Consiglio Nazionale delle Ricerche

Tipo di prodottoArticolo in rivista
TitoloA network centred on the inferior frontal cortex is critically involved in levodopa-induced dyskinesias
Anno di pubblicazione2015
FormatoElettronico
Autore/iAntonio Cerasa,1,* Giacomo Koch,2,3,* Giulia Donzuso,1 Graziella Mangone,1 Maurizio Morelli,4 Livia Brusa,5 Mario Stampanoni Bassi,2,3 Viviana Ponzo,2 Silvia Picazio,2 Luca Passamonti,1 Maria Salsone,1 Antonio Augimeri,1 Carlo Caltagirone2 and Aldo Quattrone1,4
Affiliazioni autori1 Consiglio Nazionale delle Ricerche, IBFM, 88100, Catanzaro, Italy 2 Non-Invasive Brain Stimulation Unit, Neurologia Clinica e Comportamentale, Fondazione Santa Lucia IRCCS, Rome, Italy 3 Stroke Unit, Policlinico Tor Vergata, Rome, Italy 4 Universita` degli studi 'Magna Graecia', Clinica Neurologica, 88100, Catanzaro, Italy 5 UOC Neurologia, Ospedale Sant'Eugenio, Rome, Italy
Autori CNR e affiliazioni
  • LUCA PASSAMONTI
  • ANTONIO CERASA
  • MARIA SALSONE
Lingua/e
  • inglese
AbstractLevodopa-induced dyskinesias are disabling motor complications of long-term dopamine replacement in patients with Parkinson's disease. In recent years, several alternative models have been proposed to explain the pathophysiological mechanisms underlying this hyperkinetic motor disorder. In particular, our group has shed new light on the role of the prefrontal cortex as a key site of interest, demonstrating that, among other areas, the inferior frontal cortex is particularly characterized by altered patterns of anatomical and functional changes. However, how neural activity varies depending on levodopa treatment in patients with dyskinesias and whether the reported prefrontal abnormalities may have a critical role in dyskinesias is debated. To answer these questions we performed independent functional magnetic resonance imaging and repetitive transcranial magnetic stimulation studies. In the first experiment we applied resting state functional magnetic resonance imaging on 12 patients with Parkinson's disease with levodopa-induced dyskinesias and 12 clinically matched patients without dyskinesias, before and after administration of levodopa. Functional connectivity of brain networks in the resting state was assessed in both groups. We chose the right inferior frontal cortex as the seed region given the evidence highlighting the role of this region in motor control. In a second experiment, we applied different forms of repetitive transcranial magnetic stimulation over the right inferior frontal cortex in a new group of dyskinetic patients who were taking a supramaximal dose of levodopa, to verify the clinical relevance of this area in controlling the development of hyperkinetic movements. The resting state functional imaging analysis revealed that in patients with levodopa-induced dyskinesias connectivity of the right inferior frontal cortex was decreased with the left motor cortex and increased with the right putamen when compared to patients without levodopa-induced dyskinesias. This abnormal pattern of connectivity was evident only during the ON phase of levodopa treatment and the degree of such alteration correlated with motor disability. The repetitive TMS experiments showed that a session of continuous but not intermittent or sham theta burst stimulation applied over the inferior frontal cortex was able to reduce the amount of dyskinesias induced by a supramaximal single dose of levodopa, suggesting that this area may play a key role in controlling the development of dyskinesias. Our combined resting state functional magnetic resonance and transcranial magnetic stimulation studies demonstrate that pathophysiological mechanisms underlying levodopa-induced dyskinesias may extend beyond the 'classical' basal ganglia dysfunctions model, including the modulation performed by the neural network centred on the inferior frontal cortex.
Lingua abstractinglese
Altro abstract-
Lingua altro abstract-
Pagine da414
Pagine a427
Pagine totali-
RivistaBrain (Online)
Attiva dal 1999
Editore: Oxford University Press - Oxford
Paese di pubblicazione: Regno Unito
Lingua: inglese
ISSN: 1460-2156
Titolo chiave: Brain (Online)
Titolo proprio: Brain (Online)
Titolo abbreviato: Brain (Online)
Numero volume della rivista138
Fascicolo della rivistaPt-2
DOI10.1093/brain/awu329
Verificato da referee-
Stato della pubblicazione-
Indicizzazione (in banche dati controllate)
  • PubMed (Codice:25414038)
Parole chiaveParkinson's disease, levodopa-induced dyskinesias, resting state functional MRI, TMS, inferior frontal cortex
Link (URL, URI)-
Titolo parallelo-
Licenza-
Scadenza embargo-
Data di accettazione-
Note/Altre informazioni*These authors contributed equally to this work. Pubblicato on-line: 19 Novembre 2014
Strutture CNR
  • IBFM — Istituto di bioimmagini e fisiologia molecolare
Moduli/Attività/Sottoprogetti CNR
  • ME.P02.028.001 : Neuroimaging clinico dei disordini neurodegenerativi del movimento
Progetti Europei-
Allegati