Cross-Frequency Multilayer Network Analysis with Bispectrum-based Functional Connectivity:A Study of Alzheimer's Disease

Alzheimer's disease (AD) is a neurodegenerative disorder known to affect functional connectivity (FC) across many brain regions. Linear FC measures have been applied to study the differences in AD by splitting neurophysiological signals, such as electroencephalography (EEG) recordings, into discrete frequency bands and analysing them in isolation from each other. We address this limitation by quantifying cross-frequency FC in addition to the traditional within-band approach. Cross-bispectrum, a higher-order spectral analysis approach, is used to measure the nonlinear FC and is compared with the cross-spectrum, which only measures the linear FC within bands. This work reports the reconstruction of a cross-frequency FC network where each frequency band is treated as a layer in a multilayer network with both inter- and intra-layer edges. Cross-bispectrum detects cross-frequency differences, mainly increased FC in AD cases in δ-θ coupling. Overall, increased strength of low-frequency coupling and decreased level of high-frequency coupling is observed in AD cases in comparison to healthy controls (HC). We demonstrate that a graph-theoretic analysis of cross-frequency brain networks is crucial to obtain a more detailed insight into their structure and function. Vulnerability analysis reveals that the integration and segregation properties of networks are enabled by different frequency couplings in AD networks compared to HCs. Finally, we use the reconstructed networks for classification. The extra cross-frequency coupling information can improve the classification performance significantly, suggesting an important role of cross-frequency FC. The results highlight the importance of studying nonlinearity and including cross-frequency FC in characterising AD.UnknownSupports Open Acces

A wavelet-based correlation analysis framework to study cerebromuscular activity in essential tremor

Deep brain stimulation (DBS) provides dramatic tremor relief in patients with severe essential tremor (ET). Typically, the VIM nucleus is the most effective brain area to target for high-frequency electrical stimulation in these patients. Correlation analysis between electrical local field potential (LFP) recordings from the thalamic DBS leads and electrical muscle activity from the contralateral tremulous limb has become an attractive practical tool to interpret the LFPs and their association with the tremulous clinical manifestations. Although functional connectivity analysis between brain electrical recordings and electromyographic (EMG) signals from the tremor has been of interest to an increasing number of engineering researchers, there is no well-accepted tailored framework to consistently characterise the association between thalamic electrical recordings and the tremorogenic EMG activity. Methods. This paper proposes a novel framework to address this challenge, including an estimation of the interaction strength using wavelet cross-spectrum and phase lag index while demonstrating the statistical significance of the findings. Results. Consistent results were estimated for single and multiple trials of consecutive or partially overlapping epochs of data. The latter approach reveals a substantial increase on the range of statistically significant dynamic low-frequency interrelationships while decreasing the dynamic range of high-frequency interactions. Conclusion. Results from both simulation and real data demonstrate the feasibility and robustness of the proposed framework. Significance. This study offers the proof of principle required to implement this methodology to uncover VIM thalamic LFP-EMG interactions for (i) better understanding of the pathophysiology of tremor; (ii) objective selection of the DBS electrode contacts with the highest strength of association with the tremorogenic EMG, a particularly useful feature for the implementation of novel multicontact directional leads in clinical practice; and (iii) future research on DBS closed-loop devices

Ultra-high-resolution time-frequency analysis of EEG to characterise brain functional connectivity with the application in Alzheimer's disease

Objective. This study aims to explore the potential of high-resolution brain functional connectivity based on electroencephalogram, a non-invasive low-cost technique, to be translated into a long-overdue biomarker and a diagnostic method for Alzheimer's disease (AD). Approach. The paper proposes a novel ultra-high-resolution time-frequency nonlinear cross-spectrum method to construct a promising biomarker of AD pathophysiology. Specifically, using the peak frequency estimated from a revised Hilbert–Huang transformation (RHHT) cross-spectrum as a biomarker, the support vector machine classifier is used to distinguish AD from healthy controls (HCs). Main results. With the combinations of the proposed biomarker and machine learning, we achieved a promising accuracy of 89%. The proposed method performs better than the wavelet cross-spectrum and other functional connectivity measures in the temporal or frequency domain, particularly in the Full, Delta and Alpha bands. Besides, a novel visualisation approach developed from topography is introduced to represent the brain functional connectivity, with which the difference between AD and HCs can be clearly displayed. The interconnections between posterior and other brain regions are obviously affected in AD. Significance. Those findings imply that the proposed RHHT approach could better track dynamic and nonlinear functional connectivity information, paving the way for the development of a novel diagnostic approach

Using interictal seizure-free EEG data to recognise patients with epilepsy based on machine learning of brain functional connectivity

Most seizures in adults with epilepsy occur rather infrequently and as a result, the interictal EEG plays a crucial role in the diagnosis and classification of epilepsy. However, empirical interpretation, of a first EEG in adult patients, has a very low sensitivity ranging between 29-55%. Useful EEG information remains buried within the signals in seizure-free EEG epochs, far beyond the observational capabilities of any specialised physician in this field. Unlike most of the existing works focusing on either seizure data or single-variate method, we introduce a multi-variate method to characterise sensor level brain functional connectivity from interictal EEG data to identify patients with generalised epilepsy. A total of 9 connectivity features based on 5 different measures in time, frequency and time frequency domains have been tested. The solution has been validated by the K-Nearest Neighbour algorithm, classifying an epilepsy group (EG) vs healthy controls (HC) and subsequently with another cohort of patients characterised by non-epileptic attacks (NEAD), a psychogenic type of disorder. A high classification accuracy (97%) was achieved for EG vs HC while revealing significant spatio temporal deficits in the frontocentral areas in the beta frequency band. For EG vs NEAD, the classification accuracy was only about 73%, which might be a reflection of the well-described coexistence of NEAD with epileptic attacks. Our work demonstrates that seizure-free interictal EEG data can be used to accurately classify patients with generalised epilepsy from HC and that more systematic work is required in this direction aiming to produce a clinically useful diagnostic method

Bispectrum-based Cross-frequency Functional Connectivity: Classification of Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disease known to affect brain functional connectivity (FC). Linear FC measures have been applied to study the differences in AD by splitting neurophysiological signals such as electroencephalography (EEG) recordings into discrete frequency bands and analysing them in isolation. We address this limitation by quantifying cross-frequency FC in addition to the traditional within-band approach. Cross-bispectrum, a higher-order spectral analysis, is used to measure the nonlinear FC and is compared with the cross-spectrum, which only measures the linear FC within bands. Each frequency coupling is then used to construct an FC network, which is in turn vectorised and used to train a classifier. We show that fusing features from networks improves classification accuracy. Although both within-frequency and cross-frequency networks can be used to predict AD with high accuracy, our results show that bispectrum-based FC outperforms cross-spectrum suggesting an important role of cross-frequency FC.Comment: 5 pages, 4 figures, conferenc

Bispectrum-based Cross-frequency Functional Connectivity: Classification of Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disease known to affect brain functional connectivity (FC). Linear FC measures have been applied to study the differences in AD by splitting neurophysiological signals such as electroencephalography (EEG) recordings into discrete frequency bands and analysing them in isolation. We address this limitation by quantifying cross-frequency FC in addition to the traditional within-band approach. Cross-bispectrum, a higher-order spectral analysis, is used to measure the nonlinear FC and is compared with the cross-spectrum, which only measures the linear FC within bands. Each frequency coupling is then used to construct an FC network, which is in turn vectorised and used to train a classifier. We show that fusing features from networks improves classification accuracy. Although both within-frequency and cross-frequency networks can be used to predict AD with high accuracy, our results show that bispectrum-based FC outperforms cross-spectrum suggesting an important role of cross-frequency FC.Comment: 5 pages, 4 figures, conferenc