Evolution of source EEG synchronization in early Alzheimer's disease

Alzheimer's disease (AD) disrupts functional connectivity in distributed cortical networks. We analyzed changes in the S-estimator, a measure of multivariate intraregional synchronization, in electroencephalogram (EEG) source space in 15 mild AD patients versus 15 age-matched controls to evaluate its potential as a marker of AD progression. All participants underwent 2 clinical evaluations and 2 EEG recording sessions on diagnosis and after a year. The main effect of AD was hyposynchronization in the medial temporal and frontal regions and relative hypersynchronization in posterior cingulate, precuneus, cuneus, and parietotemporal cortices. However, the S-estimator did not change over time in either group. This result motivated an analysis of rapidly progressing AD versus slow-progressing patients. Rapidly progressing AD patients showed a significant reduction in synchronization with time, manifest in left frontotemporal cortex. Thus, the evolution of source EEG synchronization over time is correlated with the rate of disease progression and should be considered as a cost-effective AD biomarker.     

Topography of EEG multivariate phase synchronization in early Alzheimer's disease

Alzheimer's disease (AD) is likely to disrupt the synchronization of the bioelectrical processes in the distributed cortical networks underlying cognition. We analyze the surface topography of the multivariate phase synchronization (MPS) of multichannel EEG in 17 patients (Clinical Dementia Rating (CDR) Scale: 0.5-1; Functional Assessment Staging (FAST): 3-4) compared to 17 controls by applying a combination of global and regional MPS measures to the resting EEG. In early AD, whole-head mapping reveals a specific landscape of synchronization characterized by a decrease in MPS over the fronto-temporal region and an increase over the temporo-parieto-occipital region predominantly of the left hemisphere. These features manifest themselves through the EEG delta-beta bands and discriminate patients from controls with an accuracy of up to 94%. Moreover, the abnormal MPS in both anterior and posterior clusters correlates with the Mini Mental State Examination score, binding regional EEG synchronization to cognitive decline in AD patients. The MPS technique reveals that the EEG phenotype of early AD is relevant to the clinical picture and may ultimately become its sensitive and specific biomarker.     

Decreased EEG synchronization in Alzheimer's disease and mild cognitive impairment

The hypothesis of a functional disconnection of neuro-cognitive networks in patients with mild cognitive impairment (MCI) and Alzheimer Dementia was investigated using baseline resting EEG data. EEG databases from New York (264 subjects) and Stockholm (155 subjects), including healthy controls and patients with varying degrees of cognitive decline or Alzheimer Dementia were analyzed using Global Field Synchronization (GFS), a novel measure of global EEG synchronization. GFS reflects the global amount of phase-locked activity at a given frequency by a single number; it is independent of the recording reference and of implicit source models. Patients showed decreased GFS values in Alpha, Beta, and Gamma frequency bands, and increased GFS values in the Delta band, confirming the hypothesized disconnection syndrome. The results are discussed within the framework of current knowledge about the functional significance of the affected frequency bands.     

Decreased EEG synchronization and its correlation with symptom severity in Alzheimer's disease

BACKGROUND: Global field synchronization (GFS) has recently been introduced to measure functional synchronization in frequency-domain EEG data. This study explored GFS values and its clinical significance in patients with Alzheimer's disease (AD). METHOD: EEGs were recorded from 22 AD patients and 23 age-matched healthy controls. GFS values were computed in the delta, theta, alpha, beta1, beta2, beta3, gamma, and full frequency bands. The Mini-Mental Status Examination (MMSE) and the Clinical Dementia Rating scale (CDR) were used to assess the symptom severity in AD patients. RESULTS: GFS values in the beta1, beta2, beta3, and full bands were lower in AD patients than in healthy controls. GFS values in the alpha, beta1, beta2, beta3, and full bands were positively correlated with the MMSE and CDR scores in combined group (AD patients and healthy controls). In AD patients, GFS values were positively correlated with MMSE scores in the beta1, beta 3, and full bands, and with CDR scores in the delta band. CONCLUSION: GFS values were significantly lower in AD patients than in healthy controls, and they were positively correlated with MMSE and CDR scores. Our results suggest that GFS values are a useful biological correlate of cognitive decline in AD patients.     

The EEG spectra of Alzheimer's disease

Sixteen Alzheimer's and 16 non-Alzheimer's dementia patients, the two groups being matched for dementia, as well as 10 normal controls were given an EEG examination with 12 monopolar leads during an awake-resting condition. Power spectra (16 s) were obtained in 12 brain areas for 18 frequency bands (0–36 Hz). An 11-point dementia scale furnished the dementia scores. Analyses of variance were performed. Data confirmed earlier findings of an increase in slow activity and a decrease in fast activity for the demented groups. It further demonstrated that these EEG features were not related to dementia per se since the Alzheimer's group (matched for dementia) exhibited a spectral curve having a maximum at 1 Hz and an exponential asymptotic power characterized by decreasing power with increasing frequency without additional features or remnant of dominant activity. The study demonstrated that the decrease in frequency of alpha activity is perhaps more significant in identifying dementia of the non-Alzheimer type even though this characteristic may be present in the earlier stages of Alzheimer's dementia. It is hypothesized that the characteristics shown by the Alzheimer's group may be related to the presence of neurofibrillary tangles and plaques which are more prevalent in Alzheimer's patients.     

阿尔茨海默病脑电信号的同步似然分析

目的：研究阿尔茨海默病（AD）患者脑电时间序列的同步性。方法采集AD患者和正常对照者各8名的16导联脑电图（EEG）数据,分别对2组EEG的全频段、δ（0.5~4 Hz）、θ（4~8 Hz）、α（8~13 Hz）和β频段（13~30 Hz）信号进行同步似然分析,比较不同频段的平均同步似然系数值并进行统计学分析。结果 AD组全频段、θ频段和α频段的平均同步似然系数值均小于对照组,差异有统计学意义（P<0.05）;2组δ和β频段的平均同步似然系数值差异无统计学意义（P>0.05）。结论 AD组全频段、θ频段和α频段的EEG同步性降低,提示在θ和α频段内AD患者不同脑区的协同信息处理能力下降,为进一步研究AD患者大脑功能连接特性提供支持。     

Variability of EEG synchronization during a working memory task in healthy subjects.

Working memory is associated with an increase in EEG theta synchronization and a decrease in lower alpha band synchronization. We investigated whether such changes in mean synchronization level are accompanied by changes in small scale fluctuations of synchronization. EEGs (19 channels; average reference; sample frequency 250 Hz) were recorded in 21 healthy subjects (12 males; mean age 62.5 years; S.D. 2.1) at rest and during a visual working memory condition. EEG synchronization was computed in six frequency bands (2-6; 6-10; 10-14; 14-18; 18-22; 22-50 Hz) using the synchronization likelihood. Variability of the synchronization was quantified with synchronization entropy. During the working memory condition synchronization increased in the 2-6 Hz band, and decreased in the 6-10, 14-18 and 18-22 Hz bands. Working memory was associated with increased variability in the 2-6 Hz band, and decreased variability in the 6-10 Hz band and, to a lesser extent, in the 14-18 and 18-22 Hz bands. Working memory is accompanied not only by characteristic changes in the mean level of interactions between neural networks, but also by changes in small scale fluctuations in such interactions. Strong, but rapidly fluctuating coupling between neural systems might provide a mechanism to optimize the balance between local differentiation and global integration of brain activity.     

Brain dysfunction in subjects at risk of Alzheimer's disease

Visual evoked potentials versus flash (VEP) and brain DC-potentials were studied in the first-order relatives of patients (mean age 42.6 +/- 1.6 years) with Alzheimer's disease (AD) and probands (mean age 60.9 +/- 0.9 years) and age-matched healthy controls for the relatives and probands. In the relatives of AD patients, the latencies of N2, P3, N3 components were found to be delayed as compared with the controls. There was a delay in the latencies of the same components in the patients and their relatives, but it was smaller in the relatives of AD patients. The brain DC-potentials were higher in the relatives of AD patients than in the controls. Neurophysiological changes in the relatives of AD patients may be considered to be signs of latent neurodegeneration in the limbicoreticulocortical pathways, which may be associated with the excitotoxic processes and abnormal hyperactivity in the limbicoreticulocortical structures.     

Cortical networks generating movement-related EEG rhythms in Alzheimer's disease: an EEG coherence study

Patients with mild Alzheimer's disease (AD) present with abnormally strong values of frontal and ipsilateral central sensorimotor rhythms. The authors tested 2 working hypotheses of the related electroencephalographic (EEG) coherence: disconnection, defined as a sign of a reduced coordination within the frontoparietal and interhemispheric networks, and cooperation, defined as a reflection of the reorganization of the brain sensorimotor networks. Results showed that, compared with healthy controls, patients with mild AD had an unreactive and abnormally low interhemispheric EEG coherence and an unreactive and abnormally high frontoparietal EEG coherence. These findings support the hypothesis of an impaired mechanism of sensorimotor cortical coupling (disconnection) in mild AD.     

Gender-related dissociations of categorical fluency in normal subjects and in subjects with Alzheimer's disease

Semantic fluency tasks, with the categories of birds and furniture as stimuli, were administered to normal subjects and patients with Alzheimer's disease (AD). Normal subjects showed a gender-related double dissociation consistent with the literature data because men were more fluent with the birds category and women with the furniture category. Also, patients with AD showed a Gender x Category interaction, but the double dissociation between birds and furniture was not present because of a prevalent impairment of the living category birds that was irrespective of gender. This pattern of impairment in patients with AD was independent from the disease stage. The authors conclude that (a) gender-related categorical effects cannot be considered as inborn, sex-related cognitive differences but as familiarity effects and (b) both lesion-related and familiarity-related factors must be taken into account to explain category-specific effects of patients with brain damage and patients with AD.     

Memory-related EEG power and coherence reductions in mild Alzheimer's disease.

OBJECTIVES: To examine memory-related EEG power and coherence over temporal and central recording sites in patients with early Alzheimer's disease (AD) and normal controls. METHOD: EEG was recorded from central (Fz, Cz and Pz) and temporal (T3 and T4) electrodes while ten very mild AD patients and ten controls performed a Sternberg-type memory scanning task with three levels of working memory load. Spectral power in delta (0-3 Hz), theta (3-5 Hz), lower alpha1 (5-7 Hz), lower alpha2 (7-9 Hz), upper alpha (9-11 Hz) and beta (15-30 Hz) was averaged for temporal and central electrodes. Coherence was averaged between central electrodes, between central and right temporal electrodes and between central and left temporal electrodes. RESULTS: While behavioral performance of very mild AD patients did not differ significantly from that of normal controls, findings suggest that normal controls but not AD patients respond to memory demands by increasing upper alpha power over temporal cortex. When compared with normal controls, AD patients had reduced upper alpha coherence between central and right temporal cortex. DISCUSSION: Results are consistent with previous research on the role of upper alpha in semantic memory and suggest that very mild AD may inhibit selective synchronization of upper alpha in temporal lobes. Reduced coherence between central and temporal cortex is discussed in light of a neurological model of AD that hypothesizes reduced electrocortical efficiency and a breakdown of neural network communication to temporal lobes possibly resulting from temporal lobe atrophy.     

Size of neocortical neurons in control subjects and in Alzheimer's disease

The aim of the present study was to estimate mean neuronal volume and absolute size distributions of the neocortical neurons in brains from controls and AD patients using stereological methods based on unbiased principles to determine whether changes in absolute cell size are part of the neuropathological pattern of Alzheimer's disease. The neocortex of 8 patients with Alzheimer's disease (AD), mean age 81·1 (68–94) y was compared with 9 nondemented controls, mean age 80·9 (65–101) y. The brains came from Johns Hopkins University Hospital (JHUH) in Baltimore, USA, the Netherlands Brain Bank (NBB), and from a large brain repository in Denmark. The rotator method was used to obtain an estimate of cell volumes providing absolute size distributions of the volume of both cell perikaryon and cell nuclei. The geometric mean volume of cell nuclei in neocortical neurons was 328 μm³ (interindividual CV = 0·15) in the Alzheimer group compared with 277 μm³ (interindividual CV = 0·17) in controls which was a statistically significant increase ( P = 0·049). The perikaryal volume was 1117 μm³ in the Alzheimer group compared with 999 μm³ in controls which was a nonsignificant difference ( P = 0·20). There was a highly significant correlation between the nuclear and perikaryal volumes in all individuals. The average slope of the regression lines was significantly higher in the Alzheimer patients than in the controls, illustrating that nuclear hypertrophy was more pronounced in the largest neurons.     

A method for detection of Alzheimer's disease using ICA-enhanced EEG measurements

OBJECTIVE: Many researchers have studied automatic EEG classification and recently a lot of work has been done on artefact-removal from EEG data using independent component analyses (ICA). However, demonstrating that a ICA-processed multichannel EEG measurement becomes more interpretable compared to the raw data (as is usually done in work on ICA-processing of EEG data) does not yet prove that detection of (incipient) anomalies is also better possible after ICA-processing. The objective of this study is to show that ICA-preprocessing is useful when constructing a detection system for Alzheimer's disease. METHODS AND MATERIAL: The paper describes a method for detection of EEG patterns indicative of Alzheimer's disease using automatic pattern recognition techniques. Our method incorporates an artefact removal stage based on ICA prior to automatic classification. The method is evaluated on measurements of a length of 8s from two groups of patients, where one group is in an initial stage of the disease (28 patients), whereas the other group is in a more progressed stage (15 patients). Both setups include a control group that should be classified as normal (10 and 21, respectively). RESULTS: Our final classification results for the group with severe Alzheimer's disease are comparable to the best results from literature. We show that ICA-based reduction of artefacts improves classification results for patients in an initial stage. CONCLUSION: We conclude that a more robust detection of Alzheimer's disease related EEG patterns may be obtained by employing ICA as ICA based pre-processing of EEG data can improve classification results for patients in an initial stage of Alzheimer's disease.     

脑电同步性分析在癫痫机制研究中的应用

脑电相位同步性是研究癫痫超同步放电机制的方向之一。介绍了应用Hilbert变换提取脑电的瞬时相位的方法,分析脑电相位同步性的互相关法、互信息法和同步指数法,以及脑电信号的小波变换,综述了以上方法在癫痫发作的超同步放电机制研究中的应用。     

Computer analysis of EEG activity in dementia of the Alzheimer's type and Huntington's disease

Computer analysis of the EEG was obtained in the course of evaluation of 35 patients with Dementia of the Alzheimer's Type (DAT) and Huntington's disease (HD), and compared to 20 age-matched normal controls. On-line computer analysis of the EEG consisted of: 1) compressed spectral array (CSA) displays (2-6 channels); 2) relative frequency power (4 bands) and 3) an averaged frequency power function [( alpha/alpha + theta power (microV 2)] X 100 = % EEG Power function). Frequency power reflected increased theta, and reduced alpha components, in patient groups. Significant correlation was obtained between % EEG Power function, and clinical stage of dementia. This function correctly identified 17/25 DAT, and 7/10 HD patients, and gave additional quantification to the primary EEG.     

EEG phase synchronization during hypnosis induction

Hypnosis is a mental state or set of attitudes usually induced by a procedure known as hypnotic induction. In order to provide the basic physiological conditions for potentially successful hypnosis treatment of medical and psychological problems, the determination of a subject's hypnotizability level is important. Currently, the hypnotizability level is determined using different standard subjective tests. To avoid the different drawbacks of these subjective clinical tests, a practical objective method based on the correlation between electroencephalograph (EEG) phase synchronization and hypnosis susceptibility levels is presented in this study. This method can be used by clinicians instead of the traditional subjective methods to classify hypnotizability level. Thirty-two subjects with different hypnosis susceptibility levels contributed to this research. Using statistical analyses, it was concluded that, in highly hypnotizable people, the EEG phase synchronization between different paired channels, located on the frontal lobe, is significantly different from that in subjects with medium or low hypnotizability.     

EEG phase synchronization during hypnosis induction

Hypnosis is a mental state or set of attitudes usually induced by a procedure known as hypnotic induction. In order to provide the basic physiological conditions for potentially successful hypnosis treatment of medical and psychological problems, the determination of a subject’s hypnotizability level is important. Currently, the hypnotizability level is determined using different standard subjective tests. To avoid the different drawbacks of these subjective clinical tests, a practical objective method based on the correlation between electroencephalograph (EEG) phase synchronization and hypnosis susceptibility levels is presented in this study. This method can be used by clinicians instead of the traditional subjective methods to classify hypnotizability level. Thirty-two subjects with different hypnosis susceptibility levels contributed to this research. Using statistical analyses, it was concluded that, in highly hypnotizable people, the EEG phase synchronization between different paired channels, located on the frontal lobe, is significantly different from that in subjects with medium or low hypnotizability.     

Quantitative EEG in Alzheimer's disease: Cognitive state,resting state and association with disease severity

Background

Quantitative electroencephalogram (qEEG) recorded during cognitive tasks has been shown to differentiate between patients with Alzheimer's disease (AD) and healthy individuals. However, the association between various qEEG markers recorded during mnestic paradigms and clinical measures of AD has not been studied in detail.

Objective

To evaluate if ‘cognitive’ qEEG is a useful diagnostic option, particularly if memory paradigms are used as cognitive stimulators.

Methods

This study is part of the Prospective Registry on Dementia in Austria (PRODEM), a multicenter dementia research project. A cohort of 79 probable AD patients was included in a cross-sectional analysis. qEEG recordings performed in resting states were compared with recordings during cognitively active states. Cognition was evoked with a face–name paradigm and a paired-associate word list task, respectively. Relative band powers, coherence and auto-mutual information were computed as functions of MMSE scores for the memory paradigms and during rest. Analyses were adjusted for the co-variables age, sex, duration of dementia and educational level.

Results

MMSE scores explained 36–51% of the variances of qEEG-markers. Face–name encoding with eyes open was superior to resting state with eyes closed in relative theta and beta1 power as well as coherence, whereas relative alpha power and auto-mutual information yielded more significant results during resting state with eyes closed. The face–name task yielded stronger correlations with MMSE scores than the verbal memory task.

Conclusion

qEEG alterations recorded during mnestic activity, particularly face–name encoding showed the highest association with the MMSE and may serve as a clinically valuable marker for disease severity.