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Understanding the neural mechanisms underlying metacontrol and conflict regulation is crucial for insights into cognitive flexibility and persistence. This study employed electroencephalography (EEG), EEG-beamforming and directed connectivity analyses to explore how varying metacontrol states influence conflict regulation at a neurophysiological level. Metacontrol states were manipulated by altering the frequency of congruent and incongruent trials across experimental blocks in a modified flanker task, and both behavioral and electrophysiological measures were analyzed. Behavioral data confirmed the experimental manipulation's efficacy, showing an increase in persistence bias and a reduction in flexibility bias during increased conflict regulation. Electrophysiologically, theta band activity paralleled the behavioral data, suggesting that theta oscillations reflect the mismatch between expected metacontrol bias and actual task demands. Alpha and beta band dynamics differed across experimental blocks, though these changes did not directly mirror behavioral effects. Post-response alpha and beta activity were more pronounced in persistence-biased states, indicating a neural reset mechanism preparing for future cognitive demands. By using a novel artificial neural networks method, directed connectivity analyses revealed enhanced inter-regional communication during persistence states, suggesting stronger top-down control and sensorimotor integration. Overall, theta band activity was closely tied to metacontrol processes, while alpha and beta bands played a role in resetting the neural system for upcoming tasks. These findings provide a deeper understanding of the neural substrates involved in metacontrol and conflict monitoring, emphasizing the distinct roles of different frequency bands in these cognitive processes., Competing Interests: Declaration of competing interest There are no conflicts of interest, (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

A major concept in cognitive neuroscience is that brains are "prediction machines". Yet, conceptual frameworks on how perception and action become integrated still lack the concept of predictability and it is unclear how neural processes may implement predictive coding during dynamic perception-action integration. We show that distinct neurophysiological mechanisms of nonlinearly directed connectivities in the theta and alpha band between cortical structures underlie these processes. During the integration of perception and motor codes, especially theta band activity in the insular cortex and temporo-hippocampal structures is modulated by the predictability of upcoming information. Here, the insular cortex seems to guide processes. Conversely, the retrieval of such integrated perception-action codes during actions heavily relies on alpha band activity. Here, directed top-down influence of alpha band activity from inferior frontal structures on insular and temporo-hippocampal structures is key. This suggests that these top-down effects reflect attentional shielding of retrieval processes operating in the same neuroanatomical structures previously involved in the integration of perceptual and motor codes. Through neurophysiology, the present study connects predictive coding mechanisms with frameworks specifying the dynamic integration of perception and action., Competing Interests: Declaration of competing interest There are no conflicts of interest, (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Executive functions are essential for adaptive behavior. One executive function is the so-called 'interference control' or conflict monitoring another one is inhibitory control (i.e., action restraint and action cancelation). Recent evidence suggests an interplay of these processes, which is conceptually relevant given that newer conceptual frameworks imply that nominally different action/response control processes are explainable by a small set of cognitive and neurophysiological processes. The existence of such overarching neural principles has as yet not directly been examined. In the current study, we therefore use EEG tensor decomposition methods, to look into possible common neurophysiological signatures underlying conflict-modulated action restraint and action cancelation as mechanism underlying response inhibition. We show how conflicts differentially modulate action restraint and action cancelation processes and delineate common and distinct neural processes underlying this interplay. Concerning the spatial information modulations are similar in terms of an importance of processes reflected by parieto-occipital electrodes, suggesting that attentional selection processes play a role. Especially theta and alpha activity seem to play important roles. The data also show that tensor decomposition is sensitive to the manner of task implementation, thereby suggesting that switch probability/transitional probabilities should be taken into consideration when choosing tensor decomposition as analysis method. The study provides a blueprint of how to use tensor decomposition methods to delineate common and distinct neural mechanisms underlying action control functions using EEG data., Competing Interests: Declaration of competing interest There are no conflicts of interest, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Catecholamines and amino acid transmitter systems are known to interact, the exact links and their impact on cognitive control functions have however remained unclear. Using a multi-modal imaging approach combining EEG and proton-magnetic resonance spectroscopy ( 1 H-MRS), we investigated the effect of different degrees of pharmacological catecholaminergic enhancement onto theta band activity (TBA) as a measure of interference control during response inhibition and execution. It was central to our study to evaluate the predictive impact of in-vivo baseline GABA+ concentrations in the striatum, the anterior cingulate cortex (ACC) and the supplemental motor area (SMA) of healthy adults under varying degrees of methylphenidate (MPH) stimulation. We provide evidence for a predictive interrelation of baseline GABA+ concentrations in cognitive control relevant brain areas onto task-induced TBA during response control stimulated with MPH. Baseline GABA+ concentrations in the ACC, the striatum, and the SMA had a differential impact on predicting interference control-related TBA in response execution trials. GABA+ concentrations in the ACC appeared to be specifically important for TBA modulations when the cognitive effort needed for interference control was high - that is when no prior task experience exists, or in the absence of catecholaminergic enhancement with MPH. The study highlights the predictive role of baseline GABA+ concentrations in key brain areas influencing cognitive control and responsiveness to catecholaminergic enhancement, particularly in high-effort scenarios., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Our everyday activities require the maintenance and continuous updating of information in working memory (WM). To control this dynamic, WM gating mechanisms have been suggested to be in place, but the neurophysiological mechanisms behind these processes are far from being understood. This is especially the case when it comes to the role of oscillatory neural activity. In the current study we combined EEG recordings, and anodal transcranial direct current stimulation (atDCS) and pupil diameter recordings to triangulate neurophysiology, functional neuroanatomy and neurobiology. The results revealed that atDCS, compared to sham stimulation, affected the WM gate opening mechanism, but not the WM gate closing mechanism. The altered behavioral performance was associated with specific changes in alpha band activities (reflected by alpha desynchronization), indicating a role for inhibitory control during WM gate opening. Functionally, the left superior and inferior parietal cortices, were associated with these processes. The findings are the first to show a causal relevance of alpha desynchronization processes in WM gating processes. Notably, pupil diameter recordings as an indirect index of the norepinephrine (NE) system activity revealed that individuals with stronger inhibitory control (as indexed through alpha desynchronization) showed less pupil dilation, suggesting they needed less NE activity to support WM gate opening. However, when atDCS was applied, this connection disappeared. The study suggests a close link between inhibitory controlled WM gating in parietal cortices, alpha band dynamics and the NE system., Competing Interests: Declaration of competing interest There are no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

In recent years, there has been many efforts to establish a comprehensive theoretical framework explaining the working mechanisms involved in perception-action integration. This framework stresses the importance of the immediate past on mechanisms supporting perception-action integration. The present study investigates the neurophysiological principles of dynamic perception-action bindings, particularly considering the influence of the immediate history on action control mechanisms. For this purpose, we conducted an established stimulus-response binding paradigm during EEG recording. The SR-task measures stimulus-response binding in terms of accuracy and reaction time differences depending on the degree of feature overlap between conditions. Alpha, beta and theta band activity in distinct time domains as well as associated brain regions were investigated applying time-frequency analyses, a beamforming approach as well as correlation analyses. We demonstrate, for the first time, interdependencies of neuronal processes relying on the immediate past. The reconfiguration of an action seems to overwrite immediately preceding processes. The analyses revealed modulations of theta (TBA), alpha (ABA) and beta band activity (BBA) in connection with fronto-temporal structures supporting the theoretical assumptions of the considered conceptual framework. The close interplay of attentional modulation by gating irrelevant information (ABA) and binding and retrieval processes (TBA) is reflected by the correlation of ABA in all pre-probe-intervals with post-probe TBA. Likewise, the role of BBA in maintaining the event file until retrieval is corroborated by BBA preceding the TBA-associated retrieval of perception-action codes. Following action execution, TBA shifted towards visual association cortices probably reflecting preparation for upcoming information, while ABA and BBA continue to reflect processes of attentional control and information selection for goal-directed behavior. The present work provides the first empirical support for concepts about the neurophysiological mechanisms of dynamic management of perception and action., Competing Interests: Declaration of competing interest There are no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Accumulating evidence suggests that peripheral physiological processes, such as the cardiac cycle, impact the individual's ability to appropriately exert control over behavior and emotional responses. We examine, whether response selection processes during cognitive-emotional control and its neurophysiological correlates, can be experimentally controlled in a cardiac-cycle dependent manner. To this end, we designed an experimental setup in which the EEG experiment, an emotional Stroop task, was controlled by the individual's electrocardiogram (ECG). Since theoretical considerations suggest that the effects of the cardiac cycle may affect only specific aspects during information processing, we apply EEG signal decomposition before examining functional neuroanatomical regions associated with cardiac-cycle dependent effects with EEG-beamforming approaches. Analyzing N = 27 healthy participants, we show that the cardiac-cycle specifically affects response selection processes, when demands on cognitive-emotional control are low. Response execution processes are sped up when trials are presented shortly after the ECG R peak. These effects were confined to conditions were response selection is not modulated by cognitive-emotional conflicts, which is in line with theoretical concepts on response selection. Corroborating the behavioural data, the EEG data show that particularly motor response-related processes encoded in the theta frequency band in middle and superior frontal regions (BA6) are differentially modulated by cardiac phase and difficulty to select a response. The presented work has an essential methodological focus in cognitive neuroscience for investigating brain-body interaction. It shows how peripheral-physiological parameters can be used to control EEG experiments and that the cardiac cycle has very specific effects in neurophysiological processes and associated functional neuroanatomical structures., (Copyright © 2020 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.)

The ability to cope with distracting information is a major requirement for goal-directed behavior. It is particularly challenged when distracting information is either potentially relevant or temporally close to goal-directed responses, resulting in so-called distractor-response bindings. According to the theory of event coding (TEC), distractor-response bindings should be reflected by processes in the event file, but not in object file (which stores stimulus features) or the action file (which stores response features). But even though the predictions of this theory are quite elaborated, their electrophysiological underpinnings and the associated functional neuroanatomical structures have remained largely elusive. To examine this, we used a distractor-response binding paradigm in combination with temporal EEG signal decomposition (RIDE) and source localization techniques. We showed that distractor-response binding effects are exclusively evident in the N450 time window of the central C-cluster. Source reconstructions revealed that distractor-response binding effects were associated with brain regions involved in updating internal representations by using task-relevant information to decide on response execution (temporo-parietal junction, BA40), alongside with brain regions involved in conflict resolution processes (right middle frontal gyrus, BA8). Our results suggest that RIDE can be used to dissociate binding processes from stimulus- and response-related processes. On top of this, the results of EEG decomposition match the key assumption of the TEC, that distractor-response bindings occur in event files, but not in object files or action files. The results show how cognitive-theoretical frameworks, such as the TEC, can directly be mapped onto the underlying neurophysiological processes using EEG signal decomposition., Competing Interests: Declaration of competing interest None., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Goal-directed behavior is affected by subliminally and consciously induced conflicts. Both seem to be modulated by catecholamines, especially dopamine. On the basis of cognitive theoretical and neurobiological considerations, we investigated the effects of dopamine D1 and D2 signaling with the help of unweighted polygenic scores in n = 207 healthy young human subjects. We used a task that combines subliminal primes with conscious flankers to induce conflicts. Dopamine D1 scores were formed based on DRD1 rs4532, CALY rs2298122 and TH rs10770141 single nucleotide polymorphisms (SNPs), while dopamine D2 scores were formed based on DRD2 rs6277 and NPY2R rs2234759 SNPs. We used EEG recordings and source localization analyses to identify differentially modulated neurophysiological sub-processes and functional neuroanatomical structures. Increased dopamine D1 signaling was associated with decreases in consciously induced conflicts. This decrease was due to enhanced stimulus-response mapping in the premotor cortex (BA6), as reflected by an increased P3 amplitude in incongruent trials. Attentional processes remained unaffected by dopamine D1 signaling. The effect of dopamine D2 signaling on conscious conflicts did not reach significance. Subliminally induced conflicts were neither modulated by dopamine D1, nor by dopamine D2 signaling. Our findings suggest that dopamine D1 signaling benefits consciously induced conflicts, presumably by improving the suppression of distracting information via gain control-initiated increases in top-down control processes associated with pre-motor regions. Dopamine D2 signaling does not seem to mediate behavioral differences. Probably, this is because the D2 state facilitates switching between (conflicting) top-down-selected mental representations, but not necessarily between top-down processes and bottom-up distractor information., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Successful action control requires the ability to attend to relevant sensory signals in the environment. This, however, can be complicated when different sensory inputs compete for the brain's limited resources. Under such conditions, sensory processes interact with top-down attention to selectively process goal-relevant stimuli, while inhibiting irrelevant or distracting sensory signals. In the current study, we set out to provide causal mechanistic insights for whether and how prefrontal regions are involved in resolving attentional-perceptual conflicts. To this end, we applied atDCS and examined neurophysiological processes of selective auditory perception. To evaluate whether atDCS differentially affects intermingled neurophysiological subprocesses involved during conflict resolution, we decomposed the EEG data using residue iteration decomposition (RIDE). We show that the right prefrontal regions are causally involved in resolving attentional-perceptual conflicts and that atDCS increases the efficacy to do so. The data show that dissociable neurophysiological signals are specifically affected by atDCS. Conflict resolution processes that involve inhibition of competing stimuli and response evaluation and are associated with right middle frontal gyrus (BA46) seem to become intensified by atDCS during the resolution of attentional-perceptual conflicts. After stimulation the early stimulus processing level was also less prone to sensory conflicts, but this alone could not explain the increased behavioral efficacy associated with atDCS. These observed effects likely reflect changes in neuronal gain control mechanisms. Taken together, results of this study may have implications for treating attentional hyperactivity disorder, for which pharmacological intervention is currently the common therapeutic approach., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

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.)

Until recently, investigating microscopic changes in the integrity of human brain matter has not been possible in vivo. It has hence remained unknown whether and how small non-pathological variations in cytoskeletal neuronal integrity affect human cognitive functioning. We investigated the role of neuronal cytoskeleton integrity for complex multicomponent behavior, which is relevant to real-life situations, as complex goals are often achieved by assembling a series of sub-tasks. For this, we quantified scaffolding proteins (i.e. neurofilament light; NF-L) using a single-molecule array (SIMOA), a new and uniquely ultra-sensitive method, and integrated this with behavioral and neurophysiological (EEG) data. For the first time, we showcase that slightest non-pathological variations in cytoskeletal integrity strongly modulate the efficiency of cognitive control processes. We show that the architecture and efficiency of theta-oscillations networks during cognitive control processes reflects a mechanism that establishes the relationship between neuronal cytoskeleton integrity and multicomponent behavior. Attentional selection processes do however not seem to play a role. The efficiency and network architecture of theta oscillations provides an important missing neural link that helps to explain how diffuse and seemingly miniscule variations in neuronal integrity may lead to reduced or even impaired cognitive functioning that is important for everyday activities., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Many gene variants may impair our health and cognitive abilities at old age, but some of them paradoxically improve the same or similar functions at much younger age (antagonistic pleiotropy hypothesis). Such a diametric pattern may also hold true for the ancestral Apolipoprotein E (APOE) ε4 allele, which increases the risk for Alzheimer's disease and cognitive decline in old age, but may benefit (pre)frontal (executive) functions in young carriers. We therefore investigated potential cognitive benefits of the risk allele on cognitive control capacities and top-down control allocation ("metacontrol") in n = 190 healthy young adults. On a behavioral level, we found young APOE ε4 carriers to better adapt to different degrees of cognitive control requirements, with superior performance in case of high control demands. On a neurophysiological level, these group differences were reflected by modulations of the N450 component, which were rooted in activation differences of the superior frontal gyrus (SFG, BA8). Taken together, our results suggest that young ε4 carriers are more efficient than non-carriers at allocating cognitive control resources based on the actual task requirements (i.e. metacontrol), as they seem to experience less conflict/exert less effort and recruit fewer additional prefrontal areas when task set complexity increases. We further found that ε2 carriers processed implicit spatial stimulus features to a stronger degree than ε3 and ε4 carriers, but failed to benefit from this, as the additional information likely increased response selection conflicts. This finding should however be treated with ample caution as the group of ε2 carriers was comparatively small., (Copyright © 2018 Elsevier Inc. All rights reserved.)

There is a strong inter-relation of cognitive and emotional processes as evidenced by emotional conflict monitoring processes. In the cognitive domain, proactive effects of conflicts have widely been studied; i.e. effects of conflicts in the n-1 trial on trial n. Yet, the neurophysiological processes and associated functional neuroanatomical structures underlying such proactive effects during emotional conflicts have not been investigated. This is done in the current study combining EEG recordings with signal decomposition methods and source localization approaches. We show that an emotional conflict in the n-1 trial differentially influences processing of positive and negative emotions in trial n, but not the processing of conflicts in trial n. The dual competition framework stresses the importance of dissociable 'perceptual' and 'response selection' or cognitive control levels for interactive effects of cognition and emotion. Only once these coding levels were isolated in the neurophysiological data, processes explaining the behavioral effects were detectable. The data show that there is not only a close correspondence between theoretical propositions of the dual competition framework and neurophysiological processes. Rather, processing levels conceptualized in the framework operate in overlapping time windows, but are implemented via distinct functional neuroanatomical structures; the precuneus (BA31) and the insula (BA13). It seems that decoding of information in the precuneus, as well as the integration of information during response selection in the insula is more difficult when confronted with angry facial emotions whenever cognitive control resources have been highly taxed by previous conflicts., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The neural architecture of the corpus callosum shows pronounced inter-individual differences. These differences are thought to affect timing of interhemispheric interactions and, in turn, functional hemispheric asymmetries. The present study aimed at elucidating the neuronal mechanisms underlying this relationship. To this end, we used a combined DTI and EEG study design. In 103 right-handed and healthy adult participants, we determined the microstructural integrity of the posterior third of the corpus callosum and examined in how far this microstructural integrity was related to between-hemisphere timing differences in neurophysiological correlates of attentional processes in the dichotic listening task. The results show that microstructural integrity of the posterior callosal third correlated with attentional timing differences in a verbal dichotic listening condition but not in a noise control condition. Hence, this association between callosal microstructure and between-hemisphere timing differences is specific for stimuli, which trigger hemispheric bottom-up processing in an asymmetric fashion. Specifically, higher microstructural integrity was associated with decreased left-right differences in the latency of the N1 event-related potential component and hence more symmetric processing of dichotic stimuli between the two hemispheres. Our data suggest that microstructure of the posterior callosal third affects functional hemispheric asymmetries by modulating the timing of interhemispheric interactions., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Binge-drinking is very prevalent and potentially harmful, yet very little is known about the specificity of its effects on behavior and the underlying neurophysiologic mechanisms. While it is generally accepted that alcohol impairs top-down cognitive control and conflict monitoring, it has remained unclear whether this also applies to subliminally triggered conflicts, as alcohol may not impair automated processes to the same extent. To investigate this, we used a within-subjects design in a sample of n = 22 healthy young male subjects who performed a complex response conflict paradigm while an EEG was recorded. Behavioral data showed that a binge-like intoxication of 1.1‰ increased the response conflict induced by consciously perceived flankers, but paradoxically decreased the response conflict induced by subliminal primes. The latter was found to be reflected in decreased amplitude differences in the visual N1, which reflects attentional aspects of stimulus processing, and the N2 as well as a following central negativity, which are thought to reflect conflict monitoring and cognitive effort. On the neuroanatomical level, we found the decrease in subliminally induced response conflicts to be based on changes in fronto-parietal networks (including BA 7/the precuneus, BA 40/the postcentral gyrus, BA 23 & 24/the cingulate cortex and BA 13/the insular cortex) that subserve attention allocation, the processing of complex stimuli and cognitive conflict. It can be concluded that alcohol intoxication paradoxically reduces subliminally triggered response conflicts, which may be caused by decreased allocation of attention towards less salient/noticeable stimuli., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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.)

The ability to exert cognitive control is a major function of the prefrontal cortex, the efficiency of which depends on the phasic release of norepinephrine (NE) at particular time points. However, different aspects of information are simultaneously processed at any given moment. This raises the question of whether the norepinephrine system is also capable of specifically modulating selected aspects of all ongoing information processing, especially when several of those processes are carried out by the same functional neuroanatomical structure at the same time. We examine this question in humans using a flanker paradigm by integrating neurophysiological (EEG) and pupil diameter data using novel signal processing techniques including Residue Iteration Decomposition (RIDE) and source localization. We show that during conflict monitoring, motor response-related processes are more strongly modulated by the NE system than stimulus-related processes or central decision processes between stimulus and response. This was the case even though these processes occurred at the same time point and were mediated by overlapping medial frontal cortical structures. The results indicate that the NE system exerts specific modulatory effects for different informational contents that are simultaneously processed in the medial frontal cortex., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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.)

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.)

Mechanisms responsible for the integration of perceptual events and appropriate actions (sensorimotor processes) have been subject to intense research. Different theoretical frameworks have been put forward with the "Theory of Event Coding (TEC)" being one of the most influential. In the current study, we focus on the concept of 'event files' within TEC and examine what sub-processes being dissociable by means of cognitive-neurophysiological methods are involved in voluntary event coding. This was combined with EEG source localization. We also introduce reward manipulations to delineate the neurophysiological sub-processes most relevant for performance variations during event coding. The results show that processes involved in voluntary event coding included predominantly stimulus categorization, feature unbinding and response selection, which were reflected by distinct neurophysiological processes (the P1, N2 and P3 ERPs). On a system's neurophysiological level, voluntary event-file coding is thus related to widely distributed parietal-medial frontal networks. Attentional selection processes (N1 ERP) turned out to be less important. Reward modulated stimulus categorization in parietal regions likely reflecting aspects of perceptual decision making but not in other processes. The perceptual categorization stage appears central for voluntary event-file coding., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Every day, a multitude of interfering sensory inputs needs to be integrated and adequately processed using response selection processes. Interference effects are typically investigated using classical paradigms like the Flanker and Simon task. The sources of interference for Flanker and Simon effect are known to be different and according to dual process accounts, two distinct functional pathways are involved in resolving these types of interference. It is an open question how far these sources of interference are related to each other and interact. We investigated this question in a system neurophysiological study utilizing a hybrid paradigm combining both Flanker effect-like and Simon effect-like features. We focus on event-related theta oscillations and use beamforming methods to examine functional neuroanatomical networks. The results show that Simon and Flanker interference interacted in a non-additive fashion by modulating theta band activity, probably reflecting the recruitment of cognitive control processes. Beamforming source reconstruction revealed that theta band activity was related to a broad neuronal network comprising prefrontal and cerebellar regions, including the MFG, SFG, IFG, and SMA. These regions were connected to interference processing and conflict resolution, but differed in the amount of specificity for different sources of interference., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Both fronto-parietal networks and the basal ganglia play an important role in action cascading. It is well-known that cortical structures mediate sensorimotor transformation for this purpose. The striatum receives extensive input from those cortical structures and has been shown to be modulated by the predictability of cortical input. Until today, it has however remained unclear whether the processing of spatial codes or even sensorimotor transformation processes for the purpose of action cascading involve the striatum. We therefore examined this question by means of fMRI using a stop-change task that varied the predictability as well as the complexity of sensorimotor transformations required for correct responding in the context of action cascading. On the behavioral level, we found that the complexity of sensorimotor transformation processes only prolonged reaction times when the requirement for this transformation was predictable. fMRI results matched this effect showing enhanced activity of the caudate in case a complex sensorimotor transformation could be anticipated. Irrespective of the complexity of the required transformations, the putamen was furthermore involved in the prediction of imminent action cascading demands. Taken together, our findings give rise to a conceptual advance regarding basal ganglia function by showing that the anticipation and, more importantly, processing of complex sensorimotor transformation processes involves the striatum., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The selection of appropriate responses is a complex endeavor requiring the integration of many different sources of information in fronto-striatal-thalamic circuits. An often neglected but relevant piece of information is provided by proprioceptive inputs about the current position of our limbs. This study examines the importance of striatal and thalamic GABA levels in these processes using GABA-edited magnetic resonance spectroscopy (GABA-MRS) and a Simon task featuring proprioception-induced interference in healthy subjects. As a possible model of deficits in the processing of proprioceptive information, we also included Parkinson's disease (PD) patients in this study. The results show that proprioceptive information about unusual postures complicates response selection processes in controls, but not in PD patients. The well-known deficits of PD patients in processing proprioceptive information can turn into a benefit when altered proprioceptive information would normally complicate response selection processes. Striatal and thalamic GABA levels play dissociable roles in the modulation of response selection processes by proprioceptive information: Striatal GABA levels seem to be important for the general speed of responding, most likely because striatal GABA promotes response selection. In contrast, the modulation of response conflict by proprioceptive information is closely related to thalamic GABA concentrations with higher concentration being related to a smaller response conflict effect. The most likely explanation for this finding is that the thalamus is involved in the integration of sensorimotor, attentional, and cognitive information for the purpose of response formation. Yet, this effect in the thalamus vanishes when controls and PD patients were analyzed separately., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The inhibition of inappropriate responses is a function known to rely on prefrontal cortex (PFC) functioning. Similarly, working memory processes are known to rely on the PFC. Even though these processes are usually closely intertwined and the functional neuroanatomy underlying these processes is largely overlapping, the influence of working memory load on inhibitory control process has remained largely elusive. In the current study, we therefore examine how response inhibition processes are modulated by working memory load. For this, we systematically increased the working memory load of participants by integrating mental rotation processes in a Go/NoGo paradigm. To examine the system neurophysiology of these processes in detail, and to examine whether there are differential effects of working memory load on distinct response inhibition subprocesses, we applied event-related potentials (ERPs) in combination with source localization techniques. The data shows that after exceeding a certain threshold, inhibitory control processes are aggravated by working memory load. The neurophysiological data paralleled the behavioral data. However, it suggests that distinguishable response inhibition subprocesses are differentially modulated by working memory load: Changes were evident in the NoGo-P3 amplitude but not in the NoGo-N2 amplitude. On a system level, this distinctive modulation of response inhibition subprocesses was related to differences in neural activity in the left inferior and middle frontal gyri. We show that inhibitory control processes are impaired when the working memory load surpasses a certain threshold. This, however only applies to situations in which the necessity of inhibitory control processes cannot be easily detected on the basis of perceptual factors., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Every day, we encounter situations in which we have to deal with multiple response options. In order not to overstrain response selection resources, we need to cascade the associated task goals. Yet, the neurobiological foundations of these action cascading processes are largely unknown. Aiming at determining the possible relevance of the neuropeptide Y Y2 receptor for action cascading processes, this study investigates a functional promoter variation (rs2234759) in the neuropeptide Y Y2 receptor gene (NPY2R). 176 healthy subjects completed a stop-change paradigm. Applying mathematical constraints to the obtained behavioral data allowed for a classification of the action cascading processing mode on a serial to parallel continuum. Neurophysiological data (EEG) were analyzed along this mathematical constraint. The behavioral data show that the Y2-receptor high expression G allele is associated with a less efficient mode of action cascading where different task goals are activated in parallel. The neurophysiological data indicate that this effect is based on modulations at the response selection stage but not on changes in the preceding attentional selection processes. Analyses show that the interrelation between behavioral and neurophysiological data is mediated by genotype effects. At the level of response selection, genotype effects are associated with activity changes in the anterior cingulate cortex (ACC). Changes in the reliability of neural synchronization processes in the theta frequency band are also related to these effects. Possibly, these Y2-receptor-related effects emerge from the receptor's strong interrelation with the dopamine system., (Copyright © 2014 Elsevier Inc. All rights reserved.)

This study examined whether the memory encoding and short term maintenance of olfactory stimuli is associated with neurophysiological activation patterns which parallel those described for sensory modalities such as vision and auditory. We examined olfactory event-related potentials in an olfactory change detection task in twenty-four healthy adults and compared the measured activation to that found during passive olfactory stimulation. During the early olfactory post-processing phase, we found a sustained negativity over bilateral frontotemporal areas in the passive perception condition which was enhanced in the active memory task. There was no significant lateralization in either experimental condition. During the maintenance interval at the end of the delay period, we still found sustained activation over bilateral frontotemporal areas which was more negative in trials with correct - as compared to incorrect - behavioural responses. This was complemented by a general significantly stronger frontocentral activation. Summarizing, we were able to show that olfactory short term memory involves a parallel sequence of activation as found in other sensory modalities. In addition to olfactory-specific frontotemporal activations in the memory encoding phase, we found slow cortical potentials over frontocentral areas during the memory maintenance phase indicating the activation of a supramodal memory maintenance system. These findings could represent the neurophysiological underpinning of the 'olfactory flacon', the olfactory counter-part to the visual sketchpad and phonological loop embedded in Baddeley's working memory model., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The neuropeptide S (NPS) system has been suggested to contribute to the pathogenesis of anxiety. In order to further characterize the cognitive-neurophysiological relevance of neuropeptide S in the etiology of anxiety, the influence of a functional neuropeptide S receptor gene (NPSR1) variant on response inhibition and error monitoring was investigated under consideration of the dimensional phenotype of anxiety sensitivity (AS). In a sample of N=97 healthy probands, event-related potential (ERP) measurement using a modified Flanker task was applied allowing for a distinct neurophysiological examination of processes related to response inhibition (Nogo-N2, Nogo-P3) and error monitoring (Ne/ERN). All subjects were genotyped for the functional NPSR1 A/T (Asn(107)Ile) variant (rs324981) and characterized for anxiety sensitivity using the Anxiety Sensitivity Index (ASI). Carriers of the NPSR1 T allele displayed intensified response inhibition (Nogo-P3) and error monitoring (Ne/ERN), which was in both cases paralleled by the behavioral data. Furthermore, anxiety sensitivity was found to be higher in NPSR1 T allele carriers and to correlate with Nogo-P3 and Ne/ERN. A mediation analysis revealed the ERN to mediate the effect between NPSR1 genotype and anxiety sensitivity. In summary, the more active NPSR1 T allele may confer enhanced response inhibition and increased error monitoring and might drive particularly error monitoring as a neurophysiological endophenotype of anxiety as reflected by increased anxiety sensitivity. These findings further corroborate a major role of the neuropeptide S system in the pathogenesis of anxiety and suggest a potentially beneficial use of therapeutic agents targeting the NPS system in anxiety disorders., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Aging affects the ability to focus attention on a given task and to ignore distractors. These functions subserve response control processes for which fronto-striatal networks have been shown to play an important role. Within these networks, the brain-derived-neurotrophic-factor (BDNF), which is known to underlie aging effects, plays a pivotal role. We investigated how cognitive subprocesses constituting a cycle of distraction, orientation and refocusing of attention are affected by the functional BDNF Val66Met polymorphism using event-related potentials (ERPs) in 122 healthy elderly. Using an auditory distraction paradigm we found that the Val/Val genotype confers a disadvantage to its carriers. This disadvantage was partly compensated by intensified attentional shifting mechanisms. It could be based on response selection processes being more vulnerable against interference from distractors in this genotype group. Processes reflecting transient sensory memory processes, or the re-orientation of attention were not affected by the BDNF Val66Met polymorphism, suggesting a higher importance of BDNF for mechanisms related to response control, than stimulus processing. The results add on recent literature showing that the Met allele confers some benefit to its carriers. We suggest an account for unifying different results of BDNF Val66Met association studies in executive functions, based on the role of BDNF in fronto-striatal circuits., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Flexible response adaptation and the control of conflicting information play a pivotal role in daily life. Yet, little is known about the neuronal mechanisms mediating parallel control of these processes. We examined these mechanisms using a multi-methodological approach that integrated data from event-related potentials (ERPs) with structural MRI data and source localisation using sLORETA. Moreover, we calculated evoked wavelet oscillations. We applied this multi-methodological approach in healthy subjects and patients in a prodromal phase of a major basal ganglia disorder (i.e., Huntington's disease), to directly focus on fronto-striatal networks. Behavioural data indicated, especially the parallel execution of conflict monitoring and flexible response adaptation was modulated across the examined cohorts. When both processes do not co-incide a high integrity of fronto-striatal loops seems to be dispensable. The neurophysiological data suggests that conflict monitoring (reflected by the N2 ERP) and working memory processes (reflected by the P3 ERP) differentially contribute to this pattern of results. Flexible response adaptation under the constraint of high conflict processing affected the N2 and P3 ERP, as well as their delta frequency band oscillations. Yet, modulatory effects were strongest for the N2 ERP and evoked wavelet oscillations in this time range. The N2 ERPs were localized in the anterior cingulate cortex (BA32, BA24). Modulations of the P3 ERP were localized in parietal areas (BA7). In addition, MRI-determined caudate head volume predicted modulations in conflict monitoring, but not working memory processes. The results show how parallel conflict monitoring and flexible adaptation of action is mediated via fronto-striatal networks. While both, response monitoring and working memory processes seem to play a role, especially response selection processes and ACC-basal ganglia networks seem to be the driving force in mediating parallel conflict monitoring and flexible adaptation of actions., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Functional cerebral asymmetries (FCAs) are an important modulator of cognitive functions. Here, we investigated the temporal and spectral dynamics as well as the cortical networks underlying the lateralized modulation of executive functions related to response inhibition. To this end, we recorded event-related potentials (ERPs) during tachistoscopic presentation of verbal 'Go' and 'Nogo' stimuli in the left (LVF) and the right visual field (RVF). Participants committed fewer false alarms to verbal Nogo stimuli presented in the RVF than to stimuli presented in the LVF. This asymmetry was paralleled by neurophysiological data. The Nogo-N2 and related delta frequency band power were stronger when response inhibition was driven by stimuli presented in the LVF, implying a stronger response conflict. This effect was mediated by stronger activations in bilateral medial-prefrontal and especially left parietal networks. This shows that asymmetries in behavioural performance do not necessarily reflect differences in the overall capability of one hemisphere to solve a task. Even though information is initially confined to one hemisphere after tachistoscopic presentation, this does not primarily cause behavioural asymmetries. Instead, hemispheric dominances in information processing can induce differences in demands on cognitive processes operating via bilateral networks that ultimately drive behavioural asymmetries., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Glutamate is an important excitatory neurotransmitter within functional prefrontal-basal ganglia loops. These distinct loops mediate different cognitive functions. One function of the anterior-cingulate loop is error processing. One function of the orbito-frontal loop is response inhibition. These functions are altered in several neuro-psychiatric disorders like Huntington's disease (HD). Because of the known role of the GRIN2B C2664T polymorphism in HD neuropathology, which is partly due to increased glutamatergic neural transmission, we analyze how this polymorphism influences error processing and response inhibition in a sample of healthy probands (N=65). Combining a genetic approach with event-related potential (ERP) measurements of response inhibition (OFC-loop function) and error processing (ACC-loop function), we provide robust results showing a selective modulation of response inhibition processes by the GRIN2B C2664T polymorphism at the behavioural and neurophysiological level. Response inhibition processes were stronger in the CT/TT genotype group, compared to the CC genotype group. Since error processing functions were not affected, the results suggest for differential influences of the GRIN2B C2664T polymorphism on response inhibition and error processing functions. The results provide first insight into cognitive-neurophysiological effects of the GRIN2B C2664T polymorphism. The dissociation obtained may be due to a differential importance of N-methyl-D-aspartate receptors for glutamatergic neural transmission in different striatal compartments (matrix and striosomes). We provide a model on this that may be a target for future research., (Copyright 2010 Elsevier Inc. All rights reserved.)

Response selection and control are supposed to reflect important basal ganglia functions. Recently, we showed that the dopaminergic system may be especially important for response selection in compatible, but not in incompatible stimulus-response (S-R) relations. Research indicates that the dopaminergic system is influenced by the serotonergic system, but little is known about the involvement of the serotonergic system in response selection. Analyzing event-related potentials (ERPs) in a sample of healthy probands (N=74), we show the 5-HT1A C(-1019)G polymorphism modulating response-related processes, as reflected in the N2 component, in compatible, but not incompatible, S-R relations. This modulation was a function of the number of -1019 G alleles. Decreasing numbers of -1019 G alleles were stepwise related to increases in the N2 on compatible trials and concomitant increases in response times. The functional effect of the 5-HT1A C(-1019)G polymorphism has previously been shown to be specific for serotonergic 1 A autoreceptors of serotonergic neurons in the dorsal raphe nucleus (DRN). Due to this close relation of genotype effects to neuroanatomically dissociable structures, the results suggest that DRN serotonin 1 A autoreceptors are important for compatible S-R relations, i.e., response selection, but not for incompatible S-R relations, i.e. response conflict or inhibition. The results extend previous findings on the dopaminergic system to the serotonergic system. The examined functions are precisely regulated on a neuronal level, since neurophysiological and behavioural effects are driven in an allele-dose fashion. Because of this, the results are of importance for future clinical applications., (Copyright 2009 Elsevier Inc. All rights reserved.)