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      Working Memory Decline in Alzheimer’s Disease Is Detected by Complexity Analysis of Multimodal EEG-fNIRS

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          Abstract

          Alzheimer’s disease (AD) is characterized by working memory (WM) failures that can be assessed at early stages through administering clinical tests. Ecological neuroimaging, such as Electroencephalography (EEG) and functional Near Infrared Spectroscopy (fNIRS), may be employed during these tests to support AD early diagnosis within clinical settings. Multimodal EEG-fNIRS could measure brain activity along with neurovascular coupling (NC) and detect their modifications associated with AD. Data analysis procedures based on signal complexity are suitable to estimate electrical and hemodynamic brain activity or their mutual information (NC) during non-structured experimental paradigms. In this study, sample entropy of whole-head EEG and frontal/prefrontal cortex fNIRS was evaluated to assess brain activity in early AD and healthy controls (HC) during WM tasks (i.e., Rey–Osterrieth complex figure and Raven’s progressive matrices). Moreover, conditional entropy between EEG and fNIRS was evaluated as indicative of NC. The findings demonstrated the capability of complexity analysis of multimodal EEG-fNIRS to detect WM decline in AD. Furthermore, a multivariate data-driven analysis, performed on these entropy metrics and based on the General Linear Model, allowed classifying AD and HC with an AUC up to 0.88. EEG-fNIRS may represent a powerful tool for the clinical evaluation of WM decline in early AD.

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          Deep learning.

          Deep learning allows computational models that are composed of multiple processing layers to learn representations of data with multiple levels of abstraction. These methods have dramatically improved the state-of-the-art in speech recognition, visual object recognition, object detection and many other domains such as drug discovery and genomics. Deep learning discovers intricate structure in large data sets by using the backpropagation algorithm to indicate how a machine should change its internal parameters that are used to compute the representation in each layer from the representation in the previous layer. Deep convolutional nets have brought about breakthroughs in processing images, video, speech and audio, whereas recurrent nets have shone light on sequential data such as text and speech.
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            EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis

            We have developed a toolbox and graphic user interface, EEGLAB, running under the crossplatform MATLAB environment (The Mathworks, Inc.) for processing collections of single-trial and/or averaged EEG data of any number of channels. Available functions include EEG data, channel and event information importing, data visualization (scrolling, scalp map and dipole model plotting, plus multi-trial ERP-image plots), preprocessing (including artifact rejection, filtering, epoch selection, and averaging), independent component analysis (ICA) and time/frequency decompositions including channel and component cross-coherence supported by bootstrap statistical methods based on data resampling. EEGLAB functions are organized into three layers. Top-layer functions allow users to interact with the data through the graphic interface without needing to use MATLAB syntax. Menu options allow users to tune the behavior of EEGLAB to available memory. Middle-layer functions allow users to customize data processing using command history and interactive 'pop' functions. Experienced MATLAB users can use EEGLAB data structures and stand-alone signal processing functions to write custom and/or batch analysis scripts. Extensive function help and tutorial information are included. A 'plug-in' facility allows easy incorporation of new EEG modules into the main menu. EEGLAB is freely available (http://www.sccn.ucsd.edu/eeglab/) under the GNU public license for noncommercial use and open source development, together with sample data, user tutorial and extensive documentation.
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              Physiological time-series analysis using approximate entropy and sample entropy.

              Entropy, as it relates to dynamical systems, is the rate of information production. Methods for estimation of the entropy of a system represented by a time series are not, however, well suited to analysis of the short and noisy data sets encountered in cardiovascular and other biological studies. Pincus introduced approximate entropy (ApEn), a set of measures of system complexity closely related to entropy, which is easily applied to clinical cardiovascular and other time series. ApEn statistics, however, lead to inconsistent results. We have developed a new and related complexity measure, sample entropy (SampEn), and have compared ApEn and SampEn by using them to analyze sets of random numbers with known probabilistic character. We have also evaluated cross-ApEn and cross-SampEn, which use cardiovascular data sets to measure the similarity of two distinct time series. SampEn agreed with theory much more closely than ApEn over a broad range of conditions. The improved accuracy of SampEn statistics should make them useful in the study of experimental clinical cardiovascular and other biological time series.
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                Author and article information

                Journal
                Entropy (Basel)
                Entropy (Basel)
                entropy
                Entropy
                MDPI
                1099-4300
                06 December 2020
                December 2020
                : 22
                : 12
                : 1380
                Affiliations
                [1 ]Institute for Advanced Biomedical Technologies, Department of Neuroscience and Imaging, University G. D’Annunzio of Chieti-Pescara, Via Luigi Polacchi 13, 66100 Chieti, Italy; antonio.chiarelli@ 123456unich.it (A.M.C.); chiara.filippini@ 123456unich.it (C.F.); d.cardone@ 123456unich.it (D.C.); pierpaolo.croce@ 123456unich.it (P.C.); f.zappasodi@ 123456unich.it (F.Z.); arcangelo.merla@ 123456unich.it (A.M.)
                [2 ]Department of Medicine and Science of Ageing, University G. D’Annunzio, Via Dei Vestini 31, 66100 Chieti, Italy; ludorotunno@ 123456gmail.com (L.R.); nelson.anzoletti@ 123456gmail.com (N.A.); m.zito@ 123456dmsi.unich.it (M.Z.)
                Author notes
                [* ]Correspondence: david.perpetuini@ 123456unich.it ; Tel.: +39-0871-3556954
                Author information
                https://orcid.org/0000-0003-1903-0501
                https://orcid.org/0000-0002-5347-8417
                https://orcid.org/0000-0003-2282-3537
                https://orcid.org/0000-0002-1506-1995
                https://orcid.org/0000-0001-7279-3052
                Article
                entropy-22-01380
                10.3390/e22121380
                7762102
                33279924
                627a8e07-ae48-42e6-9c96-4ff38c768adb
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 30 October 2020
                : 03 December 2020
                Categories
                Article

                alzheimer’s disease (ad),electroencephalography (eeg),functional near-infrared spectroscopy (fnirs),multimodal neuroimaging,neurovascular coupling (nc),complexity analysis,sample entropy,conditional entropy,rey–osterrieth complex figure,raven’s progressive matrices

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