Neurosciences Commons^™

The Landscape Of Malignant Transition: Unraveling Cancer Cell-Of-Origin And Heterogeneous Tissue Microenvironment, Ruihan Luo, Jiajia Liu, Tiangang Wang, Weiling Zhao, Yanfei Wang, Jianguo Wen, Hongyu Wang, Shanli Ding, Xiaobo Zhou

Faculty, Staff and Student Publications

Understanding disease progression and sophisticated tumor ecosystems is imperative for investigating tumorigenesis mechanisms and developing novel prevention strategies. Here, we dissected heterogeneous microenvironments during malignant transitions by leveraging data from 1396 samples spanning 13 major tissues. Within transitional stem-like subpopulations highly enriched in precancers and cancers, we identified 30 recurring cellular states strongly linked to malignancy, including hypoxia and epithelial senescence, revealing a high degree of plasticity in epithelial stem cells. By characterizing dynamics in stem-cell crosstalk with the microenvironment along the pseudotime axis, we found differential roles of ANXA1 at different stages of tumor development. In precancerous stages, reduced …

Intracranial Injury Following Nasogastric Tube Placement After Skull Base Surgery: A Case Report And Systematic Review, Gabrielle Wolter, Zain U Naqvi, Ali Jalali, Tran Locke, K Kelly Gallagher, Meha G Fox

Faculty, Staff and Students Publications

Inadvertent intracranial nasogastric tube placement is a recognized risk following skull base fracture, but prior skull base surgery also poses a significant and underrecognized risk for this potentially fatal complication. We report the case of a 75-year-old female admitted with Clostridioides difficile colitis, six months after endoscopic endonasal resection of a pituitary macroadenoma. A systematic review identified 10 prior cases of intracranial tube placement following skull base or sinonasal surgery, including nasotracheal and feeding tube insertions. Literature suggests that using small-bore flexible tubes and preserving anatomical barriers, such as the position of the middle turbinate and intact bony structures like …

Baseline Cognition And Demographic, Lifestyle, And Cardiovascular Risk Factors In Us Pointer, Kathryn V Papp, Sarah Tomaszewski Farias, Marjorie Howard, Amber Thro, Tiia Ngandu, Brad Caudle, Bonnie C Sachs, Michelle Chan, Kristin R Krueger, Elizabeth R T Hartman, Athene Lee, Michele K York, Marie T Austin, Kathryn E Demos, Thomas M Holland, Xiaoyan Leng, Rema Raman, Heather M Snyder, Maria C Carrillo, Rachel A Whitmer, Mark A Espeland, Laura D Baker

Faculty, Staff and Students Publications

Introduction: Validation of the primary cognitive composite and baseline cognitive characteristics are presented for the US-Study-to-Protect-Brain-Health-Through-Lifestyle-Intervention-to-Reduce-Risk (US POINTER).

Methods: US POINTER is a multicenter, randomized clinical trial of two lifestyle interventions testing cognitive benefit in older adults without significant cognitive impairment but at-risk for decline due to well-established factors. Cognition is measured using a global cognitive composite (US POINTER modified Neuropsychological Test Battery-PmNTB).

Results: The PmNTB is a valid cognitive composite, exhibiting good psychometric properties and tracking with other established outcomes. Among the 2111 enrolled participants (mean age = 68.2 years, 69% women, 31% from race and ethnic minoritized groups), …

Diagnostic Accuracy Of Screening Tools For Depression And Anxiety In Cervical Dystonia, Davide Martino, Mehrafarin Ramezani, Steven Bellows, Brian D Berman, Florence Ching-Fen Chang, Jeanne Feuerstein, Victor Fung, Gamze Kilic Berkmen, Irene A Malaty, Claire Maciver, Scott A Norris, Kathryn J Peall, Joel S Perlmutter, Sarah Pirio Richardson, Laura J Wright, Zahra Goodarzi, Hyder A Jinnah

Faculty, Staff and Students Publications

Introduction: Despite their high prevalence and impact, depression and anxiety are not routinely screened for, and accuracy of screening procedures is unknown in adult-onset dystonia. We evaluated accuracy parameters of selected self-rated scales for depression and anxiety in patients with idiopathic cervical dystonia (CD).

Methods: Two-hundred-and-ten patients with idiopathic CD were recruited from 10 movement disorders centers from the US, Canada, Australia, and UK. At the end of each botulinum toxin cycle, participants were administered the Adult Standard Mini-International Neuropsychiatric Interview (MINI) as reference standard for depression and anxiety. Participants completed 8 self-administered index instruments (2 for depression, 2 for …

Distinguishing Pex2 And Pex16 Gene Variant Severity For Mild, Severe And Atypical Peroxisome Biogenesis Disorders, Vanessa A Gomez, Oguz Kanca, Sharayu V Jangam, Saurabh Srivastav, Jonathan C Andrews, Michael F Wangler

Duncan NRI Faculty and Staff Publications

Peroxisomal biogenesis disorders (PBD) are autosomal recessive diseases caused by mutations in specific PEX genes that impair peroxisome formation, leading to multi-systemic failure. Symptoms vary, even in patients with variants in the same PEX gene. Our goal is to select PEX mutations and use Drosophila to model a severity spectrum based on genotype-phenotype correlations. Utilizing KozakGAL4 (KZ) cassettes, we replaced the coding sequence of Pex with a GAL4 driver, ideal for making 'humanized' flies in which human PEX can replace the fly loss. We generated Pex2KZ and Pex16KZ lines and assessed them in various behavior assays, confirming their severe phenotypes. …

C-Terminal Frameshift Variants In Gpkow Are Associated With A Multisystemic X-Linked Disorder, Jung-Wan Mok, Laura Mackay, Maria Blazo, Elizabeth Mizerik, Jozef Gecz, Renee Carroll, Mathilde Nizon, Sophie Rondeau, Madeleine Joubert, Silvestre Cuinat, Wallid Deb, Fernanda Valle Sirias, Monika Weisz-Hubshman, Shamika Ketkar, Urszula Polak, Alyssa A Tran, Debra Kearney, Neil A Hanchard, Oguz Kanca, Michael F Wangler, Hugo J Bellen, Brendan H Lee, Shinya Yamamoto, Keren Machol

Duncan NRI Faculty and Staff Publications

Purpose: GPKOW, a gene on the X-chromosome, encodes a nuclear RNA-binding protein important in messenger RNA (mRNA) processing as a spliceosome subunit. This work aims to establish GPKOW as a disease-associated gene.

Methods: We describe 3 males from 2 unrelated families with hemizygous frameshift variants affecting the last exon of GPKOW p.(Arg441SerfsTer30) and p.(Ser444GlufsTer28). The effect of p.(Ser444GlufsTer28) on gene expression was evaluated in patient's fibroblasts. In vivo studies in Drosophila melanogaster targeting the sole GPKOW fly ortholog, CG10324 (Gpkow) were performed.

Results: Clinical presentations included intrauterine growth restriction, microcephaly/microencephaly, and eye, brain, skin, and skeletal abnormalities. Heterozygote females presented …

Formation Of An Expanding Memory Representation In The Hippocampus, Sachin P Vaidya, Guanchun Li, Raymond A Chitwood, Yiding Li, Jeffrey C Magee

Faculty, Staff and Students Publications

How brain networks connected by labile synapses store new information without catastrophically overwriting previous memories remains poorly understood. To examine this, we tracked the same population of hippocampal CA1 place cells (PCs) as mice learned a task for 7 days. We found evidence of memory formation as both the number of PCs maintaining a stable place field and the stability of individual PCs progressively increased across the week until most of the representation was composed of long-term stable PCs. The stable PCs disproportionately represented task-related learned information, were retrieved earlier within a behavioral session and showed a strong correlation with …

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

Research outputs 2022 to 2026

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

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

Research outputs 2022 to 2026

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

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

Theses and Dissertations

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

Spinoplastic Surgery: A Review Of Techniques, Indications, And Optimal Patient Selection, Daniel Vernik, Camryn Payne, Krishna Sinha, Casey Martinez, Walter Nicholas Jungbauer, Jonathan L Jeger, Michael Bohl, Alexander E Ropper, Sebastian Winocour, Edward Reece

Faculty, Staff and Students Publications

Background/Objectives: Spinoplastic surgery is an emerging multidisciplinary field developed to address and reduce the complication of pseudoarthrosis following complex spinal reconstructions. While the number of spinal fusion procedures continues to rise every year, fusion failure rates remain as high as 40%. Although pseudoarthrosis may not always manifest clinically, it remains a leading cause of persistent pain and need for subsequent revision surgeries. The multidisciplinary collaboration between spine and plastic surgeons in spinoplastic surgery has therefore emerged as a proactive strategy aimed at preventing complications, particularly in patients identified as high-risk for pseudoarthrosis. As the patient population expands and spinoplastic surgery …

Spinoplastic Surgery: A Review Of Techniques, Indications, And Optimal Patient Selection, Daniel Vernik, Camryn Payne, Krishna Sinha, Casey Martinez, Walter Nicholas Jungbauer, Jonathan L Jeger, Michael Bohl, Alexander E Ropper, Sebastian Winocour, Edward Reece

Faculty, Staff and Students Publications

Background/Objectives: Spinoplastic surgery is an emerging multidisciplinary field developed to address and reduce the complication of pseudoarthrosis following complex spinal reconstructions. While the number of spinal fusion procedures continues to rise every year, fusion failure rates remain as high as 40%. Although pseudoarthrosis may not always manifest clinically, it remains a leading cause of persistent pain and need for subsequent revision surgeries. The multidisciplinary collaboration between spine and plastic surgeons in spinoplastic surgery has therefore emerged as a proactive strategy aimed at preventing complications, particularly in patients identified as high-risk for pseudoarthrosis. As the patient population expands and spinoplastic surgery …

Author Correction: Beta Activity In Human Anterior Cingulate Cortex Mediates Reward Biases, Jiayang Xiao, Joshua A Adkinson, John Myers, Anusha B Allawala, Raissa K Mathura, Victoria Pirtle, Ricardo Najera, Nicole R Provenza, Eleonora Bartoli, Andrew J Watrous, Denise Oswalt, Ron Gadot, Adrish Anand, Ben Shofty, Sanjay J Mathew, Wayne K Goodman, Nader Pouratian, Xaq Pitkow, Kelly R Bijanki, Benjamin Hayden, Sameer A Sheth

Faculty, Staff and Students Publications

No abstract provided.

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

School of Medicine Publications

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

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

Communication Sciences and Disorders Faculty Articles and Research

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

Treatment Outcomes Of Successful M1 Versus M2 Thrombectomy For Low-Aspects Stroke Patients, Huanwen Chen, Marco Colasurdo, Hidetoshi Matsukawa, Conor Cunningham, Ilko Maier, Pascal Jabbour, Joon-Tae Kim, Stacey Quintero Wolfe, Ansaar Rai, Robert M Starke, Marios-Nikos Psychogios, Amir Shaban, Nitin Goyal, Shinichi Yoshimura, Hugo Cuellar, Brian Howard, Ali Alawieh, Ali Alaraj, Mohamad Ezzeldin, Daniele G Romano, Omar Tanweer, Justin Mascitelli, Isabel Fragata, Adam Polifka, Fazeel Siddiqui, Joshua Osbun, Roberto Crosa, Ramesh Grandhi, Charles Matouk, Min S Park, Michael R Levitt, Waleed Brinjikji, Mark Moss, Ergun Daglioglu, Richard Williamson, Pedro Navia, Shakeel Chowdhry, David J Altschul, Alejandro M Spiotta, Peter Kan

Faculty, Staff and Students Publications

Background

The effectiveness of endovascular thrombectomy (EVT) for low Alberta Stroke Program Early CT score (ASPECTS) stroke patients with occlusion of the second segment of the middle cerebral artery (M2) is unclear.

Methods

This was a multicenter retrospective study. Patients with M1 or M2 occlusions and low ASPECTS (< 6) who underwent successful EVT (modified treatment in cerebral ischemia score of 2b or higher) were included. Primary outcome was futile EVT reperfusion (defined as 90-day modified Rankin scale of 5 or 6). Other outcomes of interest include acceptable outcomes (modified Rankin scale of 3 or less) and intracranial hemorrhage (ICH), and all-cause 90-day mortality. Outcomes for M1 patients were compared to M2 patients with multivariable logistic regression models accounting for potential confounders.

Results

173 patients with M1 or M2 occlusions and low ASPECTS (< 6) who underwent successful EVT were identified. After multivariable adjustments, M2 patients had significantly higher odds of futile reperfusion (OR 5.48 [95%CI 1.91 to 15.7], p = 0.002), lower odds of acceptable outcomes (OR 0.33 [95%CI 0.12 to 0.89], p = 0.028), and higher odds of all-cause mortality (OR 4.90 [95%CI 1.65 to 14.5], p = 0.004). These findings suggest that EVT's efficacy for low-ASPECTS stroke patients may be diminished for patients with M2 occlusions. M2 occlusion was not significantly associated with ICH.

Conclusions

Among low-ASEPCTS stroke patients who underwent successful EVT, those with M2 occlusions had significantly higher odds of poor outcome compared to those with M1 occlusions.

Integrating Endocannabinoid Signaling, Cck Interneurons, And Hippocampal Circuit Dynamics In Behaving Animals, Shreya Malhotra, Florian Donneger, Jordan S Farrell, Barna Dudok, Attila Losonczy, Ivan Soltesz

Faculty, Staff and Students Publications

The brain's endocannabinoid signaling system modulates a diverse range of physiological phenomena and is also involved in various psychiatric and neurological disorders. The basic components of the molecular machinery underlying endocannabinoid-mediated synaptic signaling have been known for decades. However, limitations associated with the short-lived nature of endocannabinoid lipid signals had made it challenging to determine the spatiotemporal specificity and dynamics of endocannabinoid signaling in vivo. Here, we discuss how novel technologies have recently enabled unprecedented insights into endocannabinoid signaling taking place at specific synapses in behaving animals. In this review, we primarily focus on cannabinoid-sensitive inhibition in the hippocampus in …

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

University Honors Theses

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

Early Results With Embotrap Iii Stent Retriever: A Multicenter Us Experience, Georgios S Sioutas, Alex N Hoang, Fadi Al Saiegh, Oz Haim, Sanjana Salwi, Avi A Gajjar, Mohamed M Salem, Peter Kan, Omar Tanweer, Justin R Mascitelli, Brian T Jankowitz, Jan-Karl Burkhardt, Visish M Srinivasan

Faculty, Staff and Students Publications

Background

Mechanical thrombectomy with stent retrievers has become a standard treatment for acute ischemic stroke due to large vessel occlusion. Here we present a multicenter US experience using the EmboTrap III stent retriever, the latest iteration within its class.

Methods

We retrospectively reviewed patients with acute ischemic stroke treated with the EmboTrap III device at 4 US centers. We recorded baseline demographics, clinical characteristics, and procedural details. Outcomes included first-pass effect (FPE), modified FPE (mFPE), final mTICI scores, 90-day functional outcomes, and complications.

Results

A total of 92 patients were included, median age of 72 years, and 56.5% were women. …

Asymmetric Cingulum Bundle Connectivity Is Modulated By Paracingulate Sulcus Morphology, Isabel A Danstrom, Joshua A Adkinson, Meghan E Robinson, Lu Lin, Atul Maheshwari, Ben Shofty, Garrett Banks, Mohammed Hasen, Sameer A Sheth, Alica M Goldman, Eleonora Bartoli, Sarah R Heilbronner, Kelly R Bijanki

Faculty, Staff and Students Publications

The cingulum bundle (CB) is a group of axons supporting connectivity among several functional brain networks relevant in healthy and diseased states. The paracingulate sulcus (PCS) is present in at least one cerebral hemisphere across 70% of the population. PCS presence versus absence is linked to differences in structure and function of the anterior cingulate cortex, though the influence of PCS on the white matter of the CB remains unknown. The objective of this work was to define the CB electrographic connectivity profile and determine the impact of PCS morphology on CB engagement. Single-pulse electrical stimulation in combination with stereo-electroencephalography …