Neurosciences Commons^™

The Therapeutic Potential Of Butyrate And Lauric Acid In Modulating Glial And Neuronal Activity In Alzheimer’S Disease, Rathnayaka Mudiyanselage Uththara Sachinthanie Senarath, Lotta E. Oikari, Prashant Bharadwaj, Vijay Jayasena, Ralph N. Martins, Wanakulasuriya Mary Ann Dipika Binosha Fernando

Research outputs 2022 to 2026

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by amyloid-β plaque accumulation, tau tangles, and extensive neuroinflammation. Neuroinflammation, driven by glial cells like microglia and astrocytes, plays a critical role in AD progression. Initially, these cells provide protective functions, such as debris clearance and neurotrophic support. However, as AD progresses, chronic activation of these cells exacerbates inflammation, contributing to synaptic dysfunction, neuronal loss, and cognitive decline. Microglia release pro-inflammatory cytokines and reactive oxygen species (ROS), while astrocytes undergo reactive astrogliosis, further impairing neuronal health. This maladaptive response from glial cells significantly accelerates disease pathology. Current AD treatments primarily aim …

Amyloid Accumulation, Brain Atrophy, And Cognitive Decline In Emergent Alzheimer's Disease, Ying Xia, Pierrick Bourgeat, Vincent Doré, Jurgen Fripp, Yen Ying Lim, Simon M. Laws, Christopher Fowler, Christopher C. Rowe, Colin L. Masters, Elizabeth J. Coulson, Paul Maruff

Research outputs 2022 to 2026

Introduction : Emergent Alzheimer's disease (AD) represents a transitional stage where cognitively unimpaired (CU) individuals exhibit subthreshold but increasing amyloid-β (Aβ) levels. The impact of Aβ accumulation on brain volume loss and cognition during this early stage remains unclear. Methods: This retrospective cohort study analyzed data from 408 CU participants who were initially Aβ− (< 15 Centiloids) and followed for up to 15 years. Changes in basal forebrain and hippocampal volume, along with domain-specific cognitive performance, were compared between those who progressed to Aβ+ (≥20 Centiloids) and those who remained Aβ−. Results: Sixty-five CU participants progressed to Aβ+, indicating emergent AD, and showed faster Aβ accumulation and subtle memory decline. However, no significant differences in rate of BF and hippocampal atrophy were observed between groups. Discussion: The results suggest that during this emergent phase of AD, Aβ accumulation is associated with episodic memory loss, in the absence of detectable accelerated brain atrophy. Highlights: Identified cognitively unimpaired individuals in the emergent stage of Alzheimer's disease (AD). Emergent AD exhibits a greater rate of amyloid-β (Aβ) accumulation. No accelerated volume loss detected in the basal forebrain or hippocampus. Emergent AD is also associated with a subtle decline in memory. Early Aβ accumulation may impair cognitive function before structural atrophy.

Effects Of Stressor Exposure And Locus Coeruleus Opioid Signaling On Coping And Anxiety-Like Behavior In Rats, John Arthur Tkaczynski

Theses and Dissertations

Stress is a physiological state of altered neuroendocrine signaling and heightened indices of behavioral vigilance and arousal in response to threatening stimuli. This project aimed to investigate the adaptations to stress that occur in the noradrenergic locus coeruleus (LC) and how these changes affect stress coping behavior. We began by investigating how adolescent restraint and predator odor stress affects coping when presented with a secondary noxious stimulus in the defensive shock probe burying task one week following stressor exposure, finding that stressed male rats demonstrate a more active coping response and stressed female rats demonstrate a more passive coping response, …

African Leadership In Brain Diplomacy: The Yaoundé Declaration Advances The Global Brain Economy Playbook For Better Brain Health, Alfred Kongnyu Njamnshi, Jacques Fame Ndongo, Ferdinand Ngoh Ngoh, Lejeune Mbella Mbella, Paul M. Ghogomu, Séraphin M. Fouda, Marie-Thérèse A. Ondoa Obama, Madeleine Tchuinte, Alamine O. Mey, Gladys Maestre

School of Medicine Publications

Africa, the world’s second-largest continent is home to 1.5 billion people, accounting for nearly 20% of the global population, (60% under age 25). By 2050, Africa’s population will be 2.5 billion, and by 2035, more young Africans will be entering the workforce each year than in the rest of the world combined. Africa also hosts a rich social, cultural, and geopolitical diversity across its 5 geopolitical zones covering 54 countries. It is the most genetically, culturally, and linguistically diverse region on the planet. However, Africa’s contribution to the global economy could be more significant if it urgently embraces the brain …

Partial Least Squares Multimodal Analysis Of Brain Network Correlates Of Language Deficits In Aphasia, Sigfus Kristinsson, Dirk B. Den Ouden, Chris Rorden, Roger Newman-Norlund, Lisa Johnson, Janina Wilmskoetter, Ezequiel Gleichgerrcht, Argye E. Hillis, Gregory Hickok, Julius Fridriksson, Leonardo Bonilha

Communication Sciences and Disorders Faculty Articles and Research

Lesion-symptom mapping techniques are essential to determine brain regions critical for language functions. However, high collinearity in neuroimaging and behavioural data remains a challenge for distinguishing neural substrates supporting multiple language domains (shared variance) and those subserving specific language functions (unique variance). Here, we employed a novel approach to multimodal lesion-symptom mapping using multivariate partial least squares regression to delineate the latent structure of lesion-behavioural mapping in aphasia and decompose the shared and unique neural determinants of language impairments. A total of 86 participants with chronic (>12-month post-stroke) aphasia after left hemisphere strokes were examined. Language impairment was assessed …

Beyond The Genome: The Racialized Exposome, Flourishing, And Stress Biology In African Americans, A Non-Exhaustive Review, Enye Washington

University Honors Theses

Racial health disparities remain an enduring challenge in the United States, disproportionately impacting African American communities through higher rates of chronic disease and premature mortality. This non-exhaustive literature explores how the racialized exposome - a term denoting the totality of social, environmental, and structural stressors rooted in systemic racism - biologically embeds itself via stress-responsive pathways. Specifically, it examines the interaction between racial stress, flourishing, and key biological markers, including allostatic load and telomere length, considering the gut-brain axis. The review highlights robust evidence that chronic exposure to racial discrimination and structural adversity contributes to multisystem dysregulation and accelerated cellular …

The Impact Of Type 2 Diabetes Mellitus On The Severity Of Alzheimer's Disease In Hispanic Populations In The Rio Grande Valley: A Pilot Retrospective Chart Review, Maria Camila Gonzalez Tovar, Daniel Salinas, Kelsey Baker

School of Medicine Publications

Background: Alzheimer's disease (AD) is becoming more prevalent worldwide, leading to a growing demand to understand the impact of risk factors on disease progression. Notably, type 2 diabetes mellitus (DM) has emerged as a significant risk factor for the development of AD, given the pathophysiological role of insulin resistance in cognitive impairment. In particular, the impact of type 2 DM on AD development and severity may be heightened in Hispanic populations due to the high prevalence of both conditions in this community. Here, we sought to understand the role of type 2 DM in AD severity in a Hispanic population …

Loss Of Neuropeptide F (Npf) Signaling Reduces The Strength Of Circadian Rest-Activity Rhythms But Not Feeding-Fasting Rhythms, Katelyn Ann Wendt

Master's Theses

The circadian system governs crucial physiological and behavioral processes, dictating activities like movement, hormone release, and sleep patterns over a 24-hour cycle. Disruptions to these rhythms can lead to various health problems, including cardiometabolic dysfunction. Research has demonstrated the presence of circadian rhythms of feeding behavior in diverse organisms, but the specific molecules involved are not yet identified. Neuropeptide Y (NPY) influences metabolic activity in mammals, and its counterpart, NPF, affects locomotor activity and feeding in Drosophila melanogaster. Our study aims to investigate whether NPF, its receptor (NPFR), and NPF-expressing cells play a role in regulating circadian rest-activity and feeding-fasting …

Mechanisms Underlying Estrous Cycle-Dependent Changes In Incubated Cocaine Craving, Erin Elizabeth Wannen

Theses and Dissertations

Cues associated with cocaine use are one of the most common relapse triggers and understanding what promotes cue-induced cocaine craving and relapse is a critical question in the field. Human studies have shown that these measures are impacted by fluctuations in ovarian hormone levels, as higher levels of estradiol promote cue-induced cocaine craving in women while higher levels of progesterone reduce craving in both sexes. Enhanced or incubated cue-induced cocaine seeking or craving also changes across the rodent reproductive (estrous) cycle as levels of estradiol and progesterone fluctuate, with enhanced seeking behavior observed during the estrus stage of the cycle. …

The Effect Of Birthweight And Gestational Age On Cognitive Function In Midlife: The Bogalusa Heart Study, Eunsun Gill, David J Libon, Soo Jung Kang, Ileana De Anda-Duran, Lydia A Bazzano, Wei Chen, Camilo Fernandez-Alonso, Emily W Harville

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Although the relationships between birthweight, gestational age (GA), and cognitive function (CF) before midlife have been demonstrated, the relationships after midlife and potential racial disparities remain inconclusive. This study examined the association between birthweight, GA, and midlife CF stratified by race.

METHOD: 1,032 subjects from the Bogalusa Heart Study (67% Whites, 33% Blacks, mean age 48.1 ± 5.3 years) were studied. Cognition was assessed with tests measuring verbal episodic memory, working memory, attention, graphomotor information processing speed, and global CF. Each test was standardized by sex and age, then averaged. The global CF was computed by averaging all cognitive …

Acute Dentate Nucleus Deep Brain Stimulation Modulates Corticomotor Excitability In Chronic Stroke Survivors, Xin Li, Kenneth B. Baker, Kyle O'Laughlin, Yin-Liang Lin, Kelsey Baker, Robert Chen, Jacqueline Chen, Andre G. Machado, Ela B. Plow

School of Medicine Publications

Background

Deep brain stimulation of the dentate nucleus (DN-DBS) is an emerging therapy to improve upper extremity (UE) motor function after stroke. This study sought to investigate the physiologic mechanisms of acuteDN-DBS in chronic stroke survivors enrolled in a phase I trial for DN-DBS.

Methods

Twelve chronic stroke participants with moderate-to-severe UE impairment received (acute) single sessions (≥45 min) of active DBS and sham DBS in a sham-controlled, double-blind, cross-over experiment (order randomized). Transcranial magnetic stimulation (TMS) was used to evaluate corticomotor physiology. We also characterized the relationship between acute DBS effects on physiology and baseline clinical …

Nf2 Loss-Of-Function And Hypoxia Drive Radiation Resistance In Grade 2 Meningiomas, Bhuvic Patel, Sangami Pugazenthi, Collin W English, Vijay Nitturi, Shree S Pari, Tatenda Mahlokozera, William A Leidig, Hsiang-Chih Lu, Alicia Yang, Kaleigh Roberts, Patrick Desouza, Kyle P Mcgeehan, Diane D Mao, Namita Sinha, Joseph E Ippolito, Sonika Dahiya, Allegra Petti, Hiroko Yano, Tiemo J Klisch, Akdes S Harmanci, Akash J Patel, Albert H Kim

Duncan NRI Faculty and Staff Publications

Background: World Health Organization Grade 2 meningiomas (G2Ms) often recur and resist therapies. Grade 2 meningiomas with histopathological necrosis have been associated with worse local control (LC) after radiation therapy, but the drivers and biomarkers of radiation resistance in G2Ms remain unknown.

Methods: We performed genetic sequencing and histopathological analysis of 113 G2Ms and investigated the role of genetic and microenvironmental factors on clonogenic survival after ionizing radiation. We performed transcriptional profiling of our in vitro model and 18 human G2M tumors by bulk RNA sequencing as well as 8 G2Ms by single nuclei RNA sequencing.

Results: NF2 loss-of-function (LOF) …

Longitudinal Associations Between Self-Reported Exercise Levels And Cognition In Adad, Kelsey R. Sewell, James D. Doecke, Ralph N. Martins, Stephanie R. Rainey-Smith, Jeremiah Peiffer, Samantha L. Gardener, Hamid R. Sohrabi, Kirk I. Erickson, Belinda M. Brown

Research outputs 2022 to 2026

Introduction: This study examined longitudinal associations between self-reported exercise and cognition, with moderation by sex, in individuals with autosomal dominant Alzheimer's disease (ADAD) mutations. We also examined whether changes in exercise over time differed in ADAD mutation carriers versus non-carriers in the years preceding first cognitive symptom onset. Methods: Participants (n = 491) were ADAD mutation carriers (63%) and non-carriers (37%) from the Dominantly Inherited Alzheimer Network aged 37.6 ± 11.1 years. Participants reported their average time partaking in various leisure-time exercise activities over the past 12 months. Results: Greater baseline exercise predicted better longitudinal cognitive performance. Sex did not …

Measuring And Interpreting Individual Differences In Fetal, Infant, And Toddler Neurodevelopment, Halie A Olson, M Catalina Camacho, Gavkhar Abdurokhmonova, Sahar Ahmad, Emily M Chen, Haerin Chung, Renata Di Lorenzo, Áine T Dineen, Melanie Ganz, Roxane Licandro, Caroline Magnain, Natasha Marrus, Sarah A Mccormick, Tara M Rutter, Lauren Wagner, Kali Woodruff Carr, Lilla Zöllei, Kelly A Vaughn, Kathrine Skak Madsen

Faculty, Staff and Student Publications

As scientists interested in fetal, infant, and toddler (FIT) neurodevelopment, our research questions often focus on how individual children differ in their neurodevelopment and the predictive value of those individual differences for long-term neural and behavioral outcomes. Measuring and interpreting individual differences in neurodevelopment can present challenges: Is there a "standard" way for the human brain to develop? How do the semantic, practical, or theoretical constraints that we place on studying "development" influence how we measure and interpret individual differences? While it is important to consider these questions across the lifespan, they are particularly relevant for conducting and interpreting research …

Enhancing Seizure Control In Ultra-Refractory Postencephalitic Epilepsies Using Multinodal Network Neuromodulation, Subhiksha Srinivasan, Surya Suresh, Ganne Chaitanya, Manoj Saranathan, Nitin Tandon, Sandipan Pati

Faculty, Staff and Student Publications

This case series reports the formidable challenge posed by postencephalitic epilepsies, characterized by frequent drug-resistant seizures and neuropsychiatric and cognitive comorbidities. Polypharmacy is frequently required, and surgical resection may not be feasible due to multifocality. Neuromodulation therapies, including Deep Brain Stimulation (DBS) and Responsive Neurostimulation (RNS), offer a potential lifeline. In this case series, we shed light on the intricate landscape of seizure management and neuropsychiatric comorbidities in five individuals with frequent seizures (often weekly) and ultra-refractory epilepsy (defined as resistance to more than six different antiseizure medications, including failed epilepsy surgery) following catastrophic encephalitis. Four out of five patients …

Glutamatergic Regulation Of Mirna-Containing Intraluminal Vesicle Trafficking And Extracellular Vesicle Secretion From Cortical Neurons, Marcela Bertolio, Qiyi Li, Francesca E Mowry, Kathryn E Reynolds, Rashed Alananzeh, Haichao Wei, Kyoeun Keum, Rachel Jarvis, Jiaqian Wu, Yongjie Yang

Faculty, Staff and Student Publications

Neuronal extracellular vesicles (microvesicles and exosomes) are emerging secreted vesicular signals that play important roles in the CNS. Currently, little is known about how glutamatergic signalling affects the subcellular localisation of exosome precursor intraluminal vesicles (ILVs), microRNA (miR) packaging into ILVs and in vivo spreading of neuronal EVs. By selectively labelling ILVs and exosomes (but not plasma membrane-derived MVs) with GFP-tagged human CD63 (hCD63-GFP) in cortical neurons, we found that glutamate stimulation significantly redistributes subcellular localisation of hCD63-GFP+ ILVs, especially decreasing its co-localisation with multi-vesicular body (MVB) marker Rab7 while substantially promoting EV secretion. Interestingly, glutamate stimulation only modestly alters …

Baseline Habitual Dietary Nitrate Intake And Alzheimer's Disease Related Neuroimaging Biomarkers In The Australian Imaging, Biomarkers And Lifestyle Study Of Ageing, Anjana Rajendra, Nicola P. Bondonno, Kevin Murray, Liezhou Zhong, Stephanie R. Rainey-Smith, Samantha L. Gardener, Lauren C. Blekkenhorst, Vincent Doré, Victor L. Villemagne, Simon M. Laws, Belinda M. Brown, Kevin Taddei, Colin L. Masters, Christopher C. Rowe, Ralph N. Martins, Jonathan M. Hodgson, Catherine P. Bondonno

Research outputs 2022 to 2026

Background: Dietary nitrate, as a nitric oxide (NO) precursor, may support brain health and protect against dementia. Objective: Our primary aim was to investigate whether dietary nitrate is associated with neuroimaging markers of brain health linked with Alzheimer's disease (AD). Participants: Study participants were cognitively unimpaired individuals from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing (AIBL) who had β-amyloid positron emission tomography (PET) scans (n = 554) and magnetic resonance imaging (MRI) scans (n = 335) and had completed a Food Frequency Questionnaire at baseline. Methods: Source-specific nitrate intakes were estimated using comprehensive nitrate food composition databases. Rates …

Benchmarking Machine Learning Models In Lesion-Symptom Mapping For Predicting Language Outcomes In Stroke Survivors, Deepa Tilwani, Christian O'Reilly, Nicholas Riccardi, Valerie L. Shalin, Dirk B. Den Ouden, Julius Fridriksson, Svetlana V. Shinkareva, Amit P. Sheth, Rutvik H. Desai

Communication Sciences and Disorders Faculty Articles and Research

Several decades of research have investigated the neural connections between stroke-induced brain damage and language difficulties. Typically, lesion-symptom mapping (LSM) studies that address this connection have relied on mass univariate statistics, which do not account for multidimensional relationships between variables. Machine learning (ML) techniques, which can capture these intricate connections, offer a promising complement to LSM methods. To test this promise, we benchmarked ML models on structural and functional MRI to predict aphasia severity (N = 238) and naming impairment (N = 191) for a cohort of chronic-stage stroke survivors. We used nested cross-validation to examine performance along …

Long-Term Neurocognitive And Behavioral Outcomes In Survivors Of Pediatric Brain Tumors: A Systematic Review, Tirath Patel, Pulkit Johar, Vaishnavi Kanisetti, Megan Szobody, Tori Sayers, Sriya Gullapalli, Murali Yallapu, Mushfiq Hassan Shaikh, Nikhilesh Anand, Kelsey Baker, Bharathi Gadad

School of Medicine Publications

Background: Brain tumors are among the most common neoplasms in children. These patients suffer from neurocognitive impairment, treatment-related side effects, and experience a subpar quality of life (QoL), affecting academic endeavors, social interaction, and mental wellbeing.

Methods: This review investigated different long-term neurocognitive and behavioral outcomes in pediatric brain tumor survivors and evaluated various effective treatment methods. We identified 75 relevant articles published between 2019 and 2024 using PubMed, PMC, Embase, and Google Scholar databases. Duplicates were removed, and 14 studies were finally selected following the PRISMA guidelines. Initial observations noted significant variations in the study methodologies and inclusion criteria. …

Time To Treatment In Pediatric Patients With Repeated Episodes Of Status Epilepticus, Jennifer V Gettings, Iván Sánchez Fernández, Anne Anderson, J Nicholas Brenton, Afra Can, Justice Clark, Raquel Farias Moeller, Howard P Goodkin, Yi-Chen Lai, Mohamad A Mikati, Lindsey A Morgan, Edward Novotny, Adam P Ostendorf, Juan Piantino, James J Riviello, Kumar Sannagowdara, Robert C Tasker, Dmitry Tchapyjnikov, Mark S Wainwright, Angus Wilfong, Korwyn Williams, Bo Zhang, Tobias Loddenkemper, Marina Gaínza-Lein, Pediatric Status Epilepticus Research Group (Pserg)

Duncan NRI Faculty and Staff Publications

Objective: To compare pediatric patients who presented with repeated status epilepticus episodes to patients with a single episode of status epilepticus and identify distinguishing clinical factors.

Methods: Retrospective analysis of a multicenter, prospective observational cohort of pediatric patients with status epilepticus between 2011 and 2019.

Results: Out of 504 status epilepticus episodes in 420 patients, 50 patients (10.3%) had repeated episodes of status epilepticus. The only predictor of repeated status epilepticus was a prior diagnosis of epilepsy. There was no difference in time to treatment with the first benzodiazepine in patients presenting with their first status epilepticus episode compared to …