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Neurobiol Aging. 2020 Jan;85:58-73. doi: 10.1016/j.neurobiolaging.2019.09.008. Epub 2019 Sep 19.

What electrophysiology tells us about Alzheimer's disease: a window into the synchronization and connectivity of brain neurons.

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Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, Rome, Italy; Hospital San Raffaele Cassino, Cassino (FR), Italy. Electronic address:
Faculty of Physics, University of Warsaw and Nalecz Institute of Biocybernetics, Warsaw, Poland.
Department of Neuroscience Imaging and Clinical Sciences and CESI, University G D'Annunzio of Chieti-Pescara, Chieti, Italy.
Skolkovo Institute of Science and Technology (SKOLTECH), Moscow, Russia; Systems Research Institute PAS, Warsaw, Poland; Nicolaus Copernicus University (UMK), Torun, Poland.
Amsterdam Neuroscience, Department of Neurology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, Rome, Italy.
Institute of Memory and Alzheimer's Disease (IM2A), Department of Neurology, Pitié-Salpêtrière Hospital, AP-HP, Boulevard de l'hôpital, Paris, France; Institut du Cerveau et de la Moelle épinière, ICM, INSERM U1127, Sorbonne Université, Paris, France.
School of Engineering, Institute for Digital Communications, The University of Edinburgh, Edinburgh, UK.
Laboratory of Cognitive and Computational Neuroscience, Center for Biomedical Technology, Universidad Complutense and Universidad Politécnica de Madrid, Madrid, Spain.
IRCCS San Giovanni di Dio Fatebenefratelli, Brescia, Italy; Memory Clinic and LANVIE - Laboratory of Neuroimaging of Aging, University Hospitals and University of Geneva, Geneva, Switzerland.
Department of Biophysics, International School of Medicine, Istanbul Medipol University, Istanbul, Turkey.
Translational Neuropharmacology, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA.
Institute of Memory and Alzheimer's Disease (IM2A), Department of Neurology, Pitié-Salpêtrière Hospital, AP-HP, Boulevard de l'hôpital, Paris, France; Institut du Cerveau et de la Moelle épinière, ICM, INSERM U1127, Sorbonne Université, Paris, France; GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, Sorbonne University, Paris, France.
School of Computing, Electronics and Mathematics, Faculty of Science and Engineering, Plymouth University, Plymouth, UK.
School of Psychology, University of Glasgow, Glasgow, UK.
Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Mentis Cura ehf, Reykjavík, Iceland.
Department of Bio and Brain Engineering/Program of Brain and Cognitive Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea.
Institute for Neuroscience, Newcastle University, Newcastle upon Tyne, UK.
IRCCS SDN, Napoli, Italy.
Center of Neurosciences, Swammerdam Institute of Life Sciences, University of Amsterdam, Amsterdam, The Netherlands.
School of Psychological Sciences and Health, University of Strathclyde, Glasgow, UK.
IRCCS San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
Department of Neuroscience (DINOGMI), University of Genoa, Genoa, Italy; Clinica Neurologica, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
UC Davis Department of Neurology, Center for Neuroscience, Davis, CA, USA.
Gladstone Institute of Neurological Disease, San Francisco, CA, USA.
Department of Pharmacology and Therapeutics, Trinity College Dublin, Dublin, Ireland.
IRCCS San Raffaele Pisana, Rome, Italy.
RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan; Graduate School of Education, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; Advanced Center for Computing and Communication, RIKEN, 2-1 Hirosawa, Wako 351-0198, Saitama, Japan; Faculty of Physics, The University of Warsaw, Pasteur 5, 02-093 Warsaw, Poland.
A. I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland.
German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany; Department of Psychosomatic and Psychotherapeutic Medicine, University of Rostock, Rostock, Germany.
Experimental Neuropsychopharmacology, Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM), Bonn, Germany.
Department of Neurosciences and Department of Neurology, Dokuz Eylül University Medical School, Izmir, Turkey.
Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
Janssen Research & Development, Janssen Pharmaceutica NV, Beerse, Belgium.
Vertex Pharmaceuticals Incorporated, Boston, MA, USA.


Electrophysiology provides a real-time readout of neural functions and network capability in different brain states, on temporal (fractions of milliseconds) and spatial (micro, meso, and macro) scales unmet by other methodologies. However, current international guidelines do not endorse the use of electroencephalographic (EEG)/magnetoencephalographic (MEG) biomarkers in clinical trials performed in patients with Alzheimer's disease (AD), despite a surge in recent validated evidence. This position paper of the ISTAART Electrophysiology Professional Interest Area endorses consolidated and translational electrophysiological techniques applied to both experimental animal models of AD and patients, to probe the effects of AD neuropathology (i.e., brain amyloidosis, tauopathy, and neurodegeneration) on neurophysiological mechanisms underpinning neural excitation/inhibition and neurotransmission as well as brain network dynamics, synchronization, and functional connectivity, reflecting thalamocortical and corticocortical residual capacity. Converging evidence shows relationships between abnormalities in EEG/MEG markers and cognitive deficits in groups of AD patients at different disease stages. The supporting evidence for the application of electrophysiology in AD clinical research as well as drug discovery pathways warrants an international initiative to include the use of EEG/MEG biomarkers in the main multicentric projects planned in AD patients, to produce conclusive findings challenging the present regulatory requirements and guidelines for AD studies.


Alzheimer's disease (AD); Electroencephalography and magnetoencephalography (EEG and MEG); Event-related potentials and magnetic fields; Preclinical and clinical research; Resting-state condition; The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART)

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