Inhibitory control in WM gate-opening: Insights from alpha desynchronization and norepinephrine activity under atDCS stimulation.

Our everyday activities require the maintenance and continuous updating of information in working memory (WM). To control this dynamic, WM gating mechanisms have been suggested to be in place, but the neurophysiological mechanisms behind these processes are far from being understood. This is especially the case when it comes to the role of oscillatory neural activity. In the current study we combined EEG recordings, and anodal transcranial direct current stimulation (atDCS) and pupil diameter recordings to triangulate neurophysiology, functional neuroanatomy and neurobiology. The results revealed that atDCS, compared to sham stimulation, affected the WM gate opening mechanism, but not the WM gate closing mechanism. The altered behavioral performance was associated with specific changes in alpha band activities (reflected by alpha desynchronization), indicating a role for inhibitory control during WM gate opening. Functionally, the left superior and inferior parietal cortices, were associated with these processes. The findings are the first to show a causal relevance of alpha desynchronization processes in WM gating processes. Notably, pupil diameter recordings as an indirect index of the norepinephrine (NE) system activity revealed that individuals with stronger inhibitory control (as indexed through alpha desynchronization) showed less pupil dilation, suggesting they needed less NE activity to support WM gate opening. However, when atDCS was applied, this connection disappeared. The study suggests a close link between inhibitory controlled WM gating in parietal cortices, alpha band dynamics and the NE system.

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.

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.

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.