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Lack of LTP-like plasticity in primary motor cortex in Parkinson's disease
Authors:Suppa A  Marsili L  Belvisi D  Conte A  Iezzi E  Modugno N  Fabbrini G  Berardelli A
Affiliation:aDepartment of Neurology and Psychiatry, Sapienza, University of Rome, Rome, Italy;bNeuromed Institute, Sapienza, University of Rome, Rome, Italy
Abstract:In this study in patients with Parkinson's disease (PD), off and on dopaminergic therapy, with and without L-dopa-induced dyskinesias (LIDs), we tested intermittent theta-burst stimulation (iTBS), a technique currently used for non-invasively inducing long-term potentiation (LTP)-like plasticity in primary motor cortex (M1). The study group comprised 20 PD patients on and off dopaminergic therapy (11 patients without and 9 patients with LIDs), and 14 age-matched healthy subjects. Patients had mild-to-moderate PD, and no additional neuropsychiatric disorders. We clinically evaluated patients using the Unified Parkinson's Disease Rating Scale (UPDRS) and the Unified Dyskinesia Rating Scale (UDysRS). The left M1 was conditioned with iTBS at 80% active motor threshold intensity. Twenty motor evoked potentials (MEPs) were recorded from right first interosseous muscle before and at 5, 15 and 30 min after iTBS. Between-group analysis of variance (ANOVA) testing healthy subjects versus patients with and without LIDs, on and off therapy showed a significant interaction between factors “Group” and “Time”. After iTBS, MEP amplitudes in healthy subjects increased significantly at 5, 15 and 30 min (p < 0.01 at all time-points) but in PD patients with and without LIDs, on and off therapy, remained unchanged. In PD patients with and without LIDs, on and off therapy iTBS fails to increase MEP responses. This finding suggests lack of iTBS-induced LTP-like plasticity in M1 in PD regardless of patients' clinical features.
Keywords:Abbreviations: ANOVA, analysis of variance   AMT, active motor threshold   cTBS, continuous theta burst stimulation   EMG, electromyography   FDI, first dorsal interosseus   H&  Y, Hoehn &   Yahr scale   iTBS, intermittent theta burst stimulation   LIDs, L-dopa-induced dyskinesias   LTP, long-term potentiation   LTD, long-term depression   M1, primary motor cortex   MEPs, motor-evoked potentials   MVC, maximum voluntary contraction   NMDA, N-methyl-  font-variant: small-caps"  >d-aspartate   PAS, paired associative stimulation   PD, Parkinson's disease   RMT, resting motor threshold   rTMS, repetitive transcranial magnetic stimulation   SNr, substantia nigra pars reticulata   STP, short-term plasticity   TBS, theta burst stimulation   TDCS, transcranial direct current stimulation   TMS, transcranial magnetic stimulation   UDysRS, Unified Dyskinesia Rating Scale   UPDRS, Unified Parkinson's Disease Rating Scale
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