Directionality of EEG synchronization in Alzheimer's disease subjects

Is directionality of electroencephalographic (EEG) synchronization abnormal in amnesic mild cognitive impairment (MCI) and Alzheimer's disease (AD)? EEG data were recorded in 64 normal elderly (Nold), 69 amnesic MCI, and 73 mild AD subjects at rest condition (closed eyes). Direction of information flux within EEG functional coupling at electrode pairs was performed by directed transfer function (DTF) at delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10 Hz), alpha 2 (10-12 Hz), beta 1 (13-20 Hz), beta 2 (20-30 Hz), and gamma (30-40 Hz). Parietal to frontal direction of the information flux within EEG functional coupling was stronger in Nold than in MCI and/or AD subjects, namely for alpha and beta rhythms. In contrast, the directional flow within inter-hemispheric EEG functional coupling did not discriminate among the three groups. These results suggest that directionality of parieto-to-frontal EEG synchronization is abnormal not only in AD but also in amnesic MCI.     

基于全局排序模式同步的多通道脑电同步特性分析

脑电同步是脑功能区域整合的重要表现。基于时间序列的排序模式,提出一种简单易行的多通道脑电信号同步分析方法--全局排序模式同步(GMS)。仿真分析显示,该算比基于加权排序互信息的全局同步因子对弱耦合的检测更为灵敏。对26例遗忘型轻度认知障碍和20例认知功能正常的2型糖尿病患者闭眼静息态的脑电信号,采用基于小波增强的独立分量分析算法进行预处理,将32路脑电信号分为前额、中央区、顶区、枕区、左颞和右颞6个区域进行全局同步分析,并利用独立样本t检验对两组被试之间的人口学特征、神经心理学检查和同步值进行统计分析,利用皮尔森线性相关分析研究各区域同步值和认知功能之间的关系。结果显示,糖尿病轻度认知障碍患者与正常对照组相比,各脑区的全局排序模式同步值均减小,尤其是中央区(P<0.01)、顶区(P<0.05)和枕区(P<0.05)有显著性的降低,且前额(r=0.298,P=0.045)、中央区(r=0.327,P=0.026)、顶区(r=0.32,P=0.03)的全局排序模式同步值均与MOCA得分有显著的正相关性,表明GMS是与认知功能下降相关的脑电特征。     

Electroencephalographic Evidence of Altered Top–Down Attentional Modulation in Fibromyalgia Patients During a Working Memory Task

Fibromyalgia (FM) is a chronic syndrome involving widespread pain of unclear pathophysiology. FM patients frequently complain about cognitive symptoms that interfere with their daily life activities. Several studies have reported attentional deficits and working memory impairment in FM patients. Nevertheless, the mechanisms involved in these alterations are still poorly understood. In this study we recorded electroencephalographic activity in 32 women with FM and 30 matched controls while they performed a 2-back working memory task. We analyzed behavioural data, posterior alpha and midfrontal theta frequency power, and theta phase synchronization between midfrontal locations and the remaining scalp-recorded areas. Task performance was similar in patients and controls; however, time–frequency analysis showed a smaller decrease in the amplitude of the posterior alpha (related to attentional processing) and a smaller increase in midfrontal theta power (related to mental effort) in FM patients than in healthy controls. The FM patients also showed lower functional connectivity between midfrontal locations and rest of the scalp-recorded areas in the theta band (related to information transfer across distant brain regions when top-down control is required). To our knowledge, this is the first study relating alterations in oscillatory activity and impaired connectivity to attentional working memory complaints in FM patients. Reduced power in the theta band during performance of the task suggests that the medial frontal cortex may play an important role in the attentional deficits reported in FM.     

轻度认知障碍老年人脑电的非线性相互依赖脑网络分析

本研究旨在初步探究患轻度认知障碍(MCI)的老年人及正常老年人进行情绪调控时的大脑网络特性。记录了14位MCI患者及18个正常人进行认知重评的情绪调控实验时的头皮脑电信号(EEG),包括中性观看、负性观看和负性重评任务。并采用非线性相互依赖性的方法衡量不同频段的大脑区域间的连接强度,然后根据非线性相互依赖性指数构建两组受试者的大脑功能网络,并运用全局效率和平均局部效率来分析脑区的信息传递效率。研究结果显示,MCI患者脑电theta(F=6.805, P=0.014,η²=0.185)和alpha(负性观看任务:t=2.437,P=0.021, Cohen's d=0.865)活动的非线性相互依赖性指数显著低于正常对照组。在特定阈值下(低gamma频段阈值0.070;theta频段阈值0.075;alpha频段阈值0.115和0.125),MCI患者的网络效率显著低于正常对照组。此外还发现(阈值0.115)正常对照组表现出显著的重评效应(F=5.549,P=0.008,η²=0.246),即负性观看条件下(P=0.018) 的alpha全局效率(0.713±0.042)显著高于负性重评条件下的alpha全局效率(0.699±0.045),MCI组没有发现类似的重评效应。研究表明,MCI患者的情绪调控脑网络异常,表现在大脑信息交换效率低下。未发现非线性相互依赖性、网络效率与行为学、认知分数之间的显著皮尔逊相关性。未来可以对非线性相关性进行深入研究,从而发现更稳定的MCI情绪调控脑网络特征。     

Resting state functional connectivity alterations in primary lateral sclerosis

Resting state functional connectivity of the sensorimotor and extramotor brain networks was studied in 24 patients with primary lateral sclerosis (PLS) relative to 26 healthy controls. The relationships of RS functional connectivity with patient clinical and cognitive status and white matter tract damage (i.e., corticospinal tracts, corpus callosum, and superior longitudinal fasciculus) were investigated. Compared with controls, PLS patients showed an increased functional connectivity within the sensorimotor, frontal, and left frontoparietal networks spanning the pre- and postcentral, medial and dorsal frontal, insular, and superior temporal regions. Patients with more severe physical disability and a more rapid rate of disease progression had increased sensorimotor connectivity values. The increased functional connectivity within the frontal network was associated with executive dysfunction. In addition, higher functional connectivity correlated with greater structural damage to network-specific white matter tracts. This study shows clinically meaningful increased resting state functional connectivity in PLS.     

Volumetric correlates of memory and executive function in normal elderly, mild cognitive impairment and Alzheimer's disease

In Alzheimer's disease (AD), atrophy negatively impacts cognition while in healthy adults, inverse relationships between brain volume and cognition may occur. We investigated correlations between gray matter volume and cognition in elderly controls, AD and mild cognitive impairment (MCI) patients with memory and executive deficits. AD demonstrated substantial loss in temporal, parietal and frontal regions while MCI exhibited moderate volume loss in temporal and frontal regions. In controls, memory and executive function were negatively correlated with frontal regions, while in AD, memory was positively correlated with temporal and frontal gyri, and executive function with frontal regions. The combination of the two patterns may explain the lack of correlations in MCI. Developmental versus pathological contributions to these relationships are discussed.     

Divergent brain network connectivity in amyotrophic lateral sclerosis

Using resting state (RS) functional magnetic resonance imaging and independent component analysis, the integrity of brain networks related to cognition and behavior was investigated in 20 nondemented patients with amyotrophic lateral sclerosis (ALS). The association between RS functional connectivity and executive functions was assessed in 16 patients with neuropsychological assessment. ALS patients compared with control subjects showed a decreased connectivity of the right orbitofrontal cortex, and an enhanced connectivity of the left precuneus in the default mode network; a decreased connectivity of the left inferior frontal cortex, and an increased connectivity of the right angular gyrus in the right frontoparietal network; and an increased connectivity of the parietal cortex in the left frontoparietal network. The enhanced parietal connectivity was associated with the clinical and cognitive deficits of the patients. In ALS, an alteration of large-scale functional brain networks associated with cognition does occur, even in the absence of overt dementia. The increased parietal connectivity may have a role in an attempt to maintain cognitive efficiency in the presence of structural frontotemporal injury.     

Working memory load-related electroencephalographic parameters can differentiate progressive from stable mild cognitive impairment

Recent studies described several changes of endogenous event-related potentials (ERP) and brain rhythm synchronization during memory activation in patients with Alzheimer's disease (AD). To examine whether memory-related EEG parameters may predict cognitive decline in mild cognitive impairment (MCI), we assessed P200 and N200 latencies as well as beta event-related synchronization (ERS) in 16 elderly controls (EC), 29 MCI cases and 10 patients with AD during the successful performance of a pure attentional detection task as compared with a highly working memory demanding two-back task. At 1 year follow-up, 16 MCI patients showed progressive cognitive decline (PMCI) and 13 remained stable (SMCI). Both P200 and N200 latencies in the two-back task were longer in PMCI and AD cases compared with EC and SMCI cases. During the interval 1000 ms to 1700 ms after stimulus, beta ERS at parietal electrodes was of lower amplitude in PMCI and AD compared with EC and SMCI cases. Univariate models showed that P200, N200 and log% beta values were significantly related to the SMCI/PMCI distinction with areas under the receiver operating characteristic curve of 0.93, 0.78 and 0.72, respectively. The combination of all three EEG hallmarks was the stronger predictor of MCI deterioration with 90% of correctly classified MCI cases. Our data reveal that PMCI and clinically overt AD share the same pattern of working memory-related EEG activation characterized by increased P200-N200 latencies and decreased beta ERS. They also show that P200 latency during the two-back task may be a simple and promising EEG marker of rapid cognitive decline in MCI.     

Event-related synchronization of alpha activity in early Alzheimer's disease and mild cognitive impairment: an MEG study combining beamformer and group comparison

In patients with Alzheimer's disease (AD), it is sometimes challenging to identify typical findings in electroencephalography (EEG) or magnetoencephalography (MEG) such as a slowing of the posterior dominant activity or an increase in slow activity. In this MEG study, we evaluated the event-related synchronization (ERS) of alpha activity after eye closing in patients with early AD and mild cognitive impairment (MCI) who presented no slow MEG pattern. Thirteen patients with probable AD and thirteen patients with MCI, who met NINCDS-ADRDA and Petersen's diagnostic criteria, respectively, were enrolled. We also selected fourteen age-matched normal control subjects. MEG activity was acquired during eye-open and eye-closed states. The ERS after eye closing within 8-15Hz frequency band was calculated and its cortical source was superimposed on the individual's MRI by using the beamformer implemented in Brain Electrical Source Analysis (BESA). The Source image was converted into a standardized image, and group comparisons across patients with AD, MCI and controls were performed using BrainVoyager QX. The averaged ERS was observed dominantly in posterior regions in all three groups. Significant difference in ERS was observed only for the comparison between AD patients and controls, with AD patients showing increased ERS in frontal regions. Frontal shift of posterior alpha activity was observed clearly in AD patients using the combination of beamformer and group comparison.     

Assessment of Event-Related EEG Power After Single-Pulse TMS in Unresponsive Wakefulness Syndrome and Minimally Conscious State Patients

In patients without a behavioral response, non-invasive techniques and new methods of data analysis can complement existing diagnostic tools by providing a method for detecting covert signs of residual cognitive function and awareness. The aim of this study was to investigate the brain oscillatory activities synchronized by single-pulse transcranial magnetic stimulation (TMS) delivered over the primary motor area in the time–frequency domain in patients with the unresponsive wakefulness syndrome or in a minimally conscious state as compared to healthy controls. A time–frequency analysis based on the wavelet transform was used to characterize rapid modifications of oscillatory EEG rhythms induced by TMS in patients as compared to healthy controls. The pattern of EEG changes in the patients differed from that of healthy controls. In the controls there was an early synchronization of slow waves immediately followed by a desynchronization of alpha and beta frequency bands over the frontal and centro-parietal electrodes, whereas an opposite early synchronization, particularly over motor areas for alpha and beta and over the frontal and parietal electrodes for beta power, was seen in the patients. In addition, no relevant modification in slow rhythms (delta and theta) after TMS was noted in patients. The clinical impact of these findings could be relevant in neurorehabilitation settings for increasing the awareness of these patients and defining new treatment procedures.     

Homocysteine and electroencephalographic rhythms in Alzheimer disease: a multicentric study

High plasma concentration of homocysteine is an independent risk factor for Alzheimer’s disease (AD), due to microvascular impairment and consequent neural loss [Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D’Agostino RB, Wilson PW, Wolf PA (2002) Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med 346(7):476–483]. Is high plasma homocysteine level related to slow electroencephalographic (EEG) rhythms in awake resting AD subjects, as a reflection of known relationships between cortical neural loss and these rhythms? To test this hypothesis, we enrolled 34 mild AD patients and 34 subjects with mild cognitive impairment (MCI). Enrolled people were then subdivided into four sub-groups of 17 persons: MCI and AD subjects with low homocysteine level (MCI− and AD−, homocysteine level <11 μmol/l); MCI and AD subjects with high homocysteine level (MCI+ and AD+, homocysteine level ≥11 μmol/l). Resting eyes-closed EEG data were recorded. EEG rhythms of interest were delta (2–4 Hz), theta (4–8 Hz), alpha 1 (8–10.5 Hz), alpha 2 (10.5–13 Hz), beta 1 (13–20 Hz), and beta 2 (20–30 Hz). EEG cortical sources were estimated by low-resolution brain electromagnetic tomography (LORETA). Results showed that delta (frontal and temporal), theta (central, frontal, parietal, occipital, and temporal), alpha 1 (parietal, occipital, and temporal), and alpha 2 (parietal and occipital) sources were stronger in magnitude in AD+ than AD− group. Instead, no difference was found between MCI− and MCI+ groups. In conclusion, high plasma homocysteine level is related to unselective increment of cortical delta, theta, and alpha rhythms in mild AD, thus unveiling possible relationships among that level, microvascular concomitants of advanced neurodegenerative processes, and synchronization mechanisms generating EEG rhythms.     

基于功能连接算法的斜视性弱视儿童静息态功能磁共振成像的研究

目的探索斜视性弱视儿童脑功能区及其功能连接的改变,揭示斜视性弱视的发生与脑功能改变的相关性。方法在静息态下采集22位斜视性弱视儿童和10名健康儿童脑功能磁共振图像,利用DPARSF软件计算全脑与ROI功能区的连接系数,并应用t检验对实验组和健康对照组进行组内和组间功能连接系数分析。结果发现斜视性弱视儿童部分脑功能连接低于正常对照组的相应脑区连接,这些功能区主要分布于枕叶、颞叶、小脑后叶、顶叶、额叶、扣带回等脑区。结论基于静息态的f MRI的脑功能连接算法可以反映斜视性弱视儿童视皮层的变化和多脑区神经活动的变化。     

Resting-state fMRI changes in Alzheimer's disease and mild cognitive impairment

Regional functional connectivity (FC) of 39 patients with Alzheimer's disease (AD), 23 patients with mild cognitive impairment (MCI), and 43 healthy elderly controls was studied using resting-state functional magnetic resonance imaging (rs-fMRI). After a mean follow-up of 2.8 ± 1.9 years, 7 MCI patients converted to AD, while 14 patients remained cognitively stable. Resting-state functional magnetic resonance imaging scans were analyzed using independent component analysis (ICA), followed by a "dual-regression" technique to create and compare subject-specific maps of each independent spatiotemporal component, correcting for age, sex, and gray matter atrophy. AD patients displayed lower FC within the default-mode network (DMN) in the precuneus and posterior cingulate cortex compared with controls, independent of cortical atrophy. Regional FC values of MCI patients were numerically in between AD patients and controls, but only the difference between AD and stable MCI patients was statistically significant. Correlation with cognitive dysfunction demonstrated the clinical relevance of FC changes within the DMN. In conclusion, clinically relevant decreased FC within the DMN was observed in AD.     

Regional homogeneity of the resting-state brain activity correlates with individual intelligence

Resting-state functional magnetic resonance imaging has confirmed that the strengths of the long distance functional connectivity between different brain areas are correlated with individual differences in intelligence. However, the association between the local connectivity within a specific brain region and intelligence during rest remains largely unknown. The aim of this study is to investigate the relationship between local connectivity and intelligence. Fifty-nine right-handed healthy adults participated in the study. The regional homogeneity (ReHo) was used to assess the strength of local connectivity. The associations between ReHo and full-scale intelligence quotient (FSIQ) scores were studied in a voxel-wise manner using partial correlation analysis controlling for age and sex. We found that the FSIQ scores were positively correlated with the ReHo values of the bilateral inferior parietal lobules, middle frontal, parahippocampal and inferior temporal gyri, the right thalamus, superior frontal and fusiform gyri, and the left superior parietal lobule. The main findings are consistent with the parieto-frontal integration theory (P-FIT) of intelligence, supporting the view that general intelligence involves multiple brain regions throughout the brain.     

Brain activation disturbance for target detection in patients with mild cognitive impairment: an fMRI study

Functional brain imaging in mild cognitive impairment (MCI) reveals differences in activation of task-relevant brain areas between patients and age-matched healthy controls. However, some studies reported hyperactivation and others hypoactivation in MCI compared with controls. The inconsistencies may be explained by compensatory mechanisms due to high complexity of the applied tasks. The oddball task is a simple paradigm that is known to activate a widespread network in the brain, involving attentional and monitoring mechanisms. In the present study, we examined amnestic or amnestic multidomain MCI patients (n = 12) and healthy controls (n = 13) in an auditory oddball task. Participants had to respond to infrequent targets and inhibit response to infrequent novel-nontarget stimuli. Lower stimulus related activation was found in MCI patients compared with healthy controls in parts of the middle temporal gyrus, the temporal pole, regions along the superior temporal sulcus, in the left cuneus, the left supramarginal gyrus, the anterior cingulated cortex and in the left inferior and middle frontal gyrus. Activation for oddball stimuli is assumed to reflect an automatic reflexive engagement of many brain regions in response to potentially important changes in the environment as well as cognitive control to monitor responses. The mechanisms of attention and cognitive control may be severely impaired in MCI and thus, underlie the cognitive deficits of this clinical group.     

酗酒者皮层脑电同步性分析

同步性可以度量不同脑区之间的相互作用,但目前对脑电的同步性研究多数是基于头皮数据进行的。脑电的容积导体效应,可能导致头皮电极之间出现伪相关,从而影响同步性的度量。实验所用的数据集包括正常(28例)和酗酒(28例)两类被试的61通道EEG时间序列,每一个被试参与3种条件的实验任务:单刺激(S1)、双刺激匹配(S2 match)、双刺激不匹配(S2 no match)。利用eLoreta溯源技术,在大脑皮层上自定义了61个感兴趣区域(ROI),计算两类被试之间的同步似然性,最后对酗酒被试和正常被试执行认知任务时的同步性差异进行统计分析。结果发现,执行相同认知任务时,酗酒被试全脑平均同步似然均小于正常被试,且在α、β1和θ波段上均有P<0.05,差异达到统计显著。在执行不同认知任务时,正常被试的同步性可以准确反映出不同认知任务的复杂程度(S2 match > S2 no match > S1),而酗酒被试的同步性则无规律变化。不同被试之间的区域MSL结果表明,在执行S2 match任务时,酗酒被试多个区域MSL均小于正常被试,且在α波段上额叶、左颞叶、中央和右颞叶区均有P<0.05,差异达到统计显著;在β1波段上,额叶区P<0.05,差异达到统计显著;在β2波段上,额叶、左颞叶区均有P<0.05,差异达到统计显著。研究结果表明,酗酒被试大脑不同区域之间的连接受到一定程度的损伤,这为研究酗酒引起的脑损伤提供一个新的角度和有力的证据。     

Functional Connectivity and Quantitative EEG in Women with Alcohol Use Disorders: A Resting-State Study

This study was aimed at exploring the electroencephalographic features associated with alcohol use disorders (AUD) during a resting-state condition, by using quantitative EEG and Functional Connectivity analyses. In addition, we explored whether EEG functional connectivity is associated with trait impulsivity. Absolute and relative powers and Synchronization Likelihood (SL) as a measure of functional connectivity were analyzed in 15 AUD women and fifteen controls matched in age, gender and education. Correlation analysis between self-report impulsivity as measured by the Barratt impulsiveness Scale (BIS-11) and SL values of AUD patients were performed. Our results showed increased absolute and relative beta power in AUD patients compared to matched controls, and reduced functional connectivity in AUD patients predominantly in the beta and alpha bands. Impaired connectivity was distributed at fronto-central and occipito-parietal regions in the alpha band, and over the entire scalp in the beta band. We also found that impaired functional connectivity particularly in alpha band at fronto-central areas was negative correlated with non-planning dimension of impulsivity. These findings suggest that functional brain abnormalities are present in AUD patients and a disruption of resting-state EEG functional connectivity is associated with psychopathological traits of addictive behavior.     

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.     

Study on Functional Connectivity Density in Patients with Frontal Lobe Tumor at Resting-State

At present, the neuropathological mechanisms and the plastic changes of brain cognitive function in patents with front lobe tumor remain unclear, most studies just focused on global measures of brain functional connectivity without considering the time correlation in the different regions of the brain. This study aims to investigate brain cognitive alterations and functional plasticity in patients with front lobe tumor at resting-state by conducting functional connectivity density(FCD) mapping and granger causality analysis(GCA). Firstly, FCD mapping was used to extract abnormal functional connectivity(FC) of patients with frontal lobe tumor, and analyzed altered brain FC in both short-and long-range FCD. Then, the voxel-wise GCA method was used to analyze the causal relationship between altered FC regions and other regions in order to detect the time correlation between regions of interest(ROI) and reveal the direction of information flow between brain ROIs. It was found that patients had increased short-range FCD in motor and space attention function areas, had increased short-and long-range FCDs both in Temporal and Insula, and the causal coefficients were changed obviously in Temporal and Frontal. The results show that there is a functional plasticity in space attention function areas. Temporal and Insula are affected by tumor in frontal lobe, and functional reorganization appears inside Temporal.     

Cortical correlate of spatial presence in 2D and 3D interactive virtual reality: an EEG study

The present study is the first that examined neuronal underpinnings of spatial presence using multi-channel EEG in an interactive virtual reality (VR). We compared two VR-systems: a highly immersive Single-Wall-VR-system (three-dimensional view, large screen) and a less immersive Desktop-VR-system (two-dimensional view, small screen). Twenty-nine participants performed a spatial navigation task in a virtual maze and had to state their sensation of "being there" on a 5-point rating scale. Task-related power decrease/increase (TRPD/TRPI) in the Alpha band (8-12Hz) and coherence analyses in different frequency bands were used to analyze the EEG data. The Single-Wall-VR-system caused a more intense presence experience than the Desktop-VR-system. This increased feeling of presence in the Single-Wall-VR-condition was accompanied by an increased parietal TRPD in the Alpha band, which is associated with cortical activation. The lower presence experience in the Desktop-VR-group was accompanied by a stronger functional connectivity between frontal and parietal brain regions indicating that the communication between these two brain areas is crucial for the presence experience. Hence, we found a positive relationship between presence and parietal brain activation and a negative relationship between presence and frontal brain activation in an interactive VR-paradigm, supporting the results of passive non-interactive VR-studies.