Medicine and Health Sciences Commons^™

Pediatric Neurotropic Infection Alters Synaptic Development In The Developing Brain, Anuoluwapo Grace Fadare, Yashika S. Kamte, Manish N. Chandwani, Lauren A. O'Donnell

Rowan-Virtua Research Day

Many neurotropic viruses cause more significant pathology in younger hosts as their brains are still developing. This experiment asked how central nervous system (CNS) viral-infections affect the development of synapses in the pediatric brain during infection and post-infection. Synaptogenesis is at its peak in pediatric mice (10 days old) and we hypothesized that a neurotropic infection could disrupt synaptic proteins. We used a transgenic mouse model where measles virus (MV) infects only mature neurons, leading us to question whether synapses were impacted. We examined synaptic markers in the cerebellum and hippocampus in MV-infected and uninfected mice 9 days and 90 …

Unsupervised Deep Representation Learning Enables Phenotype Discovery For Genetic Association Studies Of Brain Imaging, Khush Patel, Ziqian Xie, Hao Yuan, Sheikh Muhammad Saiful Islam, Yaochen Xie, Wei He, Wanheng Zhang, Assaf Gottlieb, Han Chen, Luca Giancardo, Alexander Knaack, Evan Fletcher, Myriam Fornage, Shuiwang Ji, Degui Zhi

Journal Articles

Understanding the genetic architecture of brain structure is challenging, partly due to difficulties in designing robust, non-biased descriptors of brain morphology. Until recently, brain measures for genome-wide association studies (GWAS) consisted of traditionally expert-defined or software-derived image-derived phenotypes (IDPs) that are often based on theoretical preconceptions or computed from limited amounts of data. Here, we present an approach to derive brain imaging phenotypes using unsupervised deep representation learning. We train a 3-D convolutional autoencoder model with reconstruction loss on 6130 UK Biobank (UKBB) participants' T1 or T2-FLAIR (T2) brain MRIs to create a 128-dimensional representation known as Unsupervised Deep learning …

Dna Methylation-Based Epigenetic Biomarkers In Cell-Type Deconvolution And Tumor Tissue Of Origin Identification, Ze Zhang

Dartmouth College Ph.D Dissertations

DNA methylation is an epigenetic modification that regulates gene expression and is essential to establishing and preserving cellular identity. Genome-wide DNA methylation arrays provide a standardized and cost-effective approach to measuring DNA methylation. When combined with a cell-type reference library, DNA methylation measures allow the assessment of underlying cell-type proportions in heterogeneous mixtures. This approach, known as DNA methylation deconvolution or methylation cytometry, offers a standardized and cost-effective method for evaluating cell-type proportions. While this approach has succeeded in discerning cell types in various human tissues like blood, brain, tumors, skin, breast, and buccal swabs, the existing methods have major …

Chromosome 10q2432 Variants Associate With Brain Arterial Diameters In Diverse Populations: A Genome-Wide Association Study, Minghua Liu, Farid Khasiyev, Sanjeev Sariya, Antonio Spagnolo-Allende, Danurys L Sanchez, Howard Andrews, Qiong Yang, Alexa Beiser, Ye Qiao, Emy A Thomas, Jose Rafael Romero, Tatjana Rundek, Adam M Brickman, Jennifer J Manly, Mitchell Sv Elkind, Sudha Seshadri, Christopher Chen, Saima Hilal, Bruce A Wasserman, Giuseppe Tosto, Myriam Fornage, Jose Gutierrez

Journal Articles

BACKGROUND: Brain arterial diameters (BADs) are novel imaging biomarkers of cerebrovascular disease, cognitive decline, and dementia. Traditional vascular risk factors have been associated with BADs, but whether there may be genetic determinants of BADs is unknown.

METHODS AND RESULTS: The authors studied 4150 participants from 6 geographically diverse population-based cohorts (40% European, 14% African, 22% Hispanic, 24% Asian ancestries). Brain arterial diameters for 13 segments were measured and averaged to obtain a global measure of BADs as well as the posterior and anterior circulations. A genome-wide association study revealed 14 variants at one locus associated with global BAD at genome-wide …

Effect Of Acute And Repeated Noise Exposure On The Behaviour And Lipid Peroxidation In Brain Tissue Of Male And Female Mice, Gabriella Korsós, Kinga Fodor, Annamária Kiss, Anna Blázovics, Sándor György Fekete

Turkish Journal of Veterinary & Animal Sciences

Despite the increasingly obvious sex differences, male animals are still predominantly used to study stress and related disorders. The aim of this study was to evaluate the effects of repeated noise stress in female and male mice. In the experiment, 12 male and 12 and female SPF/VAF 6-week-old Crl:CD1(lcr) mice were used. After 5 days of acclimatization all animals were placed in the open-field for three consecutive days where each mouse spent 10 min daily without any noise treatment in order to get used to the circumstances of the test. On day 9 to record baseline behaviour the animals were …

Combined 3d Bioprinting And Tissue-Specific Ecm System Reveals The Influence Of Brain Matrix On Stem Cell Differentiation, Martina Zamponi, Peter A. Mollica, Yara Khodour, Julie S. Bjerring, Robert D. Bruno, Patrick C. Sachs

Medical Diagnostics & Translational Sciences Faculty Publications

We have previously shown that human and murine breast extracellular matrix (ECM) can significantly impact cellular behavior, including stem cell fate determination. It has been established that tissue-specific extracellular matrix from the central nervous system has the capacity to support neuronal survival. However, the characterization of its influence on stem cell differentiation and its adaptation to robust 3D culture models is underdeveloped. To address these issues, we combined our 3D bioprinter with hydrogels containing porcine brain extracellular matrix (BMX) to test the influence of the extracellular matrix on stem cell differentiation. Our 3D bioprinting system generated reproducible 3D neural structures …

Meta-Analytic Connectivity Modelling Of Healthy Swallowing, Chris R. Tilton

Honors Theses and Capstones

A quantitative, voxel-wise meta-analysis was performed to investigate the brain regions involved in healthy human swallowing. Studies included in the meta-analysis (1) examined water swallowing, saliva swallowing, or both, (2) included healthy, normal subjects, and (3) reported stereotaxic brain activation coordinates in standard space. Following these criteria, a systematic literature review identified 8 studies that met the criteria. An activation likelihood estimation (ALE) meta-analysis and meta-analytic connectivity modelling (MACM) analysis were performed with BrainMap software. Ten clusters with high activation likelihood were found in the bilateral precentral gyri, right insula, left declive, right medial frontal gyrus, right dorsal nucleus of …

Markers Of Neuroinflammatory And Degenerative Processes In Professional Athletes With Traumatic Encephalopathy Syndrome, Brooke Conway Kleven

UNLV Theses, Dissertations, Professional Papers, and Capstones

Introduction: The clinical criteria for Traumatic encephalopathy syndrome (ccTES) were developed to improve the diagnosis of Chronic traumatic encephalopathy (CTE). This study aimed to determine whether there was an association between a clinical diagnosis of Traumatic encephalopathy syndrome (TES) and changes in serum biomarkers, balance, neuroimaging, and cognition among athletes in the Professional Athletes Brain Health Study (PABHS).Methods: Of the cohort, 130 professional fighters met age or retirement criteria and went to a consensus conference, with 52 fighters (40%) meeting the criteria for TES. A generalized linear model with generalized estimating equations was utilized to assess the odds of disease …

Differential Expression And Activities Of Cytochrome P450 3a In The Rat Brain Microsomes And Mitochondria, Nouf Alshammari, Devaraj Venkatapura Chandrashekar, Mamunur Rashid, Reza Mehvar

Pharmacy Faculty Articles and Research

Midazolam (MDZ), a benzodiazepine derivative, is metabolized to 1′- and 4-hydroxylated metabolites (1′-OH-MDZ and 4-OH-MDZ, respectively) by cytochrome P450 3A (CYP3A). The purpose of this study was to investigate the CYP3A-mediated hydroxylation of MDZ in the rat brain mitochondria (MT). Brain microsomes (MC) and MT fractions were prepared from rats (n = 8) using differential and density gradient centrifugations, and the purity of the fractions was evaluated using VDAC1 and calreticulin as markers of MT and MC, respectively. The formation rates of 1′-OH-MDZ and 4-OH-MDZ in the rat brain MC and MT samples were determined using an LC–MS/MS method …

Planning System For The Optimization Of Electric Field Delivery Using Implanted Electrodes For Brain Tumor Control, Erin Iredale, Brynn Voigt, Adam Rankin, Kyungho W Kim, Jeff Z Chen, Susanne Schmid, Matthew O Hebb, Terry M Peters, Eugene Wong

Anatomy and Cell Biology Publications

BACKGROUND: The use of non-ionizing electric fields from low-intensity voltage sources (< 10 V) to control malignant tumor growth is showing increasing potential as a cancer treatment modality. A method of applying these low-intensity electric fields using multiple implanted electrodes within or adjacent to tumor volumes has been termed as intratumoral modulation therapy (IMT).

PURPOSE: This study explores advancements in the previously established IMT optimization algorithm, and the development of a custom treatment planning system for patient-specific IMT. The practicality of the treatment planning system is demonstrated by implementing the full optimization pipeline on a brain phantom with robotic electrode implantation, postoperative imaging, and treatment stimulation.

METHODS: The integrated planning pipeline in 3D Slicer begins with importing and segmenting patient magnetic resonance images (MRI) or computed tomography (CT) images. The segmentation process is manual, followed by a semi-automatic smoothing step that allows …

Resistance Training Improves White Matter Structural Connectivity In Older Adults At-Risk For Cognitive Decline, Ryu Lien

Undergraduate Student Research Internships Conference

Diabetes is a global health concern that impacts 415 million people worldwide. Individuals who are at-risk for diabetes (characterized by high blood glucose and/or being overweight) have white matter atrophy, decreased cognitive function, and an increased risk of Alzheimer’s disease (AD). Recently, resistance training (RT) has been shown to lower white matter atrophy and white matter lesion volume. However, investigating changes in white matter tracts is complex, hence previous findings remain inconclusive. Diffusion tensor imaging (DTI) serves as a highly sensitive tool that enables visualization and characterization of white matter tracts and has the potential to combat this complexity. The …

Novel App Knock-In Mouse Model Shows Key Features Of Amyloid Pathology And Reveals Profound Metabolic Dysregulation Of Microglia., Dan Xia, Steve Lianoglou, Thomas Sandmann, Meredith Calvert, Jung H Suh, Elliot Thomsen, Jason Dugas, Michelle E Pizzo, Sarah L Devos, Timothy K Earr, Chia-Ching Lin, Sonnet Davis, Connie Ha, Amy Wing-Sze Leung, Hoang Nguyen, Roni Chau, Ernie Yulyaningsih, Isabel Lopez, Hilda Solanoy, Shababa T Masoud, Chun-Chi Liang, Karin Lin, Giuseppe Astarita, Nathalie Khoury, Joy Yu Zuchero, Robert G Thorne, Kevin Shen, Stephanie Miller, Jorge J Palop, Dylan Garceau, Michael Sasner, Jennifer D Whitesell, Julie A Harris, Selina Hummel, Johannes Gnörich, Karin Wind, Lea Kunze, Artem Zatcepin, Matthias Brendel, Michael Willem, Christian Haass, Daniel Barnett, Till S Zimmer, Anna G Orr, Kimberly Scearce-Levie, Joseph W Lewcock, Gilbert Di Paolo, Pascal E Sanchez

Faculty Research 2022

BACKGROUND: Genetic mutations underlying familial Alzheimer's disease (AD) were identified decades ago, but the field is still in search of transformative therapies for patients. While mouse models based on overexpression of mutated transgenes have yielded key insights in mechanisms of disease, those models are subject to artifacts, including random genetic integration of the transgene, ectopic expression and non-physiological protein levels. The genetic engineering of novel mouse models using knock-in approaches addresses some of those limitations. With mounting evidence of the role played by microglia in AD, high-dimensional approaches to phenotype microglia in those models are critical to refine our understanding …

Ciliogenesis Mechanisms Mediated By Pak2-Arl13b Signaling In Brain Endothelial Cells Is Responsible For Vascular Stability, Karthikeyan Thirugnanam, Shubhangi Prabhudesai, Emma Van Why, Amy Pan, Ankan Gupta, Koji Foreman, Rahima Zennadi, Kevin R. Rarick, Surya M. Nauli, Sean P. Palacek, Ramani Ramchandran

Pharmacy Faculty Articles and Research

In the developing vasculature, cilia, microtubule-based organelles that project from the apical surface of endothelial cells (ECs), have been identified to function cell autonomously to promote vascular integrity and prevent hemorrhage. To date, the underlying mechanisms of endothelial cilia formation (ciliogenesis) are not fully understood. Understanding these mechanisms is likely to open new avenues for targeting EC-cilia to promote vascular stability. Here, we hypothesized that brain ECs ciliogenesis and the underlying mechanisms that control this process are critical for brain vascular stability. To investigate this hypothesis, we utilized multiple approaches including developmental zebrafish model system and primary cell culture systems. …

Musmorph, A Database Of Standardized Mouse Morphology Data For Morphometric Meta-Analyses., Jay Devine, Marta Vidal-García, Wei Liu, Amanda Neves, Lucas D Lo Vercio, Rebecca M Green, Heather A Richbourg, Marta Marchini, Colton M Unger, Audrey C Nickle, Bethany Radford, Nathan M Young, Paula N Gonzalez, Robert E Schuler, Alejandro Bugacov, Campbell Rolian, Christopher J Percival, Trevor Williams, Lee Niswander, Anne L Calof, Arthur D Lander, Axel Visel, Frank R Jirik, James M Cheverud, Ophir D Klein, Ramon Y Birnbaum, Amy E Merrill, Rebecca R Ackermann, Daniel Graf, Myriam Hemberger, Wendy Dean, Nils D Forkert, Stephen A. Murray, Henrik Westerberg, Ralph S Marcucio, Benedikt Hallgrímsson

Faculty Research 2022

Complex morphological traits are the product of many genes with transient or lasting developmental effects that interact in anatomical context. Mouse models are a key resource for disentangling such effects, because they offer myriad tools for manipulating the genome in a controlled environment. Unfortunately, phenotypic data are often obtained using laboratory-specific protocols, resulting in self-contained datasets that are difficult to relate to one another for larger scale analyses. To enable meta-analyses of morphological variation, particularly in the craniofacial complex and brain, we created MusMorph, a database of standardized mouse morphology data spanning numerous genotypes and developmental stages, including E10.5, E11.5, …

Impact Forces And Patterns Of Axonal Injury Differ Between Two Models Of Tbi, Edward Lai, David M Devilbiss

Rowan-Virtua Research Day

Traumatic brain injury (TBI) affects approximately 3.8 million Americans a year and results in complex neuropathological and neurocognitive sequelae. Animal models of TBI attempt to replicate the impact forces and pathology of injury in humans. However, in these models, the forces generated at the time of impact are poorly understood. Nonetheless, a variety of shear and strain forces generated at the time of impact can produce diffuse axonal injury. Injury to axons and neurons across a variety of brain regions resulting from axonal injury underlies the cognitive and behavioral impairments observed after TBI. Three critical brain regions, the corpus callosum …

Translational Approaches To Understanding Resilience To Alzheimer's Disease., Sarah M Neuner, Maria Telpoukhovskaia, Vilas Menon, Kristen M S O'Connell, Timothy J Hohman, Catherine Kaczorowski

Faculty Research 2022

Individuals who maintain cognitive function despite high levels of Alzheimer's disease (AD)-associated pathology are said to be 'resilient' to AD. Identifying mechanisms underlying resilience represents an exciting therapeutic opportunity. Human studies have identified a number of molecular and genetic factors associated with resilience, but the complexity of these cohorts prohibits a complete understanding of which factors are causal or simply correlated with resilience. Genetically and phenotypically diverse mouse models of AD provide new and translationally relevant opportunities to identify and prioritize new resilience mechanisms for further cross-species investigation. This review will discuss insights into resilience gained from both human and …

Optical Illusions To Schizophrenic Delusions: How Your Brain Can Alter Reality, Kathryn Stanislaski

Honors College

Widely misunderstood, stigmatized and understudied, schizophrenia is often misdiagnosed and incorrectly treated. While people diagnosed with schizophrenia are often thought to misinterpret reality, they may be more adept at processing visual sensory information and perceive reality better than those without schizophrenia. Studies involving patients with schizophrenia have shown consistent and extensive insusceptibility of these patients to a variety of optical illusions. In this paper, I propose that when processing visual information, people with schizophrenia rely greater upon the dorsal stream and areas in the brain associated with bottom-up processing, as opposed to those without schizophrenia that utilize the ventral stream …

Genome-Wide Variant Calling In Reanalysis Of Exome Sequencing Data Uncovered A Pathogenic Tubb3 Variant., Elke De Boer, Burcu Yaldiz, Anne-Sophie Denommé-Pichon, Leslie Matalonga, Steve Laurie, Solve-Rd Snv-Indel Working Group, Daniel Danis, Peter N Robinson, Solve-Rd-Ditf Ithaca

Faculty Research 2022

Almost half of all individuals affected by intellectual disability (ID) remain undiagnosed. In the Solve-RD project, exome sequencing (ES) datasets from unresolved individuals with (syndromic) ID (n = 1,472 probands) are systematically reanalyzed, starting from raw sequencing files, followed by genome-wide variant calling and new data interpretation. This strategy led to the identification of a disease-causing de novo missense variant in TUBB3 in a girl with severe developmental delay, secondary microcephaly, brain imaging abnormalities, high hypermetropia, strabismus and short stature. Interestingly, the TUBB3 variant could only be identified through reanalysis of ES data using a genome-wide variant calling approach, despite …

Regulation Of Brain Primary Cilia Length By Mch Signaling: Evidence From Pharmacological, Genetic, Optogenetic, And Chemogenic Manipulations, Wedad Alhassen, Yuki Kobayashi, Jessica Su, Brianna Robbins, Henry Nguyen, Thant Myint, Micah Yu, Surya M. Nauli, Yumiko Saito, Amal Alachkar

Pharmacy Faculty Articles and Research

The melanin-concentrating hormone (MCH) system is involved in numerous functions, including energy homeostasis, food intake, sleep, stress, mood, aggression, reward, maternal behavior, social behavior, and cognition. In rodents, MCH acts on MCHR1, a G protein-coupled receptor, which is widely expressed in the brain and abundantly localized to neuronal primary cilia. Cilia act as cells’ antennas and play crucial roles in cell signaling to detect and transduce external stimuli to regulate cell differentiation and migration. Cilia are highly dynamic in terms of their length and morphology; however, it is not known if cilia length is causally regulated by MCH system activation …

Uplc-Ms/Ms Analysis Of The Michaelis-Menten Kinetics Of Cyp3a-Mediated Midazolam 1′- And 4-Hydroxylation In Rat Brain Microsomes, Devaraj Venkatapura Chandrashekar, Barent Dubois, Reza Mehvar

Pharmacy Faculty Articles and Research

Midazolam (MDZ) is a short-acting benzodiazepine with rapid onset of action, which is metabolized by CYP3A isoenzymes to two hydroxylated metabolites, 1′-hydroxymidazolam and 4-hydroxymidazolam. The drug is also commonly used as a marker of CYP3A activity in the liver microsomes. However, the kinetics of CYP3A-mediated hydroxylation of MDZ in the brain, which contains much lower CYP content than the liver, have not been reported. In this study, UPLC-MS/MS and metabolic incubation methods were developed and validated for simultaneous measurement of low concentrations of both hydroxylated metabolites of MDZ in brain microsomes. Different concentrations of MDZ (1–500 µM) were incubated with …

Homozygous Mtap Deletion In Primary Human Glioblastoma Is Not Associated With Elevation Of Methylthioadenosine., Yasaman Barekatain, Jeffrey J Ackroyd, Victoria C Yan, Sunada Khadka, Lin Wang, Ko-Chien Chen, Anton H Poral, Theresa Tran, Dimitra K Georgiou, Kenisha Arthur, Yu-Hsi Lin, Nikunj Satani, Elliot S Ballato, Eliot I Behr, Ana C Decarvalho, Roel G W Verhaak, John De Groot, Jason T Huse, John M Asara, Raghu Kalluri, Florian L Muller

Faculty Research 2021

Homozygous deletion of methylthioadenosine phosphorylase (MTAP) in cancers such as glioblastoma represents a potentially targetable vulnerability. Homozygous MTAP-deleted cell lines in culture show elevation of MTAP's substrate metabolite, methylthioadenosine (MTA). High levels of MTA inhibit protein arginine methyltransferase 5 (PRMT5), which sensitizes MTAP-deleted cells to PRMT5 and methionine adenosyltransferase 2A (MAT2A) inhibition. While this concept has been extensively corroborated in vitro, the clinical relevance relies on exhibiting significant MTA accumulation in human glioblastoma. In this work, using comprehensive metabolomic profiling, we show that MTA secreted by MTAP-deleted cells in vitro results in high levels of extracellular MTA. We further demonstrate …

Christianity And Fear: The Neuropsychological Processes Involved In The Relationship Between Fear And Religion, Courtney Welch-Horstman

Obsculta

Religion frames the lives and minds of individuals who practice the Christian faith. Regarding the mind, this statement can be understood both figuratively and literally. The thought processes of human beings who claim to believe in God are strongly influenced by their perspective of Deity and what they think God's primary characteristic is. While some view God as loving, others view God as mainly angry and punishing. The way this question is answered by an individual reveals much about his or her neurocircuitry and which brain structures are most active and developed. These circuits and structures then impact the behaviors …

Medical Schools Ignore The Nature Of Consciousness At Great Cost, Anoop Kumar

Journal of Wellness

The essential question of the relationship between consciousness and matter is ignored in medical school curricula, leading to a machine-like view of the human being that contributes to physician burnout and intellectual dissatisfaction. The evidence suggesting that the brain may not be the seat of consciousness is generally ignored to preserve the worldview of the primacy of matter. By investigating new frameworks detailing the nature of consciousness at different levels of hierarchy, we can bring intellectual rigor to a once opaque subject that supports a fundamental reality about our experience: We are human beings, not only human bodies.

Insects Provide Unique Systems To Investigate How Early-Life Experience Alters The Brain And Behavior, Rebecca R. Westwick, Clare C. Rittschof

Entomology Faculty Publications

Early-life experiences have strong and long-lasting consequences for behavior in a surprising diversity of animals. Determining which environmental inputs cause behavioral change, how this information becomes neurobiologically encoded, and the functional consequences of these changes remain fundamental puzzles relevant to diverse fields from evolutionary biology to the health sciences. Here we explore how insects provide unique opportunities for comparative study of developmental behavioral plasticity. Insects have sophisticated behavior and cognitive abilities, and they are frequently studied in their natural environments, which provides an ecological and adaptive perspective that is often more limited in lab-based vertebrate models. A range of cues, …

Creatine Supplementation On Cognitive Performance Following Exercise In Female Muay Thai Athletes, Lawert A.M. Pires, Scott C. Forbes, Darren G. Candow, Marco Machado

Journal for Sports Neuroscience

BACKGROUND: Creatine supplementation has some beneficial effects on cognitive processing in healthy adults, including athletes; however the effects on cognitive function following exhaustive exercise in athletes is unknown. Therefore, the purpose was to determine the effects of 28 days of creatine supplementation on tasks of cognitive performance immediately following exhaustive exercise in Muay Thai female athletes compared to placebo. METHODS: Using a repeated measures, double-blind, placebo controlled design, 26 female Muay Thai athletes (age: 26 ± 5 years; body mass: 65.1 ± 6.6 kg; height: 162 ± 5 cm; training experience: 2.6 ± 0.6 years) were randomized to supplement with …

Open Neuroscience Initiative, Austin Lim

College of Science and Health Full Text Publications

The Open Neuroscience Initiative is a free-to-use textbook

This project began as a means to overcoming the financial burden that face undergraduate neuroscience students when buying textbooks. By compiling and writing a completely free-to-access textbook that covers the foundations of a typical college introduction to neuroscience course, students would have one less obstacle to overcome in their educational career, allowing them to focus their valuable time and attention on learning rather than finances. To make this project a reality, I began with a humble tweet in May 2019 that managed to gain a tiny bit of traction among the neuroscience …

Cortical Iron Disrupts Functional Connectivity Networks Supporting Working Memory Performance In Older Adults, Valentinos Zachariou, Christopher E. Bauer, Elayna R. Seago, Flavius D. Raslau, David K. Powell, Brian T. Gold

Neuroscience Faculty Publications

Excessive brain iron negatively affects working memory and related processes but the impact of cortical iron on task-relevant, cortical brain networks is unknown. We hypothesized that high cortical iron concentration may disrupt functional circuitry within cortical networks supporting working memory performance. Fifty-five healthy older adults completed an N-Back working memory paradigm while functional magnetic resonance imaging (fMRI) was performed. Participants also underwent quantitative susceptibility mapping (QSM) imaging for assessment of non-heme brain iron concentration. Additionally, pseudo continuous arterial spin labeling scans were obtained to control for potential contributions of cerebral blood volume and structural brain images were used to control …

Molecular Estimation Of Neurodegeneration Pseudotime In Older Brains., Sumit Mukherjee, Laura Heath, Christoph Preuss, Suman Jayadev, Gwenn A Garden, Anna K Greenwood, Solveig K Sieberts, Philip L De Jager, Nilüfer Ertekin-Taner, Gregory W. Carter, Lara M Mangravite, Benjamin A Logsdon

Faculty Research 2020

The temporal molecular changes that lead to disease onset and progression in Alzheimer's disease (AD) are still unknown. Here we develop a temporal model for these unobserved molecular changes with a manifold learning method applied to RNA-Seq data collected from human postmortem brain samples collected within the ROS/MAP and Mayo Clinic RNA-Seq studies. We define an ordering across samples based on their similarity in gene expression and use this ordering to estimate the molecular disease stage-or disease pseudotime-for each sample. Disease pseudotime is strongly concordant with the burden of tau (Braak score, P = 1.0 × 10-5), Aβ (CERAD score, …

Visual Corticocortical Inputs To Ferret Area 18, Reem Khalil, Moody Roberne Jensy Saint Louis, Shaima Alsuwaidi, Jonathan B. Levitt

Publications and Research

Visual cortical areas in the adult mammalian brain are linked by a network of interareal feedforward and feedback circuits. We investigated the topography of feedback projections to ferret (Mustela putorius furo) area 18 from extrastriate areas 19, 21, and Ssy. Our objective was to characterize the anatomical organization of the extrastriate feedback pool to area 18. We also wished to determine if feedback projections to area 18 share similar features as feedback projections to area 17. We injected the tracer cholera toxin B subunit (CTb) into area 18 of adult ferrets to visualize the distribution and pattern of retrogradely labeled …

The Raphe-Hippocampal Tract And Its Age Differences: Diffusion Tensor Imaging And Probabilistic Tractography Study, Ashley Sekul

Honors Theses

The raphe-hippocampal tract links the raphe nuclei to the hippocampus and is responsible for the production of the neurotransmitter serotonin. The hippocampus is key in regulating emotional and stress responses. This study utilized diffusion tensor imaging which uses Functional Magnetic Resonance Imaging to provide scans of the brain for analyzing differences in the raphe-hippocampal tract as one ages. In this specific study, 491 samples were visually analyzed to gather data about the fractional anisotropy of the raphe nuclei in both male and female brains ranging from 6 to 85 years old. Through the ranking of images, some were discarded, and …