功能磁共振成像在认知功能领域的研究进展

功能磁共振成像(functional magnetic resomnce imaging，fMRI)是九十年代初逐步发展起来的一种全新的磁共振成像技术。它把神经代谢活动的检测与高分辨率磁共振成像结合起来，能够准确地对神经元活动进行定位，并且具有较好的可重复性，无创伤、无侵人性等优点。目前fMRI在神经科学领域的应用已愈来愈广泛，特别为人脑高级神经功能的研究提供了很好的研究手段，在神经心理学与认知领域的研究已取得了一系列令人鼓舞的进展。本文主要就近年来fMRI在认知方面的研究进展作一概述。     

fMRI及DTI技术在成人工作记忆研究的初步探索

目的：联合应用脑功能磁共振成像（BOLD—fMRI）和弥散张量成像（DTI）两种磁共振技术,探索工作记忆功能激活部位与叶间白质纤维束的关系。方法：健康志愿者16名,以步进式视觉累加试验作为刺激模式,扫描获得fMRI激活图及各向异性（FA）图。将两者叠加,选取双侧额顶叶白质兴趣区测量其部分FA值。结果：①额顶叶皮质为工作记忆功能最主要的激活区;②脑的激活像素几乎均位于FA程度低的区域（P〈0．01）;③左额顶间白质FA值较对侧高（P〈0．02）。结论：联合应用fMRI和DTI技术提示成人工作记忆功能与额顶叶白质纤维髓鞘化程度密切相关。     

ERP-fMRI同步记录在认知功能成像中的应用

认知功能成像是指利用各种成像技术对大脑认知功能活动进行显示的过程,包括事件相关电位（event-related potentials,ERPs）、功能磁共振成像（functional magnetic resonance imaging,fMRI）、正电子发射计算机断层（positron emission tomography,PET）等。当前在脑认知功能的研究中ERPs和fMRI研究应用较多,而单独应用ERPi或fMRI进行研究应用都有明显的缺点：     

功能磁共振成像在神经精神药理研究中的应用

功能磁共振成像（fMRI）为可在体采集生物信号间接反映神经元活动的无创性技术，是目前探寻人脑功能的有效工具之一。fMRI技术的成熟及完善，使其能够用于探讨药物对中枢神经系统的作用机制，广泛应用于物质成瘾及神经精神活性药物等方面的研究。我们就fMRI在神经精神药理方面的应用进展，作如下综述。     

BOLD-fMRI和DTI结合神经导航在枕叶视觉功能区附近病变切除中的应用

目的 探讨血氧水平依赖性功能磁共振成像（BOLD - fMRI）与磁共振弥散张量成像技术(DTI)融合结合神经导航在枕叶视觉功能区附近病变切除术中的应用价值。方法 利用BOLD-fMRI、DTI结合神经导航进行图像融合,在20例视觉功能区附近病变患者术前设计手术入路,术中定位视觉功能区,指导手术,合理保护功能区,切除病变。结果 15例镜下全切除,5例大部切除。术后复查MRI及DTI视皮层及视辐射保护完好。结论 BOLD - fMRI和DTI融合技术在神经导航下应用可以准确确定大脑枕叶视觉功能区和视辐射走行,术前精确定位功能区,提高病变切除程度,降低术后致残率,提高患者术后生活质量。     

帕金森病的功能磁共振成像研究进展

帕金森病（PD）的主要病理改变是黑质多巴胺能神经元变性坏死并引起多巴胺递质减少,通过神经环路可引起包括脑皮质在内广泛的功能及结构改变.功能磁共振成像（fMRI）作为一项功能影像技术能灵敏地检测出这些变化,进而有可能为PD早期诊断提供依据.本文就PD的fMRI研究进展进行综述.     

功能磁共振成像技术在神经心理疾病研究中的应用

Ogawa等于1990年首次在活体大鼠显示了血氧浓度对脑血管显影的影响。奠定了功能磁共振成像（fMRI）的实验基础。1991年Kwong小组和Ogawa小组分别在美国哈佛大学麻省总医院和明尼苏达大学独立完成了世界上第一批人脑fMRI实验。从而揭开了脑功能研究历史的崭新一页。该项技术以脱氧血红蛋白为内源性对比剂，是一种完全不需要放射性核素和其他对比剂的非侵人性体层扫描成像技术。并具有较高的空间分辨力和可在同一个体反复测量的特点。从而大大提高了定位的准确性。目前相关研究已经成为神经科学、心理科学和认知神经科学领域最为活跃的研究方向。而随着数据采集和分析技术的发展以及基础研究的积累。fMRI近年来也开始逐渐应用于临床神经科学的研究，并取得了令人瞩目的成就，该项技术正逐渐从基础研究走向临床应用。     

功能磁共振与皮层电刺激定位感觉运动区的比较

目的 通过功能磁共振(fMRI)与皮层电刺激做点对点的比较,以判断fMRI对感觉运动区定位的精确性,从而评价其在功能定位中的意义及其临床应用价值.方法 对14例EEG示异常放电部位位于感觉运动区的难治性癫痫患者,术前采用双手握拳-伸缩运动任务进行血氧依赖水平(BOLD)扫描,运用BOLD技术的fMRI定位皮质感觉运动区.皮层电极植入术后给予头颅连续无间断CT扫描获取电极与颅骨的对应关系,通过神经导航仪将CT、fMRI影像与导航序列MRI图像融合后,得出含有皮层激活区和电极的融合图像建立三维立体图像,与皮层电刺激.结果进行比较,以评价fMRI定位皮质感觉运动区的准确性.结果 14例fMRI可见激活部位主要分布于对侧中央区、辅助运动区和小脑.其中11例成功完成皮层电刺激,结果显示fMRI与电刺激的吻合率为91.7%.结论 BOLD技术具有较高的敏感性和精确率,对感觉运动区定位有重要的临床应用价值.     

静息态脑功能磁共振在精神障碍中的研究进展

脑功能磁共振是应用功能性磁共振成像(functional magnetic resonance imaging, fMRI)测量脑神经元活动所致血流动力学的改变,以确定脑功能的反应区域.fMRI一般采用血氧水平依赖性(blood oxygen level dependent, BOLD)信号[1].由于其无创性的最大优势,近十年来fMRI在精神疾病的研究中发挥越来越大的作用.目前大多数的fMRI研究通过执行任务或给予外在刺激得到脑功能的变化,对照静息状态以BOLD信号改变的形式反映在大脑的相应区域,称为任务态[2].1995年,Biswal等[3]最先报道在无任何运动行为的情况下,大脑左侧躯体运动皮层的自发BOLD信号波动与右侧躯体运动皮层的自发信号波动相关.这个观察结果说明自发的BOLD信号活动并不是无意义的,由此引发了一系列非任务态,即静息态的脑功能磁共振的研究.     

癫(癎)fMRI的研究与进展

功能磁共振成像(fMRI)是利用磁共振成像的原理与方法研究神经系统功能的成像方法.作为癫(癎)的首选检查方法之一,fMRI已较广泛地应用于癫(癎)病人的语言优势半球定侧、记忆功能评估及癫(癎)术后神经功能损伤的风险评估等认知神经科学方面,与脑电图(EEG)结合也广泛应用癫(癎)灶定位,而近年来发展迅速的静息态fMRI技术成为癫(癎)fMRI研究的热点之一.本文对癫(癎)的fMRI研究及其进展进行综述.     

超高场磁共振功能成像辅助切除躯体感觉区胶质瘤(附5例报告)

目的应用超高场磁共振功能成像技术进行手术前后研究脑躯体感觉功能区肿瘤与功能区的定位,辅助切除躯体感觉功能区胶质瘤。方法5例邻近或累及躯体感觉功能区的胶质瘤患者,术前行双手持物对接刺激策略,在3.0T磁共振采用血氧水平依赖(BOLD)原理进行图像采集,经工作站(Leonardo syngo 2003A,Siemens)提供的BOLD功能图像分析软件包进行分析获得脑运动功能区的激活图像,参与神经外科手术方案的制定。所有患者均在唤醒麻醉下进行显微外科手术,在术前脑功能磁共振图像指导下利用皮质直接电刺激定位感觉区与运动区。在保护脑功能区功能不受损的前提下,最大程度地切除胶质瘤。术前、术后均行KPS评分,判断患者的状态。结果(1)5例躯体感觉功能区胶质瘤,通过此项技术获得了较好的BOLD功能磁共振成像感觉功能区激活图像,定位躯体感觉功能区。(2)患者在唤醒麻醉下,在术前脑功能磁共振图像指导下利用直接皮质电刺激快捷、准确进行中央后回定位,两者具有良好的一致性。结论应用3.0T MRI可以于术前更好地利用BOLD技术显示躯体感觉功能区与脑胶质瘤的解剖关系,以指导唤醒麻醉下直接皮质电刺激定位躯体感觉功能区的手术,实现最大程度保护患者重要的功能并最大程度地切除肿瘤。     

Multi-modality mapping of motor cortex: comparing echoplanar BOLD fMRI and transcranial magnetic stimulation

Summary Multiple non-invasive methods of imaging brain function are now available for presurgical planning and neurobiological research. As these new methods become available, it is important to understand their relative advantages and liabilities, as well as how the information gained compares across different methods. A current and future trend in neurobiological studies as well as presurgical planning is to combine information from different imaging techniques. Multi-modal integration may perhaps give more powerful information than each modality alone, especially when one of the methods is transcranial magnetic stimulation (TMS), with its ability to non-invasively activate the brain. As an initial venture in cross comparing new imaging methods, we performed the following 2 studies, locating motor cortex with echoplanar BOLD fMRI and TMS. The two methods can be readily integrated, with concurring results, although each have important limitations.     

Functional localization in the human brain: Gradient‐echo,spin‐echo,and arterial spin‐labeling fMRI compared with neuronavigated TMS

A spatial mismatch of up to 14 mm between optimal transcranial magnetic stimulation (TMS) site and functional magnetic resonance imaging (fMRI) signal has consistently been reported for the primary motor cortex. The underlying cause might be the effect of magnetic susceptibility around large draining veins in Gradient‐Echo blood oxygenation level‐dependent (GRE‐BOLD) fMRI. We tested whether alternative fMRI sequences such as Spin‐Echo (SE‐BOLD) or Arterial Spin‐Labeling (ASL) assessing cerebral blood flow (ASL‐CBF) may localize neural activity closer to optimal TMS positions and primary motor cortex than GRE‐BOLD. GRE‐BOLD, SE‐BOLD, and ASL‐CBF signal changes during right thumb abductions were obtained from 15 healthy subjects at 3 Tesla. In 12 subjects, tissue at fMRI maxima was stimulated with neuronavigated TMS to compare motor‐evoked potentials (MEPs). Euclidean distances between the fMRI center‐of‐gravity (CoG) and the TMS motor mapping CoG were calculated. Highest SE‐BOLD and ASL‐CBF signal changes were located in the anterior wall of the central sulcus [Brodmann Area 4 (BA4)], whereas highest GRE‐BOLD signal changes were significantly closer to the gyral surface. TMS at GRE‐BOLD maxima resulted in higher MEPs which might be attributed to significantly higher electric field strengths. TMS‐CoGs were significantly anterior to fMRI‐CoGs but distances were not statistically different across sequences. Our findings imply that spatial differences between fMRI and TMS are unlikely to be caused by spatial unspecificity of GRE‐BOLD fMRI but might be attributed to other factors, e.g., interactions between TMS‐induced electric field and neural tissue. Differences between techniques should be kept in mind when using fMRI coordinates as TMS (intervention) targets. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.     

EEG Monitoring during Functional MRI in Animal Models

Summary:  Despite its excellent temporal resolution, electroencephalogram (EEG) has poor spatial resolution to study the participation of different brain areas in epileptic discharges, and the propagation of seizures to subcortical areas is not revealed. Furthermore, EEG provides no information about metabolic changes that occur in the brain before and during the epileptic discharges. Thus, monitoring variations in blood flow and oxygenation in response to epileptic discharges can provide additional complementary information. Functional magnetic resonance imaging (fMRI) technology can be used to study the hemodynamic changes associated with interictal epileptiform discharges or epileptic seizures (i.e., before, during or after them) in experimental animal models and may noninvasively monitor these changes over time. Blood oxygenation level-dependent fMRI has superior spatial resolution compared with other functional imaging modalities and utilizes changes in local magnetic field properties to measure the amount of deoxyhemoglobin in each brain areas as an indicator of brain activity. Simultaneous recording of EEG and fMRI is required to achieve this objective. This article describes methods of acquiring and monitoring EEG during fMRI studies in experimental animals. Particular attention will be paid to methods used to eliminate artifacts induced in the acquired magnetic resonance images by EEG equipment and MR-related artifacts in EEG recordings.     

The resting‐state neurovascular coupling relationship: rapid changes in spontaneous neural activity in the somatosensory cortex are associated with haemodynamic fluctuations that resemble stimulus‐evoked haemodynamics

Although promise exists for patterns of resting‐state blood oxygen level‐dependent (BOLD) functional magnetic resonance imaging (fMRI) brain connectivity to be used as biomarkers of early brain pathology, a full understanding of the nature of the relationship between neural activity and spontaneous fMRI BOLD fluctuations is required before such data can be correctly interpreted. To investigate this issue, we combined electrophysiological recordings of rapid changes in multi‐laminar local field potentials from the somatosensory cortex of anaesthetized rats with concurrent two‐dimensional optical imaging spectroscopy measurements of resting‐state haemodynamics that underlie fluctuations in the BOLD fMRI signal. After neural ‘events’ were identified, their time points served to indicate the start of an epoch in the accompanying haemodynamic fluctuations. Multiple epochs for both neural ‘events’ and the accompanying haemodynamic fluctuations were averaged. We found that the averaged epochs of resting‐state haemodynamic fluctuations taken after neural ‘events’ closely resembled the temporal profile of stimulus‐evoked cortical haemodynamics. Furthermore, we were able to demonstrate that averaged epochs of resting‐state haemodynamic fluctuations resembling the temporal profile of stimulus‐evoked haemodynamics could also be found after peaks in neural activity filtered into specific electroencephalographic frequency bands (theta, alpha, beta, and gamma). This technique allows investigation of resting‐state neurovascular coupling using methodologies that are directly comparable to that developed for investigating stimulus‐evoked neurovascular responses.     

About being BOLD

The last decade has seen an unprecedented increase in the use of functional magnetic resonance imaging (fMRI) to understand the neural basis of cognition and behavior. Being non-invasive and relatively easy to use, most studies relied on changes in the blood oxygenation level dependent (BOLD) contrast as an indirect marker of variations in brain activity. However, the fact that BOLD fMRI is dependent on the blood flow response that follows neural activity and does not measure neural activity per se is seen as an inherent cause for concern while interpreting data from these studies. In order to characterize the BOLD signal correctly, it is imperative that we have a better understanding of neural events that lead to the BOLD response. A review of recent studies that addressed several aspects of BOLD fMRI including events at the level of the synapse, the nature of the neurovascular coupling, and some parameters of the BOLD signal is provided. This is intended to serve as background information for the interpretation of fMRI data in normal subjects and in patients with compromised neurovascular coupling. One of the aims is also to encourage researchers to interpret the results of functional imaging studies in light of the dynamic interactions between different brain regions, something that often is neglected.     

Blood oxygenation level dependent signal and neuronal adaptation to optogenetic and sensory stimulation in somatosensory cortex in awake animals

The adaptation of neuronal responses to stimulation, in which a peak transient response is followed by a sustained plateau, has been well‐studied. The blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal has also been shown to exhibit adaptation on a longer time scale. However, some regions such as the visual and auditory cortices exhibit significant BOLD adaptation, whereas other such as the whisker barrel cortex may not adapt. In the sensory cortex a combination of thalamic inputs and intracortical activity drives hemodynamic changes, although the relative contributions of these components are not entirely understood. The aim of this study is to assess the role of thalamic inputs vs. intracortical processing in shaping BOLD adaptation during stimulation in the somatosensory cortex. Using simultaneous fMRI and electrophysiology in awake rabbits, we measured BOLD, local field potentials (LFPs), single‐ and multi‐unit activity in the cortex during whisker and optogenetic stimulation. This design allowed us to compare BOLD and haemodynamic responses during activation of the normal thalamocortical sensory pathway (i.e., both inputs and intracortical activity) vs. the direct optical activation of intracortical circuitry alone. Our findings show that whereas LFP and multi‐unit (MUA) responses adapted, neither optogenetic nor sensory stimulation produced significant BOLD adaptation. We observed for both paradigms a variety of excitatory and inhibitory single unit responses. We conclude that sensory feed‐forward thalamic inputs are not primarily responsible for shaping BOLD adaptation to stimuli; but the single‐unit results point to a role in this behaviour for specific excitatory and inhibitory neuronal sub‐populations, which may not correlate with aggregate neuronal activity.     

Electrophysiological correlates of the BOLD signal for EEG‐informed fMRI

Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) are important tools in cognitive and clinical neuroscience. Combined EEG–fMRI has been shown to help to characterise brain networks involved in epileptic activity, as well as in different sensory, motor and cognitive functions. A good understanding of the electrophysiological correlates of the blood oxygen level‐dependent (BOLD) signal is necessary to interpret fMRI maps, particularly when obtained in combination with EEG. We review the current understanding of electrophysiological–haemodynamic correlates, during different types of brain activity. We start by describing the basic mechanisms underlying EEG and BOLD signals and proceed by reviewing EEG‐informed fMRI studies using fMRI to map specific EEG phenomena over the entire brain (EEG–fMRI mapping), or exploring a range of EEG‐derived quantities to determine which best explain colocalised BOLD fluctuations (local EEG–fMRI coupling). While reviewing studies of different forms of brain activity (epileptic and nonepileptic spontaneous activity; cognitive, sensory and motor functions), a significant attention is given to epilepsy because the investigation of its haemodynamic correlates is the most common application of EEG‐informed fMRI. Our review is focused on EEG‐informed fMRI, an asymmetric approach of data integration. We give special attention to the invasiveness of electrophysiological measurements and the simultaneity of multimodal acquisitions because these methodological aspects determine the nature of the conclusions that can be drawn from EEG‐informed fMRI studies. We emphasise the advantages of, and need for, simultaneous intracranial EEG–fMRI studies in humans, which recently became available and hold great potential to improve our understanding of the electrophysiological correlates of BOLD fluctuations. Hum Brain Mapp, 36:391–414, 2015. © 2014 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.     

The postprandial increase in blood triglycerides has no direct effect on the brain BOLD response

A previous study showed that ingestion of a liquid meal high in polyunsaturated lipids decreased the blood-oxygenation-level-dependent (BOLD) response measured by functional magnetic resonance imaging (fMRI) during a finger-tapping motor task, and suggested that this effect was due to a direct effect of blood lipids on the cerebral vasculature. This study compared the time course and magnitude of the BOLD response in fixed anatomic locations before and 3 h after ingestion of high versus low lipid content liquid meals (235 ml Ensure Plus [Abbot Labs] with or without 50 ml added canola oil). Blood triglyceride content peaked 3 h after the high lipid meal and was elevated by 33% compared with the low lipid meal. There was no significant effect of meal composition on the time course or magnitude of the BOLD response in fixed-location clusters of voxels which were activated during either a motor (finger-tapping), a visual (flashing checkerboard), or an integrative/cognitive (number addition) block-design task paradigm. The results indicate that increased blood total triglyceride content after a meal with relatively high polyunsaturated fat does not directly alter the hemodynamic BOLD response to neural activity. However, the postprandial effect on BOLD response of other meals with varying fat types and amounts, as well as other nutrients and phytochemicals, remains to be determined.     

Noninvasive measurement of the cerebral blood flow response in human lateral geniculate nucleus with arterial spin labeling fMRI

To date, functional magnetic resonance imaging (fMRI) studies of the lateral geniculate nucleus (LGN) have primarily focused on measures of the blood oxygenation level dependent (BOLD) signal. Arterial spin labeling (ASL) is an MRI method that can provide direct measures of functional cerebral blood flow (CBF) changes. Because CBF is a well-defined physiological quantity that contributes to BOLD contrast, CBF measures can be used to improve the quantitative interpretation of fMRI studies. However, due in part to the low intrinsic signal-to-noise ratio of the ASL method, measures of functional CBF changes in the LGN are challenging and have not previously been reported. In this study, we demonstrate the feasibility of using ASL fMRI to measure the CBF response of the LGN to visual stimulation on a 3 T MRI system. The use of background suppression and physiological noise reduction techniques allowed reliable detection of LGN activation in all five subjects studied. The measured percent CBF response during activation ranged from 40 to 100%, assuming no interaction between the left and right LGN.