Stimulation of subthalamic nuclei restores a near normal planning strategy in Parkinson's patients

Abstract

A fundamental function of the motor system is to gather key information from the environment in order to implement behavioral strategies appropriate to the context. Although several lines of evidence indicate that Parkinson's disease affects the ability to modify behavior according to task requirements, it is currently unknown whether deep brain stimulation (DBS) of the subthalamic nucleus (STN) affects context-related planning. To explore this issue, we asked 12 Parkinson's patients with bilateral STN DBS and 13 healthy subjects to execute similar arm reaching movements in two different paradigms: go-only and countermanding tasks. In the former task patients had to perform speeded reaching movements to a peripheral target. In contrast, in the countermanding task participants had to perform the same reaches unless an infrequent and unpredictable stop-signal was shown during the reaction time (RT) indicating that they should withhold the ongoing action. We compared the performance of Parkinson's patients in different DBS conditions. We found that patients with both DBS-ON behaved similarly to healthy subjects, in that RTs of no-stop trial increased while movement times (MTs) decreased with respect to those of go-only-trials. However, when both DBS were off, both RTs and MTs were longer in no-stop trials than in go-only trials. These findings indicate that bilateral DBS of STN can partially restore the appropriate motor strategy according to the given cognitive contexts.

Figure 1. Temporal sequence of the visual displays for no-stop and stop trials in the countermanding reaching task.

Temporal sequence of the visual displays for each task. All trials began with the appearance of a central stimulus. The subject had to reach and hold it with the index of the right (dominant) hand for a variable period of 500–800 ms. In the go-only task and in the no-stop trials of the countermanding task, the central stimulus disappeared and, simultaneously, a target appeared to the right, acting as a go-signal. Subjects were instructed to perform a speeded reaching movement toward the peripheral target. Randomly, in the 33% of trials of the countermanding task (stop trials), the central stimulus (stop signal) reappeared at variable delays after the go signal (SSDs), indicating that the subject should cancel the pending movement. If subjects executed the reaching movement the trial was scored as a stop-failure trial (not shown). The dotted circle (which was not visible to the subjects) indicates the size of the tolerance window for the touches (3.5 cm diameter).

Figure 2. Reaction times (RTs) and movement times (MTs) for reaching movements in Parkinson’s patients with right- and left-side body onset of the disease.

A. Cumulative distributions of RTs and MTs. These distributions were obtained by considering separately, according to laterality of onset of motor symptoms, the single RTs and MTs of no-stop and of go-only trials of subjects with right-body onset(n = 7; upper row) with left-body onset of the disease (n = 5; lower row). Bold lines represent RTs, dotted lines represent MTs. For each condition the p-value of Kolmogorov–Smirnov test is given, both for RTs and for MTs. B. Histograms of average RTs (upper row) and of MTs (lower row) of no-stop and go-only trials in each DBS condition. Bars represent the standard error of the mean.

Figure 3. Reaction times (RTs) and movement times (MTs) for reaching movements across the populations of Parkinson’s patients and control subjects.

A. Cumulative distribution of RTs (solid lines) and MTs (dotted lines) of healthy subjects (n = 13) for go-only (grey) and no-stop trials (black). B. Cumulative distributions of RTs (solid lines) and MTs (dotted lines) of DBS patients (n = 12) in DBS-ON and DBF-OFF conditions for both go-only (grey lines) and no-stop (black lines) trials. For each condition the p-value of Kolmogorov-Smirnov test is given, both for RTs and for MTs. C. Histograms of average RTs of no-stop and go-only trials in DBS-ON and DBF-OFF conditions. Bars represent the standard error of the mean. D. Histograms of average MTs of no-stop and go-only trials in each DBS-ON and DBF-OFF conditions. Bars represent the standard error of the mean.

Figure 4. Magnitude and modulation of the context effect.

(see Results for more details) A. Percentage of PD patients (in each DBS state) and healthy subjects showing simultaneously a significant increase in reaction times (RTs) and a significant decrease in movements times (MTs) in no-stop trials with respect to go-only-trials (black bars), and a significant lengthening of both RTs and MTs in no-stop-trials with respect to go-only trials (gray bars). B. Percentage change (±SEM) for both RTs (black bars) and MTs (grey bars) of no-stop-trials with respect to go-only trials in PD patients (in each DBS state) and control subjects.