Neurosciences Commons^™

Understanding Visual Memory Encoding And The Effects Of Endurance Exercise In Healthy Adults And People With Temporal Lobe Epilepsy, Brandon Steve Mitchell

All ETDs from UAB

The visual memory encoding (VME) of indoor and outdoor scenes is a complex cognitive process that primarily utilizes the bilateral hippocampi and medial temporal lobe (MTL) structures along the parahippocampal gyrus. Alpha and theta frequency band oscillations are important in the processing of visual information and memory formation, respectively. We completed hree studies investigating the cognitive process of VME in healthy adults and people with temporal lobe epilepsy (pwTLE). The first study was cross-sectional and utilized a functional magnetic resonance imaging (fMRI)-constrained magnetoencephalography (MEG) analysis in healthy adults to explore VME. The fMRI results were used as spatial priors to …

Understanding The Functional Consequence Of Cul3 Deletion In The Mammalian Brain, Prathibha Sekar

All ETDs from UAB

Polyubiquitination is a post-translational modification which often results in degradation of the ubiquitin-tagged protein. E3 ubiquitin ligases are multi-subunit protein complexes that assist in this ubiquitination process. Multiple genes that play a role in ubiquitination are implicated in autism spectrum disorder, a highly heterogeneous neurodevelopmental disorder. CULLIN3 (CUL3), a scaffolding protein part of the E3 ubiquitin ligase complex, is the product of a high-risk autism gene implicated across multiple large scale sequencing studies of autism patients. Additionally, CUL3 haploinsufficiency is associated with a syndromic disorder called NEDAUS (Neurodevelopmental disorder with or without autism or seizures) characterized by intellectual disability (ID), …

An Analysis Of Gamma-Aminobutyric Acid Levels With Structural And Functional Connectivity In Antipsychotic Medication-Naïve First Episode Psychosis Patients, Genelle Dano Samson

All ETDs from UAB

Schizophrenia is a complex psychiatric disorder characterized by hallucinations, delusions, disorganized thinking, and abnormalities in emotional expression, social interaction, and motivation. Cognitive deficits and alterations in perception are core features of psychosis spectrum disorders, though the neurobiological bases of these impairments are not thoroughly understood. Examination of the structures responsible for cognition, along with how their connectivity and neurochemistry are altered in psychosis, is crucial to understanding and treating schizophrenia. Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system and plays a crucial role in the regulation of neuronal activity. Evidence from animal models and postmortem …

Identifying The Neurobiological Substrates Of Gulf War Illness, Chloe Lisette Jones

All ETDs from UAB

Gulf War Illness (GWI) affects approximately 30% of veterans who served in the 1991 Persian Gulf War and is characterized by chronic pain and fatigue, as well as cognitive, mood, gastrointestinal, and respiratory symptoms. Animal research has suggested that GWI is caused by a combination of neurotoxicants such as nerve gas, anti-nerve agent pills, and pesticides, though a definitive pathophysiological model has not been established. In this human observational study, 20 veterans with GWI and 20 healthy Gulf War veterans (HV) underwent whole-brain magnetic resonance spectroscopy (MRS) to non-invasively measure several metabolites associated with neuroinflammation. Whole blood was also collected …

A High-Salt Diet Modulates Renal Afferent Nerve Activity; Potential Role Of The Endothelin System, Jiaxi Shen

All ETDs from UAB

Hypertension is a prevalent disease around the world. Increased blood pressure leads to a higher risk of stroke and coronary heart disease. Diet, lifestyle, and gene regulation are potential causative factors, and salt-sensitive hypertension is one common types of hypertension. In response to a high-salt diet, blood pressure may elevate with increasing risks of cardiovascular disease (CVD). Endothelin-1, which binds to endothelin A (ETA) and B (ETB) receptors, is strongly involved in controlling the blood vessels and sensory nerve signaling pathway between the kidney and the central nervous system during high salt dietary challenge. The function of the ETB receptor …

Myelin Mapping In Psychosis, Victoria Lynn King

All ETDs from UAB

It is well established that myelin in the central nervous system is an axonal insulator which speeds the conduction velocity of action potentials. However, its role in the cortex has also been shown to support metabolic demands and aid in cortical plasticity. Myelin develops throughout childhood and adolescence from sensorimotor areas to association areas and peaks during adolescence. Importantly, this is the same time that psychosis-spectrum disorders (PSDs) begin to present clinically; thus, given the critical role of myelination in shaping the mature cortex, disruptions in this process – particularly during adolescence – are thought to partially explain the onset …

Impact Of Alpha-Synuclein Aggregation On Corticostriatal Synaptic Function And Morphology, Charlotte Franziska Brzozowski

All ETDs from UAB

Lewy Body Dementias (LBDs), including Parkinson’s Disease Dementia (PDD) and Dementia with Lewy Bodies (DLB), are defined by α-synuclein (α-syn) accumulation in Lewy Pathology (LP). LP is abundant in cortical layer V intratelencephalic (IT) neurons, a subset of neurons that also degenerate in the pre-supplementary motor area (preSMA) in humans, which is homologous to the secondary motor cortex (M2) in mice, as observed in PD postmortem tissue. IT neuron projections to the striatum are an intrinsic part of the motor basal ganglia circuitry, believed to modulate cognitive aspects of executive motor control, such as updating motor plans. M2 projections to …

Amygdala Npy+ Interneurons Are Activated By Aversive Stim-Uli, Patric Perez

All ETDs from UAB

Neuropeptide Y (NPY) serves as a critical endogenous anxiolytic and stress-buffering molecule, yet the temporal and spatial dynamics of NPY+ cells during fear learning re-main unknown. Temporal dynamics can be measured with in vivo calcium imaging tech-niques, which enable real-time monitoring of cell-type-specific neural activity in freely behaving animals. Snapshots of neuronal activation can be measured using c-Fos im-munohistochemistry, thereby providing excellent spatial resolution. Here, I employ cut-ting-edge approaches to characterize the temporal and spatial activation patterns of NPY+ cells in amygdala, a key fear-regulating brain region negatively impacted by aversive events. I first used in vivo fiber photometry, together …

Understanding Psychotic Disorders Using Normative Modeling-Derived Individual-Level Brain Structural Abnormalities, Natalie Remiszewski

All ETDs from UAB

Psychosis is an heterogenous condition that occurs in many psychiatric disorders. It has a variable symptom presentation and recent initiatives have suggested that investigating the underlying neurobiology of psychiatric disorders rather than their symptomatology would provide a more accurate picture for diagnosis, prognosis, and treatment. Grey matter has been implicated in the pathophysiology of psychosis and psychotic disorders, though significant natural variation due to age and sex have impeded the distinction of pathologically relevant grey matter abnormalities in psychosis. Additionally, case-control approaches to exploring grey matter abnormalities in psychotic disorders often obscure subtle variation in individuals. Here, we utilize a …

Murder On The Axonal Express: Synucleinopathy Disruption Of 14-3-3 Protein-Protein Interactions Impairs Axonal Trafficking, Frank Sanders Pair

All ETDs from UAB

14-3-3s are a family of proteins highly expressed in the brain. These proteins exert their functions mainly through protein-protein interactions (PPIs) and have thousands of binding partners. 14-3-3s have been shown to be present in pro-teinaceous aggregates of alpha-synuclein (αsyn), a pathological hallmark of synucleinopathies. This includes such diseases as Parkinson’s Disease (PD) and Dementia with Lewy Bodies (DLB). 14-3-3 proteins, particularly the 14-3-3θ isoform, have been shown to be protective in multiple synucleinopathy models. However, reduced soluble levels of 14-3-3s and increased phosphorylation of 14-3-3θ at S232 observed in synucleinopathies like DLB may impair their protec-tive ability, potentially due …

Development Of A Patient-Centered Outcome Tool For Blepharospasm: A Stepwise Modified Delphi Study, Brian D Berman, Fares Qeadan, Amanda D Henderson, Andrew R Harrison, Giovanni Defazio, Mark Hallett, Gamze Kilic-Berkmen, Laura Wright, Samantha Pentecost, Paul Reyes, Anna Tingin, Joseph Jankovic, Jane Boyd, Charlene Hudgins, Janet Hieshetter, Joel S Perlmutter, Hyder A Jinnah, Sarah Pirio Richardson

Faculty, Staff and Students Publications

Blepharospasm (BSP) is characterized by excessive orbicularis oculi muscle activity leading to abnormal blinking and involuntary eyelid closure. Botulinum neurotoxin (BoNT) injections are the main treatment for BSP, but they only partially and transiently relieve symptoms, leading to a waxing and waning therapeutic response. A patient-centered outcome (PCO) tool that measures BSP symptoms in a simple and efficient way could inform the development of better treatments. Using a stepwise modified Delphi approach, potential PCO items were first identified using the Dystonia Coalition Database with data from over 200 individuals with BSP who had provided responses to existing clinical assessment scales. …

Computationally Resolved Neuroprogenitor Cell Biomarkers Associate With Human Disorders, Gerarda Cappuccio, William T Choi, Fatih Semerci, Jill A Rosenfeld, Toni Claire Tacorda, Guantong Qi, Anthony W Zoghbi, Yi Zhong, Hu Chen, Pengfei Liu, Zhandong Liu, Mirjana Maletić-Savatić

Duncan NRI Faculty and Staff Publications

Adult hippocampal neurogenesis, the process of generating new neurons, relies on a rare population of neural stem and progenitor cells (NPCs) within the dentate gyrus complex microenvironment. Discovering the specific genes that define these cells is vital yet challenging due to overlapping expression patterns, limiting detection of rare cell populations using traditional approaches. By employing the computational digital sorting algorithm (DSA) that deconvolves complex gene expression data based on pattern recognition, we identified 129 genes enriched in murine NPCs. We validated these genes against published single-cell RNA sequencing (scRNA-seq) data and discovered that 25 human orthologs were known to cause …

Gene Context Drift Identifies Drug Targets To Mitigate Cancer Treatment Resistance, Amir Jassim, Birgit V Nimmervoll, Sabrina Terranova, Erica Nathan, Linda Hu, Jessica T Taylor, Katherine E Masih, Lisa Ruff, Matilde Duarte, Elizabeth Cooper, Gunjan Katyal, Melika Akhbari, Reuben J Gilbertson, Jennifer C Coleman, Joseph S Toker, Colton Terhune, Gabriel Balmus, Stephen P Jackson, Hailong Liu, Tao Jiang, Michael D Taylor, Kui Hua, Jean E Abraham, Mariella G Filbin, Anthony Hill, Anarita Patrizi, Neil Dani, Aviv Regev, Maria K Lehtinen, Richard J Gilbertson

Faculty, Staff and Students Publications

Cancer treatment often fails because combinations of different therapies evoke complex resistance mechanisms that are hard to predict. We introduce REsistance through COntext DRift (RECODR): a computational pipeline that combines co-expression graph networks of single-cell RNA sequencing profiles with a graph-embedding approach to measure changes in gene co-expression context during cancer treatment. RECODR is based on the idea that gene co-expression context, rather than expression level alone, reveals important information about treatment resistance. Analysis of tumors treated in preclinical and clinical trials using RECODR unmasked resistance mechanisms -invisible to existing computational approaches- enabling the design of highly effective combination treatments …

Regulation Of Food Intake By Connexin43 Via Adipocyte-Sensory Neuron Electrical Synapses, Xi Chen, Xing Fang, Hong Zhou, Jieyi Meng, Yang He, Leon G Straub, Andrew Lemoff, Clair Crewe, Shangang Zhao, Yong Xu, Yi Zhu

Duncan NRI Faculty and Staff Publications

Background and objective: Connexin43 (Cx43), encoded by Gja1, forms gap junctions between adjacent cells. In adipose tissue, it is upregulated during adipose beiging while downregulated by high-fat-diet (HFD) feeding. Adipocyte-specific Gja1 overexpression enhances adipose tissue beiging in response to mild cold stress of room temperature. Moreover, those mice display a surprising decrease in food intake, but the mechanism remains unclear. This study investigates how adipocyte Cx43 influences feeding behavior.

Methods: Mice with adipose tissue-specific Gja1 overexpression (Adipoq-Cx43) were fed with HFD. Food intake, weight gain, substrate utilization, and serum lipolysis were assessed. RNA-seq, proteomics, and cytokine measurements were employed to …

Human Adipose Stem Cell-Derived Small Extracellular Vesicles Modulate Glial Cell Response In Aged And Young Tbi Mouse Models, Salma S. Abdelmaboud

USF Tampa Graduate Theses and Dissertations

Traumatic brain injury (TBI) is a leading cause of long-term neurological impairment, with aging significantly increasing vulnerability and worsening outcomes. Older individuals experience greater cognitive and motor deficits after TBI and often show diminished responses to therapeutic interventions. Both aging and TBI independently promote heightened neuroinflammation and cognitive dysfunction, increasing susceptibility to poor recovery. This study investigated the therapeutic potential of small extracellular vesicles (sEVs) derived from human adipose-derived stem cells (hASCs) to promote neurological recovery and modulate neuroinflammation in a mouse model of TBI. Male C57BL/6 mice aged 3, 15, and 20 months underwent controlled cortical impact (CCI) and …

Implementing A Training Resource For Large-Scale Genomic Data Analysis In The All Of Us Researcher Workbench, Jasmine Baker, Erik Stricker, Julie Coleman, Shamika Ketkar, Taotao Tan, Ashley M Butler, Laterrica Williams, Latanya Hammonds-Odie, Debra Murray, Brendan Lee, Kim C Worley, Elizabeth G Atkinson

Duncan NRI Faculty and Staff Publications

A lack of representation in genomic research and limited access to computational training create barriers for many researchers seeking to analyze large-scale genetic datasets. The All of Us Research Program provides an unprecedented opportunity to address these gaps by offering genomic data from a broad range of participants, but its impact depends on equipping researchers with the necessary skills to use it effectively. The All of Us Biomedical Researcher (BR) Scholars Program at Baylor College of Medicine aims to break down these barriers by providing early-career researchers with hands-on training in computational genomics through the All of Us Evenings with …

Neonatal Striatal Volume Is Associated With Infant Anhedonia, Melissa Nevarez-Brewster, Catherine H. Demers, Jessica L. Irwin, Laura M. Glynn, Martin A. Styner, Mercedes Hoeflich Haase, M. Camille Hoffman, Diego A. Pizzagalli, Benjamin L. Hankin, Elysia Poggi Davis

Psychology Faculty Articles and Research

Anhedonia is increasingly recognized as a transdiagnostic risk factor for psychopathology. New evidence demonstrates that anhedonia is present in infancy and early childhood. Structural variability in striatal regions involved in reward processing and pleasure seeking is concurrently linked to anhedonia, yet few studies have examined whether striatal differences presage anhedonia, and none have examined prospective associations before middle childhood. The present study examined whether neuroanatomical markers that confer risk for anhedonia can be detected as early as the neonatal period. Specifically, we tested whether the volume of striatal regions in neonates predicted the emergence of infant anhedonic behaviors at six …

Systematic Review And Evidence Gap Mapping Of Alzheimer's Disease Biomarker Studies In Those With Intellectual And Developmental Disability, Lubnaa B. Abdullah, Ney Alex Alliey, Emma Elizondo, Ney Alliey Rodriguez, Gladys Maestre, James Hall

School of Medicine Publications

There are a relatively small number of investigations into brain aging in those with intellectual and developmental disability (I/DD). This project seeks to (1) characterize the internationally available multi-omics Alzheimer's disease (AD) biomarker studies including those with I/DD, and (2) discuss future research directions. PubMed, Web of Science, and Scopus were searched under the following criteria: cross-sectional or longitudinal AD-omics studies on adults (18 +) with I/DD. 532 studies were identified, 186 studies were evaluated for full-text, 79 studies were excluded, and 117 studies were extracted. Most biological specimens were analyzed in blood, plasma, or serum. Metabolomics, hormonomics, and transcriptomics …

High-Resolution Mapping Of Alcohol-Related Brain Connectivity In Adults Using 7t Fmri And Multivoxel Pattern Classification, Alan N. Francis, Ihsan Salloum

School of Medicine Publications

Background: Emerging evidence suggests that alcohol use disrupts large-scale brain network interactions, particularly within the triple network model-comprising the Salience Network (SN), Default Mode Network (DMN), and Frontoparietal Network (FPN). However, few studies have examined how these connectivity alterations vary across the full spectrum of alcohol consumption, especially using ultra-high-field imaging and data-driven approaches. This study leverages 7 Tesla resting-state fMRI and multivariate pattern analysis (MVPA) to characterize distinct brain connectivity patterns across heavy, moderate, and non-drinking adults, aiming to identify neural signatures that differentiate alcohol use severity levels.

Methods: We analyzed resting-state functional connectivity data from 69 adults (Mean …

Optimal Head-Of-Bed Positioning Before Thrombectomy In Large Vessel Occlusion Stroke: A Randomized Clinical Trial, Anne W Alexandrov, Anne J Shearin, Pitchaiah Mandava, Gabriel Torrealba-Acosta, Cheran Elangovan, Balaji Krishnaiah, Katherine Nearing, Elizabeth Robinson, Cara Guthrie-Chu, Matthew Holzmann, Bryan Fill, Dharti R Trivedi, Alicia Richardson, Sandy Middleton, Barbara B Brewer, David S Liebeskind, Nitin Goyal, James C Grotta, Andrei V Alexandrov

Faculty, Staff and Students Publications

Importance: Small studies show that 0° head positioning of patients with large vessel occlusion (LVO) stroke improves penumbral blood flow and clinical stability. Understanding whether 0° head position maintains clinical stability would allow for optimal patient positioning before thrombectomy.

Objective: To determine superiority of 0° over 30° head positioning at maintaining clinical stability in patients with LVO before thrombectomy.

Design, setting, and participants: This was a prospective randomized clinical trial with blinding to study enrollment/end points conducted from May 2018 to November 2023. There were 3 planned interim analyses, and the study was conducted at certified thrombectomy hospitals in the …