Neuroscience and Neurobiology Commons^™

A 24-Week Double-Blind Placebo-Controlled Study Of The Efficacy And Safety Of The Ampa Modulator S47445 In Patients With Mild To Moderate Alzheimer's Disease And Depressive Symptoms, Eileen M. Bulger, Sylvie Gouttefangeas, Sylvie Bretin, Stéphanie Galtier, Philippe Robert, Vjera Holthoff-Detto, Jeffrey Cummings, Maria Pueyo

School of Medicine Faculty Research

Introduction S47445 is a novel positive allosteric modulator of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors that may emerge as a favorable candidate for the symptomatic treatment of cognitive and depressive disorders in patients suffering from Alzheimer's disease (AD) of mild to moderate severity and with depressive symptoms. Methods For this double-blind, placebo-controlled 24-week phase II trial, 520 outpatients aged between 55 and 85 years, with probable AD at mild to moderate stages (a Mini-Mental State Examination score of 24-15 inclusive) and exhibiting depressive symptoms (Cornell Scale for Depression in Dementia [CSDD] ≥ 8) were recruited in twelve countries and randomized to 3 doses …

Associations Between Comorbid Tdp-43, Lewy Body Pathology And Neuropsychiatric Symptoms In Alzheimer's Disease, Ece Bayram, Guogen Shan, Jeffrey L. Cummings

School of Public Health Faculty Research

More than half of the patients with Alzheimer’s disease (AD) have comorbidities including TDP-43 and Lewy bodies, which are also associated with frontotemporal lobar degeneration and dementia with Lewy bodies, respectively. These comorbidities may help explain the overlapping neuropsychiatric symptoms between AD and other dementias. Data on 221 AD patients with Neuropsychiatric Inventory-Questionnaire were obtained from the National Alzheimer’s Coordinating Center. TDP-43 was associated with aberrant motor activity, whereas Lewy bodies were associated with anxiety, irritability, sleep behavior, and appetite problems. The associations between these comorbidities and neuropsychiatric symptoms were more significant for patients with sparse diffuse plaques.

Acc Theta Improves Hippocampal Contextual Processing During Remote Recall, Ryan A. Wirt, James M. Hyman

Psychology Faculty Research

Consolidation studies show that, over time, memory recall becomes independent of the medial temporal lobes. Multiple lines of research show that the medial frontal cortex, including the anterior cingulate cortex (ACC), is involved with contextual information processing and remote recall. We hypothesize that interactions between the ACC and hippocampal area CA1 will change as memories became more remote. Animals are re-exposed to multiple environments at different retention intervals. During remote recall, ACC-CA1 theta coherence increases, with the ACC leading area CA1. ACC theta regulates unit spike timing, gamma oscillations, and ensemble and single-neuron information coding in CA1. Over the course …

Changes In Hippocampal-Anterior Cingulate Cortex Interactions During Remote Memory Recall, Ryan A. Wirt

UNLV Theses, Dissertations, Professional Papers, and Capstones

Spatial memory is an important cognitive process that relies on extensive neural networks throughout the brain. The hippocampus (HC) is important for the formation of these memories but over time, in a process referred to as consolidation, recall becomes increasingly reliant on other brain areas. The anterior cingulate cortex (ACC), a region within the medial prefrontal cortex, is important for spatial learning, spatial working memory, and remote memory recall, but the mechanisms underlying recall processes are still unknown. To better understand the role of the ACC and HC during memory recall, we introduced rodents into a series of spatially and …

Investigating Multiple Streams Of Consciousness: Using Descriptive Experience Sampling To Explore Internally And Externally Directed Streams Of Thought, Charles Fernyhough, Ben Alderson-Day, Russel T. Hurlburt, Simone Kühn

Psychology Faculty Research

Research into resting-state cognition has often struggled with the challenge of assessing inner experience in the resting state. We employed Descriptive Experience Sampling (DES), a method aimed at generating detailed and high-fidelity descriptions of experience, to investigate how experience in the resting state can vary between internal, external, and multiple simultaneous streams. Using a large body of experiential and brain activation data acquired from five DES participants, independent raters classified sampled moments of experience according to whether they were internally directed, externally directed, or contained elements of both at the same time. In line with existing models, comparison of internal …

Developmental Dependence For Functional Eye Regrowth In Xenopus Laevis, Cindy X. Kha, Kelly Ai-Sun Tseng

Life Sciences Faculty Research

A key challenge in designing tissue repair strategies is knowing whether and how developmental mechanisms are used for successful repair of mature/adult tissues. Although it is known that developmental components are used in repair, it remains mostly unclear which ones are required and whether they act similarly as during development. This issue is further complicated by the fact that it is difficult to assess the similarities and differences between development and the repair of mature tissues, since the two contexts are highly dissimilar. A potentially useful yet underutilized approach is to understand developmental regrowth (defined here as the ability to …

An Evaluation Of Alzheimer's Disease-Related Pathology In Two Different Models Of Diabetes In Immune-Challenged Mice, Andrew Scott Murtishaw

UNLV Theses, Dissertations, Professional Papers, and Capstones

Obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome are related disorders with wide-ranging and devastating effects that can be observed throughout the body. One important and understudied organ of damage is the brain. Clinical and epidemiological studies have found that T2DM, and more specifically hyperinsulinemia, significantly increases the risk of cognitive decline and increases the likelihood of Alzheimer’s disease (AD) and other forms of dementia in the elderly. Insulin has slightly different functions in the peripheral body than in the central nervous system and the dysregulation of these functions may contribute to the onset and progression of late-life neurodegenerative …

Network-Based Assessment Of Collaborative Research In Neuroscience, Gwen C. Marchand, Jonathan C. Hilpert, Kristine M. Bragg, Jeffrey Cummings

Educational Psychology, Leadership, and Higher Education Faculty Research

The purpose of this study was to describe collaborative research in neuroscience within the context of the Center for Neurodegeneration and Translational Neuroscience (CNTN), a Center of Biomedical Research Excellence supported by the National Institute of General Medical Science. Drawing upon research on the science of team science, this study investigated the way that interactions around research emerged over the course of establishing a new research center. The objectives were to document changes in research activity and describe how human research support infrastructure functioned to support the production of science.

Exercise, Learning And Emotional Health: Interdisciplinary Approaches To Translational Action, Tessa L. Koschel

UNLV Theses, Dissertations, Professional Papers, and Capstones

Exercise positively effects physical, psychological and neurological wellbeing. Though the population at large is becoming increasingly aware of the multi-faceted benefits of exercise, the majority of people fail to meet daily exercise recommendations. Largely, demands of everyday life such as work, school and family take priority over fitness. The issue therefore becomes a matter of time. In a world of media multi-tasking and immediate gratification, the challenge to health professionals becomes incorporation and manipulation of these consistencies to improve exercise uptake and adherence. Focus must shift from the idea of making additional time for exercise, to adding exercise to time …

Environmental Effects On Drosophila Brain Development And Learning, Xia Wang, Amei Amei, J. Steven De Belle, Stephen P. Roberts

School of Medicine Faculty Research

Brain development and behavior are sensitive to a variety of environmental influences including social interactions and physicochemical stressors. Sensory input in situ is a mosaic of both enrichment and stress, yet little is known about how multiple environmental factors interact to affect brain anatomical structures, circuits and cognitive function. In this study, we addressed these issues by testing the individual and combined effects of sub-adult thermal stress, larval density and early-adult living spatial enrichment on brain anatomy and olfactory associative learning in adult Drosophila melanogaster. In response to heat stress, the mushroom bodies (MBs) were the most volumetrically impaired among …

The Psychophysiological Correlates Of Personality, Trauma, Posttraumatic Stress Disorder And Social Support, Meghan E. Pierce

UNLV Theses, Dissertations, Professional Papers, and Capstones

Theories considering the etiology of psychopathy suggest that trauma exposure, specifically childhood maltreatment and sexual abuse, is related to the development of callous-unemotional traits in children and adolescents, which are precursors to psychopathic traits in adulthood. Furthermore, posttraumatic stress disorder has an opposite relationship with many of the emotional and behavioral components of the two-factor model of psychopathy. Specifically, PTSD is positively associated to IA and traits associated with it and negatively associated with FD. Thus, this study sought to expand upon the current theories of a trauma-based etiology of psychopathy by investigating the relationship between trauma, PTSD, and psychopathic …

An Evaluation Of Gabab Receptors On Modulating Neuroinflammation In A Non-Transgenic Animal Model Of Alzheimer's Disease, Monica Bolton

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive memory loss and distinct neuropathological hallmarks, including amyloid beta plaques and neurofibrillary tau tangles (NFT). Although the etiology remains to be discovered, several risk factors exist that significantly contribute to developing AD. Diabetes is one of the major risk factors associated with AD and is characterized by disrupted insulin signaling that may contribute to or exacerbate AD pathologies. Furthermore, both disorders result in increased neuroinflammation. Considerable evidence has demonstrated that a chronic inflammatory response, in particular chronic microglia activation, promotes A production as well as the hyperphosphorylation of tau through …

Neural Processes Underlying Auditory Context Effects, Breanne Yerkes

UNLV Theses, Dissertations, Professional Papers, and Capstones

Auditory information within our natural environments is disorganized and often ambiguous, leaving our auditory systems with a complex task: organizing sound into coherent objects. The auditory system uses both current and prior information to assist in completing this task. The influences of previous context on current perception have been referred to as context effects. A contrastive context effect results in a current perception that is opposite of what is expected based on the physical stimulus properties presented during an immediate context. A facilitative context effect results in a current perception that is the same as the perception during the immediate …

Assessing Clinical Significance Of The Immediate Post-Concussion Assessment And Cognitive Testing Battery When Comparing Adjusted And Unadjusted Rci Methods For Different Ranges Of Baseline Scores, Ashley N. Figaro

UNLV Theses, Dissertations, Professional Papers, and Capstones

The growing concern revolving around the dangers of sports-related concussions have led to the most recent implementation of neurocognitive (NC) test batteries as a means to objectively determine the presence of a cognitive defect. Whereas any other sports-related injury can be diagnosed with tools such as an x-ray or MRI, a concussion represents a metabolic disturbance that cannot be identified by these diagnostic tools. Many neurocognitive test batteries employ statistical techniques to derive cut off scores in order to represent significant or insignificant changes as compared to individual baseline scores, or pre-established normative values. If an individuals’ post-injury score exceeds …

An Integrative Neurological Model For Basic Observable Human Behavior, Ryan M. Francis

Calvert Undergraduate Research Awards

The scientific method uncovers information from the natural world in small increments. This spurs the design of models to explain how the pieces fit together and to identify future targets of research. This is especially the case in psychology, where visualizing concepts is an advantageous practice. One all too common criticism of cognitive and behavioral models in psychology is the lack of a biological basis. This paper aims to alleviate part of this issue by integrating currently understood biological and neurological mechanisms that drive psychological phenomena into a predictive and descriptive model for basic human behavior. To accomplish this task, …

The Effect Of Sleep On Perceptual Learning And Memory Consolidation, Vanessa Claire Irsik

UNLV Theses, Dissertations, Professional Papers, and Capstones

An ability to segregate speech accurately is essential given that most auditory environments contain other overlapping conversations or environmental noise. While perceiving speech among background noise can be difficult in and of itself, those with hearing impairments can experience considerable difficulty. While training has been shown to benefit perceptual segregation of trained sounds, it is unclear how such training transfers to sounds not included in a training regimen. The current study aimed to address this question by training listeners on a portion of sounds during a vowel segregation task, and subsequently testing on both the trained sounds and untrained sounds. …

Functional Capacity In Schizophrenia: Relationship Among Effort, Reinforcement Learning And Self-Beliefs, Sally J. Vogel

UNLV Theses, Dissertations, Professional Papers, and Capstones

Individuals with schizophrenia exhibit a wide range of complex neurocognitive, psychiatric and behavioral impairments. Recent research suggests that this complex array of symptoms can be at least partially accounted for by dysfunction in more basic mechanisms, such as the ability to learn from positive and negative reinforcement, or the ability to exert adequate effort when completing simple tasks. Evidence also suggests that deficits in these basic mechanisms may contribute to more complex symptoms, such as functional impairment. Also, the relationship between neurocognitive deficits and functional impairment has been found to be mediated by defeatist performance beliefs. However, studies have not …

A Comparison Of The Effects Of Different Doses Of Gabab Receptor Ligands On Spatial Learning And Memory And Memory Flexibility, Chelcie Heaney

UNLV Theses, Dissertations, Professional Papers, and Capstones

The principal inhibitory neurotransmitter in the brain, gamma amino-butyric acid (GABA), mediates several types of learning and memory. Of the two main receptor subtypes for GABA, the in vivo role of GABAB receptor in learning and memory is less well characterized and the current data often conflict. Based on the current literature, it is unclear, for instance, whether enhancing GABAergic activity via the GABAB receptor could be beneficial for or detrimental to learning and memory. Hippocampally-dependent learning and memory tasks are of particular interest due to their clinical relevance to patients with schizophrenia or Alzheimer’s disease, who exhibit impaired performance …

Postural Sway And Brain Hemispheric Power Spectral Density Under Different Attentional Focus Conditions, Sharon Jalene

UNLV Theses, Dissertations, Professional Papers, and Capstones

The purpose of this study was to determine the differences, if any, in the root mean square error (RMSE) of postural sway and hemispheric power spectral density (PSD) in the alpha and beta bands (8-12Hz and 12-25Hz) during different conditions of attentional focus (i.e., internal focus (IF), and external focus (EF) and a control condition (C)). Previous studies have shown that the adoption of IF and EF significantly alter motor performance and that EF promotes automaticity (Wulf, 2013). Sports performance and balance studies utilizing EEG spectral analyses report increased alpha oscillations during expert performance and stable balance and increased beta …

Hemispheric Asymmetry In The Perception Of Musical Pitch Structure, Matthew Adam Rosenthal

UNLV Theses, Dissertations, Professional Papers, and Capstones

Both the left and right hemispheres contribute to the perception of pitch structure

in music. Music researchers have attempted to explain the observed asymmetries in the perception of musical pitch structure by characterizing the dominant processing style of each hemisphere. However, no existing characterizations have been able to account for all of the empirical findings. To better explain existing empirical findings, this dissertation characterizes the left hemisphere as dominant in temporal pitch processing (i.e. with respect to the sequential ordering of pitches) and the right hemisphere as dominant in non-temporal pitch processing (i.e. without respect to the sequential ordering of …

The Effect Of Acute Lps-Induced Immune Activation And Brain Insulin Signaling Disruption In A Diabetic Model Of Alzheimer's Disease, Andrew Scott Murtishaw

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer's disease (AD) is a neurodegenerative disorder marked by progressive cognitive impairments and pathological hallmarks that include amyloid plaques, neurofibrillary tangles, and neuronal loss. Several well-known mutations exist that lead to early-onset familial AD (fAD). However, these cases only account for a small percentage of total AD cases. The vast majority of AD cases are sporadic in origin (sAD) and are less clearly influenced by a single mutation but rather some combination of genetic and environmental risk.

The etiology of sAD remains unclear but numerous risk factors have been identified that increase the chance of developing AD. Among these risk …

Alternations Of Nmda And Gabab Receptor Function In Development: A Potential Animal Model Of Schizophrenia, Monica Bolton

UNLV Theses, Dissertations, Professional Papers, and Capstones

Schizophrenia is a debilitating mental disorder that affects up to 3% of the world population. The behavioral symptoms are categorized into positive and negative symptoms, which appear during late adolescence/early adulthood. Unfortunately, the underlying cellular and molecular mechanisms of the disease are poorly understood. Several hypotheses exist to explain mechanisms contributing to these behavioral alterations. One model proposes that a reduced function of the NMDA glutamate receptor on specific GABAergic interneurons may be responsible for deficits in schizophrenia. Post-mortem investigations provide evidence of reductions in both glutamate and GABA-related proteins in patients with schizophrenia. Further, GABAergic interneurons that are activated …

The Effects Of Chronic Calcium Dysregulation On Behavioral And Pathological Features Of Alzheimer's Disease, Jonathan Sabbagh

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer's disease (AD) is a progressive neurodegenerative disorder whose etiology is unknown. Recent studies have implicated alterations in calcium homeostasis as a pathogenic contributor to AD. Calcium dysregulation has been observed in aged and AD brains, an event which could potentially facilitate the development of multiple pathologies observed in AD. Specifically, disrupting intracellular calcium levels in vitro has been demonstrated to increase amyloid-beta (Aβ) production, tau phosphorylation, and neuronal loss. However, there is a paucity of data on the behavioral and biochemical consequences of chronic in vivo perturbation of calcium homeostasis. In a series of experiments designed to evaluate the …

Second-Order Conditioning In Drosophila, Christopher J. Tabone

UNLV Theses, Dissertations, Professional Papers, and Capstones

Animals possess the ability to associate neutral stimuli in their environment with both rewards and punishment. A conditioned stimulus (CS1) such as a smell or sound, can become associated with an unconditioned stimulus (US), such as a food reward, to elicit what is known as the conditioned response (CR). This type of learning is commonly referred to as classical conditioning or first-order conditioning (FOC). Second-order conditioning (SOC) is an extension of this type of association wherein a novel stimulus is introduced (CS2) and associated with a previously conditioning first-order stimulus (CS1). As a result, the organism may show an attraction …

Analysis Of Morris Water Maze Data With Bayesian Statistical Methods, Maxym V. Myroshnychenko, Anton Westveld, Jefferson Kinney

Festival of Communities: UG Symposium (Posters)

Neuroscientists commonly use a Morris Water Maze to assess learning in rodents. In his kind of a maze, the subjects learn to swim toward a platform hidden in opaque water as they orient themselves according to the cues on the walls. This protocol presents a challenge to statistical analysis, because an artificial cut-off must be set for those experimental subjects that do not reach the platform so as they do not drown from exhaustion. This fact leads to the data being right censored. In our experimental data, which compares learning in rodents that have chemically induced symptoms of schizophrenia to …

Environmental Influence On Brain, Behavior, And Gene Expression In Drosophila, Xia Wang

UNLV Theses, Dissertations, Professional Papers, and Capstones

Brain development and behavior are sensitive to environmental stimuli. To gain an understanding of how and to what extent environmental variations, particularly with regard to thermal stress and sensory input, affect brain development, function, and genomic activity, in this dissertation, three interrelated studies were conducted in Drosophila melanogaster.

The first study examined the effects of ecologically-relevant hyperthermia stress on development of the Drosophila mushroom body (MB), a conserved sensory integration and associative center in the insect brain. A daily hyperthermic episode throughout larval and pupal development was shown to severely disrupt MB anatomy by reducing intrinsic Kenyon cell neuron …

Presenilin Is Necessary For The Function Of Cbp In The Adult Drosophila Cns, Randy S. Boyles

UNLV Theses, Dissertations, Professional Papers, and Capstones

Dominant mutations in Presenilin (Psn) have been correlated with the formation of Aß- containing plaques in patients with inherited forms of Alzheimer's disease (AD). However, a clear mechanism directly linking amyloid plaques to the pathology of familial or sporadic forms of AD has remained elusive. Thus, recent discoveries of several new substrates for Psn protease activity have sparked alternative hypotheses to explain the preclinical symptoms of AD. CBP (CREB-binding protein) is a haplo- insufficient transcriptional co-activator with histone acetyltransferase (HAT) activity that has been proposed to be a downstream target for Psn signaling. Individuals with reduced CBP levels have cognitive …

Neuropsychological And Emotion Processing Abnormalities In Bipolar Disorder I And Ii, Carol Randall

UNLV Theses, Dissertations, Professional Papers, and Capstones

Bipolar disorder illness is marked by emotional lability and mood disturbance, as well as various neuropsychological deficits, and the neuroanatomical correlates of many of these deficits are beginning to be identified. Numerous studies have implicated specific cortical and sub-cortical abnormalities in areas associated with executive function, memory, motor function, and the processing of emotion. Although a large body of research has been devoted to the investigation of cognitive and emotion-processing deficits in bipolar disorder, relatively few studies have been devoted to the investigation of how these deficits differ among bipolar disorder subtypes. This is surprising in light of known symptomatological …

A Longitudinal Study Of Neurocognitive Deficits And Functional Outcome In Bipolar Disorder, Brian D. Leany

UNLV Theses, Dissertations, Professional Papers, and Capstones

Bipolar disorder is an affective disorder that, in addition to being characterized by depressive and expansive mood symptoms, often presents with neuropsychological deficits. Bipolar disorder not only impairs an individual’s cognitive abilities, but these cognitive impairments may also impact day-to-day activities causing functional impairment. In other psychiatric disorders such as schizophrenia, it has been shown that the neuropsychological deficits are predictive of poor, long term treatment outcome and functioning. However, while bipolar disorder affects nearly 1 - 2% of the U.S. population (Keck, McElroy, & Arnold, 2001), little is known about the extent that neurocognitive deficits may play in the …

Genes Involved In Mushroom Body Development And Behavior In Drosophila, Christine Nicole Serway

UNLV Theses, Dissertations, Professional Papers, and Capstones

Mushroom bodies (MBs) are the site of multi modal sensory integration critical for associative conditioning in Drosophila. They have been central to research on the structure function relationship in the brain for over one hundred years due to their unique shape and readily accessible physiology. This dissertation incorporates three different approaches to further elucidate the genetic and molecular nature of this structure function relationship.

First, the suite of genetic and molecular tools available in Drosophila melanogaster, facilitated the molecular mapping of a 25-year old MB structural mutant called mushroom body miniature B (mbmB) to the gene Pendulin [Pen, also known …