Dissociable Effects of Dopamine on the Initial Capture and the Reactive Inhibition of Impulsive Actions in Parkinson's Disease

Abstract

Dopamine plays a key role in a range of action control processes. Here, we investigate how dopamine depletion caused by Parkinson disease (PD) and how dopamine restoring medication modulate the expression and suppression of unintended action impulses. Fifty-five PD patients and 56 healthy controls (HCs) performed an action control task (Simon task). PD patients completed the task twice, once withdrawn from dopamine medications and once while taking their medications. PD patients experienced similar susceptibility to making fast errors in conflict trials as HCs, but PD patients were less proficient compared with HCs at suppressing incorrect responses. Administration of dopaminergic medications had no effect on impulsive error rates but significantly improved the proficiency of inhibitory control in PD patients. We found no evidence that dopamine precursors and agonists affected action control in PD differently. Additionally, there was no clear evidence that individual differences in baseline action control (off dopamine medications) differentially responded to dopamine medications (i.e., no evidence for an inverted U-shaped performance curve). Together, these results indicate that dopamine depletion and restoration therapies directly modulate the reactive inhibitory control processes engaged to suppress interference from the spontaneously activated response impulses but exert no effect on an individual's susceptibility to act on impulses.

Focused stimulation of dorsal subthalamic nucleus improves reactive inhibitory control of action impulses

“…According to the DPAS model, this suggests that Parkinson’s disease patients withdrawn from dopamine medications and from DBS were less effective at inhibiting interference from action impulses compared to HCs, a finding that replicates several prior studies of Parkinson’s disease (van Wouwe et al, 2016; Wylie et al, 2012a, b). …”

Continuous force measurements reveal no inhibitory control deficits in Parkinson’s disease

“…make a response using a button-box) which limits the generalisability of any findings to more advanced Parkinson's cases. PwP across studies often exhibit a mix of confounding characteristics, some of which have been shown to affect response inhibition and response conflict in other studies, such as subthalamic nucleus deep brain stimulation and the presence of additional ICBs (Mirabella et al, 2012;Ray et al, 2009;Swann et al, 2011;van Wouwe et al, 2016;van den Wildenberg et al, 2006;Wylie, Ridderinkhof, Bashore et al, 2010;Wylie, Ridderinkhof, Elias et al, 2010;Wylie et al, 2012). Whilst there were no participants with deep brain stimulation in our present sample, much of the literature -including this study -do not specifically exclude or account for PwP who have additional ICBs, which may well be up to 50% of any sample (Corvol et al, 2018).…”

“…Although Parkinson's has been associated with disrupted inhibitory control and a high incidence of ICBs, empirical studies investigating the effects of Parkinson's on response conflict and inhibition have produced mixed findings. For example, some studies using the Simon task have found that PwP show greater interference between competing responses (the difference in RTs for incongruent versus congruent trials e.g., Houvenaghel et al, 2016;van Wouwe et al, 2016) compared to healthy controls (HCs), whereas others have found no significant group differences (Wylie, Ridderinkhof, Bashore et al, 2010;Wylie, Ridderinkhof, Elias et al, 2010). Moreover, whilst some studies have shown that PwP produce more commission errors on the Go/No-Go task compared to HCs (Geffe et al, 2016;Nombela et al, 2014), others have reported no group differences (de Rezende Costa et al, 2016;Georgiev, Dirnberger, Wilkinson, Limousin, & Jahanshahi, 2016).…”

“…This is visible by plotting accuracy (in conditional accuracy functions) or the RT interference effect (in delta plots) as a function of RT (see van den Wildenberg et al, 2010 for a review). Using these methods, studies have consistently revealed that PwP show deficits in successful inhibition of responses at the slow end of the RT distribution (van Wouwe et al, 2016;Wylie, Ridderinkhof, Bashore et al, 2010;Wylie, Ridderinkhof, Elias et al, 2010), but are no more susceptible to fast impulsive errors than HCs on the Simon task.…”

Continuous force measurements reveal no inhibitory control deficits in Parkinson’s disease

“…Although Parkinson's has been associated with disrupted inhibitory control and a high incidence of ICBs, empirical studies investigating the effects of Parkinson's on response conflict and inhibition have produced mixed findings. For example, some studies using the Simon task have found that PwP show greater interference between competing responses (the difference in RTs for incongruent versus congruent trials e.g., Houvenaghel et al 2016;van Wouwe et al 2016) compared to healthy controls (HCs), whereas others have found no significant group differences (Wylie et al 2010a, b). Moreover, whilst some studies have shown that PwP produce more commission errors on the Go/No-Go task compared to HCs (Geffe et al 2016;Nombela et al 2014), others have reported no group differences (de Rezende Costa et al 2016;Georgiev et al 2016).…”