Medicine and Health Sciences 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 …

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.

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 …

Optimizing Preprocessing Of Fmri Data To Maximize Correspondence Of Functional Anatomy Across Individuals, Nargess Ghazaleh

Electronic Thesis and Dissertation Repository

In movie-activation fMRI, intersubject correlation (ISC) indicates a functional correspondence across viewers. Brains di↵er in shape; spatial normalization and smoothing enhance inter-subject functional overlap. We compare three normalization methods and six smoothing levels to discover which method yields the best functional overlap, indexed by ISC. This is key to optimizing data analysis in clinical studies using movie-activation fMRI in future. In a 3T scanner, 44 healthy subjects watched an 8-min movie. Both normalization and smoothing a↵ected the strength and extent of the ISC. ISC values were more robust for ANTs and DARTELthanforSPM12andwere(asymptotically)thestrongestat12mmsmoothing. When image data are preprocessed with high-dimensional volumetric …

Rehabilitative Movement Approaches And Dance Interventions In Parkinson’S Disease, Cecilia Fontanesi

Dissertations, Theses, and Capstone Projects

The scope of this work is to address the functional deficits and symptoms experienced by those living with Parkinson’s Disease through movement interventions.

Chapter 1 offers a brief overview of current pharmacotherapy and rehabilitation approaches in Parkinson’s, focusing on dance in particular as a movement intervention that may be particularly suited to this population.

Chapter 2 focuses on brain plasticity and motor learning in PD, reporting the effects of rTMS applied after the acquisition of a motor skill. In this study, adaptation tested in patients with PD was comparable in the sham and TMS sessions, while retention indices tested on …

Sex/Gender Differences In Serial Position Profiles In Patients With Mild Cognitive Impairment And Healthy Controls, Emnet Z. Gammada

Dissertations, Theses, and Capstone Projects

Introduction: Alzheimer’s disease disproportionately affects more women, but paradoxically, men have a higher incidence of Mild Cognitive Impairment (MCI). Researchers have suggested that women’s verbal memory advantage across the lifespan reflects better premorbid skills, which then require more neurodegeneration to manifest early clinical impairment. To date, measurement of sex differences in verbal memory have used total list scores. We proposed that a granular examination of serial position effects (SPE) in list-learning can refine the source of sex/gender differences.

Methods: A cross-sectional analysis of participants with Mild Cognitive Impairment (MCI) and Healthy Controls (HC) was examined from the Alzheimer’s Disease Neuroimaging …

Comparison Of Longitudinal Changes In Resting State Functional Magnetic Resonance Imaging Between Alzheimer’S And Healthy Controls, Berk Can Yilmaz

Theses

Resting State Functional Magnetic Resonance Imaging (rs-fMRI) is a technique that is widely used for analyzing brain function using different approaches and methods. This study involves rs-fMRI analysis of Blood Oxygenation Level Dependent (BOLD) signals acquired from Alzheimer’s disease (AD) Patients and Healthy Controls (HC). Each subject in the study had both functional and anatomical images with at least one rs-fMRI scan with their Anatomical (T1) scans. Previous rs-fMRI studies have demonstrated that AD shows differences in Amplitude of Low Frequency (<0.1 Hz) Fluctuations (ALFF), and Regional Homogeneity (ReHo) measures according to HCs.

The aim of the study is to investigate individual and group level differences using ReHo and mALFF related …

Optimization And Validation Of A Modified Radial-Arm Water Maze Protocol Using A Murine Model Of Mild Closed Head Traumatic Brain Injury, Teresa Macheda, Kelly N. Roberts, Josh M. Morganti, David J. Braun, Adam D. Bachstetter

Spinal Cord and Brain Injury Research Center Faculty Publications

Cognitive impairments can be a significant problem after a traumatic brain injury (TBI), which affects millions worldwide each year. There is a need for establish reproducible cognitive assays in rodents to better understand disease mechanisms and to develop therapeutic interventions towards treating TBI-induced impairments. Our goal was to validate and standardize the radial arm water maze (RAWM) test as an assay to screen for cognitive impairments caused by TBI. RAWM is a visuo-spatial learning test, originally designed for use with rats, and later adapted for mice. The present study investigates whether test procedures, such us the presence of extra-maze cues …

Nutraceutical Potential For Alzheimer's Disease Treatment, Alex Gewecke

Undergraduate Research Journal

Alzheimer’s disease (AD) is a progressive disorder involving buildup of excessive amounts of proteins such as beta amyloid in the brain that leads to memory loss, inability to perform daily functions, and an early death. By 2060, the number of cases is forecast to nearly triple current numbers. Age is the primary risk factor for AD and no new drugs have been approved since 2003. Nutraceuticals, a broad category of substances that can be utilized for both medicinal and nutritional purposes may be able to help, which is why they are being more widely researched. Overall, a number of attempts …

Variations In Slow-Wave Eeg And Working Memory Deficits During Letter Number Sequencing Task Post-Concussion, Morgan Sotoloff

Neuroscience Presentations

Concussions are associated with various types of consequences, both short-term and long-term: ranging from acute symptomatology, resting protocols, return-to-play decisions, and the lingering effects that have been found to have significant impacts on cognitive processes and function in many individuals several months post-concussion. Previous research has demonstrated that certain dimensions of executive function are especially susceptible to mild traumatic brain injury (mTBI), specifically working memory and attention. Studies that have previously utilized electroencephalography (EEG), have found that increased very low frequency oscillations (VLFO) are associated with a disruption of goal-oriented activities, difficulties in cognition, hyperactivity, and inattention in concussed individuals …

Brain Complexity, Sentience And Welfare, Donald M. Broom

Animal Sentience

Neither sentience nor moral standing is confined to animals with large or human-like brains. Invertebrates deserve moral consideration. Definition of terms clarifies the relationship between sentience and welfare. All animals have welfare but humans give more protection to sentient animals. Humans should be less human-centred.

Olfaction Modulates Inter-Subject Correlation Of Neural Responses, Paul Deguzman, Anshul Jain, Matthias H. Tabert, Lucas C. Parra

Publications and Research

Odors can be powerful stimulants. It is well-established that odors provide strong cues for recall of locations, people and events. The effects of specific scents on other cognitive functions are less well-established. We hypothesized that scents with different odor qualities will have a different effect on attention. To assess attention, we used Inter-Subject Correlation of the EEG because this metric is strongly modulated by attentional engagement with natural audiovisual stimuli.We predicted that scents known to be “energizing” would increase Inter-Subject Correlation during watching of videos as compared to “calming” scents. In a first experiment, we confirmed this for eucalyptol and …

Investigation Of The Role Of Heparin-Binding Pocket In Amyloid Fibrils Formation Of Fgf-1, I Gusti Ayu Agung Septiari

Graduate Theses and Dissertations

Human acidic fibroblast growth factor (aFGF/hFGF-1) is one of the promising molecules to be investigated to generate an in-depth understanding of the pathological mechanism of Alzheimer's disease (AD) neurodegenerative disorder characterized by the presence of amyloid fibrils. Some in vivo and human brain tissue studies proved the correlation of high-level expression of FGF-1-induced neuroinflammation and the occurrence of AD. The presence of amyloid fibrils as a hallmark of AD can be related to the generic property of the proteins to form amyloid fibrils; High level of FGF-1, in this case, may contribute to the formation of amyloid fibrils. As a …

The Impact Of A Single Session Of Mindfulness Meditation On The Attentional Blink In Non-Meditators, Arielle L. Klopsis

Dissertations, Theses, and Capstone Projects

Attentional resources are limited therefore a stimulus can go undetected if it closely follows another target by 200-500ms. This phenomenon is known as the attentional blink. Mindfulness meditation has been shown to be beneficial in target detection and in decreasing the attentional blink. Since there is no standard for the type of meditation or duration of practice that leads to attention benefits, this study compares the two most popular types of meditation in a group of non-meditators: focused attention and open monitoring meditation. This study utilized an attentional blink paradigm to measure if a single session of mindfulness meditation can …

Two Nights Of Recovery Sleep Restores Hippocampal Connectivity But Not Episodic Memory After Total Sleep Deprivation, Ya Chai, Zhuo Fang, Fan Nils Yang, Sihua Xu, Yao Deng, Andrew Raine, Jieqiong Wang, Meichen Yu, Mathias Basner, Namni Goel, Junghoon J. Kim, David A. Wolk, John A. Detre, David F. Dinges, Hengyi Rao

Publications and Research

Sleep deprivation significantly impairs a range of cognitive and brain function, particularly episodic memory and the underlying hippocampal function. However, it remains controversial whether one or two nights of recovery sleep following sleep deprivation fully restores brain and cognitive function. In this study, we used functional magnetic resonance imaging (fMRI) and examined the effects of two consecutive nights (20-hour time-in-bed) of recovery sleep on resting-state hippocampal connectivity and episodic memory deficits following one night of total sleep deprivation (TSD) in 39 healthy adults in a controlled in-laboratory protocol. TSD significantly reduced memory performance in a scene recognition task, impaired hippocampal …

Exploring Effects Of Background Music In A Serious Game On Attention By Means Of Eeg Signals In Children, Fettah Kiran

LSU Master's Theses

Music and Serious Games are separately useful alternative therapy methods for helping people with a cognitive disorder, including Attention Deficit Hyperactivity Disorder (ADHD). The goal of this thesis is to explore the effect of background music on children with and without ADHD. In this study, a simple Tetris game is designed with Beethoven, Mozart music, and no-music. There are different brainwave techniques for recording; among others, the electroencephalography (EEG) allows for the most efficient use of BCI. We recorded the EEG brain signals of the regular and ADHD subjects who played the Tetris we designed according to our protocol that …

Mental Associations And Music Therapy: Including The History Of Associationism And The Neurology Of Associations, Dianna Rose

Expressive Therapies Capstone Theses

Associations are formed in our minds based upon three elements: sensory experience, emotions, and memories. These associations, unique to each individual, dictate thoughts, beliefs, behaviors, and actions. Some are necessary and supportive, while others can be maladaptive. Established associations can be changed, and new associations can be formed, to align with a client’s goals. The literature presents a strong history of associationism, as well as a body of research that demonstrates the neurological processes of how mental associations are formed. There are also studies showing how music activates the brain. However, there is a lack of research which draws direct …

Neuroprotection Against Alzheimer’S And Lifespan Extension Induced By Dietary Restriction Are Associated With Metabolomic Changes And Depend On Oxidative Resistance Protein 1 (Oxr1), George W. Brownridge Iii

Natural Sciences and Mathematics | Biological Sciences Master's Theses

Dietary restriction (DR) has been demonstrated to be a robust means of extending the healthspan and lifespan, along with improving cognitive performance in various model organisms from yeast to primates, possibly by mediating neuroprotection. We utilized the Drosophila melanogaster model organism to better understand the molecular pathways that enable DR-induced benefits. By performing a genome-wide associated screening of the Drosophila Genetic Reference Panel (DGRP) that catalogues all natural genetic variants, we discovered that Oxidative resistance protein 1 (OXR1) showed the most significant difference in expression between DR and the inverse intervention of ad libitum (AL). Our research found that OXR1 …

The Current Neuroscientific Understanding Of Alzheimer's Disease, Rachel A. Brandes

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

Alzheimer’s disease is a degenerative neurological illness characterized by the deterioration of brain regions implicated in memory and cognitive function. While researchers have yet to find a cure or effective treatment, they have gained a better understanding of its pathology and development. Through years of neuroscience research, scientists have discovered much of what happens in the brain during Alzheimer’s disease onset and how this causes its symptoms; many hypotheses regarding this aspect of the illness involve temporal lobe atrophy, neurofibrillary tangles, and amyloid plaques. Although Alzheimer’s disease affects millions of people every day, it seems that most are unaware of …

Cpap-Compliance Of Aging Individuals With Obstructive Sleep Apnea With Or Without Mild Cognitive Impairment, Bailey Carter

Honors College

With approximately 20% of Americans affected by obstructive sleep apnea (OSA), and over 30% of sleep apneic patients non-compliant with the most common form of treatment, CPAP (Continuous Positive Airway Pressure), the proposed study looks to investigate the relationship between OSA, CPAP-compliance, and cognitive decline associated with many aging-related neurodegenerative diseases [1, 2]. Our group has performed in-home sleep studies using a patented, sensor mattress-sheet device, and standard actigraphy. Demographics including a questionnaire on OSA compliance and neurocognitive tests were administered to participants between 62 and 90 years of age. Cognitive decline meeting criteria for MCI (Mild Cognitive Impairment, the …

The Role Of Dopamine In Decision Making Processes In Drosophila Melanogaster, Michelle C. Bowers

Undergraduate Honors Theses

Understanding the neural processes that mediate decision making is a relatively new field of investigation in the scientific community. With the ultimate goal of understanding how humans decide between one path and another, simpler models such as Drosophila Melanogaster, the common fruit fly, are often utilized as a way of determining the neural circuits involved in these decision-making processes. One of the most important decisions flies make is the decision of where to lay their eggs (oviposit). Choosing the proper substrate upon which to lay eggs is a crucial decision that can ultimately impact their fecundity. This paper investigates the …

Pornography: Adolescent Brain Development & Addiction, William K. Canady

National Youth Advocacy and Resilience Conference

This presentation will explain the historical development of pornography. It will highlight three segments: 1- Porn’s impact on brain development of reward pathways, ultimately increasing the appetite for more porn. 2- Porn can be a false substitute for real intimacy, resulting in decreased sexual satisfaction with a real person and increased verbal and physical aggression. 3- Porn promotes sex trafficking, promotes multiple sex partners and reduced STD prevention.

Mechanisms Of Value-Biased Prioritization In Fast Sensorimotor Decision Making, Kivilcim Afacan-Seref

Dissertations and Theses

In dynamic environments, split-second sensorimotor decisions must be prioritized according to potential payoffs to maximize overall rewards. The impact of relative value on deliberative perceptual judgments has been examined extensively, but relatively little is known about value-biasing mechanisms in the common situation where physical evidence is strong but the time to act is severely limited. This research examines the behavioral and electrophysiological indices of how value biases split-second perceptual decisions and the possible mechanisms underlying the process. In prominent decision models, a noisy but statistically stationary representation of sensory evidence is integrated over time to an action-triggering bound, and value-biases …

Can Human Neurological Tests Of Consciousness Be Applied To Octopus?, Benedetta Cecconi, Jitka Annen, Steven Laureys

Animal Sentience

If the anatomy, physiology and behaviour of a species differ substantially from our own, can we infer that the species is unconscious? In the daily clinical care of patients with disorders of consciousness we face many similar challenges: our current approach with these patients - a combination of behavioural and brain imaging-based assessments - might also be a viable route to investigating octopus consciousness.

The Interplay Of Progestins, Matrix Metalloproteinases, And The Aging Brain, Keyana Nicole Porter

Graduate Theses, Dissertations, and Problem Reports

Progestins are synthetic hormones that are designed to mimic the biological actions of progesterone. They, however, possess other pharmacological actions and properties, in addition to their progestational activities. Medroxyprogesterone Acetate (MPA) is a progestin used globally in the hormonal contraceptive, Depo Provera®, by women in their reproductive prime and is a major compound found in hormone therapy (HT) formulations used by menopausal women. MPA is used by approximately 1 in 5 adolescents and adult women in the United States who are sexually active. Globally, nearly 48 million women utilize injectable contraceptives to prevent pregnancy, with most users utilizing MPA as …

What Makes An Image Memorable? Effects Of Encoding On The Mechanism Of Recognition, Asiya Gul

Theses and Dissertations (Comprehensive)

Memory is undoubtedly one of the most important processes of human cognition. A long line of research suggests that recognition relies on the assessment of two explicit memory phenomena: familiarity and recollection. Researchers who support the Dual Process Signal Detection (DPSD) model of recognition memory link the FN400 component (a negative ERP deflection peaking around 400 ms at frontal electrodes) with familiarity; however, it is currently unclear whether the FN400 reflects familiarity or implicit memory. Three event-related potentials (ERP) studies were conducted to determine whether implicit memory plays a role in setting up encoding strategies, and how these encoding strategies …