Vagus nerve stimulation (VNS) is used for treating refractory epilepsy and major depression. While the impact of this treatment on seizures has been established, its impact on human cognition remains equivocal. The goal of this study is to elucidate the immediate effects of vagus nerve stimulation on attention, cognition, and emotional reactivity in patients with epilepsy. Twenty patients (12 male and 8 female; 45 ± 13 years old) treated with VNS due to refractory epilepsy participated in the study. Subjects performed a computer-based test of executive functions embedded with emotional distractors while their brain activity was recorded with electroencephalography. Subjects' cognitive performance, early visual event-related potential N1, and frontal alpha asymmetry were studied when cyclic vagus nerve stimulation was on and when it was off. We found that vagus nerve stimulation improved working memory performance as seen in reduced errors on a subtask that relied on working memory, odds ratio (OR) = 0.63 (95% confidence interval, CI [0.47, 0.85]) and increased N1 amplitude, F(1, 15) = 10.17, p = .006. In addition, vagus nerve stimulation resulted in longer reaction time, F(1, 16) = 8.23, p = .019, and greater frontal alpha asymmetry, F(1, 16) = 11.79, p = .003, in response to threat-related distractors. This is the first study to show immediate improvement in working memory performance in humans with clinically relevant vagus nerve stimulation. Furthermore, vagus nerve stimulation had immediate effects on emotional reactivity evidenced in behavior and brain physiology.

We have previously shown invasive vagus nerve stimulation to improve attention and working memory and alter emotion-attention interaction in patients with refractory epilepsy, suggesting that VNS might be useful in the treatment of cognitive impairment. The current research focuses on whether non-invasive, transcutaneous vagus nerve stimulation (tVNS) has similar effects to VNS. Furthermore, we aimed to assess whether tVNS has an impact on cognitive control in general or on underlying brain physiology in a task that mimics everyday life demands where multiple executive functions are engaged while encountering intervening emotional stimuli. Event-related potentials (ERP) evoked in such a task, specifically centro-parietal P3 and frontal N2 were used as biomarkers for attention allocation and cognitive control required to carry out the task. A single-blinded, sham-controlled, within-subject study on healthy subjects ( n = 25) was conducted using Executive Reaction Time Test (RT-test), a Go/NoGo task engaging multiple executive functions along with intervening threat-related distractors while EEG was recorded. tVNS at the left tragus and sham stimulation at the left ear lobe was alternately delivered throughout the task. To assess the impact of tVNS on neural activity underlying attention and cognitive control, centro-parietal P3 and frontal N2 peak amplitudes were measured in Go and NoGo conditions. Task performance was assessed with RTs and different error types reflecting cognitive control in general and distinct executive functions, such as working memory and response inhibition.No significant effects due to tVNS on performance in the Executive RT-test were observed. For N2 there was a main effect of stimulator status and a significant interaction of trial type (Go, NoGo) and stimulator status. Post hoc analysis revealed that tVNS resulted in a significant reduction of frontal N2 only in the NoGo condition. No significant effects were observed for P3 nor were there any effects of emotion. Diminished NoGo-N2 potential along with unaltered task performance during tVNS suggests fewer cognitive control resources were required to successfully withhold a prepotent response. Though caution is warranted, we suggest that tVNS may lead to more efficient neural processing with fewer resources needed for successful cognitive control, providing promise for its potential use in cognitive enhancement.

Patients treated with deep brain stimulation (DBS) provide an opportunity to study affective processes in humans with "lesion on demand" at key nodes in the limbic circuitries, such as at the anterior thalamic nuclei (ANT). ANT has been suggested to play a role in emotional control with its connection to the orbitofrontal cortex and the anterior cingulate cortex. However, direct evidence for its role in emotional function in human subjects is lacking. Reported side effects of ANT-DBS in the treatment of refractory epilepsy include depression related symptoms. In line with these mood-related clinical side effects, we have previously reported that stimulating the anterior thalamus increased emotional interference in a visual attention task as indicated by prolonged reaction times due to threat-related emotional distractors. We used event-related potentials to investigate potential attentional mechanism behind this behavioural observation. We hypothesized that ANT-DBS leads to greater attention capture by threat-related distractors. We tested this hypothesis using centro-parietal N2-P3 peak-to-peak amplitude as a measure of allocated attentional resources. Six epileptic patients treated with deep brain stimulation at ANT participated in the study. Electroencephalography was recorded while the patients performed a computer based Executive-Reaction Time test with threat-related emotional distractors. During the task, either ANT or a thalamic control location was stimulated, or the stimulation was turned off. Stimulation of ANT was associated with increased centro-parietal N2-P3 amplitude and increased reaction time in the context of threat-related emotional distractors. We conclude that high frequency electric stimulation of ANT leads to greater attentional capture by emotional stimuli. This is the first study to provide direct evidence from human subjects with on-line electric manipulation of ANT for its role in emotion-attention interaction.

Mild traumatic brain injury (mTBI) may be associated with compromised executive functioning and altered emotional reactivity. Despite frequent affective and cognitive symptoms in mTBI, objective evidence for brain dysfunction is often lacking. Previously we have reported compromised performance in symptomatic mTBI patients in an executive reaction time (RT) test, a computer-based RT test engaging several executive functions simultaneously. Here, we investigated the cognitive control processes in mTBI in context of threat-related stimuli. We used behavioral measures and event-related potentials (ERP) to investigate attentional capture by task-relevant and task-irrelevant emotional stimuli during a Go-NoGo task requiring cognitive control. We also assessed subjective cognitive, somatic, and emotional symptoms with questionnaires. Twenty-seven subjects with previous mTBI and 17 controls with previous ankle injury participated in the study over 9 months post-injury. Electroencephalogram (EEG) was recorded while patients performed a modified executive RT-test. N2-P3 ERP component was used as a general measure of allocated attentional and executive processing resources. Although at the time of the testing, the mTBI and the control groups did not differ in symptom endorsement, mTBI patients reported having had more emotional symptoms overall since the injury than controls. The overall RT-test performance levels did not differ between groups. However, when threat-related emotional stimuli were used as Go-signals, the mTBI group was faster than the control group. In comparison to neutral stimuli, threat-related stimuli were associated with increased N2-P3 amplitude in all conditions. This threat-related enhancement of the N2-P3 complex was greater in mTBI patients than in controls in response to Go signals and NoGo signals, independent of relevance. We conclude that mTBI may be associated with enhanced attentional and executive resource allocation to threat-related stimuli. Along with behavioral evidence for enhanced attention allocation to threat stimuli, increased brain responses to threat were observed in mTBI. Enhanced attention capture by threat-related emotional stimuli may reflect inefficient top-down control of bottom-up influences of emotion, and might contribute to affective symptoms in mTBI.