Essential tremor impairs the ability to suppress involuntary action impulses.

Essential tremor (ET) is a movement disorder characterized primarily by action tremor which affects the regulation of movements. Disruptions in cerebello-thalamocortical networks could interfere with cognitive control over actions in ET, for example, the ability to suppress a strong automatic impulse over a more appropriate action (conflict control). The current study investigated whether ET impacts conflict control proficiency. Forty-one ET patients and 29 age-matched healthy controls (HCs) performed a conflict control task (Simon task). Participants were instructed to give a left or right response to a spatially lateralized arrow (direction of the arrow). When the action signaled by the spatial location and direction of the arrow were non-corresponding (induced conflict), the inappropriate action impulse required suppression. Overall, ET patients responded slower and less accurately compared to HCs. ET patients were especially less accurate on non-corresponding conflict (Nc) versus corresponding (Cs) trials. A focused analysis on fast impulsive response rates (based on the accuracy rate at the fastest reaction times on Nc trials) showed that ET patients made more fast errors compared to HCs. Results suggest impaired conflict control in ET compared to HCs. The increased impulsive errors seen in the ET population may be a symptom of deficiencies in the cerebello-thalamocortical networks, or, be caused by indirect effects on the cortico-striatal pathways. Future studies into the functional networks impacted by ET (cortico-striatal and cerebello-thalamocortical pathways) could advance our understanding of inhibitory control in general and the cognitive deficits in ET.

Impaired Action Control in Patients With Functional Movement Disorders.

OBJECTIVE: Despite being a major cause of neurological disability, the neural mechanisms of functional movement disorders (FMDs) remain poorly understood. Recent studies suggest that FMD is linked to dysfunctional motor and prefrontal regions that could lead to motor and cognitive impairments. The aim of this study was to investigate different components of action control in FMD by using choice-reaction, stop-signal, and Simon tasks. METHODS: Thirty patients with an FMD were prospectively recruited from the University of Louisville Movement Disorders Clinic and compared with 53 healthy control subjects, recruited from the Vanderbilt University Medical Center Movement Disorders Clinic. FMD motor symptom severity was rated with the Simplified Functional Movement Disorder Rating Scale (S-FMDRS). By using a computer and handheld response grips, participants completed three action-control tasks (choice-reaction task, stop-signal task, and Simon task) that tested action initiation, action cancelation, and interference control over actions. Action-control measures were compared between groups with analyses of variance. RESULTS: Patients with FMD were less proficient in suppressing incorrect response impulses on the Simon task and were slower to stop on the stop-signal task compared with healthy control subjects. No significant correlation with neuropsychological measurements, S-FMDRS scores, and action-control measurements was observed. CONCLUSIONS: These results suggest that two forms of inhibitory control, selective impulse inhibition and global action cancelation, are impaired in patients with FMD, independent of slowing on go reaction times. Improved understanding of action control in FMD may help in the development of new diagnostic and therapeutic strategies.

Action Control Deficits in Patients With Essential Tremor.

OBJECTIVES: Essential tremor (ET) is a movement disorder characterized by action tremor which impacts motor execution. Given the disrupted cerebellar-thalamo-cortical networks in ET, we hypothesized that ET could interfere with the control mechanisms involved in regulating motor performance. The ability to inhibit or stop actions is critical for navigating many daily life situations such as driving or social interactions. The current study investigated the speed of action initiation and two forms of action control, response stopping and proactive slowing in ET. METHODS: Thirty-three ET patients and 25 healthy controls (HCs) completed a choice reaction task and a stop-signal task, and measures of going speed, proactive slowing and stop latencies were assessed. RESULTS: Going speed was significantly slower in ET patients (649 ms) compared to HCs (526 ms; F(1,56) = 42.37; p <.001; η 2 = .43), whereas proactive slowing did not differ between groups. ET patients exhibited slower stop signal reaction times (320 ms) compared to HCs (258 ms, F(1,56) = 15.3; p <.00; η 2 = .22) and more severe motor symptoms of ET were associated with longer stopping latencies in a subset of patients (Spearman rho = .48; p <.05). CONCLUSIONS: In line with previous studies, ET patients showed slower action initiation. Additionally, inhibitory control was impaired whereas proactive slowing remained intact relative to HCs. More severe motor symptoms of ET were associated with slower stopping speed, and may reflect more progressive changes to the cerebellar-thalamo-cortical network. Future imaging studies should specify which structural and functional changes in ET can explain changes in inhibitory action control. (JINS, 2019, 25, 156-164).

Motivational Sensitivities Linked to Impulsive Motor Errors in Parkinson's Disease.

OBJECTIVES: We investigated how broad motivational tendencies are related to the expression and suppression of action impulses in Parkinson's disease (PD). METHODS: Sixty-nine participants with PD completed a Simon response conflict task and Behavioral Inhibition System (BIS) and Behavioral Activation System (BAS) scales based on Gray's (1987) reinforcement sensitivity theory. Analyses determined relationships between BIS, BAS, and the susceptibility to making impulsive action errors and the proficiency of inhibiting interference from action impulses. RESULTS: BIS scores correlated positively with rates of impulsive action errors, indicating that participants endorsing low BIS tendencies were much more susceptible to acting on strong motor impulses. Analyses of subgroups with high versus low BIS scores confirmed this pattern and ruled out alternative explanations in terms of group differences in speed-accuracy tradeoffs. None of the scores on the BIS or BAS scales correlated with reactive inhibitory control. CONCLUSIONS: PD participants who endorse diminished predilection toward monitoring and avoiding aversive experiences (low BIS) show much greater difficulty restraining fast, impulsive motor errors. Establishing relationships between motivational sensitivities and cognitive control processes may have important implications for treatment strategies and positive health outcomes in participants with PD, particularly those at risk for falling and driving difficulties related to impulsive reactions. (JINS, 2018, 24, 128-138).

Dopamine Selectively Modulates the Outcome of Learning Unnatural Action-Valence Associations.

Learning the contingencies between stimulus, action, and outcomes is disrupted in disorders associated with altered dopamine (DA) function in the BG, such as Parkinson disease (PD). Although the role of DA in learning to act has been extensively investigated in PD, the role of DA in "learning to withhold" (or inhibit) action to influence outcomes is not as well understood. The current study investigated the role of DA in learning to act or to withhold action to receive rewarding, or avoid punishing outcomes, in patients with PD tested "off" and "on" dopaminergic medication (n = 19) versus healthy controls (n = 30). Participants performed a reward-based learning task that orthogonalized action and outcome valence (action-reward, inaction-reward, action-punishment, inaction-punishment). We tested whether DA would bias learning toward action, toward reward, or to particular action-outcome interactions. All participants demonstrated inherent learning biases preferring action with reward and inaction to avoid punishment, and this was unaffected by medication. Instead, DA produced a complex modulation of learning less natural action-outcome associations. "Off" DA medication, patients demonstrated impairments in learning to withhold action to gain reward, suggesting a difficulty to overcome a bias toward associating inaction with punishment avoidance. On DA medication, these patterns changed, and patients showed a reduced ability to learn to act to avoid punishment, indicating a bias toward action and reward. The current findings suggest that DA in PD has a complex influence on the formation of action-outcome associations, particularly those involving less natural linkages between action and outcome valence.

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

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.

The Allure of High-Risk Rewards in Huntington's disease.

OBJECTIVES: Huntington's disease (HD) is a neurodegenerative disorder that produces a bias toward risky, reward-driven decisions in situations where the outcomes of decisions are uncertain and must be discovered. However, it is unclear whether HD patients show similar biases in decision-making when learning demands are minimized and prospective risks and outcomes are known explicitly. We investigated how risk decision-making strategies and adjustments are altered in HD patients when reward contingencies are explicit. METHODS: HD (N=18) and healthy control (HC; N=17) participants completed a risk-taking task in which they made a series of independent choices between a low-risk/low reward and high-risk/high reward risk options. RESULTS: Computational modeling showed that compared to HC, who showed a clear preference for low-risk compared to high-risk decisions, the HD group valued high-risks more than low-risk decisions, especially when high-risks were rewarded. The strategy analysis indicated that when high-risk options were rewarded, HC adopted a conservative risk strategy on the next trial by preferring the low-risk option (i.e., they counted their blessings and then played the surer bet). In contrast, following a rewarded high-risk choice, HD patients showed a clear preference for repeating the high-risk choice. CONCLUSIONS: These results indicate a pattern of high-risk/high-reward decision bias in HD that persists when outcomes and risks are certain. The allure of high-risk/high-reward decisions in situations of risk certainty and uncertainty expands our insight into the dynamic decision-making deficits that create considerable clinical burden in HD.

Stopping Manual and Vocal Actions in Tourette's Syndrome.

Evidence that Tourette's syndrome (TS) disrupts inhibitory motor control is highly mixed. The authors investigated inhibitory control of manual and vocal actions in young adults with relatively uncomplicated, persistent TS. Both TS and control groups showed similar response latencies when executing manual and vocal reactions, but individuals with TS were slower at stopping their manual and vocal responses. While alterations in inhibitory motor control may not be a generalizable phenomenon in TS, these results add to an emerging literature suggesting that individuals with relatively uncomplicated TS, whose symptoms persist into adulthood, show disruption to inhibitory control mechanisms.

Generalized motor inhibitory deficit in Parkinson's disease patients who freeze.

Freezing of gait is a disabling symptom of Parkinson's disease (PD) that involves failure to initiate and continue motor activity appropriately. PD disrupts fronto-basal ganglia circuitries that also implement the inhibition of responses, leading to the hypothesis that freezing of gait may involve fundamental changes in both initiation and inhibition of motor actions. We asked whether PD patients who show freezing of gait show selective deficits in their ability to inhibit upper and lower extremity reactions. We compared older healthy controls, older PD controls without freezing of gait, and older PD participants with freezing of gait, in stop-signal tasks that measured the initiation (go trials) and inhibition (stop trials) of both hand and foot responses. When only go trials were presented, all three groups showed similar initiation speeds across lower and upper extremity responses. When stop-signal trials were introduced, both PD groups slowed their reactions nearly twice as much as healthy controls. While this adjustment helped PD controls stop their actions as quickly as healthy controls, PD patients with freezing showed significantly delayed inhibitory control of both upper and lower extremities. When anticipating the need to stop their actions urgently, PD patients show greater adjustments (i.e., slowing) to reaction speed than healthy controls. Despite these proactive adjustments, PD patients who freeze show marked impairments in inhibiting both upper and lower extremity responses, suggesting that freezing may involve a fundamental disruption to the brain's inhibitory control system.

Focused stimulation of dorsal versus ventral subthalamic nucleus enhances action-outcome learning in patients with Parkinson's disease.

Deep brain stimulation of the subthalamic nucleus is an effective treatment for the clinical motor symptoms of Parkinson's disease, but may alter the ability to learn contingencies between stimuli, actions and outcomes. We investigated how stimulation of the functional subregions in the subthalamic nucleus (motor and cognitive regions) modulates stimulus-action-outcome learning in Parkinson's disease patients. Twelve Parkinson's disease patients with deep brain stimulation of the subthalamic nucleus completed a probabilistic stimulus-action-outcome task while undergoing ventral and dorsal subthalamic nucleus stimulation (within subjects, order counterbalanced). The task orthogonalized action choice and outcome valence, which created four action-outcome learning conditions: action-reward, inhibit-reward, action-punishment avoidance and inhibit-punishment avoidance. We compared the effects of deep brain stimulation on learning rates across these conditions as well as on computed Pavlovian learning biases. Dorsal stimulation was associated with higher overall learning proficiency relative to ventral subthalamic nucleus stimulation. Compared to ventral stimulation, stimulating the dorsal subthalamic nucleus led to a particular advantage in learning to inhibit action to produce desired outcomes (gain reward or avoid punishment) as well as better learning proficiency across all conditions providing reward opportunities. The Pavlovian reward bias was reduced with dorsal relative to ventral subthalamic nucleus stimulation, which was reflected by improved inhibit-reward learning. Our results show that focused stimulation in the dorsal compared to the ventral subthalamic nucleus is relatively more favourable for learning action-outcome contingencies and reduces the Pavlovian bias that could lead to reward-driven behaviour. Considering the effects of deep brain stimulation of the subthalamic nucleus on learning and behaviour could be important when optimizing stimulation parameters to avoid side effects like impulsive reward-driven behaviour.

Impaired inhibition of prepotent motor actions in patients with Tourette syndrome.

BACKGROUND: Evidence that tic behaviour in individuals with Tourette syndrome reflects difficulties inhibiting prepotent motor actions is mixed. Response conflict tasks produce sensitive measures of response interference from prepotent motor impulses and the proficiency of inhibiting these impulses as an act of cognitive control. We tested the hypothesis that individuals with Tourette syndrome show a deficit in inhibiting prepotent motor actions. METHODS: Healthy controls and older adolescents/adults with persistent Tourette syndrome without a history of obsessive-compulsive disorder or attention-deficit/hyperactivity disorder and presenting with stable mood functioning (i.e., no history of well-treated anxiety or depression) participated in this study. They performed a Simon task that induced conflict between prepotent actions and goal-directed actions. A novel theoretical framework distinguished group differences in acting impulsively (i.e., fast motor errors) from the proficiency of inhibiting interference by prepotent actions (i.e., slope of interference reduction). RESULTS: We included 27 controls and 28 individuals with Tourette syndrome in our study. Both groups showed similar susceptibility to making fast, impulsive motor errors (Tourette syndrome 26% v. control 23%; p = 0.10). The slope (m) reduction of the interference effect was significantly less pronounced among participants with Tourette syndrome than controls (Tourette syndrome: m = -0.07 v. control: m = -0.23; p = 0.022), consistent with deficient inhibitory control over prepotent actions in Tourette syndrome. LIMITATIONS: This study does not address directly the role of psychiatric comorbidities and medication effects on inhibitory control over impulsive actions in individuals with Tourette syndrome. CONCLUSION: The results offer empirical evidence for deficient inhibitory control over prepotent motor actions in individuals with persistent Tourette syndrome with minimal to absent psychiatric comorbidities. These findings also suggest that the frontal-basal ganglia circuits involved in suppressing unwanted motor actions may underlie deficient inhibitory control abilities in individuals with Tourette syndrome.

Huntington disease exacerbates action impulses.

Background: Impulsivity is a common clinical feature of Huntington disease (HD), but the underlying cognitive dynamics of impulse control in this population have not been well-studied. Objective: To investigate the temporal dynamics of action impulse control in HD patients using an inhibitory action control task. Methods: Sixteen motor manifest HD patients and seventeen age-matched healthy controls (HC) completed the action control task. We applied the activation-suppression theoretical model and distributional analytic techniques to differentiate the strength of fast impulses from their top-down suppression. Results: Overall, HD patients produced slower and less accurate reactions than HCs. HD patients also exhibited an exacerbated interference effect, as evidenced by a greater slowing of RT on non-corresponding compared to corresponding trials. HD patients made more fast, impulsive errors than HC, evidenced by significantly lower accuracy on their fastest reaction time trials. The slope reduction of interference effects as reactions slowed was similar between HD and controls, indicating preserved impulse suppression. Conclusion: Our results indicate that patients with HD show a greater susceptibility to act rapidly on incorrect motor impulses but preserved proficiency of top-down suppression. Further research is needed to determine how these findings relate to clinical behavioral symptoms.

Dopamine agonists and the suppression of impulsive motor actions in Parkinson disease.

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.

Differential susceptibility to motor impulsivity among functional subtypes of Parkinson's disease.

BACKGROUND AND OBJECTIVES: Parkinson's disease patients with predominant postural instability and gait difficulties (PIGD) may experience unique cognitive difficulties compared to patients with tremor predominant (TD) symptoms. PIGD patients are also at high risk for falling, and some of the worst fallers seem to react impulsively to their environment. We tested the hypothesis that PIGD patients show poorer control over motor impulses compared to TD patients. METHODS: 34 PD participants were divided into predominant PIGD (n=17) or TD (n=17) functional subtypes based on their presenting symptoms in their optimally treated motor state. All participants performed a speeded reaction task that quantified motor impulsivity and the proficiency of inhibiting prepotent motor impulses. RESULTS: The groups showed similar reaction times, but compared to TD patients, PIGD patients made significantly more impulsive motor errors. Notably, when the initial impulsive erroneous response was avoided, PIGD and TD groups were similar in their ability to suppress the incorrect motor impulse from further interfering with the selection of a correct action. CONCLUSIONS: PD patients with PIGD predominant symptoms show greater susceptibility to acting on prepotent motor impulses compared to TD patients. This finding may have direct implications for fall risk and also points to dissociable neurocognitive pathologies in TD and PIGD subtypes. Clinically, the use of specific cognitive instruments to assess the expression and inhibition of motor impulses may help identify PD patients who have difficulty 'thinking before they leap' and are at high risk of falling.

Trends and issues in characterizing early cognitive changes in Parkinson's disease.

In this review, we first discuss trends and issues in measuring cognitive changes in PD, including recent efforts to define the diagnostic classification of "PD Mild Cognitive Impairment" (PD-MCI). After reviewing some limitations associated with this diagnosis, we discuss how measures derived from the neurocognitive sciences offer better precision in detecting early cognitive changes in PD. To support this idea, we highlight 2 influential lines of current investigation that are unveiling novel insights about specific cognitive processes that are vulnerable early in PD and of critical importance to clinicians involved in treating PD: action control and reward learning and decision making. We conclude by highlighting some extant issues and unresolved questions for future investigations.

Towards Conceptual Clarification of Proactive Inhibitory Control: A Review.

The aim of this selective review paper is to clarify potential confusion when referring to the term proactive inhibitory control. Illustrated by a concise overview of the literature, we propose defining reactive inhibition as the mechanism underlying stopping an action. On a stop trial, the stop signal initiates the stopping process that races against the ongoing action-related process that is triggered by the go signal. Whichever processes finishes first determines the behavioral outcome of the race. That is, stopping is either successful or unsuccessful in that trial. Conversely, we propose using the term proactive inhibition to explicitly indicate preparatory processes engaged to bias the outcome of the race between stopping and going. More specifically, these proactive processes include either pre-amping the reactive inhibition system (biasing the efficiency of the stopping process) or presetting the action system (biasing the efficiency of the go process). We believe that this distinction helps meaningful comparisons between various outcome measures of proactive inhibitory control that are reported in the literature and extends to experimental research paradigms other than the stop task.

Developing Predictor Models of Postoperative Verbal Fluency After Deep Brain Stimulation Using Preoperative Neuropsychological Assessment.

BACKGROUND: Deep brain stimulation (DBS) for Parkinson disease provides significant improvement of motor symptoms but can also produce neurocognitive side effects. A decline in verbal fluency (VF) is among the most frequently reported side effects. Preoperative factors that could predict VF decline have yet to be identified. OBJECTIVE: To develop predictive models of DBS postoperative VF decline using a machine learning approach. METHODS: We used a prospective database of patients who underwent neuropsychological and VF assessment before both subthalamic nucleus (n = 47, bilateral = 44) and globus pallidus interna (n = 43, bilateral = 39) DBS. We used a neurobehavioral rating profile as features for modeling postoperative VF. We constructed separate models for action, semantic, and letter VF. We used a leave-one-out scheme to test the accuracy of the predictive models using median absolute error and correlation with actual postoperative scores. RESULTS: The predictive models were able to predict the 3 types of VF with high accuracy ranging from a median absolute error of 0.92 to 1.36. Across all three models, higher preoperative fluency, digit span, education, and Mini-Mental State Examination were predictive of higher postoperative fluency scores. By contrast, higher frontal system deficits, age, Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease scored by the patient, disease duration, and Behavioral Inhibition/Behavioral Activation Scale scores were predictive of lower postoperative fluency scores. CONCLUSION: Postoperative VF can be accurately predicted using preoperative neurobehavioral rating scores above and beyond preoperative VF score and relies on performance over different aspects of executive function.

Effects of deep brain stimulation target on the activation and suppression of action impulses.

OBJECTIVE: Deep brain stimulation (DBS) is an effective treatment to improve motor symptoms in Parkinson's disease (PD). The Globus Pallidus (GPi) and the Subthalamic Nucleus (STN) are the most targeted brain regions for stimulation and produce similar improvements in PD motor symptoms. However, our understanding of stimulation effects across targets on inhibitory action control processes is limited. We compared the effects of STN (n = 20) and GPi (n = 13) DBS on inhibitory control in PD patients. METHODS: We recruited PD patients undergoing DBS at the Vanderbilt Movement Disorders Clinic and measured their performance on an inhibitory action control task (Simon task) before surgery (optimally treated medication state) and after surgery in their optimally treated state (medication plus their DBS device turned on). RESULTS: DBS to both STN and GPi targets induced an increase in fast impulsive errors while simultaneously producing more proficient reactive suppression of interference from action impulses. CONCLUSIONS: Stimulation in GPi produced similar effects as STN DBS, indicating that stimulation to either target increases the initial susceptibility to act on strong action impulses while concomitantly improving the ability to suppress ongoing interference from activated impulses. SIGNIFICANCE: Action impulse control processes are similarly impacted by stimulating dissociable nodes in frontal-basal ganglia circuitry.

Handedness and motor symptom asymmetry in Parkinson's disease.

BACKGROUND: The objective of this study was to confirm whether an association between handedness and the side of symptom onset exists and to evaluate the impact of this association on specific clinical characteristics of Parkinson's disease (PD). METHODS: 1173 PD patients were identified from a clinical database. Patients with asymmetrical onset (n=1015) were divided into those with dominant-side onset and those with non-dominant-side onset, and the clinical characteristics of the two subgroups were compared. RESULTS: In our PD sample, 86.5% of patients presented asymmetrically. There was a significant association between handedness and the side of the initial symptom; that is, the dominant side was affected first in the majority of both left- and right-handed patients. Compared with patients with non-dominant side onset, more patients with dominant-side onset presented with bradykinesia, while fewer patients presented with gait difficulty. Patients with dominant-side onset were diagnosed and began dopaminergic medication after a longer symptom duration than patients with non-dominant-side onset. The only difference in Unified Parkinson Disease Rating Scale scores between the two groups was in a subscore addressing dominant-hand tasks. CONCLUSIONS: An association exists between the dominant hand and the side of the initial motor symptom in PD. Whether the initial symptom occurs on the dominant or non-dominant side has implications for the reported first symptom, the time to diagnosis and the time to dopaminergic treatment initiation. The side of disease onset does not affect the severity of disease, as measured by the Unified Parkinson Disease Rating Scale.

Subthalamic nucleus stimulation influences expression and suppression of impulsive behaviour in Parkinson's disease.

Past studies show beneficial as well as detrimental effects of subthalamic nucleus deep-brain stimulation on impulsive behaviour. We address this paradox by investigating individuals with Parkinson's disease treated with subthalamic nucleus stimulation (n = 17) and healthy controls without Parkinson's disease (n = 17) on performance in a Simon task. In this reaction time task, conflict between premature response impulses and goal-directed action selection is manipulated. We applied distributional analytic methods to separate the strength of the initial response impulse from the proficiency of inhibitory control engaged subsequently to suppress the impulse. Patients with Parkinson's disease were tested when stimulation was either turned on or off. Mean conflict interference effects did not differ between controls and patients, or within patients when stimulation was on versus off. In contrast, distributional analyses revealed two dissociable effects of subthalamic nucleus stimulation. Fast response errors indicated that stimulation increased impulsive, premature responding in high conflict situations. Later in the reaction process, however, stimulation improved the proficiency with which inhibitory control was engaged to suppress these impulses selectively, thereby facilitating selection of the correct action. This temporal dissociation supports a conceptual framework for resolving past paradoxical findings and further highlights that dynamic aspects of impulse and inhibitory control underlying goal-directed behaviour rely in part on neural circuitry inclusive of the subthalamic nucleus.