P 76. Cerebellar sensory processing alterations impact motor cortical plasticity in Parkinson’s disease: Clues from dyskinetic patients

Abstract

Introduction The plasticity of primary motor cortex (M1) in patients with Parkinson's disease (PD) and levodopa-induced dyskinesias (LIDs) is severely impaired (Morgante, 2006; Kishore, 2012). We reported that inhibitory cerebellar stimulation with continuous theta burst stimulation (cTBS) enhanced the sensori-motor plasticity of M1 induced by paired associative stimulation (PAS) in healthy subjects (Popa, 2012). Koch (2009) demonstrated a beneficial effect on LIDs of repeated sessions of cTBS to the cerebellum. Objectives To find out (1) if cerebellar inhibitory stimulation is able to enhance the deficient plasticity of M1 associated with LIDs in PD and (2) whether this could be the mechanism underlying the reduction of LIDs after repeated sessions of cerebellar stimulation reported earlier. Materials and methods Study 1: 16 PD patients with LIDs made 3 visits: (1) patients were OFF drug and received PAS to M1 opposite to the side with the worst dyskinesias; (2) in ON patients received cTBS to the cerebellum followed by PAS to the opposite M1; (3) in ON patients received sham stimulation to the cerebellum and PAS to M1. Responsiveness of M1 to PAS was tested before and after stimulations. Study 2: 20 PD patients with LIDs received 10days of bilateral cTBS stimulation of the cerebellum. Dyskinesias were scored blindly on videos before stimulations started and at 2nd ( n =20), 4th ( n =10) and 8th week ( n =10) after the end of the stimulations. Responsiveness of M1 to PAS was tested at each visit. Results Study 1. PAS-induced response of PD patients OFF and ON was weak (rANOVA P =0.5, 0.7 respectively). After real and not sham, cerebellar stimulation M1 gained responsiveness to PAS ( P Study 2. Repeated real and not sham cerebellar stimulation, led to a decrease of the total ( P P Correlation. The larger the additional plasticity generated by a single session of cTBS to the cerebellum, the greater was the decrease in the worst dyskinesia score after 10days of bilateral cerebellar stimulation ( P Conclusion The abnormal signaling within the striato-thalamo-cortical circuit, possibly due to non physiological, excessive release of striatal synaptic dopamine in dyskinetic patients, could impinge on the cerebello-thalamo-cortical circuit. Alterations in the cerebellar sensory processing function in advanced PD could lead to an inappropriate filtering of the relevant sensory volley that is responsible for a maladaptive state of cortical plasticity. Such a maladaptive state could predispose to the selection of abnormal motor programs generating abnormal movements. Cerebellar inhibition, by increasing the gain of the sensory afferent volley to M1, permits better sensori-motor integration, thereby reducing involuntary movements.