Functional (un-)Coupling: Impairment, Compensation, and Future Progression in Alzheimer's Disease.

Background: Functional (un-)coupling (task-related change of functional connectivity) between different sites of the brain is a mechanism of general importance for cognitive processes. In Alzheimer's disease (AD), prior research identified diminished cortical connectivity as a hallmark of the disease. However, little is known about the relation between the amount of functional (un-)coupling and cognitive performance and decline in AD. Method: Cognitive performance (based on CERAD-Plus scores) and electroencephalogram (EEG)-based functional (un-)coupling measures (connectivity changes from rest to a Face-Name-Encoding task) were assessed in 135 AD patients (age: M = 73.8 years; SD = 9.0). Of these, 68 patients (M = 73.9 years; SD = 8.9) participated in a follow-up assessment of their cognitive performance 1.5 years later. Results: The amounts of functional (un-)coupling in left anterior-posterior and homotopic interhemispheric connections in beta1-band were related to cognitive performance at baseline (ß = .340; p < .001; ß = .274; P = .001, respectively). For both markers, a higher amount of functional coupling was associated with better cognitive performance. Both markers also were significant predictors for cognitive decline. However, while patients with greater functional coupling in left anterior-posterior connections declined less in cognitive performance (ß = .329; P = .035) those with greater functional coupling in interhemispheric connections declined more (ß = -.402; P = .010). Conclusion: These findings suggest an important role of functional coupling mechanisms in left anterior-posterior and interhemispheric connections in AD. Especially the complex relationship with cognitive decline in AD patients might be an interesting aspect for future studies.

A new approach for estimating VAR systems in the mixed-frequency case.

In this paper we present a new estimation procedure named MF-IVL for VAR systems in the case of mixed-frequency data, where the data maybe, e.g., stock or flow data. The main idea of this new procedure is to project the slow components on the present and past fast ones in order to create instrumental variables. This procedure is shown to be generically consistent. Our claim is that the procedure is fast and more accurate when compared to the extended Yule-Walker procedure. A comparison of these two procedures is given by simulation.

On the Sensitivity of Granger Causality to Errors-In-Variables, Linear Transformations and Subsampling.

This article studies the sensitivity of Granger causality to the addition of noise, the introduction of subsampling, and the application of causal invertible filters to weakly stationary processes. Using canonical spectral factors and Wold decompositions, we give general conditions under which additive noise or filtering distorts Granger-causal properties by inducing (spurious) Granger causality, as well as conditions under which it does not. For the errors-in-variables case, we give a continuity result, which implies that: a 'small' noise-to-signal ratio entails 'small' distortions in Granger causality. On filtering, we give general necessary and sufficient conditions under which 'spurious' causal relations between (vector) time series are not induced by linear transformations of the variables involved. This also yields transformations (or filters) which can eliminate Granger causality from one vector to another one. In a number of cases, we clarify results in the existing literature, with a number of calculations streamlining some existing approaches.

Quantifying synchrony patterns in the EEG of Alzheimer's patients with linear and non-linear connectivity markers.

We analyzed the relation of several synchrony markers in the electroencephalogram (EEG) and Alzheimer's disease (AD) severity as measured by Mini-Mental State Examination (MMSE) scores. The study sample consisted of 79 subjects diagnosed with probable AD. All subjects were participants in the PRODEM-Austria study. Following a homogeneous protocol, the EEG was recorded both in resting state and during a cognitive task. We employed quadratic least squares regression to describe the relation between MMSE and the EEG markers. Factor analysis was used for estimating a potentially lower number of unobserved synchrony factors. These common factors were then related to MMSE scores as well. Most markers displayed an initial increase of EEG synchrony with MMSE scores from 26 to 21 or 20, and a decrease below. This effect was most prominent during the cognitive task and may be owed to cerebral compensatory mechanisms. Factor analysis provided interesting insights in the synchrony structures and the first common factors were related to MMSE scores with coefficients of determination up to 0.433. We conclude that several of the proposed EEG markers are related to AD severity for the overall sample with a wide dispersion for individual subjects. Part of these fluctuations may be owed to fluctuations and day-to-day variability associated with MMSE measurements. Our study provides a systematic analysis of EEG synchrony based on a large and homogeneous sample. The results indicate that the individual markers capture different aspects of EEG synchrony and may reflect cerebral compensatory mechanisms in the early stages of AD.

Predicting rapid cognitive decline in Alzheimer's disease patients using quantitative EEG markers and neuropsychological test scores.

Alzheimer's Disease (AD) can take different courses: some patients remain relatively stable while others decline rapidly within a given period of time. Losing more than 3 Mini-Mental State Examination (MMSE) points in one year is classified as rapid cognitive decline (RCD). This study used neuropsychological test scores and quantitative EEG (QEEG) markers obtained at a baseline examination to identify if an AD patient will be suffering from RCD. Data from 68 AD patients of the multi-centric cohort study PRODEM-Austria were applied. 15 of the patients were classified into the RCD group. RCD versus non-RCD support vector machine (SVM) classifiers using QEEG markers as predictors obtained 72.1% and 77.9% accuracy ratings based on leave-one-out validation. Adding neuropsychological test scores of Boston Naming Test improved the classifier to 80.9% accuracy, 80% sensitivity, and 81.1% specificity. These results indicate that QEEG markers together with neuropsychological test scores can be used as RCD predictors.

Quantitative EEG markers relate to Alzheimer's disease severity in the Prospective Dementia Registry Austria (PRODEM).

OBJECTIVE: To investigate which single quantitative electro-encephalographic (QEEG) marker or which combination of markers correlates best with Alzheimer's disease (AD) severity as measured by the Mini-Mental State Examination (MMSE). METHODS: We compared quantitative EEG markers for slowing (relative band powers), synchrony (coherence, canonical correlation, Granger causality) and complexity (auto-mutual information, Shannon/Tsallis entropy) in 118 AD patients from the multi-centric study PRODEM Austria. Signal spectra were determined using an indirect spectral estimator. Analyses were adjusted for age, sex, duration of dementia, and level of education. RESULTS: For the whole group (39 possible, 79 probable AD cases) MMSE scores explained 33% of the variations in relative theta power during face encoding, and 31% of auto-mutual information in resting state with eyes closed. MMSE scores explained also 25% of the overall QEEG factor. This factor was thus subordinate to individual markers. In probable AD, QEEG coefficients of determination were always higher than in the whole group, where MMSE scores explained 51% of the variations in relative theta power. CONCLUSIONS: Selected QEEG markers show strong associations with AD severity. Both cognitive and resting state should be used for QEEG assessments. SIGNIFICANCE: Our data indicate theta power measured during face-name encoding to be most closely related to AD severity.

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.

Automatic ictal HFO detection for determination of initial seizure spread.

High-frequency oscillations (HFOs) are a reliable indicator for the epileptic seizure onset zone (SOZ) in ECoG recordings. We propose a novel method for the automatic detection of ictal HFOs in the ripple band (80-250 Hz) based on CFAR matched sub-space filtering. This allows to track the early propagation of ictal HFOs, revealing initial and follow-up epileptic activity on the electrodes. We apply this methodology to two seizures from one patient suffering from focal epilepsy. The electrodes identified are in very good accordance with the visual HFO analysis by clinicians. Furthermore the electrodes with initial HFO activity are correlated well with the SOZ (conventional v-activity).

Influence analysis for high-dimensional time series with an application to epileptic seizure onset zone detection.

Granger causality is a useful concept for studying causal relations in networks. However, numerical problems occur when applying the corresponding methodology to high-dimensional time series showing co-movement, e.g. EEG recordings or economic data. In order to deal with these shortcomings, we propose a novel method for the causal analysis of such multivariate time series based on Granger causality and factor models. We present the theoretical background, successfully assess our methodology with the help of simulated data and show a potential application in EEG analysis of epileptic seizures.

Properties of blocked linear systems.

This paper presents a systematic study on the properties of blocked linear systems that have resulted from blocking discrete-time linear time invariant systems. The main idea is to explore the relationship between the blocked and the unblocked systems. Existing results are reviewed and a number of important new results are derived. Focus is given particularly on the zero properties of the blocked system as no such study has been found in the literature.

Autoregressive models of singular spectral matrices.

This paper deals with autoregressive (AR) models of singular spectra, whose corresponding transfer function matrices can be expressed in a stable AR matrix fraction description [Formula: see text] with [Formula: see text] a tall constant matrix of full column rank and with the determinantal zeros of [Formula: see text] all stable, i.e. in [Formula: see text]. To obtain a parsimonious AR model, a canonical form is derived and a number of advantageous properties are demonstrated. First, the maximum lag of the canonical AR model is shown to be minimal in the equivalence class of AR models of the same transfer function matrix. Second, the canonical form model is shown to display a nesting property under natural conditions. Finally, an upper bound is provided for the total number of real parameters in the obtained canonical AR model, which demonstrates that the total number of real parameters grows linearly with the number of rows in [Formula: see text].

A physiologically motivated ECoG segmentation method for epileptic seizure onset zone detection.

In this paper we propose a novel segmentation method based on the relative frequency contributions of ictal multichannel ECoG data. Segments with predominant [[see text]]-activity are classified as epileptic. The seizure onset zone is determined by the temporal delay of the epileptic [[see text]]-activity (4-9Hz) on the different channels. We apply this methodology to three seizures of one patient suffering from focal epilepsy. The resulting segments reflect the visual characteristics of the ictal ECoG well. The seizure onset zone identified by the proposed method is in very good accordance with the clinical findings.

Regression-based analysis of synchronization in multichannel EEG in epilepsy.

In this paper we assess a dependency measure for multivariate time series termed Extrinsic-to-Intrinsic-Power-Ratio (EIPR) using two different signal models. In a comparison with Partial Directed Coherence (PDC) we show that both measures correctly identify imposed couplings, but that limitations of the PDC do not affect EIPR. Moreover, EIPR is successfully used for the localization of the seizure onset zone in ECoG recordings from two epilepsy patients, given the exact seizure onset time. The electrodes identified by the proposed method are in excellent accordance with the clinical findings.