Dopamine boosts intention and action awareness in Parkinson\u2019s disease

Steven Di Costa,Christos Ganos,Carsten Buhmann,Tina Mainka,Patrick Haggard,Ute Hidding,Ewgenia Barow,Christian K E Moll,Monika Pötter-Nerger

doi:10.1007/s00221-020-05847-2

Abstract

Dopaminergic deficiency in Parkinson’s disease (PD) has been associated with underactivation of the supplementary motor area and a reduction of voluntary actions. In these patients, awareness of intention to act has been shown to be delayed. However, delayed awareness of intention to act has also been shown in patients with hyperdopaminergic states and an excess of unwilled movements, as in Tourette’s, and in patients with functional movement disorders. Hence, the role of dopamine in the awareness of intention and action remains unclear. 36 PD patients were tested ON and OFF dopaminergic medication and compared with 35 healthy age-matched controls. In addition, 17 PD patients with subthalamic deep brain stimulation (DBS) were tested ON medication and ON and OFF stimulation. Participants judged either the moment a self-generated action was performed, or the moment the urge to perform the action was felt, using the “Libet method”. Temporal judgments of intention and action awareness were comparable between unmedicated PD patients and controls. Dopaminergic medication boosted anticipatory awareness of both intentions and actions in PD patients, relative to an unmedicated condition. The difference between ON/OFF DBS was not statistically reliable. Functional improvement of motor ability in PD through dopaminergic supplementation leads to earlier awareness of both intention, and of voluntary action.

Highlights

The initiation of voluntary actions relies on a well-organized network of neural structures that evaluate the salience of a selected motor program and allow its timely execution (Haggard 2008)
Change from OFF/ON due to dopaminergic supplementation or deep brain stimulation (DBS) was associated with a significant improvement of motor function as captured by the UPDRSIII as confirmed by individual repeated-measures t tests (medication group: t(35) = 14.55, p < 0.00001; DBS group: t(16) = 7.3, p < 0.00001)
There was a significant positive correlation of movement onset estimates across researchers (r = 0.75, p < 0.01). Analysis of these estimates showed that the moment of action onset prior to button presses did not differ significantly in Parkinson’s disease (PD) patients between ON and OFF medication states (t(62) = 0.015, p = 0.98, BF01 = 3.91)

Summary

Introduction

The initiation of voluntary actions relies on a well-organized network of neural structures that evaluate the salience of a selected motor program and allow its timely execution (Haggard 2008). Different pathologies can disrupt this process and thereby lead to motor deficits related to inappropriate execution timing. Lesions of the dorsolateral prefrontal cortex have been associated with the inability to inhibit (pre-potent) actions (Aron et al 2004), whereas acute structural damage of the supplementary motor area (SMA) will typically lead to a disruption or even complete loss of the capacity to generate voluntary motor output (Brugger et al 2015). A defining feature of Parkinson’s disease (PD), results from reduced dopaminergic availability in the nigrostriatal pathway, characteristic of the neurodegenerative process in PD (Berardelli et al 2001).

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