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 PD patients completed the task twice, once withdrawn from dopamine medications and once while taking their medications.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

Goal-directed action control comes into play when selecting between competing action alternatives. Response capture reflects the susceptibility of the motor system to incitement by task-irrelevant action impulses; the subsequent selective suppression of incorrect action impulses aims to counteract response capture and facilitate the desired response. The goal of this experiment was to clarify physiological mechanisms of response capture and suppression of action impulses during conflict at the level of the motor system. We administered single-pulse TMS at various intervals preceding speeded choice responses. The correct response side was designated by stimulus color, whereas stimulus location (which could match or conflict with response side) was to be ignored. TMS pulses triggered motor evoked potential and silent period, providing sensitive indices of cortico-spinal excitation and inhibition. Motor evoked potential data showed the typical progressive increase in cortico-spinal motor excitability leading up to the imminent (correct) response, which started earlier on nonconflict than on conflict trials. On conflict trials, the irrelevant stimulus location captured the incorrect response, as expressed by an early and transient rise in excitability. Silent period data showed that, already early during the response process, inhibition of the incorrect response was stronger for conflict than for nonconflict trials. Furthermore, inhibition decreased over time for nonconflict trials facilitating the imminent correct response while maintaining higher levels of inhibition on conflict trials. In conclusion, dynamic patterns of cortico-spinal excitability provide unique physiological evidence for the expression and selective suppression of action impulses captured by competing action alternatives.

The suppression of spontaneous motor impulses is an essential facet of cognitive control that is linked to frontal-BG circuitry. BG dysfunction caused by Parkinson disease (PD) disrupts the proficiency of action suppression, but how pharmacotherapy for PD impacts impulsive motor control is poorly understood. Dopamine agonists improve motor symptoms of PD but can also provoke impulsive–compulsive behaviors (ICB). We investigated whether dopamine agonist medication has a beneficial or detrimental effect on impulsive action control in 38 PD patients, half of whom had current ICB. Participants performed the Simon conflict task, which measures susceptibility to acting on spontaneous action impulses as well as the proficiency of suppressing these impulses. Compared with an off-agonist state, patients on their agonists were no more susceptible to reacting impulsively but were less proficient at suppressing the interference from the activation of impulsive actions. Importantly, agonist effects depended on baseline performance in the off-agonist state; more proficient suppressors off agonist experienced a reduction in suppression on agonist, whereas less-proficient suppressors off agonist showed improved suppression on agonist. Patients with active ICB were actually less susceptible to making fast, impulsive response errors than patients without ICB, suggesting that behavioral problems in this subset of patients may be less related to impulsivity in motor control. Our findings provide further evidence that dopamine agonist medication impacts specific cognitive control processes and that the direction of its effects depends on individual differences in performance off medication.

Processing irrelevant visual information sometimes activates incorrect response impulses. The engagement of cognitive control mechanisms to suppress these impulses and make proactive adjustments to reduce the future impact of incorrect impulses may rely on the integrity of frontal–basal ganglia circuitry. Using a Simon task, we investigated the effects of basal ganglia dysfunction produced by Parkinson's disease (PD) on both on-line (within-trial) and proactive (between-trial) control efforts to reduce interference produced by the activation of an incorrect response. As a novel feature, we applied distributional analyses, guided by the activation–suppression model, to differentiate the strength of incorrect response activation and the proficiency of suppression engaged to counter this activation. For situations requiring on-line control, PD ( n = 52) and healthy control ( n = 30) groups showed similar mean interference effects (i.e., Simon effects) on reaction time (RT) and accuracy. Distributional analyses showed that although the strength of incorrect response impulses was similar between the groups PD patients were less proficient at suppressing these impulses. Both groups demonstrated equivalent and effective proactive control of response interference on mean RT and accuracy rates. However, PD patients were less effective at reducing the strength of incorrect response activation proactively. Among PD patients, motor symptom severity was associated with difficulties in on-line, but not in proactive, control of response impulses. These results suggest that basal ganglia dysfunction produced by PD has selective effects on cognitive control mechanisms engaged to resolve response conflict, with primary deficits in the on-line suppression of incorrect responses occurring in the context of a relatively spared ability to adjust control proactively to minimize future conflict.

The ability to stop ongoing motor responses in a split-second is a vital element of human cognitive control and flexibility that relies in large part on prefrontal cortex. We used the stop-signal paradigm to elucidate the engagement of primary motor cortex (M1) in inhibiting an ongoing voluntary motor response. The stop-signal paradigm taps the ability to flexibly countermand ongoing voluntary behavior upon presentation of a stop signal. We applied single-pulse TMS to M1 at several intervals following the stop signal to track the time course of excitability of the motor system related to generating and stopping a manual response. Electromyography recorded from the flexor pollicis brevis allowed quantification of the excitability of the corticospinal tract and the involvement of intracortical GABA B ergic circuits within M1, indexed respectively by the amplitude of the motor-evoked potential and the duration of the late part of the cortical silent period (SP). The results extend our knowledge of the neural basis of inhibitory control in three ways. First, the results revealed a dynamic interplay between response activation and stopping processes at M1 level during stop-signal inhibition of an ongoing response. Second, increased excitability of inhibitory interneurons that drives SP prolongation was evident as early as 134 msec following the instruction to stop. Third, this pattern was followed by a stop-related reduction of corticospinal excitability implemented around 180 after the stop signal. These findings point to the recruitment of GABA B ergic intracortical inhibitory circuits within M1 in stop-signal inhibition and support the notion of stopping as an active act of control.

Functional magnetic resonance imaging (fMRI) methods may help in understanding processes of response capture and response inhibition in conflict tasks, such as the Simon task. However, data-driven approaches thus far have not yielded consistent insights into these processes. Here, a theory-driven approach is introduced that capitalizes on individual differences in the processes of central interest. Based on the so-called activation-suppression model, specific behavioral parameters for each individual derived from reaction time (RT) distribution analysis were computed and entered into model-based fMRI analyses. These parameters correspond closely to the processes of inappropriate location-driven response activation (capture) and the subsequent inhibition of this activation as detailed by the model. Data from 24 participants revealed activation in the pre-supplementary motor area, which covaried with the RT distribution measure of response capture. Activation in the right inferior frontal cortex was found to covary with the RT distribution measure of response inhibition. These results, which are consistent against the backdrop of the larger literature on cognitive control, could have been derived neither from the standard data-driven fMRI approach, nor from inspecting overall mean RT alone.

The aim of the present study was to specify the involvement of the basal ganglia in motor response selection and response inhibition. Two samples were studied. The first sample consisted of patients diagnosed with Parkinson's disease (PD) who received deep-brain stimulation (DBS) of the subthalamic nucleus (STN). The second sample consisted of patients who received DBS for the treatment of PD or essential tremor (ET) in the ventral intermediate nucleus of the thalamus (Vim). Stop-signal task and go/no-go task performances were studied in both groups. Both groups performed these tasks with ( on stimulation) and without ( off stimulation) DBS to address the question of whether stimulation is effective in improving choice reaction time (RT) and stop-signal RT. The results show that DBS of the STN was associated with significantly enhanced inhibitory control, as indicated by shorter stop-signal RTs. An additional finding is that DBS of the STN led to significantly shorter choice RT. The effects of DBS on responding and response inhibition were functionally independent. Although DBS of the Vim did not systematically affect task performance in patients with ET, a subgroup of Vim-stimulated PD patients showed enhanced stop-signal RTs in on stimulation versus off stimulation. This result suggests that the change in performance to stop signals may not be directly related to STN function, but rather results from a change in PD function due to DBS in general. The findings are discussed in terms of current functional and neurobiological models that relate basal ganglia function to the selection and inhibition of motor responses.