Neurosciences Commons^™

Transient Activation Of Potent Progenitor Cells Is Required For Spinal Cord Regeneration, Chase Alexander Weinholtz

Arts & Sciences Graduate Student Theses and Dissertations

Mammalian spinal cord injury is an intractable biomedical problem driven by interlocking maladaptive cellular responses that prioritize acute stabilization over long-term recovery. However, this deficient regenerative capacity is not an inherent limitation. The zebrafish, for example, capably regenerates and regains motor function with 2 months of a full transection injury. This ability is thought to rely on the transient expansion of stem cell-like progenitors marked by sox2 expression. Yet our understanding of the identities and contributions of this crucial population remains limited. Here, we determine the molecular identities and cellular contributions of sox2+ progenitors during innate spinal cord repair in …

Relationship Identification Between Triggers And Changes In The Brain And The Overall Human Electrophysiology During Migraines, Dominic Sandell, Jonah Dematto, Gianpiero Lara, Jasmine Rosales, Legacy Wilson, Zachary Young

Discovery Day - Daytona Beach

One of the most common neurological conditions in the world is migraines; nearly 1/4th of the working population suffers from this condition and exhibits a large variety of triggers. The current treatment method for migraine uses few different medications for all migraines, regardless of triggers. Our hypothesis is that there is a specific relationship between the triggers of migraines and the electrical changes in the brain during migraines. It is known that electrical activity in the brain occurs during migraines; it is unclear whether these changes differ across triggers. The study incorporates two different data collection methods: electrophysiological tests (Electroencephalogram …

Translational Reading Frame Predicts The Pathogenicity Of C-Terminal Frameshift Deletions In Mecp2, Jacky Guy, Elena Hein, Beatrice Alexander-Howden, Timur Von Bock Und Polach, Tricia Mathieson, Benjamin P Kleinstiver, Huda Y Zoghbi, Adrian Bird

Duncan NRI Faculty and Staff Publications

Mutations in the MECP2 gene cause the severe neurological disorder Rett syndrome. A cluster of frameshift-causing C-terminal deletions (CTDs) removes ~100 amino acids and accounts for approximately 10% of RTT-causing mutations. Their pathogenicity is unexpected because this C-terminal domain is dispensable in mice. Analysis of pathogenic and benign human MECP2 variants reveals that some individuals with apparently typical CTDs do not develop Rett syndrome, confirming that C-terminal truncations are not intrinsically pathogenic. Using human sequence data and mouse models we show that pathogenicity results from a marked reduction in MeCP2 levels and depends on the presence of a proline proline …

Shared Neural Geometries For Bilingual Semantic Representations In Human Hippocampal Neurons, Xinyuan Yan, Ana G Chavez, Melissa Franch, Kalman A Katlowitz, Ivy Gautam, Brian Kim, Aaditya Krishna, Aadit Shrivastava, Katie Van Arsdel, James Belanger, Assia Chericoni, Taha Ismail, Elizabeth A Mickiewicz, Danika Paulo, Hanlin Zhu, Alica M Goldman, Vaishnav Krishnan, Atul Maheshwari, Eleonora Bartoli, Nicole R Provenza, Seng Bum Michael Yoo, Benjamin Y Hayden, Sameer A Sheth

Duncan NRI Faculty and Staff Publications

The human brain has the remarkable ability to comprehend and express similar concepts in multiple languages. To understand how it does so, we examined responses of hippocampal neurons during passive listening, directed speaking, and spontaneous conversation in both English and Spanish in a small group of balanced bilinguals. We found a small number of putative "cross-language neurons," whose responses to equivalent words (e.g., "tierra" and "earth") are correlated. However, neurons' semantic tunings differed substantially by language, suggesting language-specific neural implementations. Instead, the crucial driver of translation was a preserved geometric organization of neural responses between the two languages, one that …

Musical Training Increases Anticipatory Responding And Predictive Control In Sequence Learning, Li Ann Leow, Jarrad Lum, Sara Johnson, Emily Corti, Welber Marinovic

Research outputs 2022 to 2026

Musicians demonstrate advantages in acquiring motor sequences, showing faster learning and better explicit sequence knowledge than non-musicians. However, it is unclear whether this advantage extends beyond acquisition to the consolidation phase, which is when newly learned skills stabilize and become resistant to interference. Additionally, while interference from executing competing motor tasks is well-established, less is known about whether purely sensory information presented after learning can disrupt consolidation of a bimodal motor sequence. We investigated how post-acquisition sensory interference affects performance of a learned audio-visual sequence, and whether musical training moderates this vulnerability. Participants first learned an explicit sequence in a …

Characterising Manual Dexterity, Motor Cortex Neuroplasticity, And Intracortical Inhibition Long After Burn Injury, Grant S. Rowe, Alecia Wood, Mark Fear, Dale W. Edgar, Aleksandra Miljevic, Tyler Osborne, Natalie Morellini, Merrilee Needham, Ann Maree Vallence, Fiona Wood

Research outputs 2022 to 2026

Purpose: Persistent motor dysfunction after burn injury may be due to altered motor cortex and corticospinal tract function. This study examined manual dexterity, motor cortex neuroplasticity, and intracortical inhibition in former burn patients 1–3 years after minor injury (<10% TBSA). Method: Thirty former burn patients (TBSA: 0.78 ± 1.08%) and 30 non-injured controls participated. Manual dexterity was assessed using the Purdue Pegboard. Transcranial magnetic stimulation (TMS) was used to measure motor cortex excitability (motor evoked potential [MEP] amplitude) and short- and long-interval intracortical inhibition (SICI, LICI) before and after paired-associative stimulation (PAS) to induce neuroplasticity. Results: Former burn patients performed worse than controls on the bimanual assembly subtest of the Purdue Pegboard. PAS did not induce changes in MEP amplitude but increased LICI in both burn patients and control participants. In burn patients, baseline LICI was related to bimanual performance differently than controls. Conclusions: These findings suggest poorer bimanual motor function persists after minor burns, and differences in the association between inhibition and bimanual dexterity between burn and control groups. Further research should explore whether targeting motor cortex inhibitory circuits can improve motor performance following burn injury

Engagement Of Understudied Populations As Community Change: The South Texas Adrc Model, Gladys E. Maestre, Neela K. Patel, Rosa V. Pirela, Robin C. Hilsabeck, Kendra Stine, Neyra García, Roberto Reyes, Omar Oropeza, Cristian Maestre, Jesus D. Melgarejo, Sarah Williams-Blangero, Ney Alliey Rodriguez, Sylvia A. Robles

School of Medicine Publications

Many populations experiencing the highest burdens of Alzheimer's disease and related dementias remain understudied, in part because traditional recruitment and retention models are insufficient to support sustained engagement. The Outreach, Recruitment, and Engagement Core (OREC) of the South Texas Alzheimer's Disease Research Center reconceptualized participant recruitment as a long-term system change in a Hispanic-majority, urban–rural region. OREC institutionalizes shared power through community advisory governance, aligns research protocols with local lived realities (through patient navigators, community health workers/promotores, and decentralized access points), and employs a data-driven feedback loop for continuous improvement. In 1 year, 46 outreach events touched 10,134 individuals (71% …

Extending Genome-Wide Association Studies To Admixed Cohorts With High Degrees Of Relatedness, Taotao Tan, Alejandra Vergara-Lope, José Jaime Martínez-Magaña, Nirav N Shah, Yi-Sian Lin, Kai Yuan, Jaime Berumen, Jesus Alegre-Díaz, Pablo Kuri-Morales, Roberto Tapia-Conyer, Joel Gelenter, Janitza L Montalvo-Ortiz, Wei Zhou, Jason M Torres, Elizabeth G Atkinson

Duncan NRI Faculty and Staff Publications

Admixed populations comprise a large portion of the human population worldwide, but are often excluded from genome-wide association studies (GWASs) due to analytic challenges. Our group developed Tractor, a local-ancestry-informed GWAS tool designed for admixed samples that produces accurate ancestry-specific effect sizes and boosts the discovery power to identify ancestry-enriched loci. However, Tractor operates under an assumption of unrelated samples. Here, to address this gap, we propose Tractor-Mix, which allows for well-calibrated association studies in datasets containing admixed samples with relatedness. Extensive simulations show that this method is competitive with other state-of-the-art approaches that do not produce ancestry-specific results. Empirical …

A Blended Genome And Exome Sequencing Method Captures Genetic Variation In An Unbiased And Cost-Effective Manner, Toni A Boltz, Benjamin B Chu, Matthew Defelice, Calwing Liao, Julia M Sealock, Robert Ye, Jacqueline I Goldstein, Lerato Majara, Jack M Fu, Susan K Service, Lingyu Zhan, Sarah E Medland, Sinéad B Chapman, Simone Rubinacci, Jonna L Grimsby, Tamrat Abebe, Melkam Alemayehu, Fred K Ashaba, Elizabeth G Atkinson, Tim B Bigdeli, Amanda B Bradway, Harrison Brand, Lori B Chibnik, Samuel Deluca, Ana M Diaz-Zuluaga, Abebaw Fekadu, Michael Gatzen, Bizu Gelaye, Stella Gichuru, Marissa L Gildea, Toni C Hill, Hailiang Huang, Kalyn M Hubbard, Wilfred E Injera, Roxanne James, Moses Joloba, Christopher Kachulis, Phillip R Kalmbach, Rogers Kamulegeya, Gabriel Kigen, Soyeon Kim, Nastassja Koen, Edith K Kwobah, Joseph Kyebuzibwa, Seungmo Lee, Niall J Lennon, Penelope A Lind, Esteban A Lopera-Maya, Johnstone Makale, Serghei Mangul, Justin Mcmahon, Pierre Mowlem, Henry Musinguzi, Rehema M Mwema, Noeline Nakasujja, Carter P Newman, Lethukuthula L Nkambule, Conor R O'Neil, Ana Maria Olivares, Catherine M Olsen, Linnet Ongeri, Sophie J Parsa, Adele Pretorius, Shengying Qin, Raj Ramesar, Faye L Reagan, Chiara Sabatti, Jacquelyn A Schneider, Welelta Shiferaw, Christine Stevens, Anne Stevenson, Erik Stricker, Rocky E Stroud, Jessie Tang, Megan Townsend, David Whiteman, Mary T Yohannes, Mingrui Yu, Kai Yuan, Dickens Akena, Lukoye Atwoli, Symon M Kariuki, Karestan C Koenen, Charles R J C Newton, Dan J Stein, Solomon Teferra, Zukiswa Zingela, Carlos N Pato, Michele T Pato, Carlos Lopez-Jaramillo, Nelson B Freimer, Roel A Ophoff, Loes M Olde Loohuis, Michael E Talkowski, Benjamin M Neale, Daniel P Howrigan, Alicia R Martin

Duncan NRI Faculty and Staff Publications

Here we developed and deployed the blended genome exome (BGE) method, a DNA library approach that generates low-pass whole-genome (1–4× mean depth) and deep whole-exome (30–40× mean depth) data in a single sequencing run. BGE is cost-effective, empowers most genomic discoveries possible with deep whole-genome sequencing and captures global common single-nucleotide polymorphism diversity. We applied BGE to sequence >53,000 samples from the PUMAS Project (Populations Underrepresented in Mental Illness Associations Studies), including African, African American and Latin American populations. Imputed genotypes showed high concordance with Illumina Global Screening Array calls (R2 ≥ 95% for minor allele frequency ≥1%; …

Hippo Signaling Regulates Cuticle Pigmentation And Dopamine Metabolism In Drosophila, Shelley B Gibson, Samantha L Deal, Ye-Jin Park, Bo Sun, Yanyan Qi, Jung-Wan Mok, Hyung-Lok Chung, Hongjie Li, Shinya Yamamoto

Duncan NRI Faculty and Staff Publications

Pigmentation plays multiple important roles in development, physiology and evolution. Melanization of the insect cuticle requires dopamine as a precursor of melanin and involves key enzymes in dopamine biosynthesis including Tyrosine hydroxylase (TH) and Dopa decarboxylase (Ddc). Some studies have hinted that disruption of the evolutionarily conserved Hippo signaling pathway, which has been primarily studied in the context of tissue growth, may lead to changes in cuticle pigmentation in the fruit fly Drosophila melanogaster. However, to our knowledge, there have not been any systematic investigations into their potential mechanistic links. In this study, we identified that all genes that comprise …

The Effect Of Cerebellar Transcranial Direct Current Stimulation On Anxiety, Shivangi Bhardwaj

All-Inclusive List of Electronic Theses and Dissertations

Anxiety is one of the most prevalent mental health disorders in the U.S. Individuals of all ages are affected by anxiety. Therefore, research into anxiety and its potential treatment has constantly been an area of interest. Newer approaches to managing anxiety include non-invasive stimulation techniques, such as Transcranial Direct Current Stimulation (tDCS), because of its accessibility and effectiveness. Past tDCS work typically focused on regions in the frontal lobe. However, tDCS over the cerebellum has not received as much attention compared to the cerebrum, despite recent work demonstrating cerebellar involvement in emotion processing. Thus, a better understanding of how cerebellar …

Sarcopenic Obesity And Dementia Risk: Primary Associations And Landmark Analyses Of Muscle Strength And Body Composition Trajectories, Zhongyang Guan, Blossom C.M. Stephan, Lorenzo M. Donini, Justyna Godos, Giuseppe Grosso, Leticia Radin Pereira, Carla M. Prado, Carlos J. Toro-Huamanchumo, Jonathan C.K. Wells, Marc Sim, Mario Siervo

Research outputs 2022 to 2026

Background and aims: Sarcopenic obesity (SO) has been proposed as a risk factor for cognitive impairment. Yet evidence is inconsistent and often limited by heterogeneous definitions and lack of longitudinal assessments. This study aimed to examine associations of SO with all-cause and subtype-specific dementia, and to assess dose–response patterns and how longitudinal changes in body composition and muscle strength relate to dementia risk. Methods: We included 489,972 adults (mean age 56.5 ± 8.1 years) followed for a median of 13.6 years. SO was defined using the Sarcopenic Obesity Global Leadership Initiative (SOGLI) criteria. Cox models estimated hazard ratios (HRs) for …

Dissecting Ms4a4a Function In Microglia And Its Role In Alzheimer’S Disease Pathogenesis, Emma Pascal Danhash

Arts & Sciences Graduate Student Theses and Dissertations

Genome-wide association studies have begun to uncover the complex genetic architecture of Alzheimer's disease (AD). Expression of many AD risk loci is enriched in microglia, the resident immune cells of the brain. Common variants near the MS4A gene family have been associated with AD risk and altered soluble triggering receptor expressed on myeloid cells 2 (sTREM2) levels in the cerebrospinal fluid (CSF). MS4A4A is a microglial gene that encodes a tetraspan membrane protein that regulates anti-inflammatory responses in macrophages. However, the mechanism by which MS4A4A contributes to microglial function and AD pathogenesis remains unknown. In this dissertation, I leveraged a …

Naturalistic Classroom And Home Practices To Support Executive Function And Self-Regulation Of Typically Developing Preschool Children Between The Ages Of 3-5 Years Old: A Mixed Method Study, Michelle Ann Burek

Rehabilitation Sciences Theses & Dissertations

Executive function (EF) and self-regulation (SR) are foundational developmental processes supporting young children’s participation in play, learning, social relationships, and everyday occupations. Although important to school readiness, social competence, health, and well-being, these skills are often examined in structured settings rather than the natural environments in which children develop. Guided by ecological, developmental, and occupational therapy perspectives, this dissertation examined EF and SR within children’s everyday participation and explored caregiver and teacher roles in supporting these processes.

This dissertation consists of three interconnected studies. The first was a systematic review of peer-based interventions to improve social participation among children and …

Gut Microbiome Changes In Preclinical Alzheimer’S Disease, D. M. Sithara Dissanayaka, Stephanie R. Rainey-Smith, Hamid R. Sohrabi, Thilini N. Jayasinghe, Vincent Ho, Vijay Jayasena, Kevin Taddei, Colin L. Masters, Ralph N. Martins, W. M.A.D.Binosha Fernando

Research outputs 2022 to 2026

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that develops many years before clinical symptoms appear. The biological changes involved in the earliest stages remain poorly understood, particularly during the preclinical stage. Our previous work has identified gradual gut microbial and metabolic changes during this stage, suggesting these may represent early biological shifts that precede disease progression. Recent studies suggest that the gut microbiome may contribute to early AD processes through its effects on immune regulation, metabolism, and gut–brain communication. Changes in gut microbial composition, including reduced levels of short-chain fatty acid (SCFA)-producing bacteria, such as Faecalibacterium, Roseburia, and Eubacterium, …

Loss Of Pleasure (Anhedonia): A Sex-Dependent, Cross-Species Consequence Of Unpredictable Signals To The Perinatal Brain, Anna M. Zhou, Madison R. Tetzlaff, Laura M. Glynn, Curt A. Sandman, Hal S. Stern, Tallie Z. Baram, Elysia Poggi Davis

Psychology Faculty Articles and Research

Reward seeking is an essential component of human behavior. Anhedonia (reduced motivation for and pleasure in reward) is a core feature of several mental illnesses. Early life adversity associates with later impairments in reward behaviors and related psychopathology; however, specific aspects of early adversity that lead to disrupted reward behaviors are unknown. Capitalizing on evidence that unpredictable signals to the developing brain constitute adversity and influence neurodevelopment, we examined whether exposure to perinatal unpredictable maternal signals associated with diminished reward responsivity, and probed causality using experiments in mice. We analyzed a longitudinal human study (N=158 mother/child dyads) and a …

Editorial: Emerging Treatment Approaches For Substance Use Disorders, David Martinez Garza, Ilya O. Blokhin, Jonathan Brett, Ihsan Salloum

School of Medicine Publications

No abstract provided.

Infant Hippocampal And Amygdala Volume In An Observational Follow-Up From A Randomized Clinical Trial For Maternal Prenatal Depression, Catherine H. Demers, Benjamin L. Hankin, Lillybelle K. Deer, Robert J. Gallop, Mercedes Hoeflich Haase, M. Camille Hoffman, Martin A. Styner, Nancy K. Grote, Elysia Poggi Davis

Psychology: Data Sets

Prenatal maternal depression may have intergenerational effects on offspring brain development, with potential socioemotional consequences. In an observational follow-up of a randomized clinical trial of a prenatal depression intervention (the CARE Project; ClinicalTrials.gov NCT03011801), brain development and subsequent negative emotionality were examined among 109 infants born to mothers randomized during pregnancy to brief interpersonal psychotherapy or enhanced usual care. These data include MRI-derived hippocampal and amygdala volumes at approximately 6 weeks of age and a laboratory-based assessment of infant negative emotionality at 6 months.

Resulting Publication: Infant hippocampal and amygdala volume in an observational follow-up from a randomized clinical trial …

Online Decoding Of Rat Self-Paced Locomotion Speed From Eeg Using Recurrent Neural Networks, Alejandro De Miguel, Nelson Totah, Uri Maoz

Psychology Faculty Articles and Research

Objective. Accurate and reliable neural decoding of locomotion holds promise for advancing clinical applications such as rehabilitation and prosthetic control, as well as for understanding neural correlates of action. Recent studies have demonstrated successful decoding of locomotion kinematics across species in motorized treadmill settings. However, efforts to decode locomotion speed directly and continuously in more natural contexts—where pace is self-selected rather than externally imposed—are scarce, and those that exist generally achieve only modest accuracy and require intracranial implants. Here, we aim to decode self-paced locomotion speed non-invasively and continuously using cortex-wide electroencephalography (EEG) recordings from rats. Approach. We introduce an …

The Human Lrrk2-R1441g Mutation Drives Age-Dependent Oxidative Stress And Mitochondrial Dysfunction In Dopaminergic Neurons, Yuanxin Chen, Lianteng Zhi, Shiquan Cui, Huaixin Wang, Chenbo Zeng, Hui Zhang

Department of Neuroscience Faculty Papers

BACKGROUND: Mitochondrial dysfunction and oxidative stress are central to the pathogenesis of Parkinson's disease (PD), particularly affecting substantia nigra pars compacta (SNc) dopamine (DA) neurons. Here, we investigate how the R1441G mutation in leucine-rich repeat kinase 2 (LRRK2), a key genetic contributor to familial and sporadic PD, impacts mitochondrial function in midbrain DA neurons.

METHODS: We employed a BAC transgenic mouse model overexpressing human LRRK2-R1441G (BAC-hR1441G) and crossed it with TH-mito-roGFP mice to enable mitochondria-targeted redox imaging specifically in DA neurons. Acute midbrain slices from 3-, 6-, and 12-month-old mice were imaged using two-photon microscopy to assess mitochondrial oxidative stress. …