Functional neural network analysis in frontotemporal dementia and Alzheimer's disease using EEG and graph theory

Background  

Although a large body of knowledge about both brain structure and function has been gathered over the last decades, we still have a poor understanding of their exact relationship. Graph theory provides a method to study the relation between network structure and function, and its application to neuroscientific data is an emerging research field. We investigated topological changes in large-scale functional brain networks in patients with Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) by means of graph theoretical analysis of resting-state EEG recordings. EEGs of 20 patients with mild to moderate AD, 15 FTLD patients, and 23 non-demented individuals were recorded in an eyes-closed resting-state. The synchronization likelihood (SL), a measure of functional connectivity, was calculated for each sensor pair in 0.5–4 Hz, 4–8 Hz, 8–10 Hz, 10–13 Hz, 13–30 Hz and 30–45 Hz frequency bands. The resulting connectivity matrices were converted to unweighted graphs, whose structure was characterized with several measures: mean clustering coefficient (local connectivity), characteristic path length (global connectivity) and degree correlation (network 'assortativity'). All results were normalized for network size and compared with random control networks.     

Altered networks in bothersome tinnitus: a functional connectivity study

Background  

The objective was to examine functional connectivity linked to the auditory system in patients with bothersome tinnitus. Activity was low frequency (< 0.1 Hz), spontaneous blood oxygenation level-dependent (BOLD) responses at rest. The question was whether the experience of chronic bothersome tinnitus induced changes in synaptic efficacy between co-activated components. Functional connectivity for seed regions in auditory, visual, attention, and control networks was computed across all 2 mm³ brain volumes in 17 patients with moderate-severe bothersome tinnitus (Tinnitus Handicap Index: average 53.5 ± 3.6 (range 38-76)) and 17 age-matched controls.     

Symbiotic relationship between brain structure and dynamics

Background  

Brain structure and dynamics are interdependent through processes such as activity-dependent neuroplasticity. In this study, we aim to theoretically examine this interdependence in a model of spontaneous cortical activity. To this end, we simulate spontaneous brain dynamics on structural connectivity networks, using coupled nonlinear maps. On slow time scales structural connectivity is gradually adjusted towards the resulting functional patterns via an unsupervised, activity-dependent rewiring rule. The present model has been previously shown to generate cortical-like, modular small-world structural topology from initially random connectivity. We provide further biophysical justification for this model and quantitatively characterize the relationship between structure, function and dynamics that accompanies the ensuing self-organization.     

时变动态贝叶斯网络模型及其在皮层脑电网络连接中的应用

大脑执行语言的发音需要顶叶、颞叶、额叶等多个脑区协同完成.皮层脑电具有高时间分辨率、较高空间分辨率和高信噪比等优势,为研究大脑的电生理特性提供了重要的技术手段.为了探索大脑对语言的动态处理过程,利用多尺度皮层脑电(标准电极与微电极)分析了被试在执行音节朗读任务时的皮层脑电信号的高频gamma段特征,提出采用时变动态贝叶斯网络构建单次实验任务的有向网络.结果显示该方法能够快速有效地构建语言任务过程中标准电极、微电极以及二者之间的有向网络连接,且反映了大规模网络(标准电极之间的连接)、局部网络(微电极之间的连接)以及大规模网络与局部网络之间的连接(标准电极与微电极之间的连接)随语言任务发生的动态改变.研究还发现,发音时刻之前与之后的网络连接存在显著性差异,且发音方式不同的音节网络间也存在明显差异.该研究将有助于癫痫等神经疾病的术前临床评估以及理解大脑对语言加工的实时处理过程.     

静息状态下脑功能连接的磁共振成像研究

静息状态下脑功能连接的磁共振成像研究近年来取得了迅猛发展. 通过对fMRI信号低频涨落成分的同步性分析,可以得到大脑静息态任意脑区的功能连接和多套网络系统,其中“默认网络”的发现可能为人脑固有网络的研究提供新的思路. 而静息态网络与解剖连接之间可能存在的对应,以及在神经精神疾病患者脑中性质和连接的异常改变,使其具有重要的研究和临床应用价值. 该文总结了静息状态功能磁共振成像的主要研究成果,对静息状态脑功能网络的发现和发展、研究方法、各网络及其特点以及在临床方面的应用进行简单的介绍和分析.     

Analysis of a phase synchronized functional network based on the rhythm of brain activities

Rhythm of brain activities represents oscillations of postsynaptic potentials in neocortex, therefore it can serve as an indicator of the brain activity state. In order to check the connectivity of brain rhythm, this paper develops a new method of constructing functional network based on phase synchronization. Electroencephalogram (EEG) data were collected while subjects looking at a green cross in two states, performing an attention task and relaxing with eyes-open. The EEG from these two states was filtered by three band-pass filters to obtain signals of theta (4--7 Hz), alpha (8--13 Hz) and beta (14--30 Hz) bands. Mean resultant length was used to estimate strength of phase synchronization in three bands to construct networks of both states, and mean degree K and cluster coefficient C of networks were calculated as a function of threshold. The result shows higher cluster coefficient in the attention state than in the eyes-open state in all three bands, suggesting that cluster coefficient reflects brain state. In addition, an obvious fronto-parietal network is found in the attention state, which is a well-known attention network. These results indicate that attention modulates the fronto-parietal connectivity in different modes as compared with the eyes-open state. Taken together this method is an objective and important tool to study the properties of neural networks of brain rhythm.     

Use of random matrix theory in the discovery of resting state brain networks

Connectomics identifies brain networks in vivo in resting state functional MRI. However, the presence of noise produces spurious identification of brain networks, which have low test-retest reliability. A Network Based Statistics approach to network identification has been previously proposed that affords much better statistical power relative to Bonferroni method but nevertheless provides a sufficiently conservative, family-wise control for false positives. We propose the use of Random Matrix Theory (RMT) to discover brain networks and to associate those networks with demographic and clinical variables. We parcellated the brain into cortical and subcortical regions using either an anatomical or a functional brain atlas. We applied RMT to study functional connectivity across brain regions by first computing the correlation matrix for time courses in those brain regions and then identifying eigenvalues that deviate from the theoretical random distribution that RMT predicts, on the assumption that real brain networks would produce eigenvalues that differ significantly from the random distribution. We assessed the specificity and test-retest reliability of identified networks through application of this RMT-based approach to (1) synthetic data generated under the null-hypothesis, (2) resting state functional MRI data from 4 real-world cohorts of patients and healthy controls, and (3) synthetic data generated by the addition of increasing amounts of noise to real-world datasets. Our findings showed that RMT method was robust to the atlas used for parcellating the brain and did not discover a brain network in synthetic data when in fact a network was not present (i.e., specificity was high); RMT-identified networks in the real-world dataset had high test-retest reliability; and RMT-based method consistently discovered the same network in the presence of increasing noise in the real-world dataset.     

基于Kendall改进的同步算法癫痫脑网络分析

提出了一种基于Kendall等级相关改进的同步算法IRC(inverse rank correlation).Kendall等级相关是非线性动力学分析的一般化算法,可有效地度量变量间的非线性相关性.复杂网络的研究已逐渐深入到社会科学的各个领域,脑网络的研究已经成为当今脑功能研究的热点.利用改进的IRC算法,基于脑电EEG(electroencephalogram)数据来构建大脑功能性网络.对构建的脑功能网络的度指标进行了分析,以调查癫痫脑功能网络是否异于正常人.结果显示:使用该改进的算法能够对癫痫和正常脑功能网络显著区分,且只需要记录很短的脑电数据.实验结果数据表明,该方法适用于区分癫痫和正常脑组织网络度指标,它可有助于进一步地加深对大脑的神经动力学行为的研究,并为临床诊断提供有效工具.     

Modulating spontaneous brain activity using repetitive transcranial magnetic stimulation

Background  

When no specific stimulus or task is presented, spontaneous fluctuations in brain activity occur. Brain regions showing such coherent fluctuations are thought to form organized networks known as 'resting-state' networks, a main representation of which is the default mode network. Spontaneous brain activity shows abnormalities in several neurological and psychiatric diseases that may reflect disturbances of ongoing thought processes. Information about the degree to which such spontaneous brain activity can be modulated may prove helpful in the development of treatment options. We investigated the effect of offline low-frequency rTMS on spontaneous neural activity, as measured with fMRI, using a sequential independent-component-analysis and regression approach to investigate local changes within the default mode network.     

基于持久同调的复杂脑网络动态演化分析

有研究表明阿尔茨海默病（Alzheimer's disease,AD）的认知状态与动态功能连接时间特性的改变有关,持久同调指标分析方法可为AD动态脑网络的研究提供更深的见解,但是目前研究主要集中在空间演化方面,尚未有针对时变方面的脑网络演化研究．本文基于静息态功能磁共振成像（resting state-functional magnetic resonanceimaging,rs-fMRI）,对AD患者和正常被试（normal controls,NC）的静态脑网络和基于滑动窗口构建的动态脑网络进行功能连接性分析．对基于持久同调和基于图论的分析结果进行了比较,并采用k均值聚类进行了时间属性的分析．结果表明相对图论指标,持久同调的指标在AD患者和NC被试间具有更显著的差异性;而且相对于静态脑网络,基于持久同调的动态脑网络演化分析可为脑功能网络标志物的检测提供新思路．     

Internal representation of hierarchical sequences involves the default network

Background  

The default network is a set of brain regions that exhibit a reduction in BOLD response during attention-demanding cognitive tasks, and distinctive patterns of functional connectivity that typically include anti-correlations with a fronto-parietal network involved in attention, working memory, and executive control. The function of the default network regions has been attributed to introspection, self-awareness, and theory of mind judgments, and some of its regions are involved in episodic memory processes.     

Long-term variability of global statistical properties of epileptic brain networks

We investigate the influence of various pathophysiologic and physiologic processes on global statistical properties of epileptic brain networks. We construct binary functional networks from long-term, multichannel electroencephalographic data recorded from 13 epilepsy patients, and the average shortest path length and the clustering coefficient serve as global statistical network characteristics. For time-resolved estimates of these characteristics we observe large fluctuations over time, however, with some periodic temporal structure. These fluctuations can--to a large extent--be attributed to daily rhythms while relevant aspects of the epileptic process contribute only marginally. Particularly, we could not observe clear cut changes in network states that can be regarded as predictive of an impending seizure. Our findings are of particular relevance for studies aiming at an improved understanding of the epileptic process with graph-theoretical approaches.     

Modulation of brain functional connectivity with manual acupuncture in healthy subjects: An electroencephalograph case studying

Manual acupuncture is widely used for pain treatment and stress control. Previous studies on acupuncture have shown its modulatory effects on functional connectivity associated with one or a few preselected brain regions. To investigate how manual acupuncture modulates the organization of functional networks at a whole-brain level, we acupuncture at ST36 of right leg to obtain electroencephalograph (EEG) signals. By coherence estimation, we determine the synchronizations between all pairwise combinations of EEG channels in three acupuncture states. The resulting synchronization matrices are converted into functional networks by applying a threshold, and clustering coefficients and path lengths are computed as a function of threshold. The results show that acupuncture can increase functional connections and synchronizations between different brain areas. For a wide range of threshold, the clustering coefficient during acupuncture and post-acupuncture period is higher than that during the pre-acupuncture control period, whereas characteristic path length is shorter. We provide further support for the presence of "small-world" network characteristics in functional networks by acupuncture. These preliminary results highlight the beneficial modulations of functional connectivity by manual acupuncture, which could contribute to the understanding of acupuncture effects on the entire brain, as well as the neurophysiological mechanisms underlying acupuncture. Moreover, the proposed method may be a useful approach to the further investigation of the complexity of patterns of interrelations between EEG channels.     

Community structure and modularity in networks of correlated brain activity

Functional connectivity patterns derived from neuroimaging data may be represented as graphs or networks, with individual image voxels or anatomically-defined structures representing the nodes, and a measure of correlation between the responses in each pair of nodes determining the edges. This explicit network representation allows network-analysis approaches to be applied to the characterization of functional connections within the brain. Much recent research in complex networks has focused on methods to identify community structure, i.e. cohesive clusters of strongly interconnected nodes. One class of such algorithms determines a partition of a network into 'sub-networks' based on the optimization of a modularity parameter, thus also providing a measure of the degree of segregation versus integration in the full network. Here, we demonstrate that a community structure algorithm based on the maximization of modularity, applied to a functional connectivity network calculated from the responses to acute fluoxetine challenge in the rat, can identify communities whose distributions correspond to anatomically meaningful structures and include compelling functional subdivisions in the brain. We also discuss the biological interpretation of the modularity parameter in terms of segregation and integration of brain function.     

Biophysical and neural basis of resting state functional connectivity: Evidence from non-human primates

Functional MRI (fMRI) has evolved from simple observations of regional changes in MRI signals caused by cortical activity induced by a task or stimulus, to task-free acquisitions of images in a resting state. Such resting state signals contain low frequency fluctuations which may be correlated between voxels, and strongly correlated regions are deemed to reflect functional connectivity within synchronized circuits. Resting state functional connectivity (rsFC) measures have been widely adopted by the neuroscience community, and are being used and interpreted as indicators of intrinsic neural circuits and their functional states in a broad range of applications, both basic and clinical. However, there has been relatively little work reported that validates whether inter-regional correlations in resting state fluctuations of fMRI (rsfMRI) signals actually measure functional connectivity between brain regions, or to establish how MRI data correlate with other metrics of functional connectivity. In this mini-review, we summarize recent studies of rsFC within mesoscopic scale cortical networks (100 μm–10 mm) within a well defined functional region of primary somatosensory cortex (S1), as well as spinal cord and brain white matter in non-human primates, in which we have measured spatial patterns of resting state correlations and validated their interpretation with electrophysiological signals and anatomic connections. Moreover, we emphasize that low frequency correlations are a general feature of neural systems, as evidenced by their presence in the spinal cord as well as white matter. These studies demonstrate the valuable role of high field MRI and invasive measurements in an animal model to inform the interpretation of human imaging studies.     

Complex brain networks: From topological communities to clustered dynamics

Recent research has revealed a rich and complicated network topology in the cortical connectivity of mammalian brains. A challenging task is to understand the implications of such network structures on the functional organisation of the brain activities. We investigate synchronisation dynamics on the corticocortical network of the cat by modelling each node of the network (cortical area) with a subnetwork of interacting excitable neurons. We find that this network of networks displays clustered synchronisation behaviour and the dynamical clusters closely coincide with the topological community structures observed in the anatomical network. The correlation between the firing rate of the areas and the areal intensity is additionally examined. Our results provide insights into the relationship between the global organisation and the functional specialisation of the brain cortex.      

The modulation of brain functional connectivity with manual acupuncture in healthy subjects:An electroencephalograph case study

Manual acupuncture is widely used for pain relief and stress control.Previous studies on acupuncture have shown its modulatory effects on the functional connectivity associated with one or a few preselected brain regions.To investigate how manual acupuncture modulates the organization of functional networks at a whole-brain level,we acupuncture at ST36 of a right leg to obtain electroencephalograph(EEG) signals.By coherence estimation,we determine the synchronizations between all pairwise combinations of EEG channels in three acupuncture states.The resulting synchronization matrices are converted into functional networks by applying a threshold,and the clustering coefficients and path lengths are computed as a function of threshold.The results show that acupuncture can increase functional connections and synchronizations between different brain areas.For a wide range of thresholds,the clustering coefficient during acupuncture and postacupuncture period is higher than that during the pre-acupuncture control period,whereas the characteristic path length is shorter.We provide further support for the presence of "small-world" network characteristics in functional networks by using acupuncture.These preliminary results highlight the beneficial modulations of functional connectivity by manual acupuncture,which could contribute to the understanding of the effects of acupuncture on the entire brain,as well as the neurophysiological mechanisms underlying acupuncture.Moreover,the proposed method may be a useful approach to the further investigation of the complexity of patterns of interrelations between EEG channels.     

基于网络连接度指标的脑梗死患者脑电信号相同步分析

基于图论的脑功能网络分析是近年来的一个研究热点,而相同步分析已被证实为揭示多导联脑电信号之间功能连接的有效工具.针对当脑电采集系统中导联数目较少而不适用于采用图论分析的情况,提出使用基于导联间相同步分析的网络连接度指标研究脑功能网络的关联特性和整体特性.采用新的频带划分方法,将0.5—30 Hz带宽内的脑电信号划分到5个子带上,计算了不同数据长度下各子带分量的网络连接度指标,并对比分析了各子带分量的相对功率.结果表明:在对脑梗死患者的脑电图和正常人的脑电图进行分析时,需要合理的数据长度量化不同动力学系统之间的差异;在合理的数据长度下,在网络连接度指标的区分效果方面,19—24 Hz分量信号优于其他分量,而且仅在19—24 Hz频带上,脑梗死患者组的所有导联出现了与对照组的所有导联相同趋势的变化.研究表明19—24 Hz频带是脑梗死最佳的脑电图诊断频段,可将该频段下的网络连接度指标作为脑梗死辅助诊断的新指标.     

磁刺激穴位复杂脑功能网络构建与分析

本文采用互信息方法对磁刺激内关穴过程中的脑电信 号进行了两两通道间非线性时域关联特性分析, 构建了不同频率刺激前、刺激中、刺激后的脑功能网络, 并基于复杂网络理论对脑功能网络的特征进行了深入研究. 结果表明, 磁刺激频率为3 Hz 时, 大脑功能网络的平均度、平均聚类系数和全局效率与刺激前相比均有显著升高, 平均路径长度显著降低, 并且相应脑功能网络的"小世界"属性有所增强, 信息在大脑各区域间的传递更加高效. 本研究首次开展了磁刺激穴位复杂脑功能网络的构建与分析, 为探索磁刺激穴位对大脑神经调节的作用和机理提供新思路和新方法. 关键词： 复杂网络 磁刺激 脑功能网络 互信息     

Comparison of the small-world topology between anatomical and functional connectivity in the human brain

We applied graph analysis to both anatomical and functional connectivity in the human brain. Anatomical connectivity was acquired from diffusion tensor imaging data by probabilistic fiber tracking, and functional connectivity was extracted from resting-state functional magnetic resonance imaging data by calculating correlation maps of time series. For the same subject, anatomical networks seemed to be disassortative, while functional networks were significantly assortative. Anatomical networks showed higher efficiency and smaller diameters than functional networks. It can be proposed that anatomical connectivity, as a major constraint of functional connectivity, has a relatively stable and efficient structure to support functional connectivity that is more changeable and flexible.