Unilateral and Bilateral Subthalamic Deep Brain Stimulation Differently Favour Apathy in Parkinson's Disease

The link between subthalamic nucleus deep brain stimulation (STN-DBS) and apathy in patients with Parkinson's disease (PD) remains a controversial topic. The literature is mixed and the most supported explanation is the reduction of dopaminergic treatment. Yet a body of clinical and experimental evidences suggest that STN-DBS itself can also promote apathy in certain patients. However, the parameters accounting for apathy heterogeneity in stimulated patients along with the mechanisms underlying apathy induced by STN-DBS remain to be investigated. Whether bilateral and unilateral STN-DBS have the same influence on apathy is for instance unknown. We previously and separately showed in patients and rodents that bilateral STN-DBS can promote apathy per se. Here, we compare the effect of bilateral versus unilateral STN-DBS both in patients and in rodents. We conducted a clinical follow-up of patients with Parkinson's disease undergoing unilateral or bilateral STN-DBS and assessing apathy 3 months before and after STN-DBS. In parallel, we applied chronic and uninterrupted unilateral or bilateral DBS in rodents and extract longitudinal motivational changes with a battery of behavioural tests. While bilateral STN-DBS promotes apathy in patients and induces a loss of motivation in rodents, we found that unilateral STN-DBS did not exert such an effect both in patients and in rats. These data show that bilateral but not unilateral STN-DBS promotes apathy. This not only substantiate the induction of neuropsychiatric effects by STN-DBS but also suggest that this might be circumvented if STN-DBS is applied unilaterally instead of bilaterally.