Response Inhibition Control Research Articles

Sleep-independent offline consolidation of response inhibition during the daytime post-training period.

Appropriate inhibitory response control is associated with goal-directed behavior. Sleep accelerates the offline consolidation of acquired motor skills that are explicitly predictable; however, the effect of sleep on implicit (unpredictable) motor skills remains controversial. We speculated that a key component of response inhibition skill differentiates between these skill consolidation properties because explicit prediction can minimize the inhibitory efforts in a motor skill. We explored the offline skill learning properties of response inhibition during sleep and wakefulness using auditory Go and Go/Nogo tasks. We attempted to discriminate the possible effects of time elapsed after training (12 or 24 h), post-training sleep/wake state (sleep or wakefulness), and time of day (nighttime or daytime) in 79 healthy human subjects divided into 6 groups that underwent various sleep regimens prior to training and retesting. We found that delayed response inhibition skill improvement was achieved via a simple passage of daytime, regardless of the participants’ alertness level. Our results suggest that sleep-independent neuroplasticity occurs during the daytime and facilitates a delayed learning of response inhibition skill.

How to stop or change a motor response: Laplacian and independent component analysis approach

Response inhibition is an essential control function necessary to adapt one's behavior. This key cognitive capacity is assumed to be dependent on the prefrontal cortex and basal ganglia. It is unresolved whether varying inhibitory demands engage different control mechanisms or whether a single motor inhibitory mechanism is involved in any situation. We addressed this question by comparing electrophysiological activity in conditions that require stopping a response to conditions that require switching to an alternate response. Analyses of electrophysiological data obtained from stop-signal tasks are complicated by overlapping stimulus-related activity that is distributed over frontal and parietal cortical recording sites. Here, we applied Laplacian transformation and independent component analysis (ICA) to overcome these difficulties. Participants were faster in switching compared to stopping a response, but we did not observe differences in neural activity between these conditions. Both stop- and change-trials Laplacian transformed ERPs revealed a comparable bilateral parieto-occipital negativity around 180ms and a frontocentral negativity around 220ms. ICA results suggested an inhibition-related frontocentral component which was characterized by a negativity around 200ms with a likely source in anterior cingulate cortex. The data provide support for the importance of posterior mediofrontal areas in inhibitory response control and are consistent with a common neural pathway underlying stopping and changing of a motor response. The methodological approach proved useful to distinguish frontal and parietal sources despite similar timing and the ICA approach allowed assessment of single-trial data with respect to behavioral data.

Tryptophan Depletion Promotes Habitual over Goal-Directed Control of Appetitive Responding in Humans.

Background:Optimal behavioral performance results from a balance between goal-directed and habitual systems of behavioral control, which are modulated by ascending monoaminergic projections. While the role of the dopaminergic system in behavioral control has been recently addressed, the extent to which changes in global serotonin neurotransmission could influence these 2 systems is still poorly understood.Methods:We employed the dietary acute tryptophan depletion procedure to reduce serotonin neurotransmission in 18 healthy volunteers and 18 matched controls. We used a 3-stage instrumental learning paradigm that includes an initial instrumental learning stage, a subsequent outcome-devaluation test, and a slip-of-action stage, which directly tests the balance between hypothetical goal-directed and habitual systems. We also employed a separate response inhibition control test to assess the behavioral specificity of the results.Results:Acute tryptophan depletion produced a shift of behavioral performance towards habitual responding as indexed by performance on the slip-of-action test. Moreover, greater habitual responding in the acute tryptophan depletion group was predicted by a steeper decline in plasma tryptophan levels. In contrast, acute tryptophan depletion left intact the ability to use discriminative stimuli to guide instrumental choice as indexed by the instrumental learning stage and did not impair inhibitory response control.Conclusions:The major implication of this study is that serotonin modulates the balance between goal-directed and stimulus-response habitual systems of behavioral control. Our findings thus imply that diminished serotonin neurotransmission shifts behavioral control towards habitual responding.

The effect of acute exercise on cognitive performance in children with and without ADHD

BackgroundAttention deficit hyperactivity disorder (ADHD) is a common childhood disorder that affects approximately 11% of children in the United States. Research supports that a single session of exercise benefits cognitive performance by children, and a limited number of studies have demonstrated that these effects can also be realized by children with ADHD. The purpose of this study was to examine the effect of acute exercise on cognitive performance by children with and without ADHD. MethodsChildren with and without ADHD were asked to perform cognitive tasks on 2 days following treatment conditions that were assigned in a random, counterbalanced order. The treatment conditions consisted of a 30-min control condition on 1 day and a moderate intensity exercise condition on the other day. ResultsExercise significantly benefited performance on all three conditions of the Stroop Task, but did not significantly affect performance on the Tower of London or the Trail Making Test. Conclusionchildren with and without ADHD realize benefits in speed of processing and inhibitory control in response to a session of acute exercise, but do not experience benefits in planning or set shifting.

Right inferior frontal cortex: addressing the rebuttals.

We recently provided an updated theory of the role of posterior ventral right inferior frontal cortex (hereafter rIFC) in inhibitory response control (Aron et al., 2014). We claimed that when rIFC is triggered by a stop signal, unexpected event or endogenous rule, it engages a brake; i.e., it slows, pauses, or completely stops an action via one or more rIFC-based fronto-basal-ganglia networks.

Alpha 2A adrenergic receptor agonist, guanfacine, attenuates cocaine-related impairments of inhibitory response control and working memory in animal models

There is considerable evidence that centrally acting α2A adrenergic receptor agonists can attenuate impairments in executive function that result from dysfunction of the prefrontal cortex. Such positive effects resulted in the recent approval by the United States Food and Drug Administration (FDA) of the α2A agonists clonidine and guanfacine for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD), but also suggest that they could have beneficial effects in substance abuse disorders and other neuropsychiatric conditions. The purpose of this study was to evaluate guanfacine for its ability to attenuate behavioral alterations associated with acute cocaine exposure in rats trained to perform a task of sustained attention, the five choice serial reaction time task (5C-SRTT) and monkeys trained to perform a task of working/short term memory, the delayed match to sample (DMTS) task. In the rodent 5C-SRTT acute intraperitoneal (i.p.) administration of cocaine (3.5–15.0mg/kg) did not affect accuracy, but was associated with dose-dependent increases in premature responses and timeout responses. Guanfacine (0.1–1.0mg/kgi.p.) dose-dependently decreased premature responses and timeout responses associated with cocaine and it attenuated similar deficits in inhibitory response control observed in a variable ITI version of the 5C-SRTT. In the DMTS task in monkeys, acute intramuscular (i.m.) administration of cocaine (4.0mg/kg) was associated with impairments in accuracy at long delay intervals, an effect that was attenuated by guanfacine (0.4mg/kg). These animal studies suggest that guanfacine may have therapeutic potential for treating impairments of executive function that are associated with the abuse of cocaine.

A comparison of three types of web-based inhibition training for the reduction of alcohol consumption in problem drinkers: study protocol.

BackgroundProblem drinkers have poor inhibitory control (disinhibition). Previous studies have demonstrated that various forms of ‘inhibition training’ can reduce alcohol consumption in the laboratory and at short-term follow-up, but their longer-term efficacy and mechanisms of action are unknown. In this phase 2 randomised controlled trial we will contrast the effects of three forms of inhibition training and a control intervention, delivered via the Internet in multiple sessions over four weeks, on alcohol consumption in heavy drinkers.Methods/designHeavy drinkers who are interested in reducing their alcohol consumption will receive a brief intervention and will monitor their own alcohol intake for one week before being randomised to one of four treatment groups: 1. General inhibition training; 2. Cue-Specific inhibition training; 3. Alcohol No-Go training; or 4. Control. They will complete up to 14 sessions of training via the Internet over a four-week period, and will be followed-up for a further six weeks after the end of the training period. Primary outcome measures are reductions in alcohol consumption and heavy drinking days. The number of abstinent days is a secondary outcome measure. We will also investigate changes in inhibitory control and automatic alcohol affective associations in response to training.DiscussionThis study will establish if web-based inhibition training can help problem drinkers to reduce their alcohol intake, and it will identify which form(s) of inhibition training are most effective.Trial registationTrial Registation number: ISRCTN55671858.

Serotonin and inhibitory response control: Focusing on the role of 5-HT1A receptors

Disturbances in behavioral inhibition are key features in several neurological and psychiatric disorders, such as attention-deficit/hyperactivity disorder, Parkinson׳s disease and substance use disorders. Therefore, elucidating the neural correlates of inhibitory control processes is crucial for developing novel treatment strategies to ameliorate the symptomatology of these disorders and to improve the quality of life. The development of preclinical translational paradigms to study inhibitory control processes has greatly enhanced our neurobiological understanding of these cognitive processes. Over the last decades, emphasis has been mainly on monoamines including dopamine and serotonin and their contribution to behavioral inhibition. This short review will focus on the involvement of the serotonergic system, and in particular serotonin1A receptors, in inhibitory control processes.

Repeated exposures to diisopropylfluorophosphate result in impairments of sustained attention and persistent alterations of inhibitory response control in rats

Organophosphate (OP)-based chemicals are used worldwide for many purposes and they have likely saved millions of people from starvation and disease. However, due to their toxicity they can also pose a significant environmental risk. While considerable research has focused on the acute symptoms and long-term consequences of overtly toxic exposures to OPs, less attention has been given to the subject of repeated exposures to levels that are not associated with acute symptoms (subthreshold exposures). There is clinical evidence indicating that this type of OP exposure can lead to prolonged deficits in cognition; however only a few studies have addressed this issue prospectively in animal models. In this study, repeated subthreshold exposures to the OP nerve agent diisopropylfluorophosphate (DFP) were evaluated in a 5-Choice Serial Reaction Time Task (5C-SRTT), an animal model of sustained attention. Adult rats were trained to stably perform the 5C-SRTT and then injected subcutaneously with vehicle or DFP of 0.5mg/kg every other day for 30days. Behavioral testing occurred daily during the DFP-exposure period and throughout a 45day (OP-free) washout period. Compared to vehicle-treated controls, DFP-treated rats exhibited deficits in accuracy, increases in omissions and timeout responses during the OP exposure period, while no significant effects on premature responses, perseverative responses, or response latencies were noted. While the increase in timeout responses remained detectible during washout, all other DFP-related alterations in 5C-SRTT performance abated. When the demands of the task were increased by the presentation of variable intertrial intervals, premature responses were also elevated in DFP-treated rats during the washout period. These results indicate that repeated exposures to subthreshold doses of DFP lead to reversible impairments in sustained attention as well as persistent impairments of inhibitory response control in rats.

Acute effects of alcohol on inhibitory control and simulated driving in DUI offenders

IntroductionThe public health costs associated with alcohol-related traffic accidents have prompted considerable research aimed at identifying characteristics of individuals who drive under the influence (DUI) in order to improve treatment and prevention strategies. Survey studies consistently show that DUI offenders self-report higher levels of impulsivity compared to their nonoffending counterparts. However, little is known about how individuals with a DUI history respond under alcohol. Inhibitory control is a behavioral component of impulsivity thought to underlie risky drinking and driving behaviors. MethodThe present study examined the degree to which DUI drivers display deficits of inhibitory control in response to alcohol and the degree to which alcohol impaired their simulated driving performance. It was hypothesized that DUI offenders would display an increased sensitivity to the acute impairing effects of alcohol on simulated driving performance. Young adult drivers with a history of DUI and a demographically-comparable group of drivers with no history of DUI (controls) were tested following a 0.65g/kg dose of alcohol and a placebo. Inhibitory control was measured by using a cued go/no-go task. Drivers then completed a driving simulation task that yielded multiple indicators of driving performance, such as within-lane deviation, steering rate, centerline crossings and road edge excursions, and drive speed. ResultsResults showed that although DUI offenders self-reported greater levels of impulsivity than did controls, no group differences were observed in the degree to which alcohol impaired inhibitory control and driving performance. The findings point to the need to identify other aspects of behavioral dysfunction underlying the self-reported impulsivity among DUI offenders, and to better understand the specific driving situations that might pose greater risk to DUI offenders. Practical applicationsThe systematic study of candidate cognitive deficits in DUI offenders will provide important information on their role in risky driving behavior and decisions to drink and drive. Such information is critical for guiding new interventions for DUI offenders that will move treatment beyond general addiction counseling.

Genetics of preparation and response control in ADHD: the role of DRD4 and DAT1

Difficulties with performance and brain activity related to attentional orienting (Cue-P3), cognitive or response preparation (Cue-CNV) and inhibitory response control (Nogo-P3) during tasks tapping executive functions are familial in ADHD and may represent endophenotypes. The aim of this study was to clarify the impact of dopamine receptor D4 (DRD4) and dopamine transporter (DAT1) gene polymorphisms on these processes in ADHD and control children. Behavioural and electrophysiological parameters from cued continuous performance tests with low and high attentional load were assessed in boys with ADHD combined type (N=94) and controls without family history of ADHD (N=31). Both groups were split for the presence of at least one DRD4 7-repeat allele and the DAT1 10-6 haplotype. Children with ADHD showed diminished performance and lower Cue-P3, CNV and Nogo-P3 amplitudes. Children with DRD4 7R showed similar performance problems and lower Cue-P3 and CNV, but Nogo-P3 was not reduced. Children with the DAT1 10-6 haplotype had no difficulties with performance or Cue-P3 and CNV, but contrary to expectations increased Nogo-P3. There were no Genotype by ADHD interactions. This study detected specific effects of DRD4 7R on performance and brain activity related to attentional orienting and response preparation, while DAT1 10-6 was associated with elevated brain activity related to inhibitory response control, which potentially compensates increased impulsivity. As these genotype effects were additive to the impact of ADHD, the current results indicate that DRD4 and DAT1 polymorphisms are functionally relevant risk factors for ADHD and presumably other disorders sharing these endophenotypes.

Abnormal proactive and reactive cognitive control during conflict processing in major depression.

According to the Dual Mechanisms of Control framework, cognitive control consists of two complementary components: proactive control refers to anticipatory maintenance of goal-relevant information, whereas reactive control acts as a correction mechanism that is activated when a conflict occurs. Possibly, the well-known diminished inhibitory control in response to negative stimuli in Major Depressive Disorder (MDD) patients stems from a breakdown in proactive control, and/or anomalies in reactive cognitive control. In our study, MDD patients specifically showed increased response latencies when actively inhibiting a dominant response to a sad compared with a happy face. This condition was associated with a longer duration of a dominant ERP topography (800-900 ms poststimulus onset) and a stronger activity in the bilateral dorsal anterior cingulate cortex, reflecting abnormal reactive control when inhibiting attention to a negative stimulus. Moreover, MDD patients showed abnormalities in proactive cognitive control when preparing for the upcoming imperative stimulus (abnormal modulation of the contingent negative variation component), accompanied by more activity in brain regions belonging to the default mode network. All together, deficits to inhibit attention to negative information in MDD might originate from an abnormal use of both proactive resources and reactive control processes.

Sequential inhibitory control processes assessed through simultaneous EEG–fMRI

Inhibitory response control has been extensively investigated in both electrophysiological (ERP) and hemodynamic (fMRI) studies. However, very few multimodal results address the coupling of these inhibition markers. In fMRI, response inhibition has been most consistently linked to activation of the anterior insula and inferior frontal cortex (IFC), often also the anterior cingulate cortex (ACC). ERP work has established increased N2 and P3 amplitudes during NoGo compared to Go conditions in most studies. Previous simultaneous EEG–fMRI imaging reported association of the N2/P3 complex with activation of areas like the anterior midcingulate cortex (aMCC) and anterior insula. In this study we investigated inhibitory control in 23 healthy young adults (mean age=24.7, n=17 for EEG during fMRI) using a combined Flanker/NoGo task during simultaneous EEG and fMRI recording. Separate fMRI and ERP analysis yielded higher activation in the anterior insula, IFG and ACC as well as increased N2 and P3 amplitudes during NoGo trials in accordance with the literature. Combined analysis modelling sequential N2 and P3 effects through joint parametric modulation revealed correlation of higher N2 amplitude with deactivation in parts of the default mode network (DMN) and the cingulate motor area (CMA) as well as correlation of higher central P3 amplitude with activation of the left anterior insula, IFG and posterior cingulate. The EEG–fMRI results resolve the localizations of these sequential activations. They suggest a general role for allocation of attentional resources and motor inhibition for N2 and link memory recollection and internal reflection to P3 amplitude, in addition to previously described response inhibition as reflected by the anterior insula.

Associations between inhibitory control, respiratory sinus arrhythmia, and externalizing problems in early childhood

Polyvagal theory provides a framework for understanding connections between children's autonomic regulation, cognitive functioning, and behavioral adjustment. Parasympathetic regulation has been associated with executive functions and externalizing problems (EP), and children with EP demonstrate deficits in inhibition of prepotent responding, or inhibitory control (IC). We examined parasympathetic regulation of cardiac reactivity during two IC tasks in 144 children (M = 5.61 years, SD = 1.09) ranging from low to clinical levels of EP. Overall children with more EP evidenced greater RSA suppression during IC tasks than did children with fewer EP, and degree of RSA suppression also moderated associations between IC performance and EP. Only for children who showed stronger RSA suppression was accuracy of IC response inversely associated with EP, and latency of response for one task positively associated with EP. This study provides insight into the role of parasympathetic mechanisms in children's cognitive regulation of impulsive and aggressive behaviors.

Cognitive control of response inhibition and switching: Hemispheric lateralization and hand preference

Changing environmental constraints often make already prepared responses unnecessary or inappropriate. Under such circumstances, cognitive control enables to suppress the response or switch to alternative behavior. Here, we examine the neural dynamics of both functions in left- and right-handers who performed two variants of a paradigm that required either inhibition of the response or switching the response between hands. The EEG coherence data showed strengthening of interregional coupling in the alpha band (8–12Hz) following the target cues with an essential contribution of fronto-medial circuitry and a specific involvement of parietal areas in response switching. Brain-behavioral correlations revealed the functional significance of left-sided regions for successful response inhibition and switching, underlining the significant role of the left hemisphere for the organization of goal-directed activities. This lateralization pattern was observed for both left- and right-handers and suggests dominance of higher-order aspects of action planning in the left hemisphere.

Impaired inhibitory control in anorexia nervosa elicited by physical activity stimuli

Besides food restriction, hyperactivity is considered a key behavioral trait of anorexia nervosa (AN), playing a major role in the pathogenesis and progression of the disorder. However, the underlying neurophysiology remains poorly understood. We used functional magnetic resonance imaging during two affective go/no-go tasks to probe inhibitory control in response to stimuli depicting physical activity vs inactivity and food vs non-food in AN patients compared with 26 healthy athlete and non-athlete controls. We hypothesized that neural correlates of behavioral inhibition are biased by the emotional information of the stimuli in AN patients, leading to a differential neural inhibitory pattern during the two tasks. Indeed, we found reduced response inhibition for food and non-food images in the putamen, while stimuli depicting physical activity resulted in an exaggerated response of the prefrontal cortex (PFC) and cerebellum in AN patients. However, both AN patients and athletes revealed an increased response in the somatosensory cortex to physical activity stimuli. These results suggest that physical activity stimuli might place an increased demand on the inhibitory control system in AN patients. The resulting hyperactivity of the PFC and cerebellum may lead to altered executive function and motor control, sustaining increased physical activity in AN patients.

Prefrontal hypoactivity associated with impaired inhibition in stimulant-dependent individuals but evidence for hyperactivation in their unaffected siblings.

A neurocognitive endophenotype has been proposed for stimulant dependence, based on behavioral measures of inhibitory response control associated with white matter changes in the frontal cortex. This study investigated the functional neuroimaging correlates of inhibitory response control, as functional activity serves as a more dynamic measure than brain structure, allowing refinement of the suggested endophenotype. Stimulant-dependent individuals (SDIs), their unaffected siblings (SIBs), and healthy controls (CTs) performed the stop-signal task, including stop-signal reaction time (SSRT) as a measure of response inhibition, while undergoing functional magnetic resonance imaging. SDIs had impaired response inhibition accompanied by hypoactivation in the ventrolateral prefrontal cortex (PFC). In addition, they demonstrated hypoactivation in the anterior cingulate when failing to stop. In contrast, no hypoactivations were noted in their unaffected SIBs. Rather, they exhibited increased activation in the dorsomedial PFC relative to controls, together with inhibitory performance that was intermediate between that of the stimulant group and the healthy CT group. Such hyperactivations within the neurocircuitry underlying response inhibition and control are suggestive of compensatory mechanisms that could be protective in nature or could reflect coping with a pre-existing vulnerability, thus expressing potential aspects of resilience. The functional activation associated with response inhibition and error monitoring showed differential patterns of results between SDIs and their unaffected first-degree relatives, suggesting that the proposed endophenotype does not generalize to functional brain activity.

Temporally distinct cognitive effects following acute administration of ketamine and phencyclidine in the rat

Non-competitive N-methyl-d-aspartate receptor (NMDAR) antagonists such as phencyclidine (PCP) and ketamine are commonly and interchangeably used to model aspects of schizophrenia in animals. We compared here the effects of acute administration of these compounds over a range of pre-treatment times in tests of instrumental responding (VI 30s response schedule), simple reaction time (SRT) and cognitive flexibility (reversal learning and attentional set shifting digging task) in rats. At standard pre-treatment times (15–30min), both ketamine and PCP produced overall response suppression in VI 30 and increased reaction times in SRT suggesting that any concomitant cognitive performance deficits are likely to be confounded by motor and/or motivational changes. However, the use of extended pre-treatment times produced deficits in cognitive flexibility measured up to 4h after drug administration in the absence of motor/motivational impairment. Generally, PCP increased impulsive responding in the SRT indicating a possible loss of inhibitory response control that may have contributed to deficits observed in reversal learning and attentional set-shifting. In contrast to PCP, ketamine did not have the same effect on impulsive responding, and possibly as a consequence produced more subtle cognitive deficits in attentional set-shifting. In summary, acute treatment with NMDAR antagonists can produce cognitive deficits in rodents that are relevant to schizophrenia, provided that motor and/or motivational effects are allowed to dissipate. The use of longer pre-treatment times than commonly employed might be advantageous. Also, ketamine, which is more frequently used in clinical settings, did not produce as extensive cognitive deficits as PCP.

Strategy modulates spatial perspective-taking: evidence for dissociable disembodied and embodied routes

Previous research provides evidence for a dissociable embodied route to spatial perspective-taking that is under strategic control. The present experiment investigated further the influence of strategy on spatial perspective-taking by assessing whether participants may also elect to employ a separable “disembodied” route loading on inhibitory control mechanisms. Participants (N = 92) undertook both the “own body transformation” (OBT) perspective-taking task, requiring speeded spatial judgments made from the perspective of an observed figure, and a control task measuring ability to inhibit spatially compatible responses in the absence of a figure. Perspective-taking performance was found to be related to performance on the response inhibition control task, in that participants who tended to take longer to adopt a new perspective also tended to show a greater elevation in response times when inhibiting spatially compatible responses. This relationship was restricted to those participants reporting that they adopted the perspective of another by reversing left and right whenever confronted with a front-view figure; it was absent in those participants who reported perspective-taking by mentally transforming their spatial orientation to align with that of the figure. Combined with previously published results, these findings complete a double dissociation between embodied and disembodied routes to spatial perspective-taking, implying that spatial perspective-taking is subject to modulation by strategy, and suggesting that embodied routes to perspective-taking may place minimal demands on domain general executive functions.

Familiality of neural preparation and response control in childhood attention deficit-hyperactivity disorder

Patients with attention deficit-hyperactivity disorder (ADHD) exhibit difficulties in multiple attentional functions. Although high heritability rates suggest a strong genetic impact, aetiological pathways from genes and environmental factors to the ADHD phenotype are not well understood. Tracking the time course of deviant task processing using event-related electrophysiological brain activity should characterize the impact of familiality on the sequence of cognitive functions from preparation to response control in ADHD. Method Preparation and response control were assessed using behavioural and electrophysiological parameters of two versions of a cued continuous performance test with varying attentional load in boys with ADHD combined type (n=97), their non-affected siblings (n=27) and control children without a family history of ADHD (n=43). Children with ADHD and non-affected siblings showed more variable performance and made more omission errors than controls. The preparatory Cue-P3 and contingent negative variation (CNV) following cues were reduced in both ADHD children and their non-affected siblings compared with controls. The NoGo-P3 was diminished in ADHD compared with controls whilst non-affected siblings were located intermediate but did not differ from both other groups. No clear familiality effects were found for the Go-P3. Better task performance was further associated with higher CNV and P3 amplitudes. Impairments in performance and electrophysiological parameters reflecting preparatory processes and to some extend also for inhibitory response control, especially under high attentional load, appeared to be familially driven in ADHD and may thus constitute functionally relevant endophenotypes for the disorder.