Apathy is frequently reported in Parkinson's disease (PD) patients under subthalamic nucleus deep brain stimulation (STN-DBS). The prevailing clinical view for apathy following STN-DBS is the reduction of dopaminergic medication. However, few clinical reports and recent experimental data suggested the pathogenicity of bilateral STN-DBS on motivation, challenging the leading opinion. Here, we investigate whether bilateralism of STN-DBS influences apathy outcome after STN-DBS, combining pre-clinical and clinical approaches. We assess the motivational effects of chronic unilateral STN-DBS in rats in the exact same conditions having highlighted a loss of motivation under bilateral STN-DBS. Clinical data are obtained by the follow-up of a cohort of parkinsonian patients undergoing unilateral STN-DBS and coming from the clinical center that described apathy related to bilateral STN-DBS itself.Despite an acute effect, which fades rapidly, unilateral STN-DBS did not induce a loss of motivation reminiscent to apathy in rats. In patients, apathy did not increase between the preoperative and the post-operative assessment. Together, those data demonstrate that bilateral but not unilateral STN-DBS can induce a loss of motivation in both rats and patients.This constitutes another evidence of the role of STN-DBS itself for apathy in PD.
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