脑功能核磁共振成像在精神疾病中的应用

主要介绍了几种脑功能核磁共振成像方法以及在精神疾病中的研究情况.血氧水平依赖fMRI (BOLD-fMRI)是目前应用最广泛的fMRI技术,可利用神经激活后对局部血流的影响,间接显示神经活动.灌注加权成像是直接测定脑血流的fMRI技术,但由于它的时间分辨率比较低,对快速的脑功能难以进行研究.扩散加权象目前主要用于脑缺血的早期诊断,利用该技术也可示踪神经通路.化学位移成像能够检测局部组织代谢产物的含量,可反映不同脑区能量和物质代谢的状况,也是一种脑功能的研究手段.尽管这些技术在神经、心理学领域已经取得非常可喜的进展,目前fMRI在精神疾病方面的工作较少,相信随着技术的改进,fMRI必将在精神疾病方面大显身手.     

柠檬醛长时程嗅觉吸入的脑功能活动MEMRI研究

本文使用设计的嗅觉吸入装置使大鼠吸入挥发性柠檬醛或无气味空气，之后使用锰增强磁共振成像（MEMRI）的方法，观察长时程（24 h）吸入柠檬醛之后，大鼠脑功能活动变化情况．基于体素分析和感兴趣区（ROI）分析结果显示，与对照组相比，长时程吸入柠檬醛组大鼠伏隔核中心部（AcbC）、嗅小球层（GL）等脑区功能活动增强；而该组大鼠视皮层（VC）、听觉皮层（AC）、压后皮层（RSC）等脑区锰累积显著减少．且长时程吸入柠檬醛之后，大鼠脑区GL与关联的脑区功能相关性显著增强．从而表明MEMRI可用于长时程嗅觉吸入刺激的脑功能研究，并极具应用前景．     

核磁共振脑成像技术

 人类对自己大脑的认识相对其他器官来说非常少,一个重要的原因是大脑功能的复杂性;另一个重要的原因是大脑隐藏在封闭的头颅里,我们很难直接观察到它。但是近几年新发展起来的功能性核磁共振脑成像技术在无创伤的情况下,不仅能对大脑成像,还能辨别大脑进行思维时激活的区域,该技术被称为“人类思维的阅读器”,有人把它形象地描述为对人脑活动“拍电影”。核磁共振脑成像技术为人脑功能研究打开了一扇大门。下面介绍这种技术的理论基础及生理学基础。     

视觉非随意注意的近红外脑功能成像技术与事件相关脑电位检测技术研究

近红外脑功能成像技术(fNIRI)是近年来发展起来的新技术,与心理学研究常用的事件相关脑电位检测技术(ERP)相比,能提供电生理信号之外的与脑功能活动相关的血液动力学信息。设计了非随意注意的经典范式,对同一组被试者分别使用近红外脑功能成像技术和事件相关脑电位检测技术检测其在实验过程中脑活动变化,然后对两种技术检测的结果进行处理和比较分析。结果发现近红外脑功能成像技术测出的非随意注意源定位在前额叶,与其相关P3a脑电皮层分布一致,甚至近红外脑功能成像技术测出的源定位范围可以缩小到Brodmann46区;血液激活先于P3a并在P3a完成后显著增强的现象支持深入研究脑机理的可能性。因此,近红外脑功能成像技术可有效地应用于脑的高级功能研究。     

人脑默认模式网络的动力学行为

大脑具有自适应、自组织、多稳态等重要特征,是典型的复杂系统.人脑在静息态下的关键功能子网络--默认模式网络(DMN)的激活处于多状态间持续跳转的非平衡过程,揭示该过程背后的动力学机制具有重要的科学意义和临床应用前景.本文基于功能磁共振获得的血氧水平依赖(BOLD)信号,建立了DMN吸引子跳转非平衡过程的能量图景、吸引子非联通图、跳转关系网络等;以高级视觉皮层和听觉等皮层活动为例,通过对应激活DMN状态空间的分布,以及XGBoost、深度神经网络等算法验证了DMN状态变化与外部脑区状态的密切依赖关系;通过偏相关、收敛交叉映射等方法分析了DMN内各个脑区之间的相互作用.本文结果有助于理解静息态下大脑内在非平衡过程的动力学机制,以及从动力学的角度探索具有临床意义的脑功能障碍生物标志物.     

功能磁共振成像技术及其在脑科学研究中的应用

功能磁共振成像(functional magnetic resonance imaging,fMRI)是用磁共振成像的方法研究人脑和神经系统的功能,它是磁共振成像的一种应用和深入发展.磁共振成像(magnetic resonance imaging,MRI)是核磁共振成像的简称,它是基于核磁共振(nuclear magnetic resonance,NMR)这一物理现象发展起来的.1946年物理学家首先发现核磁共振现象,直到70年代初,它一直沿着高分辨核磁共振波谱学的方向发展.1972年达马迪安(R.Damadian)提出磁共振成像的设想,并指出可以用磁共振成像仪扫描人体检查疾病.1973年劳特伯(P.Lauterbur)在<自然>杂志上发表了用试管样品得到的磁共振截面像,显示了磁共振成像的可能性.从此开始了磁共振成像的发展时期.1980年在实验室中获得了足够清晰的有医学诊断意义的人的头部磁共振图像.磁共振成像仪逐渐形成产业,开始进入医院,主要用于观测人体内部解剖学结构,确定肿瘤和其他疾病的位置.1990年对动物的实验表明,有可能用磁共振成像研究大脑功能.1991年发表了第一幅有意义的人的大脑功能的图像,显示出视觉刺激在大脑的反应,开始了脑功能磁共振成像的研究.至今刚刚过了几年的时间,这一研究领域已经得到了迅速发展.     

基于新的微小中风模型的脑功能与疾病的光学成像研究

武汉光电国家实验室李鹏程研究组致力于采用高时间和空间分辨的光学成像方法来研究脑功能活动与神经系统疾病的病理机制。为了实时长时程全场高分辨地追踪中风的发生发展过程,该小组在综合了两种传统微小中风模型（皮层微动脉结扎模型与铜环压迫皮层模型）各自优势的基础上,提出了一种改进的微小中风模型,可以实现将缺血灶定位于特定的功能区域（如大鼠中主管胡须感觉的桶状皮层）,并且可以很便利地开展血管再通,从而研究缺血再灌注损伤机制与慢性恢复期的功能重组现象。这种模型将中风病灶定位在特定的皮层表面区域,可以最大程度地发挥光学成像的无损与高分辨优势。这项研究对建立研究功能成像生理基础、再灌注损伤以及中风康复机制的新平台有重要意义。     

功能磁共振成像

功能磁共振成像功能磁共振成像（ＦＭＲＩ）是一种利用快速磁共振成像方法探测大脑功能区域的新工具．常规的磁共振成像（ＭＲＩ）是观测高分辨率的大脑的解剖学图像，而ＦＭＲＩ只观测真正执行、控制、监视某一特定功能的那一部分的大脑结构．与已有的其他功能成像方法相...     

磁刺激穴位复杂脑功能网络构建与分析

本文采用互信息方法对磁刺激内关穴过程中的脑电信 号进行了两两通道间非线性时域关联特性分析, 构建了不同频率刺激前、刺激中、刺激后的脑功能网络, 并基于复杂网络理论对脑功能网络的特征进行了深入研究. 结果表明, 磁刺激频率为3 Hz 时, 大脑功能网络的平均度、平均聚类系数和全局效率与刺激前相比均有显著升高, 平均路径长度显著降低, 并且相应脑功能网络的"小世界"属性有所增强, 信息在大脑各区域间的传递更加高效. 本研究首次开展了磁刺激穴位复杂脑功能网络的构建与分析, 为探索磁刺激穴位对大脑神经调节的作用和机理提供新思路和新方法. 关键词： 复杂网络 磁刺激 脑功能网络 互信息     

脑功能磁共振成像在人类嗅觉研究中的应用

在人类的5种主要感觉中,嗅觉是最广泛、古老、直接和内在的感觉.这些特性使人们对人类嗅觉的研究异常艰难,以致于直到今天人们对嗅觉的功能仍不清楚,而对大脑的功能机制所知更少.与其他基于物理原理的方法一样,磁共振成像技术的广泛应用极大地推动了整个生命科学的发展.脑功能磁共振成像的优势(高分辨率、高对比度、无损性和无放射性等)为人们研究嗅觉高级中枢以及与嗅觉相关行为的脑机制等提供了强有力的技术手段.文章在简单介绍嗅觉知识的基础上,着重讨论了近十年来,脑功能磁共振成像技术在人类嗅觉研究中所取得的成果.     

Identification of activated regions during a language task

Functional magnetic resonance imaging (fMRI) techniques are based on the assumption that changes in neural activity are accompanied by modulation in the blood-oxygenation-level-dependent (BOLD) signal. In addition to conventional increases in BOLD signals, sustained negative BOLD signal changes are occasionally observed in many fMRI experiments, which show regions of cortex that seem to respond in antiphase with primary stimulus. The existence of this so-called negative BOLD response (NBR) has been observed and investigated in many functional studies. Several theoretical mechanisms have been proposed to account for it, but its origin has never been fully explained. In this study, the variability of fMRI activation, including the sources of the negative BOLD signal, during phonological and semantic language tasks, was investigated in six right-handed healthy subjects. We found significant activations in the brain regions, mainly in the left hemisphere, involved in the language stimuli [prominent in the inferior frontal gyrus, approximately Brodmann Areas (BA)7, BA44, BA45 and BA47, and in the precuneus]. Moreover, we observed activations in motor regions [precentral gyrus and supplementary motor area (SMA)], a result that suggests a specific role of these areas (particularly the SMA) in language processing. Functional analysis have also shown that certain brain regions, including the posterior cingulate cortex and the anterior cingulate cortex, have consistently greater activity during resting states compared to states of performing cognitive tasks. In our study, we observed diffuse NBR at the cortical level and a stronger negative response in correspondence to the main sinuses. These phenomena seem to be unrelated to a specific neural activity, appearing to be expressions of a mechanical variation in hemodynamics. We discussed about the importance of these responses that are anticorrelated with the stimulus. Our data suggest that particular care must be considered in the interpretation of fMRI findings, especially in the case of presurgical studies.     

Nonlinear blood oxygen level-dependent responses for transient activations and deactivations in V1 - insights into the hemodynamic response function with the balloon model

We report studies of the nonlinear nature of blood oxygen level-dependent (BOLD) responses to short transient deactivations in human visual cortex. Both functional magnetic resonance imaging (fMRI) and near-infrared spectroscopy (NIRS) have been used to compare and contrast the hemodynamic response functions (HRFs) associated with transient activation and deactivation in primary visual cortex. We show that signal decreases for short duration deactivations are smaller than corresponding signal increases in activation studies. Moreover, the standard balloon model of BOLD effects may be modified to account for the observed nonlinear nature of deactivations by appropriate changes to simple hemodynamic parameters without recourse to new assumptions about the nature of the coupling between activity and oxygen use.     

Impact of intravenous nicotine on BOLD signal response to photic stimulation

Functional magnetic resonance imaging (fMRI) is increasingly being applied in the study of brain effects of nicotine. In addition, because tobacco smoking is common, many subjects studied with fMRI for other reasons may have appreciable levels of nicotine in plasma and brain during scanning. However, there is concern that the vascular effects of nicotine may alter the coupling between blood oxygen level dependent (BOLD) signal and neuronal activity. The objective of this study was to test for evidence of alteration of BOLD signal response of occipital cortex, a region with a relatively low concentration of neuronal nicotine receptors, to photic stimulation during intravenous infusion of nicotine. Nine nicotine dependent healthy smokers were withdrawn from nicotine under controlled conditions and then scanned while receiving photic stimulation and successive intravenous infusions of saline and nicotine. No evidence for an effect of nicotine on BOLD signal response to photic stimulation was detected at the doses studied. This observation suggests that nicotine does not alter the coupling between BOLD signal and neuronal activity in the visual cortex.     

Nonlinear responses of cerebral blood volume, blood flow and blood oxygenation signals during visual stimulation

Hemodynamic-based functional magnetic resonance imaging (fMRI) techniques provide a great utility for noninvasive functional brain mapping. However, because the hemodynamic signals reflect underlying neural activity indirectly, characterization of these signals following brain activation is essential for experimental design and data interpretation. In this report, the linear (or nonlinear) responses to neuronal activation of three hemodynamic parameters based primarily on changes of cerebral blood volume, blood flow and blood oxygenation were investigated by testing these hemodynamic responses' additivity property. Using a recently developed fMRI technique that acquires vascular space occupancy (VASO), arterial spin labeling (ASL) perfusion and blood oxygenation level-dependent (BOLD) signals simultaneously, the additivity property of the three hemodynamic responses in human visual cortex was assessed using various visual stimulus durations. Experiments on healthy volunteers showed that all three hemodynamic-weighted signals responded nonlinearly to stimulus durations less than 4 s, with the degree of nonlinearity becoming more severe as the stimulus duration decreased. Vascular space occupancy and ASL perfusion signals showed similar nonlinearity properties, whereas the BOLD signal was the most nonlinear. These data suggest that caution should be taken in the interpretation of hemodynamic-based signals in fMRI.     

Percept-related activity in the human somatosensory system: functional magnetic resonance imaging studies

In this paper, we review blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies addressing the neural correlates of touch, thermosensation, pain and the mechanisms of their cognitive modulation in healthy human subjects. There is evidence that fMRI signal changes can be elicited in the parietal cortex by stimulation of single mechanoceptive afferent fibers at suprathreshold intensities for conscious perception. Positive linear relationships between the amplitude or the spatial extents of BOLD fMRI signal changes, stimulus intensity and the perceived touch or pain intensity have been described in different brain areas. Some recent fMRI studies addressed the role of cortical areas in somatosensory perception by comparing the time course of cortical activity evoked by different kinds of stimuli with the temporal features of touch, heat or pain perception. Moreover, parametric single-trial functional MRI designs have been adopted in order to disentangle subprocesses within the nociceptive system.

Available evidence suggest that studies that combine fMRI with psychophysical methods may provide a valuable approach for understanding complex perceptual mechanisms and top-down modulation of the somatosensory system by cognitive factors specifically related to selective attention and to anticipation. The brain networks underlying somatosensory perception are complex and highly distributed. A deeper understanding of perceptual-related brain mechanisms therefore requires new approaches suited to investigate the spatial and temporal dynamics of activation in different brain regions and their functional interaction.     

Rate dependence of human visual cortical response due to brief stimulation: an event-related fMRI study

The human brain response to a wide range of visual stimulus rates presented over a prolonged time period has been investigated by various neuroimaging techniques. However, to date, no imaging study has been performed to study the dynamic human brain response to various stimulus rates when presented in a short time. This report describes activation in the human brain due to brief visual stimulus presentation (1 s) for stimulus rates varying from 1 to 20 Hz using event-related functional MRI (fMRI). Our results show that the amplitude of the fMRI response increases with the stimulus frequency and plateaus at 6 Hz. This finding differs slightly from the results of previous blocked task paradigm experiments (with a longer time of stimulus presentation), in which the response peaks at approximately 8 Hz and then decreases. Our results are in close agreement with previously published psychophysical studies, suggesting that the fMRI signal in this experiment is indicative of cortical activity related to visual processing.     

A comparison of Gamma and Gaussian dynamic convolution models of the fMRI BOLD response

Blood oxygenation level-dependent (BOLD) contrast-based functional magnetic resonance imaging (fMRI) has been widely utilized to detect brain neural activities and great efforts are now stressed on the hemodynamic processes of different brain regions activated by a stimulus. The focus of this paper is the comparison of Gamma and Gaussian dynamic convolution models of the fMRI BOLD response. The convolutions are between the perfusion function of the neural response to a stimulus and a Gaussian or Gamma function. The parameters of the two models are estimated by a nonlinear least-squares optimal algorithm for the fMRI data of eight subjects collected in a visual stimulus experiment. The results show that the Gaussian model is better than the Gamma model in fitting the data. The model parameters are different in the left and right occipital regions, which indicate that the dynamic processes seem different in various cerebral functional regions.     

Direct measurement of oxygen extraction with fMRI using 6% CO2 inhalation

The blood-oxygenation-level-dependent (BOLD) signal is an indirect hemodynamic signal that is sensitive to cerebral blood flow (CBF), cerebral blood volume (CBV) and cerebral metabolic rate of oxygen. Therefore, the BOLD signal amplitude and dynamics cannot be interpreted unambiguously without additional physiological measurements, and thus, there remains a need for a functional magnetic resonance imaging (fMRI) signal, which is more closely related to the underlying neuronal activity. In this study, we measured CBF with continuous arterial spin labeling, CBV with an exogenous contrast agent and BOLD combined with intracortical electrophysiological recording in the primary visual cortex of the anesthetized monkey. During inhalation of 6% CO2, it was observed that CBF and CBV are not further increased by a visual stimulus, although baseline CBF for 6% CO2 is below the maximal value of CBF. In contrast, the electrophysiological response to the stimulation was found to be preserved during hypercapnia. As a consequence, the simultaneously measured BOLD signal responds negatively to a visual stimulation for 6% CO2 inhalation in the same voxels responding positively during normocapnia. These observations suggest that the fMRI response to a sensory stimulus for 6% CO2 inhalation occurs in the absence of a hemodynamic response, and it therefore directly reflects oxygen extraction into the tissue.     

Influence of baseline hematocrit and hemodilution on BOLD fMRI activation.

Current understanding of blood oxygenation level dependent (BOLD) fMRI physiology predicts a close relationship between BOLD signal and blood hematocrit level. However, neither this relationship nor its effect on BOLD percent activation (BPA) has been empirically examined in man. To that end, BPA in primary visual cortex in response to photic stimulation was determined in a group of 24 normal subjects. A positive linear relationship between BPA and hematocrit was seen, particularly in men. To evaluate the effect of change in hematocrit on BPA, 9 men were studied before and following isotonic saline hemodilution, resulting in an average 6% reduction in hematocrit and an 8-31% reduction in BPA. No significant change in the number of activated pixels was seen. A model of predicted BPA as a function of hematocrit and vessel size was developed, and results from this model closely mirrored the empiric data. These results suggest that hematocrit significantly influences the magnitude of BPA and that such baseline factors should be accounted for when comparing BOLD data across groups of subjects, particularly in the many instances in which hematocrit may vary systematically. Such instances include several disease states as well as studies involving sex differences, drug administration, stress and other factors. Finally, the robust agreement between predicted and empiric data serves to validate a semiquantitative approach to the analysis of BOLD fMRI data.     

Dynamics and nonlinearities of the BOLD response at very short stimulus durations

In designing a functional imaging experiment or analyzing data, it is typically assumed that task duration and hemodynamic response are linearly related to each other. However, numerous human and animal studies have previously reported a deviation from linearity for short stimulus durations (<4 s). Here, we investigated nonlinearities of blood-oxygenation-level-dependent (BOLD) signals following visual stimulation of 5 to 1000 ms duration at two different luminance levels in human subjects. It was found that (a) a BOLD response to stimulus durations as short as 5 ms can be reliably detected; this stimulus duration is shorter than employed in any previous study investigating BOLD signal time courses; (b) the responses are more nonlinear than in any other previous study: the BOLD response to 1000 ms stimulation is only twice as large as the BOLD response to 5 ms stimulation although 200 times more photons were projected onto the retina; (c) the degree of nonlinearity depends on stimulus intensity; that is, nonlinearities have to be characterized not only by stimulus duration but also by stimulus features like luminance. These findings are especially of most practical importance in rapid event-related functional magnetic resonance imaging (fMRI) experimental designs. In addition, an 'initial dip' response--thought to be generated by a rapid increase in cerebral metabolic rate of oxygen metabolism (CMRO2) relative to cerebral blood flow--was observed and shown to colocalize well with the positive BOLD response. Highly intense stimulation, better tolerated by human subjects for short stimulus durations, causes early CMRO2 increase, and thus, the experimental design utilized in this study is better for detecting the initial dip than standard fMRI designs. These results and those from other groups suggest that short stimulation combined with appropriate experimental designs allows neuronal events and interactions to be examined by BOLD signal analysis, despite its slow evolution.