慢性疼痛的脑机制及静息态功能性磁共振研究

疼痛具有多维属性,包括感觉识别、情绪动机和认知评价等3个方面,对于人类的生存具有重要意义.然而,持久的疼痛可能影响身体多器官系统的功能,导致严重的健康问题.研究表明:慢性疼痛患者普遍存在大脑皮层灰质减少,这反映出疼痛造成了大脑的结构性损伤.近年来功能性磁共振成像(functianal magnetic resonance imaging,fMRI)凭借其无创伤性及可准确定位脑功能区等特点,已成为脑功能成像研究的常用工具.静息态fMRI研究的是大脑在静息状态时的自发活动,通过对fMRI信号的分析,得到慢性疼痛患者静息状态时脑中性质和连接的异常改变.本文综述慢性疼痛患者的脑机制及静息态fMRI应用于慢性疼痛患者的研究现状与进展.     

轻微型肝性脑病患者静息状态下脑缺省模式网络

目的 利用静息功能磁共振成像(fMRI)观察轻微型肝性脑病(MHE)患者脑缺省模式网络的改变. 方法对14例MHE患者和14名正常对照者行静息状态下的功能磁共振扫描,利用独立成分分析方法,分离得到各自的脑缺省模式网络脑区,各组进行单样本t检验组内分析和两样本t检验组间分析,观察MHE患者静息状态下脑缺省模式网络的改变. 结果 MHE患者和正常对照组均显示出典型的静息态脑缺省模式网络空间分布模式.但与正常对照组相比,MHE患者大部分脑缺省模式网络脑区功能连接降低,包括:左侧后扣带回、双侧前扣带回、双侧额中回、左侧海马旁回;而右侧楔前叶的功能连接较正常对照组升高. 结论静息状态下,MHE患者大部分脑缺省模式网络脑区功能连接度下降,而楔前叶增加,反映了MHE患者的大脑内源性功能组织发生损伤.静息fMRI可用于观察MHE患者脑缺省模式网络的改变.     

基于Rs-fMRI的维、汉语脑卒中后失语症患者的脑功能研究

目的 利用静息态功能磁共振成像技术（Rs-fMRI）研究维族和汉族脑卒中失语症患者在静息态下脑自发活动的差异区,并初步探讨形成差异的原因。 方法 利用Rs-fMRI采集15例汉族脑卒中失语症患者（汉语组）和12例维族脑卒中失语症患者（维语组）静息态下的fMRI数据,对数据预处理后进行低频振幅（ALFF）指标的计算,最后对两组数据做组间统计学比较。 结果 静息状态下汉语患者的ALFF大于维语患者,汉语患者的右侧丘脑ALFF值增加。 结论 在静息态下汉族失语症患者的右侧丘脑处ALFF大于维族患者,可能是由于汉族患者左侧脑区脑卒中后,右侧丘脑部分参与了新的语言回路,对语言功能的损失起到了一定的代偿作用。     

静息态默认功能网络磁共振成像研究

大脑处于无任务的静息状态时,仍存在着某种功能活动,表明大脑在静息状态时存在有组织的网络.扣带回后部皮层、楔前叶、前额叶内侧皮层构成静息态默认功能网络.本文就这方面的研究进展作一综述.     

功能磁共振成像评价帕金森患者静息状态下脑功能连接

目的 采用功能磁共振成像(fMRI)评价帕金森病(PD)患者静息状态下脑功能连接的特点. 方法 对14例符合PD诊断标准的患者及14名健康者行静息态脑fMRI,选双侧壳核为感兴趣区,PD患者与正常对照组间脑功能连接的差异用随机效应两样本t检验.结果 与正常对照组相比,PD患者在静息状态下前额叶中内侧、双侧尾状核头部、左侧脑岛、左侧梭状回等脑区功能连接减低;双侧小脑半球、双侧舌回、双侧颞中回、右中央前回、右侧额上回、右侧额下回、右侧扣带回后部、左侧额中回等脑区功能连接增强.结论 PD患者在静息状态下存在异常的脑功能连接网络.     

正常老年人静息状态脑功能磁共振的默认网络研究

目的 探讨正常老年人静息状态下的功能磁共振(fMRI)默认网络结构及意义.方法 正常健康老年受试者18人,接受静息fMRI扫描;通过时程相关方法检测fMRI数据低频波动信号中以后扣带回为种子区的默认网络,经SPM2软件单样本t检验,激活脑区周值设为经校正的P<0.001,激活像素范围>5.结果 与后扣带回相关的静息状态网络连接的脑区有:前额叶内侧区、海马、颞极、颞中上回、丘脑枕部、楔叶及楔前叶、部分视皮层、顶下小叶.海马区和顶下小叶呈侧化性激活.结论 正常老年人存在基本完整的静息状态fMRI默认网络结构,其部分呈侧化性可能是与老年期脑功能重塑有关.     

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...     

ICA-R算法在静息态功能磁共振图像的应用研究

目的：针对传统独立成分分析（ICA）方法在处理功能磁共振（fMRI）数据时存在计算量大、效率低等问题,提出基于ICA-R算法处理数据。方法：将脑默认网络的幅值信息作为源信号的部分先验知识,以参考信号的形式引入到传统ICA算法提取静息态fMRI（rsfMRI）数据的默认网络。结果：ICA—R算法能够有效提取符合大脑在静息状态时的自发活动特征的脑默认网络。结论：ICA-R算法克服了传统ICA算法以分离所有的源信号为目标造成的效率低等缺点,避免了传统ICA算法中需要后续处理的步骤,提高了算法效率,并且能够准确地提取脑脑默认网络。     

终末期肾病患者认知功能损伤的静息态功能MRI研究进展

终末期肾病（ESRD）常伴随全身多器官功能损伤。认知功能损伤在ESRD患者中发病率较高,静息状态下脑活动异常是ESRD认知损伤的表现之一。静息态fMRI（rs-fMRI）可分为功能分离分析法和功能整合分析法两类,从不同方面反映大脑神经活动变化。rs-fMRI无创、无辐射且时间和空间分辨力较高,已逐渐成为认知损害神经生理机制的有效研究手段。本文对ESRD伴认知功能损伤的病理机制及rs-fMRI研究现状及进展进行综述。     

帕金森病静息态功能磁共振成像研究与进展

帕金森病作为神经退行性疾病,通过中枢神经环路导致整个大脑皮层内广泛的功能和结构改变,表现出不同程度的运动症状和非运动症状。功能磁共振成像（functional magnetic resonance imaging,fMRI）是一种对人体无创性高分辨率磁共振检查技术,在探测大脑内部结构变化的同时,还能分析人脑的不同区域间血氧水平依赖信号关系,研究其神经系统生物活动方式的功能联系特征,从而创立大脑功能联系网络,其中rs-fMRI是一种在静止状态下检测出大脑自发神经细胞活动的先进技术,现已广泛应用于探究PD患者脑区神经元活动性的改变。     

A wavelet-based method for measuring the oscillatory dynamics of resting-state functional connectivity in MEG

Determining the dynamics of functional connectivity is critical for understanding the brain. Recent functional magnetic resonance imaging (fMRI) studies demonstrate that measuring correlations between brain regions in resting-state activity can be used to reveal intrinsic neural networks. To study the oscillatory dynamics that underlie intrinsic functional connectivity between regions requires high temporal resolution measures of electrophysiological brain activity, such as magnetoencephalography (MEG). However, there is a lack of consensus as to the best method for examining connectivity in resting-state MEG data. Here we adapted a wavelet-based method for measuring phase-locking with respect to the frequency of neural oscillations. This method employs anatomical MRI information combined with MEG data using the minimum norm estimate inverse solution to produce functional connectivity maps from a "seed" region to all other locations on the cortical surface at any and all frequencies of interest. We test this method by simulating phase-locked oscillations at various points on the cortical surface, which illustrates a substantial artifact that results from imperfections in the inverse solution. We demonstrate that normalizing resting-state MEG data using phase-locking values computed on empty room data reduces much of the effects of this artifact. We then use this method with eight subjects to reveal intrinsic interhemispheric connectivity in the auditory network in the alpha frequency band in a silent environment. This spectral resting-state functional connectivity imaging method may allow us to better understand the oscillatory dynamics underlying intrinsic functional connectivity in the human brain.     

Modeling the outcome of structural disconnection on resting-state functional connectivity

A growing body of experimental evidence suggests that functional connectivity at rest is shaped by the underlying anatomical structure. Furthermore, the organizational properties of resting-state functional networks are thought to serve as the basis for an optimal cognitive integration. A disconnection at the structural level, as occurring in some brain diseases, would then lead to functional and presumably cognitive impairments. In this work, we propose a computational model to investigate the role of a structural disconnection (encompassing putative local/global and axonal/synaptic mechanisms) on the organizational properties of emergent functional networks. The brain's spontaneous neural activity and the corresponding hemodynamic response were simulated using a large-scale network model, consisting of local neural populations coupled through white matter fibers. For a certain coupling strength, simulations reproduced healthy resting-state functional connectivity with graph properties in the range of the ones reported experimentally. When the structural connectivity is decreased, either globally or locally, the resultant simulated functional connectivity exhibited a network reorganization characterized by an increase in hierarchy, efficiency and robustness, a decrease in small-worldness and clustering and a narrower degree distribution, in the same way as recently reported for schizophrenia patients. Theoretical results indicate that most disconnection-related neuropathologies should induce the same qualitative changes in resting-state brain activity.     

Increased power spectral density in resting-state pain-related brain networks in fibromyalgia

Fibromyalgia (FM), characterized by chronic widespread pain, is known to be associated with heightened responses to painful stimuli and atypical resting-state functional connectivity among pain-related regions of the brain. Previous studies of FM using resting-state functional magnetic resonance imaging (rs-fMRI) have focused on intrinsic functional connectivity, which maps the spatial distribution of temporal correlations among spontaneous low-frequency fluctuation in functional MRI (fMRI) resting-state data. In the current study, using rs-fMRI data in the frequency domain, we investigated the possible alteration of power spectral density (PSD) of low-frequency fluctuation in brain regions associated with central pain processing in patients with FM. rsfMRI data were obtained from 19 patients with FM and 20 age-matched healthy female control subjects. For each subject, the PSDs for each brain region identified from functional connectivity maps were computed for the frequency band of 0.01 to 0.25 Hz. For each group, the average PSD was determined for each brain region and a 2-sample t test was performed to determine the difference in power between the 2 groups. According to the results, patients with FM exhibited significantly increased frequency power in the primary somatosensory cortex (S1), supplementary motor area (SMA), dorsolateral prefrontal cortex, and amygdala. In patients with FM, the increase in PSD did not show an association with depression or anxiety. Therefore, our findings of atypical increased frequency power during the resting state in pain-related brain regions may implicate the enhanced resting-state baseline neural activity in several brain regions associated with pain processing in FM.     

Pharmacological modulation of functional connectivity: α2-adrenergic receptor agonist alters synchrony but not neural activation

Correlative low frequency fluctuations in functional MRI (fMRI) signals across brain regions at rest have been taken as a measure of functional connectivity to map large-scale neural networks; however, the neural origin is still not clear. Receptor-targeted pharmacological manipulation could elucidate the role of neuroreceptor systems in resting-state functional connectivity to provide another perspective on the mechanism. In this study, the dose-dependent effects of an α(2)-adrenergic receptor agonist, medetomidine, on brain activation and functional connectivity were investigated. Forepaw stimulation-induced activation and resting-state fluctuation in the rat somatosensory cortices and caudate putamen were measured using the blood oxygenation level dependent (BOLD) fMRI. The results showed significant dose-dependent suppression of inter-hemispheric correlation but not the amplitude in the somatosensory areas, while the stimulation-induced activation in the same areas remained unchanged. To clarify the potential change in the hemodynamic response caused by the vasoconstrictive effect of medetomidine, the resting perfusion fluctuation was studied by arterial spin labeling and showed similar results as the BOLD. This suggests that the oxygen metabolic rate and hence the neural activity may not be affected by medetomidine but only the synchrony between brain regions was suppressed. Furthermore, no change in functional connectivity with medetomidine dosages was seen in the caudate putamen, a region with much lower α(2)-receptor density. These results indicate that resting-state signal correlation may reflect underlying neuroreceptor activity and a potential role of the adrenergic system in the functional connectivity.     

左旋甲状腺素对甲状腺功能减退症患者脑默认网络静息态功能连接的影响

目的研究甲状腺功能减退症(简称甲减)患者在左旋甲状腺激素(L-T4)替代治疗前后,默认网络脑区静息态脑功能连接的改变。方法运用静息态功能磁共振(rsf MRI)技术检测14例初诊成人原发性甲减患者在左旋甲状腺素替代治疗前后及15例健康对照的静息态脑功能连接强度。结果利用基于种子的分析方法显示,健康对照组前后两次扫描双侧丘脑与后扣带回/楔前叶的功能连接强度差异无统计学意义;甲减组治疗后扫描时,双侧丘脑的丘脑枕区域与后扣带回/楔前叶之间的功能连接强度较治疗前出现显著性下降(左侧:P=0.007,右侧:P=0.001)。结论甲减患者双侧丘脑与后扣带回/楔前叶之间静息态脑功能连接强度在左旋甲状腺素替代治疗后较治疗前显著降低。     

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.     

间期痫样发放对内侧颞叶癫痫脑网络的影响

目的探讨间期痫样发放对内侧颞叶癫痫患者脑静息态网络的影响,揭示间期癫痫活动发放对全脑功能的损害机制。材料与方法从45例行同步脑电f MRI数据采集单侧颞叶癫痫患者中,挑选35例(左侧颞叶癫痫患者18例、右侧颞叶癫痫患者17例),以同步脑电图监测,每一患者均采集间期痫样发放及无痫样发放状态静息态f MRI数据。采用独立成分分析方法,分别提取患者两种状态的核心网络、背侧注意网络、执行控制网络、默认网络及感觉运动网络等7套内在连接网络。采用配对t检验比较痫样发放及无痫样发放状态m TLE患者脑内在连接网络的差异。结果相比未发放状态,发放状态下颞叶癫痫患者核心网络的前扣带回功能连接增强,听觉网络的脑岛及颞上回功能连接减低。此外,背侧注意网络的顶上小叶在左侧颞叶癫痫患者表现为功能连接增强,而在右侧表现为连接减弱。前默认网络的额中回在右侧表现为功能连接减弱,而后默认网络颞中回及后扣带回在右侧表现为功能连接增强。执行控制网络的中扣带回和视觉网络枕叶皮层在左侧表现为功能连接增强。相关分析结果显示,左侧组视觉网络及右侧组听觉网络内连接强度的变化与发放状态下IEDs发放次数呈正相关。结论内侧颞叶癫痫发作间期痫样发放对脑高级认知网络及感知觉网络均产生了广泛影响,尤其是对参与脑高级认知功能网络的损害,这有助于进一步了解海马硬化这一特异性内侧颞叶癫痫在发作间期脑功能受损机制。     

Antidepressant medications reduce subcortical-cortical resting-state functional connectivity in healthy volunteers

Studies have revealed abnormalities in resting-state functional connectivity in those with major depressive disorder specifically in areas such as the dorsal anterior cingulate, thalamus, amygdala, the pallidostriatum and subgenual cingulate. However, the effect of antidepressant medications on human brain function is less clear and the effect of these drugs on resting-state functional connectivity is unknown. Forty volunteers matched for age and gender with no previous psychiatric history received either citalopram (SSRI; selective serotonergic reuptake inhibitor), reboxetine (SNRI; selective noradrenergic reuptake inhibitor) or placebo for 7 days in a double-blind design. Using resting-state functional magnetic resonance imaging and seed based connectivity analysis we selected the right nucleus accumbens, the right amygdala, the subgenual cingulate and the dorsal medial prefrontal cortex as seed regions. Mood and subjective experience were also measured before and after drug administration using self-report scales. Despite no differences in mood across the three groups, we found reduced connectivity between the amygdala and the ventral medial prefrontal cortex in the citalopram group and the amygdala and the orbitofrontal cortex for the reboxetine group. We also found reduced striatal-orbitofrontal cortex connectivity in the reboxetine group. These data suggest that antidepressant medications can decrease resting-state functional connectivity independent of mood change and in areas known to mediate reward and emotional processing in the brain. We conclude that hypothesis-driven seed based analysis of resting-state fMRI supports the proposition that antidepressant medications might work by normalising the elevated resting-state functional connectivity seen in depressed patients.     

低频振幅fMRI评价精神分裂症患者静息状态下脑功能活动

目的 采用低频振幅(ALFF)方法评价精神分裂症患者静息状态下脑功能活动。 方法 对13例符合精神分裂症诊断标准的患者(精神分裂症组)及18名健康志愿者(正常对照组)行静息态脑fMR扫描,精神分裂症患者和正常对照者的ALFF差异用双样本t检验。 结果 与正常对照组相比,精神分裂症组静息状态下右侧胼胝体压部、右侧枕叶、左侧小脑后叶、左侧额上回和左侧楔前叶脑区ALFF增高,差异有统计学意义(P<0.001,未校正);双侧中央后回和左侧楔前叶脑区ALFF降低,差异有统计学意义(P<0.001,未校正)。 结论 精神分裂症患者静息状态下脑功能存在异常,ALFF有助于对精神分裂症患者静息状态脑功能的理解。     

静息态功能磁共振评价针刺足三里穴后效应

目的 研究针刺足三里穴后引起静息态脑功能活动的时间变化规律,探讨针刺后效应.方法 对17名健康志愿者,采集针刺双侧足三里穴拔针后的第10、25、45和60 min的静息态功能磁共振数据,利用REST软件计算低频振幅(ALFF),然后用SPM5与针刺前相应数据进行配对t检验,得到拔针后上述4个时间点相对于针刺前脑区ALFF的变化及其趋势.结果 针刺足三里穴拔针后引起了脑部ALFF变化,拔针后第10和第25 min ALFF显著增高脑区数量最多,主要包括双侧枕叶、双侧颞中回、左侧楔前叶、左侧顶下小叶、左侧中央后回、左侧小脑后叶、右侧扣带前回及右侧扣带后回等;拔针后第45和第60 min ALFF显著增高脑区逐渐减少,主要包括双侧枕叶、左侧楔前叶、左侧顶下小叶、左侧顶上小叶及右侧扣带后回等.结论 针刺后效应对静息态脑网络活动产生显著影响,拔针后第10和25 min为针刺后效应重要时间点.