Scott A. Wylie

To Head or to Heed? Beyond the Surface of Selective Action Inhibition: A Review

To head rather than heed to temptations is easier said than done. Since tempting actions are often contextually inappropriate, selective suppression is invoked to inhibit such actions. Thus far, laboratory tasks have not been very successful in highlighting these processes. We suggest that this is for three reasons. First, it is important to dissociate between an early susceptibility to making stimulus-driven impulsive but erroneous actions, and the subsequent selective suppression of these impulses that facilitates the selection of the correct action. Second, studies have focused on mean or median reaction times (RT), which conceals the temporal dynamics of action control. Third, studies have focused on group means, while considering individual differences as a source of error variance. Here, we present an overview of recent behavioral and imaging studies that overcame these limitations by analyzing RT distributions. As will become clear, this approach has revealed variations in inhibitory control over impulsive actions as a function of task instructions, conflict probability, and between-trial adjustments (following conflict or following an error trial) that are hidden if mean RTs are analyzed. Next, we discuss a selection of behavioral as well as imaging studies to illustrate that individual differences are meaningful and help understand selective suppression during action selection within samples of young and healthy individuals, but also within clinical samples of patients diagnosed with attention deficit/hyperactivity disorder or Parkinsons disease.

Neurocognitive mechanisms of action control: resisting the call of the Sirens

An essential facet of adaptive and versatile behavior is the ability to prioritize actions in response to dynamically changing circumstances. The field of potential actions afforded by a situation is shaped by many factors, such as environmental demands, past experiences, and prepotent tendencies. Selection among action affordances can be driven by deliberate, intentional processes as a product of goal-directed behavior and by extraneous stimulus-action associations as established inherently or through learning. We first review the neurocognitive mechanisms putatively linked to these intention-driven and association-driven routes of action selection. Next, we review the neurocognitive mechanisms engaged to inhibit action affordances that are no longer relevant or that interfere with goal-directed action selection. Optimal action control is viewed as a dynamic interplay between selection and suppression mechanisms, which is achieved by an elaborate circuitry of interconnected cortical regions (most prominently the pre-supplementary motor area and the right inferior frontal cortex) and basal ganglia structures (most prominently the dorsal striatum and the subthalamic nucleus). WIREs Cogni Sci 2011 2 174-192 DOI: 10.1002/wcs.99 For further resources related to this article, please visit the WIREs website.

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 Parkinsons disease treated with subthalamic nucleus stimulation (n = 17) and healthy controls without Parkinsons 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 Parkinsons 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.

The effect of Parkinson's disease on interference control during action selection

Basal ganglia structures comprise a portion of the neural circuitry that is hypothesized to coordinate the selection and suppression of competing responses. Parkinsons disease (PD) may produce a dysfunction in these structures that alters this capacity, making it difficult for patients with PD to suppress interference arising from the automatic activation of salient or overlearned responses. Empirical observations thus far have confirmed this assumption in some studies, but not in others, due presumably to considerable inter-individual variability among PD patients. In an attempt to help resolve this controversy, we measured the performance of 50 PD patients and 25 healthy controls on an arrow version of the Eriksen flanker task in which participants were required to select a response based on the direction of a target arrow that was flanked by arrows pointing in the same (congruent) or opposite (incongruent) direction. Consistent with previous findings, reaction time (RT) increased with incongruent flankers compared to congruent or neutral flankers, and this cost of incongruence was greater among PD patients. Two novel findings are reported. First, distributional analyses, guided by dual-process models of conflict effects and the activation-suppression hypothesis, revealed that PD patients are less efficient at suppressing the activation of conflicting responses, even when matched to healthy controls on RT in a neutral condition. Second, this reduced efficiency was apparent in half of the PD patients, whereas the remaining patients were as efficient as healthy controls. These findings suggest that although poor suppression of conflicting responses is an important feature of PD, it is not evident in all medicated patients.

Inefficient response inhibition in individuals with mild cognitive impairment.

Individuals diagnosed with mild cognitive impairment (MCI) show primary deficits in memory and are at increased risk for developing Alzheimers disease (AD). In light of recent evidence that executive cognitive deficits are common in AD and may be detectable in individuals diagnosed with MCI, we extend these findings to the investigation of response inhibition, an essential aspect of executive cognitive control. Twenty MCI patients and 20 healthy controls (HC) completed an arrow version of the flanker task [Eriksen, B. A., & Eriksen, C. W. (1974). Effects of noise letters upon the identification of target letters in a non-search task. Perception & Psychophysics, 16, 143-149] in which participants responded to a target arrow surrounded by distractors (i.e., flankers) that signaled a same (congruent) or a conflicting (incongruent) response. Reaction time (RT) increased in both groups when flankers signaled an incongruent response, but more so among MCI patients. MCI patients taking a cholinesterase inhibitor showed smaller flanker interference effects than those not taking this medication. Analysis of the flanker effect as a function of the entire RT distribution indicated that MCI patients show increasing interference at the slowest segments of the distribution, a finding that implicates deficient inhibition of the incongruent response [Ridderinkhof, K. R. (2002). Activation and suppression in conflict tasks: Empirical clarification through distributional analyses. In W. Prinz & B. Hommel (Eds.), Common mechanisms in perception and action. Attention & performance, Vol. XIX (pp. 494-519). Oxford: Oxford University Press]. These results suggest that deficits in response inhibition are detectable in MCI patients and merit further investigation as to whether these changes aid prediction of which MCI patients convert to AD.

The effect of parkinson's disease on the dynamics of on-line and proactive cognitive control during action selection

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 Parkinsons 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 effect of speed-accuracy strategy on response interference control in Parkinson's disease

Studies that used conflict paradigms such as the Eriksen Flanker task show that many individuals with Parkinsons disease (PD) have pronounced difficulty resolving the conflict that arises from the simultaneous activation of mutually exclusive responses. This finding fits well with contemporary views that postulate a key role for the basal ganglia in action selection. The present experiment aims to specify the cognitive processes that underlie action selection deficits among PD patients in the context of variations in speed-accuracy strategy. PD patients (n=28) and healthy controls (n=17) performed an arrow version of the flanker task under task instructions that either emphasized speed or accuracy of responses. Reaction time (RT) and accuracy rates decreased with speed compared to accuracy instructions, although to a lesser extent for the PD group. Differences in flanker interference effects among PD and healthy controls depended on speed-accuracy strategy. Compared to the healthy controls, PD patients showed larger flanker interference effects under speed stress. RT distribution analyses suggested that PD patients have greater difficulty suppressing incorrect response activation when pressing for speed. These initial findings point to an important interaction between strategic and computational aspects of interference control in accounting for cognitive impairments of PD. The results are also compatible with recent brain imaging studies that demonstrate basal ganglia activity to co-vary with speed-accuracy adjustments.

UPDRS activity of daily living score as a marker of Parkinson's disease progression

The activities of daily living (ADL) subscore of the Unified Parkinsons Disease Rating Scale (UPDRS) captures the impact of Parkinsons disease (PD) on daily function and may be less affected than other subsections by variability associated with drug cycle and motor fluctuations. We examined UPDRS mentation, ADL and motor subscores in 888 patients with idiopathic PD. Multiple linear regression analyses determined the association between disease duration and UPDRS subscores as a function of medication status at examination and in a subset of patients with multiple examinations. Independent of medication status and across cross‐sectional and longitudinal analyses, ADL subscores showed a stronger and more stable association with disease duration than other UPDRS subscores after adjusting for age of disease onset. The association between disease duration and the motor subscore depended on medication status. The strong association between ADL subscore and disease duration in PD suggests that this measure may serve as a better marker of disease progression than signs and symptoms assessed in other UPDRS sections.

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.

Activation of conflicting responses in Parkinson's disease: evidence for degrading and facilitating effects on response time.

Response selection often occurs in a context of competition among conflicting responses. According to recent models, the basal ganglia may play an integral role in resolving this competition by focusing the selection and inhibition of responses. We hypothesized that basal ganglia dysfunction produced by Parkinsons disease (PD) disrupts selection among conflicting responses. Using a version of the Eriksen flanker task, we tested the specific prediction that individuals with PD would experience greater response interference when distractors in the visual field activate a response that conflicts with the target response. In addition, we investigated whether greater response interference induced by these distractors could actually reduce normal response time costs in PD when the task required production of the response opposite the target. Compared to 16 healthy controls (HC), 16 individuals with PD showed an exacerbated slowing when target and distracting stimuli corresponded to conflicting responses. No group differences occurred when targets and distractors corresponded to the same response. Furthermore, the slowing induced by the distractors was reduced in both groups, but more so in PD, when execution of a response opposite the target response (i.e. incompatible response) was required. Moreover, among individuals with PD, the magnitude of the interference produced by the distractors was related to clinical ratings of bradykinesia. These findings are consistent with the hypothesis that basal ganglia dysfunction due to Parkinsons disease disrupts processes that resolve response conflict.