Altered small-world brain functional networks and duration of heroin use in male abstinent heroin-dependent individuals

Although previous studies reported addiction-related alteration in resting-state brain connectivity, it is unclear whether these resting-state connectivity alterations were associated with chronic heroin use. In the current study, graph theory analysis (GTA) was applied to detect abnormal topological properties in heroin-dependent individuals. Several statistical parameters, such as degree (D), clustering coefficient (C) and shortest absolute path length (L), were included to test whether or not there was significant correlation between these parameters and the duration of heroin use. Our results demonstrated abnormal topological properties in several brain regions among our heroin-dependent subjects. Some of these regions are key areas of drug addiction-related circuits (control, reward, motivation/drive and memory), while others are involved in stress regulation. In addition, the duration of heroin use was positively correlated with the parameter D in the right parahippocampal gyrus, left putamen and bilateral cerebellum, but negatively correlated with the parameter L in the same regions. Our findings suggested that there is abnormal functional organization in heroin-dependent individuals and that the duration of heroin use is a critical factor leading to the altered brain connectivity.     

海洛因成瘾者静息状态下脑功能连接研究

目的:探讨海洛因成瘾者在静息状态下脑功能连接与正常对照的区别。方法:对16例海洛因成瘾者和16例匹配的正常对照进行静息状态下的脑功能扫描。选择杏仁核为种子区,比较两组之间脑功能连接的区别。结果:同正常对照相比,海洛因成瘾者杏仁核与左右扣带回、左右扣带回前部以及右侧Brodmann 24脑区功能连接下降。结论:这种功能连接的下降可能反映出海洛因成瘾者的杏仁核功能处于脱抑制状态,造成海洛因成瘾者犒赏、动机、记忆功能异常,从而参与了海洛因成瘾行为产生和维持。     

Combining spatial and temporal information to explore resting-state networks changes in abstinent heroin-dependent individuals

Majority of previous heroin fMRI studies focused on abnormal brain function in heroin-dependent individuals. However, few fMRI studies focused on the resting-state abnormalities in heroin-dependent individuals and assessed the relationship between the resting-state functional connectivity changes and duration of heroin use. In the present study, discrete cosine transform (DCT) was employed to explore spatial distribution of low frequency BOLD oscillations in heroin-dependent individuals and healthy subjects during resting-state; meanwhile resting-state functional connectivity analysis was used to investigate the temporal signatures of overlapping brain regions obtained in DCT analysis among these two groups. Main finding of the present study is that the default mode network (DMN) and rostral anterior cingulate cortex (rACC) network of heroin-dependent individuals were changed compared with healthy subjects. More importantly, these changes negatively correlated with duration of heroin use. These resting-state functional abnormalites in heroin-dependent individuals provided evidence for abnormal functional organization in heroin-dependent individuals, such as functional impairments in decision-making and inhibitory control.     

Differential relationships between transcallosal structural and functional connectivity in young and older adults

Numerous studies have identified age differences in brain structure and function that correlate with declines in motor performance. While these investigations have typically focused on activity in isolated regions of the brain, resting state functional connectivity magnetic resonance imaging (MRI) and diffusion tensor imaging allow for more integrative assessments of spatially disparate neural networks. The novel contribution of the current study is to combine both resting state functional connectivity and diffusion tensor imaging to examine motor corticocortical circuits in young and older adults. We find that relatively greater functional connectivity between the primary motor cortices was strongly associated with decreased structural connectivity and poorer motor performance solely in older adults. We suggest that greater functional connectivity in older adults may be reflective of a release from the normally predominantly inhibitory interhemispheric communication associated with the primary motor cortices.     

Gray matter deficits and resting-state abnormalities in abstinent heroin-dependent individuals

Previous neuroimaging studies have demonstrated both structural and functional damages in heroin-dependent individuals. However, few studies investigated gray matter deficits and abnormal resting-state networks together in heroin-dependent individuals. In the present study, voxel-based morphometry (VBM) was used to identify brain regions with gray matter density reduction. Resting-state fMRI connectivity analysis was employed to assess potential functional abnormalities during resting-state. All clinical significances were investigated by examining their association with duration of heroin use. Compared with healthy subjects, heroin-dependent individuals showed significant reduction in gray matter density in the right dorsolateral prefrontal cortex (DLPFC) and a decrease in resting-state functional connectivity between the right DLPFC and left inferior parietal lobe (IPL). The gray matter density of the right DLPFC and its resting-state functional connectivity with the left IPL both showed significantly negative correlation with duration of heroin use, which were likely to be related to the functional impairments in decision-making and cognitive control exhibited by heroin-dependent individuals. Our findings demonstrated that long heroin dependence impairs the right DLPFC in heroin-dependent individuals, including structural deficits and resting-state functional impairments.     

Investigation of the effective connectivity of resting state networks in Alzheimer's disease: a functional MRI study combining independent components analysis and multivariate Granger causality analysis

Recent neuroimaging studies have shown that the cognitive and memory decline in patients with Alzheimer's disease (AD) is coupled with abnormal functions of focal brain regions and disrupted functional connectivity between distinct brain regions, as well as losses in small‐world attributes. However, the causal interactions among the spatially isolated, but functionally related, resting state networks (RSNs) are still largely unexplored. In this study, we first identified eight RSNs by independent components analysis from resting state functional MRI data of 18 patients with AD and 18 age‐matched healthy subjects. We then performed a multivariate Granger causality analysis (mGCA) to evaluate the effective connectivity among the RSNs. We found that patients with AD exhibited decreased causal interactions among the RSNs in both intensity and quantity relative to normal controls. Results from mGCA indicated that the causal interactions involving the default mode network and auditory network were weaker in patients with AD, whereas stronger causal connectivity emerged in relation to the memory network and executive control network. Our findings suggest that the default mode network plays a less important role in patients with AD. Increased causal connectivity of the memory network and self‐referential network may elucidate the dysfunctional and compensatory processes in the brain networks of patients with AD. These preliminary findings may provide a new pathway towards the determination of the neurophysiological mechanisms of AD. Copyright © 2012 John Wiley & Sons, Ltd.     

基于fMRI数据的静息脑功能连接

目的:应用功能磁共振成像数据,对静息状态下大脑视觉系统功能连接模式[1]进行考证,并对不同状态下人脑视觉功能连接网络的变化[2,3]情况进行了研究。方法:基于脑区局部同一性[4],测量出一给定体素的时间序列与全脑其他体素时间序列的相似性。我们分别采集了视觉任务和静止两种状态下的功能磁共振成像数据,先是用K-均值的聚类方法[5,6]对视觉任务状态下的功能磁共振成像数据进行分析,做出分类图。然后通过分类图找到感兴趣种子区,平均种子区中各个体素的时间响应曲线,利用这个时间序列曲线与全脑体素作互相关分析[7],得出视觉任务下的全脑功能连接图,再把同样的感兴趣种子区域定位到静息状态下的脑区中用种子相关分析方法,作出静息状态下全脑视觉系统功能连接的网络模式及分布规律。结果:分别得到了视觉任务状态下和静息状态下以相同种子区为中心的功能连接网络图。结论:无论是在静息状态还是在任务状态下,大脑视觉系统各脑区之间的确存在密切的功能连接,而且状态不同所得到的视觉功能连接网络也不相同。     

基于独立成分分析和时间相关分析的脑功能连通研究方法

目的：利用静息状态功能磁共振成像（functional magnetic resonance imaging，fMRI）技术，提出联合独立成分分析（independent component analysis，ICA）和时间相关分析的人脑功能连通性研究方法。方法：首先采用空间ICA定位任务激活的脑区；然后选择一个激活区作为感兴趣区域（region of interest，ROI），采用时间相关分析方法检测静息状态大脑特定皮层的功能连通性，并通过检测人脑运动皮层的功能连通性验证方法的有效性。结果：大脑运动皮层功能连通网络包括初级运动区、辅助运动区、初级感觉皮层、背侧前运动区和后顶骨体觉区。实验结果表明，静息状态下。时间相关分析检测到的运动皮层的功能连通网络与已知的解剖连通相一致。结论：利用静息fMRI。结合空间ICA和时间相关分析方法。检测了静息时人脑运动皮层的功能连通网络。为脑区间功能连通的研究提供了一种简便的、无损的、有效的研究方法。     

基于独立成分分析和时间相关分析的脑功能连通研究方法[英文]

目的:利用静息状态功能磁共振成像(functional magnetic resonance imaging,fMRI)技术,提出联合独立成分分析(independent component analysis,ICA)和时间相关分析的人脑功能连通性研究方法。方法:首先采用空间ICA定位任务激活的脑区;然后选择一个激活区作为感兴趣区域(region of interest,ROI),采用时间相关分析方法检测静息状态大脑特定皮层的功能连通性,并通过检测人脑运动皮层的功能连通性验证方法的有效性。结果:大脑运动皮层功能连通网络包括初级运动区、辅助运动区、初级感觉皮层、背侧前运动区和后顶骨体觉区。实验结果表明,静息状态下,时间相关分析检测到的运动皮层的功能连通网络与已知的解剖连通相一致。结论:利用静息fMRI,结合空间ICA和时间相关分析方法,检测了静息时人脑运动皮层的功能连通网络,为脑区间功能连通的研究提供了一种简便的、无损的、有效的研究方法。     

Joint amplitude and connectivity compensatory mechanisms in Parkinson's disease

Neuroimaging studies in Parkinson's disease (PD) have previously demonstrated several regions of hypo- and hyper-activation during voluntary movement. How these patterns of amplitude changes at multiple discrete foci relate to changes within functional networks recruited by a given task is unclear. Changes in both amplitude and connectivity have both been individually shown within the striato-thalamo-cortical (STC) loop in PD, as well as other regions, most consistently in the cerebellum and primary motor cortex. We have previously shown overactivation of the cerebellum and motor cortex in PD subjects off medication during a visuo-motor tracking task performed at three frequencies. Here, we show that this change in activation amplitude is also accompanied by significant changes in functional connectivity between regions of interest (ROIs), with enhanced connectivity within the cerebello-thalamo-cortical (CTC) loop as well as increased inter-hemispheric communication between several basal ganglia structures. Although changes in activation amplitude were influenced by the frequency of movement performed in the tracking task, functional connectivity changes were robustly present across all three task frequencies performed, suggesting that functional connectivity analysis in PD may be a more sensitive means of detecting plastic changes which are relatively invariant to the particulars of the experimental task. Additionally, we demonstrate amplitude and connectivity changes in structures that are typically active during the resting state, or “default-mode,” in PD. Unlike in STC/CTC loops, where the direction of change was the same for amplitude and connectivity, default-mode regions showed increased amplitude but decreased connectivity. Our results further support that the CTC is recruited in PD to compensate for dysfunctional basal ganglia circuits, and that this recruitment involves both amplitude and connectivity changes. The differing relationship between amplitude and connectivity changes within individual loops highlights the importance of jointly examining them in order to fully elucidate functional changes in Parkinson's disease.     

A review of hippocampal activation in post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is often characterized by deficits in memory encoding and retrieval and aberrant fear and extinction learning. The hippocampus plays a critical role in memory and contextual processing and has been implicated in intrinsic functional connectivity networks involved in self-referential thought and memory-related processes. This review focuses on hippocampal activation findings during memory and fear and extinction learning tasks, as well as resting state hippocampal connectivity in individuals with PTSD. A preponderance of functional neuroimaging studies to date, using memory, fear learning, and extinction tasks, report decreased or “controls comparable” hippocampal activation in individuals with PTSD, which is usually associated with poorer performance on the task imaged. Existing evidence thus raises the possibility that greater hippocampal recruitment in PTSD participants may be required for similar performance levels. Studies of resting state functional connectivity in PTSD predominantly report reduced within-network connectivity in the default mode network (DMN), as well as greater coupling between the DMN and salience network (SN) via the hippocampus. Together, these findings suggest that deficient hippocampal activation in PTSD may be associated with poorer performance during memory, extinction recall, and fear renewal tasks. Furthermore, studies of resting state connectivity implicate the hippocampus in decreased within-network DMN connectivity and greater coupling with SN regions characteristic of PTSD.     

Structural and functional abnormalities in migraine patients without aura

Migraine is a primary headache disorder characterized by recurrent attacks of throbbing pain associated with neurological, gastrointestinal and autonomic symptoms. Previous studies have detected structural deficits and functional impairments in migraine patients. However, researchers have failed to investigate the functional connectivity alterations of regions with structural deficits during the resting state. Twenty‐one migraine patients without aura and 21 age‐ and gender‐matched healthy controls participated in our study. Voxel‐based morphometric (VBM) analysis and functional connectivity were employed to investigate the abnormal structural and resting‐state properties, respectively, in migraine patients without aura. Relative to healthy comparison subjects, migraine patients showed significantly decreased gray matter volume in five brain regions: the left medial prefrontal cortex (MPFC), dorsal anterior cingulate cortex (dACC), right occipital lobe, cerebellum and brainstem. The gray matter volume of the dACC was correlated with the duration of disease in migraine patients, and thus we chose this region as the seeding area for resting‐state analysis. We found that migraine patients showed increased functional connectivity between several regions and the left dACC, i.e. the bilateral middle temporal lobe, orbitofrontal cortex (OFC) and left dorsolateral prefrontal cortex (DLPFC). Furthermore, the functional connectivity between the dACC and two regions (i.e. DLPFC and OFC) was correlated with the duration of disease in migraine patients. We suggest that frequent nociceptive input has modified the structural and functional patterns of the frontal cortex, and these changes may explain the functional impairments in migraine patients. Copyright © 2012 John Wiley & Sons, Ltd.     

Resting state connectivity of the medial prefrontal cortex covaries with individual differences in high‐frequency heart rate variability

Resting high‐frequency heart rate variability (HF‐HRV) relates to cardiac vagal control and predicts individual differences in health and longevity, but its functional neural correlates are not well defined. The medial prefrontal cortex (mPFC) encompasses visceral control regions that are components of intrinsic networks of the brain, particularly the default mode network (DMN) and the salience network (SN). Might individual differences in resting HF‐HRV covary with resting state neural activity in the DMN and SN, particularly within the mPFC? This question was addressed using fMRI data from an eyes‐open, 5‐min rest period during which echoplanar brain imaging yielded BOLD time series. Independent component analysis yielded functional connectivity estimates defining the DMN and SN. HF‐HRV was measured in a rest period outside of the scanner. Midlife (52% female) adults were assessed in two studies (Study 1, N = 107; Study 2, N = 112). Neither overall DMN nor SN connectivity strength was related to HF‐HRV. However, HF‐HRV related to connectivity of one region within mPFC shared by the DMN and SN, namely, the perigenual anterior cingulate cortex, an area with connectivity to other regions involved in autonomic control. In sum, HF‐HRV does not seem directly related to global resting state activity of intrinsic brain networks, but rather to more localized connectivity. A mPFC region was of particular interest as connectivity related to HF‐HRV was shared by the DMN and SN. These findings may indicate a functional basis for the coordination of autonomic cardiac control with engagement and disengagement from the environment.     

慢性失眠患者大脑蓝斑的异常静息态功能连接

目的:利用功能连接方法观察慢性失眠患者静息态下蓝斑的异常功能连接。方法:采集49例慢性失眠患者以及47例性别年龄和受教育程度相匹配的健康对照组的功能磁共振图像,以蓝斑为感兴趣区域,与全脑其他体素进行功能连接分析,得到两组之间功能连接的差异脑区,再对异常连接脑区的功能连接值与临床量表分数做相关分析。结果:与对照组相比,慢性失眠患者蓝斑与右楔前叶皮质、右后扣带回皮质、左颞中回皮质、左距状沟周围皮质、右眶部额上回皮质之间的功能连接增强（P<0.05, FDR校正）,并且蓝斑与左颞中回皮质之间功能连接值与抑郁自评量表呈正相关（P=0.021）。结论:慢性失眠患者蓝斑与多个脑区（主要是默认模式网络）出现的异常功能连接,可能有助于更好地理解慢性失眠的神经生物学机制,可能为失眠的高度唤醒假说提供新的影像学证据。     

Detecting Functional Connectivity in fMRI Using PCA and Regression Analysis

A fMRI connectivity analysis approach combining principal component analysis (PCA) and regression analysis is proposed to detect functional connectivity between the brain regions. By first using PCA to identify clusters within the vectors of fMRI time series, more energy and information features in the signal can be maintained than using averaged values from brain regions of interest. Then, regression analysis can be applied to the extracted principal components in order to further investigate functional connectivity. Finally, t-test is applied and the patterns with t-values lager than a threshold are considered as functional connectivity mappings. The validity and reliability of the presented method were demonstrated with both simulated data and human fMRI data obtained during behavioral task and resting state. Compared to the conventional functional connectivity methods such as average signal based correlation analysis, independent component analysis (ICA) and PCA, the proposed method achieves competitive performance with greater accuracy and true positive rate (TPR). Furthermore, the ‘default mode’ and motor network results of resting-state fMRI data indicate that using PCA may improve upon application of existing regression analysis methods in study of human brain functional connectivity.     

Changes in resting connectivity during recovery from severe traumatic brain injury

In the present study we investigate neural network changes after moderate and severe traumatic brain injury (TBI) through the use of resting state functional connectivity (RSFC) methods. Using blood oxygen level dependent functional MRI, we examined RSFC at 3 and 6 months following resolution of posttraumatic amnesia. The goal of this study was to examine how regional off-task connectivity changes during a critical period of recovery from significant neurological disruption. This was achieved by examining regional changes in the intrinsic, or “resting”, BOLD fMRI signal in separate networks: 1) regions linked to goal-directed (or external-state) networks and 2) default mode (or internal-state) networks. Findings here demonstrate significantly increased resting connectivity internal-state networks in the TBI sample during the first 6 months following recovery. The most consistent finding was increased connectivity in both internal and external state networks to the insula and medial temporal regions during recovery. These findings were dissociable from repeat measurements in a matched healthy control sample.     

Resting‐state functional connectivity differentiates anxious apprehension and anxious arousal

Brain regions in the default mode network (DMN) display greater functional connectivity at rest or during self‐referential processing than during goal‐directed tasks. The present study assessed resting‐state connectivity as a function of anxious apprehension and anxious arousal, independent of depressive symptoms, in order to understand how these dimensions disrupt cognition. Whole‐brain, seed‐based analyses indicated differences between anxious apprehension and anxious arousal in DMN functional connectivity. Lower connectivity associated with higher anxious apprehension suggests decreased adaptive, inner‐focused thought processes, whereas higher connectivity at higher levels of anxious arousal may reflect elevated monitoring of physiological responses to threat. These findings further the conceptualization of anxious apprehension and anxious arousal as distinct psychological dimensions with distinct neural instantiations.     

正常脑老化中静息态功能磁共振成像功能连接的研究进展

【摘要】静息态功能磁共振成像（fMRI）作为一种不需要任务刺激就能呈现功能脑影像的技术手段,在临床上被广泛应 用。基于静息态fMRI的静息态功能连接（RSFC）,作为一种重要的计算机辅助分析法,能够度量不同脑区的脑功能连接 强度,对脑老化相关的神经科学领域的研究具有重要意义。本文介绍了功能连接的基本概念,总结了近年来脑老化相关 的人脑功能连接的研究成果,最后提出了该研究领域存在的问题及未来的研究方向。     

EEG Signatures of Dynamic Functional Network Connectivity States

The human brain operates by dynamically modulating different neural populations to enable goal directed behavior. The synchrony or lack thereof between different brain regions is thought to correspond to observed functional connectivity dynamics in resting state brain imaging data. In a large sample of healthy human adult subjects and utilizing a sliding windowed correlation method on functional imaging data, earlier we demonstrated the presence of seven distinct functional connectivity states/patterns between different brain networks that reliably occur across time and subjects. Whether these connectivity states correspond to meaningful electrophysiological signatures was not clear. In this study, using a dataset with concurrent EEG and resting state functional imaging data acquired during eyes open and eyes closed states, we demonstrate the replicability of previous findings in an independent sample, and identify EEG spectral signatures associated with these functional network connectivity changes. Eyes open and eyes closed conditions show common and different connectivity patterns that are associated with distinct EEG spectral signatures. Certain connectivity states are more prevalent in the eyes open case and some occur only in eyes closed state. Both conditions exhibit a state of increased thalamocortical anticorrelation associated with reduced EEG spectral alpha power and increased delta and theta power possibly reflecting drowsiness. This state occurs more frequently in the eyes closed state. In summary, we find a link between dynamic connectivity in fMRI data and concurrently collected EEG data, including a large effect of vigilance on functional connectivity. As demonstrated with EEG and fMRI, the stationarity of connectivity cannot be assumed, even for relatively short periods.     

Morphometric and functional connectivity changes in the brain of patients with obstructive sleep apnea: A meta‐analysis

Existing evidence for brain morphometric changes and functional connectivity alterations in patients with obstructive sleep apnea is mixed. The current study aimed to meta‐analyse the neuroimaging data, and thus synthesize a brain map showing locations with morphometric and functional connectivity differences between patients with obstructive sleep apnea and controls. Published studies to 2018 were retrieved and included into the analysis if they reported such between‐group differences using voxel‐based morphometry or resting‐state functional magnetic resonance imaging, and reported the results in the form of brain coordinates based on whole‐brain analysis. Twelve voxel‐based morphometry and seven resting‐state functional magnetic resonance imaging studies that comprised a total of 1,113 participants fulfilled the inclusion criteria. Compared with healthy controls, patients with obstructive sleep apnea had reduced resting‐state connectivity in the right anterior cingulate and larger grey matter volume in the right insula. Patients with obstructive sleep apnea do have morphometric and resting‐state connectivity alterations in the brain. These neural correlates may help explain the effects of obstructive sleep apnea on the emotion, cognition and quality of life of patients, and may be used in future for evaluating its treatment outcome.