基于静息态功能连接模式的正常人脑扣带皮层亚区划分

基于静息态功能连接(rsFC)模式对正常人脑扣带皮层进行亚区划分,并分析不同亚区的功能连接模式。方法 收集47名右利手健康志愿者。采集结构磁共振图像及静息态功能磁共振图像。在蒙特利尔脑研究所标准空间勾画扣带皮层ROI。基于个体计算ROI中每个体素与全脑其他体素时间序列的Pearson线性相关系数,得到互相关矩阵,采用K-均值聚类算法自动聚类。采用交互验证的方法选择合适分割数。最终计算最大概率图谱。通过单样本t检验确定与每个亚区具有正功能连接的脑区。结果 扣带皮层被分为6个亚区:前扣带皮层、背侧中前扣带皮层、腹侧中前扣带皮层、中后扣带皮层、背侧后扣带皮层及腹侧后扣带皮层亚区。每个亚区有特异的静息态功能连接模式。结论 人脑扣带皮层依据不同的静息态功能连接模式分为6个亚区,每个亚区分属不同的脑功能网络,参与不同的功能。     

Reduced resting-state functional connectivity between amygdala and orbitofrontal cortex in social anxiety disorder

Social anxiety disorder patients suffer from excessive anxious responses in social interaction leading to avoidance behavior and social impairment. Although the amygdala has a central role in perception and processing of threatening cues, little is known about the involved networks and corresponding dysfunctions in social anxiety. Therefore, this study aims to investigate the functional connectivity network of the amygdala in patients with social anxiety disorder and to identify regions that might influence amygdalar reactivity via modulatory pathways. Ten patients with anxiety disorders (social and/or panic) and 27 healthy controls underwent a facial emotion processing task as well as 6-min functional MRI at resting state. Individual voxel-wise functional connectivity maps were calculated using the amygdala as seed region. Group comparisons were done by random-effects analysis in SPM. Patients exhibited an amygdala hyperactivation during the emotional task and decreased functional coupling of the left amygdala with the medial orbitofrontal cortex and the posterior cingulate cortex/precuneus. The strength of this functional connectivity showed a negative association with the severity of state anxiety. In addition, an exploratory analysis revealed further reduced functional connectivity and a marked functional separation between the medial orbitofrontal and anterior cingulate cortices in the patient group. Our results suggest alterations within the amygdalar functional connectivity network in social anxiety disorder. Combined with the amygdalar hyperactivation our findings corroborate the proposed dysfunction of the fronto-amygdalar inhibition in anxiety disorders and indicate a modulatory influence of the anterior and posterior cingulate cortices on threat perception and processing.     

A geometric view of global signal confounds in resting-state functional MRI

Resting-state functional magnetic resonance imaging (fMRI) is proving to be an effective tool for mapping the long-range functional connections of the brain in both health and disease. One of the primary measures of connectivity is the correlation between the blood oxygenation level dependent (BOLD) time series observed in different brain regions. The computation of the correlation is often dominated by the presence of a strong global component that can introduce significant variability across functional connectivity maps acquired from different experimental scans or subjects. To address this issue, a variety of global signal correction methods have been proposed, but there is currently a lack of a clear consensus on the best approach to use. Furthermore, there has been concern that some global signal correction methods, such as global signal regression, may produce significant negative bias in the correlation values. In this paper we introduce a framework for visualizing the signal structure of resting-state fMRI data and characterizing the properties of the global signal. Using this framework, we demonstrate that a portion of the global signal can be viewed as an additive confound that increases with the mean BOLD amplitude. An approach for minimizing the contribution of this additive confound is presented, and an initial comparison with existing global signal correction methods is provided.     

Mapping resting-state functional connectivity using perfusion MRI

Resting-state, low-frequency (<0.08 Hz) fluctuations of blood oxygenation level-dependent (BOLD) magnetic resonance signal have been shown to exhibit high correlation among functionally connected regions. However, correlations of cerebral blood flow (CBF) fluctuations during the resting state have not been extensively studied. The main challenges of using arterial spin labeling perfusion magnetic resonance imaging to detect CBF fluctuations are low sensitivity, low temporal resolution, and contamination from BOLD. This work demonstrates CBF-based quantitative functional connectivity mapping by combining continuous arterial spin labeling (CASL) with a neck labeling coil and a multi-channel receiver coil to achieve high perfusion sensitivity. In order to reduce BOLD contamination, the CBF signal was extracted from the CASL signal time course by high frequency filtering. This processing strategy is compatible with sinc interpolation for reducing the timing mismatch between control and label images and has the flexibility of choosing an optimal filter cutoff frequency to minimize BOLD fluctuations. Most subjects studied showed high CBF correlation in bilateral sensorimotor areas with good suppression of BOLD contamination. Root-mean-square CBF fluctuation contributing to bilateral correlation was estimated to be 29+/-19% (N=13) of the baseline perfusion, while BOLD fluctuation was 0.26+/-0.14% of the mean intensity (at 3 T and 12.5 ms echo time).     

2型糖尿病患者眶额皮层相关功能连接的功能MRI研究

目的探索2型糖尿病对眶额皮层与其它脑区之间的相关功能连接是否存在异常。材料与方法对27名不伴有脑血管病变影像征象的2型糖尿病患者及21名正常志愿者进行常规MRI及静息态功能MRI扫描,计算双侧眶额皮层与全脑其它体素间的功能连接值,并进行组间比较,选取组间具有显著差异的脑区,并计算其功能连接的平均值,与临床指标做相关性分析。结果与正常对照组相比,2型糖尿病患者左侧眶额皮层内侧后部与左侧中脑、右侧下丘脑、双侧丘脑的功能连接强度显著减低。其中2型糖尿病患者左侧眶额皮层内侧后部与左侧中脑之间的功能连接平均值与空腹血糖值存在正相关(t=2.3727,P=0.028)。结论 2型糖尿病患者眶额皮层与多个脑区的功能连接存在异常,其中左侧眶额皮层内侧后部与左侧中脑之间的功能连接异常与血糖控制的好坏程度相关。说明2型糖尿病可能损伤了奖赏系统的相关通路,从而导致摄食紊乱。     

难治性抑郁症患者静息状态默认网络的改变

目的 探索难治性抑郁症(TRD)患者脑静息状态默认网络与正常对照组间的差异.方法 10例TRD患者和12名对照者接受440 s的静息脑功能扫描.运用功能连接分析得出个体的静息状态默认网络并进行组间比较.结果 与对照组比较,TRD组双侧颞中回、直回、楔前回、左侧眶回、右侧顶下小叶与后扣带回的连接功能减弱.结论 TRD患者的静息默认网络连接中多个脑区活动减弱,可能导致患者自我控制和情感行为功能异常.     

Altered functional connectivity between the insula and the cingulate cortex in patients with temporomandibular disorder: a pilot study

Background.— Among the most common chronic pain conditions, yet poorly understood, are temporomandibular disorders (TMDs), with a prevalence estimate of 3‐15% for Western populations. Although it is increasingly acknowledged that central nervous system mechanisms contribute to pain amplification and chronicity in TMDs, further research is needed to unravel neural correlates that might abet the development of chronic pain. Objective.— The insular cortex (IC) and cingulate cortex (CC) are both critically involved in the experience of pain. The current study sought specifically to investigate IC–CC functional connectivity in TMD patients and healthy controls (HCs), both during resting state and during the application of a painful stimulus. Methods.— Eight patients with TMD, and 8 age‐ and sex‐matched HCs were enrolled in the present study. Functional magnetic resonance imaging data during resting state and during the performance of a pressure pain stimulus to the temple were acquired. Predefined seed regions were placed in the IC (anterior and posterior insular cortices) and the extracted signal was correlated with brain activity throughout the whole brain. Specifically, we were interested whether TMD patients and HCs would show differences in IC–CC connectivity, both during resting state and during the application of a painful stimulus to the face. Results.— As a main finding, functional connectivity analyses revealed an increased functional connectivity between the left anterior IC and pregenual anterior cingulate cortex (ACC) in TMD patients, during both resting state and applied pressure pain. Within the patient group, there was a negative correlation between the anterior IC–ACC connectivity and clinical pain intensity as measured by a visual analog scale. Conclusions.— Since the pregenual region of the ACC is critically involved in antinociception, we hypothesize that an increase in anterior IC–ACC connectivity is indicative of an adaptation of the pain modulatory system early in the chronification process. (Headache 2012;52:441‐454)     

2型糖尿病患者下丘脑功能连接的静息态功能磁共振研究

目的利用静息态功能磁共振技术探索2型糖尿病(T2DM)患者下丘脑与其他脑区功能连接的改变,明确T2DM是否损伤下丘脑的相关功能连接。材料与方法本研究共纳入59名T2DM患者及49名对照组志愿者,通过德国西门子MR仪采集T1WI、T2WI、T2压水序列、高分辨率3D T1WI结构像和静息态功能数据,计算下丘脑与全脑体素的功能连接值并进行组间比较,然后提取组间存在显著差异脑区的功能连接平均值并对其与临床数据进行相关性分析。结果 T2DM患者左、右侧下丘脑与右侧桥脑、左背外侧前额叶、眶额皮层、左顶下小叶、右侧枕中回间的功能连接强度均低于正常组(P0.05)。除此之外,左侧下丘脑与左侧梭状回、右侧颞下回、左侧楔前叶间的功能连接强度显著减低,左侧下丘脑与左侧岛叶间的功能连接强度显著增高(P0.05);右侧下丘脑与左侧舌回、右侧中央前回/右侧中央后回间的功能连接强度显著减低(P0.05)。相关性分析结果显示左侧下丘脑-左背外侧前额叶间功能连接强度的减低与糖化血红蛋白值存在负相关性(r=–0.24,P=0.04)。结论 T2DM损害了下丘脑与多个脑区的功能连接,其中同侧下丘脑与背外侧前额叶间功能连接减低与糖尿病严重程度相关。静息态功能磁共振能够反映2型糖尿病的严重程度。     

MRI观察精神分裂症静息态下小脑功能连接和解剖连接

目的 应用静息态功能磁共振成像(fMRI)和扩散张量成像(DTI)观察精神分裂症患者与正常人小脑功能连接与解剖连接的差异。方法 分别对10例精神分裂症患者(精神分裂组)及14名健康对照者(正常对照组)行静息态脑fMRI和DTI。对数据进行后处理后得到功能连接的相关系数r值及小脑中脚的平均FA值,应用双样本t检验比较组间差异,并对两种数据进行相关性检验。结果 ①精神分裂组与左侧小脑功能连接改变显著的区域为双侧舌回、右侧额中回、双侧缘上回和左侧小脑(P<0.001,未校正);与右侧小脑功能连接改变显著的区域为双侧舌回、左侧中央前回和左侧缘上回(P<0.001,未校正);②精神分裂组左侧小脑中脚的FA值显著降低(P<0.05);③精神分裂组右侧小脑-右侧舌回的连接强度与右侧小脑中脚的FA值呈显著正相关(r=0.84,P<0.05)。结论 联合运用多种成像方式可能为理解小脑在精神分裂症病理生理学中的作用提供新的方向;精神分裂症患者静息态下小脑与大脑皮层某些区域的连接降低和小脑中脚局部白质纤维完整性受损的同时出现以及二者之间的相关性提示功能连接与解剖解剖之间存在密切关系。     

Non-parametric model selection for subject-specific topological organization of resting-state functional connectivity

In recent years, graph theory has been successfully applied to study functional and anatomical connectivity networks in the human brain. Most of these networks have shown small-world topological characteristics: high efficiency in long distance communication between nodes, combined with highly interconnected local clusters of nodes. Moreover, functional studies performed at high resolutions have presented convincing evidence that resting-state functional connectivity networks exhibits (exponentially truncated) scale-free behavior. Such evidence, however, was mostly presented qualitatively, in terms of linear regressions of the degree distributions on log-log plots. Even when quantitative measures were given, these were usually limited to the r(2) correlation coefficient. However, the r(2) statistic is not an optimal estimator of explained variance, when dealing with (truncated) power-law models. Recent developments in statistics have introduced new non-parametric approaches, based on the Kolmogorov-Smirnov test, for the problem of model selection. In this work, we have built on this idea to statistically tackle the issue of model selection for the degree distribution of functional connectivity at rest. The analysis, performed at voxel level and in a subject-specific fashion, confirmed the superiority of a truncated power-law model, showing high consistency across subjects. Moreover, the most highly connected voxels were found to be consistently part of the default mode network. Our results provide statistically sound support to the evidence previously presented in literature for a truncated power-law model of resting-state functional connectivity.     

Anticorrelated resting-state functional connectivity in awake rat brain

Resting-state functional connectivity (RSFC) measured by functional magnetic resonance imaging has played an essential role in understanding neural circuitry and brain diseases. The vast majority of RSFC studies have been focused on positive RSFC, whereas our understanding about its conceptual counterpart - negative RSFC (i.e. anticorrelation) - remains elusive. To date, anticorrelated RSFC has yet been observed without the commonly used preprocessing step of global signal correction. However, this step can induce artifactual anticorrelation (Murphy et al., 2009), making it difficult to determine whether the observed anticorrelation in humans is a processing artifact (Fox et al., 2005). In this report we demonstrated robust anticorrelated RSFC in a well characterized frontolimbic circuit between the infralimbic cortex (IL) and amygdala in the awake rat. This anticorrelation was anatomically specific, highly reproducible and independent of preprocessing methods. Interestingly, this anticorrelated relationship was absent in anesthetized rats even with global signal correction, further supporting its functional significance. Establishing negative RSFC independent of data preprocessing methods will significantly enhance the applicability of RSFC in better understanding neural circuitries and brain networks. In addition, combining the neurobiological data of the IL-amygdala circuit in rodents, the finding of the present study will enable further investigation of the neurobiological basis underlying anticorrelation.     

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。     

Pleasant human touch is represented in pregenual anterior cingulate cortex

Touch massage (TM) is a form of pleasant touch stimulation used as treatment in clinical settings and found to improve well-being and decrease anxiety, stress, and pain. Emotional responses reported during and after TM have been studied, but the underlying mechanisms are still largely unexplored. In this study, we used functional magnetic resonance (fMRI) to test the hypothesis that the combination of human touch (i.e. skin-to-skin contact) with movement is eliciting a specific response in brain areas coding for pleasant sensations. The design included four different touch conditions; human touch with or without movement and rubber glove with or without movement. Force (2.5 N) and velocity (1.5 cm/s) were held constant across conditions. The pleasantness of the four different touch stimulations was rated on a visual analog scale (VAS-scale) and human touch was rated as most pleasant, particularly in combination with movement. The fMRI results revealed that TM stimulation most strongly activated the pregenual anterior cingulate cortex (pgACC). These results are consistent with findings showing pgACC activation during various rewarding pleasant stimulations. This area is also known to be activated by both opioid analgesia and placebo. Together with these prior results, our finding furthers the understanding of the basis for positive TM treatment effects.     

正常人运动皮质的功能连接网络及其小世界性

目的 利用静息态fMRI观察运动皮质的功能连接网络及其小世界性.方法 对90名健康成年志愿者行静息态fMRI数据采集,分别以双侧M1区为种子点获得全脑正性及负性功能连接脑图.以这些区域作为节点,计算其平均聚类系数Cp和平均最短路径长度Lp、全脑随机网络属性Crand和Lrana;按照公式γ=Cp/C怕nd＞1和λ=Lp/Lrand≈1分别计算γ及λ值,以验证其小世界网络属性.结果 静息态以M1区为种子点的正激活区域主要包括双侧初级运动皮质、运动前区及辅助运动区;负激活区域包括双侧额上回、楔前叶、缘上回、角回、双侧颞上回及小脑后叶.在矩阵稀疏度0.1≤Sparsity＜0.5范围内,这些区域的小世界属性符合γ=Cp/Crand＞1及λ=Lp/Lrand≈1.结论 运动皮质的正性连接主要集中在运动系统内,负性连接与脑的默认网络类似,运动皮质功能网络具有小世界性.     

Frequency-dependent functional connectivity within resting-state networks: an atlas-based MEG beamformer solution

The brain consists of functional units with more-or-less specific information processing capabilities, yet cognitive functions require the co-ordinated activity of these spatially separated units. Magnetoencephalography (MEG) has the temporal resolution to capture these frequency-dependent interactions, although, due to volume conduction and field spread, spurious estimates may be obtained when functional connectivity is estimated on the basis of the extra-cranial recordings directly. Connectivity estimates on the basis of reconstructed sources may similarly be affected by biases introduced by the source reconstruction approach.Here we propose an analysis framework to reliably determine functional connectivity that is based around two main ideas: (i) functional connectivity is computed for a set of atlas-based ROIs in anatomical space that covers almost the entire brain, aiding the interpretation of MEG functional connectivity/network studies, as well as the comparison with other modalities; (ii) volume conduction and similar bias effects are removed by using a functional connectivity estimator that is insensitive to these effects, namely the Phase Lag Index (PLI).Our analysis approach was applied to eyes-closed resting-state MEG data for thirteen healthy participants. We first demonstrate that functional connectivity estimates based on phase coherence, even at the source-level, are biased due to the effects of volume conduction and field spread. In contrast, functional connectivity estimates based on PLI are not affected by these biases. We then looked at mean PLI, or weighted degree, over areas and subjects and found significant mean connectivity in three (alpha, beta, gamma) of the five (including theta and delta) classical frequency bands tested. These frequency-band dependent patterns of resting-state functional connectivity were distinctive; with the alpha and beta band connectivity confined to posterior and sensorimotor areas respectively, and with a generally more dispersed pattern for the gamma band. Generally, these patterns corresponded closely to patterns of relative source power, suggesting that the most active brain regions are also the ones that are most-densely connected.Our results reveal for the first time, using an analysis framework that enables the reliable characterisation of resting-state dynamics in the human brain, how resting-state networks of functionally connected regions vary in a frequency-dependent manner across the cortex.     

基于局部一致性的脑静息功能模式偏侧化研究

目的 应用局部一致性方法揭示静息状态下大脑左右半球在局部区域内功能模式的偏侧化差异.方法 采集21名健康的在校大学生睁眼条件下6分钟的静息状态功能磁共振扫描数据.结果 在前额下回、中央前回区域右脑局部一致性均高于左脑区域,而在颞上回、楔叶区右脑局部一致性小于左脑区域.结论 静息状态下大脑功能模式不是单一的左侧或右偏侧化...     

Sex differences in connectivity of the subgenual anterior cingulate cortex

We previously reported that women exhibit greater heat pain adaptation to a prolonged painful stimulus and greater habituation to repeated painful stimuli than men. The neural mechanism underlying this sex difference is unknown. However, Bingel et al. (2007) have shown that pain habituation after 8 days of daily pain testing is associated with an increase in pain-evoked activity of the subgenual anterior cingulate cortex (sgACC), suggesting that pain habituation may be mediated via connectivity between the sgACC and the descending pain antinociceptive system. Therefore, we investigated whether women have stronger functional connectivity (FC) and greater structural connectivity (SC) compared to men between the sgACC and the descending antinociceptive system. Our analyses revealed that 1) women exhibited greater FC between the sgACC and the periaqueductal gray (PAG), raphe nucleus, medial thalamus, and anterior midcingulate cortex (aMCC) than men; 2) men had stronger sgACC FC with the anterior insula and temporoparietal junction than women; 3) women and men exhibited comparable SC of the sgACC with the PAG, thalamus, aMCC, anterior insula, and amygdala; and 4) men have stronger sgACC SC with the hypothalamus than women. These data indicate that brain circuitry in women may provide for greater engagement of the descending modulation system mediating pain habituation. In contrast, in men, the salience network may be more engaged, which could support greater sustained attention to pain, thereby preventing pain habituation. Furthermore, the hypothalamus findings suggest a more powerful stress and endorphin-based system at play in men than women.     

麻醉大鼠皮层及纹状体静息态脑功能网络连接

目的 以功能连接分析方法探讨大鼠麻醉状态和呼吸、心跳消失早期状态不同脑部位静息态自主性BOLD低频振荡(LFBF)信号的变化。 方法 对SD大鼠20只,于吸入麻醉后应用7.0T小动物磁共振仪行MRI,采集鼠脑解剖及功能成像数据;处死大鼠,呼吸、心跳停止5 min后以相同方法行鼠脑MRI;分别以大脑皮层和纹状体为ROI,以功能连接分析方法行脑功能相关性分析。 结果 麻醉状态下皮层相关性强于纹状体,信号差异范围以皮层为主;呼吸、心跳停止早期皮层与纹状体相关性差异变小,信号差异以皮层之外的区域为主;相应ROI内两种状态相关系数差异有统计学意义。 结论 麻醉状态下大鼠脑功能活动网络依然存在。LFBF信号蕴含着神经活动的生理性信息,可能为研究局限性脑缺血早期脑神经活动变化及预后评估提供一种新的技术。     

The precuneus/posterior cingulate cortex plays a pivotal role in the default mode network: Evidence from a partial correlation network analysis

Recent research has shown that intrinsic brain activity as observed by functional magnetic resonance imaging (fMRI) manifest itself as coherent signal changes in networks encompassing brain regions that span long-range neuronal pathways. One of these networks, the so called default mode network, has become the primary target in recent investigations to link intrinsic activity to cognition and how intrinsic signal changes may be altered in disease. In this study we assessed functional connectivity within the default mode network during both rest and a continuous working memory task on a region-by-region basis using partial correlation analysis, a data-driven method that provides insight into effective connectivity within neuronal networks. Prominent features of functional connectivity within the default mode network included an overall strong level of interaction between the precuneus/posterior cingulate region and the rest of the default mode network, as well as a high degree of interaction between the left and right medial temporal lobes combined with weak interactions between the medial temporal lobes and the rest of the default mode network. Additionally, we found support for strong interactions between the precuneus/posterior cingulate cortex and the left inferior parietal lobe as well as between the dorsal and ventral sections of the medial prefrontal cortex. The suggested pivotal role of the precuneus/posterior cingulate cortex in the default mode network is discussed.     

静息态功能磁共振成像观察正常人听觉皮层功能

目的 探讨正常人听觉皮层与全脑的正相关及负相关的功能连接.方法 采用静息态下平面回波成像技术采集44名健康受试者fMRI数据,分别以左侧及右侧AⅠ区为种子点,用功能连接的方法观察左、右大脑初级听觉皮层与全脑的正相关及负相关功能连接脑图.结果 分别以双侧AⅠ区为种子点时,正激活的脑网络主要包含双侧AⅠ、AⅡ、岛叶、辅助运动区及扣带回,以同侧为主;与右侧AⅠ区相关的正激活脑区还包括同侧背侧丘脑.与双侧AⅠ区相关的负激活脑网络与脑默认网络大体一致,主要包括双侧后扣带回/楔前叶、额叶内侧回、顶下小叶,双侧小脑半球可见明显激活.结论 静息态磁共振功能连接可满意显示听觉皮层的连接脑图.正相关功能连接主要局限在听觉系统内,负相关功能连接类似于默认网络.