Neurosciences Commons^™

Energetic Heterogeneity In Retinal Ganglion Cells: Role Of Neuronal Activity And Implications For Resilience, Zelun Wang

Arts & Sciences Graduate Student Theses and Dissertations

Retinal ganglion cells (RGCs) form the only connection between the eye and the brain via their axons in the optic nerve. In diseases such as glaucoma, RGCs undergo irreversible neurodegeneration leading to vision loss. RGCs consist of multiple types differing in morphology, gene expression, and signaling properties. Moreover, these types exhibit differential survival after axon injury. What cellular properties vary between RGC types that could underlie their heterogeneous response to neurodegeneration? Given that energy metabolism is tightly optimized for the homeostatic and active functions of different neurons, physiologically distinct RGC types likely exhibit divergent energetic characteristics. Furthermore, energy metabolism is …

Pd-L1 Positivity Predicts A Unique Hyperaggressive Tumor Group Within Meng C Meningiomas, Vijay Nitturi, Shervin Hosseingholi Nouri, Collin English, Hsiang-Chih Lu, Elizabeth Ledbetter, Diego Rojas, Sean Lau, Malcolm Mcdonald, Jacob J Mandel, Abdul Basit Khan, Arif O Harmanci, Akdes S Harmanci, Tiemo Klisch, Akash J Patel

Duncan NRI Faculty and Staff Publications

Molecular profiling has identified 3 groups of meningiomas, with MenG C tumors exhibiting the vast majority of recurrences. Efforts to find effective treatments for recurrent meningiomas have remained elusive. Higher WHO-grade meningiomas have exhibited greater Programmed Death Ligand 1 (PD-L1) expression through various methods, but the prognostic value of PD-L1 expression has not been described in the context of molecular profiling. Additionally, trials investigating PD-1/PD-L1-targeted immunotherapies have produced disappointing results. Here, we find that PD-L1 positivity, while prevalent in MenG C tumors, does not predict recurrence in the benign MenG A and B tumors. PD-L1 positivity also occurs independently of …

The Relationships Between Social Network Size, Loneliness And Personality In Individuals Living With A Neurological Condition: An Exploratory Study, Isabella Branson, Kate Turner, Mitchell Turner, Manja Laws, Leah Dempsey, Simon Laws, Mandy Stanley, Johnny Lo, Travis Cruickshank

Research outputs 2022 to 2026

Background: People living with a neurological condition often report having smaller social networks and less frequent social contact, leading to greater loneliness and worse quality of life. This study explored the relationships between personality traits, social network size (SNS) and perceived loneliness in this population. Methods: Sixty-eight individuals diagnosed with a neurological condition participated in this study. Perceived loneliness was assessed using the UCLA Loneliness Scale – Version 3, SNS was evaluated by the Social Network Index and personality traits were examined using the NEO Factor Five Inventory. Path analysis was conducted to determine if loneliness was negatively associated with …

The Role Of Top-Down Appetite Self-Regulation In The Development Of Healthy Eating Behaviors Among Children: A Narrative Review And Socialization Framework, David J Bridgett, Sheryl O Hughes, Matthew Broussard, Daniela Mccourt, Christina M Croce, Jennifer O Fisher

Faculty, Staff and Students Publications

Appetite self-regulation (ASR) among children is thought to have a fundamental role in shaping the development of healthy eating behaviors, dietary intake, and growth during childhood. Parallel to developmental frameworks for understanding "general" self-regulation among children, ASR has been described as involving children's use of "top-down" cognitive processes to moderate "bottom-up" biological drives around food approach and avoidance in the interest of achieving desired eating behaviors or outcomes. Whereas bottom-up ASR processes during early childhood are well characterized, particularly in the context of dysregulation and obesity risk, the role of top-down ASR processes in the development of healthy eating behaviors …

Brain Computer Interfaces: Enhancing Low-Cost Eeg Performance Through Deep, Anwar Rassoul

Shelby Hall Graduate Research Forum Posters

The field of Brain Computer Interfacing (BCI) has traditionally been confined to clinical and research environments due to the high cost and complexity of medical-grade EEG systems. However, the emergence of low-cost hardware exemplified has catalyzed a shift toward accessible, portable BCI applications. While these devices lower the barrier to entry for developers and researchers, they often suffer from a lower signal-to-noise ratio (SNR). This increased noise makes it difficult to extract the clean neural signatures required for high-accuracy control, particularly when operating in non-shielded, real-world environments.

This research focuses on Steady-State Visually Evoked Potentials (SSVEP), a robust BCI paradigm …

Non-Synaptic Function And Localization Of Syntaxin-Binding Protein 1 In A Mouse Model Of Stxbp1-Related Epileptic Encephalopathy, Tao Yang, Rajat Banerjee, Yamei Deng, Sheetal Jahagirdar, Joo Hyun Kim, Wu Chen, Mingshan Xue, Alexey I Nesvizhskii, Michael D Uhler, Jack M Parent, Yu Wang

Duncan NRI Faculty and Staff Publications

Objective: De novo mutations in the syntaxin-binding protein 1 (STXBP1), encoded by STXBP1, are among the most prevalent causes of variable neurodevelopmental disorders, including epileptic encephalopathy, developmental delay, and movement disorders. Although STXBP1 has been proposed as a critical presynaptic protein controlling synaptic vesicle exocytosis, clinical phenotypes also suggest that its biological function could be more diverse.

Methods: The expression pattern of STXBP1 was studied using immunostaining in vitro and in vivo. Synaptosome isolation was performed to investigate the synaptic and non-synaptic localization of STXBP1 in the brain. STXBP1 immunoprecipitation followed by mass spectrometry (MS) was conducted to identify protein …

The Filamentous Ultrastructure Of The Popz Condensate Is Required For Its Cellular Function, Daniel Scholl, Tumara Boyd, Andrew P Latham, Alexandra Salazar, Asma M A M Khan, Steven Boeynaems, Alex S Holehouse, Gabriel C Lander, Andrej Sali, Donghyun Park, Ashok A Deniz, Keren Lasker

Duncan NRI Faculty and Staff Publications

Biomolecular condensates have key roles in regulating cellular processes. Yet, the relationship between atomic features and condensate function remains poorly understood. We studied this relationship using the polar organizing protein Z (PopZ). Here, we revealed hierarchical assembly of PopZ into a filamentous condensate by integrating cryo-electron tomography, biochemistry, single-molecule techniques and molecular dynamics simulations. The PopZ helical domain drives filamentation and condensation, while the disordered region inhibits them. Phase-dependent conformational changes prevent interfilament contacts in the dilute phase and expose client-binding sites in the dense phase. Perturbing filament formation in vitro alters the dynamics of scaffold and client proteins and …

Responsive Neurostimulation In Children, Adolescents, And Young Adults-Longitudinal Effectiveness And Safety, Steven T Lee, Shital Patel, Cemal Karakas, Kimberly Houck, Cristina Trandafir, Matthew J Mcginley, Deepankar Mohanty, James J Riviello, Howard L Weiner, Daniel Curry, Irfan Ali

Faculty, Staff and Students Publications

Drug-resistant epilepsy (DRE) remains challenging to treat, and seizure control often fluctuates over time. Responsive neurostimulation (RNS) is increasingly used in pediatric and young adult populations, yet long-term effectiveness and safety data are limited. We evaluated longitudinal seizure control trajectories and safety of RNS in children, adolescents, and young adults treated at our center. Seizure frequency was assessed at approximately 6-month intervals from serial follow-up visits through the most recent follow-up, with each sampled visit categorized by ≥ 50 % (all-responder, AR) or ≥90 % (super-responder, SR) seizure reduction. We examined the persistence and durability of seizure control and used …

Relationships Between Clinical Symptom Scales And Eeg Biomarkers In Oud Patients, Jess Delange, Benjamin M. Latey, John Glinski, Braden Ashcraft, Jasmine Pannu, Cassidy Beatty, Lauren Knudson, Benjamin Chafetz, Bryan Fugal, Patrick Tanner Brain, N P. Griffin, Christopher Gowans, Amanda Brandaris, Amanda Page, Blake D. Harris, Sophia Delgado, Lorissa Thorpe, Kyle Bills, Andrew Payne

Annual Research Symposium

This poster examines the relationship between clinical symptom scales and electroencephalographic (EEG) biomarkers in patients with Opioid Use Disorder (OUD). Participants from inpatient substance use treatment facilities completed validated mental health and withdrawal assessments, including the COWS, PHQ-9, HAM-A, and ASRS followed by cognitive testing while undergoing 19-lead EEG recording.

Preliminary findings indicate that synthetic opioid use is associated with prolonged P300 response latency across brain regions, suggesting measurable neurophysiologic differences tied to substance type and addiction severity. The study explores how EEG metrics may complement subjective symptom reporting to provide more objective markers of addiction status, co-morbid psychiatric burden, …

Imaging In Acute Neurovascular Emergencies: Optimizing Outcomes In Large Vessel Occlusion Stroke, Chandu Goli, Rohit Patel, Elliott Beard, Anna Liles, Saeed Saleh, Aleeza Namit, Alissa Ongaco, Kevin Steed Ph.D.

Annual Research Symposium

Purpose:

Large vessel occlusion (LVO) stroke is associated with high rates of morbidity and mortality, and patient outcomes are strongly influenced by rapid identification and timely reperfusion. Advances in acute neurovascular imaging have transformed stroke care by enabling precise patient selection, extending treatment windows, and accelerating clinical workflows. The purpose of this project is to evaluate how modern neurovascular imaging strategies influence treatment selection, workflow efficiency, and clinical outcomes in patients with acute LVO stroke.

Methods:

A narrative review of peer-reviewed literature published within the past decade was conducted. The review focused on CT-based imaging (non-contrast CT, CT angiography, CT …

Investigating Tau Pathology In The Retina And Anterior Segment Structures Of The Eye In A 3-Nitropropionic Acid–Induced Tauopathy Mouse Model, Mohamed Sayed Ahmed Abdel-Kader Qasem

Theses and Dissertations

Background and Objectives: Alzheimer's disease, the most prevalent neurodegenerative disorder in older adults, is characterized by accumulation of hyperphosphorylated tau and amyloid-beta (Aβ) plaques in the central nervous system. Given the retina's shared embryological origin with the brain, its direct neural connectivity via the optic nerve, and similarities in vasculature and age-related degeneration patterns, retinal pathology may serve as an early, non-invasive biomarker for Alzheimer's disease. This study employed 3-nitropropionic acid (3NP) as a pathway-specific tauopathy model driven by mitochondrial dysfunction. The study particularly aimed to investigate whether retinal and corneal tau pathology reflects underlying tau-related neurodegeneration triggered by …

Elucidation Of Hub Genes And Pathway Associated With Gut Microbiome Dysbiosis And Alzheimer’S Disease Via Data Analytic Approaches, Premaanand Rawi, Ying Pei Wong, Ee Xion Tan, Anna Pick Kiong Ling

Chulalongkorn Medical Journal

Background: Recent studies have highlighted the relationship between gut microbiome and Alzheimer’s disease (AD), revealing the ways of how gut microbial balance impacts conditions ranging from inflammatory bowel diseases to neurological disorders. The emerging field of the gut-brain-axis suggests production of microbial metabolites influences AD progression. However, there is limited understanding of molecular mechanisms involved in neurological disease when gut microbiome dysbiosis occurs. This study aimed to identify hub genes and pathways associated with gut microbiome dysbiosis and AD through data analytics approaches.

Methods: Public gene expression datasets on gut microbiome dysbiosis, and AD were obtained from the GEO and …

Leveraging Clinical Sleep Data Across Multiple Pediatric Cohorts For Insights Into Neurodevelopment: The Retrospective Analysis Of Sleep In Pediatric (Rasp) Cohorts Study, Naihua N Gong, Aditya Mahat, Samya Ahmad, Daniel Glaze, Mirjana Maletic-Savatic, Matthew Mcginley, Anne Marie Morse, Alcibiades J Rodriguez, Audrey Thurm, Susan Redline, Kiran Maski, Peter Davis, Shaun Purcell, Ashura Buckley

Faculty, Staff and Students Publications

Sleep disturbances are prominent across neurodevelopmental disorders (NDDs) and may reflect specific abnormalities in brain development and function. Overnight polysomnography (PSG) allows for detailed investigation of sleep architecture, offering a unique window into neurocircuit function. Analysis of existing pediatric PSGs from clinical studies could enhance the availability of sleep studies in pediatric patients with NDDs towards a better understanding of mechanisms underlying abnormal development in NDDs. Here, we introduce and characterize a retrospective collection of 1527 clinical pediatric overnight PSGs across five different sites. We first developed an automated stager trained on independent pediatric sleep data, which yielded better performance …

Consensus Paper: Models Of Cerebellar Functions, Shinji Kakei, Andreea C Bostan, Timothy J Ebner, Mohammad Amin Fakharian, Hiroaki Gomi, Xavier Guell, Marie Hemelt, Huu Hoang, Court Hull, Masato Inoue, Takahiro Ishikawa, Masashi Kameda, Mitsuo Kawato, Shigeru Kitazawa, Mario Manto, Javier F Medina, Hiroshi Mitoma, Keiko Ohmae, Shogo Ohmae, Ken-Ichi Okada, Laurentiu S Popa, Jeremy D Schmahmann, Reza Shadmehr, Peter L Strick, Hirokazu Tanaka, Masaki Tanaka, Tadashi Yamazaki

Faculty, Staff and Students Publications

For a long time, from the nineteenth century to most of the twentieth century, the cerebellum was thought to be an organ that regulates movement. Towards the end of the twentieth century, the brain functions associated with the cerebellum began to extend beyond motor control. Now, there is a consensus that the cerebellum is involved not only in motor functions but also in the most basic autonomic functions and the most complex cognitive and emotional functions, with a focus on predictions and internal models. A new functional model of the cerebellum is needed to explain all layers of brain functions …

Biologically-Inspired Multiscale Neuromorphic Architecture, Christian O'Reilly, Ramtin Zand

Publications

This white paper proposes a biologically-inspired multiscale neuromorphic architecture that bridges key gaps between artificial neural networks (ANNs), spiking neural networks (SNNs), and biological neural networks (BNNs). While SNNs offer promising energy efficiency, their broader adoption remains limited by suboptimal performance and the need for novel learning paradigms. To address these challenges, the proposed framework integrates structural and functional principles observed in the brain, including hierarchical organization, sparse and modular connectivity, predictive coding, and diverse neuronal dynamics.

The architecture operates across micro-, meso-, and macro-scales, incorporating neuron-level diversity (e.g., excitatory/inhibitory and principal/support cells), canonical microcircuits (CMCs), and large-scale hierarchical organization. …

Harmonizing Neuropsychological Test Data Across Prospective Studies, Rosita Shishegar, James D. Doecke, Yen Ying Lim, Pierrick Bourgeat, Vincent Dore, Bhargav Tallapragada, Simon M. Laws, Tenielle Porter, Samantha Burnham, Azadeh Feizpour, Ashley Gillman, Michael Weiner, Jason Hassenstab, Christopher C. Rowe, Victor L. Villemagne, Colin L. Masters, Jurgen Fripp, Hamid Sohrabi, Paul Maruff

Research outputs 2022 to 2026

Introduction: Alzheimer's disease (AD) research relies on large datasets and advanced statistical models. However, individual population studies often lack sufficient sample size for conclusive results. Harmonizing cognitive test data across studies can address this gap, despite differences in testing protocols. This study harmonizes cognitive data from three major AD cohorts to support robust clinical–pathological modelling. Methods: Information from the Alzheimer's Disease Neuroimaging Initiative (N = 1446); Australian Imaging, Biomarkers and Lifestyle (N = 1764); and Open Access Series of Imaging Studies-3 (N = 440) were integrated, including cognitive scores, demographics, genetics, and clinical and neuroimaging data. Neuropsychological tests relevant to …

Novel Small-Molecule Analogues Of Iu1 Ameliorate Amyloid-Β Mediated Toxicity In Alzheimer’S Disease Cell And Worm Models, Ajish Ariyath, Fraulein Denise Arigo, Izhar Wallach, W. M.A.D.Binosha Fernando, Ralph N. Martins, Prashant Bharadwaj

Research outputs 2022 to 2026

Dysregulation of the deubiquitinating enzyme Ubiquitin-specific peptidase 14 (USP14) is implicated in several neurodegenerative diseases, and IU1, an allosteric inhibitor, has shown neuroprotective effects by reducing protein aggregate toxicity. This study aimed to develop new IU1 analogues and evaluate their ability to mitigate amyloid-β (Aβ) accumulation and toxicity in Alzheimer’s disease (AD) cell and Caenorhabditis elegans worm models. IU1 and 71 newly designed analogues identified using the AtomNet^® virtual screening platform were assessed in an amyloid precursor protein-C terminal fragment/amyloid-β (APP-C99/Aβ)-producing AD cell model using a high-throughput toxicity assay. Lead compounds were further evaluated for their effects on neurodegeneration, …

Plasma Biomarker Progression Across The Alzheimer's Disease Amyloid Beta And Tau Positron Emission Tomography Trajectories, Rodrigo Cánovas, Christopher J. Fowler, Azadeh Feizpour, Vincent Dóre, Pierrick Bourgeat, Ziad S. Saad, Gallen Triana-Baltzer, Hartmuth C. Kolb, Manu Vandijck, Gwendlyn Kollmorgen, Clara Quijano-Rubio, Jurgen Fripp, Simon Laws, Anthony W. Bannon, Kaj Blennow, Henrik Zetterberg, Stephanie Rainey-Smith, Sulantha Mathotaarachchi, Christopher C. Rowe, Colin L. Masters, James D. Doecke

Research outputs 2022 to 2026

Introduction: With increased uptake in disease-modifying treatments for amyloid beta (Aβ) removal, it is important to measure performance of highly sensitive plasma biomarkers to detect the presence of Aβ and tau in cognitively impaired populations. Methods: In this study, we investigated a large set of plasma biomarkers for their capability to predict Aβ and tau positron emission tomography (PET) and their association with increasing Aβ and tau burden. RESULTS: From the biomarkers assessed, tau phosphorylated at threonine 217 (pTau217) showed the largest increases across the full range of Aβ and tau levels. Furthermore, pTau217/Aβ42 had the smallest proportion of participants …

Regulation Of Autophagy-Mediated Pathways By Diet, Physical Activity, And Sleep In Alzheimer's Disease, Ajish Ariyath, Zoe Mputhia, Christopher Dougherty, Bushra Kaleelur Rahuman, W. M.A.D.Binosha Fernando, Belinda Brown, Samantha L. Gardener, Stephanie R. Rainey-Smith, Ralph Martins, Prashant Bharadwaj

Research outputs 2022 to 2026

Alzheimer's disease (AD) is a progressive, age-related, neurodegenerative disorder marked by cognitive decline, memory loss, and accumulation of amyloid beta (Aβ) plaques and tau tangles. A key feature of AD is impaired protein homeostasis, often driven by autophagy dysfunction. Autophagy, a cellular degradation and recycling process, plays a vital role in maintaining neuronal health and is increasingly recognized as a therapeutic target in AD. Lifestyle factors such as diet, physical activity, and sleep can positively influence autophagy and support cognitive function. Intermittent fasting (IF) and calorie restriction (CR) activate autophagy and promote longevity; physical activity enhances cerebral blood flow and …

Minifast: A Sensitive And Fast Miniaturized Microscope For In Vivo Neural Recording, Jill Juneau, Guillaume Duret, Joshua P Chu, Blake Madruga, Conor C Dorian, Alexander V Rodriguez, Savva Morozov, Daniel Aharoni, Jacob T Robinson, François St-Pierre, Peyman Golshani, Caleb Kemere

Faculty, Staff and Students Publications

Significance: Observing the activity of large populations of neurons in vivo is critical for understanding brain function and dysfunction. The use of fluorescent genetically encoded calcium indicators (GECIs) in conjunction with miniaturized microscopes is an exciting emerging toolset for recording neural activity in unrestrained animals. Despite their potential, current miniaturized microscope designs are limited using image sensors with low frame rates, sensitivity, and resolution. Beyond GECIs, there are many neuroscience applications that would benefit from the use of other emerging neural indicators, such as fluorescent genetically encoded voltage indicators (GEVIs) that have faster temporal resolution to match neuron spiking, yet …