Neurosciences Commons^™

Mapping The Neuroexposome: Integrative Analysis Of Dementia Risk Factors Through Multi-Omics And Environmental Profiling In The Egyptian Population., Mai Ahmed Saadzaghloul Othman

Theses and Dissertations

Background: Dementia represents one of the most pressing public health challenges of the twenty-first century, with the global burden projected to reach 153 million cases by 2050. Egypt, as the most populous Arab nation, faces a corresponding rise in age-related diseases, yet comprehensive data from low- and middle-income countries remain severely limited. The neuroexposome framework, integrating genetic susceptibility, environmental exposures, and metabolic alterations, offers a powerful strategy to characterize the complex interplay between internal and external risk factors for Alzheimer's disease (AD) and Alzheimer's disease Related Dementias (ADRD).

Objectives: This thesis aimed to: (1) examine the distribution of APOE alleles …

Patterns Of Language And Visuospatial Lateralisation In Three-Year-Old Children, Josephine E. Quin-Conroy, Donna M. Bayliss, Stephanie J. Bovell, Debra Eamer, Georgina H.M. Earl, Simon E. Fisher, Clyde Francks, Murray T. Maybery, Sarah Pillar, Desiree Silva, Andrew J.O. Whitehouse, Nicholas A. Badcock

Research outputs 2022 to 2026

Little is known about how or when language and visuospatial processing lateralise in the brain, and if individual differences in lateralisation are related to early language or visuospatial abilities. We explored if patterns of language and visuospatial lateralisation are related to cognitive skills in young children. A large sample of 3-year-olds (n = 136) attempted two functional transcranial Doppler ultrasound (fTCD) tasks to estimate language and visuospatial lateralisation. At the group level, language was lateralised to the left hemisphere, but visuospatial processing was weakly lateralised to the right hemisphere. The relationship between patterns of lateralisation and cognitive skills was investigated …

Molecular And Histologic Studies Of The Amygdala And Reward Circuits In Rhesus Macaques (Macaca Mulatta) With Self-Injurious Behavior (Sib), Jackie Barua

Doctoral Dissertations

Self-injurious behavior (SIB), also known as non-suicidal self-injury (NSSI), is characterized by deliberate infliction of harming one’s own body tissues without committing suicide, and persists in a group of captive rhesus macaques despite an enhanced enrichment program and pharmacological intervention with diazepam. The aim of this dissertation was to identify the neurobiological underpinnings of SIB by combining RNA-seq guided transcriptomic discovery and targeted candidate gene validation with unbiased histological and imaging analysis. The secondary aim was to employ a complementary mouse model to investigate the endogenous opioid system in response to diazepam. The amygdala transcriptome of primates with SIB (n …

Activated Dorsomedial Hypothalamic Astrocytes Regulate Feeding Behavior, Bella M. Lisenby

Honors Projects

The dorsomedial hypothalamus (DMH) region of the brain has been shown to be important for anticipatory feeding activity and play a role in restricting excessive food intake. In obese animals that overconsume calories, astrocytes within the DMH exhibit intracellular signaling changes indicative of cellular activation. Because astrocytes are known to influence neuronal function, we hypothesize that activated astrocytes regulate behavior. In the current study, we use chemogenetics combined with stereotaxic surgery to assess the contribution of astrocyte activity in the DMH towards metabolic behaviors.

Fentanyl Mediated Distortions Of Phasic Dopamine Release Dynamics Encoding Natural Reward And Aversive Processing In The Mammalian Mesolimbic Circuit, Oliver P. Culver Iv

MUSC Theses and Dissertations

Mu opioid receptor (MOR) agonists are recognized to disinhibit tonic dopamine (DA) in the ventral striatum (VS), contributing to opioid addiction and euphoria. However, MOR agonists can also inhibit non-drug reward-seeking, and disrupt conditioned responding to aversive stimuli, a phenomenon not readily explained by tonic DA disinhibition. We hypothesized that this effect could be due in part to disruption of phasic DA responses to conditioned stimuli (CS) which critically shape and maintain behaviors during naturalistic reward and aversive processing. Because MOR effects on CS-evoked phasic DA are largely unexamined, we conducted in vivo fiber photometric recordings in water-deprived male and …

Higher Sodium Intake Is Associated With Episodic Memory Decline In Cognitively Unimpaired Older Males: A 6-Year Longitudinal Study, Francisca Chuwa, Stephanie R. Rainey-Smith, Hilal Salim Said Al Shamsi, Hamid Sohrabi, Kevin Taddei, Colin L. Masters, Ralph N. Martins, Samantha L. Gardener

Research outputs 2022 to 2026

Recent evidence has suggested an association between high sodium intake and development of cognitive impairment. However, while animal studies demonstrate consistent relationships between sodium intake and cognitive impairment, this relationship remains less clear in humans. Our aim was to investigate the relationship between self-reported baseline sodium intake and cognitive decline over 72 months. Cognitively unimpaired participants (n = 1208) from the Australian Imaging, Biomarkers and Lifestyle study were included (70.87 years of age; 41 % male). Participants completed a food frequency questionnaire to quantify sodium intake and underwent comprehensive neuropsychological assessment at baseline and four additional timepoints, 18 months apart. …

Age-Related Increase In Plasma P-Tau217 In Amyloid-Beta–Negative Cognitively Unimpaired Individuals Affects Diagnostic Interpretation, Anna E. Mammel, Fernando Gonzalez-Ortiz, Ali Mousavi, Kelsey Hallett, Mary Encarnacion, Don Biehl, Pradip Gill, Sazan Ismael, Christopher Fowler, James D. Doecke, Larry Ward, Hans Frykman

Research outputs 2022 to 2026

Introduction: The extent to which non-pathological aging influences plasma biomarkers remains unclear. Here, we investigate factors influencing plasma p-tau217 levels in cognitively unimpaired (CU), amyloid-beta–negative (Aβ-) individuals. Methods: Plasma p-tau217 was measured in CU Aβ- positron emission tomography–negative (PET-) participants using two immunoassays (ALZpath n = 360 and LUMIPULSE G1200 n = 73). Associations between p-tau217 and age groups (60–69, 70–79, and 80+ years), apolipoprotein E (APOE) genotype, and gender were evaluated. Results: ALZpath plasma p-tau217 showed a non-pathological age-related increase (p < 0.001), and increased percentage within the intermediate zone with age. Lumipulse p-tau217 showed an increase in the percentage of subjects with positive results with age, however, this trend was not significant (p > 0.05). Men had higher levels of p-tau217 only with the ALZpath assay (p = 0.02; Lumipulse: p = …

Assessing Shifts In Research Priority Areas From The Neurological Community Before And After The Covid-19 Pandemic, Leah Dempsey, Travis Cruickshank, Mitchell Turner, Manja Laws, Danielle Bartlett, Barby Singer, Onno Van Der Groen, Moira Sim, Mandy Stanley

Research outputs 2022 to 2026

Introduction: People living with a neurological condition face many difficulties in daily life, impacting their function and quality of life (QoL). There is currently no cure to many neurological conditions, therefore identifying interventions to improve QoL is of high importance. COVID-19 changed society in many ways and understanding the research priorities from the neurological community post pandemic is urgently needed to ensure resources are used efficiently and aligned with the needs and priorities of the community. To better understand the priority areas, it is essential for individuals with lived experience to have input into priority areas for research. Therefore, the …

Mitigating Disparities In Diagnosis Of Dementia, Lycia Tramujas Vasconcellos Neumann, Simin Mahinrad, Erin L. Abner, Soo Borson, Goldie S. Byrd, Maria Carrillo, Lindsay Clark, Anthony N. Correro Ii, Kacie D. Deters, Gladys E. Maestre

School of Medicine Publications

The field of Alzheimer's disease and related dementias (AD/ADRD) is undergoing a transformative shift with a better understanding of disease biology, biomarker-based diagnostics, and disease-modifying therapies. Yet, these advancements risk exacerbating existing disparities in diagnosis and care. The 2024 Alzheimer's Association International Conference (AAIC) Advancements: Exploring Equity in Diagnosis convened interdisciplinary experts to address these inequities and chart a path toward population-generalizable research and practice. This article synthesizes key insights from the conference, highlighting considerations for inclusive and representative research design, ethical approaches in diagnostic disclosure, as well as challenges and solutions at individual, community, and systemic levels to advance …

Neuroinflammation And Neuropathology In A Novel Tau, Amyloid-Beta And Alpha-Synuclein Co-Pathology Model, Jhodi Mickayla Webster

ETDs from 2020-2029

Neurodegenerative diseases including Alzheimer’s disease (AD) and Parkinson disease (PD) often present with overlapping proteinopathies rather than aggregated proteins in isolation. Amyloid-β (Aβ) and phosphorylated tau are found in a substantial proportion of idiopathic PD cases, while α-synuclein (α-syn) pathology is present in over half of AD cases. The presence of these co-pathologies is associated with accelerated cognitive decline and increase mortality in these patients. In parallel, neurodegenerative diseases are increasingly recognized as being shaped by interactions between central nervous system (CNS) pathology and the immune system. Despite this, most experimental animal models of neurodegenerative disease examine single pathologies in …

Decentralizing Dementia Research To The Us–Mexico Border: The Rio Grande Valley Ad-Rcmar As A Model For Translational Equity, Gladys E. Maestre, John Blangero, Eron Manusov, Gabriel A. De Erausquin, Francisco Fernandez, Silvia Mejia-Arango, Vincent P. Diego, Juan C. Lopez-Alvarenga, Claudia Alaniz, Neyra García, Rosa V. Pirela, Andrew Tsin, Michael Mahaney

School of Medicine Publications

Translational equity means ensuring that diagnostics, treatments, care models, and prevention strategies are developed and implemented so they work for populations with the greatest burden and least access to care. In Alzheimer's disease and related dementias (ADRD), where most evidence derives from highly educated, non-Hispanic White participants at large academic centers, translational equity is critical to prevent misclassification, limited access, and widening disparities and to ensure that underrepresented communities shape how new knowledge moves into practice. Hispanic and other populations in the United States are disproportionately affected by ADRD yet remain underrepresented in research, with gaps especially pronounced in high-poverty …

Standardizing Nutrition Protocols For Brain Tumor Patients, Wendy Aldrich, Clifford A Pierre, Jun Ma, Mariam Ishaque, Christa Seyler, Miri Kim

All Poster Presentations

No abstract provided.

Thromboembolic Outcomes In Patients Receiving Doacs With Concomitant Antiseizure Medication, Hermela Gebregiogris, Brittanii Prahl, Michael Schirmer, Barbara Branneman, Jack Huber, Lam Vo

All Poster Presentations

No abstract provided.

Optimizing Cochlear Implant Follow Up: An Analysis Of Mstb 3 Proposed Timeline Changes, Alexandra Parbery-Clark, Dylan Severson, Sachin Gupta, Nadav Brumer, Elizabeth Elkins, Chantel Hazlewood, Jake Hillyer

All Poster Presentations

No abstract provided.

Mathematical Models Of Multisensory Detection And Decision-Making, Rebecca M. Brady

Doctoral

The brain seamlessly integrates signals from multiple sensory modalities to interpret the world efficiently. By using information from various senses, the brain can enhance its ability to detect and respond to stimuli more quickly and accurately. However, combining sensory cues from multiple modalities is only sometimes beneficial as it may lead to illusions and reduced behavioural performance. Behavioural and electrophysiological experiments have revealed that detection and decision-making strategies for multisensory cues evolve throughout human development and ageing. Additionally, studies have demonstrated that maladaptive multisensory processing is a key indicator of a proclivity to falls in older adults and individuals with …

From Transcriptome To Function: Multimodal Characterization Of Transcriptionally Defined Ventral Tegmental Area Dopamine Neurons, Natalie Dalton Fitzgerald

ETDs from 2020-2029

Substance use disorder is a complex neurobiological disease characterized by impaired control over drug taking and drug seeking. Drugs of abuse exert their reinforcing effects largely through dopaminergic (DAergic) projections from the ventral tegmental area (VTA) to the nucleus accumbens, where all drugs of abuse increase DA transmission. Beyond reward processing and reward learning, the VTA contributes to a range of psychiatric conditions, including schizophrenia and attention-related disorders. Although DA signaling has long been a major focus of addiction research, recent transcriptomic studies have revealed substantial heterogeneity of cell types within the VTA. Previous work from our lab identified two …

Investigating The Effects Of Increased O-Glcnaylation On Pathology In Alzheimer’S Disease, Melissa Louise Garcia

ETDs from 2020-2029

Alzheimer’s disease (AD) is currently the 7th leading cause of death, with few treatment options. It is known that AD pathology begins 20-30 years before clinical symptoms manifest. Some of the earliest pathological changes occur in glial cells of the hippocampus, causing them to become chronically reactive, as well as the accumulation of Amyloid-β (Aβ) in the hippocampus and hyperphosphorylated Tau (pTau) in the locus coeruleus, resulting in dysfunction of the noradrenergic (NA) system. Preclinical studies have shown promise in the abilities of the post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc). O-GlcNAc is a tightly regulated reversible enzymatic modification controlled by the …

Characterizing The Role Of The Paraventricular Nucleus Of The Thalamus D2r+ Neurons In Interoceptive Predictions, Briana Machen

ETDs from 2020-2029

Interoceptive predictions are internal models through which the brain anticipates future bodily states based on past experiences and environmental cues. Under healthy conditions, these predictions allow organisms to anticipate physiological needs and proactively adjust behavior to maintain homeostasis. When these processes become dysregulated, however, environmental cues can trigger maladaptive physiological responses. Although interoceptive prediction is increasingly recognized as a key mechanism underlying adaptive behavior, the neuronal circuits responsible for generating these predictions remain poorly understood. The paraventricular nucleus of the thalamus (PVT) receives convergent inputs from brain regions involved in processing both interoceptive signals and exteroceptive cues, positioning it to …

Evidence For Direct And Sleep-Moderated Relationships Between Aquaporin-4 Genetic Variants And Alzheimer's Disease Phenotypes, Tenielle Porter, Ayeisha Milligan Armstrong, Eleanor K. O'Brien, Vincent Doré, Pierrick Bourgeat, Mitchell Turner, Paul Maruff, Christopher C. Rowe, Belinda M. Brown, Victor L. Villemagne, Stephanie R. Rainey-Smith, Simon M. Laws

Research outputs 2022 to 2026

Introduction: Variants in the aquaporin-4 gene (AQP4) have been associated with Alzheimer's disease (AD) diagnosis, cognition, and brain amyloid beta (Aβ) and may affect the sleep and Aβ relationship. Their association with other AD-related phenotypes/disease progression remain largely unknown. Methods: Associations between AQP4 variants, self-reported sleep measures, and AD-related phenotypes in cognitively unimpaired individuals with evidence of Aβ accumulation were examined using data from the Australian Imaging, Biomarkers and Lifestyle study. Results: AQP4 variants were directly associated with regional brain volumes, atrophy, and cognition. They were also associated with differences in regional brain volumes and atrophy in interaction with sleep …

Efficacy And Safety Of A Bodyweight-Adjusted Higher Dose Of Ocrelizumab In Relapsing (Musette) And Primary Progressive (Gavotte) Multiple Sclerosis: Two Multicentre, Randomised, Double-Blind, Parallel-Group Phase 3b Trials., Stephen L Hauser, Gavin Giovannoni, Xavier Montalban, Jiwon Oh, Amit Bar-Or, Maria Pia Sormani, Martin S Weber, Sharon Stoll, Jacqueline A Nicholas, Tetyana Nehrych, Robert Bonek, Krzysztof Selmaj, Maciej Maciejowski, Dusanka Zecevic, Catarina Raposo, Rebecca Owen, Ulrike Bonati, Katrin Madjar, Eva Harfst, Qing Wang, Anastasiia Raievska, Marianna Manfrini, Hans-Martin Schneble, Ludwig Kappos, Musette And Gavotte Study Groups

Neuroscience Articles

BACKGROUND: Ocrelizumab is a humanised anti-CD20 monoclonal antibody approved for people with relapsing (RMS) or primary progressive multiple sclerosis (PPMS). In a post-hoc analysis of phase 3 trials in RMS and PPMS using a 600 mg dose, higher exposure to ocrelizumab was associated with greater B-cell depletion and lower risk of confirmed disability progression. Here, we prospectively assessed the efficacy and safety of a high dose of ocrelizumab in patients with RMS or PPMS.

METHODS: Two multicentre, double-blind, phase 3 controlled trials were conducted to compare high-dose ocrelizumab with the approved 600 mg dose of the drug in patients with …