Investigating trait variability of gene co-expression network architecture in brain by controlling for genomic risk of schizophrenia.

The effect of schizophrenia (SCZ) genetic risk on gene expression in brain remains elusive. A popular approach to this problem has been the application of gene co-expression network algorithms (e.g.

Consensus molecular environment of schizophrenia risk genes in coexpression networks shifting across age and brain regions.

Schizophrenia is a neurodevelopmental brain disorder whose genetic risk is associated with shifting clinical phenomena across the life span. We investigated the convergence of putative schizophrenia risk genes in brain coexpression networks in postmortem human prefrontal cortex (DLPFC), hippocampus, caudate nucleus, and dentate gyrus granule cells, parsed by specific age periods (total  = 833). The results support an early prefrontal involvement in the biology underlying schizophrenia and reveal a dynamic interplay of regions in which age parsing explains more variance in schizophrenia risk compared to lumping all age periods together.

Analysis of the caudate nucleus transcriptome in individuals with schizophrenia highlights effects of antipsychotics and new risk genes.

Most studies of gene expression in the brains of individuals with schizophrenia have focused on cortical regions, but subcortical nuclei such as the striatum are prominently implicated in the disease, and current antipsychotic drugs target the striatum's dense dopaminergic innervation. Here, we performed a comprehensive analysis of the genetic and transcriptional landscape of schizophrenia in the postmortem caudate nucleus of the striatum of 443 individuals (245 neurotypical individuals, 154 individuals with schizophrenia and 44 individuals with bipolar disorder), 210 from African and 233 from European ancestries. Integrating expression quantitative trait loci analysis, Mendelian randomization with the latest schizophrenia genome-wide association study, transcriptome-wide association study and differential expression analysis, we identified many genes associated with schizophrenia risk, including potentially the dopamine D2 receptor short isoform.

Identification and prioritization of gene sets associated with schizophrenia risk by co-expression network analysis in human brain.

Schizophrenia polygenic risk is plausibly manifested by complex transcriptional dysregulation in the brain, involving networks of co-expressed and functionally related genes. The main purpose of this study was to identify and prioritize co-expressed gene sets in a hierarchical manner, based on the strength of the relationships with clinical diagnosis and with polygenic risk for schizophrenia. Weighted Gene Co-expression Network Analysis (WGCNA) was applied to RNA-quality-adjusted DLPFC RNA-Seq data from the LIBD Postmortem Human Brain Repository (90 controls, 74 schizophrenia cases; all Caucasians) to construct co-expression networks and detect "modules" of co-expressed genes.

Using redundancy of round-trip ultrasound signal for non-continuous arrays: Application to gap and blockage compensation.

In ultrasound imaging, an array of elements is used to image a medium. If part of the array is blocked by an obstacle, or if the array is made from several sub-arrays separated by a gap, grating lobes appear and the image is degraded. The grating lobes are caused by missing spatial frequencies, corresponding to the blocked or non-existing elements.

Finding the Elusive Psychiatric "Lesion" With 21st-Century Neuroanatomy: A Note of Caution.

The widespread use of MRI has led to a wealth of structural and functional anatomical findings in patients with diverse psychiatric disorders that may represent insights into pathobiology. However, recent technical reports indicate that data from popular MRI research-particularly structural MRI, resting--state functional MRI, and diffusion tensor imaging--are highly sensitive to common artifacts (e.g.

Grey-matter texture abnormalities and reduced hippocampal volume are distinguishing features of schizophrenia.

Neurodevelopmental processes are widely believed to underlie schizophrenia. Analysis of brain texture from conventional magnetic resonance imaging (MRI) can detect disturbance in brain cytoarchitecture. We tested the hypothesis that patients with schizophrenia manifest quantitative differences in brain texture that, alongside discrete volumetric changes, may serve as an endophenotypic biomarker.

Abnormalities in fronto-striatal connectivity within language networks relate to differences in grey-matter heterogeneity in Asperger syndrome.

Asperger syndrome (AS) is an Autism Spectrum Disorder (ASD) characterised by qualitative impairment in the development of emotional and social skills with relative preservation of general intellectual abilities, including verbal language. People with AS may nevertheless show atypical language, including rate and frequency of speech production. We previously observed that abnormalities in grey matter homogeneity (measured with texture analysis of structural MR images) in AS individuals when compared with controls are also correlated with the volume of caudate nucleus.

Effect of schizophrenia risk-associated alleles in SREB2 (GPR85) on functional MRI phenotypes in healthy volunteers.

Genetic variants in GPR85 (SREB2: rs56080411 and rs56039557) have been associated with risk for schizophrenia. Here, we test the hypothesis that these variants impact on brain function in normal subjects, measured with functional magnetic resonance imaging (fMRI) paradigms that target regions with greatest SREB2 expression (hippocampal formation and amygdaloid complex). During a facial emotion recognition paradigm, a significant interaction of rs56080411 genotype by sex was found in the left amygdaloid complex (male risk allele carriers showed less activation than male homozygotes for the non-risk allele, while females showed the opposite pattern).

Sex differences and autism: brain function during verbal fluency and mental rotation.

Autism spectrum conditions (ASC) affect more males than females. This suggests that the neurobiology of autism: 1) may overlap with mechanisms underlying typical sex-differentiation or 2) alternately reflect sex-specificity in how autism is expressed in males and females. Here we used functional magnetic resonance imaging (fMRI) to test these alternate hypotheses.

Gray matter textural heterogeneity as a potential in-vivo biomarker of fine structural abnormalities in Asperger syndrome.

Brain imaging studies contribute to the neurobiological understanding of Autism Spectrum Conditions (ASC). Herein, we tested the prediction that distributed neurodevelopmental abnormalities in brain development impact on the homogeneity of brain tissue measured using texture analysis (TA; a morphological method for surface pattern characterization). TA was applied to structural magnetic resonance brain scans of 54 adult participants (24 with Asperger syndrome (AS) and 30 controls).

Selective updating of working memory content modulates meso-cortico-striatal activity.

Accumulating evidence from non-human primates and computational modeling suggests that dopaminergic signals arising from the midbrain (substantia nigra/ventral tegmental area) mediate striatal gating of the prefrontal cortex during the selective updating of working memory. Using event-related functional magnetic resonance imaging, we explored the neural mechanisms underlying the selective updating of information stored in working memory. Participants were scanned during a novel working memory task that parses the neurophysiology underlying working memory maintenance, overwriting, and selective updating.

Biological validation of increased schizophrenia risk with NRG1, ERBB4, and AKT1 epistasis via functional neuroimaging in healthy controls.

Context: NRG1 is a schizophrenia candidate gene and plays an important role in brain development and neural function. Schizophrenia is a complex disorder, with etiology likely due to epistasis.

Objective: To examine epistasis between NRG1 and selected N-methyl-d-aspartate-glutamate pathway partners implicated in its effects, including ERBB4, AKT1, DLG4, NOS1, and NOS1AP.

Genetic modulation of GABA levels in the anterior cingulate cortex by GAD1 and COMT.

Gamma-aminobutyric acid (GABA)-ergic transmission is critical for normal cortical function and is likely abnormal in a variety of neuropsychiatric disorders. We tested the in vivo effects of variations in two genes implicated in GABA function on GABA concentrations in prefrontal cortex of living subjects: glutamic acid decarboxylase 1 (GAD1), which encodes GAD67, and catechol-o-methyltransferase (COMT), which regulates synaptic dopamine in the cortex. We studied six single nucleotide polymorphisms (SNPs) in GAD1 previously associated with risk for schizophrenia or cognitive dysfunction and the val158met polymorphism in COMT in 116 healthy volunteers using proton magnetic resonance spectroscopy.

Imaging genetics of structural brain connectivity and neural integrity markers.

We review studies that have used diffusion imaging (DI) and magnetic resonance spectroscopy (MRS) to investigate genetic associations. A brief description of the measures obtainable with these methods and of some methodological and interpretability limitations is given. The usefulness of DI and MRS in defining intermediate phenotypes and in demonstrating the effects of common genetic variants known to increase risk for psychiatric manifestations on anatomical and metabolic phenotypes is reviewed.

[Considerations about neoplastic intestinal occlusion].

Neoplastic intestinal occlusion represent a Frequently Surgical emergency. The present study deals with 96 cases of neoplastic intestinal occlusion from a group of 480 patients admitted and operated with diagnosis of intestinal occlusions in our clinic between 1998-2002. The patients had clinical evidence of intestinal occlusions confirmed by imaging and endoscopical examination.

Probing acoustic fields of clinically relevant transducers: the effect of hydrophone probes' finite apertures and bandwidths.

The influence of finite aperture and frequency response of piezoelectric ultrasonic hydrophone probes on the free-field pulse intensity integral (PII) and mechanical index (MI) was investigated using a comprehensive acoustic wave propagation model. The model developed was capable of predicting the true pressure-time waveforms at virtually any point in the field. The input to the model used pressure amplitude data measured in the immediate vicinity of the acoustic source or transducer considered.

The influence of finite aperture and frequency response of ultrasonic hydrophone probes on the determination of acoustic output.

The influence of finite aperture and frequency response of piezoelectric ultrasonic hydrophone probes on the Thermal and Mechanical Indices was investigated using a comprehensive acoustic wave propagation model. The experimental verification of the model was obtained using a commercially available, 8 MHz, dynamically focused linear array and a single element, 5 MHz, focused rectangular source. The pressure-time waveforms were recorded using piezoelectric polymer hydrophone probes of different active element diameters and bandwidths.

Interlaboratory evaluation of hydrophone sensitivity calibration from 0.1 to 2 MHz via time delay spectrometry.

Knowing the low-frequency response of hydrophones, down to 100 kHz at least, is important for accurate biomedical ultrasound measurements. However, current international standards do not extend below 500 kHz. Furthermore, commercial hydrophone sources typically do not supply sensitivity data below 1-2 MHz.

Hydrophones' effective diameter measurements as a quasi-continuous function of frequency.

The spatial averaging effect is strongly dependent on the active aperture of the hydrophone probes used to measure ultrasound fields. An experimental method was developed to determine the effective diameter of the probes as a quasi-continuous function of frequency. The implementation of the method utilizes the time delay spectrometry (TDS) technique and a set of focused acoustic sources.

Calibration of ultrasonic hydrophone probes up to 100 MHz using time gating frequency analysis and finite amplitude waves.

A number of ultrasound imaging systems employs harmonic imaging to optimize the trade off between resolution and penetration depth and center frequencies as high as 15 MHz are now used in clinical practice. However, currently available measurement tools are not fully adequate to characterize the acoustic output of such nonlinear systems primarily due to the limited knowledge of the frequency responses beyond 20 MHz of the available piezoelectric hydrophone probes. In addition, ultrasound hydrophone probes need to be calibrated to eight times the center frequency of the imaging transducer.