Neuroscience and Neurobiology Commons^™

The Role Of Semaphorins In Response To Injury In C. Elegans Neurons, Maria Belen Harreguy Alfonso

Dissertations

When neural tissue is injured by trauma, delicate neuronal processes such as axons and dendrites are prone to lesion damage and often disconnect. The molecular, cellular, and circuit mechanisms that underlie the regrowth and reconnection of these processes and the recovery of behavior are major challenges in the fields of neuroscience, regeneration, and resilience. At the molecular and cellular levels, signaling pathways that mediate neuronal growth cone guidance during development can play a role in neuronal regeneration and recovery from injury. One family of signaling proteins involved in this process comprises the highly conserved semaphorins and their receptors, the plexins. …

Neural Correlates Of Post-Traumatic Brain Injury (Tbi) Attention Deficits In Children, Meng Cao

Dissertations

Traumatic brain injury (TBI) in children is a major public health concern worldwide. Attention deficits are among the most common neurocognitive and behavioral consequences in children post-TBI which have significant negative impacts on their educational and social outcomes and compromise the quality of their lives. However, there is a paucity of evidence to guide the optimal treatment strategies of attention deficit related symptoms in children post-TBI due to the lack of understanding regarding its neurobiological substrate. Thus, it is critical to understand the neural mechanisms associated with TBI-induced attention deficits in children so that more refined and tailored strategies can …

Deep Hybrid Modeling Of Neuronal Dynamics Using Generative Adversarial Networks, Soheil Saghafi

Dissertations

Mechanistic modeling and machine learning methods are powerful techniques for approximating biological systems and making accurate predictions from data. However, when used in isolation these approaches suffer from distinct shortcomings: model and parameter uncertainty limit mechanistic modeling, whereas machine learning methods disregard the underlying biophysical mechanisms. This dissertation constructs Deep Hybrid Models that address these shortcomings by combining deep learning with mechanistic modeling. In particular, this dissertation uses Generative Adversarial Networks (GANs) to provide an inverse mapping of data to mechanistic models and identifies the distributions of mechanistic model parameters coherent to the data.

Chapter 1 provides background information on …

Probing Amyloid-Beta Protein Structure And Dynamics With A Selective Antibody, Shikha Grover

Dissertations

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. The AD brain is characterized by significant neuronal loss and accumulation of insoluble fibrillar amyloid-β protein (Aβ) plaques and tau protein neurofibrillary tangles in the brain. However, over the last decade, many studies have shown that the neurodegenerative effect of Aβ may in fact be caused by various soluble oligomeric forms as opposed to the insoluble fibrils. Furthermore, the data suggest that a pre-fibrillar aggregated form, termed protofibrils, mediates direct neurotoxicity, and triggers a robust neuroinflammatory response.

Antibodies targeting the various conformation of Aβ are important therapeutic agents to prevent the progression …

Improving The Stimulation Selectivity In The Human Cochlea By Strategic Selection Of The Current Return Electrode, Ozan Cakmak

Dissertations

The hearing quality provided by cochlear implants are poorly predicted by computer simulations. A realistic cochlear anatomy is crucial for the accuracy of predictions. In this study, the standard multipolar stimulation paradigms are revisited and Rattay’s Activating Function is evaluated in a finite element model of a realistic cochlear geometry that is based on µ-CT images and a commercial lead. The stimulation thresholds across the cochlear fibers were investigated for monopolar, bipolar, tripolar, and a novel (distant) bipolar electrode configuration using an active compartmental nerve model based on Schwartz-Eikhof-Frijns membrane dynamics. The results suggest that skipping of the stimulation point …

Sensorimotor Content Of Multi-Unit Activity In The Paramedian Lobule Of The Cerebellum, Esma Cetinkaya

Dissertations

Based on Center for Disease Control and Prevention report 2016, around 39.5 million people in the United States suffer from motor disabilities. These disabilities are due to traumatic conditions like traumatic brain injury (TBI), neurological diseases such as amyotrophic lateral sclerosis (ALS), or congenital conditions. One of the approaches for restoring the lost motor function is to extract the volitional information from the central nervous system (CNS) and control a mechanical device that can replace the function of a paralyzed limb through systems called Brain-Computer Interfaces (BCI).

One of the major challenges being faced in BCIs and also in general …

Utility Of The Motivation To Change Lifestyle And Health Behaviors For Dementia Risk Reduction Scale (Mclhb-Drr) Based On A North American Sample, Angelina E. Witbeck

Dissertations

As the population ages, the prevalence rates of dementia continue to increase. Without a cure or promising treatment for dementia, the best course of lowering the prevalence rates of dementia is through preventative measures. Through an electronic survey, the study utilized the MCLHB-DRR scale to determine whether (1) gender, age, educational background, and socioeconomic status will impact the motivational factors to change lifestyle and health behaviors to reduce the risk of developing dementia and (2) direct experiences with individuals that have a dementia diagnosis are likely to impact one's motivational factors to change lifestyle and health behaviors to reduce the …

One-Stage Blind Source Separation Via A Sparse Autoencoder Framework, Jason Anthony Dabin

Dissertations

Blind source separation (BSS) is the process of recovering individual source transmissions from a received mixture of co-channel signals without a priori knowledge of the channel mixing matrix or transmitted source signals. The received co-channel composite signal is considered to be captured across an antenna array or sensor network and is assumed to contain sparse transmissions, as users are active and inactive aperiodically over time. An unsupervised machine learning approach using an artificial feedforward neural network sparse autoencoder with one hidden layer is formulated for blindly recovering the channel matrix and source activity of co-channel transmissions. The BSS sparse autoencoder …

Repeated Low-Level Blast Induces Chronic Neuroinflammation And Neurobehavioral Changes In Rat Models, Arun Reddy Ravula

Dissertations

Blast-induced neurotrauma (bTBI) is a signature medical concern for military personnel when they are exposed to explosions in active combat zones. However, soldiers as well as law enforcement personnel are also repeatedly exposed to low-level blasts during training sessions with heavy weaponries as part of combat readiness. Service personnel who sustain brain injuries from repeated low-level blasts (rLLBs) do not display overt pathological symptoms immediately but rather develop cognitive impairments, attention deficits, anxiety, and sleep disturbances over time. An improved rat model of rLLB was developed in this thesis by applying controlled low-level blast pressures (10 psi) repeated five times …

Assessing Structural And Functional Brain Alterations And Work-Related Fatigue In Non-Hyposmic And Hyposmic Covid-19 Survivors, Rakibul Hafiz

Dissertations

In the year 2019, life began to change at the advent of a global pandemic caused by the novel coronavirus. Mask mandates and mass vaccinations have mitigated the effects significantly, yet cases keep rising with new variants, especially, in densely populated countries, like India. Recent neuroimaging evidence shows the virus can attack the central nervous system (CNS). However, exactly which brain regions undergo structural and functional changes remain largely unknown. Many patients experience 'loss of/reduced sense of smell' (i.e., hyposmic) and an alarming number of survivors develop persistent symptoms ('long-COVID') for several months after initial infection. Fatigue is the most …

Granulins In Norm And Neurodegenerative Pathologies, Anukool Bhopatkar

Dissertations

Granulins (GRNs) are small, cysteine-rich modules produced from the proteolytic cleavage of the precursor protein called progranulin (PGRN). GRNs are present in the form of seven tandem repeats within the precursor and are known to be produced in the extracellular and in lysosomal environments. In physiology, PGRN and GRNs plays pleiotropic roles such as neuronal growth and differentiation, immunomodulation, wound healing. Recent studies have implicated pathological role for PGRN in Alzheimer disease (AD) and frontotemporal dementia (FTD) but specific mechanism(s) remains unclear. However, potential interactions between GRNs and Ab42 and TDP-43 seem like a plausible underlying mechanism. Studies presented here …

Towards Understanding The Role Of Central Processing In Release From Masking, Nima Alamatsaz

Dissertations

People with normal hearing have the ability to listen to a desired target sound while filtering out unwanted sounds in the background. However, most patients with hearing impairment struggle in noisy environments, a perceptual deficit which current hearing aids and cochlear implants cannot resolve. Even though peripheral dysfunction of the ears undoubtedly contribute to this deficit, surmounting evidence has implicated central processing in the inability to detect sounds in background noise. Therefore, it is essential to better understand the underlying neural mechanisms by which target sounds are dissociated from competing maskers. This research focuses on two phenomena that help suppress …

Alcohol As A Catalyst For Hiv-Associated Neuroinflammation And Tbi-Induced Iron Toxicity, Agnieszka Agas

Dissertations

Alcohol has long been considered an exacerbator of diseases, disorders, and injuries as well as many of the accompanying symptoms. As an alternative approach, this dissertation explores alcohol as a catalyst for two different human disease conditions, human immunodeficiency virus (HIV)-associated neuroinflammation and traumatic brain injury (TBI)-induced iron toxicity. In HIV-1 infection, this dissertation presents a novel anti-viral drug, called Drug-S, for a possible inhibition and treatment of HIV-1 disease progression.

The first aim explores the influence of alcohol with HIV-associated neuroinflammation on macrophage migration across an in vitro model of the blood brain barrier. There is a gap in …

Selective Neural Stimulation By Leveraging Electrophysiological Diversity And Using Alternative Stimulus Waveforms, Bemin Ghobreal

Dissertations

Efforts on finding the principle mechanism for selective neural stimulation have concentrated on segregating the neurons based on their size and other geometric factors. However, neuronal subtypes found in different parts of the nervous system also differ in their electrophysiological properties. The primary objective of this study is to investigate the feasibility of selective activation of neurons by leveraging the diversity seen in passive and active membrane properties.

Using both a local membrane model and an axon model based on the CRRSS, the diversity of electrophysiological properties is simulated by varying four model parameters (membrane leakage-Gleak and capacitance-Cm, temperature coefficient-Ktemp, …

Mechanisms Of Oscillations And Polyglot Entrainment In Neuronal And Circadian Models, Emel Khan

Dissertations

Entrainment is a type of synchronization in which the period of an endogenous oscillator matches the period of an external forcing signal and a stable phase relationship is maintained between them. Entrainment patterns are described in terms of the number of input oscillations (N) that are phase-locked to a number of output oscillations (M), referred to as N:M patterns. Arnold tongue diagrams are used to depict the regions of N:M entrainment patterns in the input period-amplitude parameter space. Although the entrainment of self-sustained oscillators by periodic forcing are well investigated is a well-studied problem, entrainment of damped oscillators has been …

Life Satisfaction: Aging Female Informal Caregivers Of Persons With Dementia, Deborah Ann Monson

Dissertations

Purpose/Aims

The purpose of this study was to describe the relationship between aging female informal caregivers of persons with dementia (PWD) and care recipients’ PWD demographic factors, aging female informal caregivers of PWD social support factors, positive and negative feelings, a sense of flourishing, stress, and life satisfaction.

Background/Rationale

Older adults with dementia are living longer and the majority are receiving care by aging female informal caregivers. Dementia incrementally worsens over time impacting informal caregiver life satisfaction. Most studies have focused on negative aspects of informal caregiving. Therefore, this study investigated both positive and negative aspects of caregiving.

Conceptual Basis …

Characterizing Galectin And Lysosomal Rupture's Role In Spreading Parkinson Disease Pathology, Kevin Burbidge

Dissertations

The misfolding and subsequent accumulation of alpha-synuclein (α-syn) is central to the pathogenesis of Parkinson's disease (PD). Several lines of evidence suggest pathological α-syn spread cell-to-cell via a "prion-like" mechanism. Furthermore, this pathological α-syn is capable of "seeding" further misfolding of non-pathological α-syn, converting them to the pathological form. While a vast body of both genetic and experimental evidence indicates that α-syn is critical to PD development, how α-syn induces progressive neuronal dysfunction and cell death remains unclear.Autophagy, conventional for macroautophagy, is the primary degradation pathway for α-syn aggregates. Autophagy also influences the unconventional secretion of both pathological and non-pathological …

Understanding The Role Of Lipids Derived From The Gut Microbes In A Mouse Model Of Obesity-Induced Peripheral Pain, Raiza Rafael-Bonomo Hardy

Dissertations

The increase in obesity has been accompanied by a rise in the prevalence of painful peripheral neuropathy. Recently, studies have suggested a role for gut microbiome in the development of some peripheral pain, including chemotherapy- induced pain and fibromyalgia. In the present dissertation, we showed that modulation of gut microbiome in obese mice alleviated neuropathic indices, concurrent with changes in immune cell profile within the peripheral nerve system. We demonstrated that fecal transplantation from lean to obese mice decreased obesity-induced pain and restored nerve density in the skin. These improvements were accompanied by changes in peripheral nerve system gene expression, …

Mathematical Models And Tools To Understand Coupled Circadian Oscillations And Limit Cycling Systems, Guangyuan Liao

Dissertations

The circadian rhythm refers to an internal body process that regulates many body processes including the sleep-wake cycle, digestion and hormone release. The ability of a circadian system to entrain to the 24-hour light-dark cycle is one of the most important properties. There are several scenarios in which circadian oscillators do not directly receive light-dark forcing. Instead they are part of hierarchical systems in which, as \peripheral" oscillators, they are periodically forced by other \central" circadian oscillators that do directly receive light input. Such dynamics are modeled as hierarchical coupled limit cycle systems. Those models usually have a large population, …

Microglia Induced Neuroinflammation Through The Nlrp3 Inflammasome Following Blast Traumatic Brain Injury, Daniel Younger

Dissertations

The incidence of traumatic brain injury (TBI) among military personnel have been steadily increasing with modern conflicts. A recent RAND report estimated 320,000 service members, totaling 20% of deployed forces, suffer from TBI. However, of this population roughly 60% have not seen a medical professional specifically for TBI. Unlike the civilian population, the primary cause of TBI for active-duty military personnel is blast exposure. Blasts now account for over 70% of all US military casualties in operation Iraqi Freedom (OIF) and Operation enduring freedom (OEF) and are the major cause of TBI. Among many pathological mechanisms associated with blast TBI, …

Investigating The Combined Effects Of Whole Body Vibration And Vestibular Stimulation On Spasticity And Dystonia In Cerebral Palsy, Peter A. Michael

Dissertations

This study identifies and addresses three voids and potential shortcomings associated with the classification, assessment and management of Cerebral Palsy (CP). These concerns should not undermine the significant advancement that has been made in this specific branch of rehabilitation, but addressing them is necessary. Cerebral Palsy is a group of motor impairments due to hypoxic-ischemic brain damage around the time of birth and very commonly manifests as excessive muscle tone and poor motor control. There are classifications within CP including spasticity and dystonia.

First, a level of discrepancy is present in the classification of CP between the clinical and research …

Modulation Of Cerebellar Purkinje Cell Activity With Low Intensity Electric And Ultrasound Stimulation, Ahmet S. Asan

Dissertations

Non-invasive brain stimulation (NIBS) techniques garner significant interest due to their potential to offer instantaneous and region-specific treatments to neurological disorders. The cerebellum is one of the target sites for NIBS methods due to its central role in motor and cognitive functions. Among several modulation techniques, transcranial electric stimulations (tEs), in particular, transcranial direct and alternating current stimulations (tDCs/tACs), and low intensity focused ultrasound stimulation (LIFUS) show encouraging outcomes in clinical applications. tDCs and tACs are favored due to their low cost and accessibility while LIFUS offers high spatial resolution and deeper penetration without affecting the surrounding structures. In order …

Data Assimilation For Conductance-Based Neuronal Models, Matthew Moye

Dissertations

This dissertation illustrates the use of data assimilation algorithms to estimate unobserved variables and unknown parameters of conductance-based neuronal models. Modern data assimilation (DA) techniques are widely used in climate science and weather prediction, but have only recently begun to be applied in neuroscience. The two main classes of DA techniques are sequential methods and variational methods. Throughout this work, twin experiments, where the data is synthetically generated from output of the model, are used to validate use of these techniques for conductance-based models observing only the voltage trace. In Chapter 1, these techniques are described in detail and the …

The Roles Of Inhibition In C. Elegans Locomotion, Lan Deng

Dissertations

Inhibition plays important roles in modulating neural activities at different levels from small synapses to brain regions, and different systems from sensory to motor. To achieve translocation, locomotor systems produce alternation of antagonist muscles, including axial posture and limb movement and alternation. In the nematode C. elegans, a cross-inhibition circuit, involving excitatory cholinergic and inhibitory GABAergic motoneurons, is believed to generate the dorsoventral alternation of body-wall muscles that supports backward undulatory locomotion. This dissertation challenges this prevalent hypothesis, delves into studying different roles of inhibition, and depicts the expression pattern and functional role of ionotropic GABAA receptor, UNC-49, in motoneurons …

Sedative And Neurotoxic Properties Of Brexanolone Compared To Midazolam In The Developing Rodent Brain, Jacob Huffman

Dissertations

The developing brain is susceptible to extensive neurotoxicity following exposure to sedative/anesthetic drugs (SADs). Every year hundreds of thousands of children around the world are exposed to SADs with no viable non-neurotoxic agents approved for clinical use. Allopregnanolone (AlloP) has well-established sedative effects in adults and neonates. AlloP and many SADs produce sedation/anesthesia through allosteric modulation of GABA_A receptors, which is one of two principal mechanisms behind SAD-induced neurotoxicity. Evidence suggests AlloP has the unique capacity to regulate key apoptotic factors in adults and is widely involved with critical stages of neurodevelopment, indicating this neurosteroid might serve as a …

Perivascular Waste Metabolites Clearance In Central Nervous System (Cns), Yiming Cheng

Dissertations

Efficient clearance of interstitial waste metabolites is essential for normal brain homeostasis. Such effective clearance is hampered by the lack of a lymphatic system in the brain, and the cerebrospinal fluid (CSF) is unable to clear large size waste metabolites in the brain. Here, a novel idea that brain arterial endothelium and smooth muscle cells reactivity regulates the clearance of these water-insoluble large size waste metabolites through the perivascular dynamic exchange, and that low dose ethanol promotes this perivascular clearance is proposed.

In Aim 1, the biodistribution of a large size waste metabolite (Amyloid-β protein mimic) in rat perivascular space …

Cerebro-Vascular Disruption Mediated Initiation And Propagation Of Traumatic Brain Injury In A Fluid Percussion Injury Model, Xiaotang Ma

Dissertations

Traumatic brain injury (TBI) is a major health problem for over 3.17 million people in the US. There is no FDA-approved drug for the treatment because the injury mechanisms have not been clearly identified. The knowledge gap is addressed here by the lateral fluid percussion injury (FPI) rat model, through the understanding of layer-structured mechanisms from physical vascular rupture to acute necrosis, as well as biochemical changes in perivascular space as secondary events.

Firstly, the cerebrovascular hemorrhage and related infarct volume are investigated as the primary events in moderate FPI, which is found to be increased with injury severity in …

A Computational Study Of Sleep And The Hemispheres Of The Brain, Tera Ashley Glaze

Dissertations

Sleep and sleep cycles have been studied for over a century, and scientists have worked on modeling sleep for nearly as long as computers have existed. Despite this extensive study, sleep still holds many mysteries. Larger and more extensive sleep-wake models have been developed, and the circadian drive has been depicted in numerous fashions, as well as incorporated into scores of studies. With the ever-growing knowledge of sleep comes the need to find more ways to examine, quantify, and define it in the context of the most complex part of the human anatomy – the brain. Presented here is the …

Developmental And Sex Modulated Neurological Alterations In Autism Spectrum Disorder, Azeezat Azeez

Dissertations

Autism Spectrum Disorder (ASD) was first described in 1943 by Dr. Leo Kranner in a case study published in The Nervous Child. It is a neurodevelopment disorder, with a range of clinical symptoms. According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), used by clinicians to diagnose mental disorders, a child needs to have persistent social deficits, language impairments, and repetitive behaviors, that cannot be explained by neurological damage or intellectual disability. It is known that children diagnosed with ASD are often are developmentally delayed therefore alterations in the typical developmental trajectory should be a major factor in …

Redefining Burnout: Exploring Common Conceptualizations And The Neurophysiology Of Chronic Stress To Establish An Integrated Allostatic Model, Danny A. Guzzi

Dissertations

Burnout is a widely researched stress-related phenomenon associated with numerous adverse outcomes for employees and organizations. Unfortunately, burnout is not well understood and research to this point has been flawed due to a lack of consensus on the definition, dimensionality, and context of the construct. Prevalent conceptualizations of burnout have been criticized for being arbitrarily developed without solid theoretical foundation and for failing to clearly distinguish burnout from depression or other work-related conditions such as compassion fatigue, secondary traumatization, and vicarious traumatization. The current project first examines relevant literature to identify commonalities among prevalent burnout conceptualizations. Then relevant stress research …