Small-world directed networks in the human brain: multivariate Granger causality analysis of resting-state fMRI

Small-world organization is known to be a robust and consistent network architecture, and is a hallmark of the structurally and functionally connected human brain. However, it remains unknown if the same organization is present in directed influence brain networks whose connectivity is inferred by the transfer of information from one node to another. Here, we aimed to reveal the network architecture of the directed influence brain network using multivariate Granger causality analysis and graph theory on resting-state fMRI recordings. We found that some regions acted as pivotal hubs, either being influenced by or influencing other regions, and thus could be considered as information convergence regions. In addition, we observed that an exponentially truncated power law fits the topological distribution for the degree of total incoming and outgoing connectivity. Furthermore, we also found that this directed network has a modular structure. More importantly, according to our data, we suggest that the human brain directed influence network could have a prominent small-world topological property.     

静息态fMRI评估酒精注射急性期恒河猴脑功能改变

目的 采用静息态fMRI基于分数低频振荡幅度（fALFF）算法评价酒精急性期恒河猴脑功能改变。方法 分别对7只雄性健康恒河猴于给予酒精前（对照组）及10 min后（酒精组）行静息态fMRI扫描,采用fALFF算法获得两组fALFF值存在差异的脑区。结果 静息态下,酒精组fALFF值低于对照组的脑区为右枕叶、右侧颞中回、左侧中央后回、右侧楔叶/距状沟、右侧额上回、后扣带回及小脑、丘脑（P<0.01）;酒精组fALFF值高于对照组的脑区包括双侧额上回、双侧颞下回、右侧中央前回、楔前叶、后扣带回、左侧海马、双侧岛叶及脑干、小脑、右侧基底核（P均<0.01）。结论 酒精急性期恒河猴脑功能的改变具有全脑效应。     

吸烟者静息态fMRI脑功能连接研究

目的 采用静息态fMRI分数低频振幅技术（fALFF）及功能连接方法分析吸烟者脑功能活动。方法 收集53名吸烟者（吸烟组）和53名不吸烟者（对照组）的静息态fMRI资料,并将吸烟组分为少量吸烟亚组与大量吸烟亚组、轻度成瘾亚组与重度成瘾亚组,计算受检者fALFF值,观察2组及不同亚组间fALFF值、全脑功能连接差异。结果 与对照组相比,吸烟组左侧边缘叶等脑区fALFF值增加,右侧颞上回等脑区fALFF值下降;与少量吸烟亚组相比,大量吸烟亚组右侧颞上回等脑区fALFF值升高,双侧边缘叶等脑区fALFF值下降;与轻度成瘾亚组相比,重度成瘾亚组双侧额中回等脑区fALFF值增加,左侧边缘叶等脑区fALFF值下降。吸烟组较对照组可见多发功能连接增强和减低的脑区。结论 吸烟者与成瘾相关脑区活动增强、情绪控制脑区活动减弱,且部分脑区活动改变与吸烟量及烟瘾程度有关。     

Large-scale directional connections among multi resting-state neural networks in human brain: a functional MRI and Bayesian network modeling study

This study examined the large-scale connectivity among multiple resting-state networks (RSNs) in the human brain. Independent component analysis was first applied to the resting-state functional MRI (fMRI) data acquired from 12 healthy young subjects for the separation of RSNs. Four sensory (lateral and medial visual, auditory, and sensory-motor) RSNs and four cognitive (default-mode, self-referential, dorsal and ventral attention) RSNs were identified. Gaussian Bayesian network (BN) learning approach was then used for the examination of the conditional dependencies among these RSNs and the construction of the network-to-network directional connectivity patterns. The BN based results demonstrated that sensory networks and cognitive networks were hierarchically organized. Specially, we found the sensory networks were highly intra-dependent and the cognitive networks were strongly intra-influenced. In addition, the results depicted dominant bottom-up connectivity from sensory networks to cognitive networks in which the self-referential and the default-mode networks might play respectively important roles in the process of resting-state information transfer and integration. The present study characterized the global connectivity relations among RSNs and delineated more characteristics of spontaneous activity dynamics.     

A semi-parametric approach to estimate the family-wise error rate in fMRI using resting-state data

One of the most important considerations in any hypothesis based fMRI data analysis is to choose the appropriate threshold to construct the activation maps, which is usually based on p-values. However, in fMRI data, there are three factors which necessitate severe corrections in the process of estimating the p-values. First, the fMRI time series at an individual voxel has strong temporal autocorrelation which needs to be estimated to obtain the corrected parametric p-value. The second factor is the multiple comparisons problem arising from simultaneously testing tens of thousands of voxels for activation. A common way in the statistical literature to account for multiple testing is to consider the family-wise error rate (FWE) which is related to the distribution of the maximum observed value over all voxels. The third problem, which is not mentioned frequently in the context of adjusting the p-value, is the effect of inherent low frequency processes present even in resting-state data that may introduce a large number of false positives without proper adjustment. In this article, a novel and efficient semi-parametric method, using resampling of normalized spacings of order statistics, is introduced to address all the three problems mentioned above. The new method makes very few assumptions and demands minimal computational effort, unlike other existing resampling methods in fMRI. Furthermore, it will be demonstrated that the correction for temporal autocorrelation is not critical in implementing the proposed method. Results using the proposed method are compared with SPM2.     

鞍区占位视力受损患者与视觉皮层相关的静息态fMRI研究

目的静息态功能磁共振成像探索鞍区占位视力受损患者引起的脑功能活动改变情况。方法筛选21例鞍区占位视力受损患者,并选择与之年龄和性别相匹配的健康对照者21名。计算ALFF、ReHo、FC值,然后采用双样本t检验统计学方法进行研究。结果与正常对照组相比,鞍区占位视力受损患者组双侧楔叶、左侧舌回、右侧SMA区域ALFF值降低,双侧豆状核ALFF值升高。双侧楔叶ReHo值降低,楔前叶、左侧岛叶皮层和左侧豆状核ReHo值升高,并且楔前叶和左侧岛叶皮层的ReHo值与常规磁共振手动测量的占位的左右直径存在明显正相关性。在功能连接结果中,高级视觉皮层与双侧楔叶、双侧顶上小叶、双侧颞上回、双侧缘上回、中央前回、中央后回及SMA存在功能连接减弱。结论鞍区占位视力受损患者存在视觉以及视觉以外相关脑区神经元活动异常。     

Enhanced functional connectivity between habenula and salience network in medication-overuse headache complicating chronic migraine positions it within the addiction disorders: an ICA-based resting-state fMRI study

BackgroundMedication-overuse headache (MOH) is a relatively frequently occurring secondary headache caused by overuse of analgesics and/or acute migraine medications. It is believed that MOH is associated with dependence behaviors and substance addiction, in which the salience network (SN) and the habenula may play an important role. This study aims to investigate the resting-state (RS) functional connectivity between the habenula and the SN in patients with MOH complicating chronic migraine (CM) compared with those with episodic migraine (EM) and healthy controls (HC).MethodsRS-fMRI and 3-dimensional T1-weighted images of 17 patients with MOH + CM, 18 patients with EM and 30 matched healthy HC were obtained. The RS-fMRI data were analyzed using the independent component analysis (ICA) method to investigate the group differences of functional connectivity between the habenula and the SN in three groups. Correlation analysis was performed thereafter with all clinical variables by Pearson correlation.ResultsIncreased functional connectivity between bilateral habenula and SN was detected in patients with MOH + CM compared with patients with EM and HC respectively. Correlation analysis showed significant correlation between medication overuse duration and habenula-SN connectivity in MOH + CM patients.ConclusionsThe current study supported MOH to be lying within a spectrum of dependence and addiction disorder. The enhanced functional connectivity of the habenula with SN may correlate to the development or chronification of MOH. Furthermore, the habenula may be an indicator or treatment target for MOH for its integrative role involved in multiple aspects of MOH.     

静息态功能磁共振数据处理方法的应用

目的 比较静息态fMRI数据处理方法中的分数低频振幅(fALFF)、局部一致性(Reho)和功能连接(FC)在数据分析中的侧重点和敏感性。 方法 采集10名正常志愿者和10例脑干梗死患者亚急性期静息态fMRI数据,采用各种算法分别处理数据,提取患者的静息态脑网络(RSN),并比较其相对正常人改变的区域。 结果 fALFF和Reho提取的患者RSN包含脑默认网络后部和初级视皮质,FC提取的RSN与脑默认网络基本一致。比较患者与正常对照,Reho方法无有意义结果,fALFF和FC得到不同结果,选择不同ROI的FC也得到不同的结果。 结论 fALFF与Reho侧重脑局部功能活动的分析,FC侧重脑整体功能活动的分析;Reho对本数据敏感性最差,而FC最好,其中ROI的选择对结果影响很大,依据本数据的特性选择比依据先验知识选择得到的结果敏感性更高。     

Alteration of brain default network in subacute phase of injury in concussed individuals: resting-state fMRI study

There are a number of symptoms, both neurological and behavioral, associated with a single episode of r mild traumatic brain injury (mTBI). Neuropsychological testing and conventional neuroimaging techniques are not sufficiently sensitive to detect these changes, which adds to the complexity and difficulty in relating symptoms from mTBI to their underlying structural or functional deficits. With the inability of traditional brain imaging techniques to properly assess the severity of brain damage induced by mTBI, there is hope that more advanced neuroimaging applications will be more sensitive, as well as specific, in accurately assessing mTBI. In this study, we used resting state functional magnetic resonance imaging to evaluate the default mode network (DMN) in the subacute phase of mTBI. Fourteen concussed student-athletes who were asymptomatic based upon clinical symptoms resolution and clearance for aerobic exercise by medical professionals were scanned using resting state functional magnetic resonance imaging. Nine additional asymptomatic yet not medically cleared athletes were recruited to investigate the effect of a single episode of mTBI versus multiple mTBIs on the resting state DMN. In concussed individuals the resting state DMN showed a reduced number of connections and strength of connections in the posterior cingulate and lateral parietal cortices. An increased number of connections and strength of connections was seen in the medial prefrontal cortex. Connections between the left dorso-lateral prefrontal cortex and left lateral parietal cortex showed a significant reduction in magnitude as the number of concussions increased. Regression analysis also indicated an overall loss of connectivity as the number of mTBI episodes increased. Our findings indicate that alterations in the brain resting state default mode network in the subacute phase of injury may be of use clinically in assessing the severity of mTBI and offering some insight into the pathophysiology of the disorder.     

Caffeine increases the temporal variability of resting-state BOLD connectivity in the motor cortex

Correlations between spontaneous fluctuations in the blood oxygenation level dependent (BOLD) signal measured with functional MRI are finding increasing use as measures of functional connectivity in the brain, where differences can potentially predict cognitive performance and diagnose disease. Caffeine, which is a widely consumed neural stimulant and vasoactive agent, has been found to decrease the amplitude and correlation of resting-state BOLD fluctuations, and hence is an important factor to consider in functional connectivity studies. However, because the BOLD signal is sensitive to neural and vascular factors, the physiological mechanisms by which caffeine alters spontaneous BOLD fluctuations remain unclear. Resting-state functional connectivity has traditionally been assessed using stationary measures, such as the correlation coefficient between BOLD signals measured across the length of a scan. However, recent work has shown that the correlation of resting-state networks can vary considerably over time, with periods as short as 10 s. In this study, we used a sliding window correlation analysis to assess temporal variations in resting-state functional connectivity of the motor cortex before and after caffeine ingestion. We found that the temporal variability of BOLD correlation was significantly higher following a caffeine dose, with transient periods of strong correlation alternating with periods of low or negative correlation. This phenomenon was primarily due to increased variability in the phase difference between BOLD time courses in the left and right motor cortices. These results indicate that caffeine may cause underlying spontaneous neural fluctuations to go in and out of coherence more frequently, and emphasizes the need to consider non-stationary measures when studying changes in functional connectivity.     

fMRI分析非临床抑郁大学生杏仁核及海马静息态功能连接的改变

目的 分析非临床抑郁症状(nCDSs)被试杏仁核及海马静息态功能连接的特征。方法 采用贝克抑郁量表(BDI)对1105名大学生进行抑郁症状评估,对其中17例符合nCDSs的被试(nCDSs组)及20名对照组被试进行静息态fMRI检查。以双侧杏仁核及海马为种子点,分别对全脑进行基于体素的rsFC分析,比较两组间的rsFC差异,并与nCDSs者的BDI评分进行相关分析。结果 与对照组比较,nCDSs组以双侧杏仁核为种子点,右侧眶额叶内侧面rsFC均增强;以左侧海马为种子点,右侧枕叶舌回、双侧额叶直回及左侧楔前叶rsFC增强;以右侧海马为种子点,右侧小脑后叶、右侧枕叶舌回、双侧额叶直回、左侧楔前叶及左侧中央旁小叶rsFC增强。nCDSs被试双侧杏仁核及海马rsFC改变与BDI评分无相关性(P>0.05)。结论 nCDSs被试杏仁核及海马的rsFC存在异常,可能在nCDSs的病理机制中发挥重要作用。     

2型糖尿病患者静息态功能磁共振自发性脑活动改变的Meta分析

目的 通过Meta分析探讨2型糖尿病（T2DM）患者的fMRI静息态脑自发性活动改变规律。方法 检索PubMed、EMbase、中国生物医学文献数据库中已公开发表的有关静息态fMRI（rs-fMRI）研究T2DM患者自发性脑活动改变的文献,并进行文献筛选及资料提取。采用SDM软件对纳入文献的低频振幅（ALFF）值或分数低频振幅（fALFF）值进行基于体素的Meta分析。结果 共6项符合要求的文献纳入分析,包括137例T2DM患者和140例正常对照者。Meta分析结果显示,静息状态下T2DM组患者ALFF、fALFF值减低区域主要集中在右侧枕中回、右侧舌回及左侧嗅皮层;而ALFF、fALFF值增高区域主要为双侧小脑、双侧前扣带回、左侧颞下回。结论 T2DM患者在静息状态下存在自发性脑活动的改变。右侧枕中回、右侧舌回及左侧嗅皮层活动减低可能提示微结构损伤,同时双侧小脑、双侧前扣带回、左侧颞下回活动增强可能提示代偿性改变。     

Characterizing dynamic functional connectivity in the resting brain using variable parameter regression and Kalman filtering approaches

The cognitive activity of the human brain benefits from the functional connectivity of multiple brain regions that form specific, functional brain networks. Recent studies have indicated that the relationship between brain regions can be investigated by examining the temporal interaction (known as functional connectivity) of spontaneous blood oxygen level-dependent (BOLD) signals derived from resting-state functional MRI. Most of these studies plausibly assumed that inter-regional interactions were temporally stationary. However, little is known about the dynamic characteristics of resting-state functional connectivity (RSFC). In this study, we thoroughly examined this question within and between multiple functional brain networks. Twenty-two healthy subjects were scanned in a resting state. Several of the RSFC networks observed, including the default-mode, motor, attention, memory, auditory, visual, language and subcortical networks, were first identified using a conventional voxel-wise correlation analysis with predefined region of interests (ROIs). Then, a variable parameter regression model combined with the Kalman filtering method was employed to detect the dynamic interactions between each ROI and all other brain voxels within each of the RSFC maps extracted above. Experimental results revealed that the functional interactions within each RSFC map showed time-varying properties, and that approximately 10-20% of the voxels within each RSFC map showed significant functional connectivity to each ROI during the scanning session. This dynamic pattern was also observed for the interactions between different functional networks. In addition, the spatial pattern of dynamic connectivity maps obtained from neighboring time points had a high similarity. Overall, this study provides insights into the dynamic properties of resting-state functional networks.     

针刺足三里穴PET和fMRI脑功能成像的初步探讨

目的探讨针刺足三里穴脑功能成像的实验方法和针灸治疗的中枢机制。方法利用18FDG PET和fMRI BOLD脑功能成像方法 ,获取针刺足三里穴脑内葡萄糖代谢和脑血流变化有关的实验数据 ,利用SPM和感兴趣区图像分析方法 (ROI)获得脑功能变化的可视性实验依据。结果针刺右侧足三里穴引起视丘下部、同侧室旁核和双侧颞叶的葡萄糖代谢和脑血流增加。结论针刺足三里穴可引起植物神经中枢和颞叶功能变化 ,与足三里穴的治疗胃肠疾病和改善精神和睡眠状态的治疗作用密切相关     

Differential alteration of fMRI signal variability in the ascending trigeminal somatosensory and pain modulatory pathways in migraine

BackgroundThe moment-to-moment variability of resting-state brain activity has been suggested to play an active role in chronic pain. Here, we investigated the regional blood-oxygen-level-dependent signal variability (BOLD_SV) and inter-regional dynamic functional connectivity (dFC) in the interictal phase of migraine and its relationship with the attack severity.MethodsWe acquired resting-state functional magnetic resonance imaging from 20 migraine patients and 26 healthy controls (HC). We calculated the standard deviation (SD) of the BOLD time-series at each voxel as a measure of the BOLD signal variability (BOLD_SV) and performed a whole-brain voxel-wise group comparison. The brain regions showing significant group differences in BOLD_SV were used to define the regions of interest (ROIs). The SD and mean of the dynamic conditional correlation between those ROIs were calculated to measure the variability and strength of the dFC. Furthermore, patients’ experimental pain thresholds and headache pain area/intensity levels during the migraine ictal-phase were assessed for clinical correlations.ResultsWe found that migraineurs, compared to HCs, displayed greater BOLD_SV in the ascending trigeminal spinal-thalamo-cortical pathways, including the spinal trigeminal nucleus, pulvinar/ventral posteromedial (VPM) nuclei of the thalamus, primary somatosensory cortex (S1), and posterior insula. Conversely, migraine patients exhibited lower BOLD_SV in the top-down modulatory pathways, including the dorsolateral prefrontal (dlPFC) and inferior parietal (IPC) cortices compared to HCs. Importantly, abnormal interictal BOLD_SV in the ascending trigeminal spinal-thalamo-cortical and frontoparietal pathways were associated with the patient’s headache severity and thermal pain sensitivity during the migraine attack. Migraineurs also had significantly lower variability and greater strength of dFC within the thalamo-cortical pathway (VPM-S1) than HCs. In contrast, migraine patients showed greater variability and lower strength of dFC within the frontoparietal pathway (dlPFC-IPC).ConclusionsMigraine is associated with alterations in temporal signal variability in the ascending trigeminal somatosensory and top-down modulatory pathways, which may explain migraine-related pain and allodynia. Contrasting patterns of time-varying connectivity within the thalamo-cortical and frontoparietal pathways could be linked to abnormal network integrity and instability for pain transmission and modulation.     

汉字与英文字形辨认的脑功能磁共振成像初步研究

目的:探讨功能磁共振成像(fMRI)技术研究人脑汉字与英文字形辨认方面的价值。材料与方法:12例(男5例,女7例)母语为汉语且裸眼视力正常的大学生参加实验。设备为GE Signa 1.5T MR仪,采用EPI序列,BOLD法行脑功能磁共振扫描。实验任务分别将汉字与英文(真字、假字、非字)投射到屏幕上,受试者通过头线圈反光镜观看屏幕并辨认。数据分析使用SPM 99升级软件,经过数据采集、预处理和建立模型显示结果。结果:汉字真字刺激在左额叶、中央前回(BA6)及枕叶(BA18)显著激活;左顶叶、中央后回(BA3)、右额下回(BA9)及双侧颞叶少量激活。英文真字刺激时左额中回、中央前回、左额下回显著激活;左颞梭状回(BA37)、右枕语言回(BA18)及左顶叶(BA40)也有激活。汉字和英文假字与非字只引起少量激活(P>0.05)。汉字与英文刺激左大脑半球的激活体积明显大于右半球;除枕叶外,英文在额、颞及顶叶引起的激活体积均大于汉字。结论:fMRI是研究人脑汉字和英文语言加工理想的无创性影像学方法,其脑加工优势半球均为左半球;母语为汉语者,其英文脑处理过程需更多的脑活动来参与和完成。     

人脑对事件相关食物视觉刺激反应的功能磁共振成像的初步研究

目的通过功能磁共振成像(fMRI)初步研究人脑对事件相关食物视觉刺激反应.方法本研究利用fMRI技术具有时间分辨率高、对人体无创并且可以对单例数据处理分析的优势,采用平面回波成像(EPI)序列,检测在饥饿状态下,人脑对事件相关食物视觉刺激反应.实验中2名健康志愿受试者,选择事件相关任务模式禁食12 h后扫描.扫描的同时接受随机播放的食物图片、非食物图片和空白模糊图片的视觉刺激.用SPM 2软件处理功能成像数据,对由三类图片所引发的感兴趣区(ROI)做相关t检验统计.结果与食物渴求相关的脑区分布在杏仁核、眶额皮质以及枕叶皮质,与既往的正电子放射扫描成像(PET)实验结果相符.结论确定与食物渴求相关的奖赏通路,对于了解人类在饥饿状态下对食物渴求的复杂认知规律,为进一步寻找有效调控人类摄食行为的手段有重要意义.     

The human parietal cortex is involved in spatial processing of tongue movement-an fMRI study

The human tongue is so sensitive and dexterous that spatial representations of the inside of the oral cavity for the tongue movement are naturally expected to exist. In the present study, we examined the brain activity associated with spatial processing during tongue movements using a functional magnetic resonance imaging technique. Twenty-four normal subjects participated in the study, which consisted of a periodic series of three blocks; resting of the tongue, tongue movement (pressing the inside of a tooth with the tip of the tongue), and tongue retraction. The cerebral fields of activation during the tongue movement to the left and right side relative to those during rest were found in the primary sensorimotor area and supplementary motor area bilaterally, and in the left inferior parietal lobule (IPL). The activation areas during the tongue retraction relative to those during rest were almost the same, except that activation in the left IPL was not observed. The fields of activation during tongue movement to the left and right side relative to those during tongue retraction were found bilaterally in the dorsal premotor area, superior parietal lobule (SPL), and the IPL. The results indicate that the bilateral SPL and IPL were specifically involved in the processing for human tongue movement. Although no significant laterality was observed, the left parietal area tended to show greater activation in statistical values and area than the right parietal area, thus indicating the possibility that this processing for human tongue movement is related to that for language.     

Investigating the consistency of brain activation using individual trial analysis of high-resolution fMRI in the human primary visual cortex

Conventional functional magnetic resonance imaging using blood oxygenation level dependent contrast requires signal averaging and statistical methods to detect activation. Signal averaging implicitly assumes that brain activation in response to a stimulus is reproducible on the scale of the imaging voxel. This assumption is examined in the absence of averaging by analyzing individual trials of individual voxels that approach the size of the functional unit, the cortical column, in the human primary visual cortex. In the absence of spatial and temporal averaging, even highly active voxels demonstrate inconsistent activation to the same repeated stimulus despite consistent behavioral responses. This observation implies a variable selection of suitable cortical columns from a population of available functional units to produce consistent perception of the stimulus. The implication of this observation for neuroplasticity and behavioral consistency at the level of functional units is discussed.