Neuroscience and Neurobiology Commons^™

Influence Of Demographic, Clinical, And Neuroimaging Variables On Neuropsychological Recovery Trajectories After Moderate-To-Severe Traumatic Brain Injury, Elizabeth J. Leif

Dissertations, Theses, and Capstone Projects

Traumatic brain injury (TBI) is prevalent in people of all ages and all walks of life. Cognitive deficits are common after TBI and the recovery patterns are known to be variable across individuals. The current study investigates diffuse axonal injury (DAI), cerebral blood flow (CBF), and focal lesions, in addition to post-traumatic amnesia (PTA), as possible predictors of cognitive trajectory in moderate-to-severe TBI patients. Cognitive trajectory was evaluated with a battery of neuropsychological tests that were combined into three domains: processing speed, verbal learning, and executive function. Patients (N=44) were tested three times at 3, 6, and 12 months post-injury. …

Third Harmonic Generation: A Method For Visualizing Myelin In The Murine Cerebral Cortex, Michael Redlich

Dissertations, Theses, and Capstone Projects

Here we present the use of Third Harmonic Generation (THG) for the label-free imaging of myelinated axons in the murine cerebral cortex. Myelin plays an important role in the processes of learning and disease. However, much of the myelin biology research thus far has focused on white matter tracts where myelin is more visible. Much is still unknown, particularly with regard to myelin in gray matter. First, we engage in THG microscopy using an optical parametric oscillator pumped by a titanium-sapphire laser to demonstrate the utility of the technique for imaging myelin in vivo. Second, we investigate the use of …

The Zebrafish Visual System Transmits Dimming Information Via Multiple Segregated Pathways, Estuardo Robles, Nicholas P. Fields, Herwig Baier

Neuroscience: Faculty Publications

Vertebrate retinas contain circuits specialized to encode light level decrements. This information is transmitted to the brain by dimming-sensitive OFF retinal ganglion cells (OFF-RGCs) that respond to light decrements with increased firing. It is known that OFF-RGCs with distinct photosensitivity profiles form parallel visual channels to the vertebrate brain, yet how these channels are processed by first- and higher order brain areas has not been well characterized in any species. To address this question in the larval zebrafish visual system, we examined the visual response properties of a genetically identified population of tectal neurons with a defined axonal projection to …

White-Matter Tract Connecting Anterior Insula To Nucleus Accumbens Predicts Greater Future Motivation In Adolescents, Josiah K. Leong, Tiffany C. Ho, Natalie L. Colich, Lucinda Sisk, Brian Knutson, Ian H. Gotlib

Psychological Science Faculty Publications and Presentations

The motivation to approach or avoid incentives can change during adolescence. Advances in neuroimaging allow researchers to characterize specific brain circuits that underlie these developmental changes. Whereas activity in the nucleus accumbens (NAcc) can predict approach toward incentive gain, activity in anterior insula (AIns) is associated with avoidance of incentive loss. Recent research characterized the structural white-matter tract connecting the two brain regions, but the tract has neither been characterized in adolescence nor linked to functional activity during incentive anticipation. In this study, we collected diffusion MRI and characterized the tract connecting the AIns to the NAcc for the first …

Effects Of Mindfulness Meditation On Selective, Sustained Attention, Brain Neural Oscillations, And Short-Term Memory, Anamaria Guzman

Honors Program: Senior Projects (Public)

The following extended literature review and research proposal study started initially as a complete research proposal but, due to the challenges COVID-19 has brought, it has become a stand-alone piece of work without data collection. The goal is to synthesize a broad range of literature and previous research on mindfulness meditation and its effects on attention, memory, and brain activity and thus, offering a new perspective and a proposed research path on this subject. This proposed research study, besides previous studies, indicates that mindfulness meditation is expected to improve and enhance selective and sustained attention, which results in better attentional …

Cognitive Changes Caused By Lps-Induced Neuroinflammation, Nancy De La Torre

Dissertations, Theses, and Capstone Projects

The brain performs cognitive processes finely orchestrated by timely precise action of neurons. Neurons functioning at their highest standard communicate with each other through perfectly functioning synapses. Microglia, as part of the immune system assist synaptic processing and have the ability to affect cognition. Indeed, microglia play a role in cognition. To investigate the link between microglia and cognition we utilized lipopolysaccharide (LPS) to pharmacologically activate microglia. LPS, normally present in the environment on the wall of Gram-negative bacteria is a pharmacological agent used to cause microglia activation in mice. LPS is a typical model to study changes induced by …

Caffeine Modulation Of Attention And Focus In Task Performance, Claudia R. Berger

Dissertations, Theses, and Capstone Projects

Caffeine has been a heavily researched drug for decades given its prevalence in global consumption, as well as its large impacts on metabolic and executive function research alike. The present study aims to combine a behavioral study (Experiment 1) with a feasibility study (Experiment 2) to test the impacts of variable caffeine consumption on task performance. For both studies, participants filled out a questionnaire regarding caffeine use. Experiment 1 examined whether caffeine modulated attention in an online behavioral task in which participants were asked to identify a target (e.g., female “ahpa”). Participants were tested twice once after consuming 12 ounces …

Changes In The Gut Microbiome Following Traumatic Stress Exposure In A Mouse Model Of Post-Traumatic Stress Disorder (Ptsd), Rebecca Schultz, Veronica Piggott, Alana C. Conti

Medical Student Research Symposium

Posttraumatic stress disorder (PTSD) can occur following exposure to extreme adverse events, affecting 6.8% of adult Americans. There is a positive correlation between PTSD and gastrointestinal (GI) pain and upset, with the origin of these GI issues attributed to bacterial changes in the gut microbiome. Animal studies have shown a relationship between stress and GI dysfunction, leading to increased systemic lipopolysaccharide (LPS) levels, which have been linked to neuroinflammation and cognitive impairment. The bidirectional and complex communication between microbiota and the brain is not fully understood and therefore would benefit from further experimental studies. Therefore, the goal of my project …

Regional N-Glycan And Lipid Analysis From Tissues Using Maldi-Mass Spectrometry Imaging, Alexandra E. Stanback, Lindsey R. Conroy, Lyndsay E. A. Young, Tara R. Hawkinson, Kia H. Markussen, Harrison A. Clarke, Derek B. Allison, Ramon C. Sun

Neuroscience Faculty Publications

N-glycans and lipids are structural metabolites that play important roles in cellular processes. Both show unique regional distribution in tissues; therefore, spatial analyses of these metabolites are crucial to our understanding of cellular physiology. Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) is an innovative technique that enables in situ detection of analytes with spatial distribution. This workflow details a MALDI-MSI protocol for the spatial profiling of N-glycans and lipids from tissues following application of enzyme and MALDI matrix.

For complete details on the use and execution of this protocol, please refer to Drake et al. (2018) and Andres et al. (2020).

Survey Of Prevention And Intervention Strategies Reducing Return To Play Post-Concussion In Division 1 Football, Joseph F. Clark, Enna Selmanovic, Kip Drewry, Jon Vincent, Aaron Himmler, Bob Mangine, Kim Hasselfeld, Jane Khoury, David Polanski, Jon Divine

Journal for Sports Neuroscience

Abstract.

Introduction

Sports related concussion, also considered mTBI, has remained in the public eye due to heightened fear concerning playing football and other collision based sports. Concussion prevention, as well as rehabilitating the brain after a concussion, is a high priority for many sports medical practitioners as well as for athletes. For these reasons, researchers associated with the American Athletic Conference (AAC) have surveyed concussion incidence in football. One of the AAC teams engaged in regular neurovisual training (NVT) and concluded this training program is associated with faster return to play post-injury in this observational cohort study.

Methods

The …

Next-Generation Diamond Electrodes For Neurochemical Sensing: Challenges And Opportunities, Erin K. Purcell, Michael F. Becker, Yue Guo, Seth A. Hara, Kip A. Ludwig, Collin J. Mckinney, Elizabeth M. Monroe, Robert Rechenberg, Cory A. Rusinek, Akash Saxena, James R. Siegenthaler, Caryl E. Sortwell, Cort H. Thompson, James K. Trevathan, Suzanne Witt, Wen Li

Chemistry and Biochemistry Faculty Research

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. Carbon-based electrodes combined with fast-scan cyclic voltammetry (FSCV) enable neurochemical sensing with high spatiotemporal resolution and sensitivity. While their attractive electrochemical and conductive properties have established a long history of use in the detection of neurotransmitters both in vitro and in vivo, carbon fiber microelectrodes (CFMEs) also have limitations in their fabrication, flexibility, and chronic stability. Diamond is a form of carbon with a more rigid bonding structure (sp3-hybridized) which can become conductive when boron-doped. Boron-doped diamond (BDD) is characterized by an extremely wide potential window, low background current, and good …

An Objective Method To Assess And Recommend Exertion And Exercise Targets For Return To Play Post Concussion, Joseph F. Clark Phd Atc, Robert E. Mangine Pt Med Atc, Kimberly A. Hasselfeld Ms, Violet T. Schramm, Angelo J. Colosimo Md, Aaron Kuehn-Himmler At Ms, Gerald M. Holloway Ms Atc, Faniel Fosselman Do Mba, Jon Vincent, Nicole Giordano, Jon G. Divine Md Ms

Journal for Sports Neuroscience

Introduction.

Concussions are of significant concern for athletic trainers, and there is a critical need to objectively and safely allow an athlete to return to play. In sports the objective is return as safely and soon as possible. Exertion is a consideration regarding progressing an athlete back to play. The ability to exert in cardiovascular and strength and conditioning contexts are two critical steps in most return to play protocols. Being able to make objective recommendations is urgently needed, as trial and error leads to unnecessary risk of eliciting symptoms and/or causing setbacks.

Objective.

The object of this paper is …

Behavioral Arrest And A Characteristic Slow Waveform Are Hallmark Responses To Selective 5-Ht2a Receptor Activation, April Contreras, Matthew Khumnark, Rochelle M. Hines, Dustin J. Hines

Psychology Faculty Research

© 2021, The Author(s). Perception, emotion, and mood are powerfully modulated by serotonin receptor (5-HTR) agonists including hallucinogens. The 5-HT2AR subtype has been shown to be central to hallucinogen action, yet the precise mechanisms mediating the response to 5-HT2AR activation remain unclear. Hallucinogens induce the head twitch response (HTR) in rodents, which is the most commonly used behavioral readout of hallucinogen pharmacology. While the HTR provides a key behavioral signature, less is known about the meso level changes that are induced by 5-HT2AR activation. In response to administration of the potent and highly selective 5-HT2AR agonist 25I-NBOH in mice, we …

A Pathogenic Ufsp2 Variant In An Autosomal Recessive Form Of Pediatric Neurodevelopmental Anomalies And Epilepsy, Min Ni, Bushra Afroze, Chao Xing, Chunxiao Pan, Yanqiu Shao, Ling Cai, Brandi L. Cantarel, Jimin Pei, Nick V. Grishin, Stacy Hewson

Department of Paediatrics and Child Health

Purpose: Neurodevelopmental disabilities are common and genetically heterogeneous. We identified a homozygous variant in the gene encoding UFM1-specific peptidase 2 (UFSP2), which participates in the UFMylation pathway of protein modification. UFSP2 variants are implicated in autosomal dominant skeletal dysplasias, but not neurodevelopmental disorders. Homozygosity for the variant occurred in eight children from four South Asian families with neurodevelopmental delay and epilepsy. We describe the clinical consequences of this variant and its effect on UFMylation.
Methods: Exome sequencing was used to detect potentially pathogenic variants and identify shared regions of homozygosity. Immunoblotting assessed protein expression and post-translational modifications in patient-derived fibroblasts. …

Prediction Of Alzheimer’S Disease-Specific Phospholipase C Gamma-1 Snv By Deep Learning-Based Approach For High-Throughput Screening, Sung Hyun Kim, Sumin Yang, Key Hwan Lim, Euiseng Ko, Hyun Jun Jang, Mingon Kang, Pann Ghill Suh, Jae Yeol Joo

Computer Science Faculty Research

© 2021 National Academy of Sciences. All rights reserved. Exon splicing triggered by unpredicted genetic mutation can cause translational variations in neurodegenerative disorders. In this study, we discover Alzheimer’s disease (AD)-specific single-nucleotide variants (SNVs) and abnormal exon splicing of phospholipase c gamma-1 (PLCγ1) gene, using genome-wide association study (GWAS) and a deep learning-based exon splicing prediction tool. GWAS revealed that the identified single-nucleotide variations were mainly distributed in the H3K27ac-enriched region of PLCγ1 gene body during brain development in an AD mouse model. A deep learning analysis, trained with human genome sequences, predicted 14 splicing sites in human PLCγ1 gene, …

Nmda Receptors Enhance The Fidelity Of Synaptic Integration, Chenguang Li, Allan Gulledge

Dartmouth Scholarship

Excitatory synaptic transmission in many neurons is mediated by two coexpressed ionotropic glutamate receptor subtypes, AMPA and NMDA receptors, that differ in kinetics, ion selectivity, and voltage-sensitivity. AMPA receptors have fast kinetics and are voltage-insensitive, while NMDA receptors have slower kinetics and increased conductance at depolarized membrane potentials. Here, we report that the voltage dependency and kinetics of NMDA receptors act synergistically to stabilize synaptic integration of EPSPs across spatial and volt- age domains. Simulations of synaptic integration in simplified and morphologically realistic dendritic trees re- vealed that the combined presence of AMPA and NMDA conductances reduce the variability of …

Practical Recommendations For Timely, Accurate Diagnosis Of Symptomatic Alzheimer’S Disease (Mci And Dementia) In Primary Care: A Review And Synthesis, J. L. Liss, S. Seleri Assunção, Jeffrey Cummings, A. Atri, D. S. Geldmacher, S. F. Candela, D. P. Devanand, H. M. Fillit, J. Susman, J. Mintzer, T. Bittner, S. A. Brunton, D. R. Kerwin, W. C. Jackson, G. W. Small, G. T. Grossberg, C. K. Clevenger, V. Cotter, R. Stefanacci, A. Wise-Brown, M. N. Sabbagh

School of Medicine Faculty Research

The critical role of primary care clinicians (PCCs) in Alzheimer’s disease (AD) prevention, diagnosis and management must evolve as new treatment paradigms and disease-modifying therapies (DMTs) emerge. Our understanding of AD has grown substantially: no longer conceptualized as a late-in-life syndrome of cognitive and functional impairments, we now recognize that AD pathology builds silently for decades before cognitive impairment is detectable. Clinically, AD first manifests subtly as mild cognitive impairment (MCI) due to AD before progressing to dementia. Emerging optimism for improved outcomes in AD stems from a focus on preventive interventions in midlife and timely, biomarker-confirmed diagnosis at early …

Oligodendroglial Epigenetics, From Lineage Specification To Activity-Dependent Myelination, Mathilde Mathilde Pruvost, Sarah Moyon

Advanced Science Research Center

Oligodendroglial cells are the myelinating cells of the central nervous system. While myelination is crucial to axonal activity and conduction, oligodendrocyte progenitor cells and oligodendrocytes have also been shown to be essential for neuronal support and metabolism. Thus, a tight regulation of oligodendroglial cell specification, proliferation, and myelination is required for correct neuronal connectivity and function. Here, we review the role of epigenetic modifications in oligodendroglial lineage cells. First, we briefly describe the epigenetic modalities of gene regulation, which are known to have a role in oligodendroglial cells. We then address how epigenetic enzymes and/or marks have been associated with …

Neural Coding And Organization Principles In The Drosophila Olfactory System, Haoyang Rong

McKelvey School of Engineering Graduate Student Theses & Dissertations

Sensory systems receive and process external stimuli to allow an organism to perceive and react to the environment. How is sensory information subsequently represented, transformed, and interpreted in the neural system? In this dissertation, I have investigated this fundamental question using the fruit fly (Drosophila melanogaster) olfactory system.Chemical cues are transduced into neural signals in the insect antenna by the olfactory receptor neurons (ORNs). The ORNs send their axons to the antennal lobe (AL), with each ORN type innervating a specific neuropil (glomerulus), where they synapse onto excitatory and inhibitory projection neurons (ePNs and iPNs). The ePNs project their axons …

Constructing And Analyzing Neural Network Dynamics For Information Objectives And Working Memory, Elham Ghazizadeh Ahsaei

McKelvey School of Engineering Graduate Student Theses & Dissertations

Creation of quantitative models of neural functions and discovery of underlying principles of how neural circuits learn and compute are long-standing challenges in the field of neuroscience. In this work, we blend ideas from computational neuroscience, information and control theories with machine learning to shed light on how certain key functions are encoded through the dynamics of neural circuits. In this regard, we pursue the ‘top-down’ modeling approach of engineering neuroscience to relate brain functions to basic generative dynamical mechanisms. Our approach encapsulates two distinct paradigms in which ‘function’ is understood. In the first part of this research, we explore …