Bilateral deep brain stimulation of the subthalamic nucleus increases pointing error during memory-guided sequential reaching

Abstract

Deep brain stimulation of the subthalamic nucleus (STN DBS) significantly improves clinical motor symptoms, as well as intensive aspects of movement like velocity and amplitude in patients with Parkinson's disease (PD). However, the effects of bilateral STN DBS on integrative and coordinative aspects of motor control are equivocal. The aim of this study was to investigate the effects of bilateral STN DBS on integrative and coordinative aspects of movement using a memory-guided sequential reaching task. The primary outcomes were eye and finger velocity and end-point error. We expected that bilateral STN DBS would increase reaching velocity. More importantly, we hypothesized that bilateral STN DBS would increase eye and finger end-point error and this would not simply be the result of a speed accuracy trade-off. Ten patients with PD and bilaterally implanted subthalamic stimulators performed a memory-guided sequential reaching task under four stimulator conditions (DBS-OFF, DBS-LEFT, DBS-RIGHT, and DBS-BILATERAL) over 4 days. DBS-BILATERAL significantly increased eye velocity compared to DBS-OFF, DBS-LEFT, and DBS-RIGHT. It also increased finger velocity compared to DBS-OFF and DBS-RIGHT. DBS-BILATERAL did not change eye end-point error. The novel finding was that DBS-BILATERAL increased finger end-point error compared to DBS-OFF, DBS-LEFT, and DBS-RIGHT even after adjusting for differences in velocity. We conclude that bilateral STN DBS may facilitate basal ganglia-cortical networks that underlie intensive aspects of movement like velocity, but it may disrupt selective basal ganglia-cortical networks that underlie certain integrative and coordinative aspects of movement such as spatial accuracy.

Bilateral subthalamic nucleus deep brain stimulation increases fixational saccades during movement preparation: evidence for impaired preparatory set

“…In the current study, we showed that there was an increased number of fixational saccades during the antisaccade task during bilateral, but not unilateral, STN DBS and that this increase was related to increased prosaccade errors suggesting that bilateral STN DBS interferes with preparatory set during the antisaccade task. These findings add to a line of previous work indicating a deleterious effect of bilateral STN DBS on tasks requiring greater levels of voluntary control, such as those required for dual-tasking and reaching memorized sequential targets (Alberts et al 2008;David et al 2018).…”

“…The current study adds to a line of previous work showing a differential effect of bilateral and unilateral STN DBS on voluntary motor control (Alberts et al 2008;David et al 2018;Goelz et al 2017). We have previously reported that bilateral STN DBS, but not unilateral STN DBS, increases prosaccade error rate on the antisaccade task, a task with high volitional control demands requiring the coordination of facilitatory and inhibitory saccade processes (Goelz et al 2017).…”

“…Bilateral STN DBS is effective at improving measures of motor function such as movement speed and amplitude (Stegemoller et al 2013;Vaillancourt et al 2004), but it is detrimental to certain voluntary tasks that rely heavily on prefrontal networks (Alberts et al 2008;David et al 2018). We propose that high-frequency STN DBS may improve neural activity of basal ganglia-primary motor pathways (Anidi et al 2018;Grill et al 2004;Vitek 2002) while simultaneously interfering with prefrontal cortical pathways associated with higher-order activity underlying complex voluntary movement (Alberts et al 2008;David et al 2018;Goelz et al 2017). It should be noted that the neural circuitry for preparatory set remains unclear.…”

Lateralized effects of deep brain stimulation in Parkinson’s disease: evidence and controversies

“…David et al used a memory-guided sequential reaching task to examine the role of STN DBS in the intensive as well as integrative and coordinative aspects of motor control in 10 right-handed PD patients treated with bilateral STN DBS in the off-medication condition. They reported that unilateral right-sided STN stimulation significantly increased finger latency and reduced finger velocity (i.e., the intensive aspect) when compared to left-sided stimulation, but the endpoint error (i.e., the integrative and coordinative aspects) was similar between the two stimulation conditions 30 . One study that investigated cognitivemotor functions in prosaccade and antisaccade tasks in 10 righthanded PD patients with bilateral STN DBS in the off-medication state also found no difference in the spatiotemporal or the cognitive aspects of oculomotor control between unilateral leftand right-sided STN stimulations 31 .…”

“…Consequently, differences in baseline characteristics between the two groups may limit the interpretation of the results. Other studies [14][15][16][17][18][19]25,26,[29][30][31][33][34][35][36][37]42 recruited PD patients with simultaneous or staged bilateral DBS and collected the outcome data under unilateral on-stimulation conditions in a randomized or counterbalanced manner. Among these, some studies applied randomized stimulation in consecutive days to ensure a sufficient 'washout' interval.…”