Early, severe and bilateral loss of LTP and LTD-like plasticity in motor cortex (M1) in de novo Parkinson's disease

Objective: To test the plasticity of bilateral motor cortices (M1) in treatment-nave (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 nave 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. (C) 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.