@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 {4570, title = {Complexity organization of resting-state functional-MRI networks.}, journal = {Hum Brain Mapp}, volume = {45}, year = {2024}, month = {2024 Aug 15}, pages = {e26809}, abstract = {

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{\textquoteright}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.

}, keywords = {Adult, Brain, Connectome, Default Mode Network, Entropy, Humans, Magnetic Resonance Imaging, Nerve Net, Rest}, issn = {1097-0193}, doi = {10.1002/hbm.26809}, author = {Trevino, Gabriel and Lee, John J and Shimony, Joshua S and Luckett, Patrick H 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 {4580, title = {Non-invasive Auricular Vagus nerve stimulation for Subarachnoid Hemorrhage (NAVSaH): Protocol for a prospective, triple-blinded, randomized controlled trial.}, journal = {medRxiv}, year = {2024}, month = {2024 Mar 19}, abstract = {

BACKGROUND: Inflammation has been implicated in driving the morbidity associated with subarachnoid hemorrhage (SAH). Despite understanding the important role of inflammation in morbidity following SAH, there is no current effective way to modulate this deleterious response. There is a critical need for a novel approach to immunomodulation that can be safely, rapidly, and effectively deployed in SAH patients. Vagus nerve stimulation (VNS) provides a non-pharmacologic approach to immunomodulation, with prior studies demonstrating VNS can reduce systemic inflammatory markers, and VNS has had early success treating inflammatory conditions such as arthritis, sepsis, and inflammatory bowel diseases. The aim of the Non-invasive Auricular Vagus nerve stimulation for Subarachnoid Hemorrhage (NAVSaH) trial is to translate the use of non-invasive transcutaneous auricular VNS (taVNS) to spontaneous SAH, with our central hypothesis being that implementing taVNS in the acute period following spontaneous SAH attenuates the expected inflammatory response to hemorrhage and curtails morbidity associated with inflammatory-mediated clinical endpoints.

MATERIALS AND METHODS: The overall objectives for the NAHSaH trial are to 1) Define the impact that taVNS has on SAH-induced inflammatory markers in the plasma and cerebrospinal fluid (CSF), 2) Determine whether taVNS following SAH reduces radiographic vasospasm, and 3) Determine whether taVNS following SAH reduces chronic hydrocephalus. Following presentation to a single enrollment site, enrolled SAH patients are randomly assigned twice daily treatment with either taVNS or sham stimulation for the duration of their intensive care unit stay. Blood and CSF are drawn before initiation of treatment sessions, and then every three days during a patient{\textquoteright}s hospital stay. Primary endpoints include change in the inflammatory cytokine TNF-α in plasma and cerebrospinal fluid between day 1 and day 13, rate of radiographic vasospasm, and rate of requirement for long-term CSF diversion via a ventricular shunt. Secondary outcomes include exploratory analyses of a panel of additional cytokines, number and type of hospitalized acquired infections, duration of external ventricular drain in days, interventions required for vasospasm, continuous physiology data before, during, and after treatment sessions, hospital length of stay, intensive care unit length of stay, and modified Rankin Scale score (mRS) at admission, discharge, and each at follow-up appointment for up to two years following SAH.

DISCUSSION: Inflammation plays a central role in morbidity following SAH. This NAVSaH trial is innovative because it diverges from the pharmacologic status quo by harnessing a novel non-invasive neuromodulatory approach and its known anti-inflammatory effects to alter the pathophysiology of SAH. The investigation of a new, effective, and rapidly deployable intervention in SAH offers a new route to improve outcomes following SAH.

TRIAL REGISTRATION: Clinical Trials Registered, NCT04557618. Registered on September 21, 2020, and the first patient was enrolled on January 4, 2021.

}, doi = {10.1101/2024.03.18.24304239}, author = {Huguenard, Anna L and Tan, Gansheng and Johnson, Gabrielle W and Adamek, Markus and Coxon, Andrew T and Kummer, Terrance T and Osbun, Joshua W and Vellimana, Ananth K and Limbrick, David D 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 {4587, title = {Optimal approaches to analyzing functional MRI data in glioma patients.}, journal = {J Neurosci Methods}, volume = {402}, year = {2024}, month = {2024 Feb}, pages = {110011}, abstract = {

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.

}, keywords = {Brain, Connectome, Glioma, Humans, Magnetic Resonance Imaging}, issn = {1872-678X}, doi = {10.1016/j.jneumeth.2023.110011}, author = {Park, Ki Yun and Shimony, Joshua S and Chakrabarty, Satrajit and Tanenbaum, Aaron B and Hacker, Carl D and Donovan, Kara M and Luckett, Patrick H and Milchenko, Mikhail and Sotiras, Aristeidis and Marcus, Daniel S and Leuthardt, Eric C and Snyder, Abraham Z} } @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 {4458, title = {Data-efficient resting-state functional magnetic resonance imaging brain mapping with deep learning.}, journal = {J Neurosurg}, year = {2023}, month = {04/2023}, pages = {1-12}, abstract = {

OBJECTIVE: Resting-state functional MRI (RS-fMRI) enables the mapping of function within the brain and is emerging as an efficient tool for the presurgical evaluation of eloquent cortex. Models capable of reliable and precise mapping of resting-state networks (RSNs) with a reduced scanning time would lead to improved patient comfort while reducing the cost per scan. The aims of the present study were to develop a deep 3D convolutional neural network (3DCNN) capable of voxel-wise mapping of language (LAN) and motor (MOT) RSNs with minimal quantities of RS-fMRI data.

METHODS: Imaging data were gathered from multiple ongoing studies at Washington University School of Medicine and other thoroughly characterized, publicly available data sets. All study participants (n = 2252 healthy adults) were cognitively screened and completed structural neuroimaging and RS-fMRI. Random permutations of RS-fMRI regions of interest were used to train a 3DCNN. After training, model inferences were compared using varying amounts of RS-fMRI data from the control data set as well as 5 patients with glioblastoma multiforme.

RESULTS: The trained model achieved 96\% out-of-sample validation accuracy on data encompassing a large age range collected on multiple scanner types and varying sequence parameters. Testing on out-of-sample control data showed 97.9\% similarity between results generated using either 50 or 200 RS-fMRI time points, corresponding to approximately 2.5 and 10 minutes, respectively (96.9\% LAN, 96.3\% MOT true-positive rate). In evaluating data from patients with brain tumors, the 3DCNN was able to accurately map LAN and MOT networks despite structural and functional alterations.

CONCLUSIONS: Functional maps produced by the 3DCNN can inform surgical planning in patients with brain tumors in a time-efficient manner. The authors present a highly efficient method for presurgical functional mapping and thus improved functional preservation in patients with brain tumors.

}, issn = {1933-0693}, doi = {10.3171/2023.3.JNS2314}, author = {Luckett, Patrick H and Park, Ki Yun and Lee, John J and Lenze, Eric J and Wetherell, Julie Loebach and Eyler, Lisa T and Snyder, Abraham Z and Ances, Beau M and Shimony, Joshua S and Leuthardt, Eric C} } @article {4449, title = {Resting state network mapping in individuals using deep learning.}, journal = {Front Neurol}, volume = {13}, year = {2023}, month = {01/2023}, pages = {1055437}, abstract = {

INTRODUCTION: Resting state functional MRI (RS-fMRI) is currently used in numerous clinical and research settings. The localization of resting state networks (RSNs) has been utilized in applications ranging from group analysis of neurodegenerative diseases to individual network mapping for pre-surgical planning of tumor resections. Reproducibility of these results has been shown to require a substantial amount of high-quality data, which is not often available in clinical or research settings.

METHODS: In this work, we report voxelwise mapping of a standard set of RSNs using a novel deep 3D convolutional neural network (3DCNN). The 3DCNN was trained on publicly available functional MRI data acquired in = 2010 healthy participants. After training, maps that represent the probability of a voxel belonging to a particular RSN were generated for each participant, and then used to calculate mean and standard deviation (STD) probability maps, which are made publicly available. Further, we compared our results to previously published resting state and task-based functional mappings.

RESULTS: Our results indicate this method can be applied in individual subjects and is highly resistant to both noisy data and fewer RS-fMRI time points than are typically acquired. Further, our results show core regions within each network that exhibit high average probability and low STD.

DISCUSSION: The 3DCNN algorithm can generate individual RSN localization maps, which are necessary for clinical applications. The similarity between 3DCNN mapping results and task-based fMRI responses supports the association of specific functional tasks with RSNs.

}, issn = {1664-2295}, doi = {10.3389/fneur.2022.1055437}, author = {Luckett, Patrick H and Lee, John J and Park, Ki Yun and Raut, Ryan V and Meeker, Karin L and Gordon, Evan M and Snyder, Abraham Z and Ances, Beau M and Leuthardt, Eric C and Shimony, Joshua S} }