Reduced distractor interference during vagus nerve stimulation.

Suppressing irrelevant information in decision making is an essential everyday skill. We studied whether this ability could be improved in epileptic patients during vagus nerve stimulation (VNS). VNS is known to increase norepinephrine (NE) in the brain. NE is thought to improve several aspects of cognitive control, including the suppression of irrelevant information. Nineteen epileptic VNS patients executed the Eriksen flanker task twice, both during on and off stimulation. Distractor interference was indexed by the congruency effect, a standard empirical marker of cognitive control. We found a reduced congruency effect during stimulation, which indicates an improved ability to suppress distractor interference. This effect was only found in patients that are clinically determined VNS-responders (n = 10). As VNS increases NE in VNS-responders, our finding suggests a beneficial role of NE in cognitive control. At the same time, it suggests that VNS does not only reduce seizure frequency in epileptic patients, but also improves cognitive control.

Posterior resting state EEG asymmetries are associated with hedonic valuation of food.

Research on the hedonic value of food has been important in understanding the motivational and emotional correlates of normal and abnormal eating behaviour. The aim of the present study was to explore associations between hemispheric asymmetries recorded during resting state electroencephalogram (EEG) and hedonic valuation of food. Healthy adult volunteers were recruited and four minutes of resting state EEG were recorded from the scalp. Hedonic food valuation and reward sensitivity were assessed with the hedonic attitude to food and behavioural activation scale. Results showed that parieto-occipital resting state EEG asymmetries in the alpha (8-12Hz) and beta (13-30Hz) frequency range correlate with the hedonic valuation of food. Our findings suggest that self-reported sensory-related attitude towards food is associated with interhemispheric asymmetries in resting state oscillatory activity. Our findings contribute to understanding the electrophysiological correlates of hedonic valuation, and may provide an opportunity to modulate the cortical imbalance by using non-invasive brain stimulation methods to change food consumption.

The effect of vagus nerve stimulation on response inhibition.

In the current study, we explored whether vagus nerve stimulation (VNS) in patients with epilepsy, which is believed to increase norepinephrine (NE) levels via activation of the locus coeruleus, would positively affect response inhibition. Moreover, we tried to identify the dynamics of the underlying neural processes by investigating event-related potentials (ERPs) and pupil size. Patients performed a stop-signal task once when stimulation was switched on and once when it was switched off. We found a correlational pattern suggesting that patients who clinically benefit more from VNS treatment also show a larger behavioral advantage, in terms of faster response inhibition, when the vagus nerve is being stimulated. Event-related potential (ERP) results suggested more pronounced reactive inhibition when stimulation was switched on, independent of the individual amount of seizure reduction. Transient go-locked pupil size was increased from go trials to successful stop trials to unsuccessful stop trials but without displaying a clear VNS effect, which however, might relate to limited sensitivity. We conclude that VNS likely has a positive effect on response inhibition, at least in patients with epilepsy that benefit clinically from the treatment, presumably relating to enhancements of response-inhibition mechanisms and, therefore, identify enhanced response inhibition as a possible cognitive benefit of VNS.

Open your eyes for prediction errors.

Previous studies have demonstrated that autonomic arousal is increased following correct task performance on a difficult, relative to an easy, task. Here, we hypothesized that this arousal response reflects the (relative) surprise of correct performance following a difficult versus an easy task. Following this line of reasoning, we would expect to find a reversed pattern following erroneous responses, because errors are less expected during an easy than during a difficult task. To test this, participants performed a flanker task while pupil size was measured online. As predicted, the results demonstrated that pupil size was larger following difficult (incongruent) correct trials than following easy (congruent) correct trials, but smaller following difficult than following easy incorrect trials. Moreover, participants with larger congruency effects, and hence a larger difference in outcome expectancies between the two trial types, showed larger differences in pupil size after both correct and incorrect responses, further corroborating the idea that pupil size increased as a measure of performance prediction errors.

The P3 event-related potential is a biomarker for the efficacy of vagus nerve stimulation in patients with epilepsy.

Currently, the mechanism of action of vagus nerve stimulation (VNS) is not fully understood, and it is unclear which factors determine a patient's response to treatment. Recent preclinical experiments indicate that activation of the locus coeruleus noradrenergic system is critical for the antiepileptic effect of VNS. This study aims to evaluate the effect of VNS on noradrenergic signaling in the human brain through a noninvasive marker of locus coeruleus noradrenergic activity: the P3 component of the event-related potential. We investigated whether VNS differentially modulates the P3 component in VNS responders versus VNS nonresponders. For this purpose, we recruited 20 patients with refractory epilepsy who had been treated with VNS for at least 18 months. Patients were divided into 2 groups with regard to their reduction in mean monthly seizure frequency: 10 responders (>50 %) and 10 nonresponders (≤50 %). Two stimulation conditions were compared: VNS OFF and VNS ON. In each condition, the P3 component was measured during an auditory oddball paradigm. VNS induced a significant increase of the P3 amplitude at the parietal midline electrode, in VNS responders only. In addition, logistic regression analysis showed that the increase of P3 amplitude can be used as a noninvasive indicator for VNS responders. These results support the hypothesis that activation of the locus coeruleus noradrenergic system is associated with the antiepileptic effect of VNS. Modulation of the P3 amplitude should be further investigated as a noninvasive biomarker for the therapeutic efficacy of VNS in patients with refractory epilepsy.

The influence of the noradrenergic system on optimal control of neural plasticity.

Decision making under uncertainty is challenging for any autonomous agent. The challenge increases when the environment's stochastic properties change over time, i.e., when the environment is volatile. In order to efficiently adapt to volatile environments, agents must primarily rely on recent outcomes to quickly change their decision strategies; in other words, they need to increase their knowledge plasticity. On the contrary, in stable environments, knowledge stability must be preferred to preserve useful information against noise. Here we propose that in mammalian brain, the locus coeruleus (LC) is one of the nuclei involved in volatility estimation and in the subsequent control of neural plasticity. During a reinforcement learning task, LC activation, measured by means of pupil diameter, coded both for environmental volatility and learning rate. We hypothesize that LC could be responsible, through norepinephrinic modulation, for adaptations to optimize decision making in volatile environments. We also suggest a computational model on the interaction between the anterior cingulate cortex (ACC) and LC for volatility estimation.

Blinking predicts enhanced cognitive control.

Recent models have suggested an important role for neuromodulation in explaining trial-to-trial adaptations in cognitive control. The adaptation-by-binding model (Verguts & Notebaert, Psychological review, 115(2), 518-525, 2008), for instance, suggests that increased cognitive control in response to conflict (e.g., incongruent flanker stimulus) is the result of stronger binding of stimulus, action, and context representations, mediated by neuromodulators like dopamine (DA) and/or norepinephrine (NE). We presented a flanker task and used the Gratton effect (smaller congruency effect following incongruent trials) as an index of cognitive control. We investigated the Gratton effect in relation to eye blinks (DA related) and pupil dilation (NE related). The results for pupil dilation were not unequivocal, but eye blinks clearly modulated the Gratton effect: The Gratton effect was enhanced after a blink trial, relative to after a no-blink trial, even when controlling for correlated variables. The latter suggests an important role for DA in cognitive control on a trial-to-trial basis.