clinical AD present with a unique pattern of insomnia-related functional alterations, highlighting the profound interaction between both conditions.

Adolescent maturation of cortical excitation-inhibition balance based on individualized biophysical network modeling.

The balance of excitation and inhibition is a key functional property of cortical microcircuits which changes through the lifespan. Adolescence is considered a crucial period for the maturation of excitation-inhibition balance. This has been primarily observed in animal studies, yet human in vivo evidence on adolescent maturation of the excitation-inhibition balance at the individual level is limited. Here, we developed an individualized in vivo marker of regional excitation-inhibition balance in human adolescents, estimated using large-scale simulations of biophysical network models fitted to resting-state functional magnetic resonance imaging data from two independent cross-sectional (N = 752) and longitudinal (N = 149) cohorts. We found a widespread relative increase of inhibition in association cortices paralleled by a relative age-related increase of excitation, or lack of change, in sensorimotor areas across both datasets. This developmental pattern co-aligned with multiscale markers of sensorimotor-association differentiation. The spatial pattern of excitation-inhibition development in adolescence was robust to inter-individual variability of structural connectomes and modeling configurations. Notably, we found that alternative simulation-based markers of excitation-inhibition balance show a variable sensitivity to maturational change. Taken together, our study highlights an increase of inhibition during adolescence in association areas using cross sectional and longitudinal data, and provides a robust computational framework to estimate microcircuit maturation in vivo at the individual level.

The spread of innovations in social networks.

Which network structures favor the rapid spread of new ideas, behaviors, or technologies? This question has been studied extensively using epidemic models. Here we consider a complementary point of view and consider scenarios where the individuals' behavior is the result of a strategic choice among competing alternatives. In particular, we study models that are based on the dynamics of coordination games. Classical results in game theory studying this model provide a simple condition for a new action or innovation to become widespread in the network. The present paper characterizes the rate of convergence as a function of the structure of the interaction network. The resulting predictions differ strongly from the ones provided by epidemic models. In particular, it appears that innovation spreads much more slowly on well-connected network structures dominated by long-range links than in low-dimensional ones dominated, for example, by geographic proximity.

Convergent functional effects of antidepressants in major depressive disorder: a neuroimaging meta-analysis.

Background: Neuroimaging studies have provided valuable insights into the macroscale impacts of antidepressants on brain functions in patients with major depressive disorder. However, the findings of individual studies are inconsistent. Here, we aimed to provide a quantitative synthesis of the literature to identify convergence of the reported findings at both regional and network levels and to examine their associations with neurotransmitter systems. Methods: Through a comprehensive search in PubMed and Scopus databases, we reviewed 5,258 abstracts and identified 37 eligible functional neuroimaging studies on antidepressant effects in major depressive disorder. Activation likelihood estimation was used to investigate regional convergence of the reported foci of consistent antidepressant effects, followed by functional decoding and connectivity mapping of the convergent clusters. Additionally, utilizing group-averaged data from the Human Connectome Project, we assessed convergent resting-state functional connectivity patterns of the reported foci. Next, we compared the convergent circuit with the circuits targeted by transcranial magnetic stimulation (TMS) therapy. Last, we studied the association of regional and network-level convergence maps with the selected neurotransmitter receptors/transporters maps. Results: We found regional convergence of the reported treatment-associated increases of functional measures in the left dorsolateral prefrontal cortex, which was associated with working memory and attention behavioral domains. No regional convergence was found across foci of alterations in functional imaging associated with antidepressants. Moreover, we found network-level convergence of functional alterations in a circuit that was prominent in the frontoparietal and salience networks. This circuit was co-aligned with a circuit targeted by anti-subgenual TMS therapy. We observed no significant correlations between our meta-analytic findings with the maps of neurotransmitter receptors/transporters. Conclusion: Our findings highlight the importance of the left dorsolateral prefrontal cortex, as well as frontoparietal network and the salience network in the therapeutic effects of anti-depressants, possibly associated with their role in improving executive functions and emotional processing.

Human cortex development is shaped by molecular and cellular brain systems.

Human brain morphology undergoes complex changes over the lifespan. Despite recent progress in tracking brain development via normative models, current knowledge of underlying biological mechanisms is highly limited. We demonstrate that human cerebral cortex development unfolds along patterns of molecular and cellular brain organization, traceable from population-level to individual developmental trajectories. During childhood and adolescence, cortex-wide spatial distributions of dopaminergic receptors, inhibitory neurons, glial cell populations, and brain-metabolic features explain up to 50% of variance associated with regional cortical thickness trajectories. Adult cortical change patterns are best explained by cholinergic and glutamatergic neurotransmission. These relationships are supported by developmental gene expression trajectories and translate to longitudinal data from over 8,000 adolescents, explaining up to 59% of developmental change at population- and 18% at single-subject level. Integrating multilevel brain atlases with normative modeling and population neuroimaging provides a biologically meaningful path to understand typical and atypical brain development in living humans.

Structural and functional neuroimaging of late-life depression: a coordinate-based meta-analysis.

Several neuroimaging studies have investigated localized aberrations in brain structure, function or connectivity in late-life depression, but the ensuing results are equivocal and often conflicting. Here, we provide a quantitative consolidation of neuroimaging in late-life depression using coordinate-based meta-analysis by searching multiple databases up to March 2020. Our search revealed 3252 unique records, among which we identified 32 eligible whole-brain neuroimaging publications comparing 674 patients with 568 controls. The peak coordinates of group comparisons between the patients and the controls were extracted and then analyzed using activation likelihood estimation method. Our sufficiently powered analysis on all the experiments, and more homogenous subsections of the data (patients > controls, controls > patients, and functional imaging experiments) revealed no significant convergent regional abnormality in late-life depression. This inconsistency might be due to clinical and biological heterogeneity of LLD, as well as experimental (e.g., choice of tasks, image modalities) and analytic flexibility (e.g., preprocessing and analytic parameters), and distributed patterns of neural abnormalities. Our findings highlight the importance of clinical/biological heterogeneity of late-life depression, in addition to the need for more reproducible research by using pre-registered and standardized protocols on more homogenous populations to identify potential consistent brain abnormalities in late-life depression.

Evaluation of curcumin as add-on therapy in patients with Parkinson's disease: A pilot randomized, triple-blind, placebo-controlled trial.

BACKGROUND AND OBJECTIVE: Preclinical studies suggest that curcumin might be a potential neuroprotective agent in Parkinson's disease (PD). This clinical trial aimed to evaluate the efficacy of adding nanomicelle curcumin on improving the motor and non-motor symptoms of PD patients and their quality of life. MATERIAL AND METHODS: Idiopathic PD patients aged ≥30≥ 30 whose symptoms were under control were included in this pilot, randomized, triple-blind, placebo-controlled, add-on trial. Eligible patients were randomly assigned to either the curcumin (n = 30, 80 mg/day) or placebo (n = 30) groups and were followed for nine months. Primary outcomes were the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Parkinson's Disease Questionnaire (PDQ-39). These variables, along with demographic data, drug history, and possible side effects of curcumin, were gathered at the beginning of the study and every three months. A mixed effects model was used to compare the group-by-time interaction, followed by post hoc analysis. RESULTS: Although the mean MDS-UPDRS and PDQ-39 scores were not significantly different between the curcumin and placebo groups at any time points, MDS-UPDRS part III (P = 0.04) showed a significant difference in its overall trend between the study groups. However, post hoc analysis failed to spot this difference at study time points. The most common side effects of curcumin were nausea and vomiting (P = 0.25) and gastroesophageal reflux (P = 0.42). CONCLUSION: While curcumin is a well-tolerated natural compound, this trial was unsuccessful in showing its efficacy in quality of life and clinical symptoms of PD patients.

Convergent regional brain abnormalities in behavioral variant frontotemporal dementia: A neuroimaging meta-analysis of 73 studies.

Introduction: Numerous studies have reported brain alterations in behavioral variant frontotemporal dementia (bvFTD). However, they pointed to inconsistent findings. Methods: We used a meta-analytic approach to identify the convergent structural and functional brain abnormalities in bvFTD. Following current best-practice neuroimaging meta-analysis guidelines, we searched PubMed and Embase databases and performed reference tracking. Then, the coordinates of group comparisons between bvFTD and controls from 73 studies were extracted and tested for convergence using activation likelihood estimation. Results: We identified convergent abnormalities in the anterior cingulate cortices, anterior insula, amygdala, paracingulate, striatum, and hippocampus. Task-based and resting-state functional connectivity pointed to the networks that are connected to the obtained consistent regions. Functional decoding analyses suggested associated dysfunction of emotional processing, interoception, reward processing, higher-order cognitive functions, and olfactory and gustatory perceptions in bvFTD. Discussion: Our findings highlighted the key role of the salience network and subcortical regions in the pathophysiology of bvFTD.

A Systematic Review and Meta-analysis of Clinical Studies on Ankylosing Spondylitis and Neutrophil to Lymphocyte Ratio.

BACKGROUND: Neutrophil to lymphocyte ratio (NLR) is a marker for many inflammatory diseases. Ankylosing spondylitis (AS) is among these inflammatory diseases, and many studies have compared the NLR ratio between patients with AS and healthy controls. AIM: This study aims to systematically review and analyze the available evidence about the significance of NLR values in AS. METHOD: Based on Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines, we searched Embase, Pubmed, ISI Web of Science, and Scopus databases from inception to August 2020 using ("Ankylosing spondyl* " OR "Bechterew Disease" OR "Rheumatoid Spondylitis") AND ((neutrophil* AND lymphocyte*) OR NLR) as key terms of the search strategy. Data selection and extraction were conducted separately by two authors. We appraised the included articles according to the Joanna Briggs checklist. Comprehensive Meta-analysis Version 2 was used for analysis and assessment of publication bias. I2 > 75% and p-value < 0.05 were considered significant. RESULT: In total, 182 studies resulted from a search in all databases. Duplicate removal, title, abstract, and full-text screening yielded 12 related studies, with 11 included in the meta-analysis. Quality assessment was satisfying in all studies. Pooled difference in NLR means value between patients and controls was 0.38 (95% CI: 0.24-0.52, p-value <0.0001). An I2 of 51% and a Cochran Q test p-value of <0.05 indicated moderate heterogeneity; thus, subgroup analysis had no indication. Publication bias was not significant (Funnel plot with an Egger's intercept of -0.07; p-value=0.95). CONCLUSION: Significant higher amounts of NLR may be strongly indicative of underlying inflammation in AS.

Thalamic shape abnormalities in patients with multiple sclerosis-related fatigue.

Thalamus plays an important role in the pathogenesis of multiple sclerosis-related fatigue (MSrF). However, the thalamus is a heterogeneous structure and the specific thalamic subregions that are involved in this condition are unclear. Here, we used thalamic shape analysis for the detailed localization of thalamic abnormalities in MSrF. Using the Modified Fatigue Impact Scale, we measured fatigue in 42 patients with relapsing-remitting multiple sclerosis (MS). The thalamic shape was extracted from T1w images using an automated pipeline. We investigated the association of thalamic surface deviations with the severity of global fatigue and its cognitive, physical and psychosocial subdomains. Cognitive fatigue was correlated with an inward deformity of the left anteromedial thalamic surface, but no other localized shape deviation was observed in correlation with global, physical or psychosocial fatigue. Our findings indicate that the left anteromedial thalamic subregions are implicated in cognitive fatigue, possibly through their role in reward processing and cognitive and executive functions.

The Accuracy of Visceral Adiposity Index for the Screening of Metabolic Syndrome: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Visceral adiposity index (VAI) is a novel marker of fat distribution and function which incorporates both anthropometric and laboratory measures. Recently, several studies have suggested VAI as a screening tool for metabolic syndrome (MetS). Here, we aimed to consolidate the results of these studies by performing a systematic review and meta-analysis. METHODS AND RESULTS: We searched PubMed and EMBASE online databases for eligible studies that investigated the association of VAI and MetS. After reviewing 294 records, we included 33 eligible papers with a sum of 20516 MetS and 53242 healthy participants. The risk of bias in the included studies was assessed, and the relevant data was extracted. All included studies reported a significant association between VAI and MetS screening, but were highly heterogeneous in their reported effects. We pooled the diagnostic test accuracy metrics of VAI for MetS screening and showed that it has a moderate-to-high accuracy with an area under the summary receiver operating characteristics curve of 0.847, a pooled sensitivity of 78%, and a pooled specificity of 79%. Besides, we pooled the difference in means of VAI between patients with MetS and healthy controls, revealing that VAI was 2.15 units higher in MetS patients. CONCLUSIONS: VAI is an accurate, low-cost, and widely available screening marker for MetS. However, further studies are needed to evaluate its applicability in clinical practice, determine an optimal cut-off, and identify populations that would benefit the most from it.

Chest computed tomography findings of COVID-19 in children younger than 1 year: a systematic review.

BACKGROUND: The aim of this systematic review is to evaluate the chest computed tomography (CT) findings in infants with confirmed COVID-19 infection by providing a comprehensive review of the existing literature. DATA SOURCES: A systematic search was conducted on PubMed and Embase from the onset of the COVID-19 outbreak to October 20, 2020, for studies that discussed the chest CT findings in infants younger than 1 year with COVID-19 infection. RESULTS: A total of 35 studies comprising 70 COVID-19 (58.5% boys) confirmed infants were included. The mean age of the included patients was 4.1 months with a range of 1 day to 12 months. Chest CT scans showed bilateral abnormalities in 34 patients, and unilateral lung involvement in 25 patients. Ground-glass opacities (GGO) (71.43%) were found to be the most prevalent chest CT manifestation, followed by peribronchial thickening (60%), linear or band-shaped opacities (32.8%), consolidation (28.57%), nodule (18.57%), effusion (7.14%) and focal lucency (7.14%). CONCLUSIONS: GGO and peribronchial thickening were the most prevalent findings in the infants' chest CT scans. Linear or band-shaped opacities, consolidation, and pulmonary nodules are more common in infants than in adults. These findings suggest that the disease is more likely to be presented as an atypical pneumonia (peribronchial thickening and linear or band-shaped opacities) in this age group. Other chest CT scan manifestations can be classified as typical COVID-19 infection (peripheral GGO), lobar pneumonia (consolidation) and opportunistic infections (pulmonary nodules).

Predictive value of inflammatory markers for functional outcomes in patients with ischemic stroke.

Background: Inflammatory processes have been proposed in the pathophysiology of ischemic stroke. The present study was designed to evaluate the relationship between tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), IL 1 beta (IL-1ß), and high sensitivity C-reactive protein (hsCRP) with the prognosis and functional outcome in patients with less severe ischemic stroke. Methods: We measured the level of IL-1ß, IL-6, hsCRP, and TNF-α on days 1 and 5 after stroke onset by enzyme-linked immunosorbent assay (ELISA). The infarct volume was assessed using Alberta Stroke Program Early CT Score (ASPECTS) and posterior circulation ASPECTS (pcASPECTS) score in brain computed tomography (CT) scan and magnetic resonance imaging (MRI). The severity of stroke was assessed by applying the National Institutes of Health Stroke Scale (NIHSS) and Modified Rankin Scale (MRS) in 24 hours on day 5 and after 3 months from stroke onset. Good outcome was defined as the third month MRS ≤ 2. The association of inflammatory markers and the course of stroke symptoms over time was examined. Results: Forty-four first-ever stroke patients without concurrent inflammatory diseases with a mean age of 65 years were included. The mean NIHSS and MRS in admission time were 6.5 ± 3.5 and 3.07, respectively. The day 1 and the day 5 levels of IL-1ß, IL-6, hsCRP, and TNF-α were not significantly different in good and poor outcome groups (all P-values > 0.05). In addition, they were not significantly associated with the ASPECTS, pcASPECTS, and changes of NIHSS and MRS over time. Conclusion: The levels of hsCRP, IL-1ß, IL-6, and TNF-α are not reliable predictors of functional outcomes in patients with less severe acute ischemic stroke (AIS).

How Gamification Affects Physical Activity: Large-scale Analysis of Walking Challenges in a Mobile Application.

Gamification represents an effective way to incentivize user behavior across a number of computing applications. However, despite the fact that physical activity is essential for a healthy lifestyle, surprisingly little is known about how gamification and in particular competitions shape human physical activity. Here we study how competitions affect physical activity. We focus on walking challenges in a mobile activity tracking application where multiple users compete over who takes the most steps over a predefined number of days. We synthesize our findings in a series of game and app design implications. In particular, we analyze nearly 2,500 physical activity competitions over a period of one year capturing more than 800,000 person days of activity tracking. We observe that during walking competitions, the average user increases physical activity by 23%. Furthermore, there are large increases in activity for both men and women across all ages, and weight status, and even for users that were previously fairly inactive. We also find that the composition of participants greatly affects the dynamics of the game. In particular, if highly unequal participants get matched to each other, then competition suffers and the overall effect on the physical activity drops significantly. Furthermore, competitions with an equal mix of both men and women are more effective in increasing the level of activities. We leverage these insights to develop a statistical model to predict whether or not a competition will be particularly engaging with significant accuracy. Our models can serve as a guideline to help design more engaging competitions that lead to most beneficial behavioral changes.