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"Metacontrol" refers to the ability to find the right balance between more persistent and more flexible cognitive control styles, depending on task demands. Recent research on tasks involving response conflict regulation indicates a consistent link between aperiodic EEG activity and task conditions that demand a more or less persistent control style. In this study, we explored whether this connection between metacontrol and aperiodic activity also applies to cognitive flexibility. We examined EEG and behavioral data from two separate samples engaged in a task-switching paradigm, allowing for an internal replication of our findings. Both studies revealed that aperiodic activity significantly decreased during task switching compared to task repetition. Our results support the predictions of metacontrol theory but contradict those of traditional control theories which would have predicted the opposite pattern of results. We propose that aperiodic activity observed in EEG signals serves as a valid indicator of dynamic neuroplasticity in metacontrol, suggesting that truly adaptive metacontrol does not necessarily bias processing towards persistence in response to every control challenge, but chooses between persistence and flexibility biases depending on the nature of the challenge., (© 2024. The Author(s).)

Deficiencies in inhibitory control are one of the hallmarks of attention-deficit-(hyperactivity) disorder (AD(H)D). Response inhibition demands can become increased through additional conflicts, namely when already integrated representations of perception-action associations have to be updated. Yet, the neural mechanisms of how such conflicts worsen response inhibition in AD(H)D are unknown, but, if identified, could help to better understand the complex nature of AD(H)D-associated impulsivity. We investigated both behavioral performance and EEG activity in the theta and alpha band of adolescents (10-18 years of age) with AD(H)D (n = 28) compared to neurotypical (NT) controls (n = 33) in a conflict-modulated Go/Nogo paradigm. We used multivariate pattern analysis (MVPA) and EEG-beamforming to examine how changes in representational content are coded by oscillatory activity and to delineate the cortical structures involved in it. The presented behavioral and neurophysiological data show that adolescents with AD(H)D are more strongly affected by increased response inhibition demands through additional conflicts than NT controls. Precisely, AD(H)D participants showed higher false alarm rates than NT controls in both, non-overlapping and overlapping Nogo trials, but performed even worse in the latter. This is likely due to an inefficient updating of representations related to delayed modulations of alpha band activity in the ventral stream and orbitofrontal regions. Theta band activity is also modulated by conflict but was not differentially affected in the two groups. By this, the present study provides novel insights into underlying neurophysiological mechanisms of the complex nature of response inhibition deficits in adolescents with AD(H)D, stressing the importance to examine the interplay of theta and alpha band activity more closely to better understand inhibitory control deficits in AD(H)D., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: "Metacontrol" describes the ability to maintain an optimal balance between cognitive control styles that are either more persistent or more flexible. Recent studies have shown a link between metacontrol and aperiodic EEG patterns. The present study aimed to gain more insight into the neurobiological underpinnings of metacontrol by using methylphenidate (MPH), a compound known to increase postsynaptic catecholamine levels and modulate cortical noise., Methods: In a double-blind, randomized, placebo-controlled study design, we investigated the effect of MPH (0.5 mg/kg) on aperiodic EEG activity during a flanker task in a sample of n = 25 neurotypical adults. To quantify cortical noise, we employed the fitting oscillations and one over f algorithm., Results: Compared with placebo, MPH increased the aperiodic exponent, suggesting that it reduces cortical noise in 2 ways. First, it did so in a state-like fashion, as the main effect of the drug was visible and significant in both pre-trial and within-trial periods. Second, the electrode-specific analyses showed that the drug also affects specific processes by dampening the downregulation of noise in conditions requiring more control., Conclusions: Our findings suggest that the aperiodic exponent provides a neural marker of metacontrol states and changes therein. Further, we propose that the effectiveness of medications targeting catecholaminergic signaling can be evaluated by studying changes of cortical noise, fostering the idea of using the quantification of cortical noise as an indicator in pharmacological treatment., (© The Author(s) 2024. Published by Oxford University Press on behalf of CINP.)

The ability to find the right balance between more persistent and more flexible cognitive-control styles is known as "metacontrol." Recent findings suggest a relevance of aperiodic EEG activity and task conditions that are likely to elicit a specific metacontrol style. Here we investigated whether individual differences in aperiodic EEG activity obtained off-task (during resting state) predict individual cognitive-control styles under task conditions that pose different demands on metacontrol. We analyzed EEG resting-state data, task-EEG, and behavioral outcomes from a sample of N = 65 healthy participants performing a Go/Nogo task. We examined aperiodic activity as indicator of "neural noise" in the EEG power spectrum, and participants were assigned to a high-noise or low-noise group according to a median split of the exponents obtained for resting state. We found that off-task aperiodic exponents predicted different cognitive-control styles in Go and Nogo conditions: Overall, aperiodic exponents were higher (i.e., noise was lower) in the low-noise group, who however showed no difference between Go and Nogo trials, whereas the high-noise group exhibited significant noise reduction in the more persistence-heavy Nogo condition. This suggests that trait-like biases determine the default cognitive-control style, which however can be overwritten or compensated for under challenging task demands. We suggest that aperiodic activity in EEG signals represents valid indicators of highly dynamic arbitration between metacontrol styles, representing the brain's capability to reorganize itself and adapt its neural activity patterns to changing environmental conditions., (© 2024 The Authors. Psychophysiology published by Wiley Periodicals LLC on behalf of Society for Psychophysiological Research.)

Background: The catecholaminergic system influences response inhibition, but the magnitude of the impact of catecholaminergic manipulation is heterogeneous. Theoretical considerations suggest that the voluntary modulability of theta band activity can explain this variance. The study aimed to investigate to what extent interindividual differences in catecholaminergic effects on response inhibition depend on voluntary theta band activity modulation., Methods: A total of 67 healthy adults were tested in a randomized, double-blind, cross-over study design. At each appointment, they received a single dose of methylphenidate or placebo and performed a Go/Nogo task with stimuli of varying complexity. Before the first appointment, the individual's ability to modulate theta band activity was measured. Recorded EEG data were analyzed using temporal decomposition and multivariate pattern analysis., Results: Methylphenidate effects and voluntary modulability of theta band activity showed an interactive effect on the false alarm rates of the different Nogo conditions. The multivariate pattern analysis revealed that methylphenidate effects interacted with voluntary modulability of theta band activity at a stimulus processing level, whereas during response selection methylphenidate effects interacted with the complexity of the Nogo condition., Conclusions: The findings reveal that the individual's theta band modulability affects the responsiveness of an individual's catecholaminergic system to pharmacological modulation. Thus, the impact of pharmacological manipulation of the catecholaminergic system on cognitive control most likely depends on the existing ability to self-modulate relevant brain oscillatory patterns underlying the cognitive processes being targeted by pharmacological modulations., (© The Author(s) 2024. Published by Oxford University Press on behalf of CINP.)

Response inhibition is an important instance of cognitive control and can be complicated by perceptual conflict. The neurophysiological mechanisms underlying these processes are still not understood. Especially the relationship between neural processes directly preceding cognitive control (proactive control) and processes underlying cognitive control (reactive control) has not been examined although there should be close links. In the current study, we investigate these aspects in a sample of N = 50 healthy adults. Time-frequency and beamforming approaches were applied to analyze the interrelation of brain states before (pre-trial) and during (within-trial) cognitive control. The behavioral data replicate a perceptual conflict-dependent modulation of response inhibition. During the pre-trial period, insular, inferior frontal, superior temporal, and precentral alpha activity was positively correlated with theta activity in the same regions and the superior frontal gyrus. Additionally, participants with a stronger pre-trial alpha activity in the primary motor cortex showed a stronger (within-trial) conflict effect in the theta band in the primary motor cortex. This theta conflict effect was further related to a stronger theta conflict effect in the midcingulate cortex until the end of the trial. The temporal cascade of these processes suggests that successful proactive preparation (anticipatory information gating) entails a stronger reactive processing of the conflicting stimulus information likely resulting in a realization of the need to adapt the current action plan. The results indicate that theta and alpha band activity share and transfer aspects of information when it comes to the interrelationship between proactive and reactive control during conflict-modulated motor inhibition., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Inhibitory control processes are an important aspect of executive functions and goal-directed behavior. However, the mostly correlative nature of neurophysiological studies was not able to provide insights which aspects of neural dynamics can best predict whether an individual is confronted with a situation requiring the inhibition of a response. This is particularly the case when considering the complex spatio-temporal nature of neural processes captured by EEG data. In the current study, we ask whether independent spatial activity profiles in the EEG data are useful to predict whether an individual is confronted with a situation requiring response inhibition. We combine independent component analysis (ICA) with explainable artificial intelligence approaches (EEG-based deep learning) using data from a Go/Nogo task (N = 255 participants). We show that there are four dissociable spatial activity profiles important to classify Go and Nogo trials as revealed by deep learning. Of note, for all of these four independent activity profiles, neural activity in the time period between 300 and 550 ms after stimulus presentation was most informative. Source localization analyses further revealed regions in the pre-central gyrus (BA6), the middle frontal gyrus (BA10), the inferior frontal gyrus (BA46), and the insular cortex (BA13) were associated with the isolated spatial activity profiles. The data suggest concomitant processes being reflected in the identified time window. This has implications for the ongoing debate on the functional significance of event-related potential correlates of inhibitory control., (© 2023 The Authors. Psychophysiology published by Wiley Periodicals LLC on behalf of Society for Psychophysiological Research.)

Everyday tasks and goal-directed behavior involve the maintenance and continuous updating of information in working memory (WM). WM gating reflects switches between these two core states. Neurobiological considerations suggest that the catecholaminergic and the GABAergic are likely involved in these dynamics. Both of these neurotransmitter systems likely underlie the effects to auricular transcutaneous vagus nerve stimulation (atVNS). We examine the effects of atVNS on WM gating dynamics and their underlying neurophysiological and neurobiological processes in a randomized crossover study design in healthy humans of both sexes. We show that atVNS specifically modulates WM gate closing and thus specifically modulates neural mechanisms enabling the maintenance of information in WM. WM gate opening processes were not affected. atVNS modulates WM gate closing processes through the modulation of EEG alpha band activity. This was the case for clusters of activity in the EEG signal referring to stimulus information, motor response information, and fractions of information carrying stimulus-response mapping rules during WM gate closing. EEG-beamforming shows that modulations of activity in fronto-polar, orbital, and inferior parietal regions are associated with these effects. The data suggest that these effects are not because of modulations of the catecholaminergic (noradrenaline) system as indicated by lack of modulatory effects in pupil diameter dynamics, in the inter-relation of EEG and pupil diameter dynamics and saliva markers of noradrenaline activity. Considering other findings, it appears that a central effect of atVNS during cognitive processing refers to the stabilization of information in neural circuits, putatively mediated via the GABAergic system. SIGNIFICANCE STATEMENT Goal-directed behavior depends on how well information in short-term memory can be flexibly updated but also on how well it can be shielded from distraction. These two functions were guarded by a working memory gate. We show how an increasingly popular brain stimulation techniques specifically enhances the ability to close the working memory gate to shield information from distraction. We show what physiological and anatomic aspects underlie these effects., (Copyright © 2023 the authors.)

It seems natural that motor responses unfold smoothly and that we are able to easily concatenate different components of movements to achieve goal-directed actions. Theoretical frameworks suggest that different motor features have to be bound to each other to achieve a coherent action. Yet, the nature of the "glue" (i.e., bindings) between elements constituting a motor sequence and enabling a smooth unfolding of motor acts is not well understood. We examined in how far motor feature bindings are affected by reward magnitude or the effects of an unsigned surprise signal. We show that the consistency of action file binding strength is modulated by unsigned surprise, but not by reward magnitude. On a conceptual and theoretical level, the results provide links between frameworks, which have until now not been brought into connection. In particular, theoretical accounts stating that only the unexpectedness (surprisingness) is essential for action control are connected to meta-control accounts of human action control., (© 2023. The Author(s).)

Inhibitory control processes have intensively been studied in cognitive science for the past decades. Even though the neural dynamics underlying these processes are increasingly better understood, a critical open question is how the representational dynamics of the inhibitory control processes are modulated when engaging in response inhibition in a relatively automatic or a controlled mode. Against the background of an overarching theory of perception-action integration, we combine temporal and spatial EEG signal decomposition methods with multivariate pattern analysis and source localization to obtain fine-grained insights into the neural dynamics of the representational content of response inhibition. For this purpose, we used a sample of N = 40 healthy adult participants. The behavioural data suggest that response inhibition was better in a more controlled than a more automated response execution mode. Regarding neural dynamics, effects of response inhibition modes relied on a concomitant coding of stimulus-related information and rules of how stimulus information is related to the appropriate motor programme. Crucially, these fractions of information, which are encoded at the same time in the neurophysiological signal, are based on two independent spatial neurophysiological activity patterns, also showing differences in the temporal stability of the representational content. Source localizations revealed that the precuneus and inferior parietal cortex regions are more relevant than prefrontal areas for the representation of stimulus-response selection codes. We provide a blueprint how a concatenation of EEG signal analysis methods, capturing distinct aspects of neural dynamics, can be connected to cognitive science theory on the importance of representations in action control., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

The integration of perception and action has long been studied in psychological science using overarching cognitive frameworks. Despite these being very successful in explaining perception-action integration, little is known about its neurophysiological and especially the functional neuroanatomical foundations. It is unknown whether distinct brain structures are simultaneously involved in the processing of perception-action integration codes and also to what extent demands on perception-action integration modulate activities in these structures. We investigate these questions in an EEG study integrating temporal and ICA-based EEG signal decomposition with source localization. For this purpose, we used data from 32 healthy participants who performed a 'TEC Go/Nogo' task. We show that the EEG signal can be decomposed into components carrying different informational aspects or processing codes relevant for perception-action integration. Importantly, these specific codes are processed independently in different brain structures, and their specific roles during the processing of perception-action integration differ. Some regions (i.e., the anterior cingulate and insular cortex) take a 'default role' because these are not modulated in their activity by demands or the complexity of event file coding processes. In contrast, regions in the motor cortex, middle frontal, temporal, and superior parietal cortices were not activated by 'default' but revealed modulations depending on the complexity of perception-action integration (i.e., whether an event file has to be reconfigured). Perception-action integration thus reflects a multi-region processing of specific fractions of information in the neurophysiological signal. This needs to be taken into account when further developing a cognitive science framework detailing perception-action integration., (© 2022 The Authors. Psychophysiology published by Wiley Periodicals LLC on behalf of Society for Psychophysiological Research.)

Response inhibition and the ability to navigate distracting information are both integral parts of cognitive control and are imperative to adaptive behavior in everyday life. Thus far, research has only inconclusively been able to draw inferences regarding the association between response stopping and the effects of interfering information. Using a novel combination of the Simon task and a stop signal task, the current study set out to investigate the behavioral as well as the neurophysiological underpinnings of the relationship between response stopping and interference processing. We tested n  = 27 healthy individuals and combined temporal EEG signal decomposition with source localization methods to delineate the precise neurophysiological dynamics and functional neuroanatomical structures associated with conflict effects on response stopping. The results showed that stopping performance was compromised by conflicts. Importantly, these behavioral effects were reflected by specific aspects of information coded in the neurophysiological signal, indicating that conflict effects during response stopping are not mediated via purely perceptual processes. Rather, it is the processing of specific, stop-relevant stimulus features in the sensory regions during response selection, which underlies the emergence of conflict effects in response stopping. The findings connect research regarding response stopping with overarching theoretical frameworks of perception-action integration., (© The Author(s) 2023. Published by Oxford University Press.)

Actions can fail - even though this is well known, little is known about what distinguishes neurophysiological processes preceding errors and correct actions. In this study, relying on the Theory of Event Coding, we test the assumption that only specific aspects of information coded in EEG activity are relevant for understanding processes leading to response errors. We examined N = 69 healthy participants who performed a mental rotation task and combined temporal EEG signal decomposition with multivariate pattern analysis (MVPA) and source localization analyses. We show that fractions of the EEG signal, primarily representing stimulus-response translation (event file) processes and motor response representations, are essential. Stimulus representations were less critical. The source localization results revealed widespread activity modulations in structures including the frontopolar, the middle and superior frontal, the anterior cingulate cortex, the cuneus, the inferior parietal cortex, and the ventral stream regions. These are associated with differential effects of the neural dynamics preceding correct/erroneous responses. The temporal-generalization MVPA showed that event file representations and representations of the motor response were already distinct 200 ms after stimulus presentation and this lasted till around 700 ms. The stability of this representational content was predictive for the magnitude of posterror slowing, which was particularly strong when there was no clear distinction between the neural activity profile of event file representations associated with a correct or an erroneous response. The study provides a detailed analysis of the dynamics leading to an error/correct response in connection to an overarching framework on action control., (© 2022 The Authors. Psychophysiology published by Wiley Periodicals LLC on behalf of Society for Psychophysiological Research.)

An efficient integration of sensory and motor processes is crucial to goal-directed behavior. Despite this high relevance, and although cognitive theories provide clear conceptual frameworks, the neurobiological basis of these processes remains insufficiently understood. In a double-blind, randomized placebo-controlled pharmacological study, we examine the relevance of catecholamines for perception-motor integration processes. Using EEG data, we perform an in-depth analysis of the underlying neurophysiological mechanisms, focusing on sensorimotor integration processes during response inhibition. We show that the catecholaminergic system affects sensorimotor integration during response inhibition by modulating the stability of the representational content. Importantly, catecholamine levels do not affect the stability of all aspects of information processing during sensorimotor integration, but rather-as suggested by cognitive theory-of specific codes in the neurophysiological signal. Particularly fronto-parietal cortical regions are associated with the identified mechanisms. The study shows how cognitive science theory-driven pharmacology can shed light on the neurobiological basis of perception-motor integration and how catecholamines affect specific information codes relevant to cognitive control., (© 2022. The Author(s).)

Even simple actions like opening a door require integration/binding and flexible reactivation of different motor elements. Yet, the neural mechanisms underlying the processing of such "embedded response plans" are largely elusive, despite theoretical frameworks, such as the theory of event coding, describing the involved cognitive processes. In a sample of n = 40 healthy participants, we combine time-frequency decomposition and various beamforming methods to examine the neurophysiological dynamics of such action plans, with special emphasis on the interplay of theta and beta frequency activity during the processing of these plans. We show that the integration and rule-guided reactivation of embedded response plans is modulated by a complex interplay of theta and beta activity. Pretrial beta-band activity (BBA) is related to different functional neuroanatomical structures that are activated in a consecutive fashion. Enhanced preparatory activity is positively associated with higher binding-related BBA in the precuneus/parietal areas, indicating that activity in the precuneus/parietal cortex facilitates the execution of an embedded action sequence. Increased preparation subsequently leads to reduced working memory retrieval demands. A cascading pattern of interactions between pretrial and within-trial activity indicates the importance of preparatory brain activity. The study shows that there are multiple roles of beta and theta oscillations associated with different functional neuroanatomical structures during the integration and reactivation of motor elements during actions. NEW & NOTEWORTHY Even simple actions like opening a door require integration/binding and flexible reactivation of different motor elements. Yet, the neural mechanisms underlying the processing of such "embedded response plans" are largely elusive. The study shows that there are multiple roles of beta and theta oscillations associated with different functional neuroanatomical structures during the integration and reactivation of motor elements during actions.

Background: Pursuing goals is compromised when being confronted with interfering information. In such situations, conflict monitoring is important. Theoretical considerations on the neurobiology of response selection and control suggest that auricular transcutaneous vagus nerve stimulation (atVNS) should modulate conflict monitoring. However, the neurophysiological-functional neuroanatomical underpinnings are still not understood., Methods: AtVNS was applied in a randomized crossover study design (n = 45). During atVNS or sham stimulation, conflict monitoring was assessed using a Flanker task. EEG data were recorded and analyzed with focus on theta and alpha band activity. Beamforming was applied to examine functional neuroanatomical correlates of atVNS-induced EEG modulations. Moreover, temporal EEG signal decomposition was applied to examine different coding levels in alpha and theta band activity., Results: AtVNS compromised conflict monitoring processes when it was applied at the second appointment in the crossover study design. On a neurophysiological level, atVNS exerted specific effects because only alpha-band activity was modulated. Alpha-band activity was lower in middle and superior prefrontal regions during atVNS stimulation and thus lower when there was also a decline in task performance. The same direction of alpha-band modulations was evident in fractions of the alpha-band activity coding stimulus-related processes, stimulus-response translation processes, and motor response-related processes., Conclusions: The combination of prior task experience and atVNS compromises conflict monitoring processes. This is likely due to reduction of the alpha-band-associated inhibitory gating process on interfering information in frontal cortices. Future research should pay considerable attention to boundary conditions affecting the direction of atVNS effects., (© The Author(s) 2022. Published by Oxford University Press on behalf of CINP.)

The electroencephalogram (EEG) is one of the most widely used techniques in cognitive neuroscience. We present a protocol showing how to combine a temporal signal decomposition approach (RIDE, Residue iteration decomposition) with multivariate pattern analysis (MVPA) to obtain insights into the temporal stability of representations coded in distinct informational fractions of the EEG signal. In this protocol, we describe pre-processing of human EEG data, followed by the set-up and use of MATLAB-based toolboxes for RIDE and MVPA analysis. For complete details on the use and execution of this protocol, please refer to Petruo et al. (2021)., Competing Interests: The authors declare no competing interests., (© 2022.)

The ability to inhibit responses is central for situational behavior. However, the mechanisms how sensory information is used to inform inhibitory control processes are incompletely understood. In the current study, we examined neurophysiological processes of perception-action integration in response inhibition using the theory of event coding as a conceptual framework. Based on theoretical considerations, we focused on theta and alpha band activity in close connection to the functional neuroanatomical level using EEG beamforming. Moreover, we performed a network-based analysis of theta and alpha band activity. We show a seesaw-like relationship between medial and superior frontal cortex theta band activity and frontoparietal cortex alpha band activity during perception-action integration in response inhibition, depending on the necessity to reconfigure perception-action associations. When perception-action integration was more demanding, because perception-action associations (bindings) have to be reconfigured, there was an increase of theta and a decrease of alpha band activity. Vice versa, when there was no need to reconfigure perception-action bindings, theta band activity was low and alpha band activity was high. However, theta band processes seem to be most important for perception-action integration in response inhibition, because only the sensor-level network organization of theta band activity showed variations depending on the necessity to reconfigure perception-action associations. When no reconfiguration was necessary, the network architecture was more small-world-like, likely enabling efficient processing. When reconfigurations were necessary, the network organization becomes more random. These differences were particularly strong for fractions of the neurophysiological signal supposed to reflect response selection processes., (© 2022 Massachusetts Institute of Technology.)

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).)

Goal-directed actions frequently require a balance between antagonistic processes (e.g., executing and inhibiting a response), often showing an interdependency concerning what constitutes goal-directed behavior. While an inter-dependency of antagonistic actions is well described at a behavioral level, a possible inter-dependency of underlying processes at a neuronal level is still enigmatic. However, if there is an interdependency, it should be possible to predict the neurophysiological processes underlying inhibitory control based on the neural processes underlying speeded automatic responses. Based on that rationale, we applied artificial intelligence and source localization methods to human EEG recordings from N = 255 participants undergoing a response inhibition experiment (Go/Nogo task). We show that the amplitude and timing of scalp potentials and their functional neuroanatomical sources during inhibitory control can be inferred by conditional generative adversarial networks (cGANs) using neurophysiological data recorded during response execution. We provide insights into possible limitations in the use of cGANs to delineate the interdependency of antagonistic actions on a neurophysiological level. Nevertheless, artificial intelligence methods can provide information about interdependencies between opposing cognitive processes on a neurophysiological level with relevance for cognitive theory., (© 2022. The Author(s).)

Inhibitory control has multiple facets, and one possible distinction can be made between 'inhibition of interferences' and the 'inhibition of actions'. Both facets of inhibitory control show an interdependency. Even though some neurophysiological processes underlying this interdependency have been examined, the role of neuro-modulatory processes in their interplay are not understood. In the current study, we examine the role of the norepinephrine (NE) system in these processes. We did so by combining a Go/Nogo and Simon task. We recorded the EEG and pupil diameter data as an indirect index of NE system activity during the task. EEG theta band activity data and pupil diameter data were then integrated after conducting a temporal signal decomposition of the EEG data. We show that particularly theta band activity coding stimulus-response translation processes associated with middle frontal cortices, but not stimulus-driven processes are modulated by the interplay between the 'inhibition of interferences' and the 'inhibition of actions'. Modulations in stimulus-response translation processes were systematically correlated with pupil-diameter responses. The pattern of correlations suggests that phasic NE system activity particularly modulates stimulus-response mapping processes during conflict monitoring in incongruent Nogo trials, which may explain behavioral performance effects. Phasic NE system activity reflects essential modulators of the interplay between the 'inhibition of interferences' and the 'inhibition of actions'., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Impairment of cognitive performance is often observed in time-on tasks. Theoretical considerations suggest that especially prefrontal cortex cognitive control functions is affected by time-on-task effects, but the role of effort/task engagement is not understood. We examine time-on-task effects in cognitive control on a neurophysiological level using a working-memory modulated response inhibition task and inter-relate prefrontal neuroanatomical region-specific theta-band activity with pupil diameter data using EEG-beamforming approaches. We show that task performance declines with time-on tasks, which was paralleled by a concomitant decreases of task-evoked superior frontal gyrus theta-band activity and a reduction in phasic pupil diameter modulations. A strong relation between cognitive control-related superior frontal theta-band activity and effort/task engagement indexed by phasic pupil diameter modulations was observed in the beginning of the experiment, especially for tasks requiring inhibitory controls and demanding high working memory. This strong relation vanished at the end of the experiment, suggesting a decoupling of cognitive control resources useable for a task and effort invested that characterizes time-on-task effects in prefrontal cortical structures., (© 2022. The Author(s).)

Performance impairment as an effect of prolonged engagement in a specific task is commonly observed. Although this is a well-known effect in everyday life, little is known about how this affects central cognitive functions such as working memory (WM) processes. In the current study, we ask how time-on-task affects WM gating processes and thus processes regulating WM maintenance and updating. To this end, we combined electroencephalography methods and recordings of the pupil diameter as an indirect of the norepinephrine (NE) system activity. Our results showed that only WM gate opening but not closing processes showed time-on-task effects. On the neurophysiological level, this was associated with modulation of dorsolateral prefrontal theta band synchronization processes, which vanished with time-on-task during WM gate opening. Interestingly, also the modulatory pattern of the NE system, as inferred using pupil diameter data, changed. At the beginning, a strong correlation of pupil diameter data and theta band synchronization processes during WM gate opening is observed. This modulatory effect vanished at the end of the experiment. The results show that time-on-task has very specific effects on WM gate opening and closing processes and suggests an important role of NE system in the time-on-task effect on WM gate opening process., (© The Author(s) 2022. Published by Oxford University Press.)

Cognitive control and working memory (WM) processes are essential for goal-directed behaviour. Cognitive control and WM are probably based on overlapping neurophysiological mechanisms. For example, theta-band activity (TBA) plays an important role in both functions. For cognitive control processes, it is known that different aspects of information about stimulus content, motor processes and stimulus-response relationships are encoded simultaneously in the TBA. All this information is probably processed during WM gating processes and must be controlled during them. However, direct data for this are lacking. This question is investigated in this study by combining methods of EEG temporal signal decomposition, time-frequency decomposition and beamforming. We show that portions of stimulus-related information, motor response-related information and information related to the interaction between the stimulus and motor responses in the TBA are influenced in parallel and to a similar extent by WM gate opening and gate closing processes. Nevertheless, it is stimulus-related information in the theta signal in particular that modulates behavioural performance in WM-gating. The data suggest that the identified processes are implemented in specific neuroanatomical structures. In particular, the medial frontal cortex, temporal cortical regions and insular cortex are involved in these dynamics. The study shows that principles of information coding relevant to cognitive control processes are also crucial for understanding WM gating., Competing Interests: Conflict of interests The authors declare no conflicts of interest., (Copyright © 2021 IBRO. Published by Elsevier Ltd. All rights reserved.)

Cognitive flexibility is essential to achieve higher level goals. Cognitive theories assume that the activation/deactivation of goals and task rules is central to understand cognitive flexibility. However, how this activation/deactivation dynamic is implemented on a neurophysiological level is unclear. Using EEG-based multivariate pattern analysis (MVPA) methods, we show that activation of relevant information occurs parallel in time at multiple levels in the neurophysiological signal containing aspects of stimulus-related processing, response selection, and motor response execution, and relates to different brain regions. The intensity with which task sets are activated and processed dynamically decreases and increases. The temporal stability of these activations could, however, hardly explain behavioral performance. Instead, task set deactivation processes associated with left orbitofrontal regions and inferior parietal regions selectively acting on motor response task sets are relevant. The study shows how propositions from cognitive theories stressing the importance task set activation/deactivation during cognitive flexibility are implemented on a neurophysiological level., Competing Interests: There is no financial and non-financial competing interest., (© 2021 The Author(s).)

Tourette syndrome is a common neurodevelopmental disorder defined by multiple motor and phonic tics. Tics in Tourette syndrome resemble spontaneously occurring movements in healthy controls and are therefore sometimes difficult to distinguish from these. Tics may in fact be mis-interpreted as a meaningful action, i.e. a signal with social content, whereas they lack such information and could be conceived a surplus of action or 'motor noise'. These and other considerations have led to a 'neural noise account' of Tourette syndrome suggesting that the processing of neural noise and adaptation of the signal-to-noise ratio during information processing is relevant for the understanding of Tourette syndrome. So far, there is no direct evidence for this. Here, we tested the 'neural noise account' examining 1/ f noise, also called scale-free neural activity as well as aperiodic activity, in n  = 74 children, adolescents and adults with Tourette syndrome and n  = 74 healthy controls during task performance using EEG data recorded during a sensorimotor integration task. In keeping with results of a previous study in adults with Tourette syndrome, behavioural data confirmed that sensorimotor integration was also stronger in this larger Tourette syndrome cohort underscoring the relevance of perceptual-action processes in this disorder. More importantly, we show that 1/ f noise and aperiodic activity during sensorimotor processing is increased in patients with Tourette syndrome supporting the 'neural noise account'. This implies that asynchronous/aperiodic neural activity during sensorimotor integration is stronger in patients with Tourette syndrome compared to healthy controls, which is probably related to abnormalities of GABAergic and dopaminergic transmission in these patients. Differences in 1/ f noise and aperiodic activity between patients with Tourette syndrome and healthy controls were driven by high-frequency oscillations and not lower-frequency activity currently discussed to be important in the pathophysiology of tics. This and the fact that Bayesian statistics showed that there is evidence for the absence of a correlation between neural noise and clinical measures of tics, suggest that increased 1/ f noise and aperiodic activity are not directly related to tics but rather represents a novel facet of Tourette syndrome., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

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.)

Cognitive flexibility is an essential prerequisite for goal-directed behavior, and daily observations already show that it deteriorates when one is engaged in a task for a (too) long time. Yet, the neural mechanisms underlying such fatigability effect in cognitive flexibility are poorly understood. We examined how theta, alpha, and beta frequency event-related synchronization and desynchronization processes during cued memory-based task switching are modulated by time-on-task effects. We put special emphasis on the examination of functional neuroanatomical regions being associated with these modulations, using EEG beamforming. We show clear declines in task switching performance (increased switch costs) with time on task. For processes occurring before rule switching or repetition processes, we show that anticipatory attentional sampling and selection mechanisms associated with fronto-parietal structures are modulated by time-on-task effects but sensory areas (occipital cortex) also show fatigability-dependent modulations. After target stimulus presentation, the allocation of processing resources for response selection as reflected by theta-related activity in parietal cortices is compromised with time on task and similarly a concomitant increase in alpha and beta band-related attentional processing or gating mechanisms in frontal and occipital regions. Yet, considering the behavioral data showing an apparent decline in performance, this probably compensatory increase is still insufficient to allow reasonable performance. The same is likely the case for processes occurring before rule switching or repetition processes. Comparative analyses show that modulations of alpha band activity are as strongly modulated by fatigability as theta band activity. Implications of these findings for theoretical concepts on fatigability are discussed. NEW & NOTEWORTHY We examine the neurophysiological and functional neuroanatomical basis of fatigability in cognitive flexibility. We show that alpha and theta modulations in fronto-parietal and primary sensory areas are central for the understanding of fatigability effects in cognitive flexibility.

The investigation of action control processes is one major field in cognitive neuroscience and several theoretical frameworks have been proposed. One established framework is the "Theory of Event Coding" (TEC). However, only rarely, this framework has been used in the context of response inhibition and how stimulus-response association or binding processes modulate response inhibition performance. Particularly the neural dynamics of stimulus-response representations during inhibitory control are elusive. To address this, we examined n = 40 healthy controls and combined temporal EEG signal decomposition with source localization and temporal generalization multivariate pattern analysis (MVPA). We show that overlaps in features of stimuli used to trigger either response execution or inhibition compromised task performance. According to TEC, this indicates that binding processes in event file representations impact response inhibition through partial repetition costs. In the EEG data, reconfiguration of event files modulated processes in time windows well-known to reflect distinct response inhibition mechanisms. Crucially, event file coding processes were only evident in a specific fraction of neurophysiological activity associated with the inferior parietal cortex (BA40). Within that specific fraction of neurophysiological activity, the decoding of the dynamics of event file representations using temporal generalization MVPA suggested that event file representations are stable across several hundred milliseconds, and that event file coding during inhibitory control is reflected by a sustained activation pattern of neural dynamics. NEW & NOTEWORTHY The "mental representation" of how stimulus input translate into the appropriate response is central for goal-directed behavior. However, little is known about the dynamics of such representations on the neurophysiological level when it comes to the inhibition of motor processes. This dynamic is shown in the current study.

Background: The process underlying the integration of perception and action is a focal topic in neuroscientific research and cognitive frameworks such as the theory of event coding have been developed to explain the mechanisms of perception-action integration. The neurobiological underpinnings are poorly understood. While it has been suggested that the catecholaminergic system may play a role, there are opposing predictions regarding the effects of catecholamines on perception-action integration., Methods: Methylphenidate (MPH) is a compound commonly used to modulate the catecholaminergic system. In a double-blind, randomized crossover study design, we examined the effect of MPH (0.25 mg/kg) on perception-action integration using an established "event file coding" paradigm in a group of n = 45 healthy young adults., Results: The data reveal that, compared with the placebo, MPH attenuates binding effects based on the established associations between stimuli and responses, provided participants are already familiar with the task. However, without prior task experience, MPH did not modulate performance compared with the placebo., Conclusions: Catecholamines and learning experience interactively modulate perception-action integration, especially when perception-action associations have to be reconfigured. The data suggest there is a gain control-based mechanism underlying the interactive effects of learning/task experience and catecholaminergic activity during perception-action integration., (© The Author(s) 2021. Published by Oxford University Press on behalf of CINP.)

Patients with attention deficit/(hyperactivity) disorder (AD(H)D) show increased intra-individual variability (IIV) in behavioral performance. This likely reflects dopaminergic deficiencies. However, the precise performance profile across time and the pattern of fluctuations within it have not yet been considered, partly due to insufficient methods. Yet, such an analysis may yield important theory-based implications for clinical practice. Thus, in a case-control cross-sectional study, we introduce a new method to investigate performance fluctuations in patients with ADD (n = 76) and ADHD (n = 67) compared to healthy controls (n = 45) in a time estimation task. In addition, we also evaluate the effects of methylphenidate (MPH) treatment on this performance pattern in 29 patients with AD(H)D. Trial-by-trial differences in performance between healthy controls and patients with AD(H)D do not persist continuously over longer time periods. Periods during which no differences in performance between healthy controls and patients occur alternate with periods in which such differences are present. AD(H)D subtype and surprisingly also medication status does not affect this pattern. The presented findings likely reflect (phasic) deficiencies of the dopaminergic system in patients with AD(H)D which are not sufficiently ameliorated by first-line pharmacological treatment. The presented findings carry important clinical and scientific implications.

Background: Gilles de la Tourette Syndrome (GTS) is a neurodevelopmental disorder with a peak of symptom severity around late childhood and early adolescence. Previous findings in adult GTS suggest that changes in perception-action integration, as conceptualized in the theory of event coding framework, are central for the understanding of GTS. However, the neural mechanisms underlying these processes in adolescence are elusive., Methods: A total of 59 children/adolescents aged 9 to 18 years ( n  = 32 with GTS, n  = 27 typically developing youths) were examined using a perception-action integration task (event file task) derived from the theory of event coding. Event-related electroencephalogram recordings (theta and beta band activity) were analyzed using electroencephalogram-beamforming methods., Results: Behavioral data showed robust event file binding effects in both groups without group differences. Neurophysiological data showed that theta and beta band activity were involved in event file integration in both groups. However, the functional neuroanatomical organization was markedly different for theta band activity between the groups. The typically developing group mainly relied on superior frontal regions, whereas the GTS group engaged parietal and inferior frontal regions. A more consistent functional neuroanatomical activation pattern was observed for the beta band, engaging inferior parietal and temporal regions in both groups., Conclusions: Perception-action integration processes lag behind in persisting GTS but not in the GTS population as a whole, underscoring differences in developmental trajectories and the importance of longitudinal investigations for the understanding of GTS. The findings corroborate known differences in the functional/structural brain organization in GTS and suggest an important role of theta band activity in these patients., (© 2021 The Authors.)

To respond as quickly as possible in a given task is a widely used instruction in cognitive neuroscience; however, the neural processes modulated by this common experimental procedure remain largely elusive. We investigated the underlying neurophysiological processes combining electroencephalography (EEG) signal decomposition (residue iteration decomposition, RIDE) and source localization. We show that trial-based response speed instructions enhance behavioral performance in conflicting trials, but slightly impair performance in nonconflicting trials. The modulation seen in conflicting trials was found at several coding levels in EEG data using RIDE. In the S-cluster N2 time window, this modulation was associated with modulated activation in the posterior cingulate cortex and the superior frontal gyrus. Furthermore, in the C-cluster P3 time window, this modulation was associated with modulated activation in the middle frontal gyrus. Interestingly, in the R-cluster P3 time window, this modulation was strongest according to statistical effect sizes, associated with modulated activity in the primary motor cortex. Reaction-time feedback mainly modulates response motor execution processes, whereas attentional and response selection processes are less affected. The study underlines the importance of being aware of how experimental instructions influence the behavior and neurophysiological processes., (© The Author(s) 2021. Published by Oxford University Press.)

Functional connectivity in EEG resting-state is not stable but fluctuates considerably. The aim of this study was to investigate how efficient information flows through a network, i.e. how resting-state EEG networks are organized and whether this organization it also subject to fluctuations. Differences of the network organization (small-worldness), degree of clustered connectivity, and path length as an indicator of how information is integrated into the network across time was compared between theta, alpha and beta bands. We show robust differences in network organization (small-worldness) between frequency bands. Fluctuations in network organization were larger in the theta, compared to the alpha and beta frequency. Variation in network organization and not the frequency of fluctuations differs between frequency bands. Furthermore, the degree of clustered connectivity and its modulation across time is the same across frequency bands, but the path length revealed the same modulatory pattern as the small-world metric. It is therefore the interplay of local processing efficiency and global information processing efficiency in the brain that fluctuates in a frequency-specific way. Properties of how information can be integrated is subject to fluctuations in a frequency-specific way in the resting-state. The possible relevance of these resting-state EEG properties is discussed including its clinical relevance., (Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.)

Brain electrical activity in the theta frequency band is essential for cognitive control (e.g., during conflict monitoring), but is also evident in the resting state. The link between resting state theta activity and its relevance for theta-related neural mechanisms during cognitive control is still undetermined. Yet, theoretical considerations suggest that there may be a connection. To examine the link between resting state theta activity and conflict-related theta activity, we combined temporal EEG signal decomposition methods with time-frequency decomposition and beamforming methods in N = 86 healthy participants. Results indicate that resting state theta activity is closely associated with the strength of conflict-related neural activity at the level of ERPs and total theta power (consisting of phase-locked and nonphase-locked aspects of theta activity). The data reveal that resting state theta activity is related to a specific aspect of conflict-related theta activity, mainly in superior frontal regions and in the supplemental motor area (SMA, BA6) in particular. The signal decomposition showed that only stimulus-related, but not motor-response-related coding levels in the EEG signal and the event-related total theta activity were associated with resting theta activity. This specificity of effects may explain why the association between resting state theta activity and overt conflict monitoring performance may not be as strong as often assumed. The results suggest that resting state theta activity is particularly important to consider for input integration processes during cognitive control., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Consciously and subliminally processed information can both lead to conflicts that hinder goal-directed behaviour. Conflict monitoring processes are required to cope with situations where one or multiple conflicts occur. It has been suggested, that medial-frontal theta oscillations are associated with the implementation of cognitive control and that conflicts increase theta band activity. Still, a causal mechanistic understanding of theta oscillations during the resolution of combined subliminal and conscious conflicts is missing. To investigate this, we combined EEG signal decomposition methods with EEG beamforming approaches and used the obtained information to modulate theta oscillations with tACS in a second experiment. This showed that theta oscillations in the superior frontal cortex (BA6) and the left paracentral lobule encoded stimulus-related processes during the resolution of conflicts arising from both conscious and subliminal information processing. Response selection and motor-related processes encoded by theta oscillations were not similarly modulated. Thus, the joint modulation of conflicts by conscious and subliminal information affects very specific aspects of the information coded in theta oscillations. Results indicate, that entraining theta-oscillations using tACS modulates conflict resolution depending on the already existing theta activity level. In summary, the study provides further evidence that frontal theta oscillations play a crucial role in conflict monitoring and control., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Binge drinking is a frequent phenomenon in many western societies and has been associated with an increased risk of developing alcohol use disorder later in life. Yet, the effects of high-dose alcohol intoxication on neurophysiological processes are still quite poorly understood. This is particularly the case given that neurophysiological brain activity not only contains recurring (oscillatory) patterns of activity, but also a significant fraction of "scale-free" or arrhythmic dynamics referred to as 1/f type activity, pink noise, or 1/f neural noise. Neurobiological considerations suggest that it should be modulated by alcohol intoxication. To investigate this assumption, we collected resting state EEG data from n = 23 healthy young male subjects in a crossover design, where each subject was once tested sober and once tested while intoxicated (mean breath alcohol concentration of 1.1 permille ±0.2). Analyses of the 1/f neural dynamics showed that ethanol intoxication decreased resting state 1/f neural noise, as compared with a sober state. The effects were strongest when the eyes were closed and particularly reliable in the beta frequency band. Given that the dynamics of the beta band have been shown to strongly depend on GABA A receptor neural transmission, this finding nicely aligns with the fact that ethanol increases GABAergic signaling. The study reveals a currently unreported effect of binge drinking on neurophysiological dynamics, which likely revealed a higher sensitivity for ethanol effects than most commonly considered measures of power in neural oscillations. Implications and applicability of these findings are discussed., (© 2019 Society for the Study of Addiction.)

The assessment of neuropsychological functions and especially dual-tasking abilities is considered to be increasingly relevant in the assessment of neurological disease, and Multiple Sclerosis (MS) in particular. However, the assessment of dual-tasking abilities is hindered by specific software requirements and extensive testing times. We designed a novel e-health (progressive web application-based) device for the assessment of dual-tasking abilities usable in "bedside" and outpatient clinic settings and examined its reliability in a sample of N = 184 MS patients in an outpatient setting. Moreover, we examined the relevance of dual-tasking assessment using this device with respect to clinically relevant parameters in MS. We show that a meaningful assessment of dual-tasking is possible within 6 min and that the behavioral readouts overall show good reliability depending on dual-tasking difficulty. We show that dual-tasking readouts were correlated with clinically relevant parameters (e.g., EDSS, disease duration, processing speed) and were not affected by fatigue levels. We consider the tested dual-tasking assessment device suitable for routine clinical neuropsychological assessments of dual-tasking abilities. Future studies may further evaluate this test regarding its suitability in the long-term follow up assessments and to assess dual-tasking abilities in other neurological and psychiatric disorders.

The neurophysiological mechanisms underlying the integration of perception and action are an important topic in cognitive neuroscience. Yet, connections between neurophysiology and cognitive theoretical frameworks have rarely been established. The theory of event coding (TEC) details how perceptions and actions are associated (bound) in a common representational domain (the "event file"), but the neurophysiological mechanisms underlying these processes are hardly understood. We used complementary neurophysiological methods to examine the neurophysiology of event file processing (i.e., event-related potentials [ERPs], temporal EEG signal decomposition, EEG source localization, time-frequency decomposition, EEG network analysis). We show that the P3 ERP component and activity modulations in inferior parietal regions (BA40) reflect event file binding processes. The relevance of this parietal region is corroborated by source localization of temporally decomposed EEG data. We also show that temporal EEG signal decomposition reveals a pattern of results suggesting that event file processes can be dissociated from pure stimulus and response-related processes in the EEG signal. Importantly, it is also documented that event file binding processes are reflected by modulations in the network architecture of theta frequency band activity. That is, when stimulus-response bindings in event files hamper response selection this was associated with a less efficient theta network organization. A more efficient organization was evident when stimulus-response binding in event files facilitated response selection. Small-world network measures seem to reflect event file processing. The results show how cognitive-theoretical assumptions of TEC can directly be mapped to the neurophysiology of response selection., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

Sequential cognitive flexibility is a major requirement for goal-directed behavior. Recent findings show that inhibitory control processes are crucial for sequential cognitive flexibility. These processes are indicated by the 'backward inhibition (BI) effect' which emerges when a mental representation that has recently been suppressed in favour of another task has to be re-activated. Alterations in the catecholaminergic neural transmission including the norepinephrine (NE) system have been shown to modulate inhibitory processes. However, a possible role of the NE system in sequential cognitive flexibility is elusive. The present study examines the relevance of the NE system for sequential cognitive flexibility by integrating pupil diameter data and electrophysiological (EEG) data applying signal decomposition techniques and source localization. We show that the BI effects modulated amplitudes in the P1/N1 time window, as well as in the N2 time window. Correlating this data with the pupil diameter data only revealed substantial correlations in the P1/N1 time window. Moreover, it is shown that regions in the right inferior frontal gyrus are activated during modulations in the P1 time window, in which correlations with the pupil diameter data were also evident. The results are interpreted that sequential cognitive flexibility modulates early inhibitory gating processes (P1) which are related to the suppression of task-irrelevant information in inferior frontal regions. These processes are likely modulated by the NE system., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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.)

Goal-directed actions require proper associations between stimuli and response. This has been delineated by cognitive theory, for example, in the theory of event coding framework, which proposes that event files represent such bindings. Yet, how such event file representations are coded on a neurophysiological level is unknown. We close this gap combining temporal electroencephalography (EEG) signal decomposition methods and multivariate pattern analysis (MVPA). We show that undecomposed neurophysiological data is unsuitable to decode event file representations because different aspects of information coded in the neurophysiological signal reveal distinct and partly opposed dynamics in the representational content. This is confirmed by applying MVPA to temporal decomposed EEG data. After intermixed aspects of information in the EEG during response selection have been separated, a reliable examination of the event file's representational content and its temporal stability was possible. We show that representations of stimulus-response bindings are activated and decay in a gradual manner and that event file representations resemble distributed neural activity. Especially representations of stimulus-response bindings, as well as stimulus-related representations, are coded and reveal temporal stability. Purely motor-related representations are not found in neurophysiological signals during event coding., (© The Author(s) 2020. Published by Oxford University Press.)

We ask whether actions of the norepinephrine (NE) system during response inhibition are affected by properties of lower level sensory stimulus processing. We used a somato-sensory Go/Nogo task and combined ERP recordings with pupil diameter recordings as an index of NE system activity. The Go/Nogo task was designed to achieve processing of tactile stimuli predominantly over primary somatosensory (SI) and secondary somatosensory (SII) areas. The data show that response inhibition was better when stimuli were processed via SII, compared to SI areas. This was reflected by variations in the Nogo-N2/P3 associated with anterior cingulate structures. Correlations with the pupil diameter data, indicting modulations of the NE system during inhibitory control processes, were only evident when SI sensory areas were involved. These dissociable modulatory effects were associated with activations in the superior frontal gyrus. Actions of the NE system during response inhibition are modulated by properties of lower level processing., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)