Dysfunctional inhibitory control in Parkinson’s disease patients with levodopa-induced dyskinesias

Abstract

Introduction

Chronic dopamine replacement therapies in Parkinson’s disease can induce side effects, such as levodopa-induced dyskinesias and impulse control disorders. A dysfunction of inhibitory brain networks has been related to both disorders; however, there is no clear behavioral evidence supporting this hypothesis. We aimed to determine whether PD patients with levodopa-induced dyskinesias show features of increased impulsivity in parallel with altered motor inhibition.

Methods

Two matched samples of Parkinson’s disease patients with (n = 14) or without (n = 14) levodopa-induced dyskinesias and a control group (n = 10) participated in the study. All groups were evaluated by the Barratt Impulsiveness Scale-11 to assess impulsivity traits. Furthermore, participants performed a stop signal task to evaluate reactive-motor inhibition and a Go/NoGo task to evaluate proactive-inhibitory control. PD patients were tested both in OFF and ON levodopa medication.

Results

Parkinson’s disease patients with levodopa-induced dyskinesias showed higher impulsivity scores than PD patients without levodopa-induced dyskinesias. Dyskinetic patients presented also delayed stop signal reaction times indicating a worse performance in reactive inhibition. The slowness in inhibiting a motor command correlated with the impulsiveness scores. Furthermore, in the dyskinetic group, a positive correlation was found between stop reaction times and the severity of involuntary movements. Under the effect of levodopa, all patients were faster but dyskinetic patients were significantly less accurate in proactive inhibition.

Conclusion

Inhibitory control is compromised in dyskinetic patients in parallel with increased impulsivity, revealing an impairment of motor and behavioral inhibitory control in Parkinson’s disease patients with levodopa-induced dyskinesias.

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Acknowledgements

Sincere thanks to Gianluigi Rubino, Marilena Minei and to Prof. Fabio Ferlazzo for their essential contribution in reviewing the manuscript.

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Correspondence to Giacomo Koch.

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On behalf of all authors, the corresponding author states that there is no conflict of interest.

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The Local Ethics Committee of the IRCCS “Santa Lucia” Foundation according to the Helsinki Declaration approved the study.

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Written consent was obtained from all participants.

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Picazio, S., Ponzo, V., Caltagirone, C. et al. Dysfunctional inhibitory control in Parkinson’s disease patients with levodopa-induced dyskinesias. J Neurol 265, 2088–2096 (2018). https://doi.org/10.1007/s00415-018-8945-1

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Keywords

  • Parkinson’s disease
  • Levodopa-induced dyskinesia
  • Motor inhibition
  • Impulsivity
  • Go/NoGo
  • Stop-signal task