Tracing conflict-induced cognitive-control adjustments over time using aperiodic EEG activity.

Cognitive-control theories assume that the experience of response conflict can trigger control adjustments. However, while some approaches focus on adjustments that impact the selection of the present response (in trial N), other approaches focus on adjustments in the next upcoming trial (N + 1). We aimed to trace control adjustments over time by quantifying cortical noise by means of the fitting oscillations and one over f algorithm, a measure of aperiodic activity. As predicted, conflict trials increased the aperiodic exponent in a large sample of 171 healthy adults, thus indicating noise reduction. While this adjustment was visible in trial N already, it did not affect response selection before the next trial. This suggests that control adjustments do not affect ongoing response-selection processes but prepare the system for tighter control in the next trial. We interpret the findings in terms of a conflict-induced switch from metacontrol flexibility to metacontrol persistence, accompanied or even implemented by a reduction of cortical noise.

Auricular Transcutaneous Vagus Nerve Stimulation Specifically Enhances Working Memory Gate Closing Mechanism: A System Neurophysiological Study.

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

Catecholaminergic Modulation of Metacontrol Is Reflected by Changes in Aperiodic EEG Activity.

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

Interindividual aperiodic resting-state EEG activity predicts cognitive-control styles.

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

Regaining control over opioid use? The potential application of auricular transcutaneous vagus nerve stimulation to improve opioid treatment in China.

Opioid use disorder (OUD) is a critical problem in China and is accompanied by depression and deficits in cognitive control. In China, the most successful intervention for OUD is the community drug rehabilitation where methadone maintenance treatment (MMT) plays a key role. Even though methadone for the treatment of OUD can be helpful, it can cause severe somatic side-effects, which limit its effectivity. Even worse, it can have detrimental effects on cognitive control, which is crucial to regain control over drug intake. Here, we consider the potential use of auricular transcutaneous vagus nerve stimulation (atVNS) as an addition to MMT for opioid withdrawal treatment. Compared to other non-invasive brain stimulation methods, atVNS also targets the locus coeruleus (LC) important for noradrenaline (NA) synthesis. NA is an essential neurotransmitter impacted in opioid withdrawal and also critically involved in cognitive control processes. Its ADD-ON to MMT might be a useful mean to improve mood and enhance cognitive control processes impacted in OUD. We discuss the translational advantages of atVNS in China such as the cultural acceptance of the modality of treatment similar to electroacupuncture. Additionally, the wearability of the ear electrode and at-home self-administration without intense medical supervision makes of atVNS a useful tool to enhance clinical and cognitive outcomes especially in everyday life situation. We discuss how atVNS can be integrated in tele-medical health approaches allowing that innovative treatments can widely be disseminated and continued even in situations of restricted medical access.

Auricular Transcutaneous Vagus Nerve Stimulation Diminishes Alpha-Band-Related Inhibitory Gating Processes During Conflict Monitoring in Frontal Cortices.

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

Auricular transcutaneous vagus nerve stimulation for alcohol use disorder: A chance to improve treatment?

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.

Recognizing emotions in bodies: Vagus nerve stimulation enhances recognition of anger while impairing sadness.

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.

An Oppositional Tolerance Account for Potential Cognitive Deficits Caused by the Discontinuation of Antidepressant Drugs.

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.

A literature review on the neurophysiological underpinnings and cognitive effects of transcutaneous vagus nerve stimulation: challenges and future directions.

Brain stimulation approaches are important to gain causal mechanistic insights into the relevance of functional brain regions and/or neurophysiological systems for human cognitive functions. In recent years, transcutaneous vagus nerve stimulation (tVNS) has attracted considerable popularity. It is a noninvasive brain stimulation technique based on the stimulation of the vagus nerve. The stimulation of this nerve activates subcortical nuclei, such as the locus coeruleus and the nucleus of the solitary tract, and from there, the activation propagates to the cortex. Since tVNS is a novel stimulation technique, this literature review outlines a brief historical background of tVNS, before detailing underlying neurophysiological mechanisms of action, stimulation parameters, cognitive effects of tVNS on healthy humans, and, lastly, current challenges and future directions of tVNS research in cognitive functions. Although more research is needed, we conclude that tVNS, by increasing norepineprine (NE) and gamma-aminobutyric acid (GABA) levels, affects NE- and GABA-related cognitive performance. The review provides detailed background information how to use tVNS as a neuromodulatory tool in cognitive neuroscience and outlines important future leads of research on tVNS.

Enhancing spatial reasoning by anodal transcranial direct current stimulation over the right posterior parietal cortex.

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.

Rumination impairs the control of stimulus-induced retrieval of irrelevant information, but not attention, control, or response selection in general.

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.

The COMT Val158 Met polymorphism does not modulate the after-effect of tDCS on working memory.

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 Val158 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 Val158 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.

The Role of DRD1 and DRD2 Receptors for Response Selection Under Varying Complexity Levels: Implications for Metacontrol Processes.

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 Effect of Cerebellar tDCS on Sequential Motor Response Selection.

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.

Increased picture-word interference in chronic and recreational users of cocaine.

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.

Food for thought: association between dietary tyrosine and cognitive performance in younger and older adults.

The fact that tyrosine increases dopamine availability that, in turn, may enhance cognitive performance has led to numerous studies on healthy young participants taking tyrosine as a food supplement. As a result of this dietary intervention, participants show performance increases in working memory and executive functions. However, the potential association between habitual dietary tyrosine intake and cognitive performance has not been investigated to date. The present study aims at clarifying the association of episodic memory (EM), working memory (WM) and fluid intelligence (Gf), and tyrosine intake in younger and older adults. To this end, we acquired habitual tyrosine intake (food frequency questionnaire) from 1724 participants of the Berlin Aging Study II (1383 older adults, 341 younger adults) and modelled its relations to cognitive performance assessed in a broad battery of cognitive tasks using structural equation modeling. We observed a significant association between tyrosine intake and the latent factor capturing WM, Gf, and EM in the younger and the older sample. Due to partial strong factorial invariance between age groups for a confirmatory factor analysis on cognitive performance, we were able to compare the relationship between tyrosine and cognition between age groups and found no difference. Above and beyond previous studies on tyrosine food supplementation the present result extend this to a cross-sectional association between habitual tyrosine intake levels in daily nutrition and cognitive performance (WM, Gf, and EM). This corroborates nutritional recommendations that are thus far derived from single-dose administration studies.

Variable heart rate and a flexible mind: Higher resting-state heart rate variability predicts better task-switching.

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) modulates flow experience.

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.