Dopaminergic Therapy Increases Go Timeouts in the Go/No-Go Task in Patients with Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is characterized by resting tremor, rigidity and bradykinesia. Dopaminergic medications such as L-dopa treat these motor symptoms, but can have complex effects on cognition. Impulse control is an essential cognitive function. Impulsivity is multifaceted in nature. Motor impulsivity involves the inability to withhold pre-potent, automatic, erroneous responses. In contrast, cognitive impulsivity refers to improper risk-reward assessment guiding behavior. Informed by our previous research, we anticipated that dopaminergic therapy would decrease motor impulsivity though it is well known to enhance cognitive impulsivity. We employed the Go/No-go paradigm to assess motor impulsivity in PD. Patients with PD were tested using a Go/No-go task on and off their normal dopaminergic medication. Participants completed cognitive, mood, and physiological measures. PD patients on medication had a significantly higher proportion of Go trial Timeouts (i.e., trials in which Go responses were not completed prior to a deadline of 750 ms) compared to off medication (p = 0.01). No significant ON-OFF differences were found for Go trial or No-go trial response times (RTs), or for number of No-go errors. We interpret that dopaminergic therapy induces a more conservative response set, reflected in Go trial Timeouts in PD patients. In this way, dopaminergic therapy decreased motor impulsivity in PD patients. This is in contrast to the widely recognized effects of dopaminergic therapy on cognitive impulsivity leading in some patients to impulse control disorders. Understanding the nuanced effects of dopaminergic treatment in PD on cognitive functions such as impulse control will clarify therapeutic decisions.

Components determining the slowness of information processing in parkinson’s disease

“…Although previous studies sing Go no‐Go task paradigm have demonstrated that patients with PD are slower and make more errors than controls (Buccino et al, 2018; Yang et al, 2018), in our study all RT tasks were performed very efficiently. Differences between groups in accuracy where not significant except for the CRT‐S task, this finding cannot be interpreted accurately as the total dopamine dosing is not standard in all the included PD subjects.…”

“…Simple Reaction Time‐Sustained Attention to Response Task (SRT‐SART): This task allowed to measure response strategy‐inhibition. Similar tasks have been used previously in PD (Yang et al, 2018). Following the model of Robertson et al (Robertson et al, 1997), participants had to press the left mouse button when the stimulus (digits 1–9) appeared in the center of the screen and inhibited the response when it appeared as the number "3."…”

Dopamine effects on frontal cortical blood flow and motor inhibition in Parkinson's disease

“…This study describes the pharmacological effect of dopamine agonist (DAA) therapy on frontal cerebral blood flow (CBF) in patients with PD, and the relationship between frontal cortical regional CBF (rCBF) and individual differences in inhibitory action control. DAA therapy improves motor symptoms in PD, and can alter the proficiency of inhibiting action impulses (Wylie et al, 2012;Claassen et al, 2015;Yang et al, 2016Yang et al, , 2018. Using noninvasive arterial spin labeling (ASL) MRI (Claassen et al, 2017), we examined a cohort of PD patients in the off-and on-DAA medication states to assess the effect of DAA on rCBF in frontal regions involved in motor inhibition, and the relationship between rCBF and action control performance as measured by a well-established cognitive test, the Simon task (Simon, 1969).…”

The Effect of Aging, Parkinson’s Disease, and Exogenous Dopamine on the Neural Response Associated with Auditory Regularity Processing

“…In fact, functions such as memory encoding , association learning , reward processing (Cools, 2006;Macdonald and Monchi, 2011;Vo et al, 2014) are intact at baseline in PD relative to healthy older controls. These cognitive functions are actually worsened by dopaminergic therapy in PD (Cools, 2006;Gotham et al, 1984;Hiebert et al, 2019;Kish et al, 1988;Swainson et al, 2000;Yang et al, 2018), as well as in healthy elderly and young controls (Fungwe et al, 1992;Olefins et al, 1986;Vo et al, 2016).The dopamine overdose hypothesis is a prevaling explanation for this effect of dopaminergic therapy in PD. In contrast to the degeneration of the SNc, dopamine-producing neurons in the ventral tegmental area (VTA) are relatively spared in PD (Kish et al, 1988).…”