04347nas a2200433 4500008004100000022001400041245015100055210006900206260001600275490000700291520297600298653001003274653000903284653001903293653002403312653001103336653001503347653001103362653000903373653001603382653002803398653004603426653002803472100001803500700002303518700002103541700002203562700001803584700001403602700001903616700001703635700002603652700002403678700002103702700002303723700001903746700002303765856012503788 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://www.neurotechcenter.org/publications/2025/effect-transcutaneous-auricular-vagus-nerve-stimulation-cardiovascular03376nas a2200409 4500008004100000022001400041245011600055210006900171260001300240300001000253490000700263520216200270653001002432653000902442653003002451653002002481653002702501653001102528653001702539653001102556653000902567653001602576653001902592653001202611653002402623653002502647653001102672653002602683653001702709653002002726100001902746700002002765700002002785700002202805700002302827856011602850 2025 eng d a1552-684400aIpsiHand Brain-Computer Interface Therapy Induces Broad Upper Extremity Motor Rehabilitation in Chronic Stroke.0 aIpsiHand BrainComputer Interface Therapy Induces Broad Upper Ext c2025 Jan a74-860 v393 a

BACKGROUND: Chronic hemiparetic stroke patients have very limited benefits from current therapies. Brain-computer interface (BCI) engaging the unaffected hemisphere has emerged as a promising novel therapeutic approach for chronic stroke rehabilitation.

OBJECTIVES: This study investigated the effectiveness of contralesionally-controlled BCI therapy in chronic stroke patients with impaired upper extremity motor function. We further explored neurophysiological features of motor recovery driven by BCI. We hypothesized that BCI therapy would induce a broad motor recovery in the upper extremity, and there would be corresponding changes in baseline theta and gamma oscillations, which have been shown to be associated with motor recovery.

METHODS: Twenty-six prospectively enrolled chronic hemiparetic stroke patients performed a therapeutic BCI task for 12 weeks. Motor function assessment data and resting state electroencephalogram signals were acquired before initiating BCI therapy and across BCI therapy sessions. The Upper Extremity Fugl-Meyer assessment served as a primary motor outcome assessment tool. Theta-gamma cross-frequency coupling (CFC) was computed and correlated with motor recovery.

RESULTS: Chronic stroke patients achieved significant motor improvement in both proximal and distal upper extremity with BCI therapy. Motor function improvement was independent of Botox application. Theta-gamma CFC enhanced bilaterally over the C3/C4 motor electrodes and positively correlated with motor recovery across BCI therapy sessions.

CONCLUSIONS: BCI therapy resulted in significant motor function improvement across the proximal and distal upper extremities of patients, which significantly correlated with theta-gamma CFC increases in the motor regions. This may represent rhythm-specific cortical oscillatory mechanism for BCI-driven rehabilitation in chronic stroke patients.

TRIAL REGISTRATION: Advarra Study: https://classic.clinicaltrials.gov/ct2/show/NCT04338971 and Washington University Study: https://classic.clinicaltrials.gov/ct2/show/NCT03611855.

10aAdult10aAged10abrain-computer interfaces10aChronic Disease10aElectroencephalography10aFemale10aGamma Rhythm10aHumans10aMale10aMiddle Aged10aMotor Activity10aParesis10aProspective Studies10aRecovery of Function10aStroke10aStroke Rehabilitation10aTheta Rhythm10aUpper Extremity1 aRustamov, Nabi1 aSouders, Lauren1 aSheehan, Lauren1 aCarter, Alexandre1 aLeuthardt, Eric, C uhttps://www.neurotechcenter.org/publications/2025/ipsihand-brain-computer-interface-therapy-induces-broad-upper03070nas a2200301 4500008004100000022001400041245007000055210006700125260001600192300001100208490000700219520218100226653001002407653001002417653001502427653002502442653001202467653001102479653003102490653001402521653000902535100002102544700001702565700002302582700002402605700002302629856011602652 2024 eng d a1097-019300aComplexity organization of resting-state functional-MRI networks.0 aComplexity organization of restingstate functionalMRI networks c2024 Aug 15 ae268090 v453 a

Entropy measures are increasingly being used to analyze the structure of neural activity observed by functional magnetic resonance imaging (fMRI), with resting-state networks (RSNs) being of interest for their reproducible descriptions of the brain's functional architecture. Temporal correlations have shown a dichotomy among these networks: those that engage with the environment, known as extrinsic, which include the visual and sensorimotor networks; and those associated with executive control and self-referencing, known as intrinsic, which include the default mode network and the frontoparietal control network. While these inter-voxel temporal correlations enable the assessment of synchrony among the components of individual networks, entropic measures introduce an intra-voxel assessment that quantifies signal features encoded within each blood oxygen level-dependent (BOLD) time series. As a result, this framework offers insights into comprehending the representation and processing of information within fMRI signals. Multiscale entropy (MSE) has been proposed as a useful measure for characterizing the entropy of neural activity across different temporal scales. This measure of temporal entropy in BOLD data is dependent on the length of the time series; thus, high-quality data with fine-grained temporal resolution and a sufficient number of time frames is needed to improve entropy precision. We apply MSE to the Midnight Scan Club, a highly sampled and well-characterized publicly available dataset, to analyze the entropy distribution of RSNs and evaluate its ability to distinguish between different functional networks. Entropy profiles are compared across temporal scales and RSNs. Our results have shown that the spatial distribution of entropy at infra-slow frequencies (0.005-0.1 Hz) reproduces known parcellations of RSNs. We found a complexity hierarchy between intrinsic and extrinsic RSNs, with intrinsic networks robustly exhibiting higher entropy than extrinsic networks. Finally, we found new evidence that the topography of entropy in the posterior cerebellum exhibits high levels of entropy comparable to that of intrinsic RSNs.

10aAdult10aBrain10aConnectome10aDefault Mode Network10aEntropy10aHumans10aMagnetic Resonance Imaging10aNerve Net10aRest1 aTrevino, Gabriel1 aLee, John, J1 aShimony, Joshua, S1 aLuckett, Patrick, H1 aLeuthardt, Eric, C uhttps://www.neurotechcenter.org/publications/2024/complexity-organization-resting-state-functional-mri-networks03030nas a2200361 4500008004100000022001400041245013300055210006900188260001700257300001200274490000700286520191700293653001002210653001102220653002702231653001102258653000902269653002302278653001002301653001602311653002802327653001402355653001602369100001802385700001602403700001802419700002202437700001902459700001902478700002402497700002302521856012402544 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://www.neurotechcenter.org/publications/2024/does-vibrotactile-stimulation-auricular-vagus-nerve-enhance-working-002504nas a2200385 4500008004100000022001400041245010500055210006900160260001600229300000900245490000700254520128700261653003001548653001701578653002701595653001101622653002501633653001801658653004601676653001901722100002201741700001901763700001701782700001301799700001901812700001601831700002201847700001801869700002301887700002101910700001901931700002401950700002301974856012101997 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://www.neurotechcenter.org/publications/2024/novel-theta-controlled-vibrotactile-brain-computer-interface-treat02755nas a2200337 4500008004100000022001400041245007600055210006900131260001300200300001100213490000800224520171700232653001001949653001501959653001101974653001101985653003101996100001802027700002302045700002602068700002402094700002002118700002102138700002402159700002302183700002402206700002202230700002302252700002302275856011902298 2024 eng d a1872-678X00aOptimal approaches to analyzing functional MRI data in glioma patients.0 aOptimal approaches to analyzing functional MRI data in glioma pa c2024 Feb a1100110 v4023 a

BACKGROUND: Resting-state fMRI is increasingly used to study the effects of gliomas on the functional organization of the brain. A variety of preprocessing techniques and functional connectivity analyses are represented in the literature. However, there so far has been no systematic comparison of how alternative methods impact observed results.

NEW METHOD: We first surveyed current literature and identified alternative analytical approaches commonly used in the field. Following, we systematically compared alternative approaches to atlas registration, parcellation scheme, and choice of graph-theoretical measure as regards differentiating glioma patients (N = 59) from age-matched reference subjects (N = 163).

RESULTS: Our results suggest that non-linear, as opposed to affine registration, improves structural match to an atlas, as well as measures of functional connectivity. Functionally- as opposed to anatomically-derived parcellation schemes maximized the contrast between glioma patients and reference subjects. We also demonstrate that graph-theoretic measures strongly depend on parcellation granularity, parcellation scheme, and graph density.

COMPARISON WITH EXISTING METHODS AND CONCLUSIONS: Our current work primarily focuses on technical optimization of rs-fMRI analysis in glioma patients and, therefore, is fundamentally different from the bulk of papers discussing glioma-induced functional network changes. We report that the evaluation of glioma-induced alterations in the functional connectome strongly depends on analytical approaches including atlas registration, choice of parcellation scheme, and graph-theoretical measures.

10aBrain10aConnectome10aGlioma10aHumans10aMagnetic Resonance Imaging1 aPark, Ki, Yun1 aShimony, Joshua, S1 aChakrabarty, Satrajit1 aTanenbaum, Aaron, B1 aHacker, Carl, D1 aDonovan, Kara, M1 aLuckett, Patrick, H1 aMilchenko, Mikhail1 aSotiras, Aristeidis1 aMarcus, Daniel, S1 aLeuthardt, Eric, C1 aSnyder, Abraham, Z uhttps://www.neurotechcenter.org/publications/2024/optimal-approaches-analyzing-functional-mri-data-glioma-patients03236nas a2200481 4500008004100000022001400041245011400055210006900169260001300238300001200251490000800263520183300271653001002104653000902114653001002123653002002133653001102153653001102164653001102175653002102186653003102207653000902238653001602247653002102263653001402284653000902298653002602307100002402333700002402357700001802381700002302399700001902422700003302441700001702474700001602491700001602507700001802523700002102541700002302562700002302585700002302608856012302631 2024 eng d a1573-737300aPredicting post-surgical functional status in high-grade glioma with resting state fMRI and machine learning.0 aPredicting postsurgical functional status in highgrade glioma wi c2024 Aug a175-1850 v1693 a

PURPOSE: High-grade glioma (HGG) is the most common and deadly malignant glioma of the central nervous system. The current standard of care includes surgical resection of the tumor, which can lead to functional and cognitive deficits. The aim of this study is to develop models capable of predicting functional outcomes in HGG patients before surgery, facilitating improved disease management and informed patient care.

METHODS: Adult HGG patients (N = 102) from the neurosurgery brain tumor service at Washington University Medical Center were retrospectively recruited. All patients completed structural neuroimaging and resting state functional MRI prior to surgery. Demographics, measures of resting state network connectivity (FC), tumor location, and tumor volume were used to train a random forest classifier to predict functional outcomes based on Karnofsky Performance Status (KPS < 70, KPS ≥ 70).

RESULTS: The models achieved a nested cross-validation accuracy of 94.1% and an AUC of 0.97 in classifying KPS. The strongest predictors identified by the model included FC between somatomotor, visual, auditory, and reward networks. Based on location, the relation of the tumor to dorsal attention, cingulo-opercular, and basal ganglia networks were strong predictors of KPS. Age was also a strong predictor. However, tumor volume was only a moderate predictor.

CONCLUSION: The current work demonstrates the ability of machine learning to classify postoperative functional outcomes in HGG patients prior to surgery accurately. Our results suggest that both FC and the tumor's location in relation to specific networks can serve as reliable predictors of functional outcomes, leading to personalized therapeutic approaches tailored to individual patients.

10aAdult10aAged10aBrain10aBrain Neoplasms10aFemale10aGlioma10aHumans10amachine learning10aMagnetic Resonance Imaging10aMale10aMiddle Aged10aNeoplasm Grading10aPrognosis10aRest10aRetrospective Studies1 aLuckett, Patrick, H1 aOlufawo, Michael, O1 aPark, Ki, Yun1 aLamichhane, Bidhan1 aDierker, Donna1 aVerastegui, Gabriel, Trevino1 aLee, John, J1 aYang, Peter1 aKim, Albert1 aButt, Omar, H1 aChheda, Milan, G1 aSnyder, Abraham, Z1 aShimony, Joshua, S1 aLeuthardt, Eric, C uhttps://www.neurotechcenter.org/publications/2024/predicting-post-surgical-functional-status-high-grade-glioma-resting