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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.

Alcohol use disorder (AUD) is a relapsing-remitting condition characterized by excessive and/or continued alcohol consumption despite harmful consequences. New adjuvant tools, such as noninvasive brain stimulation techniques, might be helpful additions to conventional treatment approaches or even provide an alternative option for patients who fail to respond adequately to other treatment options. Here, we discuss the potential use of auricular transcutaneous vagus nerve stimulation (atVNS) as an ADD-ON intervention in AUD. Compared with other techniques, atVNS has the advantage of directly stimulating nuclei that synthesize GABA and catecholamines, both of which are functionally altered by alcohol intake in AUD patients. Pharmacological options targeting those neurotransmitters are widely available, but have relatively limited beneficial effects on cognition, even though restoring normal cognitive functioning, especially cognitive control, is key to maintaining abstinence. Against this background, atVNS could be a particularly useful add-on because there is substantial meta-analytic evidence based on studies in healthy individuals that atVNS can enhance cognitive control processes that are crucial to regaining control over drug intake. We discuss essential future research on using atVNS as an ADD-ON intervention in AUD to enhance clinical and cognitive outcomes by providing a translational application. Given that this novel technique can be worn like an earpiece and can be employed without medical supervision/outside the clinical settings, atVNS could be well integratable into the daily life of the patients, where the task of regaining control over drug intake is most challenging.

Background: Previous studies in Dutch young adults revealed that individuals with self-reported impaired wound healing reported poorer mood, increased inattention and impulsivity, poorer quality of life, and poorer immune fitness compared to healthy controls. Another study revealed that the negative impact of lockdowns during the 2019 coronavirus disease (COVID-19) pandemic was significantly more profound among the impaired wound healing group than the control group. The purpose of the current study was to replicate and extend these findings among young adults living in Germany. Methods: A retrospective, cross-sectional survey was conducted among N = 317 young adults living in Germany, 18–35 years old. They were allocated to the IWH group (N = 66) or the control group (N-251). Participants completed the Attention Control Scale, and mood, quality of life, and immune fitness were assessed with single-item ratings. All assessments were made for (1) the period before the COVID-19 pandemic, (2) the first lockdown period, March–May 2020, (3) the first no-lockdown period, summer 2020, (4) the second lockdown, November 2020 to May 2021, and (5) the second no-lockdown period, summer 2021. Results: The impaired wound healing group reported significantly poorer mood, quality of life, and immune fitness. The effects were evident before the pandemic. The impaired wound healing group scored significantly poorer on attention focusing, but no significant differences between the groups were found for attention shifting. During the pandemic, negative lockdown effects (i.e., further aggravation of mood and immune fitness and lower quality of life) were evident in both groups but significantly more profound in the impaired wound healing group. No differences between the groups were found for the no-lockdown periods. Conclusion: Individuals with self-reported impaired wound healing have significantly poorer mood, attention focusing, and immune fitness and report a poorer quality of life than healthy controls. The impact of COVID-19 lockdowns was significantly more profound in the impaired wound-healing group.

The ability to inhibit a prepotent response is a crucial prerequisite of goal-directed behavior. So far, research on response inhibition has mainly examined these processes when there is little to no cognitive control during the decision to respond. We manipulated the “context” in which response inhibition has to be exerted (i.e., a controlled or an automated context) by combining a Simon task with a go/no-go task and focused on theta band activity. To investigate the role of “context” in response inhibition, we also examined how far theta band activity in the pretrial period modulates context-dependent variations of theta band activity during response inhibition. This was done in an EEG study applying beamforming methods. Here, we examined n = 43 individuals. We show that an automated context, as opposed to a controlled context, compromises response inhibition performance and increases the need for cognitive control. This was also related to context-dependent modulations of theta band activity in superior frontal and middle frontal regions. Of note, results showed that theta band activity in the pretrial period, associated with the right inferior frontal cortex, was substantially correlated with context-dependent modulations of theta band activity during response inhibition. The direction of the obtained correlation provides insights into the functional relevance of a pretrial theta band activity. The data suggest that pretrial theta band activity reflects some form of attentional sampling to inform possible upcoming processes signaling the need for cognitive control.

Goal-directed behavior often requires the inhibition of prepotent automatic responses. Response inhibition encompasses several top-down cognitive operations embedded in a neural network extending from fronto-cortical regions to subcortical nuclei. Yet, it has remained unclear whether the early allocation of cognitive resources also modulates response inhibition performance and neural structures involved in this process. To investigate this question, we used a Simon Nogo task, which was designed to manipulate the relationship between automaticity and cognitive control during response inhibition, and combined it with an electroencephalogram (EEG) and source localization approach. We showed that the early allocation of cognitive resources, as reflected by the P2 amplitude, might be a critical determinant in the interplay between automaticity and cognitive control in response inhibition. Specifically, the obtained results demonstrated that individual variations in cognitive resource allocation modulated the need for conflict monitoring and engagement in cognitive control processes, as reflected by N2 and P3b amplitudes, respectively. Importantly, larger P2 amplitudes were associated with higher activation in cortical regions encompassing the temporo-parietal junction (TPJ). This stresses the importance of this cortical region for the encoding of relevant stimulus information to resolve conflicting contexts in response inhibition. The increased cognitive control in more automatic contexts was also reflected by higher activation of the superior and medial frontal cortices. These findings provide a new perspective on response inhibition, suggesting that early resource allocation is a central modulator of the interaction between automaticity and cognitive control.

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'.

Goal-directed behavior has been shown to be affected by consciously and subliminally induced conflicts. Both types of conflict conjointly modulate behavioral performance, but the underlying neuronal mechanisms have remained unclear. While cognitive control is linked to oscillations in the theta frequency band, there are several mechanisms via which theta oscillations may enable cognitive control: via the coordination and synchronization of a large and complex neuronal network and/or via local processes within the medial frontal cortex. We, therefore, investigated this issue with a focus on theta oscillations and the underlying neuronal networks. For this purpose, n = 40 healthy young participants performed a conflict paradigm that combines conscious and subliminal distractors while an EEG was recorded. The data show that separate processes modulate the theta-based activation and organization of cognitive control networks: EEG beamforming analyses showed that variations in theta band power generated in the supplementary motor area reflected the need for control and task-relevant goal shielding, as both conflicts as well as their conjoint effect on behavior increased theta power. Yet, large networks were not modulated by this and graph theoretical analyses of the efficiency (i.e. small worldness) of theta-driven networks did not reflect the need for control. Instead, theta network efficiency was decreased by subliminal conflicts only. This dissociation suggests that while both kinds of conflict require control and goal shielding, which are induced by an increase in theta band power and modulate processes in the medial frontal cortex, only non-conscious conflicts diminish the efficiency of theta-driven large-scale networks.

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

Depression is the leading cause of disability worldwide, making antidepressant drugs the most used psychiatric drugs in the USA. Withdrawal effects and rebound symptoms frequently occur after the reduction and/or discontinuation of these drugs. Although these phenomena have been investigated with respect to the clinical symptomatology, no studies have systematically investigated the effects of withdrawal/rebound on general cognition. We present a novel framework based on the idea of allostatic adaptation, which allows to predict how different antidepressants likely impair different cognitive processes as a result of withdrawal and rebound effects. This framework relies on the assumptions that the type of cognitive impairments evoked by an antidepressant is determined by the targeted neurotransmitter systems, while the severity of deficits depends on its half-life. Our model predicts that the severity of detrimental cognitive withdrawal and rebound effects increases with a shorter half-life of the discontinued antidepressant drug. It further proposes drug-specific effects: antidepressants mainly targeting serotonin should primarily impair aversive and emotional processing, those targeting norepinephrine should impair the processing of alerting signals, those targeting dopamine should impair motivational processes and reward processing, and those targeting acetylcholine should impair spatial learning and memory. We hope that this framework will motivate further research to better understand and explain cognitive changes as a consequence of antidepressant discontinuation.

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.

Restless legs syndrome (RLS) is a common neurological disorder characterized by a sensorimotor condition, where patients feel an uncontrollable urge to move the lower limbs in the evening and/or during the night. RLS does not only have a profound impact on quality of life due to the disturbed night-time sleep, but there is growing evidence that untreated or insufficiently managed RLS might also cause cognitive changes in patients affected by this syndrome. It has been proposed that RLS is caused by alterations in the signal-to-noise ratio (SNR) and in dopamine (DA) neurotransmission in the nervous system. Based on this evidence, we propose the “SNR-DA hypothesis” as an explanation of how RLS could affect cognitive performance. According to this hypothesis, variations/reductions in the SNR underlie RLS-associated cognitive deficits, which follow an inverted U-shaped function: In unmedicated patients, low dopamine levels worsen the SNR, which eventually impairs cognition. Pharmacological treatment enhances DA levels in medicated patients, which likely improves/normalizes the SNR in case of optimal doses, thus restoring cognition to a normal level. However, overmedication might push patients past the optimal point on the inverted U-shaped curve, where an exaggerated SNR potentially impairs cognitive performance relying on cortical noise such as cognitive flexibility. Based on these assumptions of SNR alterations, we propose to directly measure neural noise via “1/f noise” and related metrics to use transcranial random noise stimulation (tRNS), a noninvasive brain stimulation method which manipulates the SNR, as a research tool and potential treatment option for RLS.

This study aimed to provide a currently missing link between general intoxication-induced changes in overall brain activity and the multiple cognitive control deficits typically observed during acute alcohol intoxication. For that purpose, we analyzed the effects of acute alcohol intoxication (1.1‰) on the four archetypal electroencephalography (EEG) resting networks (i.e., microstates A-D) and their temporal dynamics (e.g., coverage and transitions from one microstate to another), as well as on self-reported resting-state cognition in n = 22 healthy young males using a counterbalanced within-subject design. Our microstate analyses indicated that alcohol increased the coverage of the visual processing-related microstate B at the expense of the autonomic processing-related microstate C. Add-on exploratory analyses revealed that alcohol increased transitions from microstate C to microstate B and decreased bidirectional transitions between microstate C and the attention-related microstate D. In line with the observed alcohol-induced decrease of the autonomic processing-related microstate C, participants reported decreases of their somatic awareness during intoxication, which were positively associated with more transitions from microstate C to microstate B. In sum, the observed effects provide mechanistic insights into how alcohol might hamper cognitive processing by generally prioritizing the bottom-up processing of visual stimuli over top-down internal information processing. The fact that this was found during the resting state further proves that alcohol-induced changes in brain activity are continuously present and do not only emerge during demanding situations or tasks.

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

Background: Catecholamines affect response inhibition, but the effects of methylphenidate on inhibitory control in healthy subjects are heterogenous. Theoretical considerations suggest that working memory demands and learning/familiarization processes are important factors to consider regarding catecholaminergic effects on response inhibition. Aims: The purpose of this study was to examine the role of working memory demands and familiarization for methylphenidate effects on response inhibition. Methods: Twenty-eight healthy adults received a single dose of methylphenidate (0.5 mg/kg) or placebo in a randomised, double-blind, crossover study design. The subjects were tested using a working memory-modulated response inhibition paradigm that combined a Go/Nogo task with a mental rotation task. Results: Methylphenidate effects were largest in the most challenging mental rotation condition. The direction of effects depended on the extent of the participants’ task experience. When performing the task for the first time, methylphenidate impaired response inhibition performance in the most challenging mental rotation condition, as reflected by an increased false alarm rate. In sharp contrast to this, methylphenidate seemed to improve response execution performance in the most challenging condition when performing the task for the second time as reflected by reaction times on Go trials. Conclusion: Effects of catecholamines on inhibitory control processes depend on the interplay of two factors: (a) working memory demands, and (b) learning or familiarization with a task. It seems that the net effect of increases in gain control and decreases in working memory processes determines the methylphenidate effect on response inhibition. Hence, crossover study designs likely underestimate methylphenidate effects on cognitive functions.

Frequent alcohol binges shift behavior from goal-directed to habitual processing modes. This shift in reward-associated learning strategies plays a key role in the development and maintenance of alcohol use disorders and seems to persist during (early stages of) sobriety in at-risk drinkers. Yet still, it has remained unclear whether this phenomenon might be associated with alcohol hangover and thus also be found in social drinkers. In an experimental crossover design, n = 25 healthy young male participants performed a two-step decision-making task once sober and once hungover (i.e., when reaching sobriety after consuming 2.6 g of alcohol per estimated liter of total body water). This task allows the separation of effortful model-based and computationally less demanding model-free learning strategies. The experimental induction of alcohol hangover was successful, but we found no significant hangover effects on model-based and model-free learning scores, the balance between model-free and model-based valuation (&omega, ), or perseveration tendencies (&pi, ). Bayesian analyses provided positive evidence for the null hypothesis for all measures except &pi, (anecdotal evidence for the null hypothesis). Taken together, alcohol hangover, which results from a single binge drinking episode, does not impair the application of effortful and computationally costly model-based learning strategies and/or increase model-free learning strategies. This supports the notion that the behavioral deficits observed in at-risk drinkers are most likely not caused by the immediate aftereffects of individual binge drinking events.

Exerting cognitive control is an effortful endeavor that is strongly modulated by the availability of dopamine (DA) and norepinephrine (NE), which are both synthesized from the amino acid precursor tyrosine. Supplementing tyrosine may increase the synthesis of both catecholamines. This has been suggested to improve executive functioning and potentially even counteract depletion effects in this domain. Yet, it has remained unclear whether tyrosine also improves interference control and whether subliminally and consciously triggered response conflicts are subject to the same modulation. We investigated this question in a double-blind intra-individual study design. N = 26 young healthy subjects performed two consecutive cognitive control tasks that triggered automatic incorrect response tendencies; once with tyrosine supplementation and once with a placebo. The results show that tyrosine decreased the size of consciously perceived conflicts in a Simon Task, but not a Flanker task, thus suggesting that stimulus–response conflicts might be modulated differently from stimulus–stimulus conflicts. At the same time, tyrosine supplementation increased the size of subliminally triggered conflicts whenever a different, consciously perceived conflict was also present. This suggests that control-related DA and NE release may increase visuo-motor priming, especially when no conflict-specific top-down control may be triggered to counteract subliminal priming effects. Also, these subliminal conflicts might be aggravated by concurrent control investments in other kinds of conflict. Taken together, our data suggest that beneficial effects of tyrosine supplementation do not require depletion effects, but may be limited to situations where we consciously perceive a conflict and the associated need for conflict-specific control.

Background To display goal-directed behavior, we must be able to resolve response conflicts that arise from processing various distractors. Such conflicts may be triggered by different kinds of distractor stimuli (e.g., priming and flanker stimuli), but it has remained largely unclear whether the functional and neurobiological underpinnings of both conflict types differ. We therefore investigated the functional relevance of the catecholamines dopamine and norepinephrine, which have been shown to increase the signal-to-noise ratio in neuronal processing and should therefore modulate response conflicts. Methods In a double-blind, randomized, placebo-controlled study design, we examined the effect of methylphenidate (0.5 mg/kg) on both flanker-induced and priming-induced response conflicts in a group of n=25 healthy young adults. We used EEG recordings to examine event-related potentials in combination with source localization analyses to identify the cognitive-neurophysiological subprocesses and functional neuroanatomical structures modulated by methylphenidate. Results Compared with placebo, methylphenidate decreased flanker conflicts. This was matched by increased congruency effects in the fronto-central N2/P3 event-related potential complex and associated with modulations in the right inferior frontal gyrus. In contrast to this, methylphenidate did not modulate the size of prime-evoked conflicts. Conclusions Our results suggest that catecholamine-driven increases in signal-to-noise ratio and neural gain control do not equally benefit differently evoked conflicts. This supports the hypothesis of an at least partly different neurobiological basis for flanker- and prime-evoked response conflicts. As the right inferior frontal gyrus plays an important role in inhibition, the catecholaminergic system may reduce flanker conflicts by supporting the inhibition of distracting information.

Advantageous effects of cognitive control are well-known, but cognitive control may also have adverse effects, for example when it suppresses the implicit processing of stimulus-response (S-R) bindings that could benefit task performance. Yet, the neurophysiological and functional neuroanatomical structures associated with adverse effects of cognitive control are poorly understood. We used an extreme group approach to compare individuals who exhibit adverse effects of cognitive control to individuals who do not by combining event-related potentials (ERPs), source localization, time-frequency analysis and network analysis methods. While neurophysiological correlates of cognitive control (i.e. N2, N450, theta power and theta-mediated neuronal network efficiency) and task-set updating (P3) both reflect control demands and implicit information processing, differences in the degree of adverse cognitive control effects are associated with two independent neural mechanisms: Individuals, who show adverse behavioral effects of cognitive control, show reduced small-world properties and thus reduced efficiency in theta-modulated networks when they fail to effectively process implicit information. In contrast to this, individuals who do not display adverse control effects show enhanced task-set updating mechanism when effectively processing implicit information, which is reflected by the P3 ERP component and associated with the temporo-parietal junction (TPJ, BA 40) and medial frontal gyrus (MFG; BA 8). These findings suggest that implicit S-R contingencies, which benefit response selection without cognitive control, are always 'picked up', but may fail to be integrated with task representations to guide response selection. This provides evidence for a neurophysiological and functional neuroanatomical "dual-process" account of adverse cognitive control effects.

Evidence suggests that Tourette syndrome is characterized by an increase in dopamine transmission and structural as well as functional changes in fronto-striatal circuits that might lead to enhanced multi-component behaviour integration. Behavioural and neurophysiological data regarding multi-component behaviour was collected from 15 patients with Tourette syndrome (mean age = 30.40 ± 11.10) and 15 healthy controls (27.07 ± 5.44), using the stop-change task. In this task, participants are asked to sometimes withhold responses to a Go stimulus (stop cue) and change hands to respond to an alternative Go stimulus (change cue). Different onset asynchronies between stop and change cues were implemented (0 and 300 ms) in order to vary task difficulty. Tourette patients responded more accurately than healthy controls when there was no delay between stop and change stimulus, while there was no difference in the 300 ms delay condition. This performance advantage was reflected in a smaller P3 event related potential. Enhanced multi-component behaviour in Tourette syndrome is likely based on an enhanced ability to integrate information from multiple sources and translate it into an appropriate response sequence. This may be a consequence of chronic tic control in these patients, or a known fronto-striatal networks hyperconnectivity in Tourette syndrome.

Efficient action control is indispensable for goal-directed behaviour. Different theories have stressed the importance of either attention or response selection sub-processes for action control. Yet, it is unclear to what extent these processes can be identified in the dynamics of neurophysiological (EEG) processes at the single-trial level and be used to predict the presence of conflicts in a given moment. Applying deep learning, which was blind to cognitive theory, on single-trial EEG data allowed to predict the presence of conflict in ~95% of subjects ~33% above chance level. Neurophysiological features related to attentional and motor response selection processes in the occipital cortex and the superior frontal gyrus contributed most to prediction accuracy. Importantly, deep learning was able to identify predictive neurophysiological processes in single-trial neural dynamics. Hence, mathematical (artificial intelligence) approaches may be used to foster the validation and development of links between cognitive theory and neurophysiology of human behavior., Vahid et al. use a deep-learning approach to analyze single-trial EEG data to examine theories on action control. Their approach enables the identification of spatial and temporal neurophysiological features that are predictive of the response control during the Simon task. The results confirm cognitive theory-driven approaches on the relationship between neurophysiology and human behavior.

The hangover is the most commonly reported negative consequence of alcohol use with several studies reporting the detrimental consequences of hangover on health, economy, and society. Research has emphasized the socioeconomic consequences of experiencing these physical and psychological symptoms in relation to absenteeism, increased risk of having accidents and injuries, and impairment of daily activities, such as job performance and driving a car. During the 10th Alcohol Hangover Research Group meeting, held on 29 April 2018, in Utrecht, The Netherlands, aspects of alcohol hangover were presented with regards to determinants, biological and cognitive consequences and potential treatments. Precursory and posterior factors influencing alcohol hangover, including biological, psychological, behavioral, metabolic aspects, cognitive functioning, and the role of the immune system in the development of alcohol hangover, were presented. In addition, potential preventive measures and treatments of alcohol hangover to reduce the adverse consequences of alcohol consumption and hangover symptoms were discussed. One study revealed that an average of 24% of social and heavy drinkers claimed not to experience hangover symptoms across time. Another study showed that food intake (either healthy or junk food) had no significant impact on next-day hangover severity. Research examining cognitive and psychomotor functioning during hangover revealed impairments in collective problem solving and response inhibition, but not attentional bias towards alcohol-related cues. The alcohol hangover state further significantly impaired driving performance, even for a short commute to work. With regard to the pathology of the alcohol hangover, research was presented that demonstrated increases in saliva cytokine concentrations confirming drinking alcohol and the hangover phase are both associated with an immune response. Other presentations discussed that scientific literature shows that there are no effective hangover treatments available yet. However, although promising, new hangover treatments are currently in development. Taken together, at the 10th Alcohol Hangover Research Group meeting, a comprehensive overview of the causes, consequences, and potential treatments of the alcohol hangover was presented.

One of the major risk factors for global death and disability is alcohol, tobacco, and illicit drug use. While there is increasing knowledge with respect to individual factors promoting the initiation and maintenance of substance use disorders (SUDs), disease trajectories involved in losing and regaining control over drug intake (ReCoDe) are still not well described. Our newly formed German Collaborative Research Centre (CRC) on ReCoDe has an interdisciplinary approach funded by the German Research Foundation (DFG) with a 12-year perspective. The main goals of our research consortium are (i) to identify triggers and modifying factors that longitudinally modulate the trajectories of losing and regaining control over drug consumption in real life, (ii) to study underlying behavioral, cognitive, and neurobiological mechanisms, and (iii) to implicate mechanism-based interventions. These goals will be achieved by: (i) using mobile health (m-health) tools to longitudinally monitor the effects of triggers (drug cues, stressors, and priming doses) and modify factors (eg, age, gender, physical activity, and cognitive control) on drug consumption patterns in real-life conditions and in animal models of addiction; (ii) the identification and computational modeling of key mechanisms mediating the effects of such triggers and modifying factors on goal-directed, habitual, and compulsive aspects of behavior from human studies and animal models; and (iii) developing and testing interventions that specifically target the underlying mechanisms for regaining control over drug intake.

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.

Regular binge-drinking increases the risk of developing alcohol use disorder (AUD) and induces similar acute effects on behavioral control, particularly in case of response selection conflicts. No such effects have been reported for automatic/bottom-up response selection, even though AUD alters automaticity. However, it has never been reliably tested whether this domain is truly unchanged during high-dose alcohol intoxication. To investigate this question with the help of Bayesian analyses, we subjected n=31 young healthy male participants to a within-subject design, where each participant was tested twice in a counter-balanced order (ie, once sober and once intoxicated at 1.1‰). On each appointment, the participants performed the S-R paradigm, which assesses automatic stimulus-response (S-R) binding within the framework of the theory of event coding (TEC). In short, the TEC states that stimulus features and responses become encoded in an event file when they occur simultaneously. These event files will be reactivated by any matching stimulus feature, thus facilitating the encoded response (and hampering different responses). Alcohol led to a general decrease in behavioral performance, as demonstrated by significant main effects of intoxication status on accuracy and response times (all P ≤ .009). We also reproduced typical task effects, but did not find any significant interactions with the intoxication factor (all P ≥ .099). The latter was further substantiated by Bayesian analyses providing positive to strong evidence for the null hypothesis. Taken together, our results demonstrate that even high-dose alcohol intoxication does not impair automatic response selection/S-R associations.

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.

Alcohol hangover commonly occurs after an episode of heavy drinking. It has previously been demonstrated that acute high-dose alcohol intoxication reduces cognitive control, while automatic processes remain comparatively unaffected. However, it has remained unclear whether alcohol hangover, as a consequence of binge drinking, modulates the interplay between cognitive control and automaticity in a comparable way. Therefore, the purpose of this study was to investigate the effects of alcohol hangover on controlled versus automatic response selection and inhibition. N = 34 healthy young men completed a Simon Nogo task, once sober and once hungover. Hangover symptoms were experimentally induced by a standardized administration of alcoholic drinks (with high congener content) on the night before the hangover appointment. We found no significant hangover effects, which suggests that alcohol hangover did not produce the same functional deficits as an acute high-dose intoxication. Yet still, add-on Bayesian analyses revealed that hangover slightly impaired response selection, but not response inhibition. This pattern of effects cannot be explained with the current knowledge on how ethanol and its metabolite acetaldehyde may modulate response selection and inhibition via the dopaminergic or GABAergic system.

Introduction: Chronic recreational methamphetamine use causes dopaminergic neurotoxicity, which has been linked to impairments in executive functioning. Within this functional domain, response selection and the resolution of associated conflicts have repeatedly been demonstrated to be strongly modulated by dopamine. Yet, it has never been investigated whether chronic methamphetamine use leads to general impairments in response selection (i.e., irrespective of consumption-associated behavior) after substance use is discontinued. Materials and Methods: We tested n = 24 abstinent methamphetamine users (on average 2.7 years of abstinence) and n = 24 individually matched controls in a cross-sectional design with a flanker task. Results: Compared to healthy controls, former methamphetamine consumers had significantly slower reaction times, but did not show differences in the size of the flanker or Gratton effect, or post-error slowing. Complementary Bayesian analyses further substantiated this lack of effects despite prior consumption for an average of 7.2 years. Discussion: The ability to select a correct response from a subset of conflicting alternatives, as well as the selective attention required for this seem to be largely preserved in case of prolonged abstinence. Likewise, the ability to take previous contextual information into account during response selection and to process errors seem to be largely preserved as well. Complementing previously published finding of worse inhibition/interference control in abstinent consumers, our results suggest that not all executive domains are (equally) impaired by methamphetamine, possibly because different cognitive processes require different levels of dopamine activity.

A great deal of our goal-directed behaviour depends on stimulus-response (S-R) associations, which can be established through conditioning or explicit instructions. For conditioned and reward maximizing behaviour, it has been shown that redundant information will no longer be taken into account once those associations have been formed ("blocking effect"). Following from this, new aspects will not be included in a pre-established association unless they improve behaviour. Opposing this, influential action control theories state that all kinds of information may be taken into account during action selection, thus denying the possibility of blocking redundant "surplus" information from non-conditioned goal-directed behaviour. We probed these contradicting predictions by asking two groups of healthy young adults to perform a redundant and a non-redundant version of a stop-change task in a counter-balanced order. Using behavioural and electrophysiological data, we demonstrate that contradicting current theories, blocking seems to be a general mechanism which also applies to non-conditioned goal-directed behaviour. Specifically, we show that the complexity of response selection processes associated with medial frontal cortical activity is altered by blocking. This was reflected by faster responses and smaller central P3 amplitudes originating in the ACC (BA24/BA32). Preceding attentional processes were not affected. Contradicting current views, our ability to ignore information that hampers an expedient unfolding of goal-directed behaviour is quite limited. Prior experiences have a much larger influence on which input we consider for response formation. This offers a functional explanation for why it can be hard to alter (inefficient) behaviour once it has been established.

Controlled behavior is susceptible to conflicts that can emerge from subliminal or consciously processed information. While research suggests that both sources of conflicting information may interact in their modulation of controlled behavior, it has remained unclear which cognitive sub-processes involved in controlled behavior are affected by this interaction; i.e., at which processing level subliminally and consciously induced response conflicts interact in modulating controlled behavior. Moreover, we investigated whether this interaction of subliminally and consciously induced response conflicts was due to a nexus between the two types of conflict like a common cognitive process or factor. For this, n = 38 healthy young subjects completed a paradigm which combines subliminal primes and consciously perceived flankers while an electroencephalography (EEG) was recorded. We show that the interaction of subliminal and conscious sources of conflict is not restricted to the response selection level (N2) but can already be shown at the earliest stages of perceptual and attentional processing (P1). While the degree of early attentional processing of subliminal information seems to depend on the absence of consciously perceived response conflicts, conflicts during the stage of response selection may be either reduced or enhanced by subliminal priming. Moreover, the results showed that even though the two different sources of conflict interact at the response selection level, they clearly originate from two distinct processes that interact before they detrimentally affect cognitive control.

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

The effects of high-dose ethanol intoxication on cognitive flexibility processes are not well understood, and processes related to hangover after intoxication have remained even more elusive. Similarly, it is unknown in how far the complexity of cognitive flexibility processes is affected by intoxication and hangover effects. We performed a neurophysiological study applying high density electroencephalography (EEG) recording to analyze event-related potentials (ERPs) and perform source localization in a task switching paradigm which varied the complexity of task switching by means of memory demands. The results show that high-dose ethanol intoxication only affects task switching (i.e. cognitive flexibility processes) when memory processes are required to control task switching mechanisms, suggesting that even high doses of ethanol compromise cognitive processes when they are highly demanding. The EEG and source localization data show that these effects unfold by modulating response selection processes in the anterior cingulate cortex. Perceptual and attentional selection processes as well as working memory processes were only unspecifically modulated. In all subprocesses examined, there were no differences between the sober and hangover states, thus suggesting a fast recovery of cognitive flexibility after high-dose ethanol intoxication. We assume that the gamma-aminobutyric acid (GABAergic) system accounts for the observed effects, while they can hardly be explained by the dopaminergic system.

Cognitive control is adaptive in the sense that it inhibits automatic processes to optimize goal-directed behavior, but high levels of control may also have detrimental effects in case they suppress beneficial automatisms. Until now, the system neurophysiological mechanisms and functional neuroanatomy underlying these adverse effects of cognitive control have remained elusive. This question was examined by analyzing the automatic exploitation of a beneficial implicit predictive feature under conditions of high versus low cognitive control demands, combining event-related potentials (ERPs) and source localization. It was found that cognitive control prohibits the beneficial automatic exploitation of additional implicit information when task demands are high. Bottom-up perceptual and attentional selection processes (P1 and N1 ERPs) are not modulated by this, but the automatic exploitation of beneficial predictive information in case of low cognitive control demands was associated with larger response-locked P3 amplitudes and stronger activation of the right inferior frontal gyrus (rIFG, BA47). This suggests that the rIFG plays a key role in the detection of relevant task cues, the exploitation of alternative task sets, and the automatic (bottom-up) implementation and reprogramming of action plans. Moreover, N450 amplitudes were larger under high cognitive control demands, which was associated with activity differences in the right medial frontal gyrus (BA9). This most likely reflects a stronger exploitation of explicit task sets which hinders the exploration of the implicit beneficial information in case of high cognitive control demands. Hum Brain Mapp 37:4511-4522, 2016. © 2016 Wiley Periodicals, Inc.

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

Effects of binge drinking on cognitive control and response selection are increasingly recognized in research on alcohol (ethanol) effects. Yet, little is known about how those processes are modulated by hangover effects. Given that acute intoxication and hangover seem to be characterized by partly divergent effects and mechanisms, further research on this topic is needed. In the current study, we hence investigated this with a special focus on potentially differential effects of alcohol intoxication and subsequent hangover on sub-processes involved in the decision to select a response. We do so combining drift diffusion modeling of behavioral data with neurophysiological (EEG) data. Opposed to common sense, the results do not show an impairment of all assessed measures. Instead, they show specific effects of high dose alcohol intoxication and hangover on selective drift diffusion model and EEG parameters (as compared to a sober state). While the acute intoxication induced by binge-drinking decreased the drift rate, it was increased by the subsequent hangover, indicating more efficient information accumulation during hangover. Further, the non-decisional processes of information encoding decreased with intoxication, but not during hangover. These effects were reflected in modulations of the N2, P1 and N1 event-related potentials, which reflect conflict monitoring, perceptual gating and attentional selection processes, respectively. As regards the functional neuroanatomical architecture, the anterior cingulate cortex (ACC) as well as occipital networks seem to be modulated. Even though alcohol is known to have broad neurobiological effects, its effects on cognitive processes are rather specific.

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 GABAA 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.

The restless legs syndrome (RLS) has repeatedly, but not exclusively, been associated with functional thalamic changes as well as changes in GABAergic neurotransmission. This has been linked to the well-known sensory-motor symptoms, but it has never been investigated whether those factors also account for potential cognitive changes in RLS, even though they are known to play an important role for cognitive control. To investigate the potential relationship between thalamic GABA concentrations and cognitive control in n = 25 RLS patients; a neuropsychological experimental paradigm was used in combination with magnetic resonance spectroscopy (MRS). Compared to n = 31 healthy controls, RLS patients displayed reduced cognitive control capacities, which were most likely based on working memory deficits. On the neurobiochemical level, (relatively) elevated thalamic GABA levels attenuated control deficits only in the RLS group, even though there were no group differences with respect to overall GABA levels. Given that RLS patients are known to display thalamic hyperactivity and associated thalamic hypoconnectivity, (relatively) higher GABA levels may have helped RLS patients to “compensate” for this pathological factor. Our findings specify the functional relevance of thalamic GABAergic neurotransmission for cognition in RLS, even though changes in GABAergic neurotransmission might not be the ultimate cause of control deficits.

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

The cholinergic system is one of the most important neurotransmitter systems, but knowledge about the relevance of the cholinergic muscarinergic receptor system for cognitive functions is still scarce. Evidence suggests that the cholinergic muscarinic 2 receptor (CHRM2) plays an important role in the processing of cueing/prior information that help to increase the efficacy of lower-level attentional processes. In the current study, we investigated whether this is also the case for higher-level cognitive flexibility mechanisms. To this end, we tested N = 210 healthy adults with a backward inhibition task, in which prior information needs to be used to guide cognitive flexibility mechanisms. Testing different polymorphisms of the CHRM2 gene, we found that variation in this gene play a role in cognitive flexibility. It could be demonstrated that rs8191992 TT genotype carriers are better able to suppress no longer relevant information and to use prior information for cognitive flexibility, compared to A allele carriers. We further found that rs2350780 GG genotype carriers performed worse than A allele carriers. The results broaden the relevance of the CHRM2 system for cognitive functions beyond attentional selection processes. Corroborating recent theories on the relevance of the cholinergic system for cognitive processes, these results suggest that CHRM2 is important to process of “prior information” needed to inform subsequent cognitive operations. Considering the importance of prior information for adaptive behavioral control, it is possible that CHRM2 also modulates other instances of higher-level cognitive processes as long as these require the processing of “prior information.”

The detrimental effects of acute alcohol intoxication and long-term alcohol (ab)use on cognition are well-known. Yet, only little is known about the cognitive effects of an acute alcohol hangover, even though it might affect executive functions associated with workplace performance or driving skills. Given that alcohol hangover may increase the speed of information accumulation, we assessed the behavioral effects of conflict load (induced by a subliminal prime) on cognitive control, as assessed via the Flanker effect. We employed a counter-balanced within-subject design, where n = 25 healthy young males were tested once after a sober night and once after a night of experimentally induced heavy drinking of cheap brandy/red wine (2.6375 g alcohol per estimated liter of body water within 2-3 h). Alcohol hangover neither increased the cognitive conflicts induced by consciously processed distractors alone (i.e., the Flanker effect), nor modulated conflict adaptation (i.e., the Gratton effect). Instead, hangover potentiated the detrimental effects of conflicting subliminal primes on top-down cognitive conflicts. This effect was likely due to an increase in the speed of information accumulation from visual stimuli and the resulting increase in subliminal conflict load induced by incompatible primes. We further found the size of this effect to be positively correlated with age and subjective sleepiness during the hangover state, but the hangover effect remained significant even after correcting for those covariates. We further found no correlation of the behavioral effect with the subjective overall rating of hangover symptoms or the maximal breath alcohol concentration reached during prior intoxication. Taken together, our findings suggest that alcohol hangover may affect cognitive performance due to an increase in non-conscious processing of visual distractors. While the size of this effect might increase with age and sleepiness, it is not entirely dependent on those covariates and not necessarily related to subjective ratings of general hangover symptoms/impairment.

Binge drinking is an increasingly prevalent pattern of alcohol consumption that impairs top-down cognitive control to a much stronger degree than automatic response generation. Even though an imbalance of those two antagonistic processes fosters the development and maintenance of alcohol use disorders (AUDs), it has never been directly investigated how binge drinking affects the interaction of those two processes. We therefore assessed a sample of n = 35 healthy young men who were asked to perform a newly developed Simon Nogo paradigm once sober and once intoxicated (~1.2‰) in a balanced within-subject design. Additionally, an EEG was recorded to dissociate controlled and automatic cognitive subprocesses. The results demonstrate that alcohol seems to reduce top-down cognitive control. This control impairment was associated with changes in S-R mapping (reflected by a reduced parietal P3 amplitude), top-down response selection (reflected by modulations of lateralized readiness potentials), and (the evaluation of) response inhibition (reflected by modulations of the Nogo P3). In sharp contrast to this, automatic processing does not seem to be equally altered, as we found neither increases nor decreases in this domain. Most importantly, we also found that the interaction between control and automatisms might be less impaired by alcohol than control alone, which may help to overcome alcohol-induced response inhibition deficits. These "carryover" effects of control from one domain to the other could potentially prove beneficial in AUDs.

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.

Neurophysiological features like event-related potentials (ERPs) have long been used to identify different cognitive sub-processes that may contribute to task performance. It has however remained unclear whether “classical” ERPs are truly the best reflection or even causal to observable variations in behavior. Here, we used a data-driven strategy to extract features from neurophysiological data of n = 240 healthy young individuals who performed a Go/Nogo task and used machine learning methods in combination with source localization to identify the best predictors of inter-individual performance variations. Both Nogo-N2 and Nogo-P3 yielded predictions close to chance level, but a feature in between those two processes, associated with motor cortex activity (BA4), predicted group membership with up to ~68%. We further found two Nogo-associated features in the theta and alpha bands, that predicted behavioral performance with up to ~78%. Notably, the theta band feature contributed most to the prediction and occurred at the same time as the predictive ERP feature. Our approach provides a rigorous test for established neurophysiological correlates of response inhibition and suggests that other processes, which occur in between the Nogo-N2 and P3, might be of equal, if not even greater, importance.

Chronic heavy methamphetamine use likely causes dopaminergic neurotoxicity, which is commonly thought to result in cognitive control deficits. Both of these alterations may persist even after the use is discontinued, but tend to (partly) improve with increasing duration of abstinence. While several studies have demonstrated that the reinstatement of comparatively normal dopaminergic signaling may take months, if not years, the amelioration of cognitive deficits has predominantly been investigated in much shorter intervals of several weeks to less than half a year. Against this background, we set out to investigate the effects on prolonged abstinence in n = 27 abstinent former methamphetamine users in a cross-sectional design using behavioral and neurophysiological measures of cognitive control. Our behavioral results suggest that former users struggled to identify and adapt to different degrees of cognitive control requirements, which made their behavioral performance less expedient than that of healthy controls. On the neurophysiological level, this was reflected by reduced modulations of the N2-N450 amplitude in response to high vs. low cognitive control requirements. Yet, those effects could only be observed in methamphetamine users who had been abstinent for a relatively short time (mean 9.9; max. 18 months), but not in former users who had been abstinent two years or longer. While this finding alone does not allow for causal inferences, it suggests that the amelioration of control deficits may take longer than what is commonly investigated (1–6 months). Hence, some of the statements about permanent/irreversible dopamine-dependent executive dysfunctions in former methamphetamine users should be interpreted with caution.

Much research has been devoted to investigating response inhibition and the neuronal processes constituting this essential cognitive faculty. However, the nexus between cognitive subprocesses, behavior, and electrophysiological processes remains associative in nature. We therefore investigated whether neurophysiological correlates of inhibition subprocesses merely correlate with behavioral performance or actually provide information expedient to the prediction of behavior on a single-subject level. Tackling this question, we used different data-driven classification approaches in a sample of n = 262 healthy young subjects who completed a standard Go/Nogo task while an EEG was recorded. On the basis of median-split response inhibition performance, subjects were classified as “accurate/slow” and “less accurate/fast.” Even though these behavioral group differences were associated with significant amplitude variations in classical electrophysiological correlates of response inhibition (i.e., N2 and P3), they were not predictive for group membership on a single-subject level. Instead, amplitude differences in the Go-P2 originating in the precuneus (BA7) were shown to predict group membership on a single-subject level with up to 64% accuracy. These findings strongly suggest that the behavioral outcome of response inhibition greatly depends on the amount of cognitive resources allocated to early stages of stimulus-response activation during responding. This suggests that research should focus more on early processing steps during responding when trying to understand the origin of interindividual differences in response inhibition processes.

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

Recent research has drawn interest to the effects of binge drinking on response selection. However, choosing an appropriate response is a complex endeavor that usually requires us to process and integrate several streams of information. One of them is proprioceptive information about the position of limbs. As to now, it has however remained elusive how binge drinking affects the processing of proprioceptive information during response selection and control in healthy individuals. We investigated this question using neurophysiological (EEG) techniques in a response selection task, where we manipulated proprioceptive information. The results show a reversal of alcohol-induced effects on response control due to changes in proprioceptive information processing. The most likely explanation for this finding is that proprioceptive information does not seem to be properly integrated in response selection processes during acute alcohol intoxication as found in binge drinking. The neurophysiological data suggest that processes related to the preparation and execution of the motor response, but not upstream processes related to conflict monitoring and spatial attentional orienting, underlie these binge drinking-dependent modulations. Taken together, the results show that even high doses of alcohol have very specific effects within the cascade of neurophysiological processes underlying response control and the integration of proprioceptive information during this process.

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

The ever-changing environment we are living in requires us to apply different action control strategies in order to fulfill a task goal. Indeed, when confronted with multiple response options it is fundamental to prioritize and cascade different actions. So far, very little is known about the neuromodulation of action cascading. In this study we assessed the causal role of the gamma-aminobutyric acid (GABA)-ergic and noradrenergic system in modulating the efficiency of action cascading by applying transcutaneous vagus nerve stimulation (tVNS), a new non-invasive and safe method to stimulate the vagus nerve and to increase GABA and norepinephrine concentrations in the brain. A single-blind, sham-controlled, between-group design was used to assess the effect of on-line (i.e., stimulation overlapping with the critical task) tVNS in healthy young volunteers ( n =30)–on a stop-change paradigm. Results showed that active, as compared to sham stimulation, enhanced response selection functions during action cascading and led to faster responses when two actions were executed in succession. These findings provide evidence for the important role of the GABA-ergic and noradrenergic system in modulating performance in action cascading.