Neurosciences Commons^™

Endovascular Management Of A Ruptured Aneurysm On A Posterior Inferior Cerebellar Artery With Extradural C2-Origin: Case Report And Literature Review, Rasmus Holmboe Dahl, Gary Lloyd Horn, Zeyad Metwalli, Shankar Prakash Gopinath, Goetz Benndorf

Faculty, Staff and Students Publications

Extracranial vascular pathology uncommonly causes intracranial subarachnoid hemorrhage (SAH). Among possible lesions are aneurysms at the craniocervical junction arising from a posterior inferior cerebellar artery (PICA) with an extradural origin. We describe a case of a 55-year-old female presenting with a sudden and severe headache. A computed tomography scan revealed a SAH within the fourth ventricle and cervical spinal canal, and a ruptured saccular aneurysm on a PICA with extradural C2-origin. Despite difficult access anatomy, endovascular treatment was feasible and resulted in subtotal initial occlusion and preservation of distal PICA flow. Upon 3-month follow-up, the aneurysm was completely occluded with …

A Multimodal Deep Learning Tool For Detection Of Junctional Ectopic Tachycardia In Children With Congenital Heart Disease, Yilong Ju, Jamie L S Waugh, Satpreet Singh, Craig G Rusin, Ankit B Patel, Parag N Jain

Faculty, Staff and Students Publications

BACKGROUND: Junctional ectopic tachycardia (JET) is a prevalent life-threatening arrhythmia in children with congenital heart disease. It has a marked resemblance to normal sinus rhythm, often leading to delay in diagnosis and management.

OBJECTIVE: The study sought to develop a novel multimodal automated arrhythmia detection tool that outperforms existing JET detection tools.

METHODS: This is a cohort study performed on 40 patients with congenital heart disease at Texas Children's Hospital. Electrocardiogram and central venous pressure waveform data produced by bedside monitors are captured by the Sickbay platform. Convolutional neural networks (CNNs) were trained to classify each heartbeat as either normal …

Verbal Learning And Memory Deficits Across Neurological And Neuropsychiatric Disorders: Insights From An Enigma Mega Analysis, Eamonn Kennedy, Spencer W Liebel, Hannah M Lindsey, Shashank Vadlamani, Pui-Wa Lei, Maheen M Adamson, Martin Alda, Silvia Alonso-Lana, Tim J Anderson, Celso Arango, Robert F Asarnow, Mihai Avram, Rosa Ayesa-Arriola, Talin Babikian, Nerisa Banaj, Laura J Bird, Stefan Borgwardt, Amy Brodtmann, Katharina Brosch, Karen Caeyenberghs, Vince D Calhoun, Nancy D Chiaravalloti, David X Cifu, Benedicto Crespo-Facorro, John C Dalrymple-Alford, Kristen Dams-O'Connor, Udo Dannlowski, David Darby, Nicholas Davenport, John Deluca, Covadonga M Diaz-Caneja, Seth G Disner, Ekaterina Dobryakova, Stefan Ehrlich, Carrie Esopenko, Fabio Ferrarelli, Lea E Frank, Carol E Franz, Paola Fuentes-Claramonte, Helen Genova, Christopher C Giza, Janik Goltermann, Dominik Grotegerd, Marius Gruber, Alfonso Gutierrez-Zotes, Minji Ha, Jan Haavik, Charles Hinkin, Kristen R Hoskinson, Daniela Hubl, Andrei Irimia, Andreas Jansen, Michael Kaess, Xiaojian Kang, Kimbra Kenney, Barbora Keřková, Mohamed Salah Khlif, Minah Kim, Jochen Kindler, Tilo Kircher, Karolina Knížková, Knut K Kolskår, Denise Krch, William S Kremen, Taylor Kuhn, Veena Kumari, Junsoo Kwon, Roberto Langella, Sarah Laskowitz, Jungha Lee, Jean Lengenfelder, Victoria Liou-Johnson, Sara M Lippa, Marianne Løvstad, Astri J Lundervold, Cassandra Marotta, Craig A Marquardt, Paulo Mattos, Ahmad Mayeli, Carrie R Mcdonald, Susanne Meinert, Tracy R Melzer, Jessica Merchán-Naranjo, Chantal Michel, Rajendra A Morey, Benson Mwangi, Daniel J Myall, Igor Nenadić, Mary R Newsome, Abraham Nunes, Terence O'Brien, Viola Oertel, John Ollinger, Alexander Olsen, Victor Ortiz García De La Foz, Mustafa Ozmen, Heath Pardoe, Marise Parent, Fabrizio Piras, Federica Piras, Edith Pomarol-Clotet, Jonathan Repple, Geneviève Richard, Jonathan Rodriguez, Mabel Rodriguez, Kelly Rootes-Murdy, Jared Rowland, Nicholas P Ryan, Raymond Salvador, Anne-Marthe Sanders, Andre Schmidt, Jair C Soares, Gianfranco Spalleta, Filip Španiel, Scott R Sponheim, Alena Stasenko, Frederike Stein, Benjamin Straube, April Thames, Florian Thomas-Odenthal, Sophia I Thomopoulos, Erin B Tone, Ivan Torres, Maya Troyanskaya, Jessica A Turner, Kristine M Ulrichsen, Guillermo Umpierrez, Daniela Vecchio, Elisabet Vilella, Lucy Vivash, William C Walker, Emilio Werden, Lars T Westlye, Krista Wild, Adrian Wroblewski, Mon-Ju Wu, Glenn R Wylie, Lakshmi N Yatham, Giovana B Zunta-Soares, Paul M Thompson, Mary Jo Pugh, David F Tate, Frank G Hillary, Elisabeth A Wilde, Emily L Dennis

Faculty, Staff and Student Publications

Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15–90. The effects of dementia, mild cognitive impairment, Parkinson’s disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals. Random forest …

Neuroimaging Of Vermiform Giant Arachnoid Granulations In Children, Oswaldo A Guevara Tirado, Livja Mertiri, Stephen F Kralik, Nilesh K Desai, Thierry A G M Huisman, Maarten H Lequin, Huy Brandon D Tran

Faculty, Staff and Students Publications

Arachnoid granulations (AGs) are generally benign structures within the subarachnoid space that extend into the dural sinuses and calvarial bone. They can present in a variety of sizes but are termed 'giant' arachnoid granulations (GAGs) when they are larger than 1 cm in diameter or take up a significant portion of the dural sinus' lumen. Vermiform giant arachnoid granulations are a specific type of GAG that are known for their worm-like appearance. Specifically, these vermiform GAGs can be challenging to diagnose as they can mimic other pathologies like dural sinus thrombosis, sinus cavernomas, or brain tumors. In this case series, …

Alzheimer's Disease Risk Gene Cd2ap Is A Dose-Sensitive Determinant Of Synaptic Structure And Plasticity, Taeyong Ahn, Gabrielle E Largoza, Julia Younis, Mary E Dickinson, Chih-Wei Hsu, Joshua D Wythe

Faculty, Staff and Students Publications

Tissue clearing is an essential prerequisite for 3D volumetric imaging of larger tissues or organs. Here, we present a detailed protocol for optical, aqueous-based clearing of adult murine tissues using EZ Clear. We describe steps to ensure successful perfusion and fixation of organs from the adult mouse and supply guidelines for optimal lipid removal, refractive index matching, and tissue clearing. Finally, we provide imaging parameters for visualizing both exogenous perfused fluorescent dyes and endogenous fluorescence reporters in the adult mouse. For complete details on the use and execution of this protocol, please refer to Hsu et al.

Protocol For Preclinical Evaluation Of Locoregionally Delivered Car T Cells In Patient-Derived Xenograft Models Of Brain Tumors, Benjamin Draper, Chantelle Bowers, Eleni Vassalou, Ailsa Greppi, John Anderson, Nabil Ahmed, Michael D Taylor, Laura K Donovan

Faculty, Staff and Students Publications

Here, we present a protocol for preclinical evaluation of locoregionally delivered CAR T cells in patient-derived xenograft models of primary, metastatic, and recurrent brain tumors. We provide instructions for isolating peripheral blood mononuclear cells (PBMCs), producing CAR T cells in conjunction with locoregional delivery, and preclinical trial design and analysis involving CAR T cells. Additionally, we describe comprehensive preclinical readouts and guidelines for critical endpoint sample collections. In line with clinical trial procedures, our protocol broadens available treatment modalities for direct clinical translation. For complete details on the use and execution of this protocol, please refer to Donovan et al …

Comprehensive Single-Cell Atlas Of The Mouse Retina, Jin Li, Jongsu Choi, Xuesen Cheng, Justin Ma, Shahil Pema, Joshua R Sanes, Graeme Mardon, Benjamin J Frankfort, Nicholas M Tran, Yumei Li, Rui Chen

Faculty, Staff and Students Publications

Single-cell RNA sequencing (scRNA-seq) has advanced our understanding of cellular heterogeneity by characterizing cell types across tissues and species. While several mouse retinal scRNA-seq datasets exist, each dataset is either limited in cell numbers or focused on specific cell classes, thereby hindering comprehensive gene expression analysis across all retina types. To fill the gap, we generated the largest retinal scRNA-seq dataset to date, comprising approximately 190,000 single cells from C57BL/6J mouse retinas, enriched for rare population cells via antibody-based magnetic cell sorting. Integrating this dataset with public datasets, we constructed the Mouse Retina Cell Atlas (MRCA) for wild-type mice, encompassing …

In-Silico Analysis Of Tmem2 As A Pancreatic Adenocarcinoma And Cancer-Associated Fibroblast Biomarker, And Functional Characterization Of Nsc777201, For Targeted Drug Development, Prateeti Srivastava, Vijesh Kumar Yadav, Tzu-Hao Chang, Emily Chia-Yu Su, Bashir Lawal, Alexander Th Wu, Hsu-Shan Huang

Faculty, Staff and Student Publications

Pancreatic adenocarcinoma (PAAD), known as one of the deadliest cancers, is characterized by a complex tumor microenvironment, primarily comprised of cancer-associated fibroblasts (CAFs) in the extracellular matrix. These CAFs significantly alter the matrix by interacting with hyaluronic acid (HA) and the enzyme hyaluronidase, which degrades HA - an essential process for cancer progression and spread. Despite the critical role of this interaction, the specific functions of CAFs and hyaluronidase in PAAD development are not fully understood. Our study investigates this interaction and assesses NSC777201, a new anti-cancer compound targeting hyaluronidase. This research utilized computational methods to analyze gene expression data …

Meningioma Transcriptomic Landscape Demonstrates Novel Subtypes With Regional Associated Biology And Patient Outcome, H Nayanga Thirimanne, Damian Almiron-Bonnin, Nicholas Nuechterlein, Sonali Arora, Matt Jensen, Carolina A Parada, Chengxiang Qiu, Frank Szulzewsky, Collin W English, William C Chen, Philipp Sievers, Farshad Nassiri, Justin Z Wang, Tiemo J Klisch, Kenneth D Aldape, Akash J Patel, Patrick J Cimino, Gelareh Zadeh, Felix Sahm, David R Raleigh, Jay Shendure, Manuel Ferreira, Eric C Holland

Faculty, Staff and Students Publications

Meningiomas, although mostly benign, can be recurrent and fatal. World Health Organization (WHO) grading of the tumor does not always identify high-risk meningioma, and better characterizations of their aggressive biology are needed. To approach this problem, we combined 13 bulk RNA sequencing (RNA-seq) datasets to create a dimension-reduced reference landscape of 1,298 meningiomas. The clinical and genomic metadata effectively correlated with landscape regions, which led to the identification of meningioma subtypes with specific biological signatures. The time to recurrence also correlated with the map location. Further, we developed an algorithm that maps new patients onto this landscape, where the nearest …

Rigor And Reproducibility In Human Brain Organoid Research: Where We Are And Where We Need To Go, Soraya O Sandoval, Gerarda Cappuccio, Karina Kruth, Sivan Osenberg, Saleh M Khalil, Natasha M Méndez-Albelo, Krishnan Padmanabhan, Daifeng Wang, Mark J Niciu, Anita Bhattacharyya, Jason L Stein, André M M Sousa, Elisa A Waxman, Elizabeth D Buttermore, Dosh Whye, Carissa L Sirois, Cross-Iddrc Human Stem Cell Consortium, Aislinn Williams, Mirjana Maletic-Savatic, Xinyu Zhao

Faculty, Staff and Students Publications

Human brain organoid models have emerged as a promising tool for studying human brain development and function. These models preserve human genetics and recapitulate some aspects of human brain development, while facilitating manipulation in an in vitro setting. Despite their potential to transform biology and medicine, concerns persist about their fidelity. To fully harness their potential, it is imperative to establish reliable analytic methods, ensuring rigor and reproducibility. Here, we review current analytical platforms used to characterize human forebrain cortical organoids, highlight challenges, and propose recommendations for future studies to achieve greater precision and uniformity across laboratories.

Cost-Effectiveness And Threshold Analysis Of Deep Brain Stimulation Vs Treatment-As-Usual For Treatment-Resistant Depression, Katherine E Kabotyanski, Ricardo A Najera, Garrett P Banks, Himanshu Sharma, Nicole R Provenza, Benjamin Y Hayden, Sanjay J Mathew, Sameer A Sheth

Faculty, Staff and Students Publications

Treatment-resistant depression (TRD) affects approximately 2.8 million people in the U.S. with estimated annual healthcare costs of $43.8 billion. Deep brain stimulation (DBS) is currently an investigational intervention for TRD. We used a decision-analytic model to compare cost-effectiveness of DBS to treatment-as-usual (TAU) for TRD. Because this therapy is not FDA approved or in common use, our goal was to establish an effectiveness threshold that trials would need to demonstrate for this therapy to be cost-effective. Remission and complication rates were determined from review of relevant studies. We used published utility scores to reflect quality of life after treatment. Medicare …

Methylthioadenosine Phosphorylase Genomic Loss In Advanced Gastrointestinal Cancers, Natalie Y L Ngoi, Tin-Yun Tang, Catia F Gaspar, Dean C Pavlick, Gregory M Buchold, Emma L Scholefield, Vamsi Parimi, Richard S P Huang, Tyler Janovitz, Natalie Danziger, Mia A Levy, Shubham Pant, Anaemy Danner De Armas, David Kumpula, Jeffrey S Ross, Milind Javle, Jordi Rodon Ahnert

Faculty, Staff and Student Publications

BACKGROUND: One of the most common sporadic homozygous deletions in cancers is 9p21 loss, which includes the genes methylthioadenosine phosphorylase (MTAP), CDKN2A, and CDKN2B, and has been correlated with worsened outcomes and immunotherapy resistance. MTAP-loss is a developing drug target through synthetic lethality with MAT2A and PMRT5 inhibitors. The purpose of this study is to investigate the prevalence and genomic landscape of MTAP-loss in advanced gastrointestinal (GI) tumors and investigate its role as a prognostic biomarker.

MATERIALS AND METHODS: We performed next-generation sequencing and comparative genomic and clinical analysis on an extensive cohort of 64 860 tumors comprising 5 GI …

A Process To Reanalyze Clinical Dna Sequencing Data For Biomarker Matching In The Lung-Map Master Protocol, Joel W Neal, Katherine Minichiello, Ryan Brennick, Richard S P Huang, Matthew C Hiemenz, Cornel Amler, Jyoti Patel, Roy Herbst, Karen L Reckamp, Hossein Borghaei, Louise Highleyman, Mary W Redman, Lincoln W Pasquina, David E Kozono

Faculty, Staff and Student Publications

For cancer clinical trials that require central confirmation of tumor genomic profiling, exhaustion of tissue from standard-of-care testing may prevent enrollment. For Lung-MAP, a master protocol that requires results from a defined centralized clinical trial assay to assign patients to a therapeutic substudy, we developed a process to repurpose existing commercial vendor raw genomic data for eligibility: genomic data reanalysis (GDR). Molecular results for substudy assignment were successfully generated for 369 of the first 374 patients (98.7%) using GDR for Lung-MAP, with a median time from request to result of 9 days. During the same period, 691 of 791 (87.4%) …

Incidence And Factors In Delayed Neurological Deficits After Subarachnoid Hemorrhage In Mice, William Wroe, Ari Dienel, Sungha Hong, Kanako Matsumura, Jose Guzman, Kiara Torres, Angelica Bernal, Hussein A Zeineddine, Peeyush Thankamani Pandit, Spiros L Blackburn, Devin W Mcbride

Faculty, Staff and Student Publications

Background: Delayed cerebral ischemia (DCI) is one of the most feared complications in aneurysmal subarachnoid hemorrhage (SAH). Animal models are crucial to studying the disease mechanisms and potential treatments. DCI in rodents was thought to not exist; herein we examine literature and our experience with DCI in rodents.

Methods: Daily behavioral performance was assessed every day from day 1 to up to 7 days post-SAH on mice from 5 different studies that used the endovascular perforation model. Performance was graded using an 8-test sensorimotor neuroscore previously described. The daily neuroscore was then used to identify the incidence and timing of …

Purkinje Cell Dysfunction Causes Disrupted Sleep In Ataxic Mice, Luis E Salazar Leon, Amanda M Brown, Heet Kaku, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

Purkinje cell dysfunction disrupts movement and causes disorders such as ataxia. Recent evidence suggests that Purkinje cell dysfunction may also alter sleep regulation. Here, we used an ataxic mouse model generated by silencing Purkinje cell neurotransmission (L7Cre;Vgatfx/fx) to better understand how cerebellar dysfunction impacts sleep physiology. We focused our analysis on sleep architecture and electrocorticography (ECoG) patterns based on their relevance to extracting physiological measurements during sleep. We found that circadian activity was unaltered in the mutant mice, although their sleep parameters and ECoG patterns were modified. The L7Cre;Vgatfx/fx mutant mice had decreased wakefulness and rapid eye movement (REM) sleep, …

Adaptive, Behavioral, And Emotional Outcomes Following Postoperative Pediatric Cerebellar Mutism Syndrome In Survivors Treated For Medulloblastoma, Kimberly P Raghubar, Andrew M Heitzer, Fatema Malbari, Jason Gill, Roy V Sillitoe, Livia Merrill, Johanna Escalante, M Fatih Okcu, Guillermo Aldave, Avner Meoded, Stephen Kralik, Kimberly Davis, Marina Ma, Emily A H Warren, Mark D Mccurdy, Howard L Weiner, William Whitehead, Michael E Scheurer, Lisa Rodriguez, Amy Daigle, Murali Chintagumpala, Lisa S Kahalley

Faculty, Staff and Students Publications

OBJECTIVE: Patients who experience postoperative pediatric cerebellar mutism syndrome (CMS) during treatment for medulloblastoma have long-term deficits in neurocognitive functioning; however, the consequences on functional or adaptive outcomes are unknown. The purpose of the present study was to compare adaptive, behavioral, and emotional functioning between survivors with and those without a history of CMS.

METHODS: The authors examined outcomes in 45 survivors (15 with CMS and 30 without CMS). Comprehensive neuropsychological evaluations, which included parent-report measures of adaptive, behavioral, and emotional functioning, were completed at a median of 2.90 years following craniospinal irradiation.

RESULTS: Adaptive functioning was significantly worse in …

Atp1a3 Disease Spectrum Includes Paroxysmal Weakness And Encephalopathy Not Triggered By Fever, Chetan Immanneni, Daniel Calame, Song Jiao, Lisa T Emrick, Miguel Holmgren, Sho T Yano

Faculty, Staff and Students Publications

BACKGROUND AND OBJECTIVES: Heterozygous pathogenic variants in ATP1A3, which encodes the catalytic alpha subunit of neuronal Na+/K+-ATPase, cause primarily neurologic disorders with widely variable features that can include episodic movement deficits. One distinctive presentation of ATP1A3-related disease is recurrent fever-triggered encephalopathy. This can occur with generalized weakness and/or ataxia and is described in the literature as relapsing encephalopathy with cerebellar ataxia. This syndrome displays genotype-phenotype correlation with variants at p.R756 causing temperature sensitivity of ATP1A3. We report clinical and in vitro functional evidence for a similar phenotype not triggered by fever but associated with protein loss-of-function.

METHODS: We …

Neurorehabilitation With Vagus Nerve Stimulation: A Systematic Review, Radha Korupolu, Alyssa Miller, Andrew Park, Nuray Yozbatiran

Faculty, Staff and Student Publications

OBJECTIVE: To systematically review vagus nerve stimulation (VNS) studies to present data on the safety and efficacy on motor recovery following stroke, traumatic brain injury (TBI), and spinal cord injury (SCI).

METHODS: Data sources: PubMed, EMBASE, SCOPUS, and Cochrane.

STUDY SELECTION: Clinical trials of VNS in animal models and humans with TBI and SCI were included to evaluate the effects of pairing VNS with rehabilitation therapy on motor recovery.

DATA EXTRACTION: Two reviewers independently assessed articles according to the evaluation criteria and extracted relevant data electronically.

DATA SYNTHESIS: Twenty-nine studies were included; 11 were animal models of stroke, TBI, and …

Glioblastoma Disrupts Cortical Network Activity At Multiple Spatial And Temporal Scales, Jochen Meyer, Kwanha Yu, Estefania Luna-Figueroa, Benjamin Deneen, Jeffrey Noebels

Faculty, Staff and Students Publications

The emergence of glioblastoma in cortical tissue initiates early and persistent neural hyperexcitability with signs ranging from mild cognitive impairment to convulsive seizures. The influence of peritumoral synaptic density, expansion dynamics, and spatial contours of excess glutamate upon higher order neuronal network modularity is unknown. We combined cellular and widefield imaging of calcium and glutamate fluorescent reporters in two glioblastoma mouse models with distinct synaptic microenvironments and infiltration profiles. Functional metrics of neural ensembles are dysregulated during tumor invasion depending on the stage of malignant progression and tumor cell proximity. Neural activity is differentially modulated during periods of accelerated and …

Brain Cell-Type Shifts In Alzheimer’S Disease, Autism, And Schizophrenia Interrogated Using Methylomics And Genetics, Chloe X Yap, Daniel D Vo, Matthew G Heffel, Arjun Bhattacharya, Cindy Wen, Yuanhao Yang, Kathryn E Kemper, Jian Zeng, Zhili Zheng, Zhihong Zhu, Eilis Hannon, Dorothea Seiler Vellame, Alice Franklin, Christa Caggiano, Brie Wamsley, Daniel H Geschwind, Noah Zaitlen, Alexander Gusev, Bogdan Pasaniuc, Jonathan Mill, Chongyuan Luo, Michael J Gandal

Faculty, Staff and Student Publications

Few neuropsychiatric disorders have replicable biomarkers, prompting high-resolution and large-scale molecular studies. However, we still lack consensus on a more foundational question: whether quantitative shifts in cell types-the functional unit of life-contribute to neuropsychiatric disorders. Leveraging advances in human brain single-cell methylomics, we deconvolve seven major cell types using bulk DNA methylation profiling across 1270 postmortem brains, including from individuals diagnosed with Alzheimer's disease, schizophrenia, and autism. We observe and replicate cell-type compositional shifts for Alzheimer's disease (endothelial cell loss), autism (increased microglia), and schizophrenia (decreased oligodendrocytes), and find age- and sex-related changes. Multiple layers of evidence indicate that endothelial …

Incidence And Characteristics Of Cerebellar Atrophy/Volume Loss In Children With Confirmed Diagnosis Of Tuberous Sclerosis Complex, Livja Mertiri, Eugen Boltshauser, Stephen F Kralik, Nilesh K Desai, Maarten H Lequin, Thierry A G M Huisman

Faculty, Staff and Students Publications

Objectives: The goal of our study was to determine the incidence of cerebellar atrophy, assess the imaging findings in the posterior fossa and determine the incidence of hippocampal sclerosis in a cohort of pediatric patients with confirmed tuberous sclerosis complex (TSC).

Material and methods: MRI studies of 98 TSC pediatric patients (mean age 7.67 years) were evaluated for cerebellar atrophy, cerebral/cerebellar tubers, white matter lesions, subependymal nodules, subependymal giant cell astrocytomas, ventriculomegaly, and hippocampal sclerosis. Clinical charts were revisited for clinical symptoms suggesting cerebellar involvement, for seizures and treatment for seizures, behavioral disorders and autism.

Results: Cerebral tubers were present …

Generalizing Parkinson’S Disease Detection Using Keystroke Dynamics: A Self-Supervised Approach, Shikha Tripathi, Alejandro Acien, Ashley A Holmes, Teresa Arroyo-Gallego, Luca Giancardo

Faculty, Staff and Student Publications

Objective: Passive monitoring of touchscreen interactions generates keystroke dynamic signals that can be used to detect and track neurological conditions such as Parkinson's disease (PD) and psychomotor impairment with minimal burden on the user. However, this typically requires datasets with clinically confirmed labels collected in standardized environments, which is challenging, especially for a large subject pool. This study validates the efficacy of a self-supervised learning method in reducing the reliance on labels and evaluates its generalizability.

Materials and methods: We propose a new type of self-supervised loss combining Barlow Twins loss, which attempts to create similar feature representations with reduced …

Feasibility Of Fit24, A Digital Diabetes Prevention Program For Hispanic Adolescents: Qualitative Evaluation Study, Erica G Soltero, Salma M Musaad, Teresia M O'Connor, Debbe Thompson, Keith Norris, Bettina M Beech

Faculty, Staff and Students Publications

BACKGROUND: Digital health interventions are promising for reaching and engaging high-risk youth in disease prevention opportunities; however, few digital prevention interventions have been developed for Hispanic youth, limiting our knowledge of these strategies among this population.

OBJECTIVE: This study qualitatively assessed the feasibility and acceptability of Fit24, a 12-week goal-setting intervention that uses a Fitbit watch (Fitbit Inc) and theoretically grounded SMS text messages to promote physical activity and sleep among Hispanic adolescents (aged between 14 and 16 years) with obesity.

METHODS: After completing the intervention, a subsample of youth (N=15) participated in an in-depth interview. We categorized the themes …

Astrocytes Remember Inflammation, Michael R Williamson, Benjamin Deneen

Faculty, Staff and Students Publications

Astrocytes respond to all forms of central nervous system maladies. In a recent issue of Nature, Lee et al. demonstrate that astrocytes encode inflammatory stimuli as epigenetic memory, which strengthens responses to subsequent stimuli and exacerbates pathology in disease models.

Clinical, Genetic, And Cognitive Correlates Of Seizure Occurrences In Phelan-Mcdermid Syndrome, Tess Levy, Jacob Gluckman, Paige M Siper, Danielle Halpern, Jessica Zweifach, Rajna Filip-Dhima, J Lloyd Holder, M Pilar Trelles, Kristina Johnson, Jonathan A Bernstein, Elizabeth Berry-Kravis, Craig M Powell, Latha Valluripalli Soorya, Audrey Thurm, Joseph D Buxbaum, Mustafa Sahin, Alexander Kolevzon, Siddharth Srivastava

Duncan NRI Faculty and Staff Publications

Background: Phelan-McDermid syndrome (PMS) is a genetic neurodevelopmental disorder caused by SHANK3 haploinsufficiency and is associated with an increased risk for seizures. Previous literature indicates that around one third of individuals with PMS also have epilepsy or seizures, with a wide range of types and ages of onset. Investigating the impact of seizures on intellectual and adaptive functioning for PMS is a primary concern for caregivers and is important to understanding the natural history of this syndrome.

Methods: We report on results from 98 individuals enrolled in a prospective, longitudinal study. We detailed seizure frequency, type, and age of onset, …

Dlk-Mapk Signaling Coupled With Dna Damage Promotes Intrinsic Neurotoxicity Associated With Non-Mutated Tau, Sanming Li, Ethan R Roy, Yanyu Wang, Trent Watkins, Wei Cao

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is the most prevalent form of neurodegeneration. Despite the well-established link between tau aggregation and clinical progression, the major pathways driven by this protein to intrinsically damage neurons are incompletely understood. To model AD-relevant neurodegeneration driven by tau, we overexpressed non-mutated human tau in primary mouse neurons and observed substantial axonal degeneration and cell death, a process accompanied by activated caspase 3. Mechanistically, we detected deformation of the nuclear envelope and increased DNA damage response in tau-expressing neurons. Gene profiling analysis further revealed significant alterations in the mitogen-activated protein kinase (MAPK) pathway; moreover, inhibitors of dual leucine …

Piezo1 Regulates Meningeal Lymphatic Vessel Drainage And Alleviates Excessive Csf Accumulation, Dongwon Choi, Eunkyung Park, Joshua Choi, Renhao Lu, Jin Suh Yu, Chiyoon Kim, Luping Zhao, James Yu, Brandon Nakashima, Sunju Lee, Dhruv Singhal, Joshua P Scallan, Bin Zhou, Chester J Koh, Esak Lee, Young-Kwon Hong

Faculty, Staff and Students Publications

Piezo1 regulates multiple aspects of the vascular system by converting mechanical signals generated by fluid flow into biological processes. Here, we find that Piezo1 is necessary for the proper development and function of meningeal lymphatic vessels and that activating Piezo1 through transgenic overexpression or treatment with the chemical agonist Yoda1 is sufficient to increase cerebrospinal fluid (CSF) outflow by improving lymphatic absorption and transport. The abnormal accumulation of CSF, which often leads to hydrocephalus and ventriculomegaly, currently lacks effective treatments. We discovered that meningeal lymphatics in mouse models of Down syndrome were incompletely developed and abnormally formed. Selective overexpression of …

Molecular Mechanisms Of Opioid Use Disorder In Human Brain Models, Emily Mendez

Dissertations and Theses (Open Access)

Opioid use disorder (OUD) is a national and global public health crisis with no end in sight. While studies from animal models hint at widespread epigenetic and transcriptomic alterations of opioid drugs, the molecular consequences of long-term exposure to opioid drugs in human brain is still unclear, and human-centered translational models are necessary to discern the human cell type-specific effects of OUD.

Using postmortem brain Brodmann area 9 (BA9) from the UTHealth Brain Collection for Research on Psychiatric Disorders, I identified angiogenic gene networks perturbed in the RNA and protein of OUD subjects, as well as downregulation of many neuron-correlated …

Abnormality Of Early White Matter Development In Tuberous Sclerosis Complex And Autism Spectrum Disorder: Longitudinal Analysis Of Diffusion Tensor Imaging Measures, Siddharth Srivastava, Fanghan Yang, Anna K Prohl, Peter E Davis, Jamie K Capal, Rajna Filip-Dhima, E Martina Bebin, Darcy A Krueger, Hope Northrup, Joyce Y Wu, Simon K Warfield, Mustafa Sahin, Bo Zhang, Tacern Study Group

Faculty, Staff and Student Publications

Background:

Abnormalities in white matter development may influence development of autism spectrum disorder in tuberous sclerosis complex (TSC). Our goals for this study were as follows: (1) use data from a longitudinal neuroimaging study of tuberous sclerosis complex (TACERN) to develop optimized linear mixed effects models for analyzing longitudinal, repeated diffusion tensor imaging metrics (fractional anisotropy, mean diffusivity) pertaining to select white matter tracts, in relation to positive Autism Diagnostic Observation Schedule–Second Edition classification at 36 months, and (2) perform an exploratory analysis using optimized models applied to all white matter tracts from these data.

Methods:

Eligible participants (3-12 months) …

Retinoid X Receptor As A Mediator Of Post Stroke Recovery By Reversing Age-Associated Phenotypes Of Microglia/Macrophages, Shun-Ming Ting

Dissertations and Theses (Open Access)

After stroke, microglia (MG) and blood-derived macrophages, together (MF), clear dead cells and cellular debris in the infarcted brain through phagocytosis. However, the phagocytic capability of MF declines with age. Age-related changes in MF phenotype also include overactive inflammatory responses to stroke-induced brain injury, altogether resulting in poor recovery after stroke. Retinoid-X-receptor (RXR) is a pleiotropic transcription factor. Our studies suggest that RXRa enhances MF phagocytic functions, reduces inflammatory responses, and improves post-stroke recovery. To establish phenotypes of aging MF, MG were MACS-sorted from the brains of young adults (2-4 months old) and aged (18-20 months old) mice for transcriptomic …