Neurosciences Commons^™

Molecular Target And Circuitry Underlying The Preclinical Effects Of Psychedelics In Models Of Opioid Use Disorder, Alaina M. Jaster

Theses and Dissertations

Opioid use disorder (OUD), like other substance use disorders (SUD), is characterized by maladaptive behavioral allocation away from other rewarding aspects of life following prolonged use, as well as large rates of relapse. While pharmacotherapies exist for OUD, they tend to only target the opioid receptors rather than the underlying mechanisms behind the maladaptive behaviors. Serotonin (5-hydroxytryptamine; 5-HT) is involved in modulation of cravings and regulation of motivational reward-related behaviors, thought to be due to a top-down processing method of external and internal stimuli. Serotonin 2A receptors (5-HT_2AR) are widespread throughout the brain and most densely populate layer …

Vulnerability And Adaptation Of Neocortical Neuron Subtypes In Models Of Concussive Traumatic Brain Injury And Multiple Sclerosis, Alan C. Harris Jr.

Theses and Dissertations

The pathognomonic sequela of traumatic brain injury is traumatic axonal injury, the

burden of which correlates with less favorable outcomes. Elucidation of

the intrinsic variables that endow delineated neuronal subgroups and microanatomical domains with outsized vulnerability to injury represents a critical domain of inquiry toward the successful translation of disease-modifying therapeutics. To this end, we studied mild traumatic brain injury (mTBI) within the central fluid percussion model to examine the consequences of mTBI on the morphology and functional integrity of the axon initial segment (AIS) and the relative contributions to network homeostasis mediated by distinct populations of inhibitory interneurons. One …

A Single-Case Alternating Treatments Design Utilzing Quantitative Electroencephalography To Observe And Measure Mental State Trends During Individual Participant Non-Nature-Based Small Initiative Adventure Therapy Experiences, Patrick Lane Robert Mcmillion

Graduate Research Theses & Dissertations

This single-case alternating-treatments design research study observed and measured mental state trends during the counseling approach known as Adventure Therapy (AT) using quantitative electroencephalography (qEEG). Participants wore a qEEG headset while participating in a multi-stage AT experience. Two problems were addressed in this study. The first was the lack of research in AT utilizing other empirical measures beyond subjective report surveys and the outcomes of specific programs. The second was the lack of neuroscientific measurement of counseling approaches and interventions within the field of counseling in general. There is a need for empirical evidence supporting AT to address access barriers …

Prenatal Ethanol Exposure Impairs Performance On Spatial And Tactile Sequential Discrimination Task In Juvenile Rats, Caleb S. Bailey

Theses and Dissertations--Psychology

Fetal alcohol spectrum disorders (FASDs) are a set of cognitive and behavioral abnormalities that arise in ~5% of children who have been prenatally-exposed to alcohol. Prenatal alcohol exposure (PAE) can cause impairments in learning acquisition, working memory, response inhibition, and attentional-set shifting that result in exaggerated deficits in executive function and impairments in goal-seeking behavior. There are standard procedures used in rodent research to address some components of these deficits, but few procedures are sensitive enough to comprehensively assess such deficits. To address this issue in FASDs research techniques, we developed a procedure that requires prolonged executive function in a …

Ethanol Decreases Expression Of Developing Neurons, But Not Neuronal Viability, In A Cultured Rat Hippocampus, Cassidy Count

Theses and Dissertations--Psychology

As of 2019, alcohol use disorders (AUDs) affect roughly 14.1 million individuals over the age of 18 and cost up to $249 billion in economic burden in the United States. In addition to central nervous system (CNS), those affected by AUDs can present with cognitive and behavioral abnormalities. Specifically, those affected by AUDs experience deficits in memory consolidation and retrieval as well as executive functioning, which may be due to cellular changes within the hippocampus. There are at least two prominent and contended theories which explain the mechanism of functional impairment caused by alcohol: 1) alcohol induces excitotoxic neuronal death …

Investigating The Viral Nature Of Neuronal Capsid Genes, Michael Manuel Long

Master's Theses

Memory formation is an essential part of everyday life. Neuronal communication is thought to be a key driver behind memory formation. There are two heavily studied methods of neuronal communication: chemical (neurotransmitter-mediated) and electrical (physically attached). When issues arise environmentally or genetically, people can experience one of many devastating memory disorders i.e. Alzheimer’s disease and other Dementias. Due to their prevalence, the treatments for disorders that hinder memory formation are a high priority for pharmaceutical companies. Currently, many of the treatments available focus on neurotransmitters or neuronal activity, and scientists are far from a cure. However, there may be an …

Preexisting Depression And Ambulatory Status After Stroke: Florida-Puerto Rico Collaboration To Reduce Stroke Disparities, Amy K Starosciak, Kefeng Wang, Hao Ying, Kaushik Ravipati, Samantha Spring, Carolina M Gutierrez, Hannah Gardener, David Z Rose, Dianne Foster, Chuanhui Dong, Angus Jameson, Ayham Alkhachroum, Jose G Romano, Ralph L Sacco, Tatjana Rundek, Negar Asdaghi

Faculty, Staff and Student Publications

OBJECTIVE: Stroke is a global public health burden, and therefore it is critical to identify modifiable risk factors to reduce stroke incidence and improve outcomes. Depression is such a risk factor; however, the association between preexisting depression and stroke outcomes, such as independent ambulation, is not well studied, especially among racial-ethnic minority groups. To address this gap in the literature, effects of preexisting depression on ambulatory status at hospital discharge after stroke were evaluated among individuals participating in the racially and ethnically diverse Florida-Puerto Rico Collaboration to Reduce Stroke Disparities project.

METHODS: Data were analyzed from a total of 42,031 …

A Comparison Of One Year Outcomes Between Standardized Locomotor Training And Usual Care After Motor Incomplete Spinal Cord Injury: Community Participation, Quality Of Life And Re-Hospitalization, Candace Tefertiller, Meghan Rozwod, Sandra Wojciehowski, Mitch Sevigny, Susan Charlifue, Jessica M Ketchum, Jeffrey Berliner, Heather B Taylor, Andrea L Behrman, Susan Harkema, Gail Forrest, Mary Schmidt Read, Michelle Basso

Faculty, Staff and Student Publications

CONTEXT/OBJECTIVE: Spinal cord injury (SCI) often results in a significant loss of mobility and independence coinciding with reports of decreased quality of life (QOL), community participation, and medical complications often requiring re-hospitalization. Locomotor training (LT), the repetition of stepping-like patterning has shown beneficial effects for improving walking ability after motor incomplete SCI, but the potential impact of LT on psychosocial outcomes has not been well-established. The purpose of this study was to evaluate one year QOL, community participation and re-hospitalization outcomes between individuals who participated in a standardized LT program and those who received usual care (UC).

DESIGN/SETTING/PARTICIPANTS: A retrospective …

Interpersonal Violence Against Women With Spinal Cord Injury: Adding Insult To Injury, Susan Robinson-Whelen, Rosemary B Hughes, Kimberley Aguillard, Diana Gonzalez, Heather B Taylor

Faculty, Staff and Student Publications

BACKGROUND: Mounting empirical evidence suggests that, compared to women without disabilities, women with disabilities are more likely to experience interpersonal violence (IPV). However, there is extremely limited research attention on IPV against women with spinal cord injury (SCI), a particularly understudied and underserved population.

OBJECTIVES: To conduct the first known examination of lifetime IPV experience in women with SCI, to explore demographic and disability-related correlates of IPV, and to examine the health impacts of IPV.

METHODS: The sample included 175 women with traumatic SCI from across the United States who enrolled in a randomized controlled trial of an online psychological …

Bacterial Meningitis In Africa, Tatiana Barichello, Carlos Henrique Rocha Catalão, Ursula K Rohlwink, Martijn Van Der Kuip, Dan Zaharie, Regan S Solomons, Ronald Van Toorn, Marceline Tutu Van Furth, Rodrigo Hasbun, Federico Iovino, Vivian Ssonko Namale

Faculty, Staff and Student Publications

Bacterial meningitis differs globally, and the incidence and case fatality rates vary by region, country, pathogen, and age group; being a life-threatening disease with a high case fatality rate and long-term complications in low-income countries. Africa has the most significant prevalence of bacterial meningitis illness, and the outbreaks typically vary with the season and the geographic location, with a high incidence in the meningitis belt of the sub-Saharan area from Senegal to Ethiopia. Streptococcus pneumoniae (pneumococcus) and Neisseria meningitidis (meningococcus) are the main etiological agents of bacterial meningitis in adults and children above the age of one. Streptococcus agalactiae (group …

A Deep Residual Model For Characterization Of 5d Spatiotemporal Network Dynamics Reveals Widespread Spatiodynamic Changes In Schizophrenia, Behnam Kazemivash, Theo G M Van Erp, Peter Kochunov, Vince D Calhoun

Faculty, Staff and Student Publications

Schizophrenia is a severe brain disorder with serious symptoms including delusions, disorganized speech, and hallucinations that can have a long-term detrimental impact on different aspects of a patient's life. It is still unclear what the main cause of schizophrenia is, but a combination of altered brain connectivity and structure may play a role. Neuroimaging data has been useful in characterizing schizophrenia, but there has been very little work focused on voxel-wise changes in multiple brain networks over time, despite evidence that functional networks exhibit complex spatiotemporal changes over time within individual subjects. Recent studies have primarily focused on static (average) …

Non-Canonical Pathways In The Pathophysiology And Therapeutics Of Bipolar Disorder, Rodrigo Machado-Vieira, Alan C Courtes, Carlos A Zarate, Ioline D Henter, Husseini K Manji

Faculty, Staff and Student Publications

Bipolar disorder (BD) is characterized by extreme mood swings ranging from manic/hypomanic to depressive episodes. The severity, duration, and frequency of these episodes can vary widely between individuals, significantly impacting quality of life. Individuals with BD spend almost half their lives experiencing mood symptoms, especially depression, as well as associated clinical dimensions such as anhedonia, fatigue, suicidality, anxiety, and neurovegetative symptoms. Persistent mood symptoms have been associated with premature mortality, accelerated aging, and elevated prevalence of treatment-resistant depression. Recent efforts have expanded our understanding of the neurobiology of BD and the downstream targets that may help track clinical outcomes and …

Chromogranin B (Chgb) Is Dimorphic And Responsible For Dominant Anion Channels Delivered To Cell Surface Via Regulated Secretion, Gaya P Yadav, Haiyuan Wang, Joke Ouwendijk, Stephen Cross, Qiaochu Wang, Feng Qin, Paul Verkade, Michael X Zhu, Qiu-Xing Jiang

Faculty, Staff and Student Publications

Regulated secretion is conserved in all eukaryotes. In vertebrates granin family proteins function in all key steps of regulated secretion. Phase separation and amyloid-based storage of proteins and small molecules in secretory granules require ion homeostasis to maintain their steady states, and thus need ion conductances in granule membranes. But granular ion channels are still elusive. Here we show that granule exocytosis in neuroendocrine cells delivers to cell surface dominant anion channels, to which chromogranin B (CHGB) is critical. Biochemical fractionation shows that native CHGB distributes nearly equally in soluble and membrane-bound forms, and both reconstitute highly selective anion channels …

Reading-To-Writing Mediation Model Of Higher-Order Literacy, Yusra Ahmed, Shawn C Kent, Milena Keller-Margulis

Faculty, Staff and Student Publications

INTRODUCTION: Writing difficulties frequently manifest comorbidly with reading challenges, and reading is implicated in particular acts of writing, such as reviewing and editing. Despite what is known, however, there remain significant barriers to understanding the nature of reading-writing relations, as few studies are comprehensive in the number and types of literacy skills evaluated. This study consists of a secondary data analysis of two studies employing structural equation modeling (SEM) to evaluate relations among reading and writing components skills independently, using the Direct and Inferential Mediation Model (DIME) of reading comprehension and Not-so-Simple View of Writing (NSVW) as theoretical frameworks.

METHODS: …

A Deep Learning Approach To Predict Collateral Flow In Stroke Patients Using Radiomic Features From Perfusion Images, Giles Tetteh, Fernando Navarro, Raphael Meier, Johannes Kaesmacher, Johannes C Paetzold, Jan S Kirschke, Claus Zimmer, Roland Wiest, Bjoern H Menze

Faculty, Staff and Student Publications

Collateral circulation results from specialized anastomotic channels which are capable of providing oxygenated blood to regions with compromised blood flow caused by arterial obstruction. The quality of collateral circulation has been established as a key factor in determining the likelihood of a favorable clinical outcome and goes a long way to determining the choice of a stroke care model. Though many imaging and grading methods exist for quantifying collateral blood flow, the actual grading is mostly done through manual inspection. This approach is associated with a number of challenges. First, it is time-consuming. Second, there is a high tendency for …

The Insulin And Igf Signaling Pathway Sustains Breast Cancer Stem Cells By Irs2/Pi3k-Mediated Regulation Of Myc, Manoj Sivan, Stefano Negrini, Carlotte Kiekens, Fary Khan, Gerard E Francisco, Francesca Gimigliano

Faculty, Staff and Student Publications

No abstract provided.

An Individual Data-Driven Virtual Resection Model Based On Epileptic Network Dynamics In Children With Intractable Epilepsy: A Magnetoencephalography Interictal Activity Application, Pablo Cuesta, Ricardo Bruña, Ekta Shah, Christopher Laohathai, Stephanie Garcia-Tarodo, Michael Funke, Gretchen Von Allmen, Fernando Maestú

Faculty, Staff and Student Publications

Epilepsy surgery continues to be a recommended treatment for intractable (medication-resistant) epilepsy; however, 30-70% of epilepsy surgery patients can continue to have seizures. Surgical failures are often associated with incomplete resection or inaccurate localization of the epileptogenic zone. This retrospective study aims to improve surgical outcome through in silico testing of surgical hypotheses through a personalized computational neurosurgery model created from individualized patient's magnetoencephalography recording and MRI. The framework assesses the extent of the epileptic network and evaluates underlying spike dynamics, resulting in identification of one single brain volume as a candidate for resection. Dynamic-locked networks were utilized for virtual …

Sex-Biased Autophagy As A Potential Mechanism Mediating Sex Differences In Ischemic Stroke Outcome, Brian Noh, Louise D Mccullough, Jose F Moruno-Manchon

Faculty, Staff and Student Publications

Stroke is the second leading cause of death and a major cause of disability worldwide, and biological sex is an important determining factor in stroke incidence and pathology. From childhood through adulthood, men have a higher incidence of stroke compared with women. Abundant research has confirmed the beneficial effects of estrogen in experimental ischemic stroke but genetic factors such as the X-chromosome complement can also play an important role in determining sex differences in stroke. Autophagy is a self-degrading cellular process orchestrated by multiple core proteins, which leads to the engulfment of cytoplasmic material and degradation of cargo after autophagy …

Preoperative Tractography Algorithm For Safe Resection Of Tumors Located In The Descending Motor Pathways Zone, Edgar G Ordonez-Rubiano, Jason M Johnson, Nadin Abdalá-Vargas, Oscar F Zorro, Jorge H Marin-Munoz, Ricardo Álvarez-Tobián, Valeria Forlizzi, Carlos Castillo Rangel, Sabino Luzzi, Alvaro Campero, Javier G Patiño-Gómez, Matias Baldoncini

Faculty, Staff and Student Publications

BACKGROUND: Diffusion tensor imaging (DTI) tractography facilitates maximal safe resection and optimizes planning to avoid injury during subcortical dissection along descending motor pathways (DMPs). We provide an affordable, safe, and timely algorithm for preoperative DTI motor reconstruction for gliomas adjacent to DMPs.

METHODS: Preoperative DTI reconstructions were extracted from a prospectively acquired registry of glioma resections adjacent to DMPs. The surgeries were performed over a 7-year period. Demographic, clinical, and radiographic data were extracted from patients' electronic medical records.

RESULTS: Nineteen patients (12 male) underwent preoperative tractography between January 1, 2013, and May 31, 2020. The average age was 44.5 …

Grid Cells, Border Cells, And Discrete Complex Analysis, Yuri Dabaghian

Faculty, Staff and Student Publications

We propose a mechanism enabling the appearance of border cells-neurons firing at the boundaries of the navigated enclosures. The approach is based on the recent discovery of discrete complex analysis on a triangular lattice, which allows constructing discrete epitomes of complex-analytic functions and making use of their inherent ability to attain maximal values at the boundaries of generic lattice domains. As it turns out, certain elements of the discrete-complex framework readily appear in the oscillatory models of grid cells. We demonstrate that these models can extend further, producing cells that increase their activity toward the frontiers of the navigated environments. …

Retinal Alpha-Synuclein Accumulation Correlates With Retinal Dysfunction And Structural Thinning In The A53t Mouse Model Of Parkinson’S Disease, Katie K N Tran, Vickie H Y Wong, Anh Hoang, David I Finkelstein, Bang V Bui, Christine T O Nguyen

Faculty, Staff and Student Publications

Abnormal alpha-synuclein (α-SYN) protein deposition has long been recognized as one of the pathological hallmarks of Parkinson's disease's (PD). This study considers the potential utility of PD retinal biomarkers by investigating retinal changes in a well characterized PD model of α-SYN overexpression and how these correspond to the presence of retinal α-SYN. Transgenic A53T homozygous (HOM) mice overexpressing human α-SYN and wildtype (WT) control littermates were assessed at 4, 6, and 14  months of age (male and female,

The Involvement Of Kynurenine Pathway In Neurodegenerative Diseases, Lais B Martins, Ana L M Silveira, Antonio L Teixeira

Faculty, Staff and Student Publications

BACKGROUND: A growing body of evidence has shown the involvement of the kynurenine pathway (KP), the primary route of tryptophan (TRP) catabolism, in the pathophysiology of neuropsychiatric disorders.

OBJECTIVE: The study aims to provide a comprehensive and critical overview of the clinical evidence on the KP involvement in the pathophysiology of Alzheimer's disease (AD) and Parkinson's disease (PD), discussing therapeutic opportunities.

METHODS: We searched for studies investigating KP metabolites in human subjects with AD and/or PD.

RESULTS: Postmortem studies showed altered levels of KP metabolites in the brain of AD and PD patients compared with controls. Cross-sectional studies have reported …

Glial Cell-Specific Contribution Of Pkr-Like Er Kinase (Perk) In Neuroinflammation And Behavior, Anirudhya Lahiri

Graduate Theses, Dissertations, and Problem Reports (ETD)

Neurological disorders such as multiple sclerosis (MS) are a major public health concern in the US, with no available therapeutic cure. Chronic neuroinflammation and aberrant proteostasis in the central nervous system (CNS) are the major hallmarks of neurological diseases. Endoplasmic Reticulum (ER) is a major cellular organelle involved in protein synthesis, folding and maturation of various secretory and transmembrane proteins. Pathophysiological stressors such as trauma and infection result in misfolded protein accumulation in the endoplasmic reticulum (ER) lumen, which results in ER stress. To regain proteostasis (protein homeostasis), cells activate the unfolded protein response (UPR). UPR is an evolutionarily conserved …

Mass Spectrometry Imaging As An Emerging Tool For Studying Metabolism In Human Brain Organoids, Gerarda Cappuccio, Saleh M Khalil, Sivan Osenberg, Feng Li, Mirjana Maletic-Savatic

Faculty, Staff and Students Publications

Human brain organoids are emerging models to study human brain development and pathology as they recapitulate the development and characteristics of major neural cell types, and enable manipulation through an in vitro system. Over the past decade, with the advent of spatial technologies, mass spectrometry imaging (MSI) has become a prominent tool for metabolic microscopy, providing label-free, non-targeted molecular and spatial distribution information of the metabolites within tissue, including lipids. This technology has never been used for studies of brain organoids and here, we set out to develop a standardized protocol for preparation and mass spectrometry imaging of human brain …

Forniceal Deep Brain Stimulation In A Mouse Model Of Rett Syndrome Increases Neurogenesis And Hippocampal Memory Beyond The Treatment Period, Qi Wang, Bin Tang, Shuang Hao, Zhenyu Wu, Tingting Yang, Jianrong Tang

Faculty, Staff and Students Publications

BACKGROUND: Rett syndrome (RTT), caused by mutations in the X-linked gene encoding methyl-CpG binding protein 2 (MeCP2), severely impairs learning and memory. We previously showed that forniceal deep brain stimulation (DBS) stimulates hippocampal neurogenesis with concomitant improvements in hippocampal-dependent learning and memory in a mouse model of RTT.

OBJECTIVES: To determine the duration of DBS benefits; characterize DBS effects on hippocampal neurogenesis; and determine whether DBS influences MECP2 genotype and survival of newborn dentate granular cells (DGCs) in RTT mice.

METHODS: Chronic DBS was delivered through an electrode implanted in the fimbria-fornix. We tested separate cohorts of mice in contextual …

Sex-Specific Associations Between Urinary Bisphenols Concentrations During Pregnancy And Problematic Child Behaviors At Age 2 Years, Sarah Dee Geiger, Salma Musaad, Jennifer Hill, Andréa Aguiar, Susan Schantz

Faculty, Staff and Students Publications

Effects of prenatal bisphenol A (BPA) exposure on child behavior are mixed with some reports suggesting increased problematic behaviors in girls (e.g., aggression and emotional reactivity) and in boys (i.e., externalizing behaviors), while other reports suggest decreased problematic behaviors in girls. Little is known about the potential impact of pregnancy bisphenol S (BPS) exposure on child behavior. In a prospective cohort study (n=68), five maternal spot urine samples collected across pregnancy were pooled and analyzed for BPA and BPS. Child behavior at 2 years was assessed using the Child Behavior Checklist (CBCL). Linear regression models were used to assess associations …

Automated Artifact Injection Into Sensing-Capable Brain Modulation Devices For Neural-Behavioral Synchronization And The Influence Of Device State, Michaela E Alarie, Nicole R Provenza, Jeffrey A Herron, Wael F Asaad

Faculty, Staff and Students Publications

No abstract provided.

Attenuating Side Effects Of Deep Brain Stimulation In The Bed Nucleus Of The Stria Terminalis For Obsessive Compulsive Disorder Using Current-Steering Strategies, Huy Q Dang, Nicole R Provenza, Garrett P Banks, Nisha Giridharan, Michelle Avendano-Ortega, Sarah A Mckay, Ethan Devara, Ben Shofty, Eric A Storch, Sameer A Sheth, Wayne K Goodman

Faculty, Staff and Students Publications

No abstract provided.

Advances In Imaging Modalities For Pediatric Brain And Spinal Cord Tumors, Thierry A G M Huisman, Rajan Patel, Stephen Kralik, Nilesh K Desai, Avner Meoded, Karen Chen, Howard L Weiner, Daniel J Curry, Maarten Lequin, Mariette Kranendonk, Gunes Orman, George Jallo

Faculty, Staff and Students Publications

Background: Neuroimaging has evolved from anatomical imaging toward a multi-modality comprehensive anatomical and functional imaging in the past decades, important functional data like perfusion-weighted imaging, permeability imaging, diffusion-weighted imaging (DWI), and diffusion tensor imaging (DTI), tractography, metabolic imaging, connectomics, event-related functional imaging, resting state functional imaging, and much more is now being offered.

Summary: Precision diagnostics has proven to be essential for precision treatment. Many minimal invasive techniques have been developed, taking advantage of digital subtraction angiography and interventional neuroradiology. Furthermore, intraoperative CT and/or MRI and more recently MR-guided focused ultrasound have complemented the diagnostic and therapeutic armamentarium.

Key messages: …

Editorial: Molecular Mechanisms In Ocular Development And Disease, Rajalekshmy Shyam, Daisy Y Shu, Elizabeth Zuniga-Sanchez, Deepika Vasudevan

Faculty, Staff and Students Publications

No abstract provided.