Neurology Commons^™

Neurd Offers Automated Proofreading And Feature Extraction For Connectomics, Brendan Celii, Stelios Papadopoulos, Zhuokun Ding, Paul G Fahey, Eric Wang, Christos Papadopoulos, Alexander B Kunin, Saumil Patel, J Alexander Bae, Agnes L Bodor, Derrick Brittain, Joann Buchanan, Daniel J Bumbarger, Manuel A Castro, Erick Cobos, Sven Dorkenwald, Leila Elabbady, Akhilesh Halageri, Zhen Jia, Chris Jordan, Dan Kapner, Nico Kemnitz, Sam Kinn, Kisuk Lee, Kai Li, Ran Lu, Thomas Macrina, Gayathri Mahalingam, Eric Mitchell, Shanka Subhra Mondal, Shang Mu, Barak Nehoran, Sergiy Popovych, Casey M Schneider-Mizell, William Silversmith, Marc Takeno, Russel Torres, Nicholas L Turner, William Wong, Jingpeng Wu, Szi-Chieh Yu, Wenjing Yin, Daniel Xenes, Lindsey M Kitchell, Patricia K Rivlin, Victoria A Rose, Caitlyn A Bishop, Brock Wester, Emmanouil Froudarakis, Edgar Y Walker, Fabian Sinz, H Sebastian Seung, Forrest Collman, Nuno Maçarico Da Costa, R Clay Reid, Xaq Pitkow, Andreas S Tolias, Jacob Reimer

Faculty, Staff and Students Publications

We are in the era of millimetre-scale electron microscopy volumes collected at nanometre resolution1,2. Dense reconstruction of cellular compartments in these electron microscopy volumes has been enabled by recent advances in machine learning3–6. Automated segmentation methods produce exceptionally accurate reconstructions of cells, but post hoc proofreading is still required to generate large connectomes that are free of merge and split errors. The elaborate 3D meshes of neurons in these volumes contain detailed morphological information at multiple scales, from the diameter, shape and branching patterns of axons and dendrites, down to the fine-scale …

Foundation Model Of Neural Activity Predicts Response To New Stimulus Types, Eric Y Wang, Paul G Fahey, Zhuokun Ding, Stelios Papadopoulos, Kayla Ponder, Marissa A Weis, Andersen Chang, Taliah Muhammad, Saumil Patel, Zhiwei Ding, Dat Tran, Jiakun Fu, Casey M Schneider-Mizell, Microns Consortium, R Clay Reid, Forrest Collman, Nuno Maçarico Da Costa, Katrin Franke, Alexander S Ecker, Jacob Reimer, Xaq Pitkow, Fabian H Sinz, Andreas S Tolias

Faculty, Staff and Students Publications

The complexity of neural circuits makes it challenging to decipher the brain’s algorithms of intelligence. Recent breakthroughs in deep learning have produced models that accurately simulate brain activity, enhancing our understanding of the brain’s computational objectives and neural coding. However, it is difficult for such models to generalize beyond their training distribution, limiting their utility. The emergence of foundation models1 trained on vast datasets has introduced a new artificial intelligence paradigm with remarkable generalization capabilities. Here we collected large amounts of neural activity from visual cortices of multiple mice and trained a foundation model to accurately predict neuronal responses …

Functional Connectomics Reveals General Wiring Rule In Mouse Visual Cortex, Zhuokun Ding, Paul G Fahey, Stelios Papadopoulos, Eric Y Wang, Brendan Celii, Christos Papadopoulos, Andersen Chang, Alexander B Kunin, Dat Tran, Jiakun Fu, Zhiwei Ding, Saumil Patel, Lydia Ntanavara, Rachel Froebe, Kayla Ponder, Taliah Muhammad, J Alexander Bae, Agnes L Bodor, Derrick Brittain, Joann Buchanan, Daniel J Bumbarger, Manuel A Castro, Erick Cobos, Sven Dorkenwald, Leila Elabbady, Akhilesh Halageri, Zhen Jia, Chris Jordan, Dan Kapner, Nico Kemnitz, Sam Kinn, Kisuk Lee, Kai Li, Ran Lu, Thomas Macrina, Gayathri Mahalingam, Eric Mitchell, Shanka Subhra Mondal, Shang Mu, Barak Nehoran, Sergiy Popovych, Casey M Schneider-Mizell, William Silversmith, Marc Takeno, Russel Torres, Nicholas L Turner, William Wong, Jingpeng Wu, Wenjing Yin, Szi-Chieh Yu, Dimitri Yatsenko, Emmanouil Froudarakis, Fabian Sinz, Krešimir Josić, Robert Rosenbaum, H Sebastian Seung, Forrest Collman, Nuno Maçarico Da Costa, R Clay Reid, Edgar Y Walker, Xaq Pitkow, Jacob Reimer, Andreas S Tolias

Faculty, Staff and Students Publications

Understanding the relationship between circuit connectivity and function is crucial for uncovering how the brain computes. In mouse primary visual cortex, excitatory neurons with similar response properties are more likely to be synaptically connected1–8; however, broader connectivity rules remain unknown. Here we leverage the millimetre-scale MICrONS dataset to analyse synaptic connectivity and functional properties of neurons across cortical layers and areas. Our results reveal that neurons with similar response properties are preferentially connected within and across layers and areas—including feedback connections—supporting the universality of ‘like-to-like’ connectivity across the visual hierarchy. Using a validated digital twin model, …

Predictors And Outcomes Of First Pass Efficacy In Posterior Circulation Strokes: Insights From Star Collaboration, Muhammad U Hafeez, Muhammed A Essibayi, Daniel Raper, Omar Tanweer, Mithun Sattur, Sami Al-Kasab, Joshua Burks, Robert Townsend, Diana Alsbrook, Travis Dumont, Min S Park, Nitin Goyal, Adam S Arthur, Ilko Maier, Justin Mascitelli, Robert Starke, Stacey Wolfe, Kyle Fargen, Alejandro Spiotta, Peter T Kan

Faculty, Staff and Students Publications

Background: First-pass efficacy (FPE) has been established as an important predictor of favorable functional outcomes after endovascular thrombectomy (ET) in anterior circulation strokes. In this retrospective cohort study, we investigate predictors and clinical outcomes of FPE in posterior circulation strokes (pcAIS).

Methods: The Stroke Thrombectomy and Aneurysm Registry database was used to identify pcAIS patients who achieved FPE. Their baseline characteristics and outcomes were compared with the non-FPE group. The primary outcome was a 90-day modified Rankin Scale (mRS) of 0-3. Univariate (UVA) and multivariate (MVA) analyses were done to evaluate predictors of FPE. Safety outcomes included distal emboli, vessel …

Corrigendum To "Door-To-Needle Time Trends After Transition To Tenecteplase: A Multicenter Texas Stroke Registry" [Journal Of Stroke And Cerebrovascular Diseases 33 (2024) 107774], Nathaniel Rodriguez, Sidarrth Prasad, Daiwai M Olson, Sujani Bandela, Gretchel Gealogo Brown, Yoon Kwon, Mehari Gebreyohanns, Erica M Jones, Nneka L Ifejika, Suzanne Stone, Jane A Anderson, Sean I Savitz, Salvador Cruz-Flores, Steven J Warach, Mark P Goldberg, Lee A Birnbaum

Faculty, Staff and Students Publications

No abstract provided.

Glucose Uptake In Pigment Glia Suppresses Tau-Induced Inflammation And Photoreceptor Degeneration, Mikiko Oka, Sho Nakajima, Emiko Suzuki, Shinya Yamamoto, Kanae Ando

Duncan NRI Faculty and Staff Publications

Brain inflammation contributes to the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD). Glucose hypometabolism and glial activation are pathological features seen in AD brains; however, the connection between the two is not fully understood. Using a Drosophila model of AD, we identified that glucose metabolism in glia plays a critical role in neuroinflammation under disease conditions. Expression of human MATP (hereafter referred to as Tau) in the retinal cells, including photoreceptor neurons and pigment glia, causes photoreceptor degeneration accompanied by the formation of dark-stained round inclusion-like structures and swelling of the lamina cortex. We found that inclusion-like structures …

De Novo Variants In Rybp Are Associated With A Severe Neurodevelopmental Disorder And Congenital Anomalies, Monika Weisz-Hubshman, Lindsay C Burrage, Sharayu V Jangam, Jill A Rosenfeld, Sandra Von Hardenberg, Anke Bergmann, Manuela Friederike Richter, Malgorzata Rydzanicz, Rafal Ploski, Agnieszka Stembalska, Wendy K Chung, Rebecca R Hernan, Foong Y Lim, Theresa Brunet, Steffen Syrbe, Boris Keren, Solveig Heide, David R Murdock, Hongzheng Dai, Fan Xia, Shamika Ketkar, Brian Dawson, Vinodh Narayanan, Hillary K Graves, Undiagnosed Diseases Network, Michael F Wangler, Carlos Bacino, Brendan Lee

Duncan NRI Faculty and Staff Publications

Purpose: Polycomb group proteins are key epigenetic transcriptional regulators. Multiple neurodevelopmental disorders are associated with pathogenic variants of the genes encoding Polycomb group proteins. RYBP is a core component of the noncanonical Polycomb Repressor Complex 1; however, its role in disease is unclear.

Methods: Functional consequences of RYBP variants were assessed using in vitro cellular and in vivo Drosophila melanogaster studies.

Results: We described 7 individuals with heterozygous de novo variants of RYBP and their clinical findings, including severe developmental delay, dysmorphisms, and multiple congenital anomalies. We showed that all single-nucleotide variants in RYBP localize to the N-terminal domain of …

Low-Grade Glial/Glioneuronal Tumor With Yap1::Fam118b Fusion: A Novel Molecular Finding, Fouad El-Dana, Kenneth Aldape, Zied Abdullaev, Sameer Anil Sheth, Jacob Mandel, Hsiang-Chih Lu

Faculty, Staff and Students Publications

No abstract provided.

Inhibitory Specificity From A Connectomic Census Of Mouse Visual Cortex, Casey M Schneider-Mizell, Agnes L Bodor, Derrick Brittain, Joann Buchanan, Daniel J Bumbarger, Leila Elabbady, Clare Gamlin, Daniel Kapner, Sam Kinn, Gayathri Mahalingam, Sharmishtaa Seshamani, Shelby Suckow, Marc Takeno, Russel Torres, Wenjing Yin, Sven Dorkenwald, J Alexander Bae, Manuel A Castro, Akhilesh Halageri, Zhen Jia, Chris Jordan, Nico Kemnitz, Kisuk Lee, Kai Li, Ran Lu, Thomas Macrina, Eric Mitchell, Shanka Subhra Mondal, Shang Mu, Barak Nehoran, Sergiy Popovych, William Silversmith, Nicholas L Turner, William Wong, Jingpeng Wu, Jacob Reimer, Andreas S Tolias, H Sebastian Seung, R Clay Reid, Forrest Collman, Nuno Maçarico Da Costa

Faculty, Staff and Students Publications

Mammalian cortex features a vast diversity of neuronal cell types, each with characteristic anatomical, molecular and functional properties1. Synaptic connectivity shapes how each cell type participates in the cortical circuit, but mapping connectivity rules at the resolution of distinct cell types remains difficult. Here we used millimetre-scale volumetric electron microscopy2 to investigate the connectivity of all inhibitory neurons across a densely segmented neuronal population of 1,352 cells spanning all layers of mouse visual cortex, producing a wiring diagram of inhibition with more than 70,000 synapses. Inspired by classical neuroanatomy, we classified inhibitory neurons based on targeting of …

Age-Associated Proteins Explain The Role Of Medial Temporal Lobe Networks In Alzheimer’S Disease, Adam Turnbull, Yejin Kim, Kai Zhang, Xiaoqian Jiang, Zihuai He, Victor W Henderson, F Vankee Lin

Faculty, Staff and Student Publications

The structural connectivity (SC) of the medial temporal lobe and its associated cortical anterior temporal and posterior medial networks (MTL-AT-PM) is linked to pathologies and memory decline in Alzheimer's disease (AD). However, neuroimaging analyses cannot tell us how SC changes occur in AD at the molecular level and do not provide a means of intervening to slow/prevent pathology-related changes in MTL-AT-PM SC. The current study aimed to understand how and where AD-related changes occur within MTL-AT-PM using proteomics. We used a 4-step approach in 101 older adults from a local sample, aiming to understand how proteins and SC in combination …

Statins And Middle Meningeal Artery Embolization: A Literature Review In The Treatment Of Chronic Subdural Hematoma, Basel Musmar, Joanna M. Roy, Samantha Spellicy, Stavropoula I. Tjoumakaris, Michael R. Gooch, Robert H. Rosenwasswer, David Hasan, Pascal Jabbour

Department of Neurosurgery Faculty Papers

Chronic subdural hematoma (cSDH) presents a multifaceted challenge in contemporary neurological practice, necessitating innovative therapeutic strategies. This comprehensive review explores the convergence of two promising interventions: statins and middle meningeal artery (MMA) Embolization. With cSDH incidence on the rise, particularly among the aging population and those with long-term anticoagulant usage, the traditional surgical avenues face limitations in recurrence rates and associated risk factors. Statins, heralded for their anti-inflammatory, vasculogenic, and angiogenic properties, are emerging as potential allies in cSDH management. Concurrently, MMA embolization offers a nuanced approach to target the neomembrane's blood supply, with evidence supporting its efficacy and safety. …

Staged Screening Identifies People With Biomarkers Related To Neuronal Alpha-Synuclein Disease, Ethan G Brown, Lana M Chahine, Andrew Siderowf, Caroline Gochanour, Ryan Kurth, Micah J Marshall, Chelsea Caspell-Garcia, Michael C Brumm, Craig E Stanley, Monica Korell, Bridget Mcmahon, Maggie Kuhl, Kimberly Fabrizio, Laura Heathers, Luis Concha-Marambio, Claudio Soto, Sohini Chowdhury, Christopher S Coffey, Tatiana M Foroud, Tanya Simuni, Kenneth Marek, Caroline M Tanner

Faculty, Staff and Student Publications

Objective: Remote identification of individuals with severe hyposmia may enable scalable recruitment of participants with underlying alpha-synuclein aggregation. We evaluated the performance of a staged screening paradigm using remote smell testing to enrich for abnormal dopamine transporter single-photon emission computed tomography imaging (DAT-SPECT) and alpha-synuclein aggregation.

Methods: The Parkinson's Progression Markers Initiative (PPMI) recruited participants for the prodromal cohort who were 60-years and older without a Parkinson's disease diagnosis. Participants were invited to complete a University of Pennsylvania Smell Identification Test (UPSIT) independently through an online portal. Hyposmic participants were invited to complete DAT-SPECT, which determined eligibility for enrollment in …

Spetzler-Martin Grade Iv Cerebral Arteriovenous Malformations In Adult Patients: A Propensity-Score Matched Analysis Of Resection And Stereotactic Radiosurgery, Salem M. Tos, Mahmoud Osama, Georgios Mantziaris, Bardia Hajikarimloo, Nimer Adeeb, Sandeep Kandregula, Hamza Adel Salim, Basel Musmar, Christopher Ogilvy, Douglas Kondziolka, Adam A. Dmytriw, Kareem El Naamani, Ahmed Abdelsalam, Deepak Kumbhare, Sanjeev Gummadi, Cagdas Ataoglu, Muhammed Amir Essibayi, Ufuk Erginoglu, Abdullah Keles, Sandeep Muram, Daniel Sconzo, Howard Riina, Arwin Rezai, Johannes Pöppe, Rajeev D. Sen, Louis J. Kim, Omar Alwakaa, Christoph J. Griessenauer, Pascal Jabbour, Stavropoula I. Tjoumakaris, Jan-Karl Burkhardt, Robert M. Starke, Mustafa K. Baskaya, Laligam N. Sekhar, Michael R. Levitt, David J. Altschul, Neil Haranhalli, Malia Mcavoy, Abdallah Abushehab, Assala Aslan, Christian Swaid, Adib Abla, Christopher Stapleton, Matthew Koch, Visish M. Srinivasan, Peng R. Chen, Spiros Blackburn, Omar Choudhri, Bryan Pukenas, Darren Orbach, Edward Smith, Markus Möhlenbruch, Ali Alaraj, Ali Aziz-Sultan, Aman B. Patel, Amey Savardekar, Hugo H. Cuellar, Kathleen Dlouhy, Tarek El Ahmadieh, Michael Lawton

Department of Neurosurgery Faculty Papers

Spetzler-Martin Grade IV arteriovenous malformations (AVMs) are challenging due to high risks associated with both treatment and natural progression. This study compares the outcomes of microsurgical resection and stereotactic radiosurgery (SRS) in high-grade AVMs, analyzing obliteration rates, complications, and functional outcomes. A retrospective cohort of 96 patients treated with either microsurgical resection (33 patients) or SRS (63 patients) was analyzed. Propensity-score matching was employed to account for baseline variables such as AVM size (cm), preoperative embolization and rupture status. Primary endpoints included AVM obliteration, complication rates, and modified Rankin Scale (mRS) scores. After matching, 31 patients per group were analyzed. …

Management Of Parkinson's Disease Psychosis: First-Line Antipsychotic Selection And Rationale For Continuing, Combining, Or Switching, Stuart H. Isaacson, Henry Nasrallah, Rajesh Pahwa, Gustavo Alva, Daniel Kremens, Stephen M. Stahl

Department of Neurology Faculty Papers

INTRODUCTION: The past decade has seen a paradigm shift in the evaluation and management of Parkinson's disease psychosis (PDP), with the first approval of an antipsychotic in the US in 2016. An evidence-based review by the Movement Disorder Society found pimavanserin and clozapine to be clinically useful, (low-dose) quetiapine to be possibly useful, and all other antipsychotics to be avoided due to motor worsening. Clozapine and quetiapine use can be limited by provoking Parkinson's disease (PD) nonmotor symptoms of somnolence and hypotension. Quetiapine may also be limited by its risk in cognitive impairment. Pimavanserin is not associated with these symptoms. …

Effect Of Eye Position On Variability Of The Vestibulo-Ocular Reflex, Kathryn Mozzochi, Amsal Madhani, Michael D. Balkwill, Divya Chari, Faisal Karmali

Tower Health Research Day

No abstract provided.

Dyke-Davidoff-Masson Syndrome: A Rare Cause Of Drug Refractory Epilepsy In An Adult, Paresh Zanzmera, Vaidehi Chauhan, Tvisha Patel, Jaineel Patel, Ankit Dumaswala, Kinjal Shah

Tower Health Research Day

No abstract provided.

Distinct Patterns Of Pv And Sst Gabaergic Neuronal Activity In The Basal Forebrain During Olfactory-Guided Behavior In Mice, Elizabeth H Moss, Evelyne K Tantry, Elaine Le, Pey-Shyuan Chin, Priscilla Ambrosi, Katie L Brandel-Ankrapp, Benjamin R Arenkiel

Duncan NRI Faculty and Staff Publications

Sensory perception relies on the flexible detection and interpretation of stimuli across variable contexts, conditions, and behavioral states. The basal forebrain (BF) is a hub for behavioral state regulation, supplying dense cholinergic and GABAergic projections to various brain regions involved in sensory processing. Of GABAergic neurons in the BF, parvalbumin (PV) and somatostatin (SST) subtypes serve opposing roles toward regulating behavioral states. To elucidate the role of BF circuits in sensory-guided behavior, we investigated GABAergic signaling dynamics during odor-guided decision-making in male and female mice. We used fiber photometry to record cell type-specific BF activity during an odor discrimination task …

Image Quality Analysis Of Head Cts Obtained On A New Portable Scanner Compared To Stationary Ct, Mara M. Kunst, Juan E. Small, Sebastian E. Flacke, Joseph D. Burns, Maximilian Smith, Christoph D. Wald

The Lahey Journal

Background/Purpose: The use of mobile head CT scanning in the ICU setting has both clinical and economic advantages, particularly if able to provide image quality close or equal to fixed CT scanners.

The purpose of the study is to evaluate the image quality of a new portable CT scanner, compared to a fixed CT platform.

Materials/Methods: Inpatients (n=11), age> 60 requiring head CT evaluation were enrolled and consented to obtain an additional head CT on the portable CT, following their fixed exam.

Nine patients were able to complete the study; seven patients received duplicate exams with matched imaging technique, and …

Stingers—A Review Of Current Understanding And Management, Teleale Gebeyehu, James Harrop, Stavros Matsoukas, Alexander Vaccaro

Department of Neurosurgery Faculty Papers

Abstract: A stinger is the transient sensory and motor loss of one upper extremity caused by a stretch or compression injury to the brachial plexus or the exiting cervical nerve roots. Athletes from contact sports like American football, rugby, wrestling, and horseback riding are most affected. Given today’s competitive athletic culture and recent advancements in sports medicine, understanding the clinical, diagnostic, and therapeutic aspects of stingers is crucial. Thus, this narrative review highlights current knowledge of pathology, clinical features, diagnostic modalities, radiologic measurements, management, rehabilitation, and return-to-play protocols. Recent and prominent English publications on adult athletes revealed that the brachial …

What Single-Cell Rna Sequencing Taught Us About Mgmt Expression In Glioblastoma, Iyad Alnahhas, Mehak Majid Khan, Wenyin Shi

Department of Neurology Faculty Papers

Background.

The promoter methylation status of O-6-methylguanine-DNA methyltransferase (MGMTp) is an important prognostic marker in GBM. Previous studies showed that the expression of MGMT based on immunohistochemistry did not correlate with survival. This is partly because nontumor cells express MGMT. Single-cell sequencing assesses gene expression in tumor cells specifically.

Methods.

We used publicly available data from 3 recent single-cell/nucleus sequencing GBM studies that included MGMTp methylation status data for patients to evaluate MGMT expression at the single-cell level.

Results.

In the CPTAC study, a median of 0.82% and 5.7% of tumor cells expressed MGMT in the …