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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.

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.

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.

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.

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.”