A pilot study investigating a novel non-linear measure of eyes open versus eyes closed EEG synchronization in people with alzheimer’s disease and healthy controls

Daniel J. Blackburn; Yifan Zhao; Matteo De Marco; Simon M. Bell; Fei He; Hua Liang Wei; Sarah Lawrence; Zoe C. Unwin; Michelle Blyth; Jenna Angel; Kathleen Baster; Thomas F.D. Farrow; Iain D. Wilkinson; Stephen A. Billings; Annalena Venneri; Ptolemaios G. Sarrigiannis

doi:10.3390/brainsci8070134

A pilot study investigating a novel non-linear measure of eyes open versus eyes closed EEG synchronization in people with alzheimer’s disease and healthy controls

Daniel J. Blackburn, Yifan Zhao, Matteo De Marco, Simon M. Bell, Fei He, Hua Liang Wei, Sarah Lawrence, Zoe C. Unwin, Michelle Blyth, Jenna Angel, Kathleen Baster, Thomas F.D. Farrow, Iain D. Wilkinson, Stephen A. Billings, Annalena Venneri, Ptolemaios G. Sarrigiannis

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Abstract

Background: The incidence of Alzheimer disease (AD) is increasing with the ageing population. The development of low cost non-invasive diagnostic aids for AD is a research priority. This pilot study investigated whether an approach based on a novel dynamic quantitative parametric EEG method could detect abnormalities in people with AD. Methods: 20 patients with probable AD, 20 matched healthy controls (HC) and 4 patients with probable fronto temporal dementia (FTD) were included. All had detailed neuropsychology along with structural, resting state fMRI and EEG. EEG data were analyzed using the Error Reduction Ratio-causality (ERR-causality) test that can capture both linear and nonlinear interactions between different EEG recording areas. The 95% confidence intervals of EEG levels of bi-centroparietal synchronization were estimated for eyes open (EO) and eyes closed (EC) states. Results: In the EC state, AD patients and HC had very similar levels of bi-centro parietal synchronization; but in the EO resting state, patients with AD had significantly higher levels of synchronization (AD = 0.44; interquartile range (IQR) 0.41 vs. HC = 0.15; IQR 0.17, p < 0.0001). The EO/EC synchronization ratio, a measure of the dynamic changes between the two states, also showed significant differences between these two groups (AD ratio 0.78 versus HC ratio 0.37 p < 0.0001). EO synchronization was also significantly different between AD and FTD (FTD = 0.075; IQR 0.03, p < 0.0001). However, the EO/EC ratio was not informative in the FTD group due to very low levels of synchronization in both states (EO and EC). Conclusion: In this pilot work, resting state quantitative EEG shows significant differences between healthy controls and patients with AD. This approach has the potential to develop into a useful non-invasive and economical diagnostic aid in AD.

Original language	English
Article number	134
Journal	Brain Sciences
Volume	8
Issue number	7
DOIs	https://doi.org/10.3390/brainsci8070134
Publication status	Published - 17 Jul 2018
Externally published	Yes

Bibliographical note

This article is an open access article distributed under the terms and conditions of
the Creative Commons Attribution (CC BY) license.

Funding

Department of Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK; [email protected] (M.D.M.); [email protected] (A.V.); [email protected] (S.M.B.); [email protected] (T.F.D.F.) Department of Clinical Neurophysiology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S10 2JF, UK; [email protected] (P.G.S.); [email protected] (S.L.); [email protected] (Z.C.U.); [email protected] (M.B.); [email protected] (J.A.) School of Aerospace, Transport and Manufacturing, Cranfield University, Cranfield MK43, UK; [email protected] School of Mathematics & Statistics, University of Sheffield, Sheffield S1 2TN, UK; [email protected] Academic Unit of Radiology, University of Sheffield, Sheffield S1 2TN, UK; [email protected] Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London SW7, UK; [email protected] Department of Automatic Control & Systems Engineering, University of Sheffield, Sheffield S10 2TN, UK; [email protected] (H.-L.W.); [email protected] (S.A.B.) Correspondence: [email protected] Funding: This study was funded by a grant from the Alzheimer’s Research UK, grant reference number ARUK-PPG20114B-25. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement No. 601055, VPH-DARE@IT. We would like to thank all the patients and volunteers who took part in this study. This is a summary of independent research carried out at the NIHR Sheffield Biomedical Research Centre (Translational Neuroscience). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The support of the NIHR Clinical Research Facility—Sheffield Teaching Hospital is also acknowledged.

Keywords

Alzheimer’s disease
Clinical marker
Electroencephalography
Nonlinear dynamics
ROC curve

ASJC Scopus subject areas

General Neuroscience

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cite this

Blackburn, D. J., Zhao, Y., De Marco, M., Bell, S. M., He, F., Wei, H. L., Lawrence, S., Unwin, Z. C., Blyth, M., Angel, J., Baster, K., Farrow, T. F. D., Wilkinson, I. D., Billings, S. A., Venneri, A., & Sarrigiannis, P. G. (2018). A pilot study investigating a novel non-linear measure of eyes open versus eyes closed EEG synchronization in people with alzheimer’s disease and healthy controls. Brain Sciences, 8(7), Article 134. https://doi.org/10.3390/brainsci8070134

Blackburn, DJ, Zhao, Y, De Marco, M, Bell, SM, He, F, Wei, HL, Lawrence, S, Unwin, ZC, Blyth, M, Angel, J, Baster, K, Farrow, TFD, Wilkinson, ID, Billings, SA, Venneri, A & Sarrigiannis, PG 2018, 'A pilot study investigating a novel non-linear measure of eyes open versus eyes closed EEG synchronization in people with alzheimer’s disease and healthy controls', Brain Sciences, vol. 8, no. 7, 134. https://doi.org/10.3390/brainsci8070134

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abstract = "Background: The incidence of Alzheimer disease (AD) is increasing with the ageing population. The development of low cost non-invasive diagnostic aids for AD is a research priority. This pilot study investigated whether an approach based on a novel dynamic quantitative parametric EEG method could detect abnormalities in people with AD. Methods: 20 patients with probable AD, 20 matched healthy controls (HC) and 4 patients with probable fronto temporal dementia (FTD) were included. All had detailed neuropsychology along with structural, resting state fMRI and EEG. EEG data were analyzed using the Error Reduction Ratio-causality (ERR-causality) test that can capture both linear and nonlinear interactions between different EEG recording areas. The 95\% confidence intervals of EEG levels of bi-centroparietal synchronization were estimated for eyes open (EO) and eyes closed (EC) states. Results: In the EC state, AD patients and HC had very similar levels of bi-centro parietal synchronization; but in the EO resting state, patients with AD had significantly higher levels of synchronization (AD = 0.44; interquartile range (IQR) 0.41 vs. HC = 0.15; IQR 0.17, p < 0.0001). The EO/EC synchronization ratio, a measure of the dynamic changes between the two states, also showed significant differences between these two groups (AD ratio 0.78 versus HC ratio 0.37 p < 0.0001). EO synchronization was also significantly different between AD and FTD (FTD = 0.075; IQR 0.03, p < 0.0001). However, the EO/EC ratio was not informative in the FTD group due to very low levels of synchronization in both states (EO and EC). Conclusion: In this pilot work, resting state quantitative EEG shows significant differences between healthy controls and patients with AD. This approach has the potential to develop into a useful non-invasive and economical diagnostic aid in AD.",

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T1 - A pilot study investigating a novel non-linear measure of eyes open versus eyes closed EEG synchronization in people with alzheimer’s disease and healthy controls

AU - Blackburn, Daniel J.

AU - Zhao, Yifan

AU - De Marco, Matteo

AU - Bell, Simon M.

AU - He, Fei

AU - Wei, Hua Liang

AU - Lawrence, Sarah

AU - Unwin, Zoe C.

AU - Blyth, Michelle

AU - Angel, Jenna

AU - Baster, Kathleen

AU - Farrow, Thomas F.D.

AU - Wilkinson, Iain D.

AU - Billings, Stephen A.

AU - Venneri, Annalena

AU - Sarrigiannis, Ptolemaios G.

N1 - This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.

PY - 2018/7/17

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N2 - Background: The incidence of Alzheimer disease (AD) is increasing with the ageing population. The development of low cost non-invasive diagnostic aids for AD is a research priority. This pilot study investigated whether an approach based on a novel dynamic quantitative parametric EEG method could detect abnormalities in people with AD. Methods: 20 patients with probable AD, 20 matched healthy controls (HC) and 4 patients with probable fronto temporal dementia (FTD) were included. All had detailed neuropsychology along with structural, resting state fMRI and EEG. EEG data were analyzed using the Error Reduction Ratio-causality (ERR-causality) test that can capture both linear and nonlinear interactions between different EEG recording areas. The 95% confidence intervals of EEG levels of bi-centroparietal synchronization were estimated for eyes open (EO) and eyes closed (EC) states. Results: In the EC state, AD patients and HC had very similar levels of bi-centro parietal synchronization; but in the EO resting state, patients with AD had significantly higher levels of synchronization (AD = 0.44; interquartile range (IQR) 0.41 vs. HC = 0.15; IQR 0.17, p < 0.0001). The EO/EC synchronization ratio, a measure of the dynamic changes between the two states, also showed significant differences between these two groups (AD ratio 0.78 versus HC ratio 0.37 p < 0.0001). EO synchronization was also significantly different between AD and FTD (FTD = 0.075; IQR 0.03, p < 0.0001). However, the EO/EC ratio was not informative in the FTD group due to very low levels of synchronization in both states (EO and EC). Conclusion: In this pilot work, resting state quantitative EEG shows significant differences between healthy controls and patients with AD. This approach has the potential to develop into a useful non-invasive and economical diagnostic aid in AD.

AB - Background: The incidence of Alzheimer disease (AD) is increasing with the ageing population. The development of low cost non-invasive diagnostic aids for AD is a research priority. This pilot study investigated whether an approach based on a novel dynamic quantitative parametric EEG method could detect abnormalities in people with AD. Methods: 20 patients with probable AD, 20 matched healthy controls (HC) and 4 patients with probable fronto temporal dementia (FTD) were included. All had detailed neuropsychology along with structural, resting state fMRI and EEG. EEG data were analyzed using the Error Reduction Ratio-causality (ERR-causality) test that can capture both linear and nonlinear interactions between different EEG recording areas. The 95% confidence intervals of EEG levels of bi-centroparietal synchronization were estimated for eyes open (EO) and eyes closed (EC) states. Results: In the EC state, AD patients and HC had very similar levels of bi-centro parietal synchronization; but in the EO resting state, patients with AD had significantly higher levels of synchronization (AD = 0.44; interquartile range (IQR) 0.41 vs. HC = 0.15; IQR 0.17, p < 0.0001). The EO/EC synchronization ratio, a measure of the dynamic changes between the two states, also showed significant differences between these two groups (AD ratio 0.78 versus HC ratio 0.37 p < 0.0001). EO synchronization was also significantly different between AD and FTD (FTD = 0.075; IQR 0.03, p < 0.0001). However, the EO/EC ratio was not informative in the FTD group due to very low levels of synchronization in both states (EO and EC). Conclusion: In this pilot work, resting state quantitative EEG shows significant differences between healthy controls and patients with AD. This approach has the potential to develop into a useful non-invasive and economical diagnostic aid in AD.

KW - Alzheimer’s disease

KW - Clinical marker

KW - Electroencephalography

KW - Nonlinear dynamics

KW - ROC curve

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A pilot study investigating a novel non-linear measure of eyes open versus eyes closed EEG synchronization in people with alzheimer’s disease and healthy controls

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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