Penumbral Rescue by normobaric O = O administration in patients with ischemic stroke and target mismatch proFile (PROOF): Study protocol of a phase IIb trial.

RATIONALE: Oxygen is essential for cellular energy metabolism. Neurons are particularly vulnerable to hypoxia. Increasing oxygen supply shortly after stroke onset could preserve the ischemic penumbra until revascularization occurs. AIMS: PROOF investigates the use of normobaric oxygen (NBO) therapy within 6 h of symptom onset/notice for brain-protective bridging until endovascular revascularization of acute intracranial anterior-circulation occlusion. METHODS AND DESIGN: Randomized (1:1), standard treatment-controlled, open-label, blinded endpoint, multicenter adaptive phase IIb trial. STUDY OUTCOMES: Primary outcome is ischemic core growth (mL) from baseline to 24 h (intention-to-treat analysis). Secondary efficacy outcomes include change in NIHSS from baseline to 24 h, mRS at 90 days, cognitive and emotional function, and quality of life. Safety outcomes include mortality, intracranial hemorrhage, and respiratory failure. Exploratory analyses of imaging and blood biomarkers will be conducted. SAMPLE SIZE: Using an adaptive design with interim analysis at 80 patients per arm, up to 456 participants (228 per arm) would be needed for 80% power (one-sided alpha 0.05) to detect a mean reduction of ischemic core growth by 6.68 mL, assuming 21.4 mL standard deviation. DISCUSSION: By enrolling endovascular thrombectomy candidates in an early time window, the trial replicates insights from preclinical studies in which NBO showed beneficial effects, namely early initiation of near 100% inspired oxygen during short temporary ischemia. Primary outcome assessment at 24 h on follow-up imaging reduces variability due to withdrawal of care and early clinical confounders such as delayed extubation and aspiration pneumonia. TRIAL REGISTRATIONS: ClinicalTrials.gov: NCT03500939; EudraCT: 2017-001355-31.

Pets and their owners during the first COVID-19 lockdown period: Perceived changes in routines and emotions - An exploratory study.

An international online questionnaire Pets in Lockdown was conducted during the first COVID-19 lockdown during the months of April and May 2020 to assess how pet owners perceived some aspects of their relationship with their pets, including time spent together and how much they enjoyed it, difficulties taking care of their pets, the amount of comfort they obtained from interacting with their pets, and whether they had observed any changes in their pets' resting time and behavior. Most pet owners did not describe any changes in the relationship with their pets or in their pets' behaviour. Horse owners expressed more difficulties taking care of their animals than owners of other species. Approximately 20% of the animals had less time available to rest undisturbed. Of the animals that displayed behavioral changes, remaining closer to the owner was the most frequently described change followed by descriptions of higher arousal and increased negative affective states.

Pet ownership, feelings of loneliness, and mood in people affected by the first COVID-19 lockdown.

The outbreak of the COVID-19 pandemic has caused dramatic changes to our lifestyle, particularly affecting our ability to interact "in person" with our social network. These changes have had a detrimental effect on the mental welfare of the global population. The international questionnaire "Pets in Lockdown" was designed to investigate whether feelings of loneliness were affecting the mood of people during the COVID-19 lockdown and whether pet ownership may have had a positive influence on both loneliness and general mood. As expected, higher loneliness scores were associated with higher negative and lower positive affective states. In addition, lower loneliness scores were associated with pet ownership and living with other people, but not with more frequent interactions with people from outside the household, suggesting that physical and close contact has an important role in decreasing feelings of loneliness. Besides the effects on the loneliness score, pet ownership was not associated with positive or negative affective states. The strength of the attachment to animals, measured as the amount of comfort that people obtain from their pets, was stronger in people with potentially limited access to affiliative physical human contact and was associated with both higher positive and negative affective states. Additionally, people obtained significantly more comfort from dogs and horses compared with other pet species. The results suggest that during the confinement period, pets may have benefited people with smaller social networks by alleviating loneliness and offering comfort and embodied close contact.

Laryngeal Muscle-Evoked Potential Recording as an Indicator of Vagal Nerve Fiber Activation.

BACKGROUND: Vagus nerve stimulation (VNS) is an adjunctive therapy for drug-resistant epilepsy. Noninvasive evoked potential recordings in laryngeal muscles (LMEPs) innervated by vagal branches may provide a marker to assess effective vagal nerve fiber activation. We investigated VNS-induced LMEPs in patients with epilepsy in acute and chronic settings. MATERIALS AND METHODS: A total of 17 of 25 patients underwent LMEP recordings at initiation of therapy (acute group); 15 of 25 patients after one year of VNS (chronic group); and 7 of 25 patients were tested at both time points (acute + chronic group). VNS-induced LMEPs were recorded following different pulse widths and output currents using six surface laryngeal EMG electrodes to calculate input/output curves and estimate LMEP latency, threshold current for minimal (Ithreshold), half-maximal (I50), and 95% of maximal (I95) response induction and amplitude of maximal response (Vmax). These were compared with the acute + chronic group and between responders and nonresponders in the acute and chronic group. RESULTS: VNS-induced LMEPs were present in all patients. Ithreshold and I95 values ranged from 0.25 to 1.00 mA and from 0.42 to 1.77 mA, respectively. Estimated mean LMEP latencies were 10 ± 0.1 milliseconds. No significant differences between responders and nonresponders were observed. In the acute + chronic group, Ithreshold values remained stable over time. However, at the individual level in this group, Vmax was lower in all patients after one year compared with baseline. CONCLUSIONS: Noninvasive VNS-induced LMEP recording is feasible both at initiation of VNS therapy and after one year. Low output currents (0.25-1.00 mA) may be sufficient to activate vagal Aα-motor fibers. Maximal LMEP amplitudes seemed to decrease after chronic VNS therapy in patients.

The potential of invasive and non-invasive vagus nerve stimulation to improve verbal memory performance in epilepsy patients.

It has been demonstrated that acute vagus nerve stimulation (VNS) improves word recognition memory in epilepsy patients. Transcutaneous auricular vagus nerve stimulation (taVNS) has gained interest as a non-invasive alternative to improve cognition. In this prospective randomized cross-over study, we investigated the effect of both invasive VNS and taVNS on verbal memory performance in 15 patients with drug-resistant epilepsy. All patients conducted a word recognition memory paradigm in 3 conditions: VNS ON, VNS OFF and taVNS (3-period 3-treatment cross-over study design). For each condition, patients memorized 21 highlighted words from text paragraphs. Afterwards, the intervention was delivered for 30 s. Immediate recall and delayed recognition scores were obtained for each condition. This memory paradigm was repeated after 6 weeks of VNS therapy in 2 conditions: VNS ON and VNS OFF (2-period 2-treatment cross-over study design). Acute VNS and taVNS did not improve verbal memory performance. Immediate recall and delayed recognition scores were significantly improved after 6 weeks of VNS treatment irrespective of the acute intervention. We can conclude that the previously described positive effects of invasive VNS on verbal memory performance could not be replicated with invasive VNS and taVNS. An improved verbal memory performance was seen after 6 weeks of VNS treatment, suggesting that longer and more repetitive stimulation of the vagal pathway is required to modulate verbal memory performance.Clinical trial registration number: NCT05031208.

Voxel-Based Analysis of [18F]-FDG Brain PET in Rats Using Data-Driven Normalization.

Introduction: [18F]-FDG PET is a widely used imaging modality that visualizes cellular glucose uptake and provides functional information on the metabolic state of different tissues in vivo. Various quantification methods can be used to evaluate glucose metabolism in the brain, including the cerebral metabolic rate of glucose (CMRglc) and standard uptake values (SUVs). Especially in the brain, these (semi-)quantitative measures can be affected by several physiological factors, such as blood glucose level, age, gender, and stress. Next to this inter- and intra-subject variability, the use of different PET acquisition protocols across studies has created a need for the standardization and harmonization of brain PET evaluation. In this study we present a framework for statistical voxel-based analysis of glucose uptake in the rat brain using histogram-based intensity normalization. Methods: [18F]-FDG PET images of 28 normal rat brains were coregistered and voxel-wisely averaged. Ratio images were generated by voxel-wisely dividing each of these images with the group average. The most prevalent value in the ratio image was used as normalization factor. The normalized PET images were voxel-wisely averaged to generate a normal rat brain atlas. The variability of voxel intensities across the normalized PET images was compared to images that were either normalized by whole brain normalization, or not normalized. To illustrate the added value of this normal rat brain atlas, 9 animals with a striatal hemorrhagic lesion and 9 control animals were intravenously injected with [18F]-FDG and the PET images of these animals were voxel-wisely compared to the normal atlas by group- and individual analyses. Results: The average coefficient of variation of the voxel intensities in the brain across normal [18F]-FDG PET images was 6.7% for the histogram-based normalized images, 11.6% for whole brain normalized images, and 31.2% when no normalization was applied. Statistical voxel-based analysis, using the normal template, indicated regions of significantly decreased glucose uptake at the site of the ICH lesion in the ICH animals, but not in control animals. Conclusion: In summary, histogram-based intensity normalization of [18F]-FDG uptake in the brain is a suitable data-driven approach for standardized voxel-based comparison of brain PET images.

Seizures and Interictal Epileptiform Activity in the Rat Collagenase Model for Intracerebral Hemorrhage.

AIMS: Intracerebral hemorrhage (ICH) is a known risk factor for the development of acute symptomatic as well as late unprovoked seizures. The underlying pathophysiology of post-ICH seizures is incompletely understood and there are no reliable predictive biomarkers. An animal model to study post-ICH seizures is currently lacking. The aim of this study was to investigate (1) the occurrence of seizures and interictal epileptiform activity in the ICH rat collagenase model using long-term video-EEG monitoring (VEM) and (2) whether seizure occurrence was associated with interictal epileptiform activity and histological features. METHODS: Male Sprague-Dawley rats were implanted with epidural electrodes. After 1 week of baseline VEM, collagenase was injected in left striatum to induce an ICH. VEM was continued for 180 days to assess the occurrence of post-ICH seizures and interictal epileptiform activity (spikes and epileptiform discharges). At the end of the experiment, animals were euthanized for histological characterization of the hemorrhagic lesion, using cresyl violet, Prussian blue and immunofluorescence staining. RESULTS: Acute symptomatic seizures occurred in 4/12 animals between 46 and 80 h after ICH induction. Late unprovoked seizures were present in 2/12 animals and started at 90 and 103 days post-ICH. Animals with late unprovoked seizures did not have acute symptomatic seizures. All electrographic seizures were accompanied by clear behavioral changes. Interictal spikes and epileptiform discharges were observed in all animals but occurred more frequently in rats with late seizures (p = 0.019 and p < 0.001, respectively). Animals with acute symptomatic seizures had more extended hemorrhagic lesions and hemosiderin deposits in the piriform cortex. CONCLUSION: Both acute symptomatic and late unprovoked seizures were observed in the rat collagenase model. Interictal epileptiform activity was more frequently seen in animals with late seizures. Rats with acute symptomatic seizures showed more extensive lesions and hemosiderin deposits in the piriform cortex. This model could be used to further explore possible biomarkers for epileptogenesis.

Dysarthria following acute ischemic stroke: Prospective evaluation of characteristics, type and severity.

BACKGROUND: Dysarthria is a common symptom following stroke and represents an important cause of functional impairment in stroke patients. A better characterization of dysarthria could facilitate differential diagnosis and optimize healthcare service distribution. AIM: To determine the speech characteristics, dysarthria type and severity in the acute phase following ischemic stroke in a comprehensive stroke centre. METHODS & PROCEDURES: First-ever ischemic stroke patients consecutively admitted to the Stroke Unit of Ghent University Hospital were included in this prospective clinical study between March 2018 and October 2019. All participants admitted to the Stroke Unit were screened for dysarthria by a speech-language pathologist within 72 h after admission. When dysarthria was identified, speech characteristics were evaluated via auditory-perceptual assessment and objective measurement of acoustic parameters. Dysarthria type was determined based on the Mayo Classification System. Severity of impairment was scored at function and activity level using the Radboud Dysarthria Assessment and the evaluation of speech intelligibility at sentence level using the Dutch Speech Intelligibility Assessment. In addition, dysarthria recovery was separately evaluated in all participants using the National Institutes of Health Stroke Scale (NIHSS) at hospital admission, day 3 ± 2 and day 7. OUTCOMES & RESULTS: A total of 67 out of 151 participants (44%; mean age = 69 years; SD = 13; 28 females) were diagnosed with dysarthria in the acute phase following stroke. Standardized assessments were possible in 72% (48/67) of participants. Imprecise articulation of consonants, harsh voice quality and audible inspiration were the most frequent observed speech characteristics. The acoustic parameters maximum phonation time and maximum loudness deviated most from normative values. Unilateral upper motor neuron (UUMN) was the main dysarthria type present in 52% (25/48) of participants. A total of 58% (28/48) and 71% (34/48) of participants had no/minimal/mild difficulties at the functional and activity levels, respectively. Speech intelligibility was mildly impaired (median = 91%; IQR = 73-97). According to the NIHSS, sub-item speech score at hospital admission, 46% (70/151) of participants had dysarthria, of which half recovered completely from their dysarthria within 1 week after stroke symptom onset. CONCLUSIONS & IMPLICATIONS: UUMN was the dominant dysarthria type, and the majority of participants had a mild dysarthria. Half the participants showed complete recovery within 1 week following symptom onset. The observed speech characteristics mainly reflect impairments in the subsystem's articulation, phonation and respiration. Objective measurements of acoustic parameters corroborate these findings. Future research should focus on longitudinal assessment to investigate recovery of symptoms and the long-term impact of dysarthria on social participation. What this paper adds What is already known on the subject There are few data concerning the presentation of dysarthria following acute ischemic stroke. Moreover, previous research did not include objective measurements of speech characteristics and dysarthria severity. There was a need to determine prospectively speech characteristics, dysarthria type and severity in a stroke population using standardized assessments. What this paper adds to existing knowledge The findings of this study show a high prevalence of dysarthria following acute ischemic stroke. This study confirms previous findings that the speech of dysarthric patients following acute ischemic stroke was mostly characterized by imprecise articulation of consonants, a harsh voice quality and audible inspiration. The results of the objective measures confirm these findings. We added evidence that UUMN is the most prevalent dysarthria type in a stroke population, and that the majority of participants had mild dysarthria. A high rate of dysarthria recovery was seen in the first week following symptom onset. What are the potential or actual clinical implications of this work? The findings of this study contribute to the limited research performed regarding post-stroke dysarthria. The results can help optimize the distribution of healthcare resources. The majority of participants have a mild dysarthria, making the identification of the specific needs of this group an important area of concern. The evaluation of impaired speech subsystems and characteristics, especially supplemented with objective measures of acoustic parameters, and the classification of the type and severity of dysarthria can be helpful to monitor early progress in the acute phase post-stroke.

The feasibility, usability and acceptability of a tablet-based aphasia therapy in the acute phase following stroke.

QUESTION: Independent practice via an application with a language exercise program for aphasia, as an add-on to conventional care can be a good solution to intensify aphasia therapy. The aim of this prospective trial was to investigate the feasibility, usability and acceptability of the newly-developed aphasia exercise program in the 'Speech Therapy App (STAPP)' in the acute phase post-stroke. METHODS: All eligible people with aphasia following stroke (<2 weeks post-stroke) admitted to the Stroke Unit of Ghent University Hospital were recruited in this prospective clinical trial between September 2018 and December 2019. After linguistic assessments and two short training sessions, participants were asked to practice independently with 'STAPP' for at least 30 min/day during hospitalization. Exercises were individually tailored and adjusted if necessary. Outcome was measured by recruitment, adherence and retention rates, usability questionnaires and a visual analogue scale for satisfaction. RESULTS: Twenty-five (mean age 65 years (SD = 17), 14 females) of 31 eligible people with aphasia were enrolled in this trial (recruitment rate = 81 %). All participants but one (23/24) practiced with the language app until the end of hospitalization (retention rate = 96 %). Ten participants practiced at least 30 min/day (adherence rate = 42 %). Participants reported they learned to work quickly with the app (92 %; agreed/totally agreed), the app was easy to use (88 %), they could work independently (79 %), practiced their language (67 %) and wanted to continue working with the app at home (79 %). Acceptability was high (median satisfaction rate 91 %; IQR = 75-100). CONCLUSION: The aphasia exercise program in 'STAPP' is feasible to use as an additional rehabilitation tool along with standard of care in the acute phase post-stroke. Further research is needed to assess the efficacy. CLINICAL TRIAL REGISTRATION-URL: https://clinicaltrials.gov/ct2/show/NCT03679637.

Acute symptomatic seizures following intracerebral hemorrhage in the rat collagenase model.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is a known risk factor for the development of seizures, but little is known about the pathophysiology of seizures in the acute phase post-ICH and their influence on functional outcome. With the use of an animal model, the underlying pathophysiology could be further unraveled. The aim of our study was to optimize the rat collagenase stroke model for the detection of acute symptomatic seizures using video-EEG monitoring. METHODS: Male Sprague-Dawley rats were implanted with scalp electrodes and a craniotomy was made for later injection of collagenase. After one week of baseline video-EEG recording, rats were injected with 0.6 U collagenase in 0.7 µL saline in left striatum, in close proximity of the piriform cortex, and immediately reconnected to the video-EEG setup for 7 days. Occurrence of clinical and electrographic seizures was assessed and functional deficits were evaluated on several time points using the cylinder test, Neurological Deficit Scale (NDS) and forelimb placing test. At day 7 post-ICH, animals were euthanized. The volume and cortical involvement of the hemorrhage were assessed by histological examination of the brain tissue, using Cresyl violet stain. RESULTS: Collagenase injection induced ICH in all animals with a mean volume of 27 mm³ (SEM 7 mm³, range 4-92 mm³). Functional deficits were present in all animals injected with collagenase (pre-ICH vs post-ICH, p < 0.001). Epileptic seizures occurred in 5/11 animals and started between 1 and 61 h after ICH induction. Behavioral changes were observed in 13/15 seizures. CONCLUSIONS: Injecting rats with 0.6 U of collagenase is a useful model to study the occurrence of acute symptomatic seizures post-ICH as it results in ICH in all animals without mortality, 45% incidence of ICH-induced acute symptomatic seizures and measurable functional deficits.

The Protective Influence of Bilingualism on the Recovery of Phonological Input Processing in Aphasia After Stroke.

Language-related potentials are increasingly used to objectify (mal)adaptive neuroplasticity in stroke-related aphasia recovery. Using preattentive [mismatch negativity (MMN)] and attentive (P300) phonologically related paradigms, neuroplasticity in sensory memory and cognitive functioning underlying phonological processing can be investigated. In aphasic patients, MMN amplitudes are generally reduced for speech sounds with a topographic source distribution in the right hemisphere. For P300 amplitudes and latencies, both normal and abnormal results have been reported. The current study investigates the preattentive and attentive phonological discrimination ability in 17 aphasic patients (6 monolinguals and 11 bilinguals, aged 41-71 years) at two timepoints during aphasia recovery. Between the two timepoints, a significant improvement of behavioral language performance in both languages is observed in all patients with the MMN latency at timepoint 1 as a predictive factor for aphasia recovery. In contrast to monolinguals, bilingual aphasic patients have a higher probability to improve their processing speed during rehabilitation, resulting in a shortening of the MMN latency over time, which sometimes progresses toward the normative values.

Evolution of surgical treatment of carotid artery stenosis: a single center observational study.

Background: In 2009 and 2011 respectively ESVS and AHA/ASA guidelines recommended to operate patients with a symptomatic carotid artery stenosis within 14 days. This study aimed primarily to determine if an academic hospital has implemented these international guidelines about indication and timing of surgical treatment of carotid stenosis. Second, the influence of referral from another hospital on time from symptoms to surgery and the influence of time between neurological event and surgery on 30-day complication rate was studied. Third, the number of asymptomatic carotid artery lesions treated surgically was also evaluated in both periods.Methods: Retrospective study to compare patients with significant atherosclerotic carotid stenosis who underwent carotid endarterectomy (CEA) or carotid artery stenting (CAS) in 2005-2006 versus patients treated in 2014-2016. Demographic data, treatment characteristics, interval between symptom and surgery and 30-day outcomes were collected.Results: In 2005-2006 38.1% (59/155) of the patients were treated for symptomatic carotid artery stenosis, in 2014-2016 this increased to 66.5% (121/182) (p < .001, 95% CI: 0.179-0.383). Median time from neurological symptom to surgery in symptomatic patients decreased from 30 to 13 d (p <.001, 95% CI: 1.476-2.763). Early surgery did not increase the 30-day postoperative complications (p = .19, 95% CI: 0.987-1.003). Referral from another hospital almost doubled the time interval between symptoms and surgery in 2014-2016 (p <.001, 95% CI: 1.386-2.827).Conclusions: Since the publication of the international guidelines, patients with symptomatic carotid artery stenosis were preferably surgically treated within 2 weeks at an academic institution. The number of treated asymptomatic carotid stenoses was drastically reduced.

Impact of a code stroke protocol on the door-to-needle time for IV thrombolysis: a feasibility study.

INTRODUCTION: Stroke is a development of an acute focal neurological deficit with an ischemic or hemorrhagic origin. Thrombolysis within 4.5 h of ischemic stroke onset improves outcome. Guidelines recommend administration of intravenous recombinant tissue plasminogen activator within 60 min upon arrival at the hospital, meaning the door-to-needle time (DNT) should be less than 60 min. In this study, a stroke protocol was introduced at the emergency department of the Ghent University Hospital with a primary goal to shorten the DNT. METHODOLOGY: This study was an uncontrolled before-after cohort study. A 'Code Stroke' protocol (CSP) was implemented and the results from the pre-code stroke protocol period (Pre-CSP period, from 15 August 2016 until 5 March 2017) were compared with the results from the post-code stroke protocol period (Post-CSP period, from 6 March 2017 until 16 July 2017). RESULTS: The median DNT decreased significantly from 57 min in the Pre-CSP period to 33 min in the Post-CSP period (p < 0.001). The door-to-triage time (DTT), triage-to-emergency physician time (TET), emergency physician-to-CT time (ECT) and CT-to needle time (CNT) decreased significantly Post-CSP compared to Pre-CSP. When adjusting the results for other variables that might have an influence on these time intervals, the TET, ECT and CNT also decreased significantly. There was a statistically significant effect of the implementation of the CSP on the number of patients treated with a DNT within 20, 30, 45 and 60 min (p = 0.008). CONCLUSION: A significant decrease in DNT can be achieved with the implementation of this stroke protocol.

Seizure-alerting behavior in dogs owned by people experiencing seizures.

INTRODUCTION: The unpredictability of epileptic seizures is considered an important threat to the quality of life of a person with epilepsy. Currently, however, there are no tools for seizure prediction that can be applied to the domestic setting. Although the information about seizure-alert dogs - dogs that display changes in behavior before a seizure that are interpreted by the owner as an alert - is mostly anecdotal; living with an alerting dog (AD) has been reported to improve quality of life of the owner by reducing the stress originating from the unpredictability of epileptic seizures and, sometimes, diminishing the seizure frequency. AIM OF THE STUDY: The aim of the study was to investigate, at an international level, the behaviors displayed by trained and untrained dogs that are able to anticipate seizures and to identify patient- and dog-related factors associated with the presence or absence of alerting behavior. METHODOLOGY: An online questionnaire for dog owners with seizures was designed. Information about the participants (demographics, seizure type, presence of preictal symptoms) and their dogs (demographics, behavior around the time of seizures) was collected. In addition, two validated scales were included to measure the human-dog relationship (Monash Dog-Owner Relationship scale (MDORS)) and five different traits of the dogs' personality (Monash Canine Personality Questionnaire refined (MCPQ-R)). RESULTS: Two hundred and twenty-seven responses of people experiencing seizures were received from six participant countries: 132 from people with dogs that had started alerting spontaneously, 10 from owners of trained AD, and the rest from owners of dogs that did not display any alerting behavior (nonalerting dog (NAD)). Individuals' gender, age, or seizure type did not predict the presence of alerting behavior in their dogs. People who indicated that they experience preictal symptoms were more likely to have a spontaneously AD. The owner-dog bond was significantly higher with ADs compared with NADs, and ADs scored significantly higher than NADs in the personality traits "Amicability", "Motivation", and "Training focus". CONCLUSION: This study collected a large group of dog owners with seizures reporting behavioral changes in their dogs before their seizures occurred. This was associated with the presence of preictal symptoms. The seizure-alerting behavior of the dog may have a positive influence on the bond between the owner and the dog.

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.