Neurosciences Commons^™

Age-Related Longitudinal Changes In Gray Matter Microstructure, Jessica Hayes

Wayne State University Theses

Measures of the brain’s microstructure may be more sensitive markers of aging than macrostructural measures. However, it remains unclear exactly how gray matter microstructure changes during aging and how this relates to changes in macrostructure. The present study evaluated how neurite density, orientation dispersion, and gray matter volume changed over a three-year period in a sample of healthy older adults. The role of age in modifying structural change within the hippocampus, precuneus, and rostral anterior cingulate cortex was also considered. Repeated measures general linear models additionally evaluated whether degree of change in microstructure between the first two measurement occasions modified …

Plasma Neurofilament Light As A Biomarker Of Neurodegeneration And Memory Function In Older Adults, Youjin Jung

Wayne State University Dissertations

Plasma neurofilament light (NfL) is a promising biomarker for monitoring and predicting cognitive function and neurodegeneration in Alzheimer’s disease (AD). However, the field still needs a better understanding of what plasma NfL reflects about neurodegenerative and cognitive changes occurring in AD, especially in the early stages of Alzheimer’s disease, for the optimized use of plasma NfL as a biomarker for AD for clinical and research purposes. Therefore, here I investigated how NfL is associated with memory function, the functional connectivity of the default mode network, and the microstructural properties of white matter and gray matter regions vulnerable to Alzheimer’s pathologies …

Hippocampal Subfield Volumes And Memory Development From Middle Childhood To Late Adulthood: 2-Year Longitudinal Change And Modifiers Of Age Effects, Roya Homayouni

Wayne State University Dissertations

Introduction: The hippocampus (Hc) is crucial for memory function across all ages and is comprised of distinct subfields: dentate gyrus (DG), cornu ammonis sectors (CA1-3), and subiculum. Hc subfields support different aspects of memory function across the lifespan and are differentially vulnerable to late-life pathology. Increased knowledge of normative lifespan developmental trajectories of Hc subfield volumes will illuminate their cognitive and health correlates across different ages. Yet, the evidence on change and variability of Hc subfield volumes across the lifespan is sparse. Methods: Here, I conducted a meta-analysis of cross-sectional findings of subfield volumes across ages (n = 48,278 participants, …

Estradiol Signaling Improves Extinction Memory Recall To Combat Cue-Induced Heroin Relapse In Rats, Jordan S. Carter

MUSC Theses and Dissertations

We are in the midst of an opioid use disorder (OUD) epidemic. While several treatments mitigate a range of factors contributing to return to use, or relapse, the power of drug-conditioned environmental cues to precipitate relapse have not been adequately addressed. One treatment modality targeting cue reactivity, cue exposure therapy (CET), exacerbated relapse in individuals with OUD, perhaps due to a deficit in extinction memory recall (EMR). Here, EMR is the ability to override the drug-cue association and prevent relapse. Interest remains in combatting cue-induced relapse, potentially by introducing a pharmacologic adjunct with CET to enhance EMR. In the following …

Effect Of Dopamine-2-Receptor Manipulation On Social Interaction And Social Decision-Making In Juvenile Fish, Kiren Kanazawa

CMC Senior Theses

Animals interact in intricate social networks. Social behavior is imperative in shaping relationships, in communication, and adapting to changing environments. Despite its profound effects on individual fitness and health, neural-molecular mechanisms behind social behavior and social decision-making continue to be identified. In the present study, we focused on the regulation of social behavior by the Dopamine-2-Receptor (D2R), based on its role in context-dependent social behavior. We used juvenile African cichlid fish, Astatotilapia burtoni, to investigate the effect of dopamine signaling manipulation on their aggressive, territorial, and affiliative behaviors. We hypothesize that D2R manipulation affects social decision-making in juvenile A. burtoni. …

Effects Of The Injury Recovery Process On Neuromuscular Activation In An Uninjured Ankle, Mark Tankersley

CMC Senior Theses

This study was conducted to observe the effects of changed activity levels due to a major lower extremity injury on ankle function in the uninjured leg. Neuromuscular activation in the Gastric Medialis (GAS) and Tibialis Anterior (TA), the muscles primarily responsible for movement at the ankle, was assessed in 8 athletes at the Claremont Colleges while walking on a flat surface, stepping up a 15º incline, and stepping up a 27º incline. Athletes were split into two groups based on injury condition: a “recovered” group (n=4) who had suffered a major lower extremity injury in the last two years in …

Modulating The Mtor Pathway Using Inducible Retrogradely Transported Aavs As A Novel Approach To Improve Motor Recovery In Spinal Cord Injury, Christopher Bosse-Joseph

Theses and Dissertations--Medical Sciences

Spinal cord injury poses multiple regeneration barriers, including neuronal-intrinsic and extrinsic factors. Overcoming these barriers has stood as a longstanding challenge in neuroscience. A well-studied mechanism to promote spinal cord regeneration and locomotor recovery is activating the PI3K/mTOR pathway by knocking out phosphatase and tensin homolog protein (PTEN). PTEN knockout (PTEN-KO) studies have traditionally used adeno-associated virus (AAV) viral vectors to improve functional recovery. The use of traditional AAV serotypes to induce PTEN-KO has shown promise to improve functional recovery in rodent models; however, these approaches show significant limitations for translational utility. Firstly, the use of traditional AAV serotypes to …

The Effect Of Estrogen And A Mitochondrial Uncoupling Prodrug On Traumatic Brain Injury-Induced Dysfunction In Mice., Olivia J. Kalimon

Theses and Dissertations--Neuroscience

A large percent of both clinical and pre-clinical traumatic brain injury (TBI) studies report better outcomes females after severe injury compared to males. Mitochondrial dysfunction is a well-characterized driver of secondary injury and an attractive neurotherapeutic target; though, there is limited research available on mitochondrial dysfunction in females. However, a few studies have shown total mitochondria from the cortex of females appear protected from TBI-induced bioenergetic dysfunction. These results were replicated in these studies so further characterization was performed. Additionally, protein expression of some oxidative phosphorylation (OXPHOS) complexes were elevated in the uninjured cortex of females relative to uninjured males, …

Enlarged Perivascular Spaces Are A Clinically Relevant Neuroimaging Biomarker Of Cerebral Small Vessel Disease, Timothy Justin Libecap

Theses and Dissertations--Neuroscience

Vascular contributions to cognitive impairment and dementia (VCID) represents the intersection between cerebrovascular disease and cognitive decline. Cerebral small vessel disease (cSVD) is an important risk factor that may precede the onset of VCID by years. cSVD is characterized by in-vivo neuroimaging biomarkers including enlarged perivascular spaces (ePVS). PVS are the site of interchange between interstitial fluid (ISF) and cerebrospinal fluid (CSF) which is believed to play a role in the removal of brain waste. Reduced clearance may lead to enlargement of the PVS and subsequent accumulation of toxic solutes characteristic of neurodegeneration. Given the presence of ePVS in brain …

The Role Of Dystrophic Microglia In Aging And Disease, Ryan K. Shahidehpour

Theses and Dissertations--Neuroscience

Microglia are the primary immune cells of the central nervous system and are crucial in maintaining homeostasis and defense from disease and injury in the brain. Recent genome-wide association studies (GWAS) have also highlighted microglia as a central player in Alzheimer’s disease (AD). However, the mechanisms of microglia’s influence are poorly understood. Traditionally, microglial subtypes characterized physiologically as “reactive” or “activated” have been linked with disease and injury in the brain. However, morphologically, a recently described microglia category known as “dystrophic,” characterized structurally by fragmented processes and cytoplasmic decay is believed to be more strongly associated with aging and neurodegeneration. …

Inhibiting Pi3k/Akt To Enhance Brain Uptake Of Anticancer Agents In Glioblastoma, Louis Rodgers

Theses and Dissertations--Pharmacy

Glioblastoma (GBM) is the deadliest and most common malignant CNS tumor. Despite advances in understanding its biology and the development of targeted therapies, effective treatment options remain limited. As a result, patient survival rates are dismal, with a 5-year survival rate of only 6.8% and an overall survival of less than two years. This poor outcome is partly due to our inability to treat GBM cells that infiltrate the whole brain. Focal treatments like surgery and radiotherapy alone are insufficient due to these invasive tumor cells. Therefore, chemotherapy following resection and irradiation of the primary tumor is essential to eliminate …

Scares: A Clinician Guide To Spinal Cord Awareness, Response, And Emergency Support Creation And Implantation Of Scares Protocol Among Hospitalist Advanced Practice Providers, Brittany Biega

DNP Scholarly Projects

While they are more common in patients with oncological disease and trauma, SCE still exist among patients without these comorbidities. Less has been established regarding care protocols in this population. The absence of standardized procedures has been linked to preventable, adverse patient outcomes, including cases of permanent damage due to delayed treatment. This project employs Lean Six Sigma methodologies and Johns Hopkins Evidence- Based Practice to devise a robust SCE protocol, aimed at standardizing care and improving patient outcomes. A multidisciplinary team including general medicine, neurology, neurosurgery, and neuroradiology developed “Spinal Emergency Management Guidelines” protocol, which was implemented within the …

Autonomic Modulation Of Cardiac Function In Hypertrophic Cardiomyopathy, Jenna Rose Disser

Dissertations, Master's Theses and Master's Reports

Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disorder. HCM is characterized by cardiac hypertrophy, fibrosis, and an increased risk of fatal arrhythmias and sudden cardiac death. Previous studies in humans with HCM have demonstrated increased cardiac norepinephrine spillover and reduced beta-1 receptor (β1R) expression in the left ventricle (LV). We have previously demonstrated that cardiac sympathetic tone is elevated in an alpha-tropomyosin mutant mouse model of HCM. We hypothesized that HCM mice would demonstrate reduced β1R expression in the LV and attenuated heart rate (HR) and dP/dt max responses to ramped infusion of the β1R agonist, dobutamine. …

Addressing Healthcare Disparities Faced By Aging Down Syndrome Populations, Rhea Mistry

Pitzer Senior Theses

Down syndrome (DS) is a chromosomal genetic condition that impacts the development of the body and brain. The life expectancy of individuals with DS has drastically improved over the decades, increasing from 9 years in 1929 to 25 years in 1983 and further reaching 60 years by 2002. Individuals with DS face a variety of prominent co-occurring health conditions that are subject to change over time, including cognitive, visual, and hearing impairments, sleep apnea, cardiovascular defects, Down syndrome regression disorder, and dementia. Despite this increase in life span, DS is still most familiar to pediatric care providers, resulting in healthcare …

Translational Approaches To Address The Metastatic/Resistant (Mr) Phenotype Of Non-Small Cell Lung Cancer Brain Metastases, Kent L. Marshall

Graduate Theses, Dissertations, and Problem Reports (ETD)

Lung cancer remains the most frequently diagnosed malignant neoplasm shared in men and women worldwide, second only to the sexually dimorphic prostate cancer in men and breast cancer in women. Overall, lung cancer was responsible for 12.5% of new cancer cases globally in the year 2022. Of these cases, 80-85% are non-small cell lung cancer (NSCLC), a highly genotypically diverse sub-type of lung cancer. Over the past three decades, extraordinary improvement in screening, smoking cessation, early diagnosis and targeted therapy have been made, improving NSCLC survival markedly. However, as patients are surviving their primary disease better, there is a temporal …

Does Heightened Perceptual Encoding In Blind Individuals Extend To Word Learning?, Lindsay N. Harris, Marissa Renee Bamberger

CISLL Publications

Past research reported blind participants tend to encode sensory details of encounters with stimuli they will later recall or recollect, whereas sighted individuals tend to abstract meaning from sensory information when encoding memories. Here we ask whether blind individuals’ use of perceptual in addition to semantic encoding extends to a task—word learning—whose purpose amounts to semantically encoding the word and definition. After studying the definitions of spoken or written words, blind braille readers (n = 23) and sighted print readers (n = 20) re-encountered each word and indicated whether it was previously presented in the same modality. Analyses …

Emerging Unconventional Therapies For Glioblastoma Multiforme, Danielle Morang

Capstone Showcase

Glioblastoma multiforme (GBM) is the most prevalent and aggressive primary malignant brain tumor occurring in adults with a median survival of less than two years. It is a highly invasive tumor characterized by genetic heterogeneity, angiogenesis, and rapid proliferation. Patients undergo a multimodal treatment regimen consisting of surgical resection and chemoradiation therapy, yet GBM tumors almost always recur with a worsening prognosis. The molecular and genetic complexities of GBM pose a significant challenge for developing effective therapeutics. Thus, it is imperative to identify new therapeutic targets and explore novel treatment strategies to improve patients’ overall survival time and quality of …

Synthetic Neuroactive Steroids Targeting Gaba-A Receptors As A Potential Therapy For Contraceptive-Associated Mood Disorders, Alexandria A. Davis

Scripps Senior Theses

4-10% of women who use hormonal oral contraceptives (HOCs) discontinue use after experiencing symptoms of anxiety, irritability, and depression in the first 3 months of administration. Previous studies have acknowledged a relationship between HOCs and emotional dysregulation but have not identified mechanisms by which HOCs have this effect. As a result, effective treatment options for HOC-induced mood disorders are lacking. Current theories implicate combined-HOCs, particularly those containing ethinyl estradiol and levonorgestrel (EE-LNG), in reducing neuroactive steroid levels. Specifically, HOC users show decreases in allopregnanolone, a positive allosteric modulator associated with neuronal inhibition and emotional regulation. The objective of this study …

Neural Correlates Of Executive Functioning In Preschool Children, Michelle Lobermeier

Master's Theses and Doctoral Dissertations

Healthy development of executive functioning (EF) provides an important foundation for emotional and behavioral regulation as well as academic success. Preschool is a time of rapid EF development, making this a target age group for identifying and intervening on EF weaknesses. Since EF has been historically difficult to behaviorally measure in preschoolers, the current study explores neural correlates of EF as another method by which to understand its development. The goal of the present study is to explore associations between resting state electroencephalography (EEG) power (i.e., theta, alpha, beta) and EF ability in preschool and examine how early regulatory ability …

Statins Are Rarely Prescribed For Incidentally Discovered Covert Cerebrovascular Disease: A Retrospective Cohort In A Large Electronic Health Record (Ehr) Identified Using Natural Language Processing, Lester Y Leung, Eric Puttock, David F Kallmes, Patrick Luetmer, Sunyang Fu, Chengyi X Zheng, Hongfang Liu, Wansu Chen, David M Kent

Faculty, Staff and Student Publications

Introduction: While incidentally discovered covert cerebrovascular diseases (id-CCD) are associated with future stroke, it is not known if patients with id-CCD are prescribed statins.

Methods: Patients age ≥50 with id-CCD on neuroimaging from 2009 to 2019 with no prior ischaemic stroke, transient ischaemic attack or dementia were identified using natural language processing in a large real-world cohort. Robust Poisson multivariable regression was used to assess statin prescription among patients without prior statins.

Results: Among 2 41 050 patients, 74 975 patients (31.1%; 4.7% with covert brain infarcts (CBI); 29.0% with white matter disease (WMD)) had id-CCD. 53.5% (95% CI 53.2 …

Vagus Nerve Stimulation For The Therapy Of Dravet Syndrome: A Systematic Review And Meta-Analysis, Shuang Chen, Man Li, Ming Huang

Faculty, Staff and Student Publications

OBJECTIVE: Dravet syndrome (DS) is a refractory developmental and epileptic encephalopathy characterized by seizures, developmental delay and cognitive impairment with a variety of comorbidities, including autism-like behavior, speech dysfunction, and ataxia. Vagus nerve stimulation (VNS) is one of the common therapies for DS. Here, we aim to perform a meta-analysis and systematic review of the efficacy of VNS in DS patients.

METHODS: We systematically searched four databases (PubMed, Embase, Cochrane and CNKI) to identify potentially eligible studies from their inception to January 2024. These studies provided the effective rate of VNS in treating patients with DS. The proportions of DS …

A Novel Super-Resolution Microscopy Platform For Cutaneous Alpha-Synuclein Detection In Parkinson's Diseasea Novel Super-Resolution Microscopy Platform For Cutaneous Alpha-Synuclein Detection In Parkinson's Disease, Ofir Sade, Daphna Fischel, Noa Barak-Broner, Shir Halevi, Irit Gottfried, Dana Bar-On, Stefan Sachs, Anat Mirelman, Avner Thaler, Aviv Gour, Meir Kestenbaum, Mali Gana Weisz, Saar Anis, Claudio Soto, Melanie Shanie Roitman, Shimon Shahar, Kathrin Doppler, Markus Sauer, Nir Giladi, Nirit Lev, Roy N Alcalay, Sharon Hassin-Baer, Uri Ashery

Faculty, Staff and Student Publications

Alpha-synuclein (aSyn) aggregates in the central nervous system are the main pathological hallmark of Parkinson’s disease (PD). ASyn aggregates have also been detected in many peripheral tissues, including the skin, thus providing a novel and accessible target tissue for the detection of PD pathology. Still, a well-established validated quantitative biomarker for early diagnosis of PD that also allows for tracking of disease progression remains lacking. The main goal of this research was to characterize aSyn aggregates in skin biopsies as a comparative and quantitative measure for PD pathology. Using direct stochastic optical reconstruction microscopy (dSTORM) and computational tools, …

Management Of Anhedonia After Epilepsy Surgery, Gerardo Maria De Araujo Filho, Antonio L Teixeira

Faculty, Staff and Student Publications

Anhedonia is clinically defined as difficulty or inability to feel pleasure or to be motivated to perform activities that were previously pleasurable. Anhedonia is a core feature of depressive disorders but can be present in other conditions such as substance use and anxiety disorders. Herein we report the case of a 34-year-old female who developed marked anhedonia after left cortico-amygdalohippocampectomy. Despite optimal seizure control, the person struggled with anhedonia and other depressive symptoms. After ruling out medico-neurologic complications, she was prescribed with a selective serotonin reuptake inhibitor and cognitive-behavioral therapy. Anhedonia can be a challenging neuropsychiatric presentation that requires ruling …

Targeting The Renin-Angiotensin System (Ras) For Neuropsychiatric Disorders, Aline Silva De Miranda, Danielle S Macedo, Natalia P Rocha, Antonio L Teixeira

Faculty, Staff and Student Publications

BACKGROUND: Neuropsychiatric disorders, such as mood disorders, schizophrenia, and Alzheimer's disease (AD) and related dementias, are associated to significant morbidity and mortality worldwide. The pathophysiological mechanisms of neuropsychiatric disorders remain to be fully elucidated, which has hampered the development of effective therapies. The Renin Angiotensin System (RAS) is classically viewed as a key regulator of cardiovascular and renal homeostasis. The discovery that RAS components are expressed in the brain pointed out a potential role for this system in central nervous system (CNS) pathologies. The understanding of RAS involvement in the pathogenesis of neuropsychiatric disorders may contribute to identifying novel therapeutic …

Co-Occurrence Of Autism Spectrum Disorder And Attention-Deficit/Hyperactivity Disorder With Idiopathic Hypersomnia: Data From The Hypersomnia Foundation Registry, Sophie Sevan Mikkelsen

Honors Undergraduate Theses

In recent years, hypersomnia patients and researchers alike have increasingly discussed the possibility of heightened comorbidities, or co-occurrences, of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) with the central disorders of hypersomnolence: idiopathic hypersomnia (IH) and narcolepsy (N). While a few scarce studies have investigated a link between ADHD and N, there has been no research on the co-occurrence of these conditions with IH. This study, using data from the Hypersomnia Foundation’s CoRDS Patient Registry, is the first to identify self-reported rates of ASD and ADHD diagnoses by people with idiopathic hypersomnia. Four chi-square tests were conducted to determine …

Abnormal Regulation Of Mitochondrial Sphingolipids During Aging And Alzheimer’S Disease, Simone M. Crivelli, Zainuddin Quadri, Ahmed Elsherbini, Hemendra J. Vekaria, Patrick G. Sullivan, Wenbo Zhi, Pilar Martinez-Martinez, Stefka D. Spassieva, Erhard Bieberich

Markey Cancer Center Faculty Publications

During pathogenesis of Alzheimer’s disease (AD), mitochondria suffer alterations that lead to low energy production and reactive oxygen species formation. However, the mechanism of impaired mitochondria homeostasis in AD is not fully understood. We hypothesized that abnormal sphingolipid metabolism in mitochondria could be one of the contributing factors to mitochondrial dysfunction. Synaptic and non-synaptic mitochondria were isolated from 5xFAD and wild type (WT) mice at 3 and 7 months using Ficoll gradient ultracentrifugation, and their function was analyzed using Seahorse assay. Additionally, mitochondria were ana- lyzed using mass spectrometry for proteomics and sphingolipidomics analyses. Sphingolipid levels were also determined in …

Sars-Cov-2 Infection History Is Positively Correlated With Frequency Of Psychotic Symptoms In Schizophrenia, Jackson D. Beecher

Honors Undergraduate Theses

Previous work in human and animal studies has implicated aberrant insular cortex (IC) activity in the pathophysiology of hallucinations. Of note, the IC overlaps with the olfactory cortex (OC), a region of the brain that receives extensive projections from sensory neurons of the olfactory epithelium. SARS-CoV-2 (COVID-19) is a highly infectious coronavirus with a demonstrated ability to cause anosmia; the virus does this by colocalizing with and damaging support cells in the olfactory epithelium, ultimately leading to alterations in olfactory receptor cell signaling to the OC. Given the overlap between OC and IC, we asked the question of whether COVID-19 …

A Rare Case Of Early Onset Vitamin B6 Dependent Epilepsy, Rohit Thorat, Qudsiya Ansari, Kailas Randad, Vinaya Singh, Akash Sarkate

Digital Journal of Clinical Medicine

Pyridoxine dependent epilepsy (PDE) is a rare seizure disorder which manifests in neonatal period, but can be manifested in early infancy also. Seizures are seen in the first month of life in the classical form, but in the atypical form they don't show up until later in life, sometimes as late as three years old. It has an autosomal recessive inheritance caused by mutation in ALDH7A1 gene, causing deficiency of alpha-aminoadepic semialdehyde dehydrogenase commonly known as antiquitin (ATQ). Its deficiency leads to accumulation of metabolites, which causes deficiency of functional form of pyridoxine. The seizures are non-responding to antiepileptic medications, …

Memory Impairments Due To Binge Ethanol Are Impacted By Age And Sex, Maria Alexis M. Bent

Theses and Dissertations

Ethanol is the most consumed drug among adolescents, which can cause long-term effects on memory and changes in gene and protein expression. While both adolescents and adults engage in binge drinking, the neurological and behavioral effects differ, with adolescents showing fewer adverse physiological effects but greater memory deficits than adults. Sex differences related to ethanol occur with women showing higher BEC than men and similar cognitive deficits despite fewer years of ethanol consumption. During adolescence the mPFC and dHPC undergo maturation development with both brain regions playing a role in spatial and recognition memory. Proteins critically involved in memory and …

Behavioral Effects Of Adolescent Social Isolation Stress And/Or Binge Drinking And The Role Of The Vhip --> Mpfc Circuit, Jyoti Lodha

Theses and Dissertations

Adolescence is characterized by heightened social interaction and risk-taking behavior. Disruptions to cortical development by binge ethanol or social isolation can lead to attention, social, and cognitive deficits later in life, and increase risk for alcohol use disorders. During adolescence, proper development of a monosynaptic connection from the ventral hippocampus (vHip) to the medial prefrontal cortex (mPFC) is critical to proper social and working memory. We ask whether these factors affect neurobiological factors such as gene expression and the role of the vHipmPFC circuit in these behaviors. Social stress was modeled by social isolation (aSI) during adolescence. We expect aSI …