P50 Sensory Gating in Infants

Attentional deficits are common in a variety of neuropsychiatric disorders including attention deficit-hyperactivity disorder, autism, bipolar mood disorder, and schizophrenia. There has been increasing interest in the neurodevelopmental components of these attentional deficits; neurodevelopmental meaning that while the deficits become clinically prominent in childhood or adulthood, the deficits are the results of problems in brain development that begin in infancy or even prenatally. Despite this interest, there are few methods for assessing attention very early in infancy. This report focuses on one method, infant auditory P50 sensory gating.Attention has several components. One of the earliest components of attention, termed sensory gating, allows the brain to tune out repetitive, noninformative sensory information. Auditory P50 sensory gating refers to one task designed to measure sensory gating using changes in EEG. When identical auditory stimuli are presented 500 ms apart, the evoked response (change in the EEG associated with the processing of the click) to the second stimulus is generally reduced relative to the response to the first stimulus (i.e. the response is "gated"). When response to the second stimulus is not reduced, this is considered a poor sensory gating, is reflective of impaired cerebral inhibition, and is correlated with attentional deficits.Because the auditory P50 sensory gating task is passive, it is of potential utility in the study of young infants and may provide a window into the developmental time course of attentional deficits in a variety of neuropsychiatric disorders. The goal of this presentation is to describe the methodology for assessing infant auditory P50 sensory gating, a methodology adapted from those used in studies of adult populations.     

产后抑郁症患者听感觉门控P50的研究

目的：探讨产后抑郁症患者感觉门控P50 的变化特征,为产后抑郁患者的早期预防提供参考依据。方法：采用配对听觉条件（S1）、测试（S2）刺激范式,对本院2011 年1 月至2012 年6 月收治的26 例产后抑郁症患者（实验组）进行听觉诱发电位P50检测,测量P50 的潜伏期、波幅,并与25 例健康被试者（对照组）的结果进行比较。结果：（1） 与对照组相比,实验组S1-P50 潜伏期[（56.62± 17.42） ms vs. （49.86 ± 15.21） ms],S2-P50 潜伏期[（57.36 ± 15.42） ms vs. （50.04 ± 16.27） ms]的差异均无统计学意义（P〉0.05）;（2）与对照组相比,实验组S1-P50 波幅[（3.58 ± 1.72） μV vs. （1.13 ± 0.91） μV]显著降低,差异有统计学意义（P〈0.05）;S2-P50 波幅[（1.32 ± 1.16） μV vs. （1.48 ± 1.05） μV]差异无统计学意义（P〉0.05）;（3） 与对照组相比,实验组S2/S1 波幅比值[（1.17 ± 0.26） vs.（0.41 ± 0.13）]显著升高,差异有统计学意义（P〈0.05）。结论：产后抑郁症患者感觉门控抑制能力有缺陷,P50 受损指标可能为评估产后抑郁症患者的潜在生物学指标。     

产后抑郁症患者听感觉门控 P50 的研究

摘要 目的： 探讨产后抑郁症患者感觉门控 P50 的变化特征,为产后抑郁患者的早期预防提供参考依据。方法： 采用配对听觉条件 (S1)、测试(S2)刺激范式, 对本院 2011 年 1 月至 2012 年 6 月收治的 26 例产后抑郁症患者(实验组)进行听觉诱发电位 P50 检测, 测量 P50 的潜伏期、 波幅, 并与 25 例健康被试者(对照组)的结果进行比较。 结果： (1) 与对照组相比, 实验组 S1-P50 潜伏期[(56.62 ± 17.42) ms vs. (49.86 ± 15.21) ms], S2-P50 潜伏期[(57.36 ± 15.42) ms vs. (50.04 ± 16.27) ms]的差异均无统计学意义(P>0.05); (2) 与对照组相比, 实验组 S1-P50 波幅[(3.58 ± 1.72) μV vs. (1.13 ± 0.91) μV]显著降低, 差异有统计学意义(P<0.05); S2-P50 波幅[ (1.32 ± 1.16) μV vs. (1.48 ± 1.05) μV]差异无统计学意义(P>0.05); (3) 与对照组相比, 实验组 S2/S1 波幅比值[(1.17 ± 0.26) vs. (0.41 ± 0.13)]显著升高, 差异有统计学意义(P<0.05)。结论： 产后抑郁症患者感觉门控抑制能力有缺陷, P50 受损指标可能为评估 产后抑郁症患者的潜在生物学指标。     

A Decision-Tree Strategy for Combining Diagnostic Tests for Prediction

In the context of medical screening, various diagnostic tests have been developed for determining whether a disease is present in an individual. Similarly, in the context of toxicological screening, a variety of short-term assays have been developed to predict whether a chemical would be carcinogenic if tested in a long-term bioassay. In both contexts, it is a challenge to combine the results of several predictive tests in a way that improves on the predictivity of the individual tests. Increases in positive predictivity can be accompanied by decreases in negative predictivity, and vice versa. This article presents a decision-tree classification model for combining results from several independent short-term or diagnostic tests to quantify the likelihood of a true positive result (patient has disease, or chemical is carcinogenic). The decision-tree strategy determines the most advantageous sequence for conducting the predictive tests. The classification model is based on statistical confidence limits on the predictive probability of disease (carcinogenicity) rather than on the central estimate of the predictive probability. This model is applied to the assessment of the abilities of four short-term tests in the prediction of chemical carcinogenicity under the assumption of independence among the four tests, and is used to demonstrate a testing strategy for the application of three pancreatic cancer diagnostic tests.     

A Probit Latent Class Model with General Correlation Structures for Evaluating Accuracy of Diagnostic Tests

Summary Traditional latent class modeling has been widely applied to assess the accuracy of dichotomous diagnostic tests. These models, however, assume that the tests are independent conditional on the true disease status, which is rarely valid in practice. Alternative models using probit analysis have been proposed to incorporate dependence among tests, but these models consider restricted correlation structures. In this article, we propose a probit latent class model that allows a general correlation structure. When combined with some helpful diagnostics, this model provides a more flexible framework from which to evaluate the correlation structure and model fit. Our model encompasses several other PLC models but uses a parameter‐expanded Monte Carlo EM algorithm to obtain the maximum‐likelihood estimates. The parameter‐expanded EM algorithm was designed to accelerate the convergence rate of the EM algorithm by expanding the complete‐data model to include a larger set of parameters and it ensures a simple solution in fitting the PLC model. We demonstrate our estimation and model selection methods using a simulation study and two published medical studies.     

Diagnostic Tests for Primary Renal Hypouricemia

Primary renal hypouricemia is a genetic disorder characterized by defective renal uric acid (UA) reabsorption with complications such as nephrolithiasis and exercise-induced acute renal failure. The known causes are: defects in the SLC22A12 gene, encoding the human urate transporter 1 (hURAT1), and also impairment of voltage urate transporter (URATv1), encoded by SLC2A9 (GLUT9) gene. Diagnosis is based on hypouricemia (<119 μmol/L) and increased fractional excretion of UA (>10%). To date, the cases with mutations in hURAT1 gene have been reported in East Asia only. More than 100 Japanese patients have been described. Hypouricemia is sometimes overlooked; therefore, we have set up the flowchart for this disorder. The patients were selected for molecular analysis from 620 Czech hypouricemic patients. Secondary causes of hyperuricosuric hypouricemia were excluded. The estimations of (1) serum UA, (2) excretion fraction of UA, and (3) analysis of hURAT1 and URATv1 genes follow. Three transitions and one deletion (four times) in SLC22A12 gene and one nucleotide insertion in SLC2A9 gene in seven Czech patients were found. Three patients had acute renal failure and urate nephrolithiasis. In addition, five nonsynonymous sequence variants and three nonsynonymous sequence variants in SLC2A9 gene were found in two UK patients suffering from acute renal failure. Our finding of the defects in SLC22A12 and SLC2A9 genes gives further evidence of the causative genes of primary renal hypouricemia and supports their important role in regulation of serum urate levels in humans.     

Assessment of Motor Function,Sensory Motor Gating and Recognition Memory in a Novel BACHD Transgenic Rat Model for Huntington Disease

Rationale

Huntington disease (HD) is frequently first diagnosed by the appearance of motor symptoms; the diagnosis is subsequently confirmed by the presence of expanded CAG repeats (> 35) in the HUNTINGTIN (HTT) gene. A BACHD rat model for HD carrying the human full length mutated HTT with 97 CAG-CAA repeats has been established recently. Behavioral phenotyping of BACHD rats will help to determine the validity of this model and its potential use in preclinical drug discovery studies.

Objectives

The present study seeks to characterize the progressive emergence of motor, sensorimotor and cognitive deficits in BACHD rats.

Materials and Methods

Wild type and transgenic rats were tested from 1 till 12 months of age. Motor tests were selected to measure spontaneous locomotor activity (open field) and gait coordination. Sensorimotor gating was assessed in acoustic startle response paradigms and recognition memory was evaluated in an object recognition test.

Results

Transgenic rats showed hyperactivity at 1 month and hypoactivity starting at 4 months of age. Motor coordination imbalance in a Rotarod test was present at 2 months and gait abnormalities were seen in a Catwalk test at 12 months. Subtle sensorimotor changes were observed, whereas object recognition was unimpaired in BACHD rats up to 12 months of age.

Conclusion

The current BACHD rat model recapitulates certain symptoms from HD patients, especially the marked motor deficits. A subtle neuropsychological phenotype was found and further studies are needed to fully address the sensorimotor phenotype and the potential use of BACHD rats for drug discovery purposes.     

Sensory Features as Diagnostic Criteria for Autism: Sensory Features in Autism

In this study, we examined the frequency of sensory-related issues as reported by parents in a large sample of school-age adolescents and adults with autism/autism spectrum disorder (ASD) [1] as compared to a group of individuals receiving similar clinical evaluations for developmental/behavioral difficulties but whose final diagnoses were not on the autism spectrum. In no comparison were the features examined predictive of autism or autism spectrum in comparison to the non-ASD sample. Only failure to respond to noises had sensitivity above .75 in the comparison of the broader autism spectrum group, but specificity was poor. While sensory issues are relatively common in autism/ASD, they are also frequent in other disorders. These results question the rationale for including sensory items as a diagnostic criterion for autism.     

The Sensory Gating Inventory as a potential diagnostic tool for attention-deficit hyperactivity disorder

Diagnoses of attention-deficit hyperactivity disorder (ADHD) are often made rapidly in physicians' offices without thorough assessment. We examined whether adults diagnosed with ADHD would score differently from controls on a modified Sensory Gating Inventory (SGI: Hetrick et al. in Schizophr Bull 38:178-191, 2012; Kisley et al. in Psychophysiol 41:604-612, 2004), which would facilitate rapid and easy preliminary assessment of ADHD status. The modified SGI was administered to 22 controls and 22 adults with physician diagnoses of ADHD. Analysis was performed on the 17 SGI items and the three categories to which they belong (Perceptual Modulation, Distractibility, and Over-Inclusion). The Distractibility category, and its individual items, showed large group differences. In spite of a relatively small sample size, we found large effect sizes between those with and without ADHD diagnoses. The SGI is a simple, quick, paper/pencil method that may be used to facilitate accurate diagnosis of individuals experiencing ADHD symptoms, which may be especially useful when evaluations are made in settings such as physicians' offices.     

A Systematic Review of High Quality Diagnostic Tests for Chagas Disease

Background

There is significant heterogeneity in reported sensitivities and specificities of diagnostic serological assays for Chagas disease, as might be expected from studies that vary widely according to setting, research design, antigens employed, and reference standard. The purpose of this study is to summarize the reported accuracy of serological assays and to identify sources of heterogeneity including quality of research design. To avoid associated spectrum bias, our analysis was limited to cohort studies.

Methods

We completed a search of PubMed, a bibliographic review of potentially relevant articles, and a review of articles identified by a study author involved in this area of research. Studies were limited to prospective cohort studies of adults published since 1985. Measures of diagnostic accuracy were pooled using a Der Simonian Laird Random Effects Model. A subgroup analysis and meta regression were employed to identify sources of heterogeneity. The QUADAS tool was used to assess quality of included studies and Begg''s funnel plot was used to assess publication bias.

Results

Eighteen studies and 61 assays were included in the final analysis. Significant heterogeneity was found in all pre-determined subgroups. Overall sensitivity was 90% (95% CI: 89%–91%) and overall specificity was 98% (95% CI: 98%–98%).

Conclusion

Sensitivity and specificity of serological assays for the diagnosis of Chagas disease appear less accurate than previously thought. Suggestions to improve the accuracy of reporting include the enrollment of patients in a prospective manner, double blinding, and providing an explicit method of addressing subjects that have an indeterminate diagnosis by either the reference standard or index test.     

A Model for Pathological States of the Sensory System

A number of new approaches to dealing with pathological states of the sensory system have recently been devised. The concept of a threshold can serve as a model for determining not only pathological conditions but also the way such conditions develop.     

LORETA Current Source Density for Duration Mismatch Negativity and Neuropsychological Assessment in Early Schizophrenia

Introduction

Patients with schizophrenia elicit cognitive decline from the early phase of the illness. Mismatch negativity (MMN) has been shown to be associated with cognitive function. We investigated the current source density of duration mismatch negativity (dMMN), by using low-resolution brain electromagnetic tomography (LORETA), and neuropsychological performance in subjects with early schizophrenia.

Methods

Data were obtained from 20 patients meeting DSM-IV criteria for schizophrenia or schizophreniform disorder, and 20 healthy control (HC) subjects. An auditory odd-ball paradigm was used to measure dMMN. Neuropsychological performance was evaluated by the brief assessment of cognition in schizophrenia Japanese version (BACS-J).

Results

Patients showed smaller dMMN amplitudes than those in the HC subjects. LORETA current density for dMMN was significantly lower in patients compared to HC subjects, especially in the temporal lobes. dMMN current density in the frontal lobe was positively correlated with working memory performance in patients.

Conclusions

This is the first study to identify brain regions showing smaller dMMN current density in early schizophrenia. Further, poor working memory was associated with decreased dMMN current density in patients. These results are likely to help understand the neural basis for cognitive impairment of schizophrenia.     

A Financial Market Model Incorporating Herd Behaviour

Herd behaviour in financial markets is a recurring phenomenon that exacerbates asset price volatility, and is considered a possible contributor to market fragility. While numerous studies investigate herd behaviour in financial markets, it is often considered without reference to the pricing of financial instruments or other market dynamics. Here, a trader interaction model based upon informational cascades in the presence of information thresholds is used to construct a new model of asset price returns that allows for both quiescent and herd-like regimes. Agent interaction is modelled using a stochastic pulse-coupled network, parametrised by information thresholds and a network coupling probability. Agents may possess either one or two information thresholds that, in each case, determine the number of distinct states an agent may occupy before trading takes place. In the case where agents possess two thresholds (labelled as the finite state-space model, corresponding to agents’ accumulating information over a bounded state-space), and where coupling strength is maximal, an asymptotic expression for the cascade-size probability is derived and shown to follow a power law when a critical value of network coupling probability is attained. For a range of model parameters, a mixture of negative binomial distributions is used to approximate the cascade-size distribution. This approximation is subsequently used to express the volatility of model price returns in terms of the model parameter which controls the network coupling probability. In the case where agents possess a single pulse-coupling threshold (labelled as the semi-infinite state-space model corresponding to agents’ accumulating information over an unbounded state-space), numerical evidence is presented that demonstrates volatility clustering and long-memory patterns in the volatility of asset returns. Finally, output from the model is compared to both the distribution of historical stock returns and the market price of an equity index option.     

A Simple Model of Optimal Population Coding for Sensory Systems

A fundamental task of a sensory system is to infer information about the environment. It has long been suggested that an important goal of the first stage of this process is to encode the raw sensory signal efficiently by reducing its redundancy in the neural representation. Some redundancy, however, would be expected because it can provide robustness to noise inherent in the system. Encoding the raw sensory signal itself is also problematic, because it contains distortion and noise. The optimal solution would be constrained further by limited biological resources. Here, we analyze a simple theoretical model that incorporates these key aspects of sensory coding, and apply it to conditions in the retina. The model specifies the optimal way to incorporate redundancy in a population of noisy neurons, while also optimally compensating for sensory distortion and noise. Importantly, it allows an arbitrary input-to-output cell ratio between sensory units (photoreceptors) and encoding units (retinal ganglion cells), providing predictions of retinal codes at different eccentricities. Compared to earlier models based on redundancy reduction, the proposed model conveys more information about the original signal. Interestingly, redundancy reduction can be near-optimal when the number of encoding units is limited, such as in the peripheral retina. We show that there exist multiple, equally-optimal solutions whose receptive field structure and organization vary significantly. Among these, the one which maximizes the spatial locality of the computation, but not the sparsity of either synaptic weights or neural responses, is consistent with known basic properties of retinal receptive fields. The model further predicts that receptive field structure changes less with light adaptation at higher input-to-output cell ratios, such as in the periphery.     

A Hierarchical Semiparametric Model for Incorporating Intergene Information for Analysis of Genomic Data

Summary For analysis of genomic data, e.g., microarray data from gene expression profiling experiments, the two‐component mixture model has been widely used in practice to detect differentially expressed genes. However, it naïvely imposes strong exchangeability assumptions across genes and does not make active use of a priori information about intergene relationships that is currently available, e.g., gene annotations through the Gene Ontology (GO) project. We propose a general strategy that first generates a set of covariates that summarizes the intergene information and then extends the two‐component mixture model into a hierarchical semiparametric model utilizing the generated covariates through latent nonparametric regression. Simulations and analysis of real microarray data show that our method can outperform the naïve two‐component mixture model.     

A Recombinant Positive Control for Serology Diagnostic Tests Supporting Elimination of Onchocerca volvulus

Background

Serological assays for human IgG4 to the Onchocerca volvulus antigen Ov16 have been used to confirm elimination of onchocerciasis in much of the Americas and parts of Africa. A standardized source of positive control antibody (human anti-Ov16 IgG4) will ensure the quality of surveillance data using these tests.

Methodology/Principal Findings

A recombinant human IgG4 antibody to Ov16 was identified by screening against a synthetic human Fab phage display library and converted into human IgG4. This antibody was developed into different positive control formulations for enzyme-linked immunosorbent assay (ELISA) and rapid diagnostic test (RDT) platforms. Variation in ELISA results and utility as a positive control of the antibody were assessed from multiple laboratories. Temperature and humidity conditions were collected across seven surveillance activities from 2011–2014 to inform stability requirements for RDTs and positive controls. The feasibility of the dried positive control for RDT was evaluated during onchocerciasis surveillance activity in Togo, in 2014. When the anti-Ov16 IgG4 antibody was used as a standard dilution in horseradish peroxidase (HRP) and alkaline phosphatase (AP) ELISAs, the detection limits were approximately 1ng/mL by HRP ELISA and 10ng/mL by AP ELISA. Positive control dilutions and spiked dried blood spots (DBS) produced similar ELISA results. Used as a simple plate normalization control, the positive control antibody may improve ELISA data comparison in the context of inter-laboratory variation. The aggregate temperature and humidity monitor data informed temperature parameters under which the dried positive control was tested and are applicable inputs for testing of diagnostics tools intended for sub-Saharan Africa. As a packaged positive control for Ov16 RDTs, stability of the antibody was demonstrated for over six months at relevant temperatures in the laboratory and for over 15 weeks under field conditions.

Conclusions

The recombinant human anti-Ov16 IgG4 antibody-based positive control will benefit inter-laboratory validation of ELISA assays and serve as quality control (QC) reagents for Ov16 RDTs at different points of the supply chain from manufacturer to field use.