Deep-brain stimulation of the subthalamic nucleus improves overriding motor actions in Parkinson’s disease

Wery P.M Van Den Wildenberg,Nelleke C Van Wouwe,K Richard Ridderinkhof,Joseph S Neimat,W Jeffrey Elias,Theodore R Bashore,Scott A Wylie

doi:10.1016/j.bbr.2021.113124

Abstract

Findings from previous research using the classic stop-signal task indicate that the subthalamic nucleus (STN) plays an important role in the ability to inhibit motor actions. Here we extend these findings using a stop-change task that requires voluntary action override to stop an ongoing motor response and change to an alternative response. Sixteen patients diagnosed with Parkinson’s disease (PD) and 16 healthy control participants (HC) performed the stop-change task. PD patients completed the task when deep-brain stimulation (DBS) of the STN was turned on and when it was turned off. Behavioral results indicated that going, stopping, and changing latencies were shortened significantly among PD patients during STN DBS, the former two reductions replicating findings from previous DBS studies using the classic stop-signal task. The shortened go latencies observed among PD patients fell within the control range. In contrast, stopping latencies among PD patients, although reduced significantly, continued to be significantly longer than those of the HC. Like go latencies, stop-change latencies were reduced sufficiently among PD patients for them to fall within the control range, a novel finding. In conclusion, STN DBS produced a general, but differential, improvement in the ability of PD patients to override motor actions. Going, stopping, and stop-change latencies were all shortened, but only going and stop-change latencies were normalized.

Highlights

The ability to flexibly alter one’s behavior to sudden changes in the environment is a hallmark of voluntary action control [1]
deep-brain stimulation (DBS) on versus DBS turned off (DBS off) Analyses of pegboard and finger tapping performance confirmed the expectation that subthalamic nucleus (STN) stimulation improved fine motor dexterity (time to complete pegboard test: DBS on = 30, DBS off = 37 s, t(15) = 2.08, p = 0.03, one-sided; number of finger taps: DBS on = 41, DBS off = 37, t(15) = 2.52, p = 0.01, one-sided)
We used the stop-change task to study the effects of DBS of the STN on the ability to override motor actions

Summary

Introduction

The ability to flexibly alter one’s behavior to sudden changes in the environment is a hallmark of voluntary action control [1]. A neural network that includes frontal brain areas and the basal ganglia is considered vital for the selection and inhibition of voluntary actions [2]; for a review, see [3]. This study replicates and extends previous work on the ability to stop and change voluntary motor actions in individuals diagnosed with Parkinson’s disease by altering basal ganglia-cortical interactions though electrical stimulation of the subthalamic nucleus (STN). We present a comprehen sive review of relevant literature, including studies on the impact of therapeutic interventions such as dopaminergic medication and deep-brain stimulation (DBS), on inhibition of voluntary motor actions and PD.

Methods

Results

Conclusion