Exploring the disruptions of the neurophysiological organization in Alzheimer's disease: An integrative approach.

BACKGROUND AND OBJECTIVE: Alzheimer's disease (AD) is a neurological disorder that impairs brain functions associated with cognition, memory, and behavior. Noninvasive neurophysiological techniques like magnetoencephalography (MEG) and electroencephalography (EEG) have shown promise in reflecting brain changes related to AD. These techniques are usually assessed at two levels: local activation (spectral, nonlinear, and dynamic properties) and global synchronization (functional connectivity, frequency-dependent network, and multiplex network organization characteristics). Nonetheless, the understanding of the organization formed by the existing relationships between these levels, henceforth named neurophysiological organization, remains unexplored. This work aims to assess the alterations AD causes in the resting-state neurophysiological organization. METHODS: To that end, three datasets from healthy controls (HC) and patients with dementia due to AD were considered: MEG database (55 HC and 87 patients with AD), EEG1 database (51 HC and 100 patients with AD), and EEG2 database (45 HC and 82 patients with AD). To explore the alterations induced by AD in the relationships between several features extracted from M/EEG data, association networks (ANs) were computed. ANs are graphs, useful to quantify and visualize the intricate relationships between multiple features. RESULTS: Our results suggested a disruption in the neurophysiological organization of patients with AD, exhibiting a greater inclination towards the local activation level; and a significant decrease in the complexity and diversity of the ANs (p-value ¡ 0.05, Mann-Whitney U-test, Bonferroni correction). This effect might be due to a shift of the neurophysiological organization towards more regular configurations, which may increase its vulnerability. Moreover, our findings support the crucial role played by the local activation level in maintaining the stability of the neurophysiological organization. Classification performance exhibited accuracy values of 83.91%, 73.68%, and 72.65% for MEG, EEG1, and EEG2 databases, respectively. CONCLUSION: This study introduces a novel, valuable methodology able to integrate parameters characterize different properties of the brain activity and to explore the intricate organization of the neurophysiological organization at different levels. It was noted that AD increases susceptibility to changes in functional neural organization, suggesting a greater ease in the development of severe impairments. Therefore, ANs could facilitate a deeper comprehension of the complex interactions in brain function from a global standpoint.

Effect of segment length, sampling frequency, and imaging modality on the estimation of measures of brain meta-state activation: an MEG/EEG study.

The main objective of this study was to examine the influence that recording length, sampling frequency, and imaging modality have on the estimation and characterization of spontaneous brain meta-states during rest. To this end, a recently developed method of meta-state extraction and characterization was applied to a subset of 16 healthy elderly subjects from two independent electroencephalographic and magnetoencephalographic (EEG/MEG) databases. The recordings were segmented into the first 5, 10, 15, 20, 25, 30, 60 and 90-s of artifact-free activity and meta-states were extracted. Temporal activation sequence (TAS) complexity, which characterizes the complexity of the metastateactivation sequences during rest, was calculated. Then, its stability as a function of segment length, sampling frequency, and imaging modality was assessed. The results showed that, in general, the minimum segment length needed to fully characterize resting-state meta-state activation complexity ranged from 15 to 25 seconds. Moreover, it was found that the sampling frequency has a slight influence on the complexity measure, and that results were similar across EEG and MEG. The findings indicate that the proposed methodology can be applied to both EEG and MEG recordings and displays stable behavior with relatively short segments. However, methodological choices, such as sampling frequency, should be carefully considered.

Volume Conduction Effects on Connectivity Metrics: Application of Network Parameters to Characterize Alzheimer's Disease Continuum.

This study had two main objectives: (i) to study the effects of volume conduction on different connectivity metrics (Amplitude Envelope Correlation AEC, Phase Lag Index PLI, and Magnitude Squared Coherence MSCOH), comparing the coupling patterns at electrode- and sensor-level; and (ii) to characterize spontaneous EEG activity during different stages of Alzheimer's disease (AD) continuum by means of three complementary network parameters: node degree (k), characteristic path length (L), and clustering coefficient (C). Our results revealed that PLI and AEC are weakly influenced by volume conduction compared to MSCOH, but they are not immune to it. Furthermore, network parameters obtained from PLI showed that AD continuum is characterized by an increase in L and C in low frequency bands, suggesting lower integration and higher segregation as the disease progresses. These network changes reflect the abnormalities during AD continuum and are mainly due to neuronal alterations, because PLI is slightly affected by volume conduction effects.

Relationship between the Presence of the ApoE ε4 Allele and EEG Complexity along the Alzheimer's Disease Continuum.

Alzheimer's disease (AD) is the most prevalent cause of dementia, being considered a major health problem, especially in developed countries. Late-onset AD is the most common form of the disease, with symptoms appearing after 65 years old. Genetic determinants of AD risk are vastly unknown, though, ε 4 allele of the ApoE gene has been reported as the strongest genetic risk factor for AD. The objective of this study was to analyze the relationship between brain complexity and the presence of ApoE ε 4 alleles along the AD continuum. For this purpose, resting-state electroencephalography (EEG) activity was analyzed by computing Lempel-Ziv complexity (LZC) from 46 healthy control subjects, 49 mild cognitive impairment subjects, 45 mild AD patients, 44 moderate AD patients and 33 severe AD patients, subdivided by ApoE status. Subjects with one or more ApoE ε 4 alleles were included in the carriers subgroups, whereas the ApoE ε 4 non-carriers subgroups were formed by subjects without any ε 4 allele. Our results showed that AD continuum is characterized by a progressive complexity loss. No differences were observed between AD ApoE ε 4 carriers and non-carriers. However, brain activity from healthy subjects with ApoE ε 4 allele (carriers subgroup) is more complex than from non-carriers, mainly in left temporal, frontal and posterior regions (p-values < 0.05, FDR-corrected Mann-Whitney U-test). These results suggest that the presence of ApoE ε 4 allele could modify the EEG complexity patterns in different brain regions, as the temporal lobes. These alterations might be related to anatomical changes associated to neurodegeneration, increasing the risk of suffering dementia due to AD before its clinical onset. This interesting finding might help to advance in the development of new tools for early AD diagnosis.