Asha Kishore1, Thomas Joseph, Balu Velayudhan, Traian Popa, Sabine Meunier. 1. Comprehensive Care Centre for Movement Disorders, Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Kerala 695 011, India. ashakishore99@gmail.com
Abstract
OBJECTIVE: To test the plasticity of bilateral motor cortices (M1) in treatment-naïve (de novo) Parkinson's disease (PD) patients and its response to single dose of L-DOPA. METHODS:Twenty-one de novo PD patients with only unilateral motor symptoms were recruited to eliminate the effects of advanced disease and chronic treatment and were tested with intermittent (n=10) and continuous theta burst stimulation (iTBS and cTBS) (n=11) protocols to induce LTP and LTD-like plasticity on both M1 cortices. They were compared with two groups of 10 each, age-matched, healthy volunteers (HV). Severity of motor signs and effectiveness of TBS were measured bilaterally in the untreated state and after a uniform dose of L-DOPA in all patients. RESULTS: iTBS and cTBS induced significant LTP and LTD- like plasticity in M1 of HV. In de novo patients, there was no plasticity in both M1. Acute L-DOPA challenge did not improve plasticity in either M1 cortices, though motor signs of PD improved. There was no correlation of motor signs with M1 plasticity. CONCLUSION: The early, severe and bilateral loss of plasticity in M1 in de novo PD patients is a primary disease-related cortical dysfunction. The contrasting L-DOPA response of motor signs and M1 plasticity could arise from differences in neural circuits mediating them or differing effects of acute dopamine replacement on circuits recruited by specific plasticity-induction techniques, particularly in treatment naïve PD. SIGNIFICANCE: M1 plasticity defect occurs early in PD and might affect motor learning. Acute vs. chronic dopamine replacement could have different effects on plasticity in PD or in the networks recruited by a specific plasticity induction technique.
RCT Entities:
OBJECTIVE: To test the plasticity of bilateral motor cortices (M1) in treatment-naïve (de novo) Parkinson's disease (PD) patients and its response to single dose of L-DOPA. METHODS: Twenty-one de novo PDpatients with only unilateral motor symptoms were recruited to eliminate the effects of advanced disease and chronic treatment and were tested with intermittent (n=10) and continuous theta burst stimulation (iTBS and cTBS) (n=11) protocols to induce LTP and LTD-like plasticity on both M1 cortices. They were compared with two groups of 10 each, age-matched, healthy volunteers (HV). Severity of motor signs and effectiveness of TBS were measured bilaterally in the untreated state and after a uniform dose of L-DOPA in all patients. RESULTS:iTBS and cTBS induced significant LTP and LTD- like plasticity in M1 of HV. In de novo patients, there was no plasticity in both M1. Acute L-DOPA challenge did not improve plasticity in either M1 cortices, though motor signs of PD improved. There was no correlation of motor signs with M1 plasticity. CONCLUSION: The early, severe and bilateral loss of plasticity in M1 in de novo PDpatients is a primary disease-related cortical dysfunction. The contrasting L-DOPA response of motor signs and M1 plasticity could arise from differences in neural circuits mediating them or differing effects of acute dopamine replacement on circuits recruited by specific plasticity-induction techniques, particularly in treatment naïve PD. SIGNIFICANCE: M1 plasticity defect occurs early in PD and might affect motor learning. Acute vs. chronic dopamine replacement could have different effects on plasticity in PD or in the networks recruited by a specific plasticity induction technique.
Authors: Paolo Calabresi; Veronica Ghiglieri; Petra Mazzocchetti; Ilenia Corbelli; Barbara Picconi Journal: Philos Trans R Soc Lond B Biol Sci Date: 2015-07-05 Impact factor: 6.237
Authors: Lucio Marinelli; Angelo Quartarone; Mark Hallett; Giuseppe Frazzitta; Maria Felice Ghilardi Journal: Clin Neurophysiol Date: 2017-04-09 Impact factor: 3.708