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 PD patients completed the task twice, once withdrawn from dopamine medications and once while taking their medications.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.

Frontal-basal ganglia circuitry dysfunction caused by Parkinson’s disease impairs important executive cognitive processes, such as the ability to inhibit impulsive action tendencies. Subthalamic Nucleus Deep Brain Stimulation in Parkinson’s disease improves the reactive inhibition of impulsive actions that interfere with goal-directed behavior. An unresolved question is whether this effect depends on stimulation of a particular Subthalamic Nucleus subregion. The current study aimed to 1) replicate previous findings and additionally investigate the effect of chronic versus acute Subthalamic Nucleus stimulation on inhibitory control in Parkinson’s disease patients off dopaminergic medication 2) test whether stimulating Subthalamic Nucleus subregions differentially modulate proactive response control and the proficiency of reactive inhibitory control. In the first experiment, twelve Parkinson’s disease patients completed three sessions of the Simon task, Off Deep brain stimulation and medication, on acute Deep Brain Stimulation and on chronic Deep Brain Stimulation. Experiment 2 consisted of 11 Parkinson’s disease patients with Subthalamic Nucleus Deep Brain Stimulation (off medication) who completed two testing sessions involving of a Simon task either with stimulation of the dorsal or the ventral contact in the Subthalamic Nucleus. Our findings show that Deep Brain Stimulation improves reactive inhibitory control, regardless of medication and regardless of whether it concerns chronic or acute Subthalamic Nucleus stimulation. More importantly, selective stimulation of dorsal and ventral subregions of the Subthalamic Nucleus indicates that especially the dorsal Subthalamic Nucleus circuitries are crucial for modulating the reactive inhibitory control of motor actions.

Parkinson’s disease (PD) is a neurodegenerative basal ganglia disease that disrupts cognitive control processes involved in response selection. The current study investigated the effects of PD on the ability to resolve conflicts during response selection when performance emphasized response speed versus response accuracy. Twenty-one (21) PD patients and 21 healthy controls (HC) completed a Simon conflict task, and a subset of 10 participants from each group provided simultaneous movement-related potential (MRP) data to track patterns of motor cortex activation and inhibition associated with the successful resolution of conflicting response tendencies. Both groups adjusted performance strategically to emphasize response speed or accuracy (i.e., speed-accuracy effect). For HC, interference from a conflicting response was reduced when response accuracy rather than speed was prioritized. For PD patients, however, there was a reduction in interference, but it was not statistically significant. The conceptual framework of the Dual-Process Activation-Suppression (DPAS) model revealed that the groups experienced similar susceptibility to making fast impulsive errors in conflict trials irrespective of speed-accuracy instructions, but PD patients were less proficient and delayed compared to HC at suppressing the interference from these incorrect response tendencies, especially under speed pressure. Analysis of MRPs on response conflict trials showed attenuated inhibition of the motor cortex controlling the conflicting impulsive response tendency in PD patients compared to HC. These results further confirm the detrimental effects of PD inhibitory control mechanisms and their exacerbation when patients perform under speed pressure. The results also suggest that a downstream effect of inhibitory dysfunction in PD is diminished inhibition of motor cortex controlling conflicting response tendencies.

Background Parkinson Disease (PD) patients treated with Dopamine Agonist therapy can develop maladaptive reward-driven behaviors, known as Impulse Control Disorder (ICD). In this study, we assessed if ICD patients have evidence of motor-impulsivity. Methods We used the stop-signal task in a cohort of patients with and without active symptoms of ICD to evaluate motor-impulsivity. Of those with PD, 12 were diagnosed with ICD symptoms (PD-ICD) and were assessed before clinical reduction of Dopamine Agonist medication; 12 were without symptoms of ICD [PD-control] and taking equivalent dosages of Dopamine Agonist. Levodopa, if present, was maintained in both settings. Groups were similar in age, duration, and severity of motor symptoms, levodopa co-therapy, and total levodopa daily dose. All were tested in the Dopamine Agonist medicated and acutely withdrawn (24 hours) state, in a counterbalanced manner. Primary outcome measures were mean reaction time to correct go trials (Go Reaction Time), and mean stop-signal reaction time (SSRT). Results ICD patients produce faster SSRT than both Healthy Controls, and PD Controls. Faster SSRT in ICD patients is apparent in both Dopamine Agonist medication states. Also, we show unique dopamine medication effects on GoRT. In Dopamine Agonist monotherapy patients, Dopamine Agonist administration speeds Go Reaction Time. Conversely, in those with levodopa co-therapy, Dopamine Agonist administration slows Go Reaction Time. Discussion PD patients with active ICD symptoms are significantly faster at stopping initiated motor actions, and this is not altered by acute Dopamine Agonist withdrawal. In addition, the effect of Dopamine Agonist on Go Reaction Time is strongly influenced by the presence or absence of levodopa, even though levodopa co-therapy does not appear to influence SSRT. We discuss these findings as they pertain to the multifaceted definition of ‘impulsivity,’ the lack of evidence for motor-impulsivity in PD-ICD, and dopamine effects on motor-control in PD.

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A well-established motor timing paradigm, the Synchronization-Continuation Task (SCT), quantifies how accurately participants can time finger tapping to a rhythmic auditory beat (synchronization phase) then maintain this rhythm after the external auditory cue is extinguished, where performance depends on an internal representation of the beat (continuation phase). In this study, we investigated the hypothesis that Parkinson’s disease (PD) patients with clinical symptoms of freezing of gait (FOG) exhibit exaggerated motor timing deficits. We predicted that dysrhythmia is exacerbated when finger tapping is stopped temporarily and then reinitiated under the guidance of an internal representation of the beat. Healthy controls and PD patients with and without FOG performed the SCT with and without the insertion of a 7-second cessation of motor tapping between synchronization and continuation phases. With no interruption between synchronization and continuation phases, PD patients, especially those with FOG, showed pronounced motor timing hastening at the slowest inter stimulus intervals during the continuation phase. The introduction of a gap prior to the continuation phase had a beneficial effect for healthy controls and PD patients without FOG, although patients with FOG continued to show pronounced and persistent motor timing hastening. Ratings of freezing of gait severity across the entire sample of PD tracked closely with the magnitude of hastening during the continuation phase. These results suggest that PD is accompanied by a unique dysrhythmia of measured movements, with FOG reflecting a particularly pronounced disruption to internal rhythmic timing.

The present behavioral study delineates the impact of Parkinson's disease (PD) and of dopaminergic medication on action control over voluntary behavior. Previous studies reported either prolonged responding or stopping latencies in PD compared to healthy controls (HC). Few studies investigated the effects of dopaminergic medication on these processes concurrently. We administered a stop-change task, an extended version of the stop task, that required (i) speeded responding to a go signal (i.e., going), (ii) inhibiting ongoing motor responses (i.e., stopping), and (iii) changing to an alternative response. PD performance (n = 33) was collected once during regular dopaminergic medication conditions (On state) and once after a medication washout period (Off state). A group of age-matched HC (n = 21) performed the stop-change task once. Response latencies to go signals were comparable between HC and PD Off, indicative of unimpaired going. Compared to HC, PD Off showed prolonged stopping latencies. Within the clinical group, stopping latencies significantly improved after taking dopaminergic medication. Interestingly, the shorter stopping latencies observed in the On state were paralleled by longer response latencies to go signals. The degree of the inhibition improvement observed in the medication state was correlated with the degree of response slowing. Change RT did not vary between groups or between medication states. These patterns of results are discussed in terms of a tradeoff between going versus stopping of motor responses in PD patients. Shifts of this tradeoff seem to be driven by dopaminergic medication, which has potential clinical implications.

The current study aimed to shed more light on the role of dopamine in temporal attention. To this end, we pharmacologically manipulated dopamine levels in a large sample of Parkinson’s disease patients (n=63) while they performed an attentional blink (AB) task in which they had to identify two targets (T1 and T2) presented in close temporal proximity among distractors. We specifically examined 1) differences in the magnitude of the AB between unmedicated Parkinson patients, who have depleted levels of striatal dopamine, and healthy controls, and 2) effects of two dopaminergic medications (L-DOPA and dopamine agonists) on the AB in the Parkinson patients at the group level and as a function of individual baseline performance. In line with the notion that relatively low levels of striatal dopamine may impair target detection in general, Parkinson patients OFF medications displayed overall poor target perception compared to healthy controls. Moreover, as predicted, effects of dopaminergic medication on AB performance critically depended on individual baseline AB size, although this effect was only observed for L-DOPA. L-DOPA generally decreased the size of the AB in patients with a large baseline AB (i.e., OFF medications), while L-DOPA generally increased the AB in patients with a small baseline AB. These findings may support a role for dopamine in the AB and temporal attention, more generally and corroborate the notion that there is an optimum dopamine level for cognitive function. They also emphasize the need for more studies that examine the separate effects of DA agonists and L-DOPA on cognitive functioning.