Activation of cannabinoid-2 receptor protects against Pseudomonas aeruginosa induced acute lung injury and inflammation.

Background: Bacterial pneumonia is a major risk factor for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Pseudomonas aeruginosa (PA), an opportunistic pathogen with an increasing resistance acquired against multiple drugs, is one of the main causative agents of ALI and ARDS in diverse clinical settings. Given the anti-inflammatory role of the cannabinoid-2 receptor (CB2R), the effect of CB2R activation in the regulation of PA-induced ALI and inflammation was tested in a mouse model as an alternative to conventional antibiotic therapy.

Specific and common functional connectivity deficits in drug-free generalized anxiety disorder and panic disorder: A data-driven analysis.

Evidence of comparing neural network differences between anxiety disorder subtypes is limited, while it is crucial to reveal the pathogenesis of anxiety disorders. The present study aimed to investigate specific and common resting-state functional connectivity (FC) networks in generalized anxiety disorder (GAD), panic disorder (PD), and healthy controls (HC). We employed the gRAICAR algorithm to decompose the resting-state fMRI into independent components and align the components across 61 subjects (22 GAD, 18 PD and 21 HC).

Mnemonic Content and Hippocampal Patterns Shape Judgments of Time.

Our experience of time can feel dilated or compressed, rather than reflecting true "clock time." Although many contextual factors influence the subjective perception of time, it is unclear how memory accessibility plays a role in constructing our experience of and memory for time. Here, we used a combination of behavioral and functional MRI measures in healthy young adults ( = 147) to ask the question of how memory is incorporated into temporal duration judgments.

Effect of Concomitant Benzodiazepines on the Antidepressant Effects of Ketamine: Findings From the RAPID Intravenous Ketamine Study.

Ketamine is a novel and rapidly acting treatment for major depressive disorder (MDD). Benzodiazepines are commonly coprescribed with antidepressants in MDD. This study sought to examine data from a randomized clinical trial that compared a single infusion of intravenous (IV) ketamine to midazolam placebo in treatment-resistant depression ( MDD) and to assess whether the use of concomitant oral benzodiazepines differentially affected treatment response to ketamine versus midazolam.

Hippocampal Subfield Volumes Predict Disengagement from Maintenance Treatment in First Episode Schizophrenia.

Objectives: Disengagement from treatment is common in first episode schizophrenia (FES) and is associated with poor outcomes. Our aim was to determine whether hippocampal subfield volumes predict disengagement during maintenance treatment of FES.

Methods: FES patients were recruited from sites in Boston, New York, Shanghai, and Changsha.

Molecular Insights into Epigenetics and Cannabinoid Receptors.

The actions of cannabis are mediated by G protein-coupled receptors that are part of an endogenous cannabinoid system (ECS). ECS consists of the naturally occurring ligands N-arachidonylethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG), their biosynthetic and degradative enzymes, and the CB and CB cannabinoid receptors. Epigenetics are heritable changes that affect gene expression without changing the DNA sequence, transducing external stimuli in stable alterations of the DNA or chromatin structure.

High-frequency oscillations (250-500 Hz) in animal models of Alzheimer's disease and two animal models of epilepsy.

Objective: To test the hypothesis that high-frequency oscillations (HFOs) between 250 and 500 Hz occur in mouse models of Alzheimer's disease (AD) and thus are not unique to epilepsy.

Methods: Experiments were conducted in three mouse models of AD: Tg2576 mice that simulate a form of familial AD, presenilin 2 knock-out (PS2KO) mice, and the Ts65Dn model of Down's syndrome. We recorded HFOs using wideband (0.

The tie that binds: temporal coding and adaptive emotion.

Emotions are temporally dynamic, but the persistence of emotions outside of their appropriate temporal context is detrimental to health and well-being. Yet, precisely how temporal coding and emotional processing interact remains unclear. Recently unveiled temporal context representations in the hippocampus, entorhinal cortex (EC), and prefrontal cortex (PFC) support memory for what happened when.

A mechanistic framework for cardiometabolic and coronary artery diseases.

Coronary atherosclerosis results from the delicate interplay of genetic and exogenous risk factors, principally taking place in metabolic organs and the arterial wall. Here we show that 224 gene-regulatory coexpression networks (GRNs) identified by integrating genetic and clinical data from patients with ( = 600) and without ( = 250) coronary artery disease (CAD) with RNA-seq data from seven disease-relevant tissues in the Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task (STARNET) study largely capture this delicate interplay, explaining >54% of CAD heritability. Within 89 cross-tissue GRNs associated with clinical severity of CAD, 374 endocrine factors facilitated inter-organ interactions, primarily along an axis from adipose tissue to the liver ( = 152).

Long-term learning transforms prefrontal cortex representations during working memory.

The role of the lateral prefrontal cortex (lPFC) in working memory (WM) is debated. Non-human primate (NHP) electrophysiology shows that the lPFC stores WM representations, but human neuroimaging suggests that the lPFC controls WM content in sensory cortices. These accounts are confounded by differences in task training and stimulus exposure.

An analysis-ready and quality controlled resource for pediatric brain white-matter research.

We created a set of resources to enable research based on openly-available diffusion MRI (dMRI) data from the Healthy Brain Network (HBN) study. First, we curated the HBN dMRI data (N = 2747) into the Brain Imaging Data Structure and preprocessed it according to best-practices, including denoising and correcting for motion effects, susceptibility-related distortions, and eddy currents. Preprocessed, analysis-ready data was made openly available.

Annual Research Review: Perspectives on progress in ADHD science - from characterization to cause.

The science of attention-deficit/hyperactivity disorder (ADHD) is motivated by a translational goal - the discovery and exploitation of knowledge about the nature of ADHD to the benefit of those individuals whose lives it affects. Over the past fifty years, scientific research has made enormous strides in characterizing the ADHD condition and in understanding its correlates and causes. However, the translation of these scientific insights into clinical benefits has been limited.

Large-scale biophysically detailed model of somatosensory thalamocortical circuits in NetPyNE.

The primary somatosensory cortex (S1) of mammals is critically important in the perception of touch and related sensorimotor behaviors. In 2015, the Blue Brain Project (BBP) developed a groundbreaking rat S1 microcircuit simulation with over 31,000 neurons with 207 morpho-electrical neuron types, and 37 million synapses, incorporating anatomical and physiological information from a wide range of experimental studies. We have implemented this highly detailed and complex S1 model in NetPyNE, using the data available in the Neocortical Microcircuit Collaboration Portal.

Revisiting sex differences in the acquisition and extinction of threat conditioning in humans.

Findings pertaining to sex differences in the acquisition and extinction of threat conditioning, a paradigm widely used to study emotional homeostasis, remain inconsistent, particularly in humans. This inconsistency is likely due to multiple factors, one of which is sample size. Here, we pooled functional magnetic resonance imaging (fMRI) and skin conductance response (SCR) data from multiple studies in healthy humans to examine sex differences during threat conditioning, extinction learning, and extinction memory recall.

The three-dimensional landscape of cortical chromatin accessibility in Alzheimer's disease.

To characterize the dysregulation of chromatin accessibility in Alzheimer's disease (AD), we generated 636 ATAC-seq libraries from neuronal and nonneuronal nuclei isolated from the superior temporal gyrus and entorhinal cortex of 153 AD cases and 56 controls. By analyzing a total of ~20 billion read pairs, we expanded the repertoire of known open chromatin regions (OCRs) in the human brain and identified cell-type-specific enhancer-promoter interactions. We show that interindividual variability in OCRs can be leveraged to identify cis-regulatory domains (CRDs) that capture the three-dimensional structure of the genome (3D genome).

Population-level variation in enhancer expression identifies disease mechanisms in the human brain.

Identification of risk variants for neuropsychiatric diseases within enhancers underscores the importance of understanding population-level variation in enhancer function in the human brain. Besides regulating tissue-specific and cell-type-specific transcription of target genes, enhancers themselves can be transcribed. By jointly analyzing large-scale cell-type-specific transcriptome and regulome data, we cataloged 30,795 neuronal and 23,265 non-neuronal candidate transcribed enhancers.

Cognitive Impairment Associated with Schizophrenia: From Pathophysiology to Treatment.

Cognitive impairment is a core feature of schizophrenia and a major contributor to poor functional outcomes. Methods for assessment of cognitive dysfunction in schizophrenia are now well established. In addition, there has been increasing appreciation in recent years of the additional role of social cognitive impairment in driving functional outcomes and of the contributions of sensory-level dysfunction to higher-order impairments.

Curation of BIDS (CuBIDS): A workflow and software package for streamlining reproducible curation of large BIDS datasets.

The Brain Imaging Data Structure (BIDS) is a specification accompanied by a software ecosystem that was designed to create reproducible and automated workflows for processing neuroimaging data. BIDS Apps flexibly build workflows based on the metadata detected in a dataset. However, even BIDS valid metadata can include incorrect values or omissions that result in inconsistent processing across sessions.

Data-Driven Clustering of Functional Signals Reveals Gradients in Processing Both within the Anterior Hippocampus and across Its Long Axis.

A particularly elusive puzzle concerning the hippocampus is how the structural differences along its long anteroposterior axis might beget meaningful functional differences, particularly in terms of the granularity of information processing. One measure posits to quantify this granularity by calculating the average statistical independence of the BOLD signal across neighboring voxels, or intervoxel similarity (IVS), and has shown the anterior hippocampus to process coarser-grained information than the posterior hippocampus. This measure, however, has yielded opposing results in studies of developmental and healthy aging samples, which also varied in fMRI acquisition parameters and hippocampal parcellation methods.

Very Low-Level Transcranial Photobiomodulation for Major Depressive Disorder: The ELATED-3 Multicenter, Randomized, Sham-Controlled Trial.

Transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light might represent a treatment for major depressive disorder (MDD). However, the dosimetry of administered t-PBM varies widely. We tested the efficacy of t-PBM with low irradiance, low energy per session, and low number of sessions in individuals with MDD.