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.     

视听刺激脑电信号的相位同步分析

脑电(EEG)同步被认为是脑功能区域整合的表现。高级脑功能需要具有特定功能的多区域神经系统间进行不同层次的整合和协调来完成。本文提出了一种新的相位同步分析方法—互近似熵。采用分段频率,用同步指数、互信息熵与互近似熵方法对视听刺激EEG导联数据进行了相位同步的比较分析,三种分析得到了一致的结果,说明互近似熵方法也能很好反映出两导联的相位同步。文章同时通过相位同步分析结果进行了大脑反应区域的探索分析。此研究为脑机接口的设计奠定了基础。     

Phase and amplitude electroencephalography correlations change with disease progression in people with idiopathic rapid eye-movement sleep behavior disorder

Study ObjectivesIncreased phase synchronization in electroencephalography (EEG) bands might reflect the activation of compensatory mechanisms of cognitive decline in people with neurodegenerative diseases. Here, we investigated whether altered large-scale couplings of brain oscillations could be linked to the balancing of cognitive decline in a longitudinal cohort of people with idiopathic rapid eye-movement sleep behavior disorder (iRBD).MethodsWe analyzed 18 patients (17 males, 69.7 ± 7.5 years) with iRBD undergoing high-density EEG (HD-EEG), presynaptic dopaminergic imaging, and clinical and neuropsychological (NPS) assessments at two time points (time interval 24.2 ± 5.9 months). We thus quantified the HD-EEG power distribution, orthogonalized amplitude correlation, and weighted phase-lag index at both time points and correlated them with clinical, NPS, and imaging data.ResultsFour patients phenoconverted at follow-up (three cases of parkinsonism and one of dementia). At the group level, NPS scores decreased over time, without reaching statistical significance. However, alpha phase synchronization increased and delta amplitude correlations decreased significantly at follow-up compared to baseline. Both large-scale network connectivity metrics were significantly correlated with NPS scores but not with sleep quality indices or presynaptic dopaminergic imaging data.ConclusionsThese results suggest that increased alpha phase synchronization and reduced delta amplitude correlation may be considered electrophysiological signs of an active compensatory mechanism of cognitive impairment in people with iRBD. Large-scale functional modifications may be helpful biomarkers in the characterization of prodromal stages of alpha-synucleinopathies.     

Visually evoked phase synchronization changes of alpha rhythm in migraine: correlations with clinical features.

OBJECTIVE: This study aimed to compute phase synchronization of the alpha band from a multichannel electroencephalogram (EEG) recorded under repetitive flash stimulation from migraine patients without aura. This allowed examination of ongoing EEG activity during visual stimulation in the pain-free phase of migraine. METHODS: Flash stimuli at frequencies of 3, 6, 9, 12, 15, 18, 21, 24, and 27 Hz were delivered to 15 migraine patients without aura and 15 controls, with the EEG recorded from 18 scalp electrodes, referred to the linked earlobes. The EEG signals were filtered in the alpha (7.5-13 Hz) band. For all stimulus frequencies that we evaluated, the phase synchronization index was based on the Hilbert transformation. RESULTS: Phase synchronization separated the patients and controls for the 9, 24 and 27 Hz stimulus frequencies; hyper phase synchronization was observed in patients, whereas healthy subjects were characterized by a reduced phase synchronization. These differences were found in all regions of the scalp. CONCLUSIONS: During migraine, the brain synchronizes to the idling rhythm of the visual areas under certain photic stimulations; in normal subjects however, brain regions involved in the processing of sensory information demonstrate desynchronized activity. Hypersynchronization of the alpha rhythm may suggest a state of cortical hypoexcitability during the interictal phase of migraine. SIGNIFICANCE: The employment of non-linear EEG analysis may identify subtle functional changes in the migraine brain.     

相位同步性分析方法在癫痫研究中的应用

同步振荡是神经系统中普遍存在的一种现象,是理解大脑信息处理机制的重要切入点,不同频段的同步现象能够编码不同的刺激信息.癫痫是由大脑整体或局部整合的不足或异常造成的,同步振荡现象在癫痫的发生过程中扮演了重要的角色.本文介绍了应用希尔伯特变换和小波变换提取脑电的瞬时相位方法,介绍了脑电相位同步性的相干分析、相位同步指数和香侬熵法,以及这些方法在癫痫同步放电研究中的应用,为提取癫痫患者大脑功能的信息和更深入地探索癫痫发作的机理提供了理论依据.     

Different frequencies for different scales of cortical integration: from local gamma to long range alpha/theta synchronization.

Cortical activity and perception are not driven by the external stimulus alone; rather sensory information has to be integrated with various other internal constraints such as expectations, recent memories, planned actions, etc. The question is how large scale integration over many remote and size-varying processes might be performed by the brain. We have conducted a series of EEG recordings during processes thought to involve neuronal assemblies of varying complexity. While local synchronization during visual processing evolved in the gamma frequency range, synchronization between neighboring temporal and parietal cortex during multimodal semantic processing evolved in a lower, the beta1 (12-18 Hz) frequency range, and long range fronto-parietal interactions during working memory retention and mental imagery evolved in the theta and alpha (4-8 Hz, 8-12 Hz) frequency range. Thus, a relationship seems to exist between the extent of functional integration and the synchronization-frequency. In particular, long-range interactions in the alpha and theta ranges seem specifically involved in processing of internal mental context, i.e. for top-down processing. We propose that large scale integration is performed by synchronization among neurons and neuronal assemblies evolving in different frequency ranges.     

基于分段Prony建模的脑电相位同步分析方法

本研究提出采用一种分段的Prony方法(PPM),将非平稳EEG信号分解为幅度为指数上升或下降的正弦波,从而获得各频率成分的幅度、频率和初始相位,并计算两通道相位差;用香侬熵来衡量两路信号的相位同步程度.首先对该方法的频率、相位分辨率和检测同步程度的效果等进行仿真研究,结果显示了该方法具有高的频率和相位分辨率.最后将该方法用于实际的三组脑电信号,得到的结果与经典方法一致.将该方法与希尔伯特变换方法进行了比较,说明该方法具有较好的抗噪性能,可作为非平稳信号的相位同步检测的有效工具.     

The trees and the forest: Characterization of complex brain networks with minimum spanning trees

In recent years there has been a shift in focus from the study of local, mostly task-related activation to the exploration of the organization and functioning of large-scale structural and functional complex brain networks. Progress in the interdisciplinary field of modern network science has introduced many new concepts, analytical tools and models which allow a systematic interpretation of multivariate data obtained from structural and functional MRI, EEG and MEG. However, progress in this field has been hampered by the absence of a simple, unbiased method to represent the essential features of brain networks, and to compare these across different conditions, behavioural states and neuropsychiatric/neurological diseases. One promising solution to this problem is to represent brain networks by a minimum spanning tree (MST), a unique acyclic subgraph that connects all nodes and maximizes a property of interest such as synchronization between brain areas. We explain how the global and local properties of an MST can be characterized. We then review early and more recent applications of the MST to EEG and MEG in epilepsy, development, schizophrenia, brain tumours, multiple sclerosis and Parkinson's disease, and show how MST characterization performs compared to more conventional graph analysis. Finally, we illustrate how MST characterization allows representation of observed brain networks in a space of all possible tree configurations and discuss how this may simplify the construction of simple generative models of normal and abnormal brain network organization.     

EEG network connectivity changes in mild cognitive impairment — Preliminary results

Resting state EEGs were compared between patients with amnestic subtype of mild cognitive impairment (aMCI) and matched elderly controls at two times over a one year period. The study aimed at investigating the role of functional connectivity between and within different brain regions in relation to the progression of cognitive deficit in MCI. The EEG was recorded in two sessions during eyes closed and eyes open resting conditions. Functional brain connectivity was investigated based on the measurement of phase synchronization in different frequency bands. Delta and theta synchronization characteristics indicated decreased level of local and large-scale connectivity in the patients within the frontal, between the frontal and temporal, and frontal and parietal brain areas which was more pronounced 1 year later. As a consequence of opening the eyes connectivity in the alpha1 band within the parietal lobe decreased compared to the eyes closed condition but only in the control group. The lack of alpha1 band reactivity following eye opening could reliably differentiate patients from controls. Our preliminary results support the notion that the functional disconnection between distant brain areas is a characteristic feature of MCI, and may prove to be predictive in terms of the progression of this condition.     

Alpha amplitude and phase locking in obsessive-compulsive disorder during working memory

Alpha event-related desynchronization (ERD) and synchronization are known to reflect brain activation and inhibition, respectively. Alpha phase locking seems to reflect the timing in the cortical process. In a previous study, lower alpha ERD was related to working memory in obsessive-compulsive disorder (OCD) patients than in controls during the retention and retrival phases, but not in the encoding phase. However, memory deficits in OCD patients are known to be related to executive failure during the encoding phase. Thus, focusing on the encoding phase, we tested the level of alpha amplitude and phase locking in OCD patients according to memory load. The EEGs of fifteen OCD patients and fifteen controls were recorded during a Sternberg working memory task. The behavioral performance of the OCD patients was normal. However, the OCD group yielded significantly lower ERD and stronger phase locking. As memory load rose, ERD and phase locking significantly increased in both groups. A difference in event-related alpha oscillation was observed in the encoding phase. Lower alpha modulation in the OCD patient simplied abnormality of the excitatory/inhibitory process in the brain, and increased phase locking might reflect excessive attentional excitability.     

Interaction between changes in local and temporospatial spectral EEG characteristics during exposure of humans to hypoxia

The temporospatial and local characteristics of the EEG were studied in healthy subjects during the respiration of a hypoxic oxygen-nitrogen gas mixture containing 8% oxygen. Analysis of the spectral power density, coherence, phase shift, similarity of dominant frequencies in the EEG in different leads was performed separately for epochs containing and not containing visually apparent patterns of EEG spatial synchronization. In addition, assessment of spectral measures took account of the fact of the dominance of the frequency being analyzed in the EEG spectrum of the corresponding lead. The results of these studies showed that overall, hypoxia was accompanied by a decrease in EEG coherence in the alpha range and, for connections in the left mid-temporal lead, the delta range. The beta range showed an increase in the values of this measure, while the theta range showed different changes in coherence: increases in epochs containing spatial synchronization patterns and decreases from control levels in other epochs. Hypoxia was also associated with increases in the EEG phase shift in the frontal and temporal leads (in relation to the EEG recordings in the other leads) in the delta and theta ranges. In the beta range, conversely, there was a decrease in the mean phase shift. Consideration of the fact of dominance of one or another frequency in the spectra of local EEG traces is needed for correct interpretation of analyses of temporospatial measures. A mathematical model of the interaction between processes at different frequencies is presented to explain some of the observations in the current work. __________ Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 91, No. 11, pp. 1260–1280, November, 2005.     

EEG phase synchronization in patients with paranoid schizophrenia

Recent findings suggest that specific deficits in neural synchrony and binding may underlie cognitive disturbances in schizophrenia and that key aspects of schizophrenia pathology involve discoordination and disconnection of distributed processes in multiple cortical areas associated with cognitive deficits. In the present study we aimed to investigate the underlying cortical mechanism of disturbed frontal-temporal-central-parietal connectivity in schizophrenia by examination of the synchronization patterns using wavelet phase synchronization index and coherence between all defined couples of 8 EEG signals recorded at different cortical sites in its relationship to positive and negative symptoms of schizophrenia. 31 adult schizophrenic outpatients with diagnosis of paranoid schizophrenia (mean age 27.4) were assessed in the study. The obtained results present the first quantitative evidence indicating direct relationship between wavelet phase synchronization and coherence in pairs of EEG signals recorded from frontal, temporal, central and parietal brain areas and positive and negative symptoms of schizophrenia. The performed analysis demonstrates that the level of phase synchronization and coherence in some pairs of EEG signals is inversely related to positive symptoms, negative symptoms and general psychopathology in temporal scales (frequency ranges) given by wavelet frequencies (WFs) equal to or higher than 7.56 Hz, and positively related to negative symptoms in wavelet frequencies equal to or lower than 5.35 Hz. This finding suggests that higher and lower frequencies may play a specific role in binding and connectivity and may be related to decreased or increased synchrony with specific manifestation in cognitive deficits of schizophrenia.     

基于C-FFuzzyEn的神经电生理信号同步性分析

基于传统互模糊熵,结合分数阶微积分提出分数阶互模糊熵（C-FFuzzyEn）,并基于该算法分析混沌耦合系统的同步性,进行健康对照者和癫痫患者不同脑区脑电信号的耦合性对比。结果表明,与传统互模糊熵相比,C-FFuzzyEn提高了不同耦合度模型的区分能力;与健康对照者相比,癫痫患者在癫痫发作时不同通道脑电信号之间C-FFuzzyEn较小,与癫痫发作时各神经元同步放电现象相吻合;相比互模糊熵,C-FFuzzyEn区分健康对照者与癫痫患者脑区之间脑电信号同步性的效果更好。C-FFuzzyEn可应用于脑电信号等神经电生理信号的同步性分析。     

Wavelet-based estimation of EEG coherence during Chinese Stroop task

Wavelet-based estimation of instantaneous EEG coherence was applied to investigate the synchronization of different brain regions whilst 10 subjects performing Stroop task presented in Chinese. In contrast to coherence based on Fourier transform, wavelet-based coherence, which does not depend on the stationarity of signals, applies an adaptive window to the frequency of the signal and has a more accurate time-frequency resolution. In the present study, a greater negativity for the incongruent situation than congruent situation appeared from 350 to 600 ms post-stimulus onset over frontal, central, and parietal regions, and significantly higher EEG coherences for the incongruent situation than congruent situation were observed over frontal, parietal, and frontoparietal regions from 100 to 400 ms at beta1 (13-18Hz) frequency band, which was found to be sensitive in the discrimination between congruent and incongruent situations. The findings in the present study may indicate that functional synchronization as indexed by EEG coherence at beta1 frequency band is enhanced at the earlier stage while processing the conflicting information from the incongruent stimulus, and that beta1 frequency band is close related to interactions of brain areas in the selected attention task.     

Spatiotemporal reorganization of electrical activity in the human brain associated with a timing transition

We used a 61-channel electrode array to investigate the spatiotemporal dynamics of electroencephalographic (EEG) activity related to behavioral transitions in rhythmic sensorimotor coordination. Subjects were instructed to maintain a 1:1 relationship between repeated right index finger flexion and a series of periodically delivered tones (metronome) in a syncopated (anti-phase) fashion. Systematic increases in stimulus presentation rate are known to induce a spontaneous switch in behavior from syncopation to synchronization (in-phase coordination). We show that this transition is accompanied by a large-scale reorganization of cortical activity manifested in the spatial distributions of EEG power at the coordination frequency. Significant decreases in power were observed at electrode locations over left central and anterior parietal areas, most likely reflecting reduced activation of left primary sensorimotor cortex. A second condition in which subjects were instructed to synchronize with the metronome controlled for the effects of movement frequency, since synchronization is known to remain stable across a wide range of frequencies. Different, smaller spatial differences were observed between topographic patterns associated with synchronization at low versus high stimulus rates. Our results demonstrate qualitative changes in the spatial dynamics of human brain electrical activity associated with a transition in the timing of sensorimotor coordination and suggest that maintenance of a more difficult anti-phase timing relation is associated with greater activation of primary sensorimotor areas. Received: 3 September 1998 / Accepted: 3 March 1999     

Estimating cognitive workload using wavelet entropy-based features during an arithmetic task

Electroencephalography (EEG) has shown promise as an indicator of cognitive workload; however, precise workload estimation is an ongoing research challenge. In this investigation, seven levels of workload were induced using an arithmetic task, and the entropy of wavelet coefficients extracted from EEG signals is shown to distinguish all seven levels. For a subject-independent multi-channel classification scheme, the entropy features achieved high accuracy, up to 98% for channels from the frontal lobes, in the delta frequency band. This suggests that a smaller number of EEG channels in only one frequency band can be deployed for an effective EEG-based workload classification system. Together with analysis based on phase locking between channels, these results consistently suggest increased synchronization of neural responses for higher load levels.     

Parkinsonian impairment correlates with spatially extensive subthalamic oscillatory synchronization

The local strength of pathological synchronization in the region of the subthalamic nucleus (STN) is emerging as a possible factor in the motor impairment of Parkinson's Disease (PD). In particular, correlations have been repeatedly demonstrated between treatment-induced suppressions of local oscillatory activity in the beta frequency band and improvements in motor performance. However, a mechanistic role for beta activity is brought into question by the difficulty in showing a correlation between such activity at rest and the motor deficit in patients withdrawn from medication. Here we recorded local field potential (LFP) activity from 36 subthalamic regions in 18 patients undergoing functional neurosurgery for the treatment of PD. We recorded directly from the contacts of the deep brain stimulation (DBS) electrodes as they were introduced in successive 2 mm steps, and assessed phase coherence as a measure of spatially extended, rather than local, oscillatory synchronization. We found that phase coherence in the beta frequency band correlated with the severity of Parkinsonian bradykinesia and rigidity, both in the limbs and axial body. Such correlations were frequency and site specific in so far as they were reduced when the lowermost contact of the DBS electrode was above the dorsal STN. Correlations with limb tremor occurred at sub-beta band frequencies and were more lateralized than those between beta activity and limb bradykinesia and rigidity. Phase coherence could account for up to ∼25% of the variance in motor scores between sides and patients. These new data suggest that the strength of spatially extended oscillatory synchronization, as well as the strength of local synchronization, may be worthwhile incorporating into modelling studies designed to inform surgical targeting, post-operative stimulation parameter selection and closed-loop stimulation regimes in PD. In addition, they strengthen the link between pathological synchronization and the different motor features of Parkinsonism.     

Moderate-to-heavy alcohol intake is associated with differences in synchronization of brain activity during rest and mental rehearsal

In alcohol-dependent individuals, synchronization of brain activity is different from that in non-alcohol-dependent individuals as reflected by EEG differences at alpha and beta frequencies (8–30 Hz). These EEG differences may not only be related to long-term alcohol intake but also to genetic factors that are associated with alcohol dependence. Thus, it is not known what the pure effect of long-term alcohol intake on synchronization of brain activity is. Therefore, we investigated whether EEG synchronization differs between light (0.5–6 drinks per week), moderate (7–20 drinks per week), and heavy (21–53 drinks per week) drinkers. All participants (49 males and 47 females) were free of a personal and family history of alcohol dependence. Eyes-closed EEG was recorded at rest and during mental rehearsal of pictures. EEG synchronization was determined by computing Synchronization Likelihood for six frequency bands (0.5–4 Hz, 4–8 Hz, 8–12 Hz, 12–20 Hz, 20–30 Hz, 30–45 Hz). Both male and female heavy drinkers displayed a loss of lateralization in alpha (8–12 Hz) and slow-beta (12–20 Hz) synchronization. In addition, moderately and heavily drinking males had lower fast-beta (20–30 Hz) synchronization than lightly drinking males. It is concluded that both male and female drinkers who drink 21 alcoholic drinks per week or more have impaired synchronization of brain activity during rest and mental rehearsal at alpha and beta frequencies as compared to individuals who drink less. As individuals with a personal or family history of alcohol dependence were excluded, the confounding effects of genetic factors related to alcohol dependence on synchronization of brain activity were minimized.     

Electroencephalogram functional connectivity between rat hippocampus and cortex after pilocarpine treatment

The muscarinic agonist pilocarpine has been shown to increase the duration and total number of episodes presenting theta rhythm—simultaneously in hippocampus and cortex—in rats during the waking states. Theta waves are suggested to be involved in the flow of information between hippocampus and cortex during memory processes. This work investigates this functional interdependence using the spectral and phase synchronization analysis of the electroencephalogram (EEG) theta band recorded in these brain structures of rats after pilocarpine treatment. Pilocarpine was used at doses devoid of epilepticus-like seizures effects in conscious freely moving rats. The results showed that pilocarpine administration significantly increased the relative theta power during the waking states in the cortex, but not in the hippocampus of rats. Additionally, the EEG coherence between the hippocampal EEG theta band and that arising at the frontal cortex increased after pilocarpine treatment but only during the waking states. This result reveals an increase of the linear correlation between the theta waves of these two brain structures after pilocarpine treatment during the waking states. Moreover, phase synchronization results showed an effective phase locking with non-zero phase difference between hippocampus and frontal cortex theta waves that remained after pilocarpine treatment. Therefore, pilocarpine seems to reinforce the neural transmission waves from the hippocampus toward the cortex during waking. In conclusion, the present EEG study could suggest an effect of the muscarinic cholinergic agonist pilocarpine on the hippocampal-cortical functional connectivity.