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Levodopa May Affect Cortical Excitability in Parkinson's Disease

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Levodopa May Affect Cortical Excitability in Parkinson's Disease Neurobiology of Aging 73 (2019) 9e20 Contents lists available at ScienceDirect Neurobiology of Aging journal homepage: www.elsevier.com/locate/neuaging Levodopa may affect cortical excitability in Parkinson’s disease patients with cognitive deficits as revealed by reduced activity of cortical sources of resting state electroencephalographic rhythms Claudio Babiloni a,b,*, Claudio Del Percio c, Roberta Lizio a,b, Giuseppe Noce c, Susanna Lopez a, Andrea Soricelli c,d, Raffaele Ferri e, Maria Teresa Pascarelli e, Valentina Catania e, Flavio Nobili f, Dario Arnaldi f, Francesco Famà f, Francesco Orzi g, Carla Buttinelli g, Franco Giubilei g, Laura Bonanni h, Raffaella Franciotti h, Marco Onofrj h, Paola Stirpe b, Peter Fuhr i, Ute Gschwandtner i, Gerhard Ransmayr j, Lucia Fraioli b, Lucilla Parnetti k, Lucia Farotti k, Michela Pievani l, Fabrizia D’Antonio m, Carlo De Lena m, Bahar Güntekin n, Lutfu Hanoglu o, Görsev Yener p, Derya Durusu Emek-Savas¸ q, Antonio Ivano Triggiani r, John Paul Taylor s, Ian McKeith s, Fabrizio Stocchi b, Laura Vacca t, Giovanni B. Frisoni l,u, Maria Francesca De Pandis b a Department of Physiology and Pharmacology “Vittorio Erspamer”, University of Rome “La Sapienza”, Rome, Italy b Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome, Italy, and Hospital San Raffaele of Cassino, Italy c IRCCS SDN, Napoli, Italy d Department of Motor Sciences and Healthiness, University of Naples Parthenope, Naples, Italy e Oasi Research Institute - IRCCS, Troina, Italy f IRCCS Ospedale Policlinico San Martino, Italy - Dipartimento di Neuroscienze, Oftalmologia, Genetica, Riabilitazione e Scienze Materno-infantili (DiNOGMI), Università di Genova, Genova, Italy g Department of Neuroscience, Mental Health and Sensory Organs, University of Rome "La Sapienza”, Rome, Italy h Department of Neuroscience Imaging and Clinical Sciences and CESI, University G d’Annunzio of Chieti-Pescara, Chieti, Italy i Universitätsspital Basel, Abteilung Neurophysiologie, Basel, Switzerland j Department of Neurology 2, Med Campus III, Faculty of Medicine, Johannes Kepler University, Kepler University Hospital, Linz, Austria k Centre for Memory Disturbances, Lab of Clinical Neurochemistry, Section of Neurology, University of Perugia, Perugia, Italy l Laboratory of Alzheimer’s Neuroimaging and Epidemiology, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy m Department of Neurology and Psychiatry, Sapienza, University of Rome, Italy n Department of Biophysic, I stanbul Medipol University, Istanbul, Turkey o Department of Neurology, University of Istanbul-Medipol, Istanbul, Turkey p Department of Neurosciences and Department of Neurology, Dokuz Eylül University Medical School, Izmir, Turkey q Department of Psychology and Department of Neurosciences, Dokuz Eylül University, Izmir, Turkey r Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy s Institute of Neuroscience, Newcastle University, Newcastle, UK t Casa di Cura Privata del Policlinico (CCPP) Milano SpA, Milan, Italy u Memory Clinic and LANVIE - Laboratory of Neuroimaging of Aging, University Hospitals and University of Geneva, Geneva, Switzerland article info abstract Article history: We hypothesized that dopamine neuromodulation might affect cortical excitability in Parkinson’s dis- Received 13 June 2018 Received in revised form 7 August 2018 ease (PD) patients set in quiet wakefulness, as revealed by resting state eyes-closed electroencephalo- e Accepted 8 August 2018 graphic (rsEEG) rhythms at alpha frequencies (8 12 Hz). Clinical and rsEEG rhythms in PD with dementia Available online 30 August 2018 (N ¼ 35), PD with mild cognitive impairment (N ¼ 50), PD with normal cognition (N ¼ 35), and normal (N ¼ 50) older adults were available from an international archive. Cortical rsEEG sources were estimated Keywords: by exact low-resolution brain electromagnetic tomography. Compared with the normal older group, the < Functional brain connectivity PD groups showed reduced occipital alpha sources and increased widespread delta ( 4 Hz) sources. Resting state EEG rhythms Widespread frontal and temporal alpha sources exhibited an increase in PD with dementia compared Mild cognitive impairment due to with PD with mild cognitive impairment and PD with normal cognition groups, as function of dopamine * Corresponding author at: Department of Physiology and Pharmacology "V. Erspamer" University of Rome "La Sapienza", P. le A. Moro 5, Rome 00185, Italy. Tel.: þ39 0649910989; fax: þ39 0649910917. E-mail address: [email protected] (C. Babiloni). 0197-4580/$ e see front matter Ó 2018 Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.neurobiolaging.2018.08.010 10 C. Babiloni et al. / Neurobiology of Aging 73 (2019) 9e20 Alzheimer’s disease (ADMCI) depletion severity, typically greater in the former than the latter groups. A daily dose of levodopa Mild cognitive impairment due to induced a widespread reduction in cortical delta and alpha sources in a subgroup of 13 PD patients under ’ Parkinson s disease (PDMCI) standard chronic dopaminergic regimen. In PD patients in quiet wakefulness, alpha cortical source ac- tivations may reflect an excitatory effect of dopamine neuromodulation. Ó 2018 Elsevier Inc. All rights reserved. 1. Introduction reflect cortical over-excitability in quiet wakefulness (Babiloni et al., 2015), but the relationship of this effect with dopamine neuro- Parkinson’s disease (PD) is characterized by motor symptoms modulation is poorly known. This is particularly pertinent, given but often goes hand in hand with subtle mild cognitive impairment PDCD are affected by neurodegenerative neuropathology of at the disease onset. This cognitive dysfunction is progressive in subcortical projection to cerebral cortex lobe including deposition most of patients (Muslimovic et al., 2005). Indeed, the percentage of of a-synuclein in Lewy bodies and neurites, loss of tegmental PD patients progressing to dementia in 20 years is included be- dopamine cell populations, loss of basal forebrain cholinergic pro- tween 60% (Aarsland et al., 2003; Buter et al., 2008; Hughes et al., jection to the cortex, and a variable degree of coexisting AD 2000; Levy et al., 2000) and more than 80% (Hely et al., 2008). neuropathology (Barker and Williams-Gray, 2016; Irwin et al., The pathoetiology of the cognitive deficits in PD is heteroge- 2017). neous and thus patients may need personalized treatments to The present exploratory and observational study tested the hy- mitigate the cognitive decline. Ideally, this monitoring should be pothesis that the dopamine neuromodulation may affect cortical done with biomarkers reflecting those neuropathological processes excitability in PD patients set in quiet wakefulness, as assessed by or the effects of those processes on brain functions. Among various the examination of resting state cortical alpha rhythms. Our aim candidates, resting state eyes-closed electroencephalographic therefore was to make use of clinical and rsEEG rhythms in PDD, (rsEEG) rhythms are cost-effective, noninvasive, and can be mild cognitive impairment due to Parkinson’s disease (PDMCI), PD repeated several times. For this reason, they have extensively been with normal cognition, and Nold subjects from an available inter- studied as biomarkers to evaluate the neurophysiological mecha- national archive including all data coming from the PDWAVE Con- nisms of dementing disorders (Breslau et al.,1989; Briel et al.,1999). sortium. An assumption of this study was that compared to PD A prominent application of quantitative rsEEG techniques in PD patients without cognitive deficits, those with MCI and dementia patients was the computation of power (density) of rsEEG rhythms have had a longer disease with a consequent progression in the in standard frequency bands from delta (<4 Hz) to gamma (>30 Hz) depletion of dopaminergic brain neurons, although the relationship at scalp electrodes placed over the whole scalp, as a neurophysio- between duration and severity of the disease is not linear. For some logical biomarker of thalamocortical and corticothalamic neural of these patients under a standard chronic dopaminergic regimen, synchronization of oscillatory cycles of cellular excitation and in- clinical and rsEEG rhythms were available before (OFF) and after hibition. Results have shown that when compared to normal (ON) about 60 minutes from the administration of 1 daily dose of healthy elderly (Nold) individuals, PD patients with cognitive def- levodopa. From a methodological point of view, we used exact low- icits (PDCD) were characterized by widespread higher power in resolution brain electromagnetic tomography (eLORETA) freeware delta and theta (4e7 Hz) rhythms and some reduction of alpha to estimate rsEEG cortical sources at individual frequency bands power (Bonanni et al., 2008; Bosboom et al., 2006, 2009; Caviness (Pascual-Marqui, 2007) to improve the topographic analysis of et al., 2016; Fünfgeld, 1995; Kamei et al., 2010; Melgari et al., alpha rhythms. In previous studies of our group, this methodology 2014; Pugnetti et al., 2010; Serizawa et al., 2008). PDCD also unveiled different characteristics of abnormal cortical delta and showed lower frequency of the alpha (8e12 Hz) power peak, alpha source activity in PDCD in relation not only to Nold subjects greater global theta and delta power, and lower power in the alpha but also to patients with cognitive deficits due to AD and DLB and beta (13e30 Hz) frequency
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