We investigated whether functional brain networks are abnormally organized in Alzheimer's disease (AD). To this end, graph theoretical analysis was applied to matrices of functional connectivity of beta band-filtered electroencephalography (EEG) channels, in 15 Alzheimer patients and 13 control subjects. Correlations between all pairwise combinations of EEG channels were determined with the synchronization likelihood. The resulting synchronization matrices were converted to graphs by applying a threshold, and cluster coefficients and path lengths were computed as a function of threshold or as a function of degree K. For a wide range of thresholds, the characteristic path length L was significantly longer in the Alzheimer patients, whereas the cluster coefficient C showed no significant changes. This pattern was still present when L and C were computed as a function of K. A longer path length with a relatively preserved cluster coefficient suggests a loss of complexity and a less optimal organization. The present study provides further support for the presence of "small-world" features in functional brain networks and demonstrates that AD is characterized by a loss of small-world network characteristics. Graph theoretical analysis may be a useful approach to study the complexity of patterns of interrelations between EEG channels.

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.

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Encoding and retention of information in memory are associated with a sustained increase in the amplitude of neuronal oscillations for up to several seconds. We reasoned that coordination of oscillatory activity over time might be important for memory and, therefore, that the amplitude modulation of oscillations may be abnormal in Alzheimer disease (AD). To test this hypothesis, we measured magnetoencephalography (MEG) during eyes-closed rest in 19 patients diagnosed with early-stage AD and 16 agematched control subjects and characterized the autocorrelation structure of ongoing oscillations using detrended fluctuation analysis and an analysis of the life-and waiting-time statistics of oscillation bursts. We found that Alzheimer's patients had a strongly reduced incidence of alpha-band oscillation bursts with long life-or waiting-times (< 1 s) over temporo-parietal regions and markedly weaker autocorrelations on long time scales (1-25 seconds). Interestingly, the life-and waiting-times of theta oscillations over medial prefrontal regions were greatly increased. Whereas both temporo-parietal alpha and medial prefrontal theta oscillations are associated with retrieval and retention of information, metabolic and structural deficits in early-stage AD are observed primarily in temporo-parietal areas, suggesting that the enhanced oscillations in medial prefrontal cortex reflect a compensatory mechanism. Together, our results suggest that amplitude modulation of neuronal oscillations is important for cognition and that indices of amplitude dynamics of oscillations may prove useful as neuroimaging biomarkers of early-stage AD.Alzheimer's disease ͉ magnetoencephalography ͉ neuronal oscillations ͉ resting-state brain activity ͉ temporal correlations P sychological and neuroimaging data suggest that the brain performs many important functions during rest, such as retrieval and manipulation of information in short-term memory, and problem-solving and planning (1, 2). These resting-state functions may represent an essential aspect of human selfawareness and are susceptible to impairment in brain-related disorders including depression, schizophrenia, and dementia (3).Neuroimaging has identified anatomical patterns of activity that are remarkably consistent across resting-state experiments, most notably in the precuneus, lateral parietal and medial prefrontal cortices (4, 5). The existence of such a ''resting-state network'' has been suggested to reflect a ''default mode'' of brain operation in the absence of goal-directed behavior (6). Coordination of anatomically distributed activity during rest has been studied extensively by computing correlations between neuronal signals from different brain areas (Fig. 1). This approach has revealed aberrant resting-state networks in Alzheimer disease (AD) (7-9) and other disorders (4, 10, 11).For cognitive processing, coordination of local brain activity over time may be just as important as the coordination of simultaneous activity in anatomically distinct brain regions and may be refl...

In the present study we aimed to determine the topographical and laminar characteristics of cingulate projections to the parahippocampal region and hippocampal formation in the rat, using the anterograde tracers Phaseolus vulgaris-leucoagglutinin and biotinylated dextranamine. The results show that all areas of the cingulate cortex project extensively to the parahippocampal region but not to the hippocampal formation. Rostral cingulate areas (infralimbic-, prelimbic cortices, rostral 1/3 of the dorsal anterior cingulate cortex) primarily project to the perirhinal and lateral entorhinal cortices. Projections from the remaining cingulate areas preferentially target the postrhinal and medial entorhinal cortices as well as the presubiculum and parasubiculum. At a more detailed level the projections show differences in topographical specificities according to their site of origin within the cingulate cortex suggesting the functional contribution of cingulate areas may differ at an individual level. This organization of the cingulate-parahippocampal projections relates to the overall organization of postulated parallel parahippocampal-hippocampal processing streams mediated through the lateral and medial entorhinal cortex respectively. The mid-rostrocaudal part of the dorsal anterior cingulate cortex appears to be connected to both networks as well as to rostral and caudal parts of the cingulate cortex. This region may therefore responsible for integrating information across these specific networks.