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

Abstract

ObjectiveTo 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. MethodsTwenty-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. ResultsiTBS 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. ConclusionThe 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. SignificanceM1 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.