Silvia Casarotto1, Francesco Turco2, Angela Comanducci3, Alessio Perretti4, Giorgio Marotta5, Gianni Pezzoli6, Mario Rosanova7, Ioannis U Isaias8. 1. Department of Biomedical and Clinical Sciences "L. Sacco", LASEB Laboratory, University of Milan, via GB Grassi 74, 20157, Milan, Italy. Electronic address: silvia.casarotto@unimi.it. 2. Fondazione Europea di Ricerca Biomedica (FERB Onlus), via Ambrogio Uboldo 21, 20063, Cernusco sul Naviglio, Milan, Italy; Department of Neurology, University Hospital and Julius-Maximilian-University, Josef-Schneider-Str. 11, 97080, Würzburg, Germany. Electronic address: francesco.turco1989@gmail.com. 3. Department of Biomedical and Clinical Sciences "L. Sacco", LASEB Laboratory, University of Milan, via GB Grassi 74, 20157, Milan, Italy. Electronic address: angela.comanducci@unimi.it. 4. Fondazione Europea di Ricerca Biomedica (FERB Onlus), via Ambrogio Uboldo 21, 20063, Cernusco sul Naviglio, Milan, Italy. Electronic address: paramiauxparkinson@gmail.com. 5. Department of Nuclear Medicine, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, via Francesco Sforza 28, 20122, Milan, Italy. Electronic address: marottag@policlinico.mi.it. 6. Parkinson Institute ASST G. Pini-CTO, via Bignami 1, 20126, Milan, Italy. Electronic address: gianni.pezzoli@gmail.com. 7. Department of Biomedical and Clinical Sciences "L. Sacco", LASEB Laboratory, University of Milan, via GB Grassi 74, 20157, Milan, Italy; Fondazione Europea di Ricerca Biomedica (FERB Onlus), via Ambrogio Uboldo 21, 20063, Cernusco sul Naviglio, Milan, Italy. Electronic address: mario.rosanova@unimi.it. 8. Fondazione Europea di Ricerca Biomedica (FERB Onlus), via Ambrogio Uboldo 21, 20063, Cernusco sul Naviglio, Milan, Italy; Department of Neurology, University Hospital and Julius-Maximilian-University, Josef-Schneider-Str. 11, 97080, Würzburg, Germany; Parkinson Institute ASST G. Pini-CTO, via Bignami 1, 20126, Milan, Italy. Electronic address: Isaias_I@ukw.de.
Abstract
BACKGROUND: Cortical dysfunctioning significantly contributes to the pathogenesis of motor symptoms in Parkinson's disease (PD). OBJECTIVE: We aimed at testing whether an acute levodopa administration has measurable and specific cortical effects possibly related to striatal dopaminergic deficit. METHODS: In thirteen PD patients, we measured the electroencephalographic responses to transcranial magnetic stimulation (TMS/EEG) of the supplementary motor area and superior parietal lobule (n = 8) before and after an acute intake of levodopa. We also performed a single-photon emission computed tomography and [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane to identify the more affected and the less affected brain side in each patient, according to the dopaminergic innervation loss of the putamen. Cortical excitability changes before and after an acute intake of levodopa were computed and compared between the more and the less affected brain side at the single-patient as well as at the group level. RESULTS: We found that levodopa intake induces a significant increase (P < 0.01) of cortical excitability nearby the supplementary motor area in the more affected brain side, greater (P < 0.025) than in the less affected brain side. Notably, cortical excitability changes nearby the superior parietal lobule were not statistically significant. CONCLUSIONS: These results strengthen the idea that dysfunction of specific cortico-subcortical circuits may contribute to pathophysiology of PD symptoms. Most important, they support the use of navigated TMS/EEG as a non-invasive tool to better understand the pathophysiology of PD.
BACKGROUND: Cortical dysfunctioning significantly contributes to the pathogenesis of motor symptoms in Parkinson's disease (PD). OBJECTIVE: We aimed at testing whether an acute levodopa administration has measurable and specific cortical effects possibly related to striatal dopaminergic deficit. METHODS: In thirteen PDpatients, we measured the electroencephalographic responses to transcranial magnetic stimulation (TMS/EEG) of the supplementary motor area and superior parietal lobule (n = 8) before and after an acute intake of levodopa. We also performed a single-photon emission computed tomography and [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane to identify the more affected and the less affected brain side in each patient, according to the dopaminergic innervation loss of the putamen. Cortical excitability changes before and after an acute intake of levodopa were computed and compared between the more and the less affected brain side at the single-patient as well as at the group level. RESULTS: We found that levodopa intake induces a significant increase (P < 0.01) of cortical excitability nearby the supplementary motor area in the more affected brain side, greater (P < 0.025) than in the less affected brain side. Notably, cortical excitability changes nearby the superior parietal lobule were not statistically significant. CONCLUSIONS: These results strengthen the idea that dysfunction of specific cortico-subcortical circuits may contribute to pathophysiology of PD symptoms. Most important, they support the use of navigated TMS/EEG as a non-invasive tool to better understand the pathophysiology of PD.
Authors: Ida Granö; Tuomas P Mutanen; Aino Tervo; Jaakko O Nieminen; Victor H Souza; Matteo Fecchio; Mario Rosanova; Pantelis Lioumis; Risto J Ilmoniemi Journal: Open Res Eur Date: 2022-07-11