@article {4565, title = {The effect of transcutaneous auricular vagus nerve stimulation on cardiovascular function in subarachnoid hemorrhage patients: A randomized trial.}, journal = {Elife}, volume = {13}, year = {2025}, month = {2025 Jan 09}, abstract = {

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{\textquoteright}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.

}, keywords = {Adult, Aged, Blood Pressure, Electrocardiography, Female, Heart Rate, Humans, Male, Middle Aged, Subarachnoid Hemorrhage, Transcutaneous Electric Nerve Stimulation, Vagus Nerve Stimulation}, issn = {2050-084X}, doi = {10.7554/eLife.100088}, author = {Tan, Gansheng and Huguenard, Anna L and Donovan, Kara M and Demarest, Phillip and Liu, Xiaoxuan and Li, Ziwei and Adamek, Markus and Lavine, Kory and Vellimana, Ananthv K and Kummer, Terrance T and Osbun, Joshua W and Zipfel, Gregory J and Brunner, Peter and Leuthardt, Eric C} } @article {4558, title = {Does vibrotactile stimulation of the auricular vagus nerve enhance working memory? A behavioral and physiological investigation}, journal = {Brain Stimulation}, volume = {17}, year = {2024}, pages = {460{\textendash}468}, author = {Tan, Gansheng and Adams, Josh and Donovan, Kara and Demarest, Phillip and Willie, Jon T and Brunner, Peter and Gorlewicz, Jenna L and Leuthardt, Eric C} } @article {4577, title = {Does vibrotactile stimulation of the auricular vagus nerve enhance working memory? A behavioral and physiological investigation.}, journal = {Brain Stimul}, volume = {17}, year = {2024}, month = {2024 Mar-Apr}, pages = {460-468}, abstract = {

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.

}, keywords = {Adult, Female, Galvanic Skin Response, Humans, Male, Memory, Short-Term, Pupil, Vagus Nerve, Vagus Nerve Stimulation, Vibration, Young Adult}, issn = {1876-4754}, doi = {10.1016/j.brs.2024.04.002}, author = {Tan, Gansheng and Adams, Josh and Donovan, Kara and Demarest, Phillip and Willie, Jon T and Brunner, Peter and Gorlewicz, Jenna L and Leuthardt, Eric C} } @article {4578, title = {Does Vibrotactile Stimulation of the Auricular Vagus Nerve Enhance Working Memory? A Behavioral and Physiological Investigation.}, journal = {bioRxiv}, year = {2024}, month = {2024 Mar 27}, abstract = {

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 {\textquoteright} compared to the baseline but not to the sham. Moreover, we found that the reduction rate of {\textquoteright} 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.

}, issn = {2692-8205}, doi = {10.1101/2024.03.24.586365}, author = {Tan, Gansheng and Adams, Josh and Donovan, Kara and Demarest, Phillip and Willie, Jon T and Brunner, Peter and Gorlewicz, Jenna L and Leuthardt, Eric C} } @article {4575, title = {The effect of transcutaneous auricular vagus nerve stimulation on cardiovascular function in subarachnoid hemorrhage patients: a safety study.}, journal = {medRxiv}, year = {2024}, month = {2024 Sep 08}, abstract = {

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{\textquoteright}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.

}, doi = {10.1101/2024.04.03.24304759}, author = {Tan, Gansheng and Huguenard, Anna L and Donovan, Kara M and Demarest, Phillip and Liu, Xiaoxuan and Li, Ziwei and Adamek, Markus and Lavine, Kory and Vellimana, Ananth K and Kummer, Terrance T and Osbun, Joshua W and Zipfel, Gregory J and Brunner, Peter and Leuthardt, Eric C} } @article {4583, title = {A novel theta-controlled vibrotactile brain-computer interface to treat chronic pain: a pilot study.}, journal = {Sci Rep}, volume = {14}, year = {2024}, month = {2024 Feb 10}, pages = {3433}, abstract = {

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{\textquoteright}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 {\textpm} 0.25 MAD, p = 0.03, q = 0.05) and pain interference (1.79 {\textpm} 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.

}, keywords = {brain-computer interfaces, Chronic Pain, Electroencephalography, Humans, Longitudinal Studies, Neurofeedback, Non-Randomized Controlled Trials as Topic, Pilot Projects}, issn = {2045-2322}, doi = {10.1038/s41598-024-53261-3}, author = {Demarest, Phillip and Rustamov, Nabi and Swift, James and Xie, Tao and Adamek, Markus and Cho, Hohyun and Wilson, Elizabeth and Han, Zhuangyu and Belsten, Alexander and Luczak, Nicholas and Brunner, Peter and Haroutounian, Simon and Leuthardt, Eric C} } @article {4557, title = {A novel theta-controlled vibrotactile brain{\textendash}computer interface to treat chronic pain: a pilot study}, journal = {Scientific reports}, volume = {14}, year = {2024}, pages = {3433}, author = {Demarest, Phillip and Rustamov, Nabi and Swift, James and Xie, Tao and Adamek, Markus and Cho, Hohyun and Wilson, Elizabeth and Han, Zhuangyu and Belsten, Alexander and Luczak, Nicholas and others} }