Cognitive Neuroscience Commons^™

Menstrual Cycle Phase Effects On Alcohol-Impaired Driving Performance And Risk Awareness, Annie K. Griffith

Theses and Dissertations--Psychology

Growing evidence indicates that risky behavior among women is elevated during the late follicular phase of the menstrual cycle, likely due to increased estradiol levels. Furthermore, alcohol-induced impairment of women’s inhibitory control is significantly greater during the late versus early follicular phase. Consequently, cycle phase may influence outcomes of poor inhibitory control while intoxicated, such as alcohol-impaired driving. Alcohol-impaired driving risk manifests in two ways: risk-taking while driving, and risk awareness regarding the decision to drive. This dissertation tested the hypothesis that alcohol-induced increases in driver risk-taking and decreases in risk awareness would be exacerbated during the late versus early …

Daily Rhythms In Psychosocial Stress, Sleep, And Mood: A Multimethod Approach To Transdiagnostic Psychopathology Risk And Intervention, Gabriel Gilmore

Theses and Dissertations--Psychology

Rhythms are central to nearly every core physiological and psychological process and have profound influences on overall health and well-being, particularly in the context of mood disorders. This dissertation emphasizes a rhythm-centered framework for understanding transdiagnostic psychopathology, proposing that the temporal organization of psychosocial stress, sleep, and mood provides crucial information for the development and treatment of mood disorder symptomology. Current literature relies primarily on mean symptom levels, overlooking day-to-day patterns in psychosocial experiences. To address this key methodological gap, three studies are examined. Study 1 develops and validates the Psychosocial Stress Regularity Measure (PSRM), a brief single-item measure of …

Weighted Family History Density Of Substance Use: Influence On Participant Substance Use Onset, Escalation, And Duration, Carleigh A. Litteral

Theses and Dissertations--Psychology

Substance use disorders impose a staggering toll on the United States (U.S.), straining healthcare systems, destabilizing communities, and profoundly impacting both individuals and families. Approximately one in six Americans aged 12 and older had a past-year substance use disorder in 2022 (Key Substance Use, 2022), and nearly one-third of adults experience a substance use disorder in their lifetime (Wu, 2010), contributing to an economic burden exceeding $400 billion annually (National Drug Threat Assessment, 2011). Family history of substance use disorders is a key predictor of vulnerability, with individuals who have affected relatives being 2–8 times more …

Exploring The Effects Of Transcranial Direct Current Stimulation Of The Right Inferior Frontal Gyrus On Inhibitory Control In Posttraumatic Stress Disorder, Colton Rippey

Theses and Dissertations--Psychology

Background: The right inferior frontal gyrus (rIFG) is implicated in stop signal reaction time (SSRT) performance – a common measure of inhibitory control – and emotional expression and control. Individuals with posttraumatic stress disorder (PTSD) exhibit poorer stop SSRT performance, which is associated with rIFG hypoactivity. Neuromodulation of the rIFG with transcranial direct current stimulation (tDCS) can significantly improve inhibitory control and reduce fearful responding to threatening stimuli. Research has yet to test the effects of multifocal tDCS targeting the rIFG on inhibitory control or emotional reactivity in individuals with PTSD.

Methods: The current study aims to examine the impact …

Harmonious Healing: A Review Of Music Therapy, A Humanities-Based Approach To Alzheimer’S Disease Treatment, Rohan K. Desai

Kentucky Undergraduate Journal for the Health Humanities

Alzheimer’s Disease (AD) is a progressive neurodegenerative disease often characterized by memory loss, confusion, and overall cognitive decline. The aging global population has, in recent years, highlighted the fundamental lack of pharmacological treatments for individuals facing an AD diagnosis. In response, a growing body of research has shifted focus to non-pharmacological humanities-based interventions. One such intervention has been music therapy (MT). Music-focused measures have shown great promise as a method of slowing cognitive decline, but mixed results in the literature warrant the need for further investigation. Often, socioeconomic barriers can limit an individual’s access to drug-related treatments, but the affordable …

Cancer Research Provides A Model For Advancing Clinical Trials In Dementia In The Era Of Disease-Modifying Alzheimer’S-Type Dementia Therapies, Gregory Jicha, Thomas Tucker, Susanne Arnold, Peter T. Nelson

Neurology Faculty Publications

Dementia and cancer are multifactorial, widely-feared, age-associated clinical syndromes that are increasing in prevalence. There have been major breakthroughs in clinical cancer research leading to some effective treatments, whereas the field of dementia has achieved comparatively limited success in clinical research. The lessons of cancer research may help those in the dementia research field in confronting some of the dilemmas faced when the clinical care regimen is not entirely safe or efficacious. Cancer clinical trials have assumed that untreated individuals with cancer are at high risk for morbidity and mortality after primary diagnoses. Thus, patients deserve a choice of clinical …

Impact Of Amyloid And Cardiometabolic Risk Factors On Prognostic Capacity Of Plasma Neurofilament Light Chain For Neurodegeneration, Keun You Kim, Eosu Kim, Jun-Young Lee, Alzheimer’S Disease Neuroimaging Initiative

Neurology Faculty Publications

Background Plasma neurofilament light chain (NfL) is a blood biomarker of neurodegeneration, including Alzheimer’s disease. However, its usefulness may be influenced by common conditions in older adults, including amyloid‑β (Aβ) deposition and cardiometabolic risk factors like hypertension, diabetes mellitus (DM), impaired kidney function, and obesity. This longitudinal observational study using the Alzheimer’s Disease Neuroimaging Initiative cohort investigated how these conditions influence the prognostic capacity of plasma NfL. Methods Non‑demented participants (cognitively unimpaired or mild cognitive impairment) underwent repeated assessments including the Alzheimer’s Disease Assessment Scale‑Cognitive subscale (ADAS‑Cog) scores, hippocampal volumes, and white matter hyperintensity (WMH) volumes at 6‑ or 12‑month …

Characterizing Resting Cerebral Blood Flow In Obsessive-Compulsive Disorder With Arterial Spin Labeling, Hannah R. Wild

Theses and Dissertations--Psychology

Obsessive-compulsive disorder (OCD) is a condition characterized by intrusive thoughts (obsessions) and ritualistic behaviors (compulsions) profoundly impacting daily functioning and quality of life. Neuroimaging studies using various techniques have revealed inconsistent resting cerebral blood flow (rCBF) patterns in OCD patients, particularly within the cortico-striatal-thalamo-cortical (CSTC) circuit and sensorimotor network. Arterial Spin Labeling (ASL) MRI offers a promising, noninvasive method for directly measuring rCBF. This study, using data from the Yale HCP Trio study, analyzed unmedicated OCD patients and healthy controls, who underwent two consecutive resting pulsed-ASL scans. OCD patients with lower obsessional severity exhibited higher perfusion in the pre- and …

High Volume Multiplex Staining Of Mouse Model In Alzheimer’S Associated Disease Pathology, Chloe Embry

Lewis Honors College Thesis Collection

Although neurodegenerative diseases are often clinically distinct, they typically share common pathological markers. One of the most common causes of clinical dementia is Alzheimer’s disease (AD). Pathologically, AD is defined by the presence of intercellular tangles composed of hyperphosphorylated tau proteins and extracellular plaques made of abnormally cleaved amyloid-beta proteins. However recent genome-wide association studies have also found that many of the predispositions for AD are located on or near genes highly expressed in microglia. In the healthy CNS, microglia act as the brain’s immune system and are chiefly involved in neuronal support and maintaining homeostasis throughout the CNS. Typically, …

Polyrhythmic Pathways: Using Bimanual Coordination Research To Develop A New Framework For Practice, Performance, And Pedagogy, Christian Swafford

Theses and Dissertations--Music

This study reviews and compares percussion literature pertaining to polyrhythms and scientific literature pertaining to bimanual coordination. There exists a gap in the pedagogical approach to polyrhythms, and there is much disagreement between common instructional methods, especially when considered against the findings of several bimanual coordination studies. The purpose of this study is to reveal insight to the percussion community that the learning of polyrhythms is facilitated by the brain in novel ways, and the uniqueness of this learning process requires a rethinking of the current pedagogical approach. Percussion articles, method books, popular literature, and music scores are surveyed alongside …

Effect Of Menstrual Cycle Phase On The Rewarding Properties Of Alcohol In Women, Annie K. Griffith

Theses and Dissertations--Psychology

Compared with men, women are disproportionately affected by alcohol, including greater risks of behavioral impairment and relapse. One likely mechanism underlying this disparity is fluctuations of ovarian hormones, particularly estradiol (E2), across phases of the menstrual cycle. Pre-clinical and clinical studies have shown that higher E2 levels correlate with heavier patterns of alcohol consumption, suggesting E2 may modulate drinking. This relationship is thought to be mediated by the rewarding properties of alcohol. The present thesis tested the hypothesis that elevated E2 during the late follicular phase would increase the rewarding properties of alcohol. Fifty young-adult women participated in a within-subjects …

The Effects Of Extended Fructose Access On Relative Value And Demand For Fructose, Saccharin, And Ventral Tegmental Stimulation, Megan Halloran

Theses and Dissertations--Psychology

Globally, food addiction (FA) is a growing area of research and is largely attributed to the availability of foods that are both energy dense and high in fats and sugars. Further, it has been suggested, that sugar and fat, when consumed frequently, have properties similar to drugs of abuse. While the validity of FA is questioned, researchers have drawn parallels between substance use disorder (SUD) and FA. For example, sugar binge models emphasize craving, withdrawal and binging as primary components of FA, which are also hallmarks of SUD. Additionally, both natural rewards, like sugars, and drug rewards act on the …

An Investigation Of Hhv6'S Impact On The Cognitive Progression And Microglial Changes In An Alzheimer's Disease Cohort, Charles E. Seaks

Theses and Dissertations--Physiology

The role of herpesviruses and, more specifically, HHV6 in the development of Alzheimer’s disease (AD) and associated cognitive decline is still being investigated. High ubiquity and prevalence in the population have led to a high degree of skepticism about HHV6 as a potential contributor to cognitive decline and dementias. However, recent evidence related to another herpesvirus, herpes simplex virus 1, suggests that reactivation, not carriage, of the virus may be the key factor to explain the dissonance between the virus’ ubiquity and contributions to dementias. With that in mind, we set out to assess cases from the Sanders-Brown Center on …

Cognitive Abilities In Hearing Loss: Perceived And Performance Abilities Of Adults Related To Attention, Memory, And Social Cognition, Karah Gottschalk

Theses and Dissertations--Gerontology

Hearing loss is the most common sensory deficit noted in aging adults. It is commonly known to reduce an individual’s ability to detect, identify, and localize sounds and speech and to cause issues in communication. However, there are other less commonly discussed impacts that hearing loss has beyond the auditory system. Literature suggests a correlation between hearing loss and cognition in aging adults. Similar to hearing loss, the domains of cognition experience performance and functional changes across the life span. In an aging adult, changes related to cognition are also suggested to be associated with hearing loss. This study aimed …

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 …

Exploring The Role Of Insulin Receptor Signaling In Hippocampal Learning And Memory, Neuronal Calcium Dysregulation, And Glucose Metabolism, Hilaree N. Frazier

Theses and Dissertations--Pharmacology and Nutritional Sciences

In the late 90’s, emerging evidence revealed that the brain is insulin-sensitive, highlighted by broad expression of brain-specific insulin receptors and reports of circulating brain insulin. Contemporary literature robustly supports the role of insulin signaling in normal brain function and suggests that insulin-related processes diminish with aging, evidenced by decreased signaling markers, reduced insulin receptor density, and lower levels of insulin transport across the blood-brain barrier. In the context of pathological cognitive decline, clinical trials using intranasal insulin delivery have reported positive outcomes on memory and learning in patients with mild cognitive decline or early-stage Alzheimer’s disease. However, while the …

Neurobehavioral Measurements Of Natural And Opioid Reward Value, Aaron Paul Smith

Theses and Dissertations--Psychology

In the last decade, (non)prescription opioid abuse, opioid use disorder (OUD) diagnoses, and opioid-related overdoses have risen and represent a significant public health concern. One method of understanding OUD is as a disorder of choice that requires choosing opioid rewards at the expense of other nondrug rewards. The characterization of OUD as a disorder of choice is important as it implicates decision- making processes as therapeutic targets, such as the valuation of opioid rewards. However, reward-value measurement and interpretation are traditionally different in substance abuse research compared to related fields such as economics, animal behavior, and neuroeconomics and may be …

Hyperhomocysteinemia As A Risk Factor For Vascular Contributions To Cognitive Impairment And Dementia, Brittani R. Price, Donna M. Wilcock, Erica M. Weekman

Physiology Faculty Publications

Behind only Alzheimer’s disease, vascular contributions to cognitive impairment and dementia (VCID) is the second most common cause of dementia, affecting roughly 10–40% of dementia patients. While there is no cure for VCID, several risk factors for VCID, such as diabetes, hypertension, and stroke, have been identified. Elevated plasma levels of homocysteine, termed hyperhomocysteinemia (HHcy), are a major, yet underrecognized, risk factor for VCID. B vitamin deficiency, which is the most common cause of HHcy, is common in the elderly. With B vitamin supplementation being a relatively safe and inexpensive therapeutic, the treatment of HHcy-induced VCID would seem straightforward; however, …

Astrocyte Activation And The Calcineurin/Nfat Pathway In Cerebrovascular Disease, Susan D. Kraner, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

Calcineurin (CN) is a Ca²⁺/calmodulin-dependent protein phosphatase with high abundance in nervous tissue. Though enriched in neurons, CN can become strongly induced in subsets of activated astrocytes under different pathological conditions where it interacts extensively with the nuclear factor of activated T cells (NFATs). Recent work has shown that regions of small vessel damage are associated with the upregulation of a proteolized, highly active form of CN in nearby astrocytes, suggesting a link between the CN/NFAT pathway and chronic cerebrovascular disease. In this Mini Review article, we discuss CN/NFAT signaling properties in the context of vascular disease and …

Does Transcranial Direct Current Stimulation To The Prefrontal Cortex Affect Social Behavior? A Meta-Analysis, Sarah Beth Bell, Nathan Dewall

Psychology Faculty Publications

This meta-analysis (k = 48, N = 2196) examined the effect of transcranial direct current brain stimulation (tDCS) applied to the prefrontal cortex on a variety of social behaviors, including aggression, overeating, impulsivity, bias, honesty, and risk-taking. tDCS showed an overall significant effect on reducing undesirable behaviors, with an average effect size of d = −0.20. tDCS was most effective at reducing risk-taking behavior, bias, and overeating. tDCS did not affect aggression, impulsivity, or dishonesty. We examined moderators such as brain region of interest, online vs offline stimulation, within- vs between-subjects designs, dose, and duration, but none showed significant …

Ca2+, Astrocyte Activation And Calcineurin/Nfat Signaling In Age-Related Neurodegenerative Diseases, Pradoldej Sompol, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

Mounting evidence supports a fundamental role for Ca²⁺ dysregulation in astrocyte activation. Though the activated astrocyte phenotype is complex, cell-type targeting approaches have revealed a number of detrimental roles of activated astrocytes involving neuroinflammation, release of synaptotoxic factors and loss of glutamate regulation. Work from our lab and others has suggested that the Ca²⁺/calmodulin dependent protein phosphatase, calcineurin (CN), provides a critical link between Ca²⁺ dysregulation and the activated astrocyte phenotype. A proteolyzed, hyperactivated form of CN appears at high levels in activated astrocytes in both human tissue and rodent tissue around regions of amyloid and …

When Less Is More: Mindfulness Predicts Adaptive Affective Responding To Rejection Via Reduced Prefrontal Recruitment, Alexandra M. Martelli, David S. Chester, Kirk Warren Brown, Naomi I. Eisenberger, C. Nathan Dewall

Psychology Faculty Publications

Social rejection is a distressing and painful event that many people must cope with on a frequent basis. Mindfulness—defined here as a mental state of receptive attentiveness to internal and external stimuli as they arise, moment-to-moment—may buffer such social distress. However, little research indicates whether mindful individuals adaptively regulate the distress of rejection—or the neural mechanisms underlying this potential capacity. To fill these gaps in the literature, participants reported their trait mindfulness and then completed a social rejection paradigm (Cyberball) while undergoing functional magnetic resonance imaging. Approximately 1 hour after the rejection incident, participants reported their level of distress during …

An Aged Canid With Behavioral Deficits Exhibits Blood And Cerebrospinal Fluid Amyloid Beta Oligomers, Clare Rusbridge, Francisco J. Salguero, Monique Antoinette David, Kiterie M. E. Faller, Jose T. Bras, Rita J. Guerreiro, Angela C. Richard-Londt, Duncan Grainger, Elizabeth Head, Sebastian G. P. Brandner, Brian Summers, John Hardy, Mourad Tayebi

Pharmacology and Nutritional Sciences Faculty Publications

Many of the molecular and pathological features associated with human Alzheimer disease (AD) are mirrored in the naturally occurring age-associated neuropathology in the canine species. In aged dogs with declining learned behavior and memory the severity of cognitive dysfunction parallels the progressive build up and location of Aβ in the brain. The main aim of this work was to study the biological behavior of soluble oligomers isolated from an aged dog with cognitive dysfunction through investigating their interaction with a human cell line and synthetic Aβ peptides. We report that soluble oligomers were specifically detected in the dog's blood and …

Insulin-Like Growth Factor-1 Overexpression Mediates Hippocampal Remodeling And Plasticity Following Tbi, Erica Latrice Littlejohn

Theses and Dissertations--Physiology

Every year over 2.5 million traumatic brain injuries (TBI) occur and are the leading cause of death and disability among adolescents. There are no approved treatments for TBI. Survivors suffer from persistent cognitive impairment due to posttraumatic tissue damage and disruption of neural networks which significantly detract from their quality of life. Posttraumatic cognitive impairment depends in part on the brain's limited ability to repair or replace damaged cells. Immature neurons in the hippocampus dentate gyrus, a brain region required for learning and memory, are particularly vulnerable to TBI. Insulin-like growth factor-1 (IGF1) is a potential therapeutic for TBI because …

Potential Candidates For Treating Deficits Associated With Developmental Ethanol Exposure In A Rodent Model: Solidago Nemoralis & Dimethoxybenzylidene-Anabasine, Logan James Fields

Theses and Dissertations--Psychology

Prenatal alcohol exposure (Fetal Alcohol Syndrome [FAS] and Fetal Alcohol Spectrum Disorders [FASD’s]) represents the leading preventable cause of intellectual disabilities in the western world, with FASDs estimated to affect approximately 2-5% of live births in the United States at an approximate annual cost of $3.6 billion (CDC, 2015; May et al., 2009). Ethanol (ETOH) exposure during development can lead to a variety of long-term behavioral impairments including problems with executive functioning, motor coordination, spatial learning, attention, and hyperactivity (Jones, 2011; Mattson & Riley, 1998). Much research has been conducted to develop pharmacological and/or environmental interventions to reduce these deficits, …

Dynamic Range Of Frontoparietal Functional Modulation Is Associated With Working Memory Capacity Limitations In Older Adults, Jonathan G. Hakun, Nathan F. Johnson

Physical Therapy Faculty Publications

Older adults tend to over-activate regions throughout frontoparietal cortices and exhibit a reduced range of functional modulation during WM task performance compared to younger adults. While recent evidence suggests that reduced functional modulation is associated with poorer task performance, it remains unclear whether reduced range of modulation is indicative of general WM capacity-limitations. In the current study, we examined whether the range of functional modulation observed over multiple levels of WM task difficulty (N-Back) predicts in-scanner task performance and out-of-scanner psychometric estimates of WM capacity. Within our sample (60–77 years of age), age was negatively associated with frontoparietal modulation range. …

Age Drives Distortion Of Brain Metabolic, Vascular And Cognitive Functions, And The Gut Microbiome, Jared D. Hoffman, Ishita Parikh, Stefan J. Green, George Chlipala, Robert P. Mohney, Mignon Keaton, Bjoern Bauer, Anika M. S. Hartz, Ai-Ling Lin

Sanders-Brown Center on Aging Faculty Publications

Advancing age is the top risk factor for the development of neurodegenerative disorders, including Alzheimer’s disease (AD). However, the contribution of aging processes to AD etiology remains unclear. Emerging evidence shows that reduced brain metabolic and vascular functions occur decades before the onset of cognitive impairments, and these reductions are highly associated with low-grade, chronic inflammation developed in the brain over time. Interestingly, recent findings suggest that the gut microbiota may also play a critical role in modulating immune responses in the brain via the brain-gut axis. In this study, our goal was to identify associations between deleterious changes in …

Functional Human Grin2b Promoter Polymorphism And Variation Of Mental Processing Speed In Older Adults, Yang Jiang, Ming Kuan Lin, Gregory A. Jicha, Xiuhua Ding, Sabrina L. Mcilwrath, David W. Fardo, Lucas S. Broster, Frederick A. Schmitt, Richard J. Kryscio, Robert H. Lipsky

Behavioral Science Faculty Publications

We investigated the role of a single nucleotide polymorphism rs3764030 (G > A) within the human GRIN2B promoter in mental processing speed in healthy, cognitively intact, older adults. In vitro DNA-binding and reporter gene assays of different allele combinations in transfected cells showed that the A allele was a gain-of-function variant associated with increasing GRIN2B mRNA levels. We tested the hypothesis that individuals with A allele will have better memory performance (i.e. faster reaction times) in older age. Twenty-eight older adults (ages 65-86) from a well-characterized longitudinal cohort were recruited and performed a modified delayed match-to-sample task. The rs3764030 polymorphism was …

Tuning Up The Old Brain With New Tricks: Attention Training Via Neurofeedback, Yang Jiang, Reza Abiri, Xiaopeng Zhao

Sanders-Brown Center on Aging Faculty Publications

Neurofeedback (NF) is a form of biofeedback that uses real-time (RT) modulation of brain activity to enhance brain function and behavioral performance. Recent advances in Brain-Computer Interfaces (BCI) and cognitive training (CT) have provided new tools and evidence that NF improves cognitive functions, such as attention and working memory (WM), beyond what is provided by traditional CT. More published studies have demonstrated the efficacy of NF, particularly for treating attention deficit hyperactivity disorder (ADHD) in children. In contrast, there have been fewer studies done in older adults with or without cognitive impairment, with some notable exceptions. The focus of this …

The Default Mode Network And Executive Function: Influence Of Age, White Matter Connectivity, And Alzheimer’S Pathology, Christopher A. Brown

Theses and Dissertations--Neuroscience

The default mode network (DMN) consists of a set of interconnected brain regions supporting autobiographical memory, our concept of the self, and the internal monologue. These processes must be maintained at all times and consume the highest amount of the brain’s energy during its baseline state. However, when faced with an active, externally-directed cognitive task, the DMN shows a small, but significant, decrease in activity. The reduction in DMN activity during the performance of an active, externally-directed task compared to a baseline state is termed task-induced deactivation (TID), which is thought to ‘free-up’ resources required to respond to external demands. …