Unsuccessful Stop Research Articles

Differential Recruitment of Inhibitory Control Processes by Directed Forgetting and Thought Substitution.

Humans have the ability to intentionally forget information via different strategies, included suppression of encoding (directed forgetting) and mental replacement of the item to encode (thought substitution). These strategies may rely on different neural mechanisms; namely, encoding suppression may induce prefrontally mediated inhibition, whereas thought substitution is potentially accomplished through modulating contextual representations. Yet, few studies have directly related inhibitory processing to encoding suppression, or tested its involvement in thought substitution. Here, we directly tested whether encoding suppression recruits inhibitory mechanisms with a cross-task design, relating the behavioral and neural data from male and female participants in a Stop Signal task (a task specifically testing inhibitory processing) to a directed forgetting task with both encoding suppression (Forget) and thought substitution (Imagine) cues. Behaviorally, Stop Signal task performance (stop signal reaction times) was related to the magnitude of encoding suppression, but not thought substitution. Two complementary neural analyses corroborated the behavioral result. Namely, brain-behavior analysis demonstrated that the magnitude of right-frontal beta activity following stop signals was related to stop signal reaction times and successful encoding suppression, but not thought substitution; and classifiers trained to discriminate successful and unsuccessful stopping in the Stop Signal task could also classify successful and unsuccessful forgetting following Forget cues, but not Imagine cues. Importantly, inhibitory neural mechanisms were engaged following Forget cues at a later time than motor stopping. These findings not only support an inhibitory account of directed forgetting, and that thought substitution engages separate mechanisms, but also potentially identify a specific time in which inhibition occurs when suppressing encoding.SIGNIFICANCE STATEMENT Forgetting often seems like an unintended experience, but forgetting can be intentional, and can be accomplished with multiple strategies. These strategies, including encoding suppression and thought substitution, may rely on different neural mechanisms. Here, we test the hypothesis that encoding suppression engages domain-general prefrontally driven inhibitory control mechanisms, while thought substitution does not. Using cross-task analyses, we provide evidence that encoding suppression engages the same inhibitory mechanisms used for stopping motor actions, but these mechanisms are not engaged by thought substitution. These findings not only support the notion that mnemonic encoding processes can be directly inhibited, but also have broad relevance, as certain populations with disrupted inhibitory processing may be more successful accomplishing intentional forgetting through thought substitution strategies.

Using event-related potentials to characterize inhibitory control and self-monitoring across impulsive and compulsive phenotypes: a dimensional approach to OCD.

"Subsyndromal" obsessive-compulsive disorder symptoms (OCDSs) are common and cause impaired psychosocial functioning. OCDSs are better captured by dimensional models of psychopathology, as opposed to categorical diagnoses. However, such dimensional approaches require a deep understanding of the underlying neurocognitive drivers and impulsive and compulsive traits (ie, neurocognitive phenotypes) across symptoms. This study investigated inhibitory control and self-monitoring across impulsivity, compulsivity, and their interaction in individuals (n = 40) experiencing mild-moderate OCDSs. EEG recording concurrent with the stop-signal task was used to elicit event-related potentials (ERPs) indexing inhibitory control (ie, N2 and P3) and self-monitoring (ie, error-related negativity and correct-related negativity (CRN): negativity following erroneous or correct responses, respectively). During unsuccessful stopping, individuals high in both impulsivity and compulsivity displayed enhanced N2 amplitude, indicative of conflict between the urge to respond and need to stop (F(3, 33) = 1.48, P < .05, 95% Cl [-0.01, 0.001]). Individuals high in compulsivity and low in impulsivity showed reduced P3 amplitude, consistent with impairments in monitoring failed inhibitory control (F(3, 24) = 2.033, P < .05, 95% CI [-0.002, 0.045]). Following successful stopping, high compulsivity (independent of impulsivity) was associated with lower CRN amplitude, reflecting hypo-monitoring of correct responses (F(4, 32) = 4.76, P < .05, 95% CI [0.01, 0.02]), and with greater OCDS severity (F(3, 36) = 3.32, P < .05, 95% CI [0.03, 0.19]). The current findings provide evidence for differential, ERP-indexed inhibitory control and self-monitoring profiles across impulsive and compulsive phenotypes in OCDSs.

Dynamical EEG Indices of Progressive Motor Inhibition and Error-Monitoring.

Response inhibition has been widely explored using the stop signal paradigm in the laboratory setting. However, the mechanism that demarcates attentional capture from the motor inhibition process is still unclear. Error monitoring is also involved in the stop signal task. Error responses that do not complete, i.e., partial errors, may require different error monitoring mechanisms relative to an overt error. Thus, in this study, we included a “continue go” (Cont_Go) condition to the stop signal task to investigate the inhibitory control process. To establish the finer difference in error processing (partial vs. full unsuccessful stop (USST)), a grip-force device was used in tandem with electroencephalographic (EEG), and the time-frequency characteristics were computed with Hilbert–Huang transform (HHT). Relative to Cont_Go, HHT results reveal (1) an increased beta and low gamma power for successful stop trials, indicating an electrophysiological index of inhibitory control, (2) an enhanced theta and alpha power for full USST trials that may mirror error processing. Additionally, the higher theta and alpha power observed in partial over full USST trials around 100 ms before the response onset, indicating the early detection of error and the corresponding correction process. Together, this study extends our understanding of the finer motor inhibition control and its dynamic electrophysiological mechanisms.

S76. PROACTIVE AND REACTIVE RESPONSE INHIBITION IN INDIVIDUAL WITH SCHIZOTYPY: AN ERP STUDY

BackgroundSchizotypy, a subclinical group at risk for schizophrenia, have been found to show impairments in response inhibition. Recent studies differentiated proactive inhibition (a preparatory process before the stimuli appears) and reactive inhibition (the inhibition of a pre-potent or already initiated response). However, it remains unclear whether both proactive and reactive inhibition are impaired in schizotypy and what are the neural mechanisms. The present event-related potential study used an adapted stop-signal task to examine the two inhibition processes and the underlying neural mechanisms in schizotypy compared to healthy controls (HC).MethodsA total of 21 individuals with schizotypy and 25 matched HC participated in this study. To explore different degrees of proactive inhibition, we set three conditions: a “certain” go condition which no stop signal occurred, a “17% no go” condition in which stop signal would appear in 17% of trials, and a “33% no go” condition in which stop signal would appear in 33% of trials. All participants completed all the conditions, and EEG was recorded when participants completed the task.ResultsBehavioral results showed that in both schizotypy and HC, the reaction times (RT) of go trials were significantly prolonged as the no go percentage increased, and HC showed significantly longer go RT compared with schizotypy in both “17% no go” and “33% no go” conditions, suggesting greater proactive inhibition in HC. Stop signal reaction times (SSRTs) in “33% no go” condition was shorter than “17% no go” condition in both groups. Schizotypy showed significantly longer SSRTs in both “17% no go” and “33% no go” conditions than HC, indicating schizotypy relied more on reactive inhibition. ERP results showed that schizotypy showed larger overall N1 for go trials than HC irrespective of condition, which may indicate a compensation process in schizotypy. Schizotypy showed smaller N2 on both successful and unsuccessful stop trials in “17% no go” conditions than HC, while no group difference was found in “33% no go” conditions for stop trials, which may indicate impaired error processing.DiscussionThese results suggested that schizotypy tended to be impaired in both proactive control and reactive control processes.

Shared Response Inhibition Deficits but Distinct Error Processing Capacities Between Schizophrenia and Obsessive-Compulsive Disorder Patients Revealed by Event-Related Potentials and Oscillations During a Stop Signal Task.

Background: Schizophrenia (SCH) patients are at high risk for obsessive-compulsive syndrome, which can lead to difficulty in differential diagnosis between SCH and obsessive-compulsive disorder (OCD). It would be of great clinical value to identify objective markers for these diseases based on behavioral or neurological manifestations. Deficient response inhibition has been reported in both SCH and OCD; however, it is unclear if common or distinct neural abnormalities underlie this impairment. Methods: To address this question, we compared Stop signal task performance and associated event-related potentials (ERPs) and event-related oscillation (ERO) among 24 SCH patients, 25 OCD patients, and 27 healthy controls (HCs). Results: In successful Stop trials, both SCH and OCD patients showed prolonged Stop signal response time, reduced ERP-P3 component amplitude, and weaker theta-band synchronization compared to HCs, while there were no significant differences between patient groups. In unsuccessful Stop trials, however, SCH patients demonstrated significantly lower P3 amplitudes and weaker theta-band activity than OCD patients. In addition, Stop accuracy rate in SCH patients was negatively correlated with Positive subscale score of the Positive and Negative Syndrome Scale. Conclusions: These results provide evidence that impaired response inhibition in SCH and OCD arises from common underlying neural processing abnormalities. However, the lower P3 amplitude and weaker theta-band activity in SCH patients in unsuccessful Stop trials suggest distinct neural activity patterns related to error processing. These differences in ERPs and ERO may provide clues to unique neurological abnormalities in SCH and provide objective measures for differential diagnosis.

Influence of Time Pressure on Inhibitory Brain Control During Emergency Driving

It is believed that failures of people’s reaction to emergencies occurred during driving are closely related to the inhibitory mechanism of brain’s operations. To investigate the role of this function in emergency driving, two virtual realistic driving conditions based on stop signal task were designed and time limitation was manipulated to increase the stress in one condition. Sixteen subjects with behavioral encephalography recordings were collected and analyzed. By comparing successful and unsuccessful stop trials with event-related spectral perturbation analysis, ${\delta }$ and ${\theta }$ band power increases in frontal and central areas are correlated with driving inhibitory control of the brain. Moreover, ${\beta }$ and ${\gamma }$ band power in frontal and central areas showed more increases upon stress condition. Time pressure in driving could adjust the operation of brain’s inhibition control, to benefit the people’s reactive ability upon emergency.

Subthalamic Nucleus Activation Occurs Early during Stopping and Is Associated with Trait Impulsivity.

The subthalamic nucleus (STN) is thought to be a central regulator of behavioral inhibition, which is thought to be a major determinant of impulsivity. Thus, it would be reasonable to hypothesize that STN function is related to impulsivity. However, it has been difficult to test this hypothesis because of the challenges in noninvasively and accurately measuring this structure's signal in humans. We utilized a novel approach for STN signal localization that entails identifying this structure directly on fMRI images for each individual participant in native space. Using this approach, we measured STN responses during the stop signal task in a sample of healthy adult participants. We confirmed that the STN exhibited selective activation during "Stop" trials. Furthermore, the magnitude of STN activation during successful Stop trials inversely correlated with individual differences in trait impulsivity as measured by a personality inventory. Time course analysis revealed that early STN activation differentiated successful from unsuccessful Stop trials, and individual differences in the magnitude of STN activation inversely correlated with stop signal RT, an estimate of time required to stop. These results are consistent with the STN playing a central role in inhibition and related behavioral proclivities, with implications for both normal range function and clinical syndromes of inhibitory dyscontrol. Moreover, the methods utilized in this study for measuring STN fMRI signal in humans may be gainfully applied in future studies to further our understanding of the role of the STN in regulating behavior and neuropsychiatric conditions.

Effects of nicotine and atomoxetine on brain function during response inhibition

The nicotinic acetylcholine receptor (nAChR) agonist nicotine and the noradrenaline transporter inhibitor atomoxetine are widely studied substances due to their propensity to alleviate cognitive deficits in psychiatric and neurological patients and their beneficial effects on some aspects of cognitive functions in healthy individuals. However, despite growing evidence of acetylcholine-noradrenaline interactions, there are only very few direct comparisons of the two substances. Here, we investigated the effects of nicotine and atomoxetine on response inhibition in the stop-signal task and we characterised the neural correlates of these effects using blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) at 3T. Nicotine (7 mg dermal patch) and atomoxetine (60 mg per os) were applied to N = 26 young, healthy adults in a double-blind, placebo-controlled, cross-over, within-subjects design. BOLD images were collected during a stop-signal task that controlled for infrequency of stop trials. There were no drug effects on behavioural performance or subjective state measures. However, there was a pronounced upregulation of activation in bilateral prefrontal and left parietal cortex following nicotine during successful compared to unsuccessful stop trials. The effect of nicotine on BOLD during failed stop trials was correlated across individuals with a measure of trait impulsivity. Atomoxetine, however, had no discernible effects on BOLD. We conclude that nicotine effects on brain function during inhibitory control are most pronounced in individuals with higher levels of impulsivity. This finding is compatible with previous evidence of nicotine effects on stop-signal task performance in highly impulsive individuals and implicates the nAChR in the neural basis of impulsivity.

The effect of vagus nerve stimulation on response inhibition.

In the current study, we explored whether vagus nerve stimulation (VNS) in patients with epilepsy, which is believed to increase norepinephrine (NE) levels via activation of the locus coeruleus, would positively affect response inhibition. Moreover, we tried to identify the dynamics of the underlying neural processes by investigating event-related potentials (ERPs) and pupil size. Patients performed a stop-signal task once when stimulation was switched on and once when it was switched off. We found a correlational pattern suggesting that patients who clinically benefit more from VNS treatment also show a larger behavioral advantage, in terms of faster response inhibition, when the vagus nerve is being stimulated. Event-related potential (ERP) results suggested more pronounced reactive inhibition when stimulation was switched on, independent of the individual amount of seizure reduction. Transient go-locked pupil size was increased from go trials to successful stop trials to unsuccessful stop trials but without displaying a clear VNS effect, which however, might relate to limited sensitivity. We conclude that VNS likely has a positive effect on response inhibition, at least in patients with epilepsy that benefit clinically from the treatment, presumably relating to enhancements of response-inhibition mechanisms and, therefore, identify enhanced response inhibition as a possible cognitive benefit of VNS.

Phase modulation-based response-inhibition outcome prediction in translational scenario of stop-signal task.

In this paper, a method is proposed to predict the resting-state outcomes of participants based on their electroencephalogram (EEG) signals recorded before the successful /unsuccessful response inhibition. The motivation of this study is to enhance the shooter performance for shooting the target, when their EEG patterns show that they are ready. This method can be used in brain-computer interface (BCI) system. In this study, multi-channel EEG from twenty participants are collected by the electrodes placed at different scalp locations in resting-state time. The EEG trials are used to predict two possible outcomes: successful or unsuccessful stop. Four classifiers (QDC, KNNC, PARZENDC, LDC) are used in this study to evaluation the accuracy of our system. Based on the collected time-domain EEG signals, the phase locking value (PLV) from 5-pair electrodes are calculated and then used as the feature input for the classifiers. Our experimental results show that the proposed method prediction accuracy (leave-one-out) was obtained 95% by QDC classifier.

When the brain simulates stopping: Neural activity recorded during real and imagined stop-signal tasks.

It has been suggested that mental rehearsal activates brain areas similar to those activated by real performance. Although inhibition is a key function of human behavior, there are no previous reports of brain activity during imagined response cancellation. We analyzed event-related potentials (ERPs) and time-frequency data associated with motor execution and inhibition during real and imagined performance of a stop-signal task. The ERPs characteristic of stop trials-that is, the stop-N2 and stop-P3-were also observed during covert performance of the task. Imagined stop (IS) trials yielded smaller stop-N2 amplitudes than did successful stop (SS) and unsuccessful stop (US) trials, but midfrontal theta power similar to that in SS trials. The stop-P3 amplitude for IS was intermediate between those observed for SS and US. The results may be explained by the absence of error-processing and correction processes during imagined performance. For go trials, real execution was associated with higher mu and beta desynchronization over motor areas, which confirms previous reports of lower motor activation during imagined execution and also with larger P3b amplitudes, probably indicating increased top-down attention to the real task. The similar patterns of activity observed for imagined and real performance suggest that imagination tasks may be useful for training inhibitory processes. Nevertheless, brain activation was generally weaker during mental rehearsal, probably as a result of the reduced engagement of top-down mechanisms and limited error processing.

Reactive inhibitory control is reduced in older adults: A behavioural and electroencephalographic study.

Event Abstract Back to Event Reactive inhibitory control is reduced in older adults: A behavioural and electroencephalographic study. Paul Sowman1* 1 Macquarie University, Cognitive Science, Australia Aging is characterised by a decline in the competence of inhibitory processing. The current study used a variant of the stop signal task (SST) to examine two questions in relation to inhibitory control: to what extent does the normal aging process impair reactive and proactive inhibition and to what extent does proactive inhibition impact upon the stop signal reaction time (SSRT)? Two types of go signal were presented in this study. The first type, 'maybe stop' alerted the subject to the possibility that the go signal might be followed by a stop signal. The second type of go signal, 'always go', indicated that there would be no following stop signal. This task allowed a measure of caution (proactive inhibition) as well outright stopping ability (reactive inhibition) to be estimated. Additionally, by explicitly manipulating the probability of the stop signal following the 'maybe stop' signal we were able to gauge whether proactive inhibitory control affected the following reactive inhibitory process. The study was conducted on a group of 48 subjects, 32 of whom were aged 18-25 years and 16 of whom were aged over 50 years. Analysis of the behavioural results revealed a significant effect of age on SSRT and simple reaction time but there was no significant effect on proactive inhibition. In both groups stop probability significantly reduced SSRT and lengthened the response cost. Electroencephalographic (EEG) recordings revealed that the stop signal-evoked P300 was smaller in the old than the young subjects, mirroring the difference in reactive inhibition performance. Furthermore, in both groups the P300 elicited by the stop signal was reduced in amplitude and later in time for unsuccessful stopping compared to successful stopping. The current study further demonstrates that cognitive control is behaviourally impaired in aging and that neurophysiological markers of inhibition index this change. Keywords: Aging, EEG, stop signal task, Inhibitory Control, caution, Eletroencephalography Conference: XII International Conference on Cognitive Neuroscience (ICON-XII), Brisbane, Queensland, Australia, 27 Jul - 31 Jul, 2014. Presentation Type: Poster Topic: Cognition and Executive Processes Citation: Sowman P (2015). Reactive inhibitory control is reduced in older adults: A behavioural and electroencephalographic study.. Conference Abstract: XII International Conference on Cognitive Neuroscience (ICON-XII). doi: 10.3389/conf.fnhum.2015.217.00337 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 19 Feb 2015; Published Online: 24 Apr 2015. * Correspondence: Dr. Paul Sowman, Macquarie University, Cognitive Science, Sydney, Australia, paul.sowman@mq.edu.au Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Paul Sowman Google Paul Sowman Google Scholar Paul Sowman PubMed Paul Sowman Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Dissociable roles of right inferior frontal cortex and anterior insula in inhibitory control: evidence from intrinsic and task-related functional parcellation, connectivity, and response profile analyses across multiple datasets.

The right inferior frontal cortex (rIFC) and the right anterior insula (rAI) have been implicated consistently in inhibitory control, but their differential roles are poorly understood. Here we use multiple quantitative techniques to dissociate the functional organization and roles of the rAI and rIFC. We first conducted a meta-analysis of 70 published inhibitory control studies to generate a commonly activated right fronto-opercular cortex volume of interest (VOI). We then segmented this VOI using two types of features: (1) intrinsic brain activity; and (2) stop-signal task-evoked hemodynamic response profiles. In both cases, segmentation algorithms identified two stable and distinct clusters encompassing the rAI and rIFC. The rAI and rIFC clusters exhibited several distinct functional characteristics. First, the rAI showed stronger intrinsic and task-evoked functional connectivity with the anterior cingulate cortex, whereas the rIFC had stronger intrinsic and task-evoked functional connectivity with dorsomedial prefrontal and lateral fronto-parietal cortices. Second, the rAI showed greater activation than the rIFC during Unsuccessful, but not Successful, Stop trials, and multivoxel response profiles in the rAI, but not the rIFC, accurately differentiated between Successful and Unsuccessful Stop trials. Third, activation in the rIFC, but not rAI, predicted individual differences in inhibitory control abilities. Crucially, these findings were replicated in two independent cohorts of human participants. Together, our findings provide novel quantitative evidence for the dissociable roles of the rAI and rIFC in inhibitory control. We suggest that the rAI is particularly important for detecting behaviorally salient events, whereas the rIFC is more involved in implementing inhibitory control.

Voluntarily-generated unimanual preparation is associated with stopping success: evidence from LRP and lateralized mu ERD before the stop signal

According to the race models of the stop-signal paradigm, stopping success (successful vs. unsuccessful stopping) is attributed to the finishing times of a go and a stop process. In addition to those factors involving processing times, in the present study we sought to use electrophysiological measures to find factors involving activations that could affect stopping success. We hypothesized that voluntarily-generated unimanual preparation would be a factor. To assess voluntarily-generated unimanual preparation in the stop-signal paradigm, we used a selective-stopping task without any precue. The selective-stopping task also allowed us to assess reaction times (RTs) even when stopping was successful. We demonstrated shorter RTs in signal-respond (i.e., unsuccessful stopping) than in signal-inhibit (successful stopping) trials, as is predicted by the race models. More importantly, we also demonstrated different pre-signal lateralized readiness potentials between the two types of trials and larger lateralized mu ERD in signal-respond than in signal-inhibit trials, suggesting that voluntarily-generated unimanual preparation affects stopping success. In addition to what is described in the race models of the stop-signal paradigm, the present results therefore demonstrated measures of pre-signal activations that could influence stopping success.

Revealing the brain's adaptability and the transcranial direct current stimulation facilitating effect in inhibitory control by multiscale entropy

The abilities to inhibit impulses and withdraw certain responses are critical for human's survival in a fast-changing environment. These processes happen fast, in a complex manner, and sometimes are difficult to capture with fMRI or mean electrophysiological brain signal alone. Therefore, an alternative measure that can reveal the efficiency of the neural mechanism across multiple timescales is needed for the investigation of these brain functions. The present study employs a new approach to analyzing electroencephalography (EEG) signal: the multiscale entropy (MSE), which groups data points with different timescales to reveal any occurrence of repeated patterns, in order to theoretically quantify the complexity (indicating adaptability and efficiency) of neural systems during the process of inhibitory control. From this MSE perspective, EEG signals of successful stop trials are more complex and information rich than that of unsuccessful stop trials. We further applied transcranial direct current stimulation (tDCS), with anodal electrode over presupplementary motor area (preSMA), to test the relationship between behavioral modification with the complexity of EEG signals. We found that tDCS can further increase the EEG complexity of the frontal lobe. Furthermore, the MSE pattern was found to be different between high and low performers (divided by their stop-signal reaction time), where the high-performing group had higher complexity in smaller scales and less complexity in larger scales in comparison to the low-performing group. In addition, this between-group MSE difference was found to interact with the anodal tDCS, where the increase of MSE in low performers benefitted more from the anodal tDCS. Together, the current study demonstrates that participants who suffer from poor inhibitory control can efficiently improve their performance with 10min of electrical stimulation, and such cognitive improvement can be effectively traced back to the complexity within the EEG signals via MSE analysis, thereby offering a theoretical basis for clinical intervention via tDCS for deficits in inhibitory control.

Sensorimotor‐independent prefrontal activity during response inhibition

A network of brain regions involving the ventral inferior frontal gyrus/anterior insula (vIFG/AI), presupplementary motor area (pre-SMA) and basal ganglia has been implicated in stopping impulsive, unwanted responses. However, whether this network plays an equal role in response inhibition under different sensorimotor contexts has not been tested systematically. Here, we conducted an fMRI experiment using the stop signal task, a sensorimotor task requiring occasional withholding of the planned response upon the presentation of a stop signal. We manipulated both the sensory modality of the stop signal (visual versus auditory) and the motor response modality (hand versus eye). Results showed that the vIFG/AI and the preSMA along with the right middle frontal gyrus were commonly activated in response inhibition across the various sensorimotor conditions. Our findings provide direct evidence for a common role of these frontal areas, but not striatal areas in response inhibition independent of the sensorimotor contexts. Nevertheless, these three frontal regions exhibited different activation patterns during successful and unsuccessful stopping. Together with the existing evidence, we suggest that the vIFG/AI is involved in the early stages of stopping such as triggering the stop process while the preSMA may play a role in regulating other cortical and subcortical regions involved in stopping.

Fractionating the Impulsivity Construct in Adolescence

The teenage years are often associated with ‘impulsive' behavior; that is, behavior with diminished regard to potential negative consequences. Adolescent impulsivity, while often adaptive, can manifest itself in a range of sub-optimal behaviors, including use of nicotine, alcohol, or illicit substances, symptoms associated with attention deficit hyperactivity disorder (ADHD), or poorer performance on laboratory assays of impulse control. Although these maladaptive behaviors are often co-morbid, their correlation is not perfect. It is therefore increasingly recognized that impulsivity is multi-dimensional, with some predicting that ‘what is generally denoted as impulsivity will be fractionated into distinct forms that may, however, often coexist in the same individual' (Dalley et al, 2011, page 691). Fractionating impulsivity is challenging, not least because of the large sample size needed to ensure an adequate number of participants in each phenotypic group, although recently the ‘population neuroscience' (Paus, 2010) approach has provided these large samples. Data from the IMAGEN (Schumann et al, 2010) project permitted the data-driven identification of impulsivity subtypes by Whelan et al (2012). Nearly 1900 14-year-olds completed a test of motor inhibition—the Stop Signal Task (SST)—while undergoing functional magnetic resonance imaging (fMRI). The large sample size allowed functional brain activity to be decomposed into a smaller number of distinct networks using factor analysis (a data-reduction method). Next, these networks were tested for relationships with various phenotypes. Adolescents who had experimented with either alcohol, cigarettes, or illicit substances showed reduced activity in an orbitofrontal cortex network on successful stop trials, even those with only 1–4 total lifetime alcohol uses. For adolescents who had used illicit substances, there was hyperactivity in a right frontal network (inferior frontal gyrus, cingulate, and insula), an effect that remained even after controlling for nicotine and alcohol effects. In contrast, ADHD symptoms were associated with bilateral frontal (inferior frontal gyri, anterior cingulate, and anterior insula) and basal ganglia networks only on unsuccessful stop trials. Individual differences in the speed of the inhibition process on the SST were associated with activity in the right frontal network and in the basal ganglia. Finally, the right frontal network was also associated with allelic variation in a single-nucleotide polymorphism located in the SLC6A2 gene, which codes for the norepinephrine transporter (see Figure 1). Figure 1 The impulsivity networks and associated phenotypes described in Whelan et al (2012), for both trials on which subjects successfully inhibited an already initiated motor response (Stop Success) and trials on which subjects failed to inhibit (Stop Fail). ... Understanding the neural correlates of impulsivity subtypes is important because it yields insights into the etiology of maladaptive impulsive behaviors. Disentangling the biological basis of substance misuse and ADHD symptoms has proven difficult previously because, for example, adult substance misusers are more likely to retrospectively endorse childhood ADHD symptoms (Ivanov et al, 2008). However, the results of Whelan et al (2012) suggest that ADHD symptoms and adolescent substance misuse can be separated, at least in terms of brain activity during a test of inhibitory control. Furthermore, these results support the role of norepinephrine in modulating impulse control, with implications for treatment of ADHD (Chamberlain et al, 2007). A goal of future research will be to shed more light on the structural, functional, neurochemical, and genetic underpinnings of the various impulsivity brain networks.

Stop-event-related potentials from intracranial electrodes reveal a key role of premotor and motor cortices in stopping ongoing movements

In humans, the ability to withhold manual motor responses seems to rely on a right-lateralized frontal–basal ganglia–thalamic network, including the pre-supplementary motor area and the inferior frontal gyrus (IFG). These areas should drive subthalamic nuclei to implement movement inhibition via the hyperdirect pathway. The output of this network is expected to influence those cortical areas underlying limb movement preparation and initiation, i.e., premotor (PMA) and primary motor (M1) cortices. Electroencephalographic (EEG) studies have shown an enhancement of the N200/P300 complex in the event-related potentials (ERPs) when a planned reaching movement is successfully stopped after the presentation of an infrequent stop-signal. PMA and M1 have been suggested as possible neural sources of this ERP complex but, due to the limited spatial resolution of scalp EEG, it is not yet clear which cortical areas contribute to its generation. To elucidate the role of motor cortices, we recorded epicortical ERPs from the lateral surface of the fronto-temporal lobes of five pharmacoresistant epileptic patients performing a reaching version of the countermanding task while undergoing presurgical monitoring. We consistently found a stereotyped ERP complex on a single-trial level when a movement was successfully cancelled. These ERPs were selectively expressed in M1, PMA, and Brodmann's area (BA) 9 and their onsets preceded the end of the stop process, suggesting a causal involvement in this executive function. Such ERPs also occurred in unsuccessful-stop (US) trials, that is, when subjects moved despite the occurrence of a stop-signal, mostly when they had long reaction times (RTs). These findings support the hypothesis that motor cortices are the final target of the inhibitory command elaborated by the frontal–basal ganglia–thalamic network.

Roles for the pre-supplementary motor area and the right inferior frontal gyrus in stopping action: Electrophysiological responses and functional and structural connectivity

Both the pre-supplementary motor area (preSMA) and the right inferior frontal gyrus (rIFG) are important for stopping action outright. These regions are also engaged when preparing to stop. We aimed to elucidate the roles of these regions by harnessing the high spatio-temporal resolution of electrocorticography (ECoG), and by using a task that engages both preparing to stop and stopping outright. First, we validated the task using fMRI in 16 healthy control participants to confirm that both the preSMA and the rIFG were active. Next, we studied a rare patient with intracranial grid coverage of both these regions, using macrostimulation, diffusion tractography, cortico-cortical evoked potentials (CCEPs) and task-based ECoG. Macrostimulation of the preSMA induced behavioral motor arrest. Diffusion tractography revealed a structural connection between the preSMA and rIFG. CCEP analysis showed that stimulation of the preSMA evoked strong local field potentials within 30 ms in rIFG. During the task, when preparing to stop, there was increased high gamma amplitude (~70-250 Hz) in both regions, with preSMA preceding rIFG by ~750 ms. For outright stopping there was also a high gamma amplitude increase in both regions, again with preSMA preceding rIFG. Further, at the time of stopping, there was an increase in beta band activity (~16 Hz) in both regions, with significantly stronger inter-regional coherence for successful vs. unsuccessful stop trials. The results complement earlier reports of a structural/functional action control network between the preSMA and rIFG. They go further by revealing between-region timing differences in the high gamma band when preparing to stop and stopping outright. They also reveal strong between-region coherence in the beta band when stopping is successful. Implications for theories of action control are discussed.

Rule-Guided Executive Control of Response Inhibition: Functional Topography of the Inferior Frontal Cortex

BackgroundThe human inferior frontal cortex (IFC) is a large heterogeneous structure with distinct cytoarchitectonic subdivisions and fiber connections. It has been found involved in a wide range of executive control processes from target detection, rule retrieval to response control. Since these processes are often being studied separately, the functional organization of executive control processes within the IFC remains unclear.Methodology/Principal FindingsWe conducted an fMRI study to examine the activities of the subdivisions of IFC during the presentation of a task cue (rule retrieval) and during the performance of a stop-signal task (requiring response generation and inhibition) in comparison to a not-stop task (requiring response generation but not inhibition). We utilized a mixed event-related and block design to separate brain activity in correspondence to transient control processes from rule-related and sustained control processes. We found differentiation in control processes within the IFC. Our findings reveal that the bilateral ventral-posterior IFC/anterior insula are more active on both successful and unsuccessful stop trials relative to not-stop trials, suggesting their potential role in the early stage of stopping such as triggering the stop process. Direct countermanding seems to be outside of the IFC. In contrast, the dorsal-posterior IFC/inferior frontal junction (IFJ) showed transient activity in correspondence to the infrequent presentation of the stop signal in both tasks and the left anterior IFC showed differential activity in response to the task cues. The IFC subdivisions also exhibited similar but distinct patterns of functional connectivity during response control.Conclusions/SignificanceOur findings suggest that executive control processes are distributed across the IFC and that the different subdivisions of IFC may support different control operations through parallel cortico-cortical and cortico-striatal circuits.