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-upper02169nas a2200301 4500008004100000022001400041245015400055210006900209260001300278300000800291490000900299520119500308653000901503653002101512653001101533653001101544653000901555653001601564653001301580653001101593653002601604100002701630700001901657700002301676700002801699700001701727856012301744 2024 eng d a2694-060400aMultidimensional feature analysis shows stratification in robotic-motor-training gains based on the level of pre-training motor impairment in stroke.0 aMultidimensional feature analysis shows stratification in roboti c2024 Jul a1-50 v20243 a

Stroke involves heterogeneity in injury and ongoing endogenous recovery, which are seldom stratified before testing post-stroke robot assisted motor training (RAMT). Pretraining variations, especially sensory-motor differences may also affect the gains achieved from the RAMT. Moreover, one assessment test may not effectively characterize the baseline sensory-motor status or the RAMT gains. Pre-therapy stratification may help personalize therapy and increase therapy gains. Towards this goal, we propose a data-driven approach to assess multiple functional scores with t-distributed stochastic neighbor embedding and affinity propagation clustering, both for pre-therapy and RAMT gains. Data included behavioral scores from 27 people with chronic stroke who underwent RAMT for finger movement. Three clusters were observed at start-of-therapy (SoT), concurrent with the overall impairment level. Four clusters were observed for the RAMT gains, indicating specific improvements. The SoT clusters showed agreement with the RAMT gain clusters, suggesting that the pre-therapy state, assessed across multiple domains, could be useful in guiding RAMT interventions to improve outcomes.

10aAged10aCluster Analysis10aFemale10aHumans10aMale10aMiddle Aged10aRobotics10aStroke10aStroke Rehabilitation1 aRueda-Parra, Sebastian1 aPerry, Joel, C1 aWolbrecht, Eric, T1 aReinkensmeyer, David, J1 aGupta, Disha uhttps://www.neurotechcenter.org/publications/2024/multidimensional-feature-analysis-shows-stratification-robotic-motor03236nas 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-resting03132nas a2200433 4500008004100000022001400041245013100055210006900186260001200255300001100267490000800278520179900286653000902085653001002094653001502104653001902119653003002138653002302168653001802191653001102209653002902220100001702249700001902266700002202285700001902307700001702326700002602343700001802369700002702387700002002414700002102434700001802455700002102473700001702494700002402511700001902535700002002554856012402574 2023 eng d a1095-957200aComparisons of electrophysiological markers of impaired executive attention after traumatic brain injury and in healthy aging.0 aComparisons of electrophysiological markers of impaired executiv c07/2023 a1201260 v2743 a

Executive attention impairments are a persistent and debilitating consequence of traumatic brain injury (TBI). To make headway towards treating and predicting outcomes following heterogeneous TBI, cognitive impairment specific pathophysiology first needs to be characterized. In a prospective observational study, we measured EEG during the attention network test aimed at detecting alerting, orienting, executive attention and processing speed. The sample (N = 110) of subjects aged 18-86 included those with and without traumatic brain injury: n = 27, complicated mild TBI; n = 5, moderate TBI; n = 10, severe TBI; n = 63, non-brain-injured controls. Subjects with TBI had impairments in processing speed and executive attention. Electrophysiological markers of executive attention processing in the midline frontal regions reveal that, as a group, those with TBI and elderly non-brain-injured controls have reduced responses. We also note that those with TBI and elderly controls have responses that are similar for both low and high-demand trials. In subjects with moderate-severe TBI, reductions in frontal cortical activation and performance profiles are both similar to that of controls who are ∼4 to 7 years older. Our specific observations of frontal response reductions in subjects with TBI and in older adults is consistent with the suggested role of the anterior forebrain mesocircuit as underlying cognitive impairments. Our results provide novel correlative data linking specific pathophysiological mechanisms underlying domain-specific cognitive deficits following TBI and with normal aging. Collectively, our findings provide biomarkers that may serve to track therapeutic interventions and guide development of targeted therapeutics following brain injuries.

10aAged10aAging10aBiomarkers10aBrain Injuries10aBrain Injuries, Traumatic10aExecutive Function10aHealthy Aging10aHumans10aNeuropsychological Tests1 aKim, Nayoung1 aJamison, Keith1 aJaywant, Abhishek1 aGaretti, Jacob1 aBlunt, Emily1 aRoyChoudhury, Arindam1 aButler, Tracy1 aDams-O'Connor, Kristen1 aKhedr, Shahenda1 aChen, Chun-Cheng1 aShetty, Teena1 aWinchell, Robert1 aHill, Jeremy1 aSchiff, Nicholas, D1 aKuceyeski, Amy1 aShah, Sudhin, A uhttps://www.neurotechcenter.org/publications/2023/comparisons-electrophysiological-markers-impaired-executive-attention02272nas a2200337 4500008004100000022001400041245011100055210006900166260001200235300001100247490000800258520124200266653002501508653001001533653000901543653001701552653002001569653001801589653002601607653002501633653001101658653001101669653000901680653001601689100002301705700003201728700001901760700001901779700001901798856011701817 2021 eng d a1095-957200aModulation in cortical excitability disrupts information transfer in perceptual-level stimulus processing.0 aModulation in cortical excitability disrupts information transfe c11/2021 a1184980 v2433 a

Despite significant interest in the neural underpinnings of behavioral variability, little light has been shed on the cortical mechanism underlying the failure to respond to perceptual-level stimuli. We hypothesized that cortical activity resulting from perceptual-level stimuli is sensitive to the moment-to-moment fluctuations in cortical excitability, and thus may not suffice to produce a behavioral response. We tested this hypothesis using electrocorticographic recordings to follow the propagation of cortical activity in six human subjects that responded to perceptual-level auditory stimuli. Here we show that for presentations that did not result in a behavioral response, the likelihood of cortical activity decreased from auditory cortex to motor cortex, and was related to reduced local cortical excitability. Cortical excitability was quantified using instantaneous voltage during a short window prior to cortical activity onset. Therefore, when humans are presented with an auditory stimulus close to perceptual-level threshold, moment-by-moment fluctuations in cortical excitability determine whether cortical responses to sensory stimulation successfully connect auditory input to a resultant behavioral response.

10aAcoustic Stimulation10aAdult10aAged10aAlpha Rhythm10aAuditory Cortex10aBrain Mapping10aCortical Excitability10aElectrocorticography10aFemale10aHumans10aMale10aMiddle Aged1 aMoheimanian, Ladan1 aParaskevopoulou, Sivylla, E1 aAdamek, Markus1 aSchalk, Gerwin1 aBrunner, Peter uhttps://www.neurotechcenter.org/publications/2021/modulation-cortical-excitability-disrupts-information-transfer02595nas a2200421 4500008004100000022001400041245009200055210006900147260001200216300001100228490000700239520137400246653001001620653000901630653003401639653002801673653003001701653002801731653002701759653003501786653001101821653001101832653000901843653001601852653001901868653002301887653002801910653001801938100002001956700002101976700002601997700001902023700001902042700001902061700002102080700002402101856004802125 2014 eng d a2167-922300aBrain-computer interface (BCI) evaluation in people with amyotrophic lateral sclerosis.0 aBraincomputer interface BCI evaluation in people with amyotrophi c06/2014 a207-150 v153 aBrain-computer interfaces (BCIs) might restore communication to people severely disabled by amyotrophic lateral sclerosis (ALS) or other disorders. We sought to: 1) define a protocol for determining whether a person with ALS can use a visual P300-based BCI; 2) determine what proportion of this population can use the BCI; and 3) identify factors affecting BCI performance. Twenty-five individuals with ALS completed an evaluation protocol using a standard 6 × 6 matrix and parameters selected by stepwise linear discrimination. With an 8-channel EEG montage, the subjects fell into two groups in BCI accuracy (chance accuracy 3%). Seventeen averaged 92 (± 3)% (range 71-100%), which is adequate for communication (G70 group). Eight averaged 12 (± 6)% (range 0-36%), inadequate for communication (L40 subject group). Performance did not correlate with disability: 11/17 (65%) of G70 subjects were severely disabled (i.e. ALSFRS-R < 5). All L40 subjects had visual impairments (e.g. nystagmus, diplopia, ptosis). P300 was larger and more anterior in G70 subjects. A 16-channel montage did not significantly improve accuracy. In conclusion, most people severely disabled by ALS could use a visual P300-based BCI for communication. In those who could not, visual impairment was the principal obstacle. For these individuals, auditory P300-based BCIs might be effective.10aAdult10aAged10aAmyotrophic Lateral Sclerosis10aBiofeedback, Psychology10abrain-computer interfaces10aCommunication Disorders10aElectroencephalography10aEvent-Related Potentials, P30010aFemale10aHumans10aMale10aMiddle Aged10aOnline Systems10aPhotic Stimulation10aPsychomotor Performance10aReaction Time1 aMcCane, Lynn, M1 aSellers, Eric, W1 aMcFarland, Dennis, J.1 aMak, Joseph, N1 aCarmack, Steve1 aZeitlin, Debra1 aWolpaw, Jonathan1 aVaughan, Theresa, M uhttp://www.ncbi.nlm.nih.gov/pubmed/2455584303178nas a2200421 4500008004100000022001400041245009800055210006900153260001200222300001100234490000700245520196800252653001002220653000902230653001502239653002402254653003002278653003602308653002702344653002102371653003102392653001102423653001102434653000902445653002402454653001602478653001702494653002202511653002802533100002502561700001602586700001902602700002002621700002202641700002102663700002402684856004802708 2014 eng d a1741-255200aA practical, intuitive brain-computer interface for communicating 'yes' or 'no' by listening.0 apractical intuitive braincomputer interface for communicating ye c06/2014 a0350030 v113 aOBJECTIVE: Previous work has shown that it is possible to build an EEG-based binary brain-computer interface system (BCI) driven purely by shifts of attention to auditory stimuli. However, previous studies used abrupt, abstract stimuli that are often perceived as harsh and unpleasant, and whose lack of inherent meaning may make the interface unintuitive and difficult for beginners. We aimed to establish whether we could transition to a system based on more natural, intuitive stimuli (spoken words 'yes' and 'no') without loss of performance, and whether the system could be used by people in the locked-in state. APPROACH: We performed a counterbalanced, interleaved within-subject comparison between an auditory streaming BCI that used beep stimuli, and one that used word stimuli. Fourteen healthy volunteers performed two sessions each, on separate days. We also collected preliminary data from two subjects with advanced amyotrophic lateral sclerosis (ALS), who used the word-based system to answer a set of simple yes-no questions. MAIN RESULTS: The N1, N2 and P3 event-related potentials elicited by words varied more between subjects than those elicited by beeps. However, the difference between responses to attended and unattended stimuli was more consistent with words than beeps. Healthy subjects' performance with word stimuli (mean 77% ± 3.3 s.e.) was slightly but not significantly better than their performance with beep stimuli (mean 73% ± 2.8 s.e.). The two subjects with ALS used the word-based BCI to answer questions with a level of accuracy similar to that of the healthy subjects. SIGNIFICANCE: Since performance using word stimuli was at least as good as performance using beeps, we recommend that auditory streaming BCI systems be built with word stimuli to make the system more pleasant and intuitive. Our preliminary data show that word-based streaming BCI is a promising tool for communication by people who are locked in.10aAdult10aAged10aAlgorithms10aAuditory Perception10abrain-computer interfaces10aCommunication Aids for Disabled10aElectroencephalography10aEquipment Design10aEquipment Failure Analysis10aFemale10aHumans10aMale10aMan-Machine Systems10aMiddle Aged10aQuadriplegia10aTreatment Outcome10aUser-Computer Interface1 aHill, Jeremy, Jeremy1 aRicci, Erin1 aHaider, Sameah1 aMcCane, Lynn, M1 aHeckman, Susan, M1 aWolpaw, Jonathan1 aVaughan, Theresa, M uhttp://www.ncbi.nlm.nih.gov/pubmed/2483827802332nas a2200457 4500008004100000022001400041245009000055210006900145260001200214300001100226490000700237520103300244653000901277653003401286653002701320653002901347653003701376653001101413653001101424653001601435653000901451653001601460653001701476653001301493653001401506653002301520653002801543653002501571653002201596653002801618100001501646700001501661700002301676700002401699700001601723700001901739700002601758700002101784700002101805856004801826 2005 eng d a1526-632X00aPatients with ALS can use sensorimotor rhythms to operate a brain-computer interface.0 aPatients with ALS can use sensorimotor rhythms to operate a brai c05/2005 a1775-70 v643 a

People with severe motor disabilities can maintain an acceptable quality of life if they can communicate. Brain-computer interfaces (BCIs), which do not depend on muscle control, can provide communication. Four people severely disabled by ALS learned to operate a BCI with EEG rhythms recorded over sensorimotor cortex. These results suggest that a sensorimotor rhythm-based BCI could help maintain quality of life for people with ALS.

10aAged10aAmyotrophic Lateral Sclerosis10aElectroencephalography10aEvoked Potentials, Motor10aEvoked Potentials, Somatosensory10aFemale10aHumans10aImagination10aMale10aMiddle Aged10aMotor Cortex10aMovement10aParalysis10aPhotic Stimulation10aProstheses and Implants10aSomatosensory Cortex10aTreatment Outcome10aUser-Computer Interface1 aKübler, A1 aNijboer, F1 aMellinger, Jürgen1 aVaughan, Theresa, M1 aPawelzik, H1 aSchalk, Gerwin1 aMcFarland, Dennis, J.1 aBirbaumer, Niels1 aWolpaw, Jonathan uhttp://www.ncbi.nlm.nih.gov/pubmed/15911809