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Action planning can be construed as the temporary binding of action features to form a representation known as an action file. This file is distinct from other possible, but currently not required actions of the behavioral repertoire. To further this action file approach, we investigated what happens with an initially planned action, which however, is discarded before execution. In two experiments we found consistent evidence for a quick unbinding of action features with discarding. Other possible mechanisms that action discarding might invoke, be it the paradox strengthening of a discarded action plan, the selective suppression of the otherwise intact plan, or the global suppression of all subsequent action, were not or at least less consistently supported. These findings provide a novel perspective on inhibitory action control, which we discuss with respect to its applications to other instances of such inhibitory control as studied in multitasking, stop-signal, directed forgetting, or response-reprogramming paradigms. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: The principle of gain control determines the efficiency of neuronal processing and can be enhanced with pharmacological or brain stimulation methods. It is a key factor for cognitive control, but the degree of how much gain control may be enhanced underlies a physical limit., Methods: To investigate whether methylphenidate (MPH) and transcranial direct current stimulation (tDCS) share common underlying mechanisms and cognitive effects, we administered MPH and anodal tDCS (atDCS) over the right inferior frontal gyrus both separately and combined, while healthy adult participants (n = 104) performed a response selection and inhibition task. The recorded EEG data were analyzed with a focus on theta band activity, and source estimation analyses were conducted., Results: The behavioral data show that MPH and atDCS revealed interactive effects on the ability to inhibit responses. Both MPH and atDCS modulated task-related theta oscillations in the supplementary motor area when applied separately, making a common underlying mechanism likely. When both stimulation methods were combined, there was no doubling of effects in the supplementary motor area but a shift to inferior frontal areas in the cortical network responsible for theta-driven processing., Conclusions: The results indicate that both MPH and atDCS likely share a common underlying neuronal mechanism, and interestingly, they demonstrate interactive effects when combined, which are most likely due to the physical limitations of gain control increases. The current study provides critical groundwork for future combined applications of MPH and non-invasive brain stimulation., (© The Author(s) 2024. Published by Oxford University Press on behalf of CINP.)

Coping with distracting inputs during goal-directed behavior is a common challenge, especially when stopping ongoing responses. The neural basis for this remains debated. Our study explores this using a conflict-modulation Stop Signal task, integrating group independent component analysis (group-ICA), multivariate pattern analysis (MVPA), and EEG source localization analysis. Consistent with previous findings, we show that stopping performance is better in congruent (nonconflicting) trials than in incongruent (conflicting) trials. Conflict effects in incongruent trials compromise stopping more due to the need for the reconfiguration of stimulus-response (S-R) mappings. These cognitive dynamics are reflected by four independent neural activity patterns (ICA), each coding representational content (MVPA). It is shown that each component was equally important in predicting behavioral outcomes. The data support an emerging idea that perception-action integration in action-stopping involves multiple independent neural activity patterns. One pattern relates to the precuneus (BA 7) and is involved in attention and early S-R processes. Of note, three other independent neural activity patterns were associated with the insular cortex (BA13) in distinct time windows. These patterns reflect a role in early attentional selection but also show the reiterated processing of representational content relevant for stopping in different S-R mapping contexts. Moreover, the insular cortex's role in automatic versus complex response selection in relation to stopping processes is shown. Overall, the insular cortex is depicted as a brain hub, crucial for response selection and cancellation across both straightforward (automatic) and complex (conditional) S-R mappings, providing a neural basis for general cognitive accounts on action control., (© 2024 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Reward and cognitive control play crucial roles in shaping goal-directed behavior. Yet, the behavioral and neural underpinnings of interactive effects of both processes in driving our actions towards a particular goal have remained rather unclear. Given the importance of inhibitory control, we investigated the effect of reward prospect on the modulatory influence of automatic versus controlled processes during response inhibition. For this, a performance-contingent monetary reward for both correct response selection and response inhibition was added to a Simon NoGo task, which manipulates the relationship of automatic and controlled processes in Go and NoGo trials. A neurophysiological approach was used by combining EEG temporal signal decomposition and source localization methods. Compared to a non-rewarded control group, rewarded participants showed faster response execution, as well as overall lower response selection and inhibition accuracy (shifted speed-accuracy tradeoff). Interestingly, the reward group displayed a larger interference of the interactive effects of automatic versus controlled processes during response inhibition (i.e., a larger Simon NoGo effect), but not during response selection. The reward-specific behavioral effect was mirrored by the P3 amplitude, underlining the importance of stimulus-response association processes in explaining variability in response inhibition performance. The selective reward-induced neurophysiological modulation was associated with lower activation differences in relevant structures spanning the inferior frontal and parietal cortex, as well as higher activation differences in the somatosensory cortex. Taken together, this study highlights relevant neuroanatomical structures underlying selective reward effects on response inhibition and extends previous reports on the possible detrimental effect of reward-triggered performance trade-offs on cognitive control processes., (© 2023. The Author(s).)

Inhibition of inappropriate behavior is relevant in many everyday situations. Nevertheless, the mechanisms that induce response inhibition based on sensory information and what influences these mechanisms are not entirely understood. We examined neurophysiological processes of perception-action integration in response inhibition and the impact of the pre-trial neurophysiological functional connectivity state in the theta and alpha band on these integration processes. The study was motivated by the Theory of Event Coding framework. Within the trial, fronto-medial theta band activity and occipital alpha band activity revealed an opposing interplay depending on the necessity of (re-)binding event files, i.e., the disintegration and recombination of stimulus-response associations, during response inhibition. When response inhibition required the reconfiguration of event files, this was associated with increased theta band activity but lower alpha band activity, and vice versa for the retrieval of event files. Notably, the most substantial impact of pre-trial connectivity on the within-trial event file binding effect (the difference between conditions that require reconfiguration and those that do not) during response inhibition occurred between fronto-medial areas and areas of the ventral stream in the theta frequency band. This suggests a preparatory top-down control of sensory areas before stimulus presentation. Increased pre-trial connectivity was associated with a decreased event file binding effect in the alpha frequency band and an increased event file binding effect in the theta frequency band during response inhibition. This implies an impact of the pre-trial functional connectivity state on inhibitory gating processes of relevant information and event file (re-)binding during response inhibition. The study shows how perception-action integration during response inhibition is affected by preceding transient neurophysiological connectivity states., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The neurophysiological processes underlying the inhibition of impulsive responses have been studied extensively. While also the role of theta oscillations during response inhibition is well examined, the relevance of resting-state theta activity for inhibitory control processes is largely unknown. We test the hypothesis that there are specific relationships between resting-state theta activity and sensory/motor coding levels during response inhibition using EEG methods. We show that resting theta activity is specifically linked to the stimulus-related fraction of neurophysiological activity in specific time windows during motor inhibition. In contrast, concomitantly coded processes related to decision-making or response selection as well as the behavioral inhibition performance were not associated with resting theta activity. Even at the peak of task-related theta power, where task-related theta activity and resting theta activity differed the most, there was still predominantly a significant correlation between both types of theta activity. This suggests that aspects similar to resting dynamics are evident in the proportion of inhibition-related neurophysiological activity that reflects an "alarm" signal, whose function is to process and indicate the need for cognitive control. Thus, specific aspects of task-related theta power may build upon resting theta activity when cognitive control is necessary., (© 2022. The Author(s).)

High-dose alcohol intoxication is commonly associated with impaired inhibition, but the boundary conditions, as well as associated neurocognitive/neuroanatomical changes have remained rather unclear. This study was motivated by the counterintuitive finding that high-dose alcohol intoxication compromises response inhibition performance when working memory demands were low, but not when they were high. To investigate whether this is more likely to be caused by deficits in cognitive control processes or in attentional processes, we examined event-related (de)synchronization processes in theta and alpha-band activity and performed beamforming analyses on the EEG data of previously published behavioral findings. This yielded two possible explanations: There may be a selective decrease of working memory engagement in case of relatively low demand, which boosts response automatization, ultimately putting more strain on the remaining inhibitory resources. Alternatively, there may be a decrease in proactive preparatory and anticipatory attentional gating processes in case of relatively low demand, hindering attentional sampling of upcoming stimuli. Crucially, both of these interrelated mechanisms reflect differential alcohol effects after the actual motor inhibition process and therefore tend to be processes that serve to anticipate future response inhibition affordances. This provides new insights into how high-dose alcohol intoxication can impair inhibitory control., (© 2022. The Author(s).)

Resting-state neural activity plays an important role for cognitive control processes. Regarding response inhibition processes, an important facet of cognitive control, especially theta-band activity has been the focus of research. Theoretical considerations suggest that the interrelation of resting and task-related theta activity is subject to maturational effects. To investigate whether the relationship between resting theta activity and task-related theta activity during a response inhibition task changes even in young age, we tested N = 166 healthy participants between 8 and 30 years of age. We found significant correlations between resting and inhibitory control-related theta activity as well as behavioral inhibition performance. Importantly, these correlations were moderated by age. The moderation analysis revealed that higher resting theta activity was associated with stronger inhibition-related theta activity in individuals above the age of ~10.7 years. The EEG beamforming analysis showed that this activity is associated with superior frontal region function (BA6). The correlation between resting and superior frontal response inhibition-related theta activity became stronger with increasing age. A similar pattern was found for response inhibition performance, albeit only evident from the age of ~19.5 years. The results suggest that with increasing age, resting theta activity becomes increasingly important for processing the alarm/surprise signals in superior frontal brain regions during inhibitory control. Possible causes for these developmental changes are discussed., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Impulsivity and deficits in response inhibition are hallmarks of attention-deficit(-hyperactivity) disorder (AD(H)D), can cause severe problems in daily functioning, and are thus of high clinical relevance. Traditionally, research to elucidate associated neural correlates has intensively, but also quite selectively examined mechanisms during response inhibition in various tasks. Doing so, in-between trial periods or periods prior to the response inhibition process, where no information relevant to inhibitory control is presented, have been neglected. Yet, these periods may nevertheless reveal relevant information. In the present study, using a case-control cross-sectional design, we take a more holistic approach, examining the inter-relation of pre-trial and within-trial periods in a Go/Nogo task with a focus on EEG theta band activity. Applying EEG beamforming methods, we show that the dynamics between pre-trial (pro-active) and within-trial (inhibition-related) control processes significantly differ between AD(H)D subtypes. We show that response inhibition, and differences between AD(H)D subtypes, exhibit distinct patterns of (at least) three factors: (i) strength of pre-trial (pro-active control) theta-band activity, (ii) the inter-relation of pro-active control and inhibition-relation theta band activity and (iii) the functional neuroanatomical region active during theta-related pro-active control processes. This multi-factorial pattern is captured by AD(H)D subtype clinical symptom clusters. The study provides a first hint that novel cognitive-neurophysiological facets of AD(H)D may be relevant to distinguish AD(H)D subtypes., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Inhibitory control processes are indispensable for goal-directed behavior. On a neurophysiological level, theta band power has been suggested to be important during inhibitory control as well as proactive control processes. Here we ask whether theta activity in the pre-trial/between-trial time period, reflects proactive control that correlates with theta activity in the upcoming trial. Theoretical considerations also suggest that such a correlation is modulated by the demands on inhibition. To investigate these questions, we conducted an EEG study using a Go/Nogo task in which demands on inhibitory control are varied. We used different EEG beamforming approaches to focus the analysis on the functional neuroanatomical level. We show that theta band activity in the ventromedial prefrontal cortex (vmPFC, BA10) is associated with the proactive control in the pre-trial interval and correlates with theta-related processes in the right inferior frontal gyrus (rIFG, BA45) during response inhibition. In addition, we show that demands on inhibitory control modulate the inter-relation between proactive vmPFC and inhibitory control-related rIFG-theta activity. Such effects were not observed for beta frequency activity. The study is the first to emphasize the relevance of pre-trial (proactive) vmPFC theta-band activity during inhibitory control in humans. It is shown that pre-trial activity, which is often neglected in EEG research, provides valuable information about the neuronal dynamics of cognitive control., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Conflict monitoring processes are central to cope with fluctuating environmental demands. However, the efficacy of these processes depends on previous trial history/experience, which is reflected in the "congruency sequence effect" (CSE). Several theoretical accounts have been put forward to explain this effect. Some accounts stress the role of perceptual processes in the emergence of the CSE. As yet, it is elusive how these perceptual processes are implemented on a neural level. We examined this question using a newly developed moving dots flanker task. We combine decomposition methods of EEG data and source localization. We show that perceptual processes modulate the CSE and can be isolated in neurophysiological signals, especially in the N2 ERP time window. However, mechanisms relating perception to action are also coded and modulated in this time window. We show that middle frontal regions (BA 6) are associated with processes dealing with purely perceptual processes. Inferior frontal regions (BA 45) are associated with processes dealing with stimulus-response transition processes. Likely, the neurophysiological modulations reflect unbinding processes at the perceptual level, and stimulus-response translation level needed to respond correctly on the presented (changed) stimulus-response relationships. The data establish a direct relationship between psychological concepts focusing on perceptual processes during conflict monitoring and neurophysiological processes using signal decomposition.

Catecholaminergic neural transmission plays an important role during the inhibition of prepotent responses. Methylphenidate (MPH) is an important drug that modulates the catecholaminergic system. However, theoretical considerations suggest that the effects of drugs (e.g. MPH) on cognitive control may depend on prior learning effects. Here we investigate this in a conflict-modulated Go/Nogo task and evaluate neurophysiological processes associated with this dynamic using EEG signal decomposition methods and source localization analysis. The behavioral data show that prior learning experiences eliminate effects of MPH on response inhibition processes. On a neurophysiological level, we show that MPH modulates specific processes in medial frontal brain regions. Although MPH seems to consistently modulate neurophysiological processes associated with response inhibition, this is no longer sufficient to modulate behavioral performance once learning or task familiarization processes have taken place. An important consequence of this study finding is that it may be important to adjust MPH dosage depending on learning effects in a specific setting to constantly increase cognitive control functions in that setting. This has important implications for clinical practice, since MPH is the first-line pharmacological therapy in attention-deficit hyperactivity disorder (ADHD). Cross-over study designs with constant doses of MPH can mask effects on cognitive functions. The impact of learning needs careful consideration in cross-over study designs examining catecholaminergic drug effects., Competing Interests: Conflict of interest MM has nothing to disclose. V. Roessner has received payment for consulting and writing activities from Lilly, Novartis, and Shire Pharmaceuticals, lecture honoraria from Lilly, Novartis, Shire Pharmaceuticals, and Medice Pharma, and support for research from Shire and Novartis. He has carried out clinical trials in cooperation with the Novartis, Shire, and Otsuka companies. C. Beste has received payment for consulting from GlaxoSmithKline, Novartis, Teva, Biogen, Celgene, Bayer and Genzyme. He is carrying out clinical research for Genzyme., (Copyright © 2020. Published by Elsevier B.V.)

Response inhibition is of vital importance in the context of controlling inappropriate responses. The role of perceptual processes during inhibitory control has attracted increased interest. Yet, we are far from an understanding of the mechanisms. One candidate mechanism by which perceptual processes may affect response inhibition refers to "gain control" that is closely linked to the signal-to-noise ratio of incoming information. A means to modulate the signal-to-noise ratio and gain control mechanisms is perceptual learning. In the current study, we examine the impact of perceptual learning (i.e., passive repetitive sensory stimulation) on response inhibition combining EEG signal decomposition with source localization analyses. A tactile GO/NOGO paradigm was conducted to measure action restraint as one subcomponent of response inhibition. We show that passive perceptual learning modulates response inhibition processes. In particular, perceptual learning attenuates the detrimental effect of response automation during inhibitory control. Temporally decomposed EEG data show that stimulus-related and not response selection processes during conflict monitoring are linked to these effects. The superior and middle frontal gyrus (BA6), as well as the motor cortex (BA4), are associated with the effects of perceptual learning on response inhibition. Reliable neurophysiological effects were not evident on the basis of standard ERPs, which has important methodological implications for perceptual learning research. The results detail how lower level sensory plasticity protocols affect higher-order cognitive control functions in frontal cortical structures., (© 2019 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

Gilles de la Tourette Syndrome (GTS) is a developmental disorder. Empirical studies and an emerging cognitive framework on GTS suggest that GTS is a disorder of abnormally strong 'perception-action binding'. Theoretical considerations imply that the effectiveness of long-established behavioral interventions might be related to a normalization of increased binding in GTS. This has not been tested yet. We examined the effect of a standardized Comprehensive Behavior Intervention for Tics (CBIT) in N = 21 adolescent GTS patients and N = 21 healthy controls on perception-action binding in an inhibitory control paradigm. Prior to CBIT, GTS patients showed compromised performance compared to controls, specifically when inhibitory control was triggered by uni-modal visual compared to bi-modal stimuli. After CBIT intervention, GTS patient's performance was at the same level as healthy controls. This is supported by a Bayesian data analysis. CBIT specifically affected inhibitory control in a condition where reconfigurations of perception-action bindings are necessary to perform inhibitory control. A power of 95% was evident for these effects. CBIT reduces increased 'binding' between perception and action in GTS and thereby increases the ability to perform response inhibition. The results are the first to provide insights as to why CBIT is effective by relating elements of this intervention to overarching cognitive theoretical frameworks on perception-action bindings.

The modulation of theta frequency activity plays a major role in inhibitory control processes. However, the relevance of resting theta band activity and of the ability to spontaneously modulate this resting theta activity for neural mechanisms underlying inhibitory control is elusive. Various theoretical conceptions suggest to take these aspects into consideration. In the current study, we examine whether the strength of resting theta band activity or the ability to modulate the resting state theta activity affects response inhibition. We combined EEG-time frequency decomposition and beamforming in a conflict-modulated Go/Nogo task. A sample of N = 66 healthy subjects was investigated. We show that the strength of resting state theta activity modulates the effects of conflicts during motor inhibitory control. Especially when resting theta activity was low, conflicts strongly affected response inhibition performance and total theta band activity during Nogo trials. These effects were associated with theta-related activity differences in the superior (BA7) and inferior parietal cortex (BA40). The results were very specific for total theta band activity since evoked theta activity and measures of intertrial phase coherency (phase-locking factor) were not affected. The data suggest that the strength of resting state theta activity modulates processing of a theta-related alarm or surprise signal during inhibitory control. The ability to voluntarily modulate theta band activity did not affect conflict-modulated inhibitory control. These findings have important implications for approaches aiming to optimize human cognitive control., (© 2019 Wiley Periodicals, Inc.)

The ability to inhibit prepotent responses is a central facet of cognitive control. However, the role of perceptual factors in response inhibition processes is still poorly understood and an underrepresented field of research. In the current study, we focus on the role of conflicts between perceptual stimulus features (so-called S-S conflicts) for response inhibition. We introduce a novel semantic Stroop Condition task and analyze EEG data using source localization and temporal EEG signal decomposition methods to delineate the neural mechanisms how semantic S-S conflicts modulate response inhibition. We show that semantic conflicts enhance response inhibition performance by modulating neural processes relating to conflict resolution mechanisms in the middle and inferior frontal cortex, as well as the ACC. Opposed to that, Stroop-like (S-S) conflicts compromise response execution by affecting decision processes in inferior parietal cortices. The data suggest that when action control processes and their neurophysiological correlates depend on regions specialized in the processing of semantic conflicts, there is an improvement in response inhibition. The results show that Stroop-like semantic conflicts have opposite effects depending on whether a response has to be executed or inhibited. These opposing effects are then also associated with different functional-neuroanatomical structures. The results of the study show mechanisms by which stimulus-related processes influence mechanisms of response control.

Background: Gilles de la Tourette Syndrome (GTS) is a multifaceted neuropsychiatric developmental disorder with onset in childhood or adolescence and frequent remissions in early adulthood. A rather new emerging concept of this syndrome suggests that it is a disorder of purposeful actions, in which sensory processes and their relation to motor responses (actions) play a particularly important role. Thus, this syndrome might be conceived as a condition of altered 'perception-action binding'. In the current study, we test this novel concept in the context of inhibitory control., Methods: We examined N = 35 adolescent GTS patients and N = 39 healthy controls in a Go/Nogo-task manipulating the complexity of sensory information triggering identical actions; i.e. to inhibit a motor response. This was combined with event-related potential recordings, EEG data decomposition and source localization., Results: GTS patients showed worse performance compared to controls and larger performance differences when inhibitory control had to be exerted using unimodal visual compared to bimodal auditory-visual stimuli. This suggests increased binding between bimodal stimuli and responses leading to increased costs of switching between responses instructed by bimodal and those instructed by unimodal stimuli. The neurophysiological data showed that this was related to mechanisms mediating between stimulus evaluation and response selection; i.e. perception-action binding processes in the right inferior parietal cortex (BA40)., Conclusions: Stimulus-action inhibition binding is stronger in GTS patients than healthy controls and affects inhibitory control corroborating the concept suggesting that GTS might be a condition of altered perception-action integration (binding); i.e. a disorder of purposeful actions., (© 2018 Association for Child and Adolescent Mental Health.)

The ability to inhibit responses is a central requirement for goal-directed behavior but has been dominated by a top-down or cognitive control view. Only recently, the role of bottom-up perceptual factors were focused in research. However, studies usually use clearly distinguishable stimulus categories to trigger response execution or inhibition. In the current study, we present a novel Gabor patch Go/No-go task to induce perceptual ambiguity during response inhibition. To examine the neurophysiological processes in detail, we use EEG recordings and combined temporal EEG signal decomposition methods with source localization analyses. We show that perceptual similarity between Go and No-go trials compromises response inhibition performance. Interestingly, the EEG data show that this is due to a modulation of stimulus-response transition or decision processes, and not purely stimulus-related processes. This was possible by applying a temporal EEG decomposition method. We provide evidence that a prefrontal P2 (pP2) likely reflects decision processes on action execution using stimulus information. These processes were associated with superior and middle prefrontal regions (BA8). When these processes fail, occasions to execute a response become misinterpreted as occasions to inhibit a response. Successful and unsuccessful decisions to inhibit a response under high perceptual ambiguity seem to further depend on how well "what-decisions," supported by neural mechanisms in BA19, can be processed. However, these what-decisions seem to be closely linked to the specification of the required action. Stimulus processing is closely linked to response programming so that response control is already informed when uncertainty with regard to stimulus identity is detected. NEW & NOTEWORTHY This study introduces a novel Go/No-go paradigm and shows what neurophysiological subprocesses and functional neuroanatomical are involved during inhibitory control when ambiguous stimulus input is provided. The results show that bottom-up perceptual processes are important to consider during top-down controlled response inhibition. Stimulus processing is closely linked to response programming so that response control is already informed when uncertainty with regard to stimulus identity is detected.

Inhibitory control is affected by perceptual processes, but the mechanisms how perceptual features affect response inhibition are poorly understood. Theoretical frameworks detailing how variations in stimulus features that create overlaps between response categories can affect action control, like the Theory of Event Coding (TEC), have not been transferred to inhibitory control. We present a novel Go/Nogo paradigm in which we varied stimulus feature overlap between Go and Nogo trials. To examine what cognitive-neurophysiological subprocesses and functional neuroanatomical structures are modulated by stimulus-response feature overlap and recoding during inhibitory control, we combine event-related potential (ERP) recordings with source localization analyses. We show that response inhibition was compromised when stimulus features overlapped between Go and Nogo trials. The EEG data show that the recoding of stimulus-response mappings induced by such a stimulus feature overlaps affects subprocesses from perceptual gating/categorization (P1 ERP-component) to pre-motor inhibition (Nogo-N2 ERP-component) and motor inhibition (Nogo-P3 ERP-component). Although these are distinct processes, overlapping neuronal structures are associated with these modulations. The cascade of processes starts in the superior frontal cortex and is associated with perceptual categorization mechanisms. Subsequently, pre-motor inhibition or stimulus-response unbinding processes are modulated in parahippocampal structures before stimulus-response rebinding and motor inhibition is accomplished in parahippocampal and superior frontal structures. The study shows how perceptual processes can affect response inhibition using a theoretical framework, which has, until now, not been brought into connection with inhibitory control and establishes links between neurophysiology and functional neuroanatomy of inhibitory control with the TEC framework., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Alcohol intoxication and abuse are well-known to cause impairments in executive functioning and control. Still, we know surprisingly little about individuals engaging in frequent binge drinking, even though they have an increased risk to develop an alcohol use disorder (AUD) later in life. As this risk has been suggested to be linked to (premorbid) executive deficits, we assessed changes in cognitive flexibility and inhibition with the help of a switching task and a stop-change task. Both paradigms had previously been shown to be modulated by alcohol, as well as by functional variations in dopaminergic and GABAergic neurotransmission. We employed an extreme group approach, where we compared pre-selected samples of frequent binge drinkers and non-frequent binge drinkers, all of which had stably pursued their respective consumption pattern for at least 3 years. In combination with Bayes analyses, our results showed that individuals engaging in frequent binge drinking showed no impairments of cognitive flexibility or inhibition, as compared to non-frequent binge drinkers. These observations suggest that frequent binge drinking alone is not associated with the cognitive control deficits commonly observed in AUD. Importantly, the investigated executive functions are known to be altered both during binge drinking and in individuals with AUD. It could hence be speculated that their intermittent consumption pattern prevents non-AUD frequent binge drinkers from the homeostatic counter-regulations of alcohol- and control-associated neurotransmitter systems that may be observed in AUD patients. Yet, this hypothesis still needs to be tested in future research, including studies that combine MR and molecular imaging., (Copyright © 2019. Published by Elsevier Inc.)

Response inhibition is a central aspect of cognitive control. Usually, response inhibition is examined using information from a single sensory modality. Yet, evidence suggests that conflicts between information from different modalities affect response inhibition. It is, however, crucial to consider that there are modality differences in the efficiency to trigger response inhibition that may also modulate the impact of conflicts between different sensory modalities. In the current study, we compared an auditory-tactile to an auditory-visual Go/NO-GO task. We recorded EEG data and performed signal decomposition and source localization. On the behavioral level, we show stronger interference effects in the visual than the tactile modality. Despite sensory processes were experimentally varied, temporally decomposed EEG data show that response selection mechanisms are associated with these effects and not the sensory processing stage. These modulations of response selection processes occur in the temporo-parietal junction (TPJ, BA40) and inferior frontal structures (IFG, BA47). The smaller activity in the TPJ during auditory-tactile, compared to auditory-visual conflicts suggests that task representations are less affected by interfering auditory information when the tactile modality informs response inhibition processes. This also explains why less intense braking processes (reflected by IFG activity) are still able to maintain a reasonable response inhibition performance level. It can be concluded that the tactile and visual domains do not only differ in regard to their efficiency to trigger response inhibition processes but also in their susceptibility to interference while informing inhibitory control. Clinical implications are discussed., (Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.)

Response inhibition is essential for navigating everyday life. Its derailment is considered integral to numerous neurological and psychiatric disorders, and more generally, to a wide range of behavioral and health problems. Response-inhibition efficiency furthermore correlates with treatment outcome in some of these conditions. The stop-signal task is an essential tool to determine how quickly response inhibition is implemented. Despite its apparent simplicity, there are many features (ranging from task design to data analysis) that vary across studies in ways that can easily compromise the validity of the obtained results. Our goal is to facilitate a more accurate use of the stop-signal task. To this end, we provide 12 easy-to-implement consensus recommendations and point out the problems that can arise when they are not followed. Furthermore, we provide user-friendly open-source resources intended to inform statistical-power considerations, facilitate the correct implementation of the task, and assist in proper data analysis., Competing Interests: FV, GB, PB, AB, JB, CC, HC, LC, BC, JC, AD, DE, HG, IG, AH, RH, SJ, JK, IL, CL, GL, DM, SM, AM, MP, RP, KR, MR, JS, AS, KT, Mv, LV, MV, JW, RW, BZ, CB No competing interests declared, AA, NS Reviewing editor, eLife, CB has received payment for consulting and speaker's honoraria from GlaxoSmithKline, Novartis, Genzyme, and Teva. He has recent research grants with Novartis and Genzyme, SC consults for Shire, Ieso Digital Health, Cambridge Cognition, and Promentis. Dr Chamberlain's research is funded by Wellcome Trust (110049/Z/15/Z), TR consults for Cambridge Cognition, Mundipharma and Unilever. He receives royalties from Cambridge Cognition (CANTAB) and has recent research grants with Shionogi and SmallPharma, KR has received speaker's honoraria and grants for other projects from Eli Lilly and Shire, RS has consulted to Highland Therapeutics, Eli Lilly and Co., and Purdue Pharma. He has commercial interest in a cognitive rehabilitation software company, eHave, (© 2019, Verbruggen et al.)

Medial and superior frontal theta oscillations are important for response inhibition. The norepinephrine (NE) system has been shown to modulate these oscillations possibly via gain control mechanisms, which depend on the modulation of neuron membrane potentials. Because the latter are also modulated by tDCS, the interrelation of tDCS and NE effects on superior frontal theta band activity needs investigation. We test the hypothesis that anodal tDCS affects modulatory effects of the NE system on theta band activity during inhibitory control in superior frontal regions. Using EEG beamforming, theta band activity in the superior frontal gyrus (SFG) was integrated (correlated) with the pupil diameter data as an indirect index of NE activity. In a within-subject design, healthy participants completed a response inhibition task in two sessions in which they received 2 mA anodal tDCS over the vertex, or sham stimulation. There were no behavioral effects of anodal tDCS. Yet, tDCS affected correlations between SFG theta band activity time course and the pupil diameter time course. Correlations were evident after sham stimulation (r = .701; p < .004), but absent after anodal tDCS. The observed power of this dissociation was above 95%. The data suggest that anodal tDCS may eliminate neuromodulatory effects, likely of the NE system, on theta band activity during response inhibition in a structure of the response inhibition network. The NE system and tDCS seem to target similar mechanisms important for cognitive control in the prefrontal cortex. The results provide a hint why tDCS often fails to induce overt behavioral effects and shows that neurobiological systems, which may exert similar effects as tDCS on neural processes should closely be monitored in tDCS experiments.

It is well-known that alcohol impairs behavioral control and motor response inhibition, but it has remained rather unclear whether it also impairs cognitive inhibition. As automatized behavior is less vulnerable towards the detrimental effects of alcohol than cognitive control processes, potential cognitive inhibition deficits might however improve with training. We investigated the effect of an acute, binge-like alcohol intoxication in a balanced within-subjects design, asking n=32 healthy young males to perform a backward inhibition paradigm once sober and once while intoxicated (~1.1 ‰). To identify the underlying neurophysiological mechanisms, we analyzed stimulus- and response selection-related processes in neurophysiological data after Residue Iteration Decomposition (RIDE). Alcohol generally impaired behavioral task performance (accuracy and response times) during task switching. This was associated with impaired attentional processing of the task-relevant cue (reflected by reduced P1 and N1 amplitudes), which likely resulted in a larger need for reactive control at the later stage of response selection and control (reflected by increased fronto-central theta power). Without prior practice (~30 minutes), the intoxicated participants further struggled to overcome the cognitive inhibition of a previously relevant task set (reflected by a larger backward inhibition effect). This was linked to reduced posterior theta power, which reflects alcohol-induced impairments in working memory capacity and task set-relevant memory retrieval. As individuals with ~30 min task practice did not show the same alcohol-related deficit, it may be deduced that (partial) task set automatization via stimulus-response associations may help to reduce the detrimental effects of alcohol on cognitive inhibition during task switching., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Response inhibition is a central aspect of cognitive control. Yet, only recently the role of sensory mechanisms for response inhibition has been addressed and neurophysiological mechanisms are far from being understood. Here we ask in how far the physical intensity of stimuli is a relevant perceptual factor modulating motor inhibitory control. We investigated how different physical (objective) stimulus and the subjectively perceived stimulus magnitude modulated response inhibition and its neurophysiological correlates. To this end we used a somatosensory GO/NOGO task in combination with EEG recordings and applied temporal signal decomposition and source localization methods. The behavioral (false alarm) data clearly demonstrated that response inhibition performance was worse in the subjective and objective stimulation condition as compared to the reference stimulation condition with higher stimulus magnitude. Despite primary perceptual aspects were manipulated, neurophysiological correlates of lower-level perceptual and attentional selection processes did not explain effects on overt response inhibition behavior. Rather, neurophysiological processes at the response selection level were modulated. These were associated with activation differences in the right inferior frontal gyrus and suggest that "braking processes" enabling the inhibition of a to-be-executed motor response were modulated. The modulation of these braking processes depends on objective physical magnitude of incoming sensory information and not the subjectively perceived stimulus magnitude., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Cognitive flexibility is a major facet of executive functions and often refers to sequential task control; that is, it is very likely that one may re-encounter a task that has previously been abandoned to carry out a different task. In the context of sequential cognitive flexibility, the "backward inhibition (BI) effect" has been studied quite extensively. Here we ask whether there are age-related differences between adolescents and adults to overcome BI and what system-neurophysiological mechanisms underlie these modulations. This was examined using a system neurophysiological study procedure combining event-related potentials data with source localization and EEG signal decomposition methods. We show that sequential cognitive flexibility, and the ability overcome backward inhibition, is inferior in adolescents compared with adults. Accounting for intra-individual variability in the neurophysiological data, this data suggest that two partly inter-related processes underlie the differences between adolescents than adults to overcome backward inhibition: One process refers to the suppression of the inhibitory effect of the n-1 trial on the n-2 trial during perceptual categorization of incoming information that is associated with right inferior frontal regions. The other process refers to immature response selection and conflict monitoring mechanisms associated with regions in the medial frontal cortex., (© 2018 Wiley Periodicals, Inc.)

Response inhibition deficits have often been described in obsessive compulsive disorder (OCD). Yet, research on response inhibition in OCD focusses on "top-down" controlled mechanisms, and it has been neglected that response inhibition performance depends on the interplay of controlled and automatic processes during response selection. Based on pathophysiological considerations we test the counterintuitive hypothesis that OCD patients show superior inhibitory control when automatic mechanisms govern processes involved in response inhibition. We examined a group of adolescent OCD patients (n = 27) and healthy controls (n = 27) using a combined Simon-Go/NoGo task. This task is able to examine conjoint effects of automatic and controlled processes during response inhibition. EEG and source localization analyses were applied to examine the underlying neural mechanisms. OCD patients committed fewer false alarms than healthy controls (HC) in the congruent Simon-NoGo condition, which is dominated by automatic response selection mechanisms. On a neurophysiological (EEG) level, these effects were reflected by intensified correlates of 'braking' processes associated with modulation of right inferior prefrontal regions. There is no general response inhibition deficit in adolescent OCD. When considering conjoint effects of automatic and controlled processes during the inhibition of responses paradoxical response inhibition advantages can emerge in OCD. This is likely a result of otherwise pathological fronto-striatal hyperactivity and loss of a situation-specific modulation of response selection mechanisms in OCD., (Copyright © 2019. Published by Elsevier Inc.)

Background: A major facet of obsessive-compulsive disorder (OCD) is cognitive inflexibility. However, sometimes, cognitive flexibility can be needed to reuse recently abandoned mental sets. Therefore, cognitive flexibility can in certain cases be useful to reinstate some form of rigid, repetitive behavior characterizing OCD. We test the counterintuitive hypothesis that under such circumstances, cognitive flexibility is better in OCD patients than controls., Methods: We examined N = 20 adolescent OCD patients and N = 22 controls in a backward inhibition (BI) paradigm. This was combined with event-related potential (ERP) recordings and source localization. The BI effect describes the cost of overcoming the inhibition of a recently abandoned mental set that is relevant again. Therefore, a strong BI effect is disadvantageous for cognitive flexibility., Results: Compared to controls, OCD patients revealed a smaller backward inhibition effect. The EEG data revealed larger P1 amplitudes in backward inhibition trials in the OCD group, which was due to activation differences in the inferior frontal gyrus (BA47). The severity of clinical symptoms predicted these neurophysiological modulations. The power of the observed effects was about 95%., Conclusions: The study shows that cognitive flexibility can be better in OCD than controls. This may be the case in situations where superior abilities in the reactivation of repeating mental sets and difficulties to process new ones coincide. This may be accomplished by intensified inhibitory control mechanisms. The results challenge the view on OCD, since OCD is not generally associated with cognitive inflexibility., (© 2018 Association for Child and Adolescent Mental Health.)

Response inhibition processes undergo strong developmental changes. The same is true for sensory processes, and recent evidence shows that there also within-modality differences in the efficacy to trigger motor response inhibition. Yet, modulatory effects of within-modality differences during age-related changes in response inhibition between adolescence and adulthood are still indeterminate. We investigated this question in a system neurophysiological approach combining analysis of event-related potentials (ERPs) with temporal EEG signal decomposition and source localization processes. We used the somatosensory system to examine possible within-modality differences. The study shows that differences in response inhibition processes between adolescents and adults are modulated by sensory processes. Adolescents show deficient response inhibition when stimuli triggering these mechanisms are processed via SI somatosensory areas, compared to SII somatosensory areas. Opposed to this, no differences between adolescents and adults are evident, when response inhibition processes are triggered via SII cortical regions. The EEG data suggests that specific neurophysiological subprocesses are associated with this. Adolescents seem to encounter problems assigning processing resources to integrate motor with tactile information in posterior parietal areas when this information is processed via SI. Thus, basic perceptual and age-related processes interactively modulate response inhibition as an important instance of cognitive control., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Even though deficits in inhibitory control and conflict monitoring are well-known in ADHD, factors that further modulate these functions remain to be elucidated. One factor that may be of considerable importance is how inhibitory control is modulated by multisensory information processing. We examined the influence of concurrent auditory conflicting or redundant information on visually triggered response inhibition processes in adolescent ADHD patients and healthy controls. We combined high-density event-related potential (ERP) recordings with source localization to delineate the functional neuroanatomical basis of the involved neurophysiological processes. In comparison to controls, response inhibition (RI) processes in ADHD were compromised in conflicting conditions, but showed no differences to controls when redundant or no concurrent auditory information was presented. These effects were reflected by modulations at the response selection stage (P3 ERP) in the medial frontal gyrus (BA32), but not at the attentional selection (P1, N1 ERPs) or resource allocation level (P2 ERP). Conflicting information during RI exerts its influences in adolescent ADHD via response selection mechanisms, but not via attentional selection. It is not the mere presence of concurrent information, but the presence of conflicting information during RI that may destabilize goal shielding processes in medial frontal cortical regions, by means of increasing the automaticity of response tendencies. The occurring RI deficits might relate to the increased impulsivity in adolescent ADHD and a corresponding vulnerability to react to an increased automaticity of pre-potent response tendencies. ADHD patients show a bias to a specific content of information which can modulate inhibitory control.

The inhibition of prepotent responses is a requirement for goal-directed behavior and several factors determine corresponding successful response inhibition processes. One factor relates to the degree of automaticity of pre-potent response tendencies and another factor relates to the degree of cognitive control that is exerted during response inhibition. However, both factors can conjointly modulate inhibitory control. Cognitive theoretical concepts suggest that codings of stimulus-response translations may underlie such conjoint effects. Yet, it is unclear in how far such specific codes, as assumed in cognitive psychological concepts, are evident in neurophysiological processes and whether there are specific functional neuroanatomical structures associated with the processing of such codes. Applying a temporal decomposition method of EEG data in combination with source localization methods we show that there are different, intermingled codes (i.e., "stimulus codes" and "response selection codes") at the neurophysiological level during conjoint effects of "automatic" and "controlled" processes in response inhibition. Importantly, only "response selection codes" predict behavioral performance, and are subject to conjoint modulations by "automatic" and "controlled" processes. These modulations are associated with inferior and superior parietal areas (BA40/BA7), possibly reflecting an updating of internal representations when information is complex and probably difficult to categorize, but essential for behavioral control. Codes proposed by cognitive, psychological concepts seem to have a neurophysiological analogue that fits into current views on functions of inferior and superior parietal regions., (© 2018 Wiley Periodicals, Inc.)

Sensorimotor integration is essential for successful motor control and the somatosensory modality has been shown to have strong effects on the execution of motor plans. The primary (SI) and the secondary somatosensory (SII) cortices are known to differ in their neuroanatomical connections to prefrontal areas, as well as in their involvement to encode cognitive aspects of tactile processing. Here, we ask whether the area-specific processing architecture or the structural neuroanatomical connections with prefrontal areas determine the efficacy of sensorimotor integration processes for motor control. In a system neurophysiological study including EEG signal decomposition (i.e., residue iteration decomposition, RIDE) and source localization, we investigated this question using vibrotactile stimuli optimized for SI or SII processing. The behavioral data show that when being triggered via the SI area, inhibitory control of motor processes is stronger as when being triggered via the SII area. On a neurophysiological level, these effects were reflected in the C-cluster as a result of a temporal decomposition of EEG data, indicating that the sensory processes affecting motor inhibition modulate the response selection level. These modulations were associated with a stronger activation of the right inferior frontal gyrus extending to the right middle frontal gyrus as parts of a network known to be involved in inhibitory motor control when response inhibition is triggered over SI. In addition, areas important for sensorimotor integration like the postcentral gyrus and superior parietal cortex showed activation differences. The data suggest that connection patterns are more important for sensorimotor integration and control than the more restricted area-specific processing architecture.

Response inhibition mechanisms are mediated via cortical and subcortical networks. At the cortical level, the superior frontal gyrus, including the supplementary motor area (SMA) and inferior frontal areas, is important. There is an ongoing debate about the functional roles of these structures during response inhibition as it is unclear whether these structures process different codes or contents of information during response inhibition. In the current study, we examined this question with a focus on theta frequency oscillations during response inhibition processes. We used a standard Go/Nogo task in a sample of human participants and combined different EEG signal decomposition methods with EEG beamforming approaches. The results suggest that stimulus coding during inhibitory control is attained by oscillations in the upper theta frequency band (∼7 Hz). In contrast, response selection codes during inhibitory control appear to be attained by the lower theta frequency band (∼4 Hz). Importantly, these different codes seem to be processed in distinct functional neuroanatomical structures. Although the SMA may process stimulus codes and response selection codes, the inferior frontal cortex may selectively process response selection codes during inhibitory control. Taken together, the results suggest that different entities within the functional neuroanatomical network associated with response inhibition mechanisms process different kinds of codes during inhibitory control. These codes seem to be reflected by different oscillations within the theta frequency band. Hum Brain Mapp 38:5681-5690, 2017. © 2017 Wiley-Liss, Inc., (© 2017 Wiley Periodicals, Inc.)

Response inhibition processes are important for goal-directed behavior and particularly demanded when it is unlikely to inhibit automatically executed responses. It has been suggested that the norepinephrine (NE) system is important to consider for such likelihood effects. As an indirect measure of the NE system activity we used the pupil diameter and integrated this data with neurophysiological (EEG) data and beamforming analyses. The study shows that inhibitory control processes reflected by theta oscillations are strongly modulated by the likelihood to employ these processes and that these mechanisms were related to neural processes in the SMA and SFG. Probably, the modulations observed for theta band activity may reflect modulations in the encoding of a surprise, or conflict signal. Interestingly, correlation analyses of neuronal activity at the sensor and the source level with pupil diameter data revealed strong correlations that were only seen in the condition where inhibitory control processes were rarely demanded. On the basis of findings and theoretical models suggesting that the pupil diameter can be interpreted as a proximate of NE system activity the results may be interpreted that the NE system modulates inhibitory control processes via theta band activity in the SFB when the likelihood to inhibit a prepotent response tendency is low. From this it may be speculated that the NE system dynamically gains and loses relevance to modulate inhibitory control depending on boundary conditions that determine the mode of responding., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Despite cognitive inflexibility is trait like in obsessive compulsive disorder (OCD) patients and underlies clinical symptomatology, it is elusive at what stage of information processing deficits, leading to cognitive inflexibility, emerges. We hypothesize that inhibitory control mechanisms during early stimulus categorization and integration into a knowledge system underlie these deficits., Methods: We examined N = 25 adolescent OCD patients and matched healthy controls (HC) in a paradigm manipulating the importance of the knowledge system to perform task switching. This was done using a paradigm in which task switches were signaled either by visual stimuli or by working memory processes. This was combined with event-related potential recordings and source localization., Results: Obsessive compulsive disorder patients showed increased switch costs in the memory as compared with the cue-based block, while HC showed similar switch costs in both blocks. At the neurophysiological level, these changes in OCD were not reflected by the N2 and P3 reflecting response-associated processes but by the P1 reflecting inhibitory control during sensory categorization processes. Activation differences in the right inferior frontal gyrus and superior temporal gyrus are associated with the P1 effect., Conclusions: Cognitive flexibility in adolescent OCD patients is strongly modulated by working memory load. Contrary to common sense, not response-associated processes, but inhibitory control mechanisms during early stimulus categorization processes are likely to underlie cognitive inflexibility in OCD. These processes are associated with right inferior frontal and superior temporal gyrus mechanisms., (© 2017 Association for Child and Adolescent Mental Health.)

The ability to inhibit responses is a central sensorimotor function but only recently the importance of sensory processes for motor inhibition mechanisms went more into the research focus. In this regard it is elusive, whether there are differences between sensory modalities to trigger response inhibition processes. Due to functional neuroanatomical considerations strong differences may exist, for example, between the visual and the tactile modality. In the current study we examine what neurophysiological mechanisms as well as functional neuroanatomical networks are modulated during response inhibition. Therefore, a Go/NoGo-paradigm employing a novel combination of visual, tactile, and visuotactile stimuli was used. The data show that the tactile modality is more powerful than the visual modality to trigger response inhibition processes. However, the tactile modality loses its efficacy to trigger response inhibition processes when being combined with the visual modality. This may be due to competitive mechanisms leading to a suppression of certain sensory stimuli and the response selection level. Variations in sensory modalities specifically affected conflict monitoring processes during response inhibition by modulating activity in a frontal parietal network including the right inferior frontal gyrus, anterior cingulate cortex and the temporoparietal junction. Attentional selection processes are not modulated. The results suggest that the functional neuroanatomical networks involved in response inhibition critically depends on the nature of the sensory input. Hum Brain Mapp 38:1941-1951, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

There are large overlaps in cognitive deficits occurring in attention deficit disorder (ADD) and neurodevelopmental disorders like neurofibromatosis type 1 (NF1). This overlap is mostly based on clinical measures and not on in-depth analyses of neuronal mechanisms. However, the consideration of such neuronal underpinnings is crucial when aiming to integrate measures that can lead to a better understanding of the underlying mechanisms. Inhibitory control deficits, for example, are a hallmark in ADD, but it is unclear how far there are similar deficits in NF1. We thus compared adolescent ADD and NF1 patients to healthy controls in a Go/Nogo task using behavioural and neurophysiological measures. Clinical measures of ADD-symptoms were not different between ADD and NF1. Only patients with ADD showed increased Nogo errors and reductions in components reflecting response inhibition (i.e. Nogo-P3). Early perceptual processes (P1) were changed in ADD and NF1. Clinically, patients with ADD and NF1 thus show strong similarities. This is not the case in regard to underlying cognitive control processes. This shows that in-depth analyses of neurophysiological processes are needed to determine whether the overlap between ADD and NF1 is as strong as assumed and to develop appropriate treatment strategies.

The ability to execute several actions in a specific temporal order to achieve an overarching goal, a process often termed action cascading or multi-component behavior, is essential for everyday life requirements. We are only at the beginning to understand the neurobiological mechanisms important for these cognitive processes. However, it is likely that the locus coeruleus-norepinephrine (LC-NE) system may be of importance. In the current study we examine the relevance of the LC-NE system for action cascading processes using a system neurophysiological approach combining high-density EEG recordings and source localization to analyze event-related potentials (ERPs) with recordings of pupil diameter as a proximate of LC-NE system activity. N=25 healthy participants performed an action cascading stop-change paradigm. Integrating ERPs and pupil diameter using Pearson correlations, the results show that the LC-NE system is important for processes related to multi-component behavior. However, the LC-NE system does not seem to be important during the time period of response selection processes during multi-component behavior (reflected in the P3) as well as during perceptual and attentional selection (P1 and N1 ERPs). Rather, it seems that the neurophysiological processes in the fore period of a possibly upcoming imperative stimulus to initiate multi-component behavior are correlated with the LC-NE system. It seems that the LC-NE system facilitates responses to task-relevant processes and supports task-related decision and response selection processes by preparing cognitive control processes in case these are required during multi-component behavior rather than modulating these processes once they are operating., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In everyday life successful acting often requires to inhibit automatic responses that might not be appropriate in the current situation. These response inhibition processes have been shown to become aggravated with increasing automaticity of pre-potent response tendencies. Likewise, it has been shown that inhibitory processes are complicated by a concurrent engagement in additional cognitive control processes (e.g. conflicting monitoring). Therefore, opposing processes (i.e. automaticity and cognitive control) seem to strongly impact response inhibition. However, possible interactive effects of automaticity and cognitive control for the modulation of response inhibition processes have yet not been examined. In the current study we examine this question using a novel experimental paradigm combining a Go/NoGo with a Simon task in a system neurophysiological approach combining EEG recordings with source localization analyses. The results show that response inhibition is less accurate in non-conflicting than in conflicting stimulus-response mappings. Thus it seems that conflicts and the resulting engagement in conflict monitoring processes, as reflected in the N2 amplitude, may foster response inhibition processes. This engagement in conflict monitoring processes leads to an increase in cognitive control, as reflected by an increased activity in the anterior and posterior cingulate areas, while simultaneously the automaticity of response tendencies is decreased. Most importantly, this study suggests that the quality of conflict processes in anterior cingulate areas and especially the resulting interaction of cognitive control and automaticity of pre-potent response tendencies are important factors to consider, when it comes to the modulation of response inhibition processes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Inhibitory control processes are known to be modulated by working memory demands. However, the neurobiological mechanisms behind these modulations are inconclusive. One important system to consider in this regard is the locus coeruleus (LC) norepinephrine (NE) system. In the current study the role of the LC-NE system by means of pupil diameter recordings that are integrated with neurophysiological (EEG) and source localization data were examined. A combined mental-rotation Go/Nogo task was used. The results show that increases in working memory load complicate response inhibition processes. On a neurophysiological level these effects were reflected by specific modulations in event-related potentials (ERPs) reflecting motor inhibition processes (i.e., Nogo-P3). Attentional selection processes (reflected by the P1 and N1) as well as pre-motor inhibition or conflict monitoring processes (reflected by the Nogo-N2) were not affected. Activity of the LC-NE systems, as indexed by the pupil diameter data, predicted neurophysiological processes selectively in the Nogo-P3 time range. Source localization analyses suggest that this modulation occurs in the right middle and inferior frontal gyrus. The study provides evidence that the LC-NE system is an important neurobiological system modulating the effects of working memory load on response inhibition processes. More specifically, it modulates a subset of dissociable cognitive processes that are related to prefrontal cortical regions. Hum Brain Mapp 38:68-81, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Task switching is regularly required in our everyday life. To succeed in switching, it is important to inhibit the most recently performed task and instead activate the currently relevant task. The process that inhibits a recently performed task when a new task is to be performed is referred to as 'backward inhibition' (BI). While the BI effect has been subject to intense research in cognitive psychology, little is known about the neuronal mechanisms that are related to the BI effect and those that relate to differences in the magnitude of the BI effect. In the current study, we examined the system neurophysiological basis of BI processes using event-related potentials (ERPs) and sLORETA by also taking inter-individual differences in the magnitude of the BI into account. The results suggest that BI processes and inter-individual differences in them strongly depend upon attentional selection mechanisms (reflected by N1-ERP modulations in the current task/trial) mediated via networks consisting of extrastriate occipital areas, the temporo-parietal junction and the inferior frontal gyrus. Other processes and mechanisms related to conflict monitoring, response selection, or the updating, organization and implementation of a new task-set (i.e. N2 and P3 processes) were not shown to be modulated by BI processes and differences in their magnitude, as evoked with a common BI paradigm.

The ability to flexibly switch between tasks is an important faculty in daily life. One process that has been suggested to be an important aspect of flexible task switching is the inhibition of a recently performed task. This is called backward inhibition. Several studies suggest that task switching performance can be enhanced by rewards. However, it is less clear in how far backward inhibition mechanisms are also affected by rewards, especially when it comes to the neuronal mechanisms underlying reward-related modulations of backward inhibition. We therefore investigated this using a system neurophysiological approach combining EEG recordings with source localization techniques. We demonstrate that rewards reduce the strength of backward inhibition processes. The neurophysiological data shows that these reward-related effects emerge from response and/or conflict monitoring processes within medial frontal cortical structures. Upstream processes of perceptual gating and attentional selection, as well as downstream processes of context updating and stimulus-response mapping are not modulated by reward, even though they also play a role in backward inhibition effects., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Response inhibition processes are one of the most important executive control functions and have been subject to intense research in cognitive neuroscience. However, knowledge on the neurophysiology and functional neuroanatomy on response inhibition is biased because studies usually employ experimental paradigms (e.g., sustained attention to response task, SART) in which behavior is susceptible to impulsive errors. Here, we investigate whether there are differences in neurophysiological mechanisms and networks depending on the response mode that predominates behavior in a response inhibition task. We do so comparing a SART with a traditionally formatted task paradigm. We use EEG-beamforming in two tasks inducing opposite response modes during action selection. We focus on theta frequency modulations, since these are implicated in cognitive control processes. The results show that a response mode that is susceptible to impulsive errors (response mode used in the SART) is associated with stronger theta band activity in the left temporo-parietal junction. The results suggest that the response modes applied during response inhibition differ in the encoding of surprise signals, or related processes of attentional sampling. Response modes during response inhibition seem to differ in processes necessary to update task representations relevant to behavioral control.

Background: Inhibitory control processes are a central executive function. Several lines of evidence suggest that the GABAergic and the norepinephrine (NE) system modulate inhibitory control processes. Yet, the effects of conjoint increases in the GABAergic and NE system activity on inhibitory control have not been examined., Objective/hypothesis: We examine the conjoint effects of the GABA and NE system for inhibitory control., Methods: We used transcutaneous vagus nerve stimulation (tVNS), which has been shown to modulate both the GABAergic and NE system. We examine the effects of tVNS in two experimental paradigms examining different aspect of inhibitory control; i.e. a backward inhibition paradigm and a response inhibition paradigm modulating working memory load., Results: There were no effects of tVNS on backward inhibition processes, but on response inhibition processes. Yet, these only emerged when working memory processes were needed to control response inhibition. Compared to a sham stimulation, tVNS induced better response inhibition performance (i.e. fewer false alarms)., Conclusions: A concomitant modulation of the GABAergic and NE system, as induced by tVNS, affects inhibitory control processes, but only when working memory processes play an important role for inhibitory control. Even though both the GABAergic and the NE system are modulated by tVNS, the results suggest that the modulation of the NE system is most important for the emerging effects., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: In everyday life it is often required to integrate multisensory input to successfully conduct response inhibition (RI) and thus major executive control processes. Both RI and multisensory processes have been suggested to be altered in autism spectrum disorder (ASD). It is, however, unclear which neurophysiological processes relate to changes in RI in ASD and in how far these processes are affected by possible multisensory integration deficits in ASD., Method: Combining high-density EEG recordings with source localization analyses, we examined a group of adolescent ASD patients (n = 20) and healthy controls (n = 20) using a novel RI task., Results: Compared to controls, RI processes are generally compromised in adolescent ASD. This aggravation of RI processes is modulated by the content of multisensory information. The neurophysiological data suggest that deficits in ASD emerge in attentional selection and resource allocation processes related to occipito-parietal and middle frontal regions. Most importantly, conflict monitoring subprocesses during RI were specifically modulated by content of multisensory information in the superior frontal gyrus., Conclusions: RI processes are overstrained in adolescent ASD, especially when conflicting multisensory information has to be integrated to perform RI. It seems that the content of multisensory input is important to consider in ASD and its effects on cognitive control processes.

l-Tyrosine (TYR), the precursor of dopamine (DA), has been shown to enhance facets of cognitive control in situations with high cognitive demands. However some previous outcomes were mixed: some studies reported significant improvements, while other did not. Given that TYR increases DA level in the brain, we investigated, in a double-blind, randomized, placebo-controlled design, whether the C957T genotypes of a functional synonymous polymorphism in the human dopamine D2 receptor (DRD2) gene (rs6277) contribute to individual differences in the reactivity to TYR administration and whether this factor predicts the magnitude of TYR-induced performance differences on inhibiting behavioral responses in a stop-signal task and working memory (WM) updating in a N-back task. Our findings show that T/T homozygotes (i.e., individuals potentially associated with lower striatal DA level) showed larger beneficial effects of TYR supplementation than C/C homozygotes (i.e., individuals potentially associated with higher striatal DA level), suggesting that genetically determined differences in DA function may explain inter-individual differences in response to TYR supplementation. These findings reinforce the idea that genetic predisposition modulates the effect of TYR in its role as cognitive enhancer., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Wilson's disease (WD) is a rare genetic disease causing copper deposits in various tissues. Given the specificity of the underlying pathology, it is a good model to investigate the effects of copper toxicity on cognitive functions in humans. If left untreated, WD results in neurodegeneration and organ failure, but irrespective of potential brain damage, the medication might reduce cortical norepinephrine (NE) levels. In line with this, dysexecutive symptoms including increased impulsivity have been reported for WD patients, but the underlying mechanisms have remained elusive. We investigated inhibition and the associated neurophysiological correlates in n = 26 WD patients with mild-to-moderate clinical symptoms and matched healthy controls who completed a Go/Nogo task, while an EEG was recorded. Although the behavioral data do not show increased impulsivity in WD, the neurophysiological data show that evaluative processing of successful inhibition (as reflected by the P3 component) was strongly compromised. This was reflected by a decrease in ACC activity which was positively correlated with the severity of WD symptoms, stressing the importance of copper (toxicity) for neurocognitive functioning and impulsivity. These changes are most likely due to a combination of NE deficiency induced by WD medication as well as WD-induced brain damage. The fact that changes were still evident on a neurophysiological level suggests that neurophysiological correlates of cognitive processes and functions provide a more sensitive index of toxicity and/or treatment efficiency than purely behavioral measures.

Action control is achieved through a multitude of cognitive processes. One of them is the ability to inhibit responses, for which the dopaminergic systems is known to play an important role. Many lines of psychophysiological research substantiate that two distinct response inhibition subprocesses exist, but it has remained elusive whether they can be attributed to distinct neurobiological factors governing the dopaminergic system. We, therefore, investigated this question by examining the effects of DRD1 (rs4532) and DRD2 (rs6277) receptor polymorphisms on electrophysiological correlates of response inhibition subprocesses (i.e., Nogo-N2 and Nogo-P3) in 195 healthy human subjects with a standard Go/Nogo task. The results show that response inhibition performance at a behavioral level is affected by DRD1 and DRD2 receptor variation. However, from an electrophysiological point of view these effects emerge via different mechanisms selectively affected by DRD1 and DRD2 receptor variation. While the D1 receptor system is associated with pre-motor inhibition electrophysiological correlates of response inhibition processes (Nogo-N2), the D2 receptor system is associated with electrophysiological correlates of outcome evaluation processes. Dissociable cognitive-neurophysiological subprocesses of response inhibition are hence attributable to distinct dopamine receptor systems., (Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.)

Binge drinking is an increasing problem in Western societies, but we are still only beginning to unravel the effects of binge drinking on a cognitive level. While common sense suggests that all cognitive functions are compromised during high-dose ethanol intoxication, several studies suggest that the effects might instead be rather specific. Moreover, some results suggest that the degrees of automaticity and complexity of cognitive operations during response control modulate effects of binge drinking. However, this has not been tested in detail. In the current study, we therefore parametrically modulate cognitive/"mental" workload during response inhibition and examine the effects of high-dose ethanol intoxication (~1.1 ‰) in n = 18 male participants. The results suggest that detrimental effects of high-dose ethanol intoxication strongly depend on the complexity of processes involved in response inhibition. The results revealed strong effects (η (2) = .495) and are in line with findings showing that even high doses of ethanol have very specific effects on a cognitive level. Opposed to common sense, more complex cognitive operations seem to be less affected by a high-dose ethanol intoxication. Complementing this, high-dose ethanol intoxication is increasingly detrimental for action control, as stronger automated response tendencies are in charge and need to be controlled. Binge-like ethanol intoxication may take a heavier toll on cognitive control processes than on automated responses/response tendencies. Therefore, ethanol effects are more pronounced in supposedly "easier" control conditions because those facilitate the formation of automated response tendencies.

Aside from well-known physiological effects, high-dose alcohol intoxication (a.k.a. binge drinking) can lead to aversive social and legal consequences because response inhibition is usually compromised under the influence of alcohol. Although the behavioral aspects of this phenomenon were reported on extensively, the underlying neurophysiological mechanisms mediating this disinhibition are unclear. To close this gap, we used both behavioral and neurophysiological measures (event-related potentials, ERPs) to investigate which subprocesses of response inhibition are altered under the influence of high-dose alcohol intoxication. Using a within-subject design, we asked young healthy participants (n = 27) to complete a GO/NOGO task once sober and once intoxicated (approximately 1.2‰). During intoxication, high-dose alcohol effects were highest in a condition where the participants could not rely on automated stimulus-response mapping processes during response inhibition. In this context, the NOGO-P3 (ERP), that likely depends on dopaminergic signaling within mesocorticolimbic pathways and is thought to reflect motor inhibition and/or the evaluation of inhibitory processes, was altered in the intoxicated state. In contrast to this, the N2 component, which largely depends on nigrostriatal dopamine pathways and is thought to reflect inhibition on a pre-motor level, was not altered. Based on these results, we demonstrate that alcohol-induced changes of dopaminergic neurotransmission do not exert a global effect on response inhibition. Instead, changes are highly subprocess-specific and seem to mainly target mesocorticolimbic pathways that contribute to motor inhibition and the evaluation of such., (© 2014 Society for the Study of Addiction.)