04343nas a2200433 4500008004100000022001400041245015100055210006900206260001600275490000700291520297600298653001003274653000903284653001903293653002403312653001103336653001503347653001103362653000903373653001603382653002803398653004603426653002803472100001803500700002303518700002103541700002203562700001803584700001403602700001903616700001703635700002603652700002403678700002103702700002303723700001903746700002303765856012103788 2025 eng d a2050-084X00aThe effect of transcutaneous auricular vagus nerve stimulation on cardiovascular function in subarachnoid hemorrhage patients: A randomized trial.0 aeffect of transcutaneous auricular vagus nerve stimulation on ca c2025 Jan 090 v133 a

BACKGROUND: Subarachnoid hemorrhage (SAH) is characterized by intense central inflammation, leading to substantial post-hemorrhagic complications such as vasospasm and delayed cerebral ischemia. Given the anti-inflammatory effect of transcutaneous auricular vagus nerve stimulation (taVNS) and its ability to promote brain plasticity, taVNS has emerged as a promising therapeutic option for SAH patients. However, the effects of taVNS on cardiovascular dynamics in critically ill patients, like those with SAH, have not yet been investigated. Given the association between cardiac complications and elevated risk of poor clinical outcomes after SAH, it is essential to characterize the cardiovascular effects of taVNS to ensure this approach is safe in this fragile population. Therefore, this study assessed the impact of both acute and repetitive taVNS on cardiovascular function.

METHODS: In this randomized clinical trial, 24 SAH patients were assigned to either a taVNS treatment or a sham treatment group. During their stay in the intensive care unit, we monitored patient electrocardiogram readings and vital signs. We compared long-term changes in heart rate, heart rate variability (HRV), QT interval, and blood pressure between the two groups. Additionally, we assessed the effects of acute taVNS by comparing cardiovascular metrics before, during, and after the intervention. We also explored acute cardiovascular biomarkers in patients exhibiting clinical improvement.

RESULTS: We found that repetitive taVNS did not significantly alter heart rate, QT interval, blood pressure, or intracranial pressure (ICP). However, repetitive taVNS increased overall HRV and parasympathetic activity compared to the sham treatment. The increase in parasympathetic activity was most pronounced from 2 to 4 days after initial treatment (Cohen's = 0.50). Acutely, taVNS increased heart rate, blood pressure, and peripheral perfusion index without affecting the corrected QT interval, ICP, or HRV. The acute post-treatment elevation in heart rate was more pronounced in patients who experienced a decrease of more than one point in their modified Rankin Score at the time of discharge.

CONCLUSIONS: Our study found that taVNS treatment did not induce adverse cardiovascular effects, such as bradycardia or QT prolongation, supporting its development as a safe immunomodulatory treatment approach for SAH patients. The observed acute increase in heart rate after taVNS treatment may serve as a biomarker for SAH patients who could derive greater benefit from this treatment.

FUNDING: The American Association of Neurological Surgeons (ALH), The Aneurysm and AVM Foundation (ALH), The National Institutes of Health R01-EB026439, P41-EB018783, U24-NS109103, R21-NS128307 (ECL, PB), McDonnell Center for Systems Neuroscience (ECL, PB), and Fondazione Neurone (PB).

CLINICAL TRIAL NUMBER: NCT04557618.

10aAdult10aAged10aBlood Pressure10aElectrocardiography10aFemale10aHeart Rate10aHumans10aMale10aMiddle Aged10aSubarachnoid Hemorrhage10aTranscutaneous Electric Nerve Stimulation10aVagus Nerve Stimulation1 aTan, Gansheng1 aHuguenard, Anna, L1 aDonovan, Kara, M1 aDemarest, Phillip1 aLiu, Xiaoxuan1 aLi, Ziwei1 aAdamek, Markus1 aLavine, Kory1 aVellimana, Ananthv, K1 aKummer, Terrance, T1 aOsbun, Joshua, W1 aZipfel, Gregory, J1 aBrunner, Peter1 aLeuthardt, Eric, C uhttps://neurotechcenter.org/publications/2025/effect-transcutaneous-auricular-vagus-nerve-stimulation-cardiovascular03026nas a2200361 4500008004100000022001400041245013300055210006900188260001700257300001200274490000700286520191700293653001002210653001102220653002702231653001102258653000902269653002302278653001002301653001602311653002802327653001402355653001602369100001802385700001602403700001802419700002202437700001902459700001902478700002402497700002302521856012002544 2024 eng d a1876-475400aDoes vibrotactile stimulation of the auricular vagus nerve enhance working memory? A behavioral and physiological investigation.0 aDoes vibrotactile stimulation of the auricular vagus nerve enhan c2024 Mar-Apr a460-4680 v173 a

BACKGROUND: Working memory is essential to a wide range of cognitive functions and activities. Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising method to improve working memory performance. However, the feasibility and scalability of electrical stimulation are constrained by several limitations, such as auricular discomfort and inconsistent electrical contact.

OBJECTIVE: We aimed to develop a novel and practical method, vibrotactile taVNS, to improve working memory. Further, we investigated its effects on arousal, measured by skin conductance and pupil diameter.

METHOD: This study included 20 healthy participants. Behavioral response, skin conductance, and eye tracking data were concurrently recorded while the participants performed N-back tasks under three conditions: vibrotactile taVNS delivered to the cymba concha, earlobe (sham control), and no stimulation (baseline control).

RESULTS: In 4-back tasks, which demand maximal working memory capacity, active vibrotactile taVNS significantly improved the performance metric d compared to the baseline but not to the sham. Moreover, we found that the reduction rate of d with increasing task difficulty was significantly smaller during vibrotactile taVNS sessions than in both baseline and sham conditions. Arousal, measured as skin conductance and pupil diameter, declined over the course of the tasks. Vibrotactile taVNS rescued this arousal decline, leading to arousal levels corresponding to optimal working memory levels. Moreover, pupil diameter and skin conductance level were higher during high-cognitive-load tasks when vibrotactile taVNS was delivered to the concha compared to baseline and sham.

CONCLUSION: Our findings suggest that vibrotactile taVNS modulates the arousal pathway and could be a potential intervention for enhancing working memory.

10aAdult10aFemale10aGalvanic Skin Response10aHumans10aMale10aMemory, Short-Term10aPupil10aVagus Nerve10aVagus Nerve Stimulation10aVibration10aYoung Adult1 aTan, Gansheng1 aAdams, Josh1 aDonovan, Kara1 aDemarest, Phillip1 aWillie, Jon, T1 aBrunner, Peter1 aGorlewicz, Jenna, L1 aLeuthardt, Eric, C uhttps://neurotechcenter.org/publications/2024/does-vibrotactile-stimulation-auricular-vagus-nerve-enhance-working-003020nas a2200205 4500008004100000022001400041245013300055210006900188260001600257520226200273100001802535700001602553700001802569700002202587700001902609700001902628700002402647700002302671856012002694 2024 eng d a2692-820500aDoes Vibrotactile Stimulation of the Auricular Vagus Nerve Enhance Working Memory? A Behavioral and Physiological Investigation.0 aDoes Vibrotactile Stimulation of the Auricular Vagus Nerve Enhan c2024 Mar 273 a

BACKGROUND: Working memory is essential to a wide range of cognitive functions and activities. Transcutaneous auricular VNS (taVNS) is a promising method to improve working memory performance. However, the feasibility and scalability of electrical stimulation are constrained by several limitations, such as auricular discomfort and inconsistent electrical contact.

OBJECTIVE: We aimed to develop a novel and practical method, vibrotactile taVNS, to improve working memory. Further, we investigated its effects on arousal, measured by skin conductance and pupil diameter.

METHOD: This study included 20 healthy participants. Behavioral response, skin conductance, and eye tracking data were concurrently recorded while the participants performed N-back tasks under three conditions: vibrotactile taVNS delivered to the cymba concha, earlobe (sham control), and no stimulation (baseline control).

RESULTS: In 4-back tasks, which demand maximal working memory capacity, active vibrotactile taVNS significantly improved the performance metric ' compared to the baseline but not to the sham. Moreover, we found that the reduction rate of ' with increasing task difficulty was significantly smaller during vibrotactile taVNS sessions than in both baseline and sham conditions. Arousal, measured as skin conductance and pupil diameter, declined over the course of the tasks. Vibrotactile taVNS rescued this arousal decline, leading to arousal levels corresponding to optimal working memory levels. Moreover, pupil diameter and skin conductance level were higher during high-cognitive-load tasks when vibrotactile taVNS was delivered to the concha compared to baseline and sham.

CONCLUSION: Our findings suggest that vibrotactile taVNS modulates the arousal pathway and could be a potential intervention for enhancing working memory.

HIGHLIGHTS: Vibrotactile stimulation of the auricular vagus nerve increases general arousal.Vibrotactile stimulation of the auricular vagus nerve mitigates arousal decreases as subjects continuously perform working memory tasks.6 Hz Vibrotactile auricular vagus nerve stimulation is a potential intervention for enhancing working memory performance.

1 aTan, Gansheng1 aAdams, Josh1 aDonovan, Kara1 aDemarest, Phillip1 aWillie, Jon, T1 aBrunner, Peter1 aGorlewicz, Jenna, L1 aLeuthardt, Eric, C uhttps://neurotechcenter.org/publications/2024/does-vibrotactile-stimulation-auricular-vagus-nerve-enhance-working-100734nas a2200193 4500008004100000245013200041210006900173300001400242490000700256100001800263700001600281700001800297700002200315700001900337700001900356700002400375700002300399856011800422 2024 eng d00aDoes vibrotactile stimulation of the auricular vagus nerve enhance working memory? A behavioral and physiological investigation0 aDoes vibrotactile stimulation of the auricular vagus nerve enhan a460–4680 v171 aTan, Gansheng1 aAdams, Josh1 aDonovan, Kara1 aDemarest, Phillip1 aWillie, Jon, T1 aBrunner, Peter1 aGorlewicz, Jenna, L1 aLeuthardt, Eric, C uhttps://neurotechcenter.org/publications/2024/does-vibrotactile-stimulation-auricular-vagus-nerve-enhance-working03671nas a2200265 4500008004100000245014700041210006900188260001600257520272400273100001802997700002303015700002103038700002203059700001803081700001403099700001903113700001703132700002503149700002403174700002103198700002303219700001903242700002303261856012103284 2024 eng d00aThe effect of transcutaneous auricular vagus nerve stimulation on cardiovascular function in subarachnoid hemorrhage patients: a safety study.0 aeffect of transcutaneous auricular vagus nerve stimulation on ca c2024 Sep 083 a

INTRODUCTION: Subarachnoid hemorrhage (SAH) is characterized by intense central inflammation, leading to substantial post-hemorrhagic complications such as vasospasm and delayed cerebral ischemia. Given the anti-inflammatory effect of transcutaneous auricular vagus nerve stimulation (taVNS) and its ability to promote brain plasticity, taVNS has emerged as a promising therapeutic option for SAH patients. However, the effects of taVNS on cardiovascular dynamics in critically ill patients, like those with SAH, have not yet been investigated. Given the association between cardiac complications and elevated risk of poor clinical outcomes after SAH, it is essential to characterize the cardiovascular effects of taVNS to ensure this approach is safe in this fragile population. Therefore, we assessed the impact of both acute taVNS and repetitive taVNS on cardiovascular function in this study.

METHODS: In this randomized clinical trial, 24 SAH patients were assigned to either a taVNS treatment or a Sham treatment group. During their stay in the intensive care unit, we monitored patient electrocardiogram (ECG) readings and vital signs. We compared long-term changes in heart rate, heart rate variability, QT interval, and blood pressure between the two groups. Additionally, we assessed the effects of acute taVNS by comparing cardiovascular metrics before, during, and after the intervention. We also explored acute cardiovascular biomarkers in patients exhibiting clinical improvement.

RESULTS: We found that repetitive taVNS did not significantly alter heart rate, QT interval, blood pressure, or intracranial pressure. However, taVNS increased overall heart rate variability and parasympathetic activity compared to the sham treatment. The increase in parasympathetic activity was most pronounced from 2-4 days after initial treatment (Cohen's d = 0.50). Acutely, taVNS increased heart rate, blood pressure, and peripheral perfusion index without affecting the corrected QT interval, intracranial pressure, or heart rate variability. The acute post-treatment elevation in heart rate was more pronounced in patients who experienced a decrease of more than one point in their Modified Rankin Score at the time of discharge.

CONCLUSIONS: Our study found that taVNS treatment did not induce adverse cardiovascular effects, such as bradycardia or QT prolongation, supporting its development as a safe immunomodulatory treatment approach for SAH patients. The observed acute increase in heart rate after taVNS treatment may serve as a biomarker for SAH patients who could derive greater benefit from this treatment.

TRIAL REGISTRATION: NCT04557618.

1 aTan, Gansheng1 aHuguenard, Anna, L1 aDonovan, Kara, M1 aDemarest, Phillip1 aLiu, Xiaoxuan1 aLi, Ziwei1 aAdamek, Markus1 aLavine, Kory1 aVellimana, Ananth, K1 aKummer, Terrance, T1 aOsbun, Joshua, W1 aZipfel, Gregory, J1 aBrunner, Peter1 aLeuthardt, Eric, C uhttps://neurotechcenter.org/publications/2024/effect-transcutaneous-auricular-vagus-nerve-stimulation-cardiovascular02500nas a2200385 4500008004100000022001400041245010500055210006900160260001600229300000900245490000700254520128700261653003001548653001701578653002701595653001101622653002501633653001801658653004601676653001901722100002201741700001901763700001701782700001301799700001901812700001601831700002201847700001801869700002301887700002101910700001901931700002401950700002301974856011701997 2024 eng d a2045-232200aA novel theta-controlled vibrotactile brain-computer interface to treat chronic pain: a pilot study.0 anovel thetacontrolled vibrotactile braincomputer interface to tr c2024 Feb 10 a34330 v143 a

Limitations in chronic pain therapies necessitate novel interventions that are effective, accessible, and safe. Brain-computer interfaces (BCIs) provide a promising modality for targeting neuropathology underlying chronic pain by converting recorded neural activity into perceivable outputs. Recent evidence suggests that increased frontal theta power (4-7 Hz) reflects pain relief from chronic and acute pain. Further studies have suggested that vibrotactile stimulation decreases pain intensity in experimental and clinical models. This longitudinal, non-randomized, open-label pilot study's objective was to reinforce frontal theta activity in six patients with chronic upper extremity pain using a novel vibrotactile neurofeedback BCI system. Patients increased their BCI performance, reflecting thought-driven control of neurofeedback, and showed a significant decrease in pain severity (1.29 ± 0.25 MAD, p = 0.03, q = 0.05) and pain interference (1.79 ± 1.10 MAD p = 0.03, q = 0.05) scores without any adverse events. Pain relief significantly correlated with frontal theta modulation. These findings highlight the potential of BCI-mediated cortico-sensory coupling of frontal theta with vibrotactile stimulation for alleviating chronic pain.

10abrain-computer interfaces10aChronic Pain10aElectroencephalography10aHumans10aLongitudinal Studies10aNeurofeedback10aNon-Randomized Controlled Trials as Topic10aPilot Projects1 aDemarest, Phillip1 aRustamov, Nabi1 aSwift, James1 aXie, Tao1 aAdamek, Markus1 aCho, Hohyun1 aWilson, Elizabeth1 aHan, Zhuangyu1 aBelsten, Alexander1 aLuczak, Nicholas1 aBrunner, Peter1 aHaroutounian, Simon1 aLeuthardt, Eric, C uhttps://neurotechcenter.org/publications/2024/novel-theta-controlled-vibrotactile-brain-computer-interface-treat00790nas a2200229 4500008004100000245010600041210007100147300000900218490000700227100002200234700001900256700001700275700001300292700001900305700001600324700002200340700001800362700002300380700002100403700001100424856012500435 2024 eng d00aA novel theta-controlled vibrotactile brain–computer interface to treat chronic pain: a pilot study0 anovel thetacontrolled vibrotactile brain–computer interface to t a34330 v141 aDemarest, Phillip1 aRustamov, Nabi1 aSwift, James1 aXie, Tao1 aAdamek, Markus1 aCho, Hohyun1 aWilson, Elizabeth1 aHan, Zhuangyu1 aBelsten, Alexander1 aLuczak, Nicholas1 aothers uhttps://neurotechcenter.org/publications/2024/novel-theta-controlled-vibrotactile-brain%E2%80%93computer-interface-treat