Unilateral and Bilateral Subthalamic stimulation differently promote apathy: a translational approach

Abstract

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.

Deep Brain Stimulation of the Subthalamic Nucleus Modulates Reward-Related Behavior: A Systematic Review

“…In FR or PR operant tasks, STN-DBS consistently decreased intravenous self-administration of addictive drugs (Rouaud et al, 2010;Wade et al, 2017). And while the effects of STN-DBS on motivation for natural rewards is more heterogeneous, the predominant effect of STN-DBS is also a decrease in rewards earned and consumed (Rummel et al, 2016) (Vachez et al, 2020b), but see (Rouaud et al, 2010;Vachez et al, 2020a). A decrease in reward seeking was also evident in extinction tasks, i.e., where STN-DBS operant responses were decreased in the absence of a previously available food pellet (Klavir et al, 2009).…”

“…Another important factor to consider when interpreting the effects of STN-DBS on reward seeking is whether the stimulation is applied unilaterally (to a single hemisphere) or bilaterally. One set of studies performed under matched conditions from the same group reported that chronic unilateral STN-DBS during a FR1 task (Vachez et al, 2020a) did not recapitulate the sustained reward seeking deficit that occurred with chronic, bilateral stimulation (Vachez et al, 2020b). With the unilateral STN-DBS, the effect was only transient and lasted no more than 5 days.…”

“…With the unilateral STN-DBS, the effect was only transient and lasted no more than 5 days. Overall, the few studies using unilateral STN-DBS do not report robust reward seeking deficits, or report deficits that are only transient (Darbaky et al, 2003;Anderson et al, 2020;Vachez et al, 2020a). In the clinic, bilateral STN-DBS is generally associated with superior reduction in motor symptoms relative to unilateral stimulation (Bastian et al, 2003;Lizarraga et al, 2016), but may also induce more non-motor side-effects (Lee et al, 2011;Sjoberg et al, 2012).…”

“…In the clinic, bilateral STN-DBS is generally associated with superior reduction in motor symptoms relative to unilateral stimulation (Bastian et al, 2003;Lizarraga et al, 2016), but may also induce more non-motor side-effects (Lee et al, 2011;Sjoberg et al, 2012). Notably, a study within the same clinical center observed apathy following bilateral (Le Jeune et al, 2009) but not unilateral STN-DBS (Vachez et al, 2020a). These observations suggest that preserving function of one STN by applying DBS unilaterally protects against a reward seeking deficits in patients or in animal models.…”