Genetic Associations Among Inflammation, White Matter Architecture, and Extracellular Free Water.

Phenotypic and genetic relationships between white matter microstructure (i.e., fractional anisotropy [FA]) and peripheral inflammatory responses (i.

Effects of gene dosage on cognitive ability: A function-based association study across brain and non-brain processes.

Copy-number variants (CNVs) that increase the risk for neurodevelopmental disorders also affect cognitive ability. However, such CNVs remain challenging to study due to their scarcity, limiting our understanding of gene-dosage-sensitive biological processes linked to cognitive ability. We performed a genome-wide association study (GWAS) in 258,292 individuals, which identified-for the first time-a duplication at 2q12.

Development and validation of an ultra-performance liquid chromatography with tandem mass spectrometry method for determination of soluble repulsive guidance molecule A in human serum and cerebrospinal fluid.

Repulsive guidance molecule A (RGMa) is upregulated in neurodegenerative diseases. To assess RGMa levels in human serum and cerebrospinal fluid (CSF), a quantification method was developed and validated according to ICH M10 guideline. Sample preparation consisted of immunoprecipitation (IP, only for serum), digestion and purification followed by MS.

Copy-number variants differ in frequency across genetic ancestry groups.

Copy-number variants (CNVs) have been implicated in a variety of neuropsychiatric and cognitive phenotypes. We found that deleterious CNVs are less prevalent in non-European ancestry groups than they are in European ancestry groups of both the UK Biobank (UKBB) and a US replication cohort (SPARK). We also identified specific recurrent CNVs that consistently differ in frequency across ancestry groups in both the UKBB and SPARK.

Large-scale analysis of structural brain asymmetries during neurodevelopment: Associations with age and sex in 4265 children and adolescents.

Only a small number of studies have assessed structural differences between the two hemispheres during childhood and adolescence. However, the existing findings lack consistency or are restricted to a particular brain region, a specific brain feature, or a relatively narrow age range. Here, we investigated associations between brain asymmetry and age as well as sex in one of the largest pediatric samples to date (n = 4265), aged 1-18 years, scanned at 69 sites participating in the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium.

Evidence for an Association Between a pH-Dependent Potassium Channel, TWIK-1, and the Accuracy of Smooth Pursuit Eye Movements.

Purpose: Within the healthy population there is a large variation in the ability to perform smooth pursuit eye movements. Our purpose was to investigate the genetic and physiological bases for this variation.

Methods: We carried out a whole-genome association study, recording smooth pursuit movements for 1040 healthy volunteers by infrared oculography.

Neutralizing RGMa with Elezanumab Promotes Cerebroprotection and Recovery in Rabbit Middle Cerebral Artery Occlusion.

Repulsive guidance molecule A (RGMa) is an inhibitor of neuronal growth and survival which is upregulated in the damaged central nervous system following acute spinal cord injury (SCI), traumatic brain injury, acute ischemic stroke (AIS), and other neuropathological conditions. Neutralization of RGMa is neuroprotective and promotes neuroplasticity in several preclinical models of neurodegeneration and injury including multiple sclerosis, AIS, and SCI. Given the limitations of current treatments for AIS due to narrow time windows to intervention (TTI), and restrictive patient selection criteria, there is significant unmet need for therapeutic agents that enable tissue survival and repair following acute ischemic damage for a broader population of stroke patients.

Cocktail-party listening and cognitive abilities show strong pleiotropy.

Introduction: The cocktail-party problem refers to the difficulty listeners face when trying to attend to relevant sounds that are mixed with irrelevant ones. Previous studies have shown that solving these problems relies on perceptual as well as cognitive processes. Previously, we showed that speech-reception thresholds (SRTs) on a cocktail-party listening task were influenced by genetic factors.

A possible mechanism of neural read-out from a molecular engram.

What is the physical basis of declarative memory? The predominant view holds that stored information is embedded in the structure of a neural net, that is, in the signs and weights of its synaptic connections. An alternative possibility is that storage and processing are separated, and that the engram is encoded chemically, most probably in the sequence of a nucleic acid. One deterrent to adoption of the latter hypothesis has been the difficulty of envisaging how neural actively could be converted to and from a molecular code.

Identifying multiscale translational safety biomarkers using a network-based systems approach.

Animal testing is the current standard for drug and chemicals safety assessment, but hazards translation to human is uncertain. Human models can address the species translation but might not replicate complexity. Herein, we propose a network-based method addressing these translational multiscale problems that derives liver injury biomarkers applicable to human early safety screening.

Impact of Copy Number Variants and Polygenic Risk Scores on Psychopathology in the UK Biobank.

Background: Our understanding of the impact of copy number variants (CNVs) on psychopathology and their joint influence with polygenic risk scores (PRSs) remains limited.

Methods: The UK Biobank recruited 502,534 individuals ages 37 to 73 years living in the United Kingdom between 2006 and 2010. After quality control, genotype data from 459,855 individuals were available for CNV calling.

The contribution of copy number variants to psychiatric symptoms and cognitive ability.

Copy number variants (CNVs) are deletions and duplications of DNA sequence. The most frequently studied CNVs, which are described in this review, are recurrent CNVs that occur in the same locations on the genome. These CNVs have been strongly implicated in neurodevelopmental disorders, namely autism spectrum disorder (ASD), intellectual disability (ID), and developmental delay (DD), but also in schizophrenia.

Similar Rates of Deleterious Copy Number Variants in Early-Onset Psychosis and Autism Spectrum Disorder.

Objective: Copy number variants (CNVs) are strongly associated with neurodevelopmental and psychotic disorders. Early-onset psychosis (EOP), where symptoms appear before 18 years of age, is thought to be more strongly influenced by genetic factors than adult-onset psychotic disorders. However, the prevalence and effect of CNVs in EOP is unclear.

Specificity of Psychiatric Polygenic Risk Scores and Their Effects on Associated Risk Phenotypes.

Background: Polygenic risk scores (PRSs) are indices of genetic liability for illness, but their clinical utility for predicting risk for a specific psychiatric disorder is limited. Genetic overlap among disorders and their effects on allied phenotypes may be a possible explanation, but this has been difficult to quantify given focus on singular disorders and/or allied phenotypes.

Methods: We constructed PRSs for 5 psychiatric disorders (schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder, attention-deficit/hyperactivity disorder) and 3 nonpsychiatric control traits (height, type II diabetes, irritable bowel disease) in the UK Biobank ( = 31,616) and quantified associations between PRSs and phenotypes allied with mental illness: behavioral (symptoms, cognition, trauma) and brain measures from magnetic resonance imaging.

Copy Number Variant Risk Scores Associated With Cognition, Psychopathology, and Brain Structure in Youths in the Philadelphia Neurodevelopmental Cohort.

Importance: Psychiatric and cognitive phenotypes have been associated with a range of specific, rare copy number variants (CNVs). Moreover, IQ is strongly associated with CNV risk scores that model the predicted risk of CNVs across the genome. But the utility of CNV risk scores for psychiatric phenotypes has been sparsely examined.

13q32.1 as a candidate region for physiological anisocoria.

Background: Physiological anisocoria is an asymmetry of pupil size in the absence of pathology.

Methods: Images of the pupils under standard illumination were collected in the course of a whole-genome association study of a range of visual functions in 1060 healthy adults. DNA for each participant was extracted from saliva samples.

What kind of network is the brain?

The different areas of the cerebral cortex are linked by a network of white matter, comprising the myelinated axons of pyramidal cells. Is this network a neural net, in the sense that representations of the world are embodied in the structure of the net, its pattern of nodes, and connections? Or is it a communications network, where the same physical substrate carries different information from moment to moment? This question is part of the larger question of whether the brain is better modeled by connectionism or by symbolic artificial intelligence (AI), but we review it in the specific context of the psychophysics of stimulus comparison and the format and protocol of information transmission over the long-range tracts of the brain.

Dynamic and Static Cognitive Deficits in Schizophrenia and Bipolar Disorder After the First Episode.

Few studies have comprehensively examined the profile of cognitive functioning in first episode psychosis patients throughout the lifespan, and from first episode to chronic stage. We assessed functioning in general and specific cognitive functions, comparing both schizophrenia (N = 64) and bipolar I (N = 19) patients to controls (N = 103). Participants were from a population-based, case-control study of first episode psychosis patients, who were followed prospectively up to 10 years post first admission.

High diagnostic performance of independent alpha-synuclein seed amplification assays for detection of early Parkinson's disease.

Alpha-synuclein seed amplification assays (αSyn-SAAs) are promising diagnostic tools for Parkinson's disease (PD) and related synucleinopathies. They enable detection of seeding-competent alpha-synuclein aggregates in living patients and have shown high diagnostic accuracy in several PD and other synucleinopathy patient cohorts. However, there has been confusion about αSyn-SAAs for their methodology, nomenclature, and relative accuracies when performed by various laboratories.

The human hepatocyte TXG-MAPr: gene co-expression network modules to support mechanism-based risk assessment.

Mechanism-based risk assessment is urged to advance and fully permeate into current safety assessment practices, possibly at early phases of drug safety testing. Toxicogenomics is a promising source of mechanisms-revealing data, but interpretative analysis tools specific for the testing systems (e.g.

Bongard and Smirnov on the tetrachromacy of extra-foveal vision.

In Moscow in the 1950's, the physicist M. M. Bongard developed the use of silent substitution to establish the number of dimensions of human or animal colour vision and to derive colour-matching functions either for whole organisms or for individual neuronal channels.

Retinal Ganglion Cells-Diversity of Cell Types and Clinical Relevance.

Retinal ganglion cells (RGCs) are the bridging neurons that connect the retinal input to the visual processing centres within the central nervous system. There is a remarkable diversity of RGCs and the various subtypes have unique morphological features, distinct functions, and characteristic pathways linking the inner retina to the relevant brain areas. A number of psychophysical and electrophysiological tests have been refined to investigate this large and varied population of RGCs.