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The retina has been considered a "window to the brain" and shares similar innervation by the dopaminergic system with the cortex in terms of an unequal distribution of D1 and D2 receptors. Here, we provide a comprehensive overview that Optical Coherence Tomography (OCT), a non-invasive imaging technique, which provides an "in vivo" representation of the retina, shows promise to be used as a surrogate marker of dopaminergic neuromodulation in cognition. Overall, most evidence supports reduced retinal thickness in individuals with dopaminergic dysregulation (e.g., patients with Parkinson's Disease, non-demented older adults) and with poor cognitive functioning. By using the theoretical framework of metacontrol, we derive hypotheses that retinal thinning associated to decreased dopamine (DA) levels affecting D1 families, might lead to a decrease in the signal-to-noise ratio (SNR) affecting cognitive persistence (depending on D1-modulated DA activity) but not cognitive flexibility (depending on D2-modulated DA activity). We argue that the use of OCT parameters might not only be an insightful for cognitive neuroscience research, but also a potentially effective tool for individualized medicine with a focus on cognition. As our society progressively ages in the forthcoming years and decades, the preservation of cognitive abilities and promoting healthy aging will hold of crucial significance. OCT has the potential to function as a swift, non-invasive, and economical method for promptly recognizing individuals with a heightened vulnerability to cognitive deterioration throughout all stages of life., Competing Interests: Declaration of Competing Interest None. The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Neurofilaments (NFs) are not only important for axonal integrity and nerve conduction in large myelinated axons but they are also thought to be crucial for receptor and synaptic functioning. Therefore, NFs may play a critical role in cognitive functions, as cognitive processes are known to depend on synaptic integrity and are modulated by dopaminergic signaling. Here, we present a theory-driven interdisciplinary approach that NFs may link inflammation, neurodegeneration, and cognitive functions. We base our hypothesis on a wealth of evidence suggesting a causal link between inflammation and neurodegeneration and between these two and cognitive decline (see Fig. 1), also taking dopaminergic signaling into account. We conclude that NFs may not only serve as biomarkers for inflammatory, neurodegenerative, and cognitive processes but also represent a potential mechanical hinge between them, moreover, they may even have predictive power regarding future cognitive decline. In addition, we advocate the use of both NFs and MRI parameters, as their synthesis offers the opportunity to individualize medical treatment by providing a comprehensive view of underlying disease activity in neurological diseases. Since our society will become significantly older in the upcoming years and decades, maintaining cognitive functions and healthy aging will play an important role. Thanks to technological advances in recent decades, NFs could serve as a rapid, noninvasive, and relatively inexpensive early warning system to identify individuals at increased risk for cognitive decline and could facilitate the management of cognitive dysfunctions across the lifespan., Competing Interests: Declaration of Competing Interest None. The authors declare no competing interests. This work was supported by a research grant from 100 Talent Grant of the Province of Shandong, China, to L.S.C., and C.B. and by a Deutsche Forschungsgemeinschaft (DFG), SFB 940., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Long COVID, the postviral disorder caused by COVID-19, is expected to become one of the leading causes of disability in Europe. The cognitive consequences of long COVID have been described as "brain fog" and characterized by anxiety and depression, and by cognitive deficits. Long COVID is assumed to be a complex condition arising from multiple causes, including persistent brainstem dysfunction and disrupted vagal signaling. We recommend the potential application of auricular transcutaneous vagus nerve stimulation (atVNS) as an ADD-ON instrument to compensate for the cognitive decline and to ameliorate affective symptoms caused by long COVID. This technique enhances vagal signaling by directly activating the nuclei in the brainstem, which are hypoactive in long COVID to enhance mood and to promote attention, memory, and cognitive control-factors affected by long COVID. Considering that atVNS is a non-pharmacological intervention, its ADD-ON to standard pharmaceutical agents will be useful for non-responders, making of this method a suitable tool. Given that atVNS can be employed as an ecological momentary intervention (EMI), we outline the translational advantages of atVNS in the context of accelerating the cognitive and affective recovery from long COVID.

Standard clinical and psychiatric thinking follows a unipolar logic that is centered at "normal" conditions characterized by optimal performance in everyday life, with more atypical conditions being defined by the (degree of) absence of "normality." A similar logic has been used to describe cognitive control, assuming that optimal control abilities are characterized by a strong focus on the current goal and ignorance of goal-irrelevant information (the concept of willpower), while difficulties in focusing and ignoring are considered indications of the absence of control abilities. However, there is increasing evidence that willpower represents only one side of the control coin. While a strong focus on the current goal can be beneficial under some conditions, other conditions would benefit from a more open mind, from flexibility to consider alternative goals and information related to them. According to the metacontrol model, people can vary in their cognitive processing style, on a dimension with the extreme poles of "persistence" on the one hand and "flexibility" on the other. Whereas a high degree of persistence corresponds to the original idea of cognitive control as willpower, with a strong focus on one goal and the information related to it, a high degree of flexibility is characterized by a more integrative, less selective and exclusive processing style, which facilitates switching between tasks, ideas, and actions, and taking into consideration a broader range of possibilities. We argue that this approach calls for a more bipolar account in the clinical sciences as well. Rather than considering individuals as typical or atypical, it would theoretically and practically make more sense to characterize their cognitive abilities in terms of underlying dimensions, such as the persistence/flexibility dimension. This would reveal that possible weaknesses with respect to one pole, such as persistence, and tasks relying thereupon, may come with corresponding strengths with respect to the other pole, such as flexibility, and respective tasks. We bolster our claim by discussing available evidence suggesting that neurodevelopmental atypicality often comes with weaknesses in tasks related to one pole but strengths in tasks related to the other., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Colzato, Beste, Zhang and Hommel.)

Obsessive-compulsive disorder (OCD) and attention-deficit hyperactivity disorder (ADHD) are multi-faceted neuropsychiatric conditions that in many aspects appear to be each other's antipodes. We suggest a dimensional approach, according to which these partially opposing disorders fall onto a continuum that reflects variability regarding alterations of cortico-striato-thalamo-cortical (CSTC) circuits and of the processing of neural noise during cognition. By using theoretical accounts of human cognitive metacontrol, we develop a framework according to which OCD can be characterized by a chronic bias towards exaggerated cognitive persistence, equivalent to a high signal-to-noise ratio (SNR)-which facilitates perseverative behaviour but impairs mental flexibility. In contrast, ADHD is characterized by a chronic bias towards inflated cognitive flexibility, equivalent to a low SNR-which increases behavioural variability but impairs the focusing on one goal and on relevant information. We argue that, when pharmacology is not feasible, novel treatments of these disorders may involve methods to manipulate the signal-to-noise ratio via non-invasive brain stimulation techniques, in order to normalize the situational imbalance between cognitive persistence and cognitive flexibility., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Standard accounts of mental health are based on a "deficit view" solely focusing on cognitive impairments associated with psychiatric conditions. Based on the principle of neural competition, we suggest an alternative. Rather than focusing on deficits, we should focus on the cognitive potential that selective dysfunctions might bring with them. Our approach is based on two steps: the identification of the potential (i.e., of neural systems that might have benefited from reduced competition) and the development of corresponding training methods, using the testing-the-limits approach. Counterintuitively, we suggest to train not only the impaired function but on the function that might have benefitted or that may benefit from the lesser neural competition of the dysfunctional system., (© 2022. The Author(s).)

According to the Polyvagal theory, the vagus nerve is the key phylogenetic substrate that supports efficient emotion recognition for promoting safety and survival. Previous studies showed that the vagus nerve affects people's ability to recognize emotions based on eye regions and whole facial images, but not static bodies. The purpose of this study was to verify whether the previously suggested causal link between vagal activity and emotion recognition can be generalized to situations in which emotions must be inferred from images of whole moving bodies. We employed transcutaneous vagus nerve stimulation (tVNS), a noninvasive brain stimulation technique that stimulates the vagus nerve by a mild electrical stimulation to the auricular branch of the vagus, located in the anterior protuberance of the outer ear. In two sessions, participants received active or sham tVNS before and while performing three emotion recognition tasks, aimed at indexing their ability to recognize emotions from static or moving bodily expressions by actors. Active tVNS, compared to sham stimulation, enhanced the recognition of anger but reduced the ability to recognize sadness, regardless of the type of stimulus (static vs. moving). Convergent with the idea of hierarchical involvement of the vagus in establishing safety, as put forward by the Polyvagal theory, we argue that our findings may be explained by vagus-evoked differential adjustment strategies to emotional expressions. Taken together, our findings fit with an evolutionary perspective on the vagus nerve and its involvement in emotion recognition for the benefit of survival., (© 2021. The Author(s).)

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Cognitive enhancement is becoming progressively popular as a subject of scientific investigation and by the public, although possible adverse effects are not sufficiently understood. We call for cognitive enhancement to build on more specific, mechanistic theories given that a-theoretical approaches to cognitive enhancement are both a cause and a consequence of a strong, if not exclusive focus on the benefits of procedures suited to enhance human cognition. We focus on downsides of cognitive enhancement and suggest that every attempt to enhance human cognition needs to deal with two basic principles: the neuro-competition principle and the nonlinearity principle. We discuss the possibility of both principles in light of recent attempts to improve human cognition by means of transcranial direct current stimulation, a well-established brain stimulation method, and clinically relevant nootropic drugs. We propose that much stronger emphasis on mechanistic theorizing is necessary in guiding future research on both the upsides and the downsides of cognitive enhancement.

Tics, often preceded by premonitory urges, are the clinical hallmark of Tourette syndrome. They resemble spontaneous movements, but are exaggerated, repetitive and appear misplaced in a given communication context. Given that tics often go unnoticed, it has been suggested that they represent a surplus of action, or motor noise. In this conceptual position paper, we propose that tics and urges, but also patterns of the cognitive profile in Tourette syndrome might be explained by the principle of processing of neural noise and adaptation to it during information processing. We review evidence for this notion in the light of Tourette pathophysiology and outline why neurophysiological and imaging approaches are central to examine a possibly novel view on Tourette syndrome. We discuss how neurophysiological data at multiple levels of inspections, i.e., from local field potentials using intra-cranial recording to scalp-measured EEG data, in combination with imaging approaches, can be used to examine the neural noise account in Tourette syndrome. We outline what signal processing methods may be suitable for that. We argue that, as a starting point, the analysis of 1/f neural noise or scale-free activity may be suitable to investigate the role of neural noise and its adaptation during information processing in Tourette syndrome. We outline, how the neural noise perspective, if substantiated by further neurophysiological studies and re-analyses of existing data, may pave the way to novel interventions directly targeting neural noise levels and patterns in Tourette syndrome., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Gilles de la Tourette Syndrome is a multifaceted neuropsychiatric disorder typically commencing in childhood and characterized by motor and phonic tics. Its pathophysiology is still incompletely understood. However, there is convincing evidence that structural and functional abnormalities in the basal ganglia, in cortico-striato-thalamo-cortical circuits, and some cortical areas including medial frontal regions and the prefrontal cortex as well as hyperactivity of the dopaminergic system are key findings. Conventional therapeutic approaches in addition to counseling comprise behavioral treatment, particularly habit reversal therapy, oral pharmacotherapy (antipsychotic medication, alpha-2-agonists) and botulinum toxin injections. In treatment-refractory Tourette syndrome, deep brain stimulation, particularly of the internal segment of the globus pallidus, is an option for a small minority of patients. Based on pathophysiological considerations, non-invasive brain stimulation might be a suitable alternative. Repetitive transcranial magnetic stimulation appears particularly attractive. It can lead to longer-lasting alterations of excitability and connectivity in cortical networks and inter-connected regions including the basal ganglia through the induction of neural plasticity. Stimulation of the primary motor and premotor cortex has so far not been shown to be clinically effective. Some studies, though, suggest that the supplementary motor area or the temporo-parietal junction might be more appropriate targets. In this manuscript, we will review the evidence for the usefulness of repetitive transcranial magnetic stimulation and transcranial electric stimulation as treatment options in Tourette syndrome. Based on pathophysiological considerations we will discuss the rational for other approaches of non-invasive brain stimulation including state informed repetitive transcranial magnetic stimulation., (Copyright © 2020 Kleimaker, Kleimaker, Weissbach, Colzato, Beste, Bäumer and Münchau.)

Transcutaneous vagus nerve stimulation (tVNS) has been shown to promote inferences of emotional states based on eye-related information provided by facial expressions of emotions. Eye gaze direction can influence the allocation of attentional sources when processing facial emotional stimuli. Here we sought for further evidence indicating whether tVNS effects would be specific to emotional expressions or to gaze - both socially relevant stimuli - and whether they reflect the enhancement of attention. In two separate sessions receiving either active or sham tVNS, forty-three healthy young volunteers completed a Rapid Serial Visual Presentation task in which participants identified the gender of a target face (T1) with direct (salient social cue) or averted gaze (subtler social cue) with different emotional expressions or a neutral expression, and then judged the orientation of a landscape (T2) that appeared at different temporal lags after T1. Active tVNS, compared to sham stimulation, enhanced conditional T2 accuracy for both neutral and emotional faces and independently of the temporal lag, but only when gaze was directed at the participant. This suggests that tVNS modulates attention to a direct gaze (salient social cue) irrespective of the expressed emotion. We interpret that the effects of tVNS seem to reflect enhanced perception of gaze direction, which in turn attracts attention, making the observer more sensitive and increasing the impact of the socially relevant facial cue. We conclude that tVNS is a promising technique for enhancing social information processing in healthy humans., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Controlling impulsivity and delaying gratifications are key features of effective self-control. Delay Discounting (DD) indexes the ability to delay rewards and previous research has shown that discounting is influenced by affective states such as mood. According to the Somatic Marker Hypothesis (SMH), afferent somatic signals, such as mood, are carried by the vagus and can influence decision making. In the current study, we employed transcutaneous vagus nerve stimulation (tVNS), a novel non-invasive brain stimulation technique that stimulates the auricular branch of the afferent vagus nerve (located in the outer ear), to assess its effects on decision impulsivity, while taking into account individuals' mood and resting-state HRV as a possible confounding factor. Employing a within-subjects cross-over design, 94 participants received active or sham tVNS while performing delay discounting in two separate sessions. As compared to sham, active tVNS increased discounting, but only for individuals reporting lower positive mood, regardless of the level of negative mood reported. We evidence that the effect of tVNS on reward discounting depends on the level of positive mood. This result suggests that positive mood state might be a proxy of task-relevant arousal, likely influencing the effectiveness of afferent vagal stimulation on self-control processes, as temporal discounting., (Copyright © 2019. Published by Elsevier B.V.)

The aim of the study was to throw more light on the relationship between rumination and cognitive-control processes. Seventy-eight adults were assessed with respect to rumination tendencies by means of the LEIDS-r before performing a Stroop task, an event-file task assessing the automatic retrieval of irrelevant information, an attentional set-shifting task, and the Attentional Network Task, which provided scores for alerting, orienting, and executive control functioning. The size of the Stroop effect and irrelevant retrieval in the event-five task were positively correlated with the tendency to ruminate, while all other scores did not correlate with any rumination scale. Controlling for depressive tendencies eliminated the Stroop-related finding (an observation that may account for previous failures to replicate), but not the event-file finding. Taken altogether, our results suggest that rumination does not affect attention, executive control, or response selection in general, but rather selectively impairs the control of stimulus-induced retrieval of irrelevant information.

Spatial reasoning is essential for an agent's navigation and the cognitive processing of abstract arrangements. Meta-analyses of neuroimaging data reveal that both the right posterior parietal cortex and left dorsolateral prefrontal cortex (PPC and DLPFC, respectively) show increased activation during spatial relational reasoning. To investigate whether participants' reasoning performance can be modified and potentially enhanced, anodal transcranial direct current stimulation (tDCS) was applied over either region. 51 healthy adult participants solved spatial reasoning problems after the application of either anodal tDCS over the right PPC, the left DLPFC or a sham stimulation. We expect anodal stimulation to enhance cortical excitability which would be reflected by enhanced reasoning performance in participants receiving stimulation. The results demonstrate that anodal stimulation applied over the right PPC enhances participants' performance in indeterminate reasoning problems, compared to sham and anodal stimulation over the left DLPFC. This finding is highly relevant for clarifying the cognitive mechanisms of relational reasoning and for clinical applications, e.g., enhancing or restoring higher cognitive functions for spatial representation and reasoning.

Background: Highly complex tasks generally benefit from increases in cognitive control, which has been linked to dopamine. Yet, the same amount of control may actually be detrimental in tasks with low complexity so that the task-dependent allocation of cognitive control resources (also known as "metacontrol") is key to expedient and adaptive behavior in various contexts., Methods: Given that dopamine D1 and D2 receptors have been suggested to exert opposing effects on cognitive control, we investigated the impact of 2 single nucleotide polymorphisms in the DRD1 (rs4532) and DRD2 (rs6277) genes on metacontrol in 195 healthy young adults. Subjects performed 2 consecutive tasks that differed in their demand for control (starting with the less complex task and then performing a more complex task rule)., Results: We found carriers of the DRD1 rs4532 G allele to outperform noncarriers in case of high control requirements (i.e., reveal a better response accuracy), but not in case of low control requirements. This was confirmed by Bayesian analyses. No effects of DRD2 rs6277 genotype on either task were evident, again confirmed by Bayesian analyses., Conclusions: Our findings suggest that higher DRD1 receptor efficiency improves performance during high, but not low, control requirements, probably by promoting a "D1 state," which is characterized by highly stable task set representations. The null findings for DRD2 signaling might be explained by the fact that the "D2 state" is thought to enhance flexible switching between task set representations when our task only featured 1 task set at any given time., (© The Author(s) 2019. Published by Oxford University Press on behalf of CINP.)

Many studies have reported that heavy substance use is associated with impaired response inhibition. Studies typically focused on associations with a single substance, while polysubstance use is common. Further, most studies compared heavy users with light/non-users, though substance use occurs along a continuum. The current mega-analysis accounted for these issues by aggregating individual data from 43 studies (3610 adult participants) that used the Go/No-Go (GNG) or Stop-signal task (SST) to assess inhibition among mostly "recreational" substance users (i.e., the rate of substance use disorders was low). Main and interaction effects of substance use, demographics, and task-characteristics were entered in a linear mixed model. Contrary to many studies and reviews in the field, we found that only lifetime cannabis use was associated with impaired response inhibition in the SST. An interaction effect was also observed: the relationship between tobacco use and response inhibition (in the SST) differed between cannabis users and non-users, with a negative association between tobacco use and inhibition in the cannabis non-users. In addition, participants' age, education level, and some task characteristics influenced inhibition outcomes. Overall, we found limited support for impaired inhibition among substance users when controlling for demographics and task-characteristics., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Transcranial direct current stimulation (tDCS) transiently alters cortical excitability and synaptic plasticity. So far, few studies have investigated the behavioral effects of applying tDCS to the cerebellum. Given the cerebellum's inhibitory effects on cortical motor areas as well as its role in fine motor control and motor coordination, we investigated whether cerebellar tDCS can modulate response selection processes and motor sequence learning. Seventy-two participants received either cerebellar anodal (excitatory), cathodal (inhibitory), or sham (placebo) tDCS while performing a serial reaction time task (SRTT). To compare acute and long-term effects of stimulation on behavioral performance, participants came back for follow-up testing at 24 h after stimulation. Results indicated no group differences in performance prior to tDCS. During stimulation, tDCS did not affect sequence-specific learning, but anodal as compared to cathodal and sham stimulations did modulate response selection processes. Specifically, anodal tDCS increased response latencies independent of whether a trained or transfer sequence was being performed, although this effect became smaller throughout training. At the 24-h follow-up, the group that previously received anodal tDCS again demonstrated increased response latencies, but only when the previously trained sequence and a transfer sequence had to be performed in the same experimental block. This increased behavioral interference tentatively points to a detrimental effect of anodal cerebellar tDCS on sequence consolidation/retention. These results are consistent with the notion that the cerebellum exerts an inhibitory effect on cortical motor areas, which can impair sequential response selection when this inhibition is strengthened by tDCS.

Anecdotal evidence suggests that cocaine use will help overcome creative 'blocks' by enhancing flexible thinking. Given that cocaine is likely to enhance dopamine (DA) levels, which in turn are positively associated with divergent thinking (DT); is a possibility that is tested in the present study. Furthermore, the impact of cocaine is tested on convergent thinking (CT), another aspect of creative thinking, which has been reported to be impaired with high DA levels. It was hypothesized that cocaine would enhance DT and impair CT. A placebo-controlled within-subjects study including 24 healthy poly-drug users was set up to test the influence of oral cocaine (300 mg) on creativity. Verbal CT was assessed with the Remote Associates Task (RAT); figural CT was assessed with the Picture Concepts Task (PCT) and the Tower of London (TOL). Verbal DT was assessed with the Alternative Uses Task (AUT); figural DT was assessed with the Pattern/Line Meanings Task (PLMT). Findings showed that, compared to placebo, cocaine impaired figural CT (TOL) and flexible DT of verbal stimuli (AUT), while it enhanced figural DT (PLMT). No significant effects of cocaine were observed regarding the PCT and RAT. It was demonstrated that cocaine-induced effects on creativity in poly-drug users are stimulus-dependent. Cocaine enhanced performance on figural DT but impaired performance on verbal (flexible) DT. Cocaine impaired CT on only one figural task and but not on the other tasks. As creativity is an important aspect in cognitive therapies, it is important to further understand these discrepancies in creativity task performance., (Copyright © 2019. Published by Elsevier B.V.)

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

Objective: The correct production of speech depends on the effective use of inhibitory control. Cocaine abuse has been linked to impaired inhibition in the verbal and nonverbal domains. The aim of this study was to evaluate the possible impairment of the inhibitory control process engaged in the production of language among chronic cocaine users, both in rehabilitation and recreational contexts., Method: Researchers obtained an index of semantic interference from a picture-word task performed by chronic cocaine users in rehabilitation (Experiment 1) and recreational cocaine polydrug users (Experiment 2). Cocaine users in both groups were matched for age and intelligence with cocaine-free health controls. Performance on the picture-word task was analyzed by repeated-measures analyses of variance., Results: Both groups of cocaine users showed significantly more semantic interference than their respective cocaine-free control group. These results suggest a deficit in the ability to inhibit interfering information., Conclusions: The present findings suggest that cocaine use, even at recreational levels, is associated with specific impairments in the inhibitory mechanism that reduces the activation of overt competing responses in language production. This impairment results in the inefficient avoidance of irrelevant information, inducing errors and slower responses during the production of spoken language., (© 2019 John Wiley & Sons, Ltd.)

Transcranial direct current stimulation (tDCS) can alter cortical excitability, neural plasticity, and cognitive-behavioral performance; however, its effects are known to vary across studies. A partial account of this variability relates to individual differences in dopamine function. Indeed, dopaminergic manipulations alter the physiological and cognitive-behavioral effects of tDCS, and gene polymorphisms related to dopamine have predicted individual response to online tDCS (i.e., stimulation overlapping with the critical task). Notably, the role of individual differences in dopamine has not yet been properly assessed in the effect of offline tDCS (i.e., stimulation prior to the critical task). We investigated if and how the COMT Val 158 Met polymorphism (rs4680) modulates the after-effect of prefrontal tDCS on verbal working memory (WM). One hundred and thirty-nine participants were genotyped for the COMT Val 158 Met polymorphism and received anodal-over-left, cathodal-over-right (AL-CR), cathodal-over-left, anodal-over-right (CL-AR), or sham stimulation over the dorsolateral prefrontal cortex in a between-subjects, pretest-posttest study design. WM was assessed using the N-back task. The results provide no evidence that the COMT polymorphism impacts the after-effect of prefrontal tDCS on WM. Taken together with previous findings on dopamine and tDCS interactions, the results of the present study suggest that (a) indirect markers of dopamine (such as COMT) are differently related to online and offline effects of tDCS, and (b) findings from studies involving pharmacological manipulation should be generalized with caution to findings of inter-individual differences. In sum, we argue that state (i.e., a manipulation of) and trait (i.e., baseline) differences in dopamine may exert different effects on online and offline tDCS., (© 2018 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and JohnWiley & Sons Ltd.)

Introduction: Taking microdoses (a mere fraction of normal doses) of psychedelic substances, such as truffles, recently gained popularity, as it allegedly has multiple beneficial effects including creativity and problem-solving performance, potentially through targeting serotonergic 5-HT 2A receptors and promoting cognitive flexibility, crucial to creative thinking. Nevertheless, enhancing effects of microdosing remain anecdotal, and in the absence of quantitative research on microdosing psychedelics, it is impossible to draw definitive conclusions on that matter. Here, our main aim was to quantitatively explore the cognitive-enhancing potential of microdosing psychedelics in healthy adults., Methods: During a microdosing event organized by the Dutch Psychedelic Society, we examined the effects of psychedelic truffles (which were later analyzed to quantify active psychedelic alkaloids) on two creativity-related problem-solving tasks: the Picture Concept Task assessing convergent thinking and the Alternative Uses Task assessing divergent thinking. A short version of the Ravens Progressive Matrices task assessed potential changes in fluid intelligence. We tested once before taking a microdose and once while the effects were expected to be manifested., Results: We found that both convergent and divergent thinking performance was improved after a non-blinded microdose, whereas fluid intelligence was unaffected., Conclusion: While this study provides quantitative support for the cognitive-enhancing properties of microdosing psychedelics, future research has to confirm these preliminary findings in more rigorous placebo-controlled study designs. Based on these preliminary results, we speculate that psychedelics might affect cognitive metacontrol policies by optimizing the balance between cognitive persistence and flexibility. We hope this study will motivate future microdosing studies with more controlled designs to test this hypothesis.

The neurovisceral integration model proposes that heart rate variability (HRV) is linked to prefrontal cortex activity via the vagus nerve, which connects the heart and the brain. HRV, an index of cardiac vagal tone, has been found to predict performance on several cognitive control tasks that rely on the prefrontal cortex. However, the link between HRV and the core cognitive control function "shifting" between tasks and mental sets is under-investigated. Therefore, the present study tested the neurovisceral integration model by examining, in 90 participants, the relationship between vagally mediated resting-state HRV and performance in a task-switching paradigm that provides a relatively process-pure measure of cognitive flexibility. As predicted, participants with higher resting-state HRV (indexed both by time domain and frequency domain measures) showed smaller switch costs (i.e., greater flexibility) than individuals with lower resting-state HRV. Our findings support the neurovisceral integration model and indicate that higher levels of vagally mediated resting-state HRV promote cognitive flexibility.

Transcutaneous vagus nerve stimulation (tVNS) is a non-invasive and safe technique that transiently enhances brain GABA and noradrenaline levels. Although tVNS has been used mainly to treat clinical disorders such as epilepsy, recent studies indicate it is also an effective tool to investigate and potentially enhance the neuromodulation of action control. Given the key roles of GABA and noradrenaline in neural plasticity and cortical excitability, we investigated whether tVNS, through a presumed increase in level of these neurotransmitters, modulates sequential behavior in terms of response selection and sequence learning components. To this end we assessed the effect of single-session tVNS in healthy young adults ( N = 40) on performance on a serial reaction time task, using a single-blind, sham-controlled between-subject design. Active as compared to sham tVNS did not differ in terms of acquisition of an embedded response sequence and in terms of performance under randomized response schedules. However, active tVNS did enhance response selection processes. Specifically, the group receiving active tVNS did not exhibit inhibition of return during response reversals (i.e., when trial N requires the same response as trial N -2, e.g., 1-2-1) on trials with an embedded response sequence. This finding indicates that tVNS enhances response selection processes when selection demands are particularly high. More generally, these results add to converging evidence that tVNS enhances action control performance.

Creativity is one of the most important cognitive skills in our complex and fast-changing world. Previous correlative evidence showed that gamma-aminobutyric acid (GABA) is involved in divergent but not convergent thinking. In the current study, a placebo/sham-controlled, randomized between-group design was used to test a causal relation between vagus nerve and creativity. We employed transcutaneous vagus nerve stimulation (tVNS), a novel non-invasive brain stimulation technique to stimulate afferent fibers of the vagus nerve and speculated to increase GABA levels, in 80 healthy young volunteers. Creative performance was assessed in terms of divergent thinking (Alternate Uses Task) and convergent thinking tasks (Remote Associates Test, Creative Problem Solving Task, Idea Selection Task). Results demonstrate active tVNS, compared to sham stimulation, enhanced divergent thinking. Bayesian analysis reported the data to be inconclusive regarding a possible effect of tVNS on convergent thinking. Therefore, our findings corroborate the idea that the vagus nerve is causally involved in creative performance. Even thought we did not directly measure GABA levels, our results suggest that GABA (likely to be increased in active tVNS condition) supports the ability to select among competing options in high selection demand (divergent thinking) but not in low selection demand (convergent thinking)., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The polyvagal theory suggests that the vagus nerve is the key phylogenetic substrate enabling optimal social interactions, a crucial aspect of which is emotion recognition. A previous study showed that the vagus nerve plays a causal role in mediating people's ability to recognize emotions based on images of the eye region. The aim of this study is to verify whether the previously reported causal link between vagal activity and emotion recognition can be generalized to situations in which emotions must be inferred from images of whole faces and bodies. To this end, we employed transcutaneous vagus nerve stimulation (tVNS), a novel non-invasive brain stimulation technique that causes the vagus nerve to fire by the application of a mild electrical stimulation to the auricular branch of the vagus nerve, located in the anterior protuberance of the outer ear. In two separate sessions, participants received active or sham tVNS before and while performing two emotion recognition tasks, aimed at indexing their ability to recognize emotions from facial and bodily expressions. Active tVNS, compared to sham stimulation, enhanced emotion recognition for whole faces but not for bodies. Our results confirm and further extend recent observations supporting a causal relationship between vagus nerve activity and the ability to infer others' emotional state, but restrict this association to situations in which the emotional state is conveyed by the whole face and/or by salient facial cues, such as eyes., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In a randomized, double-blind, and placebo-controlled experiment, the acute effects of gamma-aminobutyric acid (GABA) supplementation on temporal and spatial attention in young healthy adults were investigated. A hybrid two-target rapid serial visual presentation task was used to measure temporal attention and integration. Additionally, a visual search task was used to measure the speed and accuracy of spatial attention. While temporal attention depends primarily on the distribution of limited attentional resources across time, spatial attention represents the engagement and disengagement by relevant and irrelevant stimuli across the visual field. Although spatial attention was unaffected by GABA supplementation altogether, we found evidence supporting improved performance in the temporal attention task. The attentional blink was numerically, albeit not significantly, attenuated at Lag 3, and significantly fewer order errors were committed at Lag 1, compared to the placebo condition. No effect was found on temporal integration rates. Although there is controversy about whether oral GABA can cross the blood-brain barrier, our results offer preliminary evidence that GABA intake might help to distribute limited attentional resources more efficiently, and can specifically improve the identification and ordering of visual events that occur in close temporal succession., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Flow has been defined as a pleasant psychological state that people experience when completely absorbed in an activity. Previous correlative evidence showed that the vagal tone (as indexed by heart rate variability) is a reliable marker of flow. So far, it has not yet been demonstrated that the vagus nerve plays a causal role in flow. To explore this we used transcutaneous vagus nerve stimulation (tVNS), a novel non-invasive brain stimulation technique that increases activation of the locus coeruleus (LC) and norepinephrine release. A sham/placebo-controlled, randomized cross-over within-subject design was employed to infer a causal relation between the stimulated vagus nerve and flow as measured using the Flow Short-Scale in 32 healthy young volunteers. In both sessions, while being stimulated, participants had to rate their flow experience after having performed a task for 30 min. Active tVNS, compared to sham stimulation, decreased flow (as indexed by absorption scores). The results can be explained by the network reset theory, which assumes that high-phasic LC activity promotes a global reset of attention over exploitation of the current focus of attention, allowing rapid behavioral adaptation and resulting in decreased absorption scores. Furthermore, our findings corroborate the hypothesis that the vagus nerve and noradrenergic system are causally involved in flow.

The neurovisceral integration model suggests that individual differences in heart rate variability (HRV), an index of vagal tone, may relate to prefrontal cortical activity and predict performance on cognitive control tasks. The aim of this study was to further verify this model by investigating the relationship between vagally-mediated resting-state HRV and action cascading, a crucial cognitive control function which refers to the ability to cope with multiple response options when confronted with various task goals. Resting-state HRV and performance on the stop-change paradigm, which provides a relatively well-established diagnostic measure of action cascading and response inhibition, was assessed in 88 healthy volunteers (age range 18-33). Compared to individuals with low resting-state HRV, participants with high resting-state HRV showed enhanced action cascading performance, both when a disruption (stopping) and change towards an alternative response were required simultaneously, and when requirements were cascaded (i.e. when the stopping process had already finished at the time the change was required). Our findings represent an important step towards extending our understanding of the neurovisceral integration model in cognitive control., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The prevalence of weight problems is increasing worldwide. There is growing evidence that high body mass index (BMI) is associated with frontal lobe dysfunction and deficits in cognitive control. The present study aims to clarify the association between weight status and the degree of impairment in cognitive flexibility, i.e., the ability to efficiently switch from one task to another, by disentangling the preparatory and residual domains of task switching. Twenty-six normal weight (BMI < 25, five males) and twenty-six overweight (BMI ≥ 25, seven males) university students performed a task-switching paradigm that provides a relatively well-established diagnostic measure of proactive vs. reactive control with regard to cognitive flexibility. Compared to individuals with a BMI lower than 25, overweight (i.e., ≥25) was associated with increased switching costs in the reactive switching condition (i.e., when preparation time is short), representing reduced cognitive flexibility in the preparatory domain. In addition, the overweight group reported significantly more depression and binge eating symptoms, although still indicating minimal depression. No between-group differences were found with regard to self-reported autism spectrum symptoms, impulsiveness, state- and trait anxiety, and cognitive reactivity to depression. The present findings are consistent with and extend previous literature showing that elevated BMI in young, otherwise healthy individuals is associated with significantly more switching costs due to inefficiency in the retrieval, implementation, and maintenance of task sets, indicating less efficient cognitive control functioning.

Humans often face binary cognitive-control dilemmas, with the choice between persistence and flexibility being a crucial one. Tackling these dilemmas requires metacontrol, i.e., the control of the current cognitive-control policy. As predicted from functional, psychometric, neuroscientific, and modeling approaches, interindividual variability in metacontrol biases towards persistence or flexibility could be demonstrated in metacontrol-sensitive tasks. These biases covary systematically with genetic predispositions regarding mesofrontal and nigrostriatal dopaminergic functioning and the individualistic or collectivistic nature of the cultural background. However, there is also evidence for mood- and meditation-induced intraindividual variability (with negative mood and focused-attention meditation being associated with a bias towards persistence, and positive mood and open-monitoring meditation being associated with a bias towards flexibility), suggesting that genetic and cultural factors do not determine metacontrol settings entirely. We suggest a theoretical framework that explains how genetic predisposition and cultural learning can lead to the implementation of metacontrol defaults, which however can be shifted towards persistence or flexibility by situational factors., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

One of the most important functions of cognitive control is action cascading: the ability to cope with multiple response options when confronted with various task goals. A recent study implicates a key role for dopamine (DA) in this process, suggesting higher D1 efficiency shifts the action cascading strategy toward a more serial processing mode, whereas higher D2 efficiency promotes a shift in the opposite direction by inducing a more parallel processing mode (Stock, Arning, Epplen, & Beste, 2014). Given that DA is found in high concentration in the retina and modulation of retinal DA release displays characteristics of D2-receptors (Peters, Schweibold, Przuntek, & Müller, 2000), color vision discrimination might serve as an index of D2 efficiency. We used color discrimination, assessed with the Lanthony Desaturated Panel D-15 test, to predict individual differences (N = 85) in a stop-change paradigm that provides a well-established measure of action cascading. In this task it is possible to calculate an individual slope value for each participant that estimates the degree of overlap in task goal activation. When the stopping process of a previous task goal has not finished at the time the change process toward a new task goal is initiated (parallel processing), the slope value becomes steeper. In case of less overlap (more serial processing), the slope value becomes flatter. As expected, participants showing better color vision were more prone to activate goals in a parallel manner as indicated by a steeper slope. Our findings suggest that color vision might represent a predictor of D2 efficiency and the predisposed processing mode of goal activation during action cascading., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Binaural beats represent the auditory experience of an oscillating sound that occurs when two sounds with neighboring frequencies are presented to one's left and right ear separately. Binaural beats have been shown to impact information processing via their putative role in increasing neural synchronization. Recent studies of feature-repetition effects demonstrated interactions between perceptual features and action-related features: repeating only some, but not all features of a perception-action episode hinders performance. These partial-repetition (or binding) costs point to the existence of temporary episodic bindings (event files) that are automatically retrieved by repeating at least one of their features. Given that neural synchronization in the gamma band has been associated with visual feature bindings, we investigated whether the impact of binaural beats extends to the top-down control of feature bindings. Healthy adults listened to gamma-frequency (40 Hz) binaural beats or to a constant tone of 340 Hz (control condition) for ten minutes before and during a feature-repetition task. While the size of visuomotor binding costs (indicating the binding of visual and action features) was unaffected by the binaural beats, the size of visual feature binding costs (which refer to the binding between the two visual features) was considerably smaller during gamma-frequency binaural beats exposure than during the control condition. Our results suggest that binaural beats enhance selectivity in updating episodic memory traces and further strengthen the hypothesis that neural activity in the gamma band is critically associated with the control of feature binding.

Charles Darwin proposed that via the vagus nerve, the tenth cranial nerve, emotional facial expressions are evolved, adaptive and serve a crucial communicative function. In line with this idea, the later-developed polyvagal theory assumes that the vagus nerve is the key phylogenetic substrate that regulates emotional and social behavior. The polyvagal theory assumes that optimal social interaction, which includes the recognition of emotion in faces, is modulated by the vagus nerve. So far, in humans, it has not yet been demonstrated that the vagus plays a causal role in emotion recognition. To investigate this we employed transcutaneous vagus nerve stimulation (tVNS), a novel non-invasive brain stimulation technique that modulates brain activity via bottom-up mechanisms. A sham/placebo-controlled, randomized cross-over within-subjects design was used to infer a causal relation between the stimulated vagus nerve and the related ability to recognize emotions as indexed by the Reading the Mind in the Eyes Test in 38 healthy young volunteers. Active tVNS, compared to sham stimulation, enhanced emotion recognition for easy items, suggesting that it promoted the ability to decode salient social cues. Our results confirm that the vagus nerve is causally involved in emotion recognition, supporting Darwin's argumentation., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Precursors of neurotransmitters are increasingly often investigated as potential, easily-accessible methods of neuromodulation. However, the amino-acid glutamine, precursor to the brain's main excitatory and inhibitory neurotransmitters glutamate and GABA, remains notably little investigated. The current double-blind, randomized, placebo-controlled study provides first evidence 2.0 g glutamine administration in healthy adults affects response selection but not motor sequence learning in a serial reaction time task. Specifically, glutamine increased response selection errors when the current target response required a different hand than the directly preceding target response, which might indicate enhanced cortical excitability via a presumed increase in glutamate levels. These results suggest glutamine can alter cortical excitability but, despite the critical roles of glutamate and GABA in motor learning, at its current dose glutamine does not affect sequence learning.

The prevalence of weight problems is increasing worldwide. There is growing evidence that high body mass index (BMI) is associated with frontal lobe dysfunction and cognitive deficits concerning mental flexibility and inhibitory control efficiency. The present study aims at replicating and extending these observations. We compared cognitive control performance of normal weight (BMI < 25) and overweight (BMI ≥ 25) university students on a task tapping either inhibitory control (Experiment 1) or interference control (Experiment 2). Experiment 1 replicated previous findings that found less efficient inhibitory control in overweight individuals. Experiment 2 complemented these findings by showing that cognitive control impairments associated with high BMI also extend to the ability to resolve stimulus-induced response conflict and to engage in conflict-driven control adaptation. The present results are consistent with and extend previous literature showing that high BMI in young, otherwise healthy individuals is associated with less efficient cognitive control functioning., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Transcranial direct current stimulation (tDCS) is an increasingly popular method of modulating cognitive functions in humans. However, some doubt its efficacy as findings are inconsistent or remain unreplicated. It is speculated dopamine (DA) might play an important role in this inconsistency, by determining the direction and strength of the cognitive-behavioral effects of tDCS. However, so far evidence for this hypothesis has been correlational in nature, precluding definitive conclusions., Objective: The present proof-of-principle study aimed at investigating a potentially causal role for DA in the effect of tDCS on cognition in healthy humans., Methods: In Experiment 1 we aimed to replicate previous findings showing administration of DA's precursor l-Tyrosine (Tyr), presumably by inducing a modest increase in DA level, can enhance working memory (WM) performance as assessed with a verbal N-back task. In Experiment 2 we investigated the effect of Tyr administration on bilateral tDCS over dorsolateral prefrontal cortex (DLPFC) and WM., Results: Experiment 1 showed Tyr administration enhances performance in a verbal N-back task. Experiment 2 showed Tyr modulates the effect of bilateral tDCS over DLPFC on WM. Specifically, tDCS had opposite effects on performance depending on current direction through the brain and Tyr administration., Conclusions: The present study provides two major findings. First, we replicate Tyr's beneficial effect on verbal WM. Second, our results indicate a causal role for DA in the effect of tDCS on cognition. For this reason, we encourage future studies to consider the modulating effect of DA, as a step towards more consistent and replicable results regarding the efficacy of tDCS., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

A recent study showed that binaural beats have an impact on the efficiency of allocating attention over time. We were interested to see whether this impact affects attentional focusing or, even further, the top-down control over irrelevant information. Healthy adults listened to gamma-frequency (40 Hz) binaural beats, which are assumed to increase attentional concentration, or a constant tone of 340 Hz (control condition) for 3 min before and during a global-local task. While the size of the congruency effect (indicating the failure to suppress task-irrelevant information) was unaffected by the binaural beats, the global-precedence effect (reflecting attentional focusing) was considerably smaller after gamma-frequency binaural beats than after the control condition. Our findings suggest that high-frequency binaural beats bias the individual attentional processing style towards a reduced spotlight of attention.

In addition to longer-term engagement in meditation, the past years have seen an increasing interest in the impact of single bouts of meditation on cognition. In this hypothesis and theory article, we adopt the distinction between focused-attention meditation (FAM) and open-monitoring meditation (OMM) and argue that these different types of meditation have different, to some degree, opposite impact on cognitive processes. We discuss evidence suggesting that single bouts of FAM and OMM are sufficient to bias cognitive control styles towards more versus less top-down control, respectively. We conclude that all meditation techniques are not equal and that successful meditation-based intervention requires the theoretically guided selection of the best-suited technique., (© The Author(s) 2017.)

An extensive body of research suggests the spontaneous eye blink rate (EBR) is a non-invasive indirect marker of central dopamine (DA) function, with higher EBR predicting higher DA function. In the present review we provide a comprehensive overview of this literature. We broadly divide the available research in studies that aim to disentangle the dopaminergic underpinnings of EBR, investigate its utility in diagnosis of DA-related disorders and responsivity to drug treatment, and, lastly, investigate EBR as predictor of individual differences in DA-related cognitive performance. We conclude (i) EBR can reflect both DA receptor subtype D1 and D2 activity, although baseline EBR might be most strongly related to the latter, (ii) EBR can predict hypo- and hyperdopaminergic activity as well as normalization of this activity following treatment, and (iii) EBR can reliably predict individual differences in performance on many cognitive tasks, in particular those related to reward-driven behavior and cognitive flexibility. In sum, this review establishes EBR as a useful predictor of DA in a wide variety of contexts., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Memory retrieval requires an effective recruitment of inhibitory control to successfully reject unnecessary memories. The use of cocaine is associated with poor cognitive control processes, but little is known about the impact of chronic and recreational use of cocaine on inhibitory control during intentional forgetting. We studied whether chronic and recreational users of cocaine show impairments on the mechanism responsible for intentional forgetting of memories. Two experiments were carried out on chronic cocaine users in rehabilitation (Experiment 1) and recreational cocaine polydrug users (Experiment 2) performing a directed forgetting (DF) task, an index of memory suppression. Participants were matched for sex, age, and intelligence (Raven's standard progressive matrices) with cocaine-free controls and compared on their performance on a DF procedure. Chronic cocaine users in rehabilitation and recreational cocaine polydrug users, as compared with controls, were not able to intentionally suppress the required information and they did not show a reliable DF effect. The consumption of cocaine appears to alter the control processes implicated in intentional suppression of nonrelevant memories in episodic memory. The use of cocaine, even for recreational purposes, seems to be associated with poor performance in effectively triggering this control mechanism. The inability to suppress interference in declarative memory may have repercussion for daily activities. (PsycINFO Database Record, ((c) 2016 APA, all rights reserved).)