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.

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.

Optical coherence tomography as a potential surrogate marker of dopaminergic modulation across the life span.

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.

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.

Neurofilaments - Small proteins of physiological significance and predictive power for future neurodegeneration and cognitive decline across the life span.

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.

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.

A Prospect to Ameliorate Affective Symptoms and to Enhance Cognition in Long COVID Using Auricular Transcutaneous Vagus Nerve Stimulation.

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.

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.

A Metacontrol Perspective on Neurocognitive Atypicality: From Unipolar to Bipolar Accounts.

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.

The metacontrol hypothesis as diagnostic framework of OCD and ADHD: A dimensional approach based on shared neurobiological vulnerability.

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.

Focusing on cognitive potential as the bright side of mental atypicality.

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.

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.

Distinguishing Multiple Coding Levels in Theta Band Activity During Working Memory Gating Processes.

Cognitive control and working memory (WM) processes are essential for goal-directed behaviour. Cognitive control and WM are probably based on overlapping neurophysiological mechanisms. For example, theta-band activity (TBA) plays an important role in both functions. For cognitive control processes, it is known that different aspects of information about stimulus content, motor processes and stimulus-response relationships are encoded simultaneously in the TBA. All this information is probably processed during WM gating processes and must be controlled during them. However, direct data for this are lacking. This question is investigated in this study by combining methods of EEG temporal signal decomposition, time-frequency decomposition and beamforming. We show that portions of stimulus-related information, motor response-related information and information related to the interaction between the stimulus and motor responses in the TBA are influenced in parallel and to a similar extent by WM gate opening and gate closing processes. Nevertheless, it is stimulus-related information in the theta signal in particular that modulates behavioural performance in WM-gating. The data suggest that the identified processes are implemented in specific neuroanatomical structures. In particular, the medial frontal cortex, temporal cortical regions and insular cortex are involved in these dynamics. The study shows that principles of information coding relevant to cognitive control processes are also crucial for understanding WM gating.