Graph theoretical analysis of magnetoencephalographic functional connectivity in Alzheimer's disease.

In this study we examined changes in the large-scale structure of resting-state brain networks in patients with Alzheimer's disease compared with non-demented controls, using concepts from graph theory. Magneto-encephalograms (MEG) were recorded in 18 Alzheimer's disease patients and 18 non-demented control subjects in a no-task, eyes-closed condition. For the main frequency bands, synchronization between all pairs of MEG channels was assessed using a phase lag index (PLI, a synchronization measure insensitive to volume conduction). PLI-weighted connectivity networks were calculated, and characterized by a mean clustering coefficient and path length. Alzheimer's disease patients showed a decrease of mean PLI in the lower alpha and beta band. In the lower alpha band, the clustering coefficient and path length were both decreased in Alzheimer's disease patients. Network changes in the lower alpha band were better explained by a 'Targeted Attack' model than by a 'Random Failure' model. Thus, Alzheimer's disease patients display a loss of resting-state functional connectivity in lower alpha and beta bands even when a measure insensitive to volume conduction effects is used. Moreover, the large-scale structure of lower alpha band functional networks in Alzheimer's disease is more random. The modelling results suggest that highly connected neural network 'hubs' may be especially at risk in Alzheimer's disease.

Disturbed fluctuations of resting state EEG synchronization in Alzheimer's disease.

OBJECTIVE: We examined the hypothesis that cognitive dysfunction in Alzheimer's disease is associated with abnormal spontaneous fluctuations of EEG synchronization levels during an eyes-closed resting state. METHODS: EEGs were recorded during an eyes-closed resting state in Alzheimer patients (N=24; 9 males; mean age 76.3 years; SD 7.8; range 59-86) and non-demented subjects with subjective memory complaints (N=19; 9 males; mean age 76.1 years; SD 6.7; range: 67-89). The mean level of synchronization was determined in different frequency bands with the synchronization likelihood and fluctuations of the synchronization level were analysed with detrended fluctuation analysis (DFA). RESULTS: The mean level of EEG synchronization was lower in Alzheimer patients in the upper alpha (10-13Hz) and beta (13-30Hz) band. Spontaneous fluctuations of synchronization were diminished in Alzheimer patients in the lower alpha (8-10Hz) and beta bands. In patients as well as controls the synchronization fluctuations showed a scale-free pattern. CONCLUSIONS: Alzheimer's disease is characterized both by a lower mean level of functional connectivity as well as by diminished fluctuations in the level of synchronization. The dynamics of these fluctuations in patients and controls was scale-free which might point to self-organized criticality of neural networks in the brain. SIGNIFICANCE: Impaired functional connectivity can manifest itself not only in decreased levels of synchronization but also in disturbed fluctuations of synchronization levels.

Synchronization likelihood with explicit time-frequency priors.

Cognitive processing requires integration of information processed simultaneously in spatially distinct areas of the brain. The influence that two brain areas exert on each others activity is usually governed by an unknown function, which is likely to have nonlinear terms. If the functional relationship between activities in different areas is dominated by the nonlinear terms, linear measures of correlation may not detect the statistical interdependency satisfactorily. Therefore, algorithms for detecting nonlinear dependencies may prove invaluable for characterizing the functional coupling in certain neuronal systems, conditions or pathologies. Synchronization likelihood (SL) is a method based on the concept of generalized synchronization and detects nonlinear and linear dependencies between two signals (Stam, C.J., van Dijk, B.W., 2002. Synchronization likelihood: An unbiased measure of generalized synchronization in multivariate data sets. Physica D, 163: 236-241.). SL relies on the detection of simultaneously occurring patterns, which can be complex and widely different in the two signals. Clinical studies applying SL to electro- or magnetoencephalography (EEG/MEG) signals have shown promising results. In previous implementations of the algorithm, however, a number of parameters have lacked a rigorous definition with respect to the time-frequency characteristics of the underlying physiological processes. Here we introduce a rationale for choosing these parameters as a function of the time-frequency content of the patterns of interest. The number of parameters that can be arbitrarily chosen by the user of the SL algorithm is thereby decreased from six to two. Empirical evidence for the advantages of our proposal is given by an application to EEG data of an epileptic seizure and simulations of two unidirectionally coupled Hénon systems.

Magnetoencephalographic evaluation of resting-state functional connectivity in Alzheimer's disease.

Statistical interdependencies between magnetoencephalographic signals recorded over different brain regions may reflect the functional connectivity of the resting-state networks. We investigated topographic characteristics of disturbed resting-state networks in Alzheimer's disease patients in different frequency bands. Whole-head 151-channel MEG was recorded in 18 Alzheimer patients (mean age 72.1 years, SD 5.6; 11 males) and 18 healthy controls (mean age 69.1 years, SD 6.8; 7 males) during a no-task eyes-closed resting state. Pair-wise interdependencies of MEG signals were computed in six frequency bands (delta, theta, alpha1, alpha2, beta and gamma) with the synchronization likelihood (a nonlinear measure) and coherence and grouped into long distance (intra- and interhemispheric) and short distance interactions. In the alpha1 and beta band, Alzheimer patients showed a loss of long distance intrahemispheric interactions, with a focus on left fronto-temporal/parietal connections. Functional connectivity was increased in Alzheimer patients locally in the theta band (centro-parietal regions) and the beta and gamma band (occipito-parietal regions). In the Alzheimer group, positive correlations were found between alpha1, alpha2 and beta band synchronization likelihood and MMSE score. Resting-state functional connectivity in Alzheimer's disease is characterized by specific changes of long and short distance interactions in the theta, alpha1, beta and gamma bands. These changes may reflect loss of anatomical connections and/or reduced central cholinergic activity and could underlie part of the cognitive impairment.