Neurosciences Commons^™

Discriminative Performance Of Externally Validated Dementia Risk Prediction Models: A Systematic Review And Meta-Analysis, Blossom C.M. Stephan, Jacob Brain, Kaarin J. Anstey, Tanya Buchanan, Claire V. Burley, Elissa Burton, Jennifer Dunne, Linda Errington, Matthew Gorringe, Zhongyang Guan, Bronwyn Myers, Serena Sabatini, Marc Sim, William Stephan, Eugene Yee Hing Tang, Narelle Warren, Mario Siervo

Research outputs 2022 to 2026

Background: Data on the external validation of current dementia risk prediction models has not yet been systematically synthesised. This systematic review and meta-analysis collated results from three previous reviews to evaluate the predictive discriminative performance of dementia risk models when validated in population-based settings. Methods: Embase (via Ovid), Medline (via Ovid), Scopus, and Web of Science were searched from inception to June 2022 with an updated search conducted up to November 2024. Included studies (1) had a population-based cohort design; (2) assessed incident late-life (i.e. ≥ 60 years) dementia; and (3) reported predictive performance of at least one dementia risk …

The Relationship Between Dietary Sodium Intake And Cognitive Function: A Narrative Review, Samantha L. Gardener, M. Fu, L. Morini, T. Schwartzkopff, G. Savage, R. N. Martins, S. R. Rainey-Smith

Research outputs 2022 to 2026

Purpose of Review: This narrative review provides discussion on current evidence regarding the relationship between sodium intake and cognitive function in animal and human studies, as well as potential mechanisms underlying this relationship. Recent Findings: Recent evidence suggests high sodium intake is associated with development of cognitive impairment and neural dysfunction. Additionally, studies have proposed that high sodium intake is associated with increased aggregation of Aβ-amyloid and that hypertension (for which high sodium intake is a risk factor) modulates the relationship between Aβ-amyloid and development of cognitive impairment and Alzheimer’s disease. However, while animal studies demonstrate a consistent relationship between …

Risk Factors Associated With Moderate And Severe Traumatic Brain Injury Mortality In Admitted Older Adults: A Retrospective, Single-Center Study At A Level Ii Trauma Center., Michael Sawyers, Katherine Graham, John Elliott, Jeff Hubartt

Trauma and Acute Care Articles

Purpose: Approximately one in four adults aged ≥65 years experiences a fall each year, and over one-third of these events require medical care. Older adults are at higher risk of complications because of comorbidities. Most prior studies have focused on incidence rather than outcomes, and few have evaluated the association between age and traumatic brain injury (TBI) mortality. This study assessed risk factors and risk-adjusted mortality and morbidity among older adults with moderate or severe TBI.

Methods: We conducted a retrospective review of data from a single-center trauma registry. Inclusion criteria were age ≥65 years, admission ≥3 days (2019-2024), Abbreviated …

Arriving At A Diagnosis: Effective Strategies Used By The Undiagnosed Diseases Network, Somin Hwang, Rachel M Brown, Dustin Baldridge, Erin E Baldwin, Alan H Beggs, Jonathan A Bernstein, Elizabeth Blue, Nicholas A Borja, Lorenzo D Botto, Lauren C Briere, Thomas Cassini, Cecilia Esteves, Elizabeth L Fieg, Gail P Jarvik, Shilpa Nadimpalli Kobren, Mia P Levanto, Julian A Martínez-Agosto, Shruti Marwaha, Stanley F Nelson, Jill A Rosenfeld, Tim Schedl, Tina K Truong, Jennifer A Wambach, Matthew T Wheeler, Shinya Yamamoto, Undiagnosed Diseases Network, Vandana Shashi, Alexa T Mccray, David R Adams, Kimberly Leblanc

Duncan NRI Faculty and Staff Publications

Purpose: Despite the increasing use of exome sequencing (ES) and genome sequencing (GS) in clinical settings, many individuals remain undiagnosed. This study examined the Undiagnosed Diseases Network (UDN)'s approach to establishing diagnoses for participants.

Methods: As a continuation of the first UDN cohort (9/16/2015-5/23/2017), this study reviewed diagnostic strategies and outcomes in the second UDN cohort (5/24/2017-6/30/2023).

Results: Over the study period, the proportion of UDN participants with prior ES/GS increased from 40.2% to 75.0%. The diagnostic rate for the UDN was 22.1% (379/1,713). Reanalysis/reinterpretation of sequencing data (prior ES: 21.4%, prior GS: 2.6%, UDN ES: 4.8%, UDN GS: 17.3%) …

Comparative Analysis Of Takagi-Sugeno And Mamdani Fuzzy Inference Architectures With Anfis-Based Automated Rule Generation For Eeg-Based Cognitive State Monitoring, Amina Radončić, Mehrija Hasičić, Jasmin Kevrić

Communications of the IIMA

Fuzzy inference systems have demonstrated considerable promise for EEG-based cognitive state monitoring in neurodegenerative conditions. However, two design decisions significantly influence system performance and clinical applicability: the choice of inference architecture (Takagi-Sugeno vs Mamdani) and the method of rule and membership function generation (manual expert-driven vs data-driven automated). This paper presents a comparative analysis of both dimensions in the context of an EEG-based Alzheimer’s disease monitoring system operating on the ds004504 OpenNeuro dataset (88 subjects: 36 AD, 23 FTD, 29 HC). A Takagi-Sugeno system, implemented as a hybrid FSM-Fuzzy architecture, is compared against a Mamdani equivalent across four axes: inference …

No Evidence For Modulation Of The Readiness Potential By Respiratory Phase During Natural Breathing, Lucas Jeay-Bizot, Raniyah Chisti, Uri Maoz, Aaron Schurger

Psychology Faculty Articles and Research

Respiratory processes are increasingly implicated in shaping neural activity and behavior. Recent studies have reported a coupling between respiratory phase and the cortical readiness potential (RP), suggesting that breathing may modulate the neural processes preceding voluntary action. Here, using electroencephalography recordings in humans, we re-examine this claim using the original dataset and a new independent dataset, as well as in simulated data with no coupling. We show that the reported association arises from a confound: both RP amplitude and respiratory phase are coupled to movement onset. The original analysis does not control for this dependency, leading to a spurious effect …

Neurochemical Impact Of Psychostimulants: Longitudinal Mri Analysis Of Brain Iron Content In Children With Adhd, Hugo A.E. Morandini, Sjoerd B. Vos, Paola Chivers, Tim J. Silk, Pradeep Rao

Research outputs 2022 to 2026

Background: Attention Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder in school-aged children and has been associated with impaired brain iron homeostasis. Evidence has shown that psychostimulant treatment may affect brain iron content in children with ADHD, however, longitudinal evidence remains limited. The present longitudinal study investigated the effect of psychostimulant treatment duration and age at treatment onset on brain iron content in children with ADHD. Methods: Neuroimaging and phenotypical data were collected from the publicly available Oregon ADHD-1000 dataset. After screening, data from 29 psychostimulant-medicated children with ADHD and 38 neurotypical children were included. Individual General Estimating Equation (GEE) …

Bivip: A Competitive Neural Network For Bilateral Visuo-Haptic Processing, Eleonore Federica Di Rosa, Aaisha Sheth, Jeffrey Min-In Yau, Laura Astolfi, Cristiano Cuppini

Faculty, Staff and Students Publications

Visuo-haptic interactions are gaining interest in perception research because of their relevance to robotics and rehabilitation. While the benefits of integrating concurrent visuo-tactile cues are well-documented, the temporal dynamics of competitive interactions between vision and touch remain less understood. Building on extant empirical evidence of unilateral intersensory switching, we ask whether bilateral detection of visual and tactile stimuli can be explained by cross-sensory competition and explore the underlying sensorineural dynamics via a multi-level neural network model. Tested against results from a speeded reaction time task to unilateral and bilateral visual, tactile, and visuo-tactile targets, the network successfully predicts higher switch …

Longitudinal Association Between Midlife Cardiovascular Health And Cognitive Change In A Bi-Ethnic Cohort, Janette Vazquez, Rebecca Bernal, Luis Aguirre, Jesus D. Melgarejo, Gladys Maestre, Sudha Seshadri, Helen P. Hazuda, Chen-Pin Wang, Claudia Satizabal

School of Medicine Publications

Introduction: Midlife cardiovascular burden contributes to cognitive decline and dementia. However, research in diverse populations remains scarce.

Methods: We included 402 San Antonio Heart Study participants (1979–1988; midlife mean age 57.9 ± 3.8, 58.5% women, 52% Mexican American) later enrolled in the San Antonio Longitudinal Study of Aging (1992–2004). Midlife cardiovascular health was assessed using Life's Simple 7. Cognition was measured up to four times with the Mini-Mental State Examination. Generalized estimating equation models adjusted for age, sex, income, and education were used to relate cardiovascular factors to cognitive change. Sensitivity analyses evaluated attrition bias.

Results: Physical activity was associated …

Variation In Meningioma Recurrence Risk Estimates Across Observational Cohorts: The Influence Of Calendar Time, Who Classifications, Geographical Settings, And Healthcare Systems, Christian Mirian, Lasse Rehné Jensen, Adam Gorm Hoffmann, Tareq A Juratli, Anders Broechner, Sverre H Torp, Helen A Shih, Ramin A Morshed, Jacob S Young, Stephen T Magill, Luca Bertero, Walter Stummer, Dorothee Cäcilia Spille, Benjamin Brokinkel, Soichi Oya, Satoru Miyawaki, Nobuhito Saito, Martin Proescholdt, Yasuhiro Kuroi, Konstantinos Gousias, Matthias Simon, Jennifer Moliterno, Ricardo Prat-Acin, Stéphane Goutagny, Vikram C Prabhu, John T Tsiang, Johannes Wach, Erdem Güresir, Junkoh Yamamoto, Young Zoon Kim, Joo Ho Lee, Daniel W Kim, Matthew Koshy, Karthikeyan Perumal, Mustafa K Baskaya, Donald M Cannon, Dennis C Shrieve, Chang-Ok Suh, Jong Hee Chang, Maria Kamenova, Sven Straumann, Jehuda Soleman, Ilker Y Eyüpoglu, Tony Catalan, Austin Lui, Philip V Theodosopoulos, Michael W Mcdermott, Fang Wang, Pedro Góes, Manoel Antonio De Paiva Neto, Ricardo Komotar, Michael E Ivan, Aria Jamshidi, Evan Luther, Luis Souhami, Marie-Christine Guiot, Tamás Csonka, Toshiki Endo, Olivia Claire Barrett, Randy Jensen, Tejpal Gupta, Akash J Patel, Tiemo J Klisch, Jun Won Kim, Francesco Maiuri, Valeria Barresi, María Dolores Tabernero, Simon Skyrman, Ian Law, Bjarne Winther Kristensen, Tina Nørgaard Munch, Torstein Meling, Kåre Fugleholm, Paul Blanche, Tiit Mathiesen, Andrea Daniela Maier

Duncan NRI Faculty and Staff Publications

Purpose: Recurrence risk estimates underpin meningioma research, including molecular classification and clinical trial benchmarking, yet are often based on retrospective or historical data. The aim of this study was to assess the variation of recurrence risk estimates across calendar periods, WHO classification editions, geographical settings, and healthcare systems.thetermine METHODS: We analyzed 4,111 patients with primary WHO-1/-2 meningiomas from 31 centers in 15 countries (1990-2019). Recurrence was defined according to local radiological assessment. The 5- and 10-year recurrence risks were estimated using regression standardization with inverse probability of censoring weights, adjusting for key clinical, surgical, and histopathological variables.

Results: Recurrence risk …

Translational Initiative To Minimize Childhood Hemiparesis After Asymmetrical Perinatal Brain Injury, Susan V. Duff, Emily Garavatti, Terrie Inder

Physical Therapy Faculty Articles and Research

The purpose of this perspective paper is to present a translational approach aimed at identifying the critical periods in brain development during which to provide neuroprotective and neurorestorative strategies, followed by prehensile training, to minimize hemiparesis and foster skill acquisition after asymmetrical perinatal brain injury (APBI). We contend that hemiparesis could be minimized after APBI through a multimodal sequential approach based on timely implementation of evidence-based intervention strategies. If APBI is identified early, neuroprotective techniques can be used in the first 10 days of life to minimize cell death. This can be followed in the next 3 months by the …

Studying What Matters: South Texas Community-Driven Dementia Research Priorities, Sara S. Masoud, Juana Escareño, Belinda Flores, Byeong Yeob Choi, Karla Daniela Lopez Lorenzo, Shanae L. Rhodes, Quetzaly Zenil, Carole L. White

School of Medicine Publications

South Texas has among the highest dementia prevalence rates in the United States, yet communities in the region remain consistently underrepresented in dementia research. Aligning research studies with what matters to communities most impacted by dementia is critical in addressing the crisis of research exclusion. This participatory study sought to identify community-driven dementia research priorities grounded in the experiences and needs of South Texas residents impacted by dementia. A two-year community-engaged study was conducted in partnership with a Community Council composed of individuals living with dementia, family caregivers, community health workers, and community-serving professionals. A plática program model was co-developed …

Amyloid-Related Imaging Abnormalities Summit Special Proceedings: Cardiovascular And Stroke Considerations For Β-Amyloid Immunotherapy In Alzheimer Disease., Steven M Greenberg, Costantino Iadecola, Sherry H-Y Chou, Petrice M Cogswell, Mitchell S V Elkind, William J Hicks, Caitlin Le, Deborah A Levine, Richard Lipton, Lauren Massimo, Stephanie M Mohl, Sudha Seshadri, Heather M Snyder, Kristine Yaffe, Kori S Zachrison, Aria Summit Working Group

Neuroscience Articles

BACKGROUND: New antiamyloid therapies (AAT) for treating patients with early Alzheimer disease (AD) have become available in the past 3 years. Although AAT can be beneficial in slowing progression of AD, they also come with potentially serious side effects, particularly for patients requiring anticoagulation or thrombolysis for cardiovascular conditions. Given that most patients with AD are older and likely to have cardiovascular risk factors, there is urgent need for additional guidance for clinicians about potential risks and benefits associated with AAT for patients with cardiovascular comorbidities, best practices for management of these patients, and special considerations with respect to emergency …

Selective Loss Of Primary Cilia And Neurotrophic Signaling In G51d Α-Synuclein Mice Highlights A Common Pathway To Parkinson’S Disease, Yu-En Lin, Ebsy Jaimon, Youngdoo Kim, Annabeth Loftman, Aaran Vijayakumaran, Benjamin D W Belfort, Claire Y Chiang, Benjamin R Arenkiel, Huda Y Zoghbi, Suzanne R Pfeffer

Duncan NRI Faculty and Staff Publications

Parkinson's disease is characterized by dopaminergic neuron loss and accumulation of α-synuclein aggregates in the brain. G51D α-synuclein knock-in mice provide a genetically and clinically relevant model of disease, exhibiting early olfactory deficits, age-dependent motor impairment, and progressive phospho-α-synuclein accumulation. In multiple Parkinson's disease models, striatal cholinergic and parvalbumin interneurons, as well as astrocytes, lose primary cilia and the neurotrophic signaling needed to sustain dopaminergic neurons. We show here that G51D α-synuclein mice share these phenotypes. Phospho-Ser129 α-synuclein accumulation correlates with cilia loss in cholinergic interneurons but not in spiny projection neurons that accumulate higher phospho-α-synuclein levels. In the piriform …

Data-Driven Staging Of Neurodegenerative Pathology Related To Alzheimer’S Disease, Thomas Earnest

McKelvey School of Engineering Graduate Student Theses & Dissertations

Alzheimer’s Disease (AD), the most common cause of dementia, is a dual proteinopathy exhibiting deposits of extracellular amyloid-beta (Aβ) and intracellular tau in brain tissue. Models which describe the spatial and temporal trajectories of these pathologies have been invaluable for understanding AD and have the potential to support diagnosis, disease monitoring, and treatment development. Disease staging systems, which provide protocols for assessing individual disease severity based on their extent of brain pathology, have been crucial for explaining and diagnosing AD. However, these systems have been primarily informed by post-mortem histological assessments and are not directly applicable to disease assessment in …

Lineage Tracing Reveals A Shared Cellular Origin For Supraclavicular Brown And Inguinal Beige Adipocytes, Yali Ran, Kai Zhang, Yi-Ting Shen, Qianxing Mo, Ziyi Wang, Hari Krishna Yalamanchili, Sharon John, Mari Kogiso, Xia Gao, Chunmei Wang, Tanvi Sinha, Brian L Black, Miao-Hsueh Chen

Duncan NRI Faculty and Staff Publications

The metabolic importance of brown adipose tissue (BAT) has been recognized, but its origins, particularly supraclavicular BAT (scBAT), remain unclear. Here, we traced scBAT to Mef2c-anterior heart field (AHF)-marked cells. Mef2c-AHF-marked cells isolated from scBAT can spontaneously differentiate into brown adipocytes, express mesenchymal stem cell markers, and can be isolated from the stromal-vascular fraction (SVF) of wild-type scBAT as [CD31

Digital Markers For Passive Remote Monitoring Of Bipolar Disorder: Systematic Review, Thomas P Kutcher, Isha Chakraborty, Kristin Kostick-Quenet, Akane Sano, Nidal Moukaddam, Jeffrey A Herron, Wayne K Goodman, Sameer A Sheth, Ashutosh Sabharwal, Nicole R Provenza

Duncan NRI Faculty and Staff Publications

Background: Bipolar disorder (BD) features episodic shifts among mania, hypomania, depression, mixed states, and euthymia. Timely detection of mood transitions is difficult due to infrequent clinical touchpoints. Digital health technologies, including wearables and smartphones, offer a unique opportunity to passively and continuously monitor behavior and physiology that could reflect underlying mood dynamics in real-world settings.

Objective: This study aimed to systematically review passively collected digital markers for BD mood states, characterize devices/modalities and analytic approaches, appraise risk of bias, and identify design gaps and priorities for clinical translation.

Methods: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) …

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 …

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 …

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 …

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

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% …

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 …

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 …

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 …

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, …

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