@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 {4567, title = {IpsiHand Brain-Computer Interface Therapy Induces Broad Upper Extremity Motor Rehabilitation in Chronic Stroke.}, journal = {Neurorehabil Neural Repair}, volume = {39}, year = {2025}, month = {2025 Jan}, pages = {74-86}, abstract = {

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.

}, keywords = {Adult, Aged, brain-computer interfaces, Chronic Disease, Electroencephalography, Female, Gamma Rhythm, Humans, Male, Middle Aged, Motor Activity, Paresis, Prospective Studies, Recovery of Function, Stroke, Stroke Rehabilitation, Theta Rhythm, Upper Extremity}, issn = {1552-6844}, doi = {10.1177/15459683241287731}, author = {Rustamov, Nabi and Souders, Lauren and Sheehan, Lauren and Carter, Alexandre and Leuthardt, Eric C} } @article {4573, title = {Predicting post-surgical functional status in high-grade glioma with resting state fMRI and machine learning.}, journal = {J Neurooncol}, volume = {169}, year = {2024}, month = {2024 Aug}, pages = {175-185}, abstract = {

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{\textquoteright}s location in relation to specific networks can serve as reliable predictors of functional outcomes, leading to personalized therapeutic approaches tailored to individual patients.

}, keywords = {Adult, Aged, Brain, Brain Neoplasms, Female, Glioma, Humans, machine learning, Magnetic Resonance Imaging, Male, Middle Aged, Neoplasm Grading, Prognosis, Rest, Retrospective Studies}, issn = {1573-7373}, doi = {10.1007/s11060-024-04715-1}, author = {Luckett, Patrick H and Olufawo, Michael O and Park, Ki Yun and Lamichhane, Bidhan and Dierker, Donna and Verastegui, Gabriel Trevino and Lee, John J and Yang, Peter and Kim, Albert and Butt, Omar H and Chheda, Milan G and Snyder, Abraham Z and Shimony, Joshua S and Leuthardt, Eric C} } @article {4461, title = {Comparisons of electrophysiological markers of impaired executive attention after traumatic brain injury and in healthy aging.}, journal = {Neuroimage}, volume = {274}, year = {2023}, month = {07/2023}, pages = {120126}, abstract = {

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.

}, keywords = {Aged, Aging, Biomarkers, Brain Injuries, Brain Injuries, Traumatic, Executive Function, Healthy Aging, Humans, Neuropsychological Tests}, issn = {1095-9572}, doi = {10.1016/j.neuroimage.2023.120126}, author = {Kim, Nayoung and Jamison, Keith and Jaywant, Abhishek and Garetti, Jacob and Blunt, Emily and RoyChoudhury, Arindam and Butler, Tracy and Dams-O{\textquoteright}Connor, Kristen and Khedr, Shahenda and Chen, Chun-Cheng and Shetty, Teena and Winchell, Robert and Hill, N Jeremy and Schiff, Nicholas D and Kuceyeski, Amy and Shah, Sudhin A} } @article {4336, title = {Modulation in cortical excitability disrupts information transfer in perceptual-level stimulus processing.}, journal = {Neuroimage}, volume = {243}, year = {2021}, month = {11/2021}, pages = {118498}, abstract = {

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.

}, keywords = {Acoustic Stimulation, Adult, Aged, Alpha Rhythm, Auditory Cortex, Brain Mapping, Cortical Excitability, Electrocorticography, Female, Humans, Male, Middle Aged}, issn = {1095-9572}, doi = {10.1016/j.neuroimage.2021.118498}, author = {Moheimanian, Ladan and Paraskevopoulou, Sivylla E and Adamek, Markus and Schalk, Gerwin and Peter Brunner} } @article {3370, title = {Brain-computer interface (BCI) evaluation in people with amyotrophic lateral sclerosis.}, journal = {Amyotroph Lateral Scler Frontotemporal Degener}, volume = {15}, year = {2014}, month = {06/2014}, pages = {207-15}, abstract = {Brain-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 {\texttimes} 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 ({\textpm} 3)\% (range 71-100\%), which is adequate for communication (G70 group). Eight averaged 12 ({\textpm} 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.}, keywords = {Adult, Aged, Amyotrophic Lateral Sclerosis, Biofeedback, Psychology, brain-computer interfaces, Communication Disorders, Electroencephalography, Event-Related Potentials, P300, Female, Humans, Male, Middle Aged, Online Systems, Photic Stimulation, Psychomotor Performance, Reaction Time}, issn = {2167-9223}, doi = {10.3109/21678421.2013.865750}, url = {http://www.ncbi.nlm.nih.gov/pubmed/24555843}, author = {McCane, Lynn M and Sellers, Eric W and Dennis J. McFarland and Mak, Joseph N and Carmack, C Steve and Zeitlin, Debra and Jonathan Wolpaw and Theresa M Vaughan} } @article {3386, title = {A practical, intuitive brain-computer interface for communicating {\textquoteright}yes{\textquoteright} or {\textquoteright}no{\textquoteright} by listening.}, journal = {J Neural Eng}, volume = {11}, year = {2014}, month = {06/2014}, pages = {035003}, abstract = {OBJECTIVE: 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 {\textquoteright}yes{\textquoteright} and {\textquoteright}no{\textquoteright}) 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{\textquoteright} performance with word stimuli (mean 77\% {\textpm} 3.3 s.e.) was slightly but not significantly better than their performance with beep stimuli (mean 73\% {\textpm} 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.}, keywords = {Adult, Aged, Algorithms, Auditory Perception, brain-computer interfaces, Communication Aids for Disabled, Electroencephalography, Equipment Design, Equipment Failure Analysis, Female, Humans, Male, Man-Machine Systems, Middle Aged, Quadriplegia, Treatment Outcome, User-Computer Interface}, issn = {1741-2552}, doi = {10.1088/1741-2560/11/3/035003}, url = {http://www.ncbi.nlm.nih.gov/pubmed/24838278}, author = {Jeremy Jeremy Hill and Ricci, Erin and Haider, Sameah and McCane, Lynn M and Susan M Heckman and Jonathan Wolpaw and Theresa M Vaughan} } @article {2169, title = {Patients with ALS can use sensorimotor rhythms to operate a brain-computer interface.}, journal = {Neurology}, volume = {64}, year = {2005}, month = {05/2005}, pages = {1775-7}, abstract = {

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.

}, keywords = {Aged, Amyotrophic Lateral Sclerosis, Electroencephalography, Evoked Potentials, Motor, Evoked Potentials, Somatosensory, Female, Humans, Imagination, Male, Middle Aged, Motor Cortex, Movement, Paralysis, Photic Stimulation, Prostheses and Implants, Somatosensory Cortex, Treatment Outcome, User-Computer Interface}, issn = {1526-632X}, doi = {10.1212/01.WNL.0000158616.43002.6D}, url = {http://www.ncbi.nlm.nih.gov/pubmed/15911809}, author = {K{\"u}bler, A. and Nijboer, F and Mellinger, J{\"u}rgen and Theresa M Vaughan and Pawelzik, H and Gerwin Schalk and Dennis J. McFarland and Niels Birbaumer and Jonathan Wolpaw} }