Does Unilateral Basal Ganglia Activity Functionally Influence the Contralateral Side? What 1 We Can Learn from Stn Stimulation in Parkinson's Disease Patients. 2

36 In humans, the control of voluntary movement, in which the cortico-basal-ganglia circuitry 37 participates, is mainly lateralised. However, several studies suggest that both the contralateral 38 and ipsilateral basal ganglia (BG) systems are implicated during unilateral movement. 39 Bilateral improvement of motor signs in Parkinson’s disease patients (PD) has been reported 40 with unilateral lesion or high-frequency stimulation of the internal part of the globus pallidus 41 (GPi) or the subthalamic nucleus (STN-HFS). To decipher the mechanisms of production of 42 ipsilateral movements induced by the modulation of unilateral BG circuitry activity, we 43 recorded left STN neuronal activity during right STN-HFS in PD patients operated for 44 bilateral deep brain stimulation. Left STN single cells were recorded in the operating room 45 during right STN-HFS while patients experienced, or did not experience, right stimulation46 induced dyskinesias. Most of the left-side STN neurones (64%) associated with the presence 47 of right dyskinesias were inhibited, with a significant decrease in burst and intraburst 48 frequencies. In contrast, left STN neurons not associated with right dyskinesias were mainly 49 activated (48%), with a predominant increase 4-5 ms after the stimulation pulse, and a 50 decrease in oscillatory activity. This suggests that unilateral neuronal STN modulation is 51 associated with changes in the activity of the contralateral STN. The fact that one-side of the 52 BG system can influence the functioning of the other could explain the occurrence of bilateral 53 dyskinesias and motor improvement observed in PD patients during unilateral STN-HFS, as a 54 result of a bilateral disruption of the pathological activity in the cortico-subcortical circuitry. 55 56