Neuroscience and Neurobiology Commons^™

A Conformation Variant Of P53 Combined With Machine Learning Identifies Alzheimer Disease In Preclinical And Prodromal Stages, Giulia Abate, Marika Vezzoli, Letizia Polito, Antonio Guaita, Diego Albani, Moira Marizzoni, Emirena Garrafa, Alessandra Marengoni, Gianluigi Forloni, Giovanni B. Frisoni, Jeffrey L. Cummings, Maurizio Memo, Daniela Uberti

School of Medicine Faculty Publications

© 2020 by the authors. Li-censee MDPI, Basel, Switzerland. Early diagnosis of Alzheimer’s disease (AD) is a crucial starting point in disease man-agement. Blood-based biomarkers could represent a considerable advantage in providing AD-risk information in primary care settings. Here, we report new data for a relatively unknown blood-based biomarker that holds promise for AD diagnosis. We evaluate a p53-misfolding conformation rec-ognized by the antibody 2D3A8, also named Unfolded p53 (U-p532D3A8+), in 375 plasma samples derived from InveCe.Ab and PharmaCog/E-ADNI longitudinal studies. A machine learning approach is used to combine U-p532D3A8+ plasma levels with Mini-Mental State Examination (MMSE) and apolipoprotein E …

Circadian Regulation Of The Timing Of Pre-Ovulatory Luteinizing Hormone Surge In Mice And Hamsters, Ajay Kumar

Doctoral Dissertations

Endogenous daily (circadian) oscillators ensure the proper timing of physiological and behavioral processes that are essential to health. A set of core clock genes and their protein products function in transcriptional/translational feedback loops (TTFLs) that time and coordinate vital homeostatic, cognitive, and hormonal processes. A master pacemaker in the suprachiasmatic nucleus (SCN) coordinates circadian function throughout the organism. Investigating the causal role of genetically defined cell types in the suprachiasmatic nucleus for circadian rhythms is essential to understand how an animal’s physiology is temporally organized. This thesis explores the role of molecular clocks within particular cell types in regulating physiology. …

Beyond Low-Earth Orbit: Characterizing Immune And Microrna Differentials Following Simulated Deep Spaceflight Conditions In Mice, Amber M. Paul, Margareth Cheng-Campbell, Elizabeth A. Blaber, Sulekha Anand, Sharmila Bhattacharya

Publications

Spaceflight missions can cause immune system dysfunction in astronauts with little understanding of immune outcomes in deep space. This study assessed immune responses in mice following ground-based, simulated deep spaceflight conditions, compared with data from astronauts on International Space Station missions. For ground studies, we simulated microgravity using the hindlimb unloaded mouse model alone or in combination with acute simulated galactic cosmic rays or solar particle events irradiation. Immune profiling results revealed unique immune diversity following each experimental condition, suggesting each stressor results in distinct circulating immune responses, with clear consequences for deep spaceflight. Circulating plasma microRNA sequence analysis revealed …

Neurocounseling And The Counseling Profession: Integrating Neuroscience Into The Practice Of Counseling, Sherri Clark

Dissertations, Theses, and Projects

Neurocounseling integrates Neuroscience into mental health counseling by using psychoeducation, teaching, and illustrations as well as other forms of therapy (CBT, Interpersonal Psychotherapy, Narrative Therapy, etc.) to assist clients in understanding the neurological basis of many mental and behavioral health concerns. Clients can benefit from Neurocounseling as they gain a more comprehensive understanding of the central nervous system and brain function in connection to the body, cognition, mood, and behaviors, also known as the mind and body connection. Neuroplasticity and neurogenesis allow us to understand the brain’s amazing capability to grow and change. Understanding neuroscience allows for more integrated case …

The Subplate And Its Role In The Gaba System In The Prefrontal Cortex, Gaeul Kyla Lee

Electronic Thesis and Dissertation Repository

During early brain development, the subplate relays thalamocortical afferents. Lesions to the subplate have been implicated in developmental abnormalities of cortical GABAergic circuits. This thesis examined the effects of subplate lesions in the prefrontal cortex of rats on the expression of GABA markers (parvalbumin and GAD67) and GABA synapse maturation [potassium-chloride cotransporter (KCC2) and sodium-potassium- chloride cotransporter (NKCC1)] with relevance to the characterization of a rat model for schizophrenia. Lesions were made on postnatal day 1 (P1). Lesioned and control rats were sacrificed between P5 and P90 and immunolabelled for parvalbumin, GAD67, KCC2, and NKCC1. We found decreased parvalbumin expression …

Quality Of Life Among Injectable And Oral Disease-Modifying Therapy Users In The Pacific Northwest Multiple Sclerosis Registry., Tamela Stuchiner, Lindsay Lucas, Elizabeth Baraban, Kateri Spinelli, Chiayi Chen, Alden Smith, Lobat Hashemi, Stanley Cohan

Articles, Abstracts, and Reports

BACKGROUND: Nine oral disease-modifying therapies (DMTs) have been approved for the treatment of multiple sclerosis (MS) in the United States. Few studies have examined self-reported quality of life (QoL) and functional status outcomes among patients who switch to oral medications from injectable MS therapies. This study compares self-reported QoL and disability status between participants switching from injectable to oral DMTs, to those who stay on injectable DMTs continuously for the same time period.

METHODS: Longitudinal data were assessed from relapsing MS participants in the Pacific Northwest MS Registry completing a minimum of two surveys between 2012 and 2018 with a …

Spatial Patterns Of Correlation Between Cortical Amyloid And Cortical Thickness In A Tertiary Clinical Population With Memory Deficit, Jagan A. Pillai, Mykol Larvie, Jacqueline Chen, Anna Crawford, Jeffery L. Cummings, Stephen E. Jones

School of Medicine Faculty Publications

© 2020, The Author(s). To estimate regional Alzheimer disease (AD) pathology burden clinically, analysis methods that enable tracking brain amyloid or tau positron emission tomography (PET) with magnetic resonance imaging (MRI) measures are needed. We therefore developed a robust MRI analysis method to identify brain regions that correlate linearly with regional amyloid burden in congruent PET images. This method was designed to reduce data variance and improve the sensitivity of the detection of cortical thickness–amyloid correlation by using whole brain modeling, nonlinear image coregistration, and partial volume correction. Using this method, a cross-sectional analysis of 75 tertiary memory clinic AD …

Association Between White Matter Hyperintensities, Cortical Thinning, And Clinical Outcomes In Mild Traumatic Brain Injury, Thomas Helmut Knoblauch

UNLV Theses, Dissertations, Professional Papers, and Capstones

Traumatic Brain Injury (TBI) is a global health challenge, with over 4.6 million confirmed cases annually in North America alone. Mild traumatic brain injuries (mTBIs) are the most common and make up approximately 81% of all TBI diagnoses worldwide [1]. Studies indicate that 10–15% of patients suffer from trauma induced symptoms (i.e. headache, loss of balance, cognitive impairments, fatigue, and mental health/affective disorders) as far as 1 year post injury [2]. Prediction and management of these post-traumatic sequalae is complicated by a lack of symptom associated neuroimaging findings. In spite of a “prominent distribution” of frontotemporal WMHs in pediatric subjects …

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 …

A Two-Clone Approach To Study Signaling Interactions Among Neuronal Cells In A Pre-Clinical Alzheimer’S Disease Model, Catherine J. Yeates, Ankita Sarkar, Prajakta Deshpande, Madhuri Kango-Singh, Amit Singh

Biology Faculty Publications

To understand the progression of Alzheimer's disease, studies often rely on ectopic expression of amyloid-beta 42 (Aβ42) throughout an entire tissue. Uniform ectopic expression of Aβ42 may obscure cell-cell interactions that contribute to the progression of the disease. We developed a two-clone system to study the signaling cross talk between GFP-labeled clones of Aβ42-expressing neurons and wild-type neurons simultaneously generated from the same progenitor cell by a single recombination event. Surprisingly, wild-type clones are reduced in size as compared with Aβ42-producing clones. We found that wild-type cells are eliminated by the induction of cell death. Furthermore, aberrant activation of c-Jun-N-terminal …

Testosterone Undecanoate Effects On Behavior And Cognitive Functions In Male Swiss Albino Mice Exposed To Chronic Social Defeat, Micheal K. Ibrahim, Rajiv Tikamdas, Mohamed M. Kamal, Roua Aref Nouh, Mostafa H. Sayed

Pharmacy

Objective: To examine the impact of exogenous testosterone undecanoate (TU) on chronic stress-induced behavioral changes of sensory contact model in adolescent male Swiss Albino mice. Design: Stress was induced by sensory contact model (SCM) for 12 consecutive days. Defeated mice were randomly assigned to control group (vehicle), testosterone undecanoate (100mg/Kg) (TU 100) or testosterone undecanoate (500mg/Kg) (TU 500) given intramuscular once for 45 days administered 2 hours after the last SCM session. Results: SCM significantly reduced distance traveled, time spent in the center, average speed in the open field test compared to negative control group. In addition, SCM significantly reduced …

Network-Level Mechanisms Underlying Effects Of Transcranial Direct Current Stimulation (Tdcs) On Visuomotor Learning, Pejman Sehatpour, Clément Dondé, Matthew J. Hoptman, Johanna Kreither, Devin Adair, Elisa Dias, Blair Vail, Stephanie Rohrig, Gail Silipo, Javier Lopez-Calderon, Antigona Martinez, Daniel C. Javitt

Publications and Research

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation approach in which low level currents are administered over the scalp to influence underlying brain function. Prevailing theories of tDCS focus on modulation of excitation-inhibition balance at the local stimulation location. However, network level effects are reported as well, and appear to depend upon differential underlying mechanisms. Here, we evaluated potential network-level effects of tDCS during the Serial Reaction Time Task (SRTT) using convergent EEG- and fMRI-based connectivity approaches. Motor learning manifested as a significant (p <.0001) shift from slow to fast responses and corresponded to a significant increase in beta-coherence (p <.0001) and fMRI connectivity (p <.01) particularly within the visual-motor pathway. Differential patterns of tDCS effect were observed within different parametric task versions, consistent with network models. Overall, these findings demonstrate objective physiological effects of tDCS at the network level that result in effective behavioral modulation when tDCS parameters are matched to network-level requirements of the underlying task.

Reversal Of Neurodegeneration By Engineered Monocytes In Alzheimer’S Disease, Chao-Hsien Chen

Dissertations & Theses (Open Access)

The health challenges posed by Alzheimer’s disease (AD) continue to grow as societies age worldwide. Accumulation of Tau-associated pathology correlates with clinical cognitive deterioration in AD. Resident myeloid cells within the central nervous system (CNS) have a limited capacity to uptake and degrade Tau; however, the resulting secretion of proinflammatory cytokines only acts to accelerate neurodegeneration. Therapeutic antibodies can reduce the neurotoxic oligomeric form of Tau (o-Tau), but in doing so they also aggravate inflammation. Attenuating mutation of the antibody Fc region can silence inflammation but also eliminates its capacity to mediate o-Tau clearance by CNS myeloid cells. Thus, there …

Restorative Potential And Working Memory Capacity Of Exposure To Vegetation In Indoor Built Environments, Jee Heon Rhee

Theses and Dissertations

This research seeks to understand how natural elements – specifically, vegetation in the indoor environment - influence people’s ability to restore attention and working memory capacity. Previous research demonstrates the benefits of nature on human beings in various ways. For instance, numerous studies show the positive effects of nature on stress reduction (Hartig, Mang, & Evans, 1991; Ulrich et al., 1991) and attention restoration (Staats, Kieviet, & Hartig, 2003). However, most of these studies focus on the effect of nature in outdoor settings. Relatively few studies focus on the presence of natural elements indoors. This is an important gap in …

Implementation Of A Guideline For Major Depressive Disorder In A Private Practice Clinic, Doreen Phillips

Doctor of Nursing Practice

Major depressive disorder (MDD) is a chief mental health illness that carries a profound economic burden. Many who suffer from MDD find little to no relief with traditional pharmacological interventions.The 2010 American Psychiatric Association Guidelines for Treatment of Patients with MDD recognized TMS as a second-line treatment choice. Several double-blind, randomized controlled trials illustrated the efficacy and safety of TMS as a viable treatment option for MDD. The purpose of this project was to implement standardized processes through the use of a treatment guideline to help provide comprehensive treatment options for patients suffering from moderate to severe major depressive disorder …

Qki-Mediated Cholesterol Biosynthesis In Eye Lens And Myelin Of The Central Nervous System, Seula Shin, Seula Shin

Dissertations & Theses (Open Access)

Cells obtain cholesterol in two ways, de novo biosynthesis and uptake from circulation. While most tissues utilize both sources, eye lens and brain depend extensively on cholesterol biosynthesis due to the limited supply from circulation. Lens cell membrane consists of highest portion of cholesterol. Brain is the most cholesterol-rich organ, which accounts for 23% of total cholesterol. Genetic mutations of cholesterol biosynthesis enzymes in humans and animal models present cataracts and hypomyelinating disorders linked to neurological impairment. Yet, it remains unclear how gene expression of cholesterol biosynthesis is regulated in lens and brain. Therefore, studying cholesterol biosynthesis in both tissues …

Inactivation Of Nucleus Reuniens Impairs Spatial Memory In Mice, Miranda Schwabe

Theses and Dissertations

Episodic memory is a complex process requiring input from several regions of the brain. Coordinated activity in the Dorsal Hippocampus (DH) and medial Prefrontal Cortex (mPFC) is required for episodic memory consolidation. Our laboratory demonstrated that simultaneous subthreshold chemogenetic inactivation of the dorsal hippocampus (DH) and medial prefrontal cortex (mPFC) impairs the consolidation of object placement (OP) and object recognition (OR) memory in female mice (Tuscher et al., 2018), suggesting that these two brain regions work in concert to promote memory consolidation. However, the mechanisms through which the DH and mPFC interact to promote memory consolidation remain poorly understood. A …

The Role Of Cerebellar Structural Plasticity And Astrocytic Activity In Motor-Skill Learning, Morgan Stevenson

Theses and Dissertations

Motor-skill learning is associated with cerebellar synaptogenesis and astrocytic hypertrophy, but most of these assessments of cerebellar ultrastructure have been completed after one month of training. After one month of training, the motor-skills necessary to complete these tasks have been acquired for weeks. Furthermore, the contributions of cerebellar astrocytes to motor-skill learning remains largely unexamined. The first experiment of this dissertation aimed to characterize cerebellar ultrastructure during the acquisition phase of motor-skill learning, at a point when motor performance is still improving. The second experiment aimed to examine the contributions of cerebellar astrocytes to motor-skill learning by activating astrocytic Gi-signaling …

Data-Driven Approach To Dynamic Resting State Functional Connectivity In Post-Traumatic Stress Disorder, Carissa Weis

Theses and Dissertations

Posttraumatic stress disorder (PTSD) is a heterogenous psychological disorder that may result from exposure to a traumatic event. Using functional magnetic resonance imaging (fMRI), symptoms of PTSD have been associated with aberrations in brain networks that emerge in the absence of a given cognitive demand or task, called resting state networks. Most previous research in resting state networks and PTSD has focused on aberrations in the static functional connectivity among specific regions of interest (ROI) in the brain and within canonical networks constrained by a priori hypotheses. However, dynamic fMRI, an approach that examines changes in brain network characteristics over …

Calcium Dyshomeostasis In Neurodegeneration, Nicholas Emanuel Karagas

Dissertations & Theses (Open Access)

Neurodegenerative diseases, despite constituting a major and growing cause of mortality globally, have few effective treatments. In order to develop novel therapeutics to combat neurodegeneration, a better understanding of the molecular mechanisms underlying these diseases is needed. Neurons rely on Ca²⁺ to mediate many of their unique functions, and aberrant Ca²⁺ signaling has been broadly implicated in neurodegeneration. The goal of this dissertation is to delineate specific examples of Ca²⁺ dyshomeostasis that I have uncovered in Drosophila models of neurodegeneration.

I first define the role a neurodegeneration-associated mutation plays in perturbing presynaptic [Ca²⁺], which is …

Qki-Mediated Cholesterol Biosynthesis In Eye Lens And Myelin Of The Central Nervous System, Seula Shin, Seula Shin

Dissertations & Theses (Open Access)

Cells obtain cholesterol in two ways, de novo biosynthesis and uptake from circulation. While most tissues utilize both sources, eye lens and brain depend extensively on cholesterol biosynthesis due to the limited supply from circulation. Lens cell membrane consists of highest portion of cholesterol. Brain is the most cholesterol-rich organ, which accounts for 23% of total cholesterol. Genetic mutations of cholesterol biosynthesis enzymes in humans and animal models present cataracts and hypomyelinating disorders linked to neurological impairment. Yet, it remains unclear how gene expression of cholesterol biosynthesis is regulated in lens and brain. Therefore, studying cholesterol biosynthesis in both tissues …

Spirituality As A Moderator Between Ptss And Cardiovascular Reactivity, Kriti Sharda

Honors Scholar Theses

Posttraumatic stress symptoms (PTSS) can be distressing and produce robust cardiovascular symptoms, such as increased heart rate and blood pressure, which have been implicated in higher risk of developing cardiovascular disease (CVD). Identifying factors that may reduce symptoms may suggest therapeutic strategies. One such potential factor is spirituality, given that spirituality is associated with both reducing PTSS and with preventing or improving CVD. We sampled 63 young college women who indicated being exposed to unwanted sexual contact. We asked them to write about their experience while we took heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) …

Extending Power Series Methods For The Hodgkin-Huxley Equations, Including Sensitive Dependence, James S. Sochacki

CODEE Journal

A neural cell or neuron is the basic building block of the brain and transmits information to other neurons. This paper demonstrates the complicated dynamics of the neuron through a numerical study of the Hodgkin-Huxley differential equations that model the ionic mechanisms of the neuron: slight changes in parameter values and inputted electrical impulses can lead to very different (unexpected) results. The methods and ideas developed for the ordinary differential equations are extended to partial differential equations for Hodgkin-Huxley networks of neurons in one, two and three dimensions.

Applications Of Non-Invasive Neuromodulation For The Management Of Disorders Related To Covid-19, Abrahão Fontes Baptista, Adriana Baltar, Alexandre Hideki Okano, Alexandre Moreira, Ana Carolina Pinheiro Campos, Ana Mércia Fernandes, André Russowsky Brunoni, Bashar W. Badran, Clarice Tanaka, Daniel Ciampi De Andrade, Daniel Gomes Da Silva Machado, Edgard Morya, Eduardo Trujillo, Jaiti K. Swami, Joan A. Camprodon, Katia Monte-Silva, Katia Nunes Sá, Isadora Nunes, Juliana Barbosa Goulardins, Marom Bikson, Pedro Sudbrack-Oliveira, Priscila De Carvalho, Rafael Jardim Duarte-Moreira, Rosana Lima Pagano, Samuel Katsuyuki Shinjo, Yossi Zana

Publications and Research

Background: Novel coronavirus disease (COVID-19) morbidity is not restricted to the respiratory system, but also affects the nervous system. Non-invasive neuromodulation may be useful in the treatment of the disorders associated with COVID-19.

Objective: To describe the rationale and empirical basis of the use of non-invasive neuromodulation in the management of patients with COVID-10 and related disorders.

Methods: We summarize COVID-19 pathophysiology with emphasis of direct neuroinvasiveness, neuroimmune response and inflammation, autonomic balance and neurological, musculoskeletal and neuropsychiatric sequela. This supports the development of a framework for advancing applications of non-invasive neuromodulation in the management COVID-19 and related disorders.

Results: …

Multimodal Computational Modeling Of Visual Object Recognition Deficits But Intact Repetition Priming In Schizophrenia, Pejman Sehatpour, Anahita Bassir Nia, Devin Adair, Zhishun Wang, Heloise M. Debaun, Gail Silipo, Antigona Martinez, Daniel C. Javitt

Publications and Research

The term perceptual closure refers to the neural processes responsible for “filling-in” missing information in the visual image under highly adverse viewing conditions such as fog or camouflage. Here we used a closure task that required the participants to identify barely recognizable fragmented line-drawings of common objects. Patients with schizophrenia have been shown to perform poorly on this task. Following priming, controls and importantly patients can complete the line-drawings at greater levels of fragmentation behaviorally, suggesting an improvement in their ability to performthe task. Closure phenomena have been shown to involve a distributed network of cortical regions, notably the lateral …

Historical Trauma Response Scores As A Function Of Unresolved Grief And Substance Use Disorder In American Indian Populations, Andrew R. Saunders

Undergraduate Research Symposium

Abstract

Researchers are interested in the outcomes of interventions, specifically, measuring historical trauma (HT) among American Indian/Alaska Native communities and the long-term distress and substance abuse as a result of historical trauma response (HTR). Previous literature has implicated limitations in the clinical conceptualization of the relationship between intergenerational transfer of HTR and substance abuse. The aim of the current study is to examine treatment efficacy of 50 homosexual, American Indian males randomized to a culturally-adapted juxtaposition of (1) Group Interpersonal Psychotherapy (IPT), (2) Cognitive Processing Therapy (CPT), and (3) Historical Trauma and Unresolved Grief Intervention (HTUG), or (4) waitlisted on …

Copyright And The Brain, Mark Bartholomew

Journal Articles

This Article exploresthe intersection of copyright law, aesthetic theory, and neuroscience. The current test for copyright infringement requires a court or jury to assess whether the parties’ works are “substantially similar” from the vantage point of the “ordinary observer. ”Embedded within this test are several assumptions about audiences and art. Brain science calls these assumptions into question. The substantial similarity test posits that aesthetic reactions are unmeasurable and uniform. In actuality, they can be quantified and vary depending on audience and artistic medium. Neuroscience has already reconfigured the law in many areas, from tort damages to the death penalty. Now …

Examining The Structure Of Symbolic Number Representations In The Parietal Cortex: An Rsa Study, Aymee Alvarez Rivero

Electronic Thesis and Dissertation Repository

Previous studies using fMRI adaptation to investigate the neural substrate of symbolic number processing have found ratio-dependent responses in regions of the parietal cortex, suggesting that number symbols are coded by overlapping neuronal populations: the larger the ratio between two numerals, the more their representation overlap. The current study analyzed the distributed patterns of activation associated with numerals presented during this task. I could not find substantial evidence supporting the ratio-dependent structure of the similarity space predicted by the univariate adaptation analyses. I also failed to find evidence in favor of the alternative model that similarities were driven by lexical …

Sexually Dimorphic Oxytocin Receptor-Expressing Neurons In The Anteroventral Periventricular Nucleus Regulates Maternal Behavior, Kaustubh Sharma

LSU Doctoral Dissertations

The neurohypophysial hormone oxytocin is involved in the regulation of social behaviors, including social recognition, pair bonding, and sex-specific parental behaviors in a variety of species. Oxytocin triggers these social behaviors by binding to oxytocin receptors (OXTR) in various parts of the brain. Oxytocin-induced sex-typical behavior, therefore, suggests a sexual dimorphic distribution of OXTR in the brain. In recent years, the oxytocin system in the brain received tremendous attention as a potential pharmacological target for treatment of many psychiatric disorders, such as anxiety, autism spectrum disorders, and even sex-specific psychiatric disorder like postpartum depression (PPD). An important problem and a …

Is Executive Function The Universal Acid?, Stephen J. Morse

All Faculty Scholarship

This essay responds to Hirstein, Sifferd and Fagan’s book, Responsible Brains (MIT Press, 2018), which claims that executive function is the guiding mechanism that supports both responsible agency and the necessity for some excuses. In contrast, I suggest that executive function is not the universal acid and the neuroscience at present contributes almost nothing to the necessary psychological level of explanation and analysis. To the extent neuroscience can be useful, it is virtually entirely dependent on well-validated psychology to correlate with the neuroscientific variables under investigation. The essay considers what executive function is and what the neuroscience adds to our …