MB-COMT promoter DNA methylation is associated with working-memory processing in schizophrenia patients and healthy controls

Many genetic studies report mixed results both for the associations between COMT polymorphisms and schizophrenia and for the effects of COMT variants on common intermediate phenotypes of the disorder. Reasons for this may include small genetic effect sizes and the modulation of environmental influences. To improve our understanding of the role of COMT in the disease etiology, we investigated the effect of DNA methylation in the MB-COMT promoter on neural activity in the dorsolateral prefrontal cortex during working memory processing as measured by fMRI - an intermediate phenotype for schizophrenia. Imaging and epigenetic data were measured in 102 healthy controls and 82 schizophrenia patients of the Mind Clinical Imaging Consortium (MCIC) study of schizophrenia. Neural activity during the Sternberg Item Recognition Paradigm was acquired with either a 3T Siemens Trio or 1.5T Siemens Sonata and analyzed using the FMRIB Software Library (FSL). DNA methylation measurements were derived from cryo-conserved blood samples. We found a positive association between MB-COMT promoter methylation and neural activity in the left dorsolateral prefrontal cortex in a model using a region-of-interest approach and could confirm this finding in a whole-brain model. This effect was independent of disease status. Analyzing the effect of MB-COMT promoter DNA methylation on a neuroimaging phenotype can provide further evidence for the importance of COMT and epigenetic risk mechanisms in schizophrenia. The latter may represent trans-regulatory or environmental risk factors that can be measured using brain-based intermediate phenotypes.     

Estradiol: A key biological substrate mediating the response to cocaine in female rats

A consistent finding in drug abuse research is that males and females show differences in their response to drugs of abuse. In women, increased plasma estradiol is associated with increased vulnerability to the psychostimulant and reinforcing effects of drugs of abuse. Our laboratory has focused on the role of estradiol in modulating the response to cocaine. We have seen that ovariectomy increases the locomotor response to a single cocaine injection, whereas estradiol exacerbates the locomotor response to repeated cocaine administration. Cocaine-induced sensitization of brain activity, as measured by fMRI, is also dependent on plasma estradiol. Moreover, we observed that although all ovariectomized rats show conditioned place preference to cocaine, it is more robust in ovariectomized rats with estradiol.Opioid receptors are enriched in brain regions associated with pleasure and reward. We find that in females, the effectiveness of kappa opioid agonists in decreasing the locomotor response to repeated cocaine varies with plasma estradiol. We also find that estradiol regulates the density of mu opioid receptors in brains areas associated with reward. These data hint that in females, estradiol modulates the behavioral effects of cocaine by regulating mu and kappa opioid signaling in mesocorticolimbic brain structures. Identifying the mechanisms that mediate differences in vulnerability to drugs of abuse may lead to effective therapeutic strategies for the treatment and prevention of addiction and relapse. We encourage health practitioners treating persons addicted to drugs to consider gender differences in response to particular pharmacotherapies, as well the sex steroid milieu of the patient.     

视皮层分区及其fMRI 研究进展

血氧水平依赖功能磁共振成像（BOLD—fMRI）作为一种无创、可精确定位的脑功能研究技术,已广泛应用于视觉系统的研究中,并取得了许多重要成果,本文就fMRI研究进展及其在大脑视觉皮层功能分区中的应用做一综述。     

功能磁共振和脑电神经成像技术与大脑刺激相结合的研究进展

随着对神经机制问题阐述水平的迅速提高,所应用的神经成像技术、方法及各种工具的复杂程度也在不断提高．一方面是神经成像技术本身的不断发展,另一方面则是大脑直接刺激与神经成像技术同步记录方法的发展．经颅磁刺激-功能磁共振成像同步技术(TMS-fMRI)和经颅磁刺激-脑电技术(TMS-EEG)能为研究大脑网络的功能和有效连通性提供技术手段,该技术在多种认知领域的发展和应用,为神经科学、认知心理学、神经信息学等学科的研究者对人脑的研究开启了多条通道,更加有利于深入地理解人类大脑的工作机制．     

Resting‐state networks of the neonate brain identified using independent component analysis

Resting‐state functional magnetic resonance imaging (rs‐fMRI) has been successfully used to probe the intrinsic functional organization of the brain and to study brain development. Here, we implemented a combination of individual and group independent component analysis (ICA) of FSL on a 6‐min resting‐state data set acquired from 21 naturally sleeping term‐born (age 26 ± 6.7 d), healthy neonates to investigate the emerging functional resting‐state networks (RSNs). In line with the previous literature, we found evidence of sensorimotor, auditory/language, visual, cerebellar, thalmic, parietal, prefrontal, anterior cingulate as well as dorsal and ventral aspects of the default‐mode‐network. Additionally, we identified RSNs in frontal, parietal, and temporal regions that have not been previously described in this age group and correspond to the canonical RSNs established in adults. Importantly, we found that careful ICA‐based denoising of fMRI data increased the number of networks identified with group‐ICA, whereas the degree of spatial smoothing did not change the number of identified networks. Our results show that the infant brain has an established set of RSNs soon after birth.     

睡眠剥夺中感觉运动皮层和视觉皮层神经活动及警觉水平的改变

在睡眠剥夺(sleep deprivation, SD)过程中,人类大脑的神经活动和警觉水平如何受到影响,尤其是感觉运动和视觉系统,目前仍是研究的热点。静息状态功能磁共振成像(resting state functional magnetic resonance imaging,rfMRI)作为一种反映人脑自发活动的非侵入式成像技术,在睡眠剥夺的研究中得到了广泛应用。本研究采用9次重复rfMRI和心理运动警觉任务(psychomotor vigilance task,PVT),以探索23名志愿者在整个36小时的睡眠剥夺过程中神经活动和警觉水平的变化。我们采用基于PVT的平均反应时间(mean reaction time, MRT)和失效率(lapses ratio, LR)评估警觉水平的变化。我们采用基于rfMRI的区域同质性(region homogeneity,ReHo)和低频波动幅度(amplitude of low frequency fluctuation,ALFF)评估大脑神经活动变化。结果表明,感觉运动网络(sensorimotor network, SMN)和视觉区域(visual network, VN)是受到睡眠剥夺影响最严重的区域。我们采用组独立成分分析(Group Independent component analysis, GICA)将视觉相关区域划分为视觉I区、视觉II区、视觉关联区,并从解剖自动标记(Anatomical automatic labeling,AAL)模板中提取运动感觉相关区域,包括中央前/中央后回、中央旁小叶和辅助运动区。我们发现,睡眠剥夺后16 - 30小时脑神经活动及警惕性下降。我们采用2×3重复测量方差分析,探讨睡眠压力、昼夜节律及其交互作用对感觉运动相关和视觉相关脑区神经活动的影响。我们观察到睡眠压力与交互作用对感觉运动相关区域和视觉相关区域有显著影响。我们采用皮尔逊相关系数评估警觉水平变化与感觉运动相关和视觉相关脑区神经活动变化的关系。睡眠剥夺期间所有感觉运动相关区域的神经活动变化与警觉变化均存在显著的相关关系。我们的研究结果证实,睡眠剥夺从第一天24：00开始改变SMN和VN的警戒水平和神经活动,睡眠压力和昼夜节律在睡眠剥夺期间调节SMN和VN的神经活动。此外,昼夜节律的效应受到睡眠压力的显著调节。感觉运动相关区域和视觉相关区域的增强导致他们远程连接的减弱,这可能是睡眠剥夺期间响应时间变慢的原因。     

Decoding visual roughness perception: an fMRI study

Abstract

The neural substrates of tactile roughness perception have been investigated by many neuroimaging studies, while relatively little effort has been devoted to the investigation of neural representations of visually perceived roughness. In this human fMRI study, we looked for neural activity patterns that could be attributed to five different roughness intensity levels when the stimuli were perceived visually, i.e., in absence of any tactile sensation. During functional image acquisition, participants viewed video clips displaying a right index fingertip actively exploring the sandpapers that had been used for the behavioural experiment. A whole brain multivariate pattern analysis found four brain regions in which visual roughness intensities could be decoded: the bilateral posterior parietal cortex (PPC), the primary somatosensory cortex (S1) extending to the primary motor cortex (M1) in the right hemisphere, and the inferior occipital gyrus (IOG). In a follow-up analysis, we tested for correlations between the decoding accuracies and the tactile roughness discriminability obtained from a preceding behavioural experiment. We could not find any correlation between both although, during scanning, participants were asked to recall the tactilely perceived roughness of the sandpapers. We presume that a better paradigm is needed to reveal any potential visuo-tactile convergence. However, the present study identified brain regions that may subserve the discrimination of different intensities of visual roughness. This finding may contribute to elucidate the neural mechanisms related to the visual roughness perception in the human brain.     

A Method for Investigating Age-related Differences in the Functional Connectivity of Cognitive Control Networks Associated with Dimensional Change Card Sort Performance

The ability to adjust behavior to sudden changes in the environment develops gradually in childhood and adolescence. For example, in the Dimensional Change Card Sort task, participants switch from sorting cards one way, such as shape, to sorting them a different way, such as color. Adjusting behavior in this way exacts a small performance cost, or switch cost, such that responses are typically slower and more error-prone on switch trials in which the sorting rule changes as compared to repeat trials in which the sorting rule remains the same. The ability to flexibly adjust behavior is often said to develop gradually, in part because behavioral costs such as switch costs typically decrease with increasing age. Why aspects of higher-order cognition, such as behavioral flexibility, develop so gradually remains an open question. One hypothesis is that these changes occur in association with functional changes in broad-scale cognitive control networks. On this view, complex mental operations, such as switching, involve rapid interactions between several distributed brain regions, including those that update and maintain task rules, re-orient attention, and select behaviors. With development, functional connections between these regions strengthen, leading to faster and more efficient switching operations. The current video describes a method of testing this hypothesis through the collection and multivariate analysis of fMRI data from participants of different ages.     

Extracting Visual Evoked Potentials from EEG Data Recorded During fMRI-guided Transcranial Magnetic Stimulation

Transcranial Magnetic Stimulation (TMS) is an effective method for establishing a causal link between a cortical area and cognitive/neurophysiological effects. Specifically, by creating a transient interference with the normal activity of a target region and measuring changes in an electrophysiological signal, we can establish a causal link between the stimulated brain area or network and the electrophysiological signal that we record. If target brain areas are functionally defined with prior fMRI scan, TMS could be used to link the fMRI activations with evoked potentials recorded. However, conducting such experiments presents significant technical challenges given the high amplitude artifacts introduced into the EEG signal by the magnetic pulse, and the difficulty to successfully target areas that were functionally defined by fMRI. Here we describe a methodology for combining these three common tools: TMS, EEG, and fMRI. We explain how to guide the stimulator''s coil to the desired target area using anatomical or functional MRI data, how to record EEG during concurrent TMS, how to design an ERP study suitable for EEG-TMS combination and how to extract reliable ERP from the recorded data. We will provide representative results from a previously published study, in which fMRI-guided TMS was used concurrently with EEG to show that the face-selective N1 and the body-selective N1 component of the ERP are associated with distinct neural networks in extrastriate cortex. This method allows us to combine the high spatial resolution of fMRI with the high temporal resolution of TMS and EEG and therefore obtain a comprehensive understanding of the neural basis of various cognitive processes.