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Bispectrum-based Cross-frequency Functional Connectivity: A Study of Alzheimer’s Disease

Dominik Klepl, View ORCID ProfileFei He, Min Wu, Daniel J. Blackburn, Ptolemaios G. Sarrigiannis
doi: https://doi.org/10.1101/2021.08.07.455499
Dominik Klepl
1Centre for Computational Science and Mathematical Modelling, Coventry University, Coventry CV1 2JH, UK
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Fei He
1Centre for Computational Science and Mathematical Modelling, Coventry University, Coventry CV1 2JH, UK
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  • For correspondence: fei.he@coventry.ac.uk
Min Wu
2Institute for Infocomm Research, Agency for Science, Technology and Research (A*STAR), 138632, Singapore
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Daniel J. Blackburn
3Department of Neuroscience, University of Sheffield, Sheffield, S10 2HQ, UK
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Ptolemaios G. Sarrigiannis
4Department of Neurophysiology, Royal Devon and Exeter NHS Foundation Trust, Exeter, EX2 5DW, UK
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Abstract

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 first use of cross-bispectrum to reconstruct 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. An increase of within-band FC in AD is observed in low-frequency bands using both methods. Bispectrum also detects multiple cross-frequency differences, mainly increased FC in AD in delta-theta coupling. An increased importance of low-frequency coupling and decreased importance of high-frequency coupling is observed in AD. Integration properties of AD networks are more vulnerable than HC, while the segregation property is maintained in AD. Moreover, the segregation property of γ is less vulnerable in AD, suggesting the shift of importance from high-frequency activity towards low-frequency components. The results highlight the importance of studying nonlinearity and including cross-frequency FC in characterising AD. Moreover, the results demonstrate the advantages and limitations of using bispectrum to reconstruct FC networks.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted August 08, 2021.
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Bispectrum-based Cross-frequency Functional Connectivity: A Study of Alzheimer’s Disease
Dominik Klepl, Fei He, Min Wu, Daniel J. Blackburn, Ptolemaios G. Sarrigiannis
bioRxiv 2021.08.07.455499; doi: https://doi.org/10.1101/2021.08.07.455499
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Bispectrum-based Cross-frequency Functional Connectivity: A Study of Alzheimer’s Disease
Dominik Klepl, Fei He, Min Wu, Daniel J. Blackburn, Ptolemaios G. Sarrigiannis
bioRxiv 2021.08.07.455499; doi: https://doi.org/10.1101/2021.08.07.455499

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