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Full-Text Articles in Neurosciences

Changes In Outcomes And Factors Associated With Survival In Melanoma Patients With Brain Metastases, Merve Hasanov, Denái R Milton, Alicia Bea Davies, Elizabeth Sirmans, Chantal Saberian, Eliza L Posada, Sylvia Opusunju, Jeffrey E Gershenwald, Carlos A Torres-Cabala, Elizabeth M Burton, Rivka R Colen, Jason T Huse, Isabella C Glitza Oliva, Caroline Chung, Mary Frances Mcaleer, Susan L Mcgovern, Debra N Yeboa, Betty Y S Kim, Sujit S Prabhu, Ian E Mccutcheon, Jeffrey S Weinberg, Frederick F Lang, Hussein A Tawbi, Jing Li, Lauren E Haydu, Michael A Davies, Sherise D Ferguson Jul 2023

Changes In Outcomes And Factors Associated With Survival In Melanoma Patients With Brain Metastases, Merve Hasanov, Denái R Milton, Alicia Bea Davies, Elizabeth Sirmans, Chantal Saberian, Eliza L Posada, Sylvia Opusunju, Jeffrey E Gershenwald, Carlos A Torres-Cabala, Elizabeth M Burton, Rivka R Colen, Jason T Huse, Isabella C Glitza Oliva, Caroline Chung, Mary Frances Mcaleer, Susan L Mcgovern, Debra N Yeboa, Betty Y S Kim, Sujit S Prabhu, Ian E Mccutcheon, Jeffrey S Weinberg, Frederick F Lang, Hussein A Tawbi, Jing Li, Lauren E Haydu, Michael A Davies, Sherise D Ferguson

Faculty, Staff and Student Publications

BACKGROUND: Treatment options for patients with melanoma brain metastasis (MBM) have changed significantly in the last decade. Few studies have evaluated changes in outcomes and factors associated with survival in MBM patients over time. The aim of this study is to evaluate changes in clinical features and overall survival (OS) for MBM patients.

METHODS: Patients diagnosed with MBMs from 1/1/2009 to 12/31/2013 (Prior Era; PE) and 1/1/2014 to 12/31/2018 (Current Era; CE) at The University of Texas MD Anderson Cancer Center were included in this retrospective analysis. The primary outcome measure was OS. Log-rank test assessed differences between groups; multivariable …


Predictors And Temporal Trends Of Withdrawal Of Life-Sustaining Therapy After Acute Stroke In The Florida Stroke Registry, Ayham Alkhachroum, Lili Zhou, Negar Asdaghi, Hannah Gardener, Hao Ying, Carolina M Gutierrez, Brian M Manolovitz, Daniel Samano, Danielle Bass, Dianne Foster, Nicole B Sur, David Z Rose, Angus Jameson, Nina Massad, Mohan Kottapally, Amedeo Merenda, Robert M Starke, Kristine O'Phelan, Jose G Romano, Jan Claassen, Ralph L Sacco, Tatjana Rundek Jul 2023

Predictors And Temporal Trends Of Withdrawal Of Life-Sustaining Therapy After Acute Stroke In The Florida Stroke Registry, Ayham Alkhachroum, Lili Zhou, Negar Asdaghi, Hannah Gardener, Hao Ying, Carolina M Gutierrez, Brian M Manolovitz, Daniel Samano, Danielle Bass, Dianne Foster, Nicole B Sur, David Z Rose, Angus Jameson, Nina Massad, Mohan Kottapally, Amedeo Merenda, Robert M Starke, Kristine O'Phelan, Jose G Romano, Jan Claassen, Ralph L Sacco, Tatjana Rundek

Faculty, Staff and Student Publications

Temporal trends and factors associated with the withdrawal of life-sustaining therapy (WLST) after acute stroke are not well determined.

DESIGN: Observational study (2008-2021).

SETTING: Florida Stroke Registry (152 hospitals).

PATIENTS: Acute ischemic stroke (AIS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH) patients.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Importance plots were performed to generate the most predictive factors of WLST. Area under the curve (AUC) for the receiver operating curve were generated for the performance of logistic regression (LR) and random forest (RF) models. Regression analysis was applied to evaluate temporal trends. Among 309,393 AIS patients, 47,485 ICH patients, and …


Bystanders Or Not? Microglia And Lymphocytes In Aging And Stroke, Justin N Nguyen, Anjali Chauhan Jul 2023

Bystanders Or Not? Microglia And Lymphocytes In Aging And Stroke, Justin N Nguyen, Anjali Chauhan

Faculty, Staff and Student Publications

As the average age of the world population increases, more people will face debilitating aging-associated conditions, including dementia and stroke. Not only does the incidence of these conditions increase with age, but the recovery afterward is often worse in older patients. Researchers and health professionals must unveil and understand the factors behind age-associated diseases to develop a therapy for older patients. Aging causes profound changes in the immune system including the activation of microglia in the brain. Activated microglia promote T lymphocyte transmigration leading to an increase in neuroinflammation, white matter damage, and cognitive impairment in both older humans and …


Stress-Induced Changes In Autonomic Reactivity Vary With Adolescent Violence Exposure And Resting-State Functional Connectivity, Heather E Dark, Nathaniel G Harnett, Adam M Goodman, Muriah D Wheelock, Sylvie Mrug, Mark A Schuster, Marc N Elliott, Susan Tortolero Emery, David C Knight Jul 2023

Stress-Induced Changes In Autonomic Reactivity Vary With Adolescent Violence Exposure And Resting-State Functional Connectivity, Heather E Dark, Nathaniel G Harnett, Adam M Goodman, Muriah D Wheelock, Sylvie Mrug, Mark A Schuster, Marc N Elliott, Susan Tortolero Emery, David C Knight

Faculty, Staff and Student Publications

Exposure to violence during childhood can lead to functional changes in brain regions that are important for emotion expression and regulation, which may increase susceptibility to internalizing disorders in adulthood. Specifically, childhood violence exposure can disrupt the functional connectivity among brain regions that include the prefrontal cortex (PFC), hippocampus, and amygdala. Together, these regions are important for modulating autonomic responses to stress. However, it is unclear to what extent changes in brain connectivity relate to autonomic stress reactivity and how the relationship between brain connectivity and autonomic responses to stress varies with childhood violence exposure. Thus, the present study examined …


Cortex-Wide Neural Dynamics Predict Behavioral States And Provide A Neural Basis For Resting-State Dynamic Functional Connectivity, Somayeh Shahsavarani, David N Thibodeaux, Weihao Xu, Sharon H Kim, Fatema Lodgher, Chinwendu Nwokeabia, Morgan Cambareri, Alexis J Yagielski, Hanzhi T Zhao, Daniel A Handwerker, Javier Gonzalez-Castillo, Peter A Bandettini, Elizabeth M C Hillman Jun 2023

Cortex-Wide Neural Dynamics Predict Behavioral States And Provide A Neural Basis For Resting-State Dynamic Functional Connectivity, Somayeh Shahsavarani, David N Thibodeaux, Weihao Xu, Sharon H Kim, Fatema Lodgher, Chinwendu Nwokeabia, Morgan Cambareri, Alexis J Yagielski, Hanzhi T Zhao, Daniel A Handwerker, Javier Gonzalez-Castillo, Peter A Bandettini, Elizabeth M C Hillman

Faculty, Staff and Student Publications

Although resting-state functional magnetic resonance imaging (fMRI) studies have observed dynamically changing brain-wide networks of correlated activity, fMRI's dependence on hemodynamic signals makes results challenging to interpret. Meanwhile, emerging techniques for real-time recording of large populations of neurons have revealed compelling fluctuations in neuronal activity across the brain that are obscured by traditional trial averaging. To reconcile these observations, we use wide-field optical mapping to simultaneously record pan-cortical neuronal and hemodynamic activity in awake, spontaneously behaving mice. Some components of observed neuronal activity clearly represent sensory and motor function. However, particularly during quiet rest, strongly fluctuating patterns of activity across …


Effects Of Spaceflight On The Eeg Alpha Power And Functional Connectivity, Sandra Pusil, Jonathan Zegarra-Valdivia, Pablo Cuesta, Christopher Laohathai, Ana Maria Cebolla, Jens Haueisen, Patrique Fiedler, Michael Funke, Fernando Maestú, Guy Cheron Jun 2023

Effects Of Spaceflight On The Eeg Alpha Power And Functional Connectivity, Sandra Pusil, Jonathan Zegarra-Valdivia, Pablo Cuesta, Christopher Laohathai, Ana Maria Cebolla, Jens Haueisen, Patrique Fiedler, Michael Funke, Fernando Maestú, Guy Cheron

Faculty, Staff and Student Publications

Electroencephalography (EEG) can detect changes in cerebral activity during spaceflight. This study evaluates the effect of spaceflight on brain networks through analysis of the Default Mode Network (DMN)'s alpha frequency band power and functional connectivity (FC), and the persistence of these changes. Five astronauts' resting state EEGs under three conditions were analyzed (pre-flight, in-flight, and post-flight). DMN's alpha band power and FC were computed using eLORETA and phase-locking value. Eyes-opened (EO) and eyes-closed (EC) conditions were differentiated. We found a DMN alpha band power reduction during in-flight (EC: p < 0.001; EO: p < 0.05) and post-flight (EC: p < 0.001; EO: p < 0.01) when compared to pre-flight condition. FC strength decreased during in-flight (EC: p < 0.01; EO: p < 0.01) and post-flight (EC: ns; EO: p < 0.01) compared to pre-flight condition. The DMN alpha band power and FC strength reduction persisted until 20 days after landing. Spaceflight caused electrocerebral alterations that persisted after return to earth. Periodic assessment by EEG-derived DMN analysis has the potential to become a neurophysiologic marker of cerebral functional integrity during exploration missions to space.


Chronic Basal Forebrain Activation Improves Spatial Memory, Boosts Neurotrophin Receptor Expression, And Lowers Bace1 And Aβ42 Levels In The Cerebral Cortex In Mice, Jacob Kumro, Ashutosh Tripathi, Yun Lei, Jeremy Sword, Patrick Callahan, Alvin Terry, Xin-Yun Lu, Sergei A Kirov, Anilkumar Pillai, David T Blake Jun 2023

Chronic Basal Forebrain Activation Improves Spatial Memory, Boosts Neurotrophin Receptor Expression, And Lowers Bace1 And Aβ42 Levels In The Cerebral Cortex In Mice, Jacob Kumro, Ashutosh Tripathi, Yun Lei, Jeremy Sword, Patrick Callahan, Alvin Terry, Xin-Yun Lu, Sergei A Kirov, Anilkumar Pillai, David T Blake

Faculty, Staff and Student Publications

The etiology of Alzheimer’s dementia has been hypothesized in terms of basal forebrain cholinergic decline, and in terms of reflecting beta-amyloid neuropathology. To study these different biological elements, we activated the basal forebrain in 5xFAD Alzheimer’s model mice and littermates. Mice received 5 months of 1 h per day intermittent stimulation of the basal forebrain, which includes cholinergic projections to the cortical mantle. Then, mice were behaviorally tested followed by tissue analysis. The 5xFAD mice performed worse in water-maze testing than littermates. Stimulated groups learned the water maze better than unstimulated groups. Stimulated groups had 2–3-fold increases in frontal cortex …


Inferring Personalized Treatment Effect Of Antihypertensives On Alzheimer's Disease Using Deep Learning, Pulakesh Upadhyaya, Yaobin Ling, Luyao Chen, Yejin Kim, Xiaoqian Jiang Jun 2023

Inferring Personalized Treatment Effect Of Antihypertensives On Alzheimer's Disease Using Deep Learning, Pulakesh Upadhyaya, Yaobin Ling, Luyao Chen, Yejin Kim, Xiaoqian Jiang

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is one of the leading causes of death in the United States, especially among the elderly. Recent studies have shown how hypertension is related to cognitive decline in elderly patients, which in turn leads to increased mortality as well as morbidity. There have been various studies that have looked at the effect of antihypertensive drugs in reducing cognitive decline, and their results have proved inconclusive. However, most of these studies assume the treatment effect is similar for all patients, thus considering only the average treatment effects of antihypertensive drugs. In this paper, we assume that the effect …


Predicting The Risk Of Alzheimer's Disease And Related Dementia In Patients With Mild Cognitive Impairment Using A Semi-Competing Risk Approach, Zhaoyi Chen, Yuchen Yang, Dazheng Zhang, Jingchuan Guo, Yi Guo, Xia Hu, Yong Chen, Jiang Bian Jun 2023

Predicting The Risk Of Alzheimer's Disease And Related Dementia In Patients With Mild Cognitive Impairment Using A Semi-Competing Risk Approach, Zhaoyi Chen, Yuchen Yang, Dazheng Zhang, Jingchuan Guo, Yi Guo, Xia Hu, Yong Chen, Jiang Bian

Faculty, Staff and Student Publications

Alzheimer's disease (AD) and AD-related dementias (AD/ADRD) are a group of progressive neurodegenerative diseases. The progression of AD can be conceptualized as a continuum in which patients progress from normal cognition to preclinical AD (i.e., no symptoms but biological changes in the brain) to mild cognitive impairment (MCI) due to AD (i.e., mild symptoms but not interfere with daily activities), followed by increasing severity of dementia due to AD. Early detection and prediction models for the transition of MCI to AD/ADRD are needed, and efforts have been made to build predictions of MCI conversion to AD/ADRD. However, most existing studies …


Sex And Gender Differences In Acute Stroke Care: Metrics, Access To Treatment And Outcome A Territorial Analysis Of The Stroke Code System Of Catalonia, Yolanda Silva, Laura Sánchez-Cirera, Mikel Terceño, Laura Dorado, Adrián Valls, Marina Martínez, Sònia Abilleira, Marta Rubiera, Helena Quesada, Laura Llull, Ana Rodríguez-Campello, Joan Martí-Fàbregas, Laia Seró, Francisco Purroy, Iago Payo, Sònia García, David Cánovas, Jurek Krupinski, Natalia Mas, Ernest Palomeras, Dolores Cocho, Maria Àngels Font, Esther Catena, Elsa Puiggròs, Claudia Pedroza, Gemma Marín, Dolors Carrión, Xavier Costa, Mari Cruz Almendros, Ivan Torres, Carla Colom, John Alejandro Velasquez, Gloria Diaz, Xavier Jiménez, Teresa Subirats, Anna Deulofeu, Verónica Hidalgo, Mercè Salvat-Plana, Natalia Pérez De La Ossa, Catalan Stroke Code And Reperfusion Consortium (Cat-Scr) Jun 2023

Sex And Gender Differences In Acute Stroke Care: Metrics, Access To Treatment And Outcome A Territorial Analysis Of The Stroke Code System Of Catalonia, Yolanda Silva, Laura Sánchez-Cirera, Mikel Terceño, Laura Dorado, Adrián Valls, Marina Martínez, Sònia Abilleira, Marta Rubiera, Helena Quesada, Laura Llull, Ana Rodríguez-Campello, Joan Martí-Fàbregas, Laia Seró, Francisco Purroy, Iago Payo, Sònia García, David Cánovas, Jurek Krupinski, Natalia Mas, Ernest Palomeras, Dolores Cocho, Maria Àngels Font, Esther Catena, Elsa Puiggròs, Claudia Pedroza, Gemma Marín, Dolors Carrión, Xavier Costa, Mari Cruz Almendros, Ivan Torres, Carla Colom, John Alejandro Velasquez, Gloria Diaz, Xavier Jiménez, Teresa Subirats, Anna Deulofeu, Verónica Hidalgo, Mercè Salvat-Plana, Natalia Pérez De La Ossa, Catalan Stroke Code And Reperfusion Consortium (Cat-Scr)

Faculty, Staff and Student Publications

INTRODUCTION: Previous studies have reported differences in the management and outcome of women stroke patients in comparison with men. We aim to analyze sex and gender differences in the medical assistance, access to treatment and outcome of acute stroke patients in Catalonia.

PATIENTS AND METHODS: Data were obtained from a prospective population-based registry of stroke code activations in Catalonia (CICAT) from January/2016 to December/2019. The registry includes demographic data, stroke severity, stroke subtype, reperfusion therapy, and time workflow. Centralized clinical outcome at 90 days was assessed in patients receiving reperfusion therapy.

RESULTS: A total of 23,371 stroke code activations were …


Vagus Nerve Stimulation Paired With Rehabilitation For Upper Limb Motor Impairment And Function After Chronic Ischemic Stroke: Subgroup Analysis Of The Randomized, Blinded, Pivotal, Vns-Rehab Device Trial, Jesse Dawson, Navzer D Engineer, Steven C Cramer, Steven L Wolf, Rushna Ali, Michael W O'Dell, David Pierce, Cecília N Prudente, Jessica Redgrave, Wuwei Feng, Charles Y Liu, Gerard E Francisco, Benjamin L Brown, Anand Dixit, Jen Alexander, Louis Demark, Vibor Krishna, Steven A Kautz, Arshad Majid, Brent Tarver, Duncan L Turner, Teresa J Kimberley Jun 2023

Vagus Nerve Stimulation Paired With Rehabilitation For Upper Limb Motor Impairment And Function After Chronic Ischemic Stroke: Subgroup Analysis Of The Randomized, Blinded, Pivotal, Vns-Rehab Device Trial, Jesse Dawson, Navzer D Engineer, Steven C Cramer, Steven L Wolf, Rushna Ali, Michael W O'Dell, David Pierce, Cecília N Prudente, Jessica Redgrave, Wuwei Feng, Charles Y Liu, Gerard E Francisco, Benjamin L Brown, Anand Dixit, Jen Alexander, Louis Demark, Vibor Krishna, Steven A Kautz, Arshad Majid, Brent Tarver, Duncan L Turner, Teresa J Kimberley

Faculty, Staff and Student Publications

BACKGROUND: Vagus Nerve Stimulation (VNS) paired with rehabilitation improved upper extremity impairment and function in a recent pivotal, randomized, triple-blind, sham-controlled trial in people with chronic arm weakness after stroke.

OBJECTIVE: We aimed to determine whether treatment effects varied across candidate subgroups, such as younger age or less injury.

METHODS: Participants were randomized to receive rehabilitation paired with active VNS or rehabilitation paired with sham stimulation (Control). The primary outcome was the change in impairment measured by the Fugl-Meyer Assessment Upper Extremity (FMA-UE) score on the first day after completion of 6-weeks in-clinic therapy. We explored the effect of VNS …


Towards Neuromarkers For Tailored Smoking Cessation Treatments, Francesco Versace, Jason D Robinson, Paul M Cinciripini Jun 2023

Towards Neuromarkers For Tailored Smoking Cessation Treatments, Francesco Versace, Jason D Robinson, Paul M Cinciripini

Faculty, Staff and Student Publications

Vulnerability to compulsive drug use stems from dysregulated activity within the neural networks that underlie reward and executive functions. Empirical evidence suggests that a) attributing high motivational salience to drug-related stimuli leads to compulsive drug seeking and b) cognitive control deficits lead to compulsive drug taking. Noninvasive neuroimaging techniques enable brain activity monitoring during affective and cognitive processing and are paving the way to precision medicine for substance use disorders. Identifying robust neuromarkers of affective and cognitive dysregulation would allow clinicians to personalize treatments by targeting individual psychophysiological vulnerabilities. However, methodological choices have biased the field toward experimental paradigms that …


Target Cell-Specific Synaptic Dynamics Of Excitatory To Inhibitory Neuron Connections In Supragranular Layers Of Human Neocortex, Mean-Hwan Kim, Cristina Radaelli, Elliot R Thomsen, Deja Monet, Thomas Chartrand, Nikolas L Jorstad, Joseph T Mahoney, Michael J Taormina, Brian Long, Katherine Baker, Trygve E Bakken, Luke Campagnola, Tamara Casper, Michael Clark, Nick Dee, Florence D'Orazi, Clare Gamlin, Brian E Kalmbach, Sara Kebede, Brian R Lee, Lindsay Ng, Jessica Trinh, Charles Cobbs, Ryder P Gwinn, C Dirk Keene, Andrew L Ko, Jeffrey G Ojemann, Daniel L Silbergeld, Staci A Sorensen, Jim Berg, Kimberly A Smith, Philip R Nicovich, Tim Jarsky, Hongkui Zeng, Jonathan T Ting, Boaz P Levi, Ed Lein May 2023

Target Cell-Specific Synaptic Dynamics Of Excitatory To Inhibitory Neuron Connections In Supragranular Layers Of Human Neocortex, Mean-Hwan Kim, Cristina Radaelli, Elliot R Thomsen, Deja Monet, Thomas Chartrand, Nikolas L Jorstad, Joseph T Mahoney, Michael J Taormina, Brian Long, Katherine Baker, Trygve E Bakken, Luke Campagnola, Tamara Casper, Michael Clark, Nick Dee, Florence D'Orazi, Clare Gamlin, Brian E Kalmbach, Sara Kebede, Brian R Lee, Lindsay Ng, Jessica Trinh, Charles Cobbs, Ryder P Gwinn, C Dirk Keene, Andrew L Ko, Jeffrey G Ojemann, Daniel L Silbergeld, Staci A Sorensen, Jim Berg, Kimberly A Smith, Philip R Nicovich, Tim Jarsky, Hongkui Zeng, Jonathan T Ting, Boaz P Levi, Ed Lein

Faculty, Staff and Student Publications

Rodent studies have demonstrated that synaptic dynamics from excitatory to inhibitory neuron types are often dependent on the target cell type. However, these target cell-specific properties have not been well investigated in human cortex, where there are major technical challenges in reliably obtaining healthy tissue, conducting multiple patch-clamp recordings on inhibitory cell types, and identifying those cell types. Here, we take advantage of newly developed methods for human neurosurgical tissue analysis with multiple patch-clamp recordings, post-hoc fluorescent in situ hybridization (FISH), machine learning-based cell type classification and prospective GABAergic AAV-based labeling to investigate synaptic properties between pyramidal neurons and PVALB- …


An Opportunity To Increase Collaborative Science In Fetal, Infant, And Toddler Neuroimaging, Marta Korom, M Catalina Camacho, Aiden Ford, Hana Taha, Dustin Scheinost, Marisa Spann, Kelly A Vaughn May 2023

An Opportunity To Increase Collaborative Science In Fetal, Infant, And Toddler Neuroimaging, Marta Korom, M Catalina Camacho, Aiden Ford, Hana Taha, Dustin Scheinost, Marisa Spann, Kelly A Vaughn

Faculty, Staff and Student Publications

The field of fetal, infant, and toddler (FIT) neuroimaging research—including magnetic resonance imaging (MRI), electroencephalography (EEG), magnetoencephalography, and functional near-infrared spectroscopy, among others—offers pioneering insights into early brain development and has grown in popularity over the past 2 decades. In broader neuroimaging research, multisite collaborative projects, data sharing, and open-source code have increasingly become the norm, fostering big data, consensus standards, and rapid knowledge transfer and development. Given the aforementioned benefits, along with recent initiatives from funding agencies to support multisite and multimodal FIT neuroimaging studies, the FIT field now has the opportunity to establish sustainable, collaborative, and open science …


Efficient Cancer Modeling Through Crispr-Cas9/Hdr-Based Somatic Precision Gene Editing In Mice, Wen Bu, Chad J Creighton, Kelsey S Heavener, Carolina Gutierrez, Yongchao Dou, Amy T Ku, Yiqun Zhang, Weiyu Jiang, Jazmin Urrutia, Wen Jiang, Fei Yue, Luyu Jia, Ahmed Atef Ibrahim, Bing Zhang, Shixia Huang, Yi Li May 2023

Efficient Cancer Modeling Through Crispr-Cas9/Hdr-Based Somatic Precision Gene Editing In Mice, Wen Bu, Chad J Creighton, Kelsey S Heavener, Carolina Gutierrez, Yongchao Dou, Amy T Ku, Yiqun Zhang, Weiyu Jiang, Jazmin Urrutia, Wen Jiang, Fei Yue, Luyu Jia, Ahmed Atef Ibrahim, Bing Zhang, Shixia Huang, Yi Li

Faculty, Staff and Student Publications

CRISPR-Cas9 has been used successfully to introduce indels in somatic cells of rodents; however, precise editing of single nucleotides has been hampered by limitations of flexibility and efficiency. Here, we report technological modifications to the CRISPR-Cas9 vector system that now allows homology-directed repair-mediated precise editing of any proto-oncogene in murine somatic tissues to generate tumor models with high flexibility and efficiency. Somatic editing of either


Functional Neuronal Circuits Promote Disease Progression In Cancer, Anthony C Restaino, Austin Walz, Samuel J Vermeer, Jeffrey Barr, Attila Kovács, Robin R Fettig, Daniel W Vermeer, Hunter Reavis, Caitlin S Williamson, Christopher T Lucido, Tuany Eichwald, Dalia K Omran, Euihye Jung, Lauren E Schwartz, Maria Bell, Desirae M Muirhead, Jody E Hooper, William C Spanos, Ronny Drapkin, Sebastien Talbot, Paola D Vermeer May 2023

Functional Neuronal Circuits Promote Disease Progression In Cancer, Anthony C Restaino, Austin Walz, Samuel J Vermeer, Jeffrey Barr, Attila Kovács, Robin R Fettig, Daniel W Vermeer, Hunter Reavis, Caitlin S Williamson, Christopher T Lucido, Tuany Eichwald, Dalia K Omran, Euihye Jung, Lauren E Schwartz, Maria Bell, Desirae M Muirhead, Jody E Hooper, William C Spanos, Ronny Drapkin, Sebastien Talbot, Paola D Vermeer

Faculty, Staff and Student Publications

The molecular and functional contributions of intratumoral nerves to disease remain largely unknown. We localized synaptic markers within tumors suggesting that these nerves form functional connections. Consistent with this, electrophysiological analysis shows that malignancies harbor significantly higher electrical activity than benign disease or normal tissues. We also demonstrate pharmacologic silencing of tumoral electrical activity. Tumors implanted in transgenic animals lacking nociceptor neurons show reduced electrical activity. These data suggest that intratumoral nerves remain functional at the tumor bed. Immunohistochemical staining demonstrates the presence of the neuropeptide, Substance P (SP), within the tumor space. We show that tumor cells express the …


Exploring 5-Minute Heart Rate Variability In Spinal Cord Injury During Acute Inpatient Rehabilitation, Argyrios Stampas, Colton Malesovas, Michael Burke, Sahira Farooq, Mani Singh, Radha Korupolu, Sheng Li May 2023

Exploring 5-Minute Heart Rate Variability In Spinal Cord Injury During Acute Inpatient Rehabilitation, Argyrios Stampas, Colton Malesovas, Michael Burke, Sahira Farooq, Mani Singh, Radha Korupolu, Sheng Li

Faculty, Staff and Student Publications

To explore the use of 5-minute heart rate variability (HRV) during inpatient rehabilitation in the acute phase of traumatic spinal cord injury (SCI). Longitudinal observational study. Acute inpatient rehabilitation (AIR). 10 patients with acute traumatic SCI. 5-minute HRV supine recordings twice daily on three different days per patient. HRV values were evaluated (1) within a single day (Early versus Late); (2) across the inpatient admission (initial, mid, and discharge); (3) by SCI phenotypes and by clinical outcomes (ex. pressure injuries (PI)). Patients had an average age of 38 years, 80% male, and 40% with tetraplegia. There were no HRV differences …


Higher Hippocampal Diffusivity Values In Welders Are Associated With Greater R2* In The Red Nucleus And Lower Psychomotor Performance, Eun-Young Lee, Juhee Kim, Janina Manzieri Prado-Rico, Guangwei Du, Mechelle M Lewis, Lan Kong, Byoung-Gwon Kim, Young-Seoub Hong, Jeff D Yanosky, Richard B Mailman, Xuemei Huang May 2023

Higher Hippocampal Diffusivity Values In Welders Are Associated With Greater R2* In The Red Nucleus And Lower Psychomotor Performance, Eun-Young Lee, Juhee Kim, Janina Manzieri Prado-Rico, Guangwei Du, Mechelle M Lewis, Lan Kong, Byoung-Gwon Kim, Young-Seoub Hong, Jeff D Yanosky, Richard B Mailman, Xuemei Huang

Faculty, Staff and Student Publications

INTRODUCTION: Chronic excessive welding exposure may be related to higher metal accumulation and structural differences in different subcortical structures. We examined how welding affected brain structures and their associations with metal exposure and neurobehavioral consequences.

METHODS: Study includes 42 welders and 31 controls without a welding history. Welding-related structural differences were assessed by volume and diffusion tensor imaging (DTI) metrics in basal ganglia, red nucleus (RN), and hippocampus. Metal exposure was estimated by both exposure questionnaires and whole blood metal levels. Brain metal accumulations were estimated by R1 (for Mn) and R2* (for Fe). Neurobehavioral status was assessed by standard …


Synaptic Scaling Of Corticostriatal Circuits Underlies Hyperactivity In Gaba Transporter-1 Deficient Mice, Yan-Jiao Wu, Xin Yi, Xue Gu, Qi Wang, Qin Jiang, Ying Li, Michael X Zhu, Jianqing Ding, Wei-Guang Li, Tian-Le Xu Apr 2023

Synaptic Scaling Of Corticostriatal Circuits Underlies Hyperactivity In Gaba Transporter-1 Deficient Mice, Yan-Jiao Wu, Xin Yi, Xue Gu, Qi Wang, Qin Jiang, Ying Li, Michael X Zhu, Jianqing Ding, Wei-Guang Li, Tian-Le Xu

Faculty, Staff and Student Publications

Homeostatic synaptic scaling entails adjustment of synaptic strength on a cell to prolonged changes of neuronal activity, which is postulated to participate in neuropsychiatric disorders in vivo. Here, we find that sustained elevation in ambient GABA levels, by either genetic deletion or pharmacological blockade of GABA transporter-1 (GAT1), leads to synaptic scaling up of corticostriatal pathways, which underlies locomotor hyperactivity. Meanwhile, medium spiny neurons of the dorsal striatum exhibit an aberrant increase in excitatory synaptic transmission and corresponding structural changes in dendritic spines. Mechanistically, GAT1 deficiency dampens the expression and function of metabotropic glutamate receptors (mGluRs) and endocannabinoid (eCB)-dependent …


Cancer Neuroscience: State Of The Field, Emerging Directions, Frank Winkler, Humsa S Venkatesh, Moran Amit, Tracy Batchelor, Ihsan Ekin Demir, Benjamin Deneen, David H Gutmann, Shawn Hervey-Jumper, Thomas Kuner, Donald Mabbott, Michael Platten, Asya Rolls, Erica K Sloan, Timothy C Wang, Wolfgang Wick, Varun Venkataramani, Michelle Monje Apr 2023

Cancer Neuroscience: State Of The Field, Emerging Directions, Frank Winkler, Humsa S Venkatesh, Moran Amit, Tracy Batchelor, Ihsan Ekin Demir, Benjamin Deneen, David H Gutmann, Shawn Hervey-Jumper, Thomas Kuner, Donald Mabbott, Michael Platten, Asya Rolls, Erica K Sloan, Timothy C Wang, Wolfgang Wick, Varun Venkataramani, Michelle Monje

Faculty, Staff and Student Publications

The nervous system governs both ontogeny and oncology. Regulating organogenesis during development, maintaining homeostasis, and promoting plasticity throughout life, the nervous system plays parallel roles in the regulation of cancers. Foundational discoveries have elucidated direct paracrine and electrochemical communication between neurons and cancer cells, as well as indirect interactions through neural effects on the immune system and stromal cells in the tumor microenvironment in a wide range of malignancies. Nervous system-cancer interactions can regulate oncogenesis, growth, invasion and metastatic spread, treatment resistance, stimulation of tumor-promoting inflammation, and impairment of anti-cancer immunity. Progress in cancer neuroscience may create an important new …


Acute Traumatic Dural Arteriovenous Fistula Of The Superior Sagittal Sinus: Illustrative Case, Mitchell L Pryce, K H Carlos Chung, Hussein A Zeineddine, Bryden H Dawes Apr 2023

Acute Traumatic Dural Arteriovenous Fistula Of The Superior Sagittal Sinus: Illustrative Case, Mitchell L Pryce, K H Carlos Chung, Hussein A Zeineddine, Bryden H Dawes

Faculty, Staff and Student Publications

Background: Dural arteriovenous fistulas (dAVFs) are aberrant vascular communications between meningeal arteries and venous sinuses or cortical veins. dAVF pathogenesis is incompletely understood; however, formation likely occurs as a result of angioneogensis.

Observations: A 78-year-old man presented after trauma with basal and cortical subarachnoid hemorrhage (SAH). Computed tomography revealed a parietal bone fracture overlying the superior sagittal sinus (SSS). Catheter angiography performed within 24 hours of the injury demonstrated an SSS dAVF supplied by the middle meningeal artery, adjacent to the fracture.

Lessons: The authors present the case of an acute traumatic dAVF adjacent to a calvarial fracture. In this …


An Expedited Strategy For Accurate And Timely Integrated Molecular Diagnosis Of Gliomas, Timothy A Gregory, Garret L Williford, Jacob M Maronge, Kristin Alfaro, Gregory N Fuller, John De Groot, Vinay K Puduvalli, Leomar Y Ballester, Nazanin K Majd Apr 2023

An Expedited Strategy For Accurate And Timely Integrated Molecular Diagnosis Of Gliomas, Timothy A Gregory, Garret L Williford, Jacob M Maronge, Kristin Alfaro, Gregory N Fuller, John De Groot, Vinay K Puduvalli, Leomar Y Ballester, Nazanin K Majd

Faculty, Staff and Student Publications

No abstract provided.


Wwox P47t Partial Loss-Of-Function Mutation Induces Epilepsy, Progressive Neuroinflammation, And Cerebellar Degeneration In Mice Phenocopying Human Scar12, Tabish Hussain, Kevin Sanchez, Jennifer Crayton, Dhurjhoti Saha, Collene Jeter, Yue Lu, Martin Abba, Ryan Seo, Jeffrey L Noebels, Laura Fonken, C Marcelo Aldaz Apr 2023

Wwox P47t Partial Loss-Of-Function Mutation Induces Epilepsy, Progressive Neuroinflammation, And Cerebellar Degeneration In Mice Phenocopying Human Scar12, Tabish Hussain, Kevin Sanchez, Jennifer Crayton, Dhurjhoti Saha, Collene Jeter, Yue Lu, Martin Abba, Ryan Seo, Jeffrey L Noebels, Laura Fonken, C Marcelo Aldaz

Faculty, Staff and Student Publications

WWOX gene loss-of-function (LoF) has been associated with neuropathologies resulting in developmental, epileptic, and ataxic phenotypes of varying severity based on the level of WWOX dysfunction. WWOX gene biallelic germline variant p.Pro47Thr (P47T) has been causally associated with a new form of autosomal recessive cerebellar ataxia with epilepsy and intellectual disability (SCAR12, MIM:614322). This mutation affecting the WW1 protein binding domain of WWOX, impairs its interaction with canonical proline-proline-X-tyrosine motifs in partner proteins. We generated a mutant knock-in mouse model of Wwox P47T mutation that phenocopies human SCAR12. Wwox


Five-Year Survivors From Brain Metastases Treated With Stereotactic Radiosurgery: Biology, Improving Treatments, Or Just Plain Luck?, Jane B Pearce, Fang-Chi Hsu, Claire M Lanier, Christina K Cramer, Jimmy Ruiz, Hui-Wen Lo, Fei Xing, Margaret Smith, Wencheng Li, Christopher Whitlow, Jaclyn J White, Stephen B Tatter, Adrian W Laxton, Michael D Chan Apr 2023

Five-Year Survivors From Brain Metastases Treated With Stereotactic Radiosurgery: Biology, Improving Treatments, Or Just Plain Luck?, Jane B Pearce, Fang-Chi Hsu, Claire M Lanier, Christina K Cramer, Jimmy Ruiz, Hui-Wen Lo, Fei Xing, Margaret Smith, Wencheng Li, Christopher Whitlow, Jaclyn J White, Stephen B Tatter, Adrian W Laxton, Michael D Chan

Faculty, Staff and Student Publications

BACKGROUND: Improvements in therapies have led to an increasing number of long-term survivors of brain metastases. The present series compares a population of 5-year survivors of brain metastases to a generalized brain metastases population to assess for factors attributable to long-term survival.

METHODS: A single institution retrospective review was performed to identify 5-year survivors of brain metastases who received stereotactic radiosurgery (SRS). A historical control population of 737 patients with brain metastases was used to assess similarities and differences between the long-term survivor population and the general population treated with SRS.

RESULTS: A total of 98 patients with brain metastases …


Enoxaparin May Be Associated With Lower Rates Of Mortality Than Unfractionated Heparin In Neurocritical And Surgical Patients, Sophie Samuel, Catherine To, Yaobin Ling, Kai Zhang, Xiaoqian Jiang, Elmer V Bernstam Apr 2023

Enoxaparin May Be Associated With Lower Rates Of Mortality Than Unfractionated Heparin In Neurocritical And Surgical Patients, Sophie Samuel, Catherine To, Yaobin Ling, Kai Zhang, Xiaoqian Jiang, Elmer V Bernstam

Faculty, Staff and Student Publications

Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are often administered to prevent venous thromboembolism (VTE) in critically ill patients. However, the preferred prophylactic agent (UFH or LMWH) is not known. We compared the all-cause mortality rate in patients receiving UFH to LMWH for VTE prophylaxis. We conducted a retrospective propensity score adjusted analysis of patients admitted to neuro-critical, surgical, or medical intensive care units. Patients were included if they were screened with venous duplex ultrasonography or computed tomography angiography for detection of VTE. The primary outcome was all-cause mortality. Secondary outcomes included the prevalence of VTE, deep vein …


Genetic Correlations Between Alzheimer’S Disease And Gut Microbiome Genera, Davis Cammann, Yimei Lu, Melika J Cummings, Mark L Zhang, Joan Manuel Cue, Jenifer Do, Jeffrey Ebersole, Xiangning Chen, Edwin C Oh, Jeffrey L Cummings, Jingchun Chen Mar 2023

Genetic Correlations Between Alzheimer’S Disease And Gut Microbiome Genera, Davis Cammann, Yimei Lu, Melika J Cummings, Mark L Zhang, Joan Manuel Cue, Jenifer Do, Jeffrey Ebersole, Xiangning Chen, Edwin C Oh, Jeffrey L Cummings, Jingchun Chen

Faculty, Staff and Student Publications

A growing body of evidence suggests that dysbiosis of the human gut microbiota is associated with neurodegenerative diseases like Alzheimer's disease (AD) via neuroinflammatory processes across the microbiota-gut-brain axis. The gut microbiota affects brain health through the secretion of toxins and short-chain fatty acids, which modulates gut permeability and numerous immune functions. Observational studies indicate that AD patients have reduced microbiome diversity, which could contribute to the pathogenesis of the disease. Uncovering the genetic basis of microbial abundance and its effect on AD could suggest lifestyle changes that may reduce an individual's risk for the disease. Using the largest genome-wide …


Interaction Analysis Of Ancestry-Enriched Variants With Apoe-Ɛ4 On Mci In The Study Of Latinos-Investigation Of Neurocognitive Aging, Einat Granot-Hershkovitz, Rui Xia, Yunju Yang, Brian Spitzer, Wassim Tarraf, Priscilla M Vásquez, Richard B Lipton, Martha Daviglus, Maria Argos, Jianwen Cai, Robert Kaplan, Myriam Fornage, Charles Decarli, Hector M Gonzalez, Tamar Sofer Mar 2023

Interaction Analysis Of Ancestry-Enriched Variants With Apoe-Ɛ4 On Mci In The Study Of Latinos-Investigation Of Neurocognitive Aging, Einat Granot-Hershkovitz, Rui Xia, Yunju Yang, Brian Spitzer, Wassim Tarraf, Priscilla M Vásquez, Richard B Lipton, Martha Daviglus, Maria Argos, Jianwen Cai, Robert Kaplan, Myriam Fornage, Charles Decarli, Hector M Gonzalez, Tamar Sofer

Faculty, Staff and Student Publications

APOE-ɛ4 risk on Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD) differs between race/ethnic groups, presumably due to ancestral genomic background surrounding the APOE locus. We studied whether African and Amerindian ancestry-enriched genetic variants in the APOE region modify the effect of the APOE-ɛ4 alleles on Mild Cognitive Impairment (MCI) in Hispanics/Latinos. We defined African and Amerindian ancestry-enriched variants as those common in one Hispanic/Latino parental ancestry and rare in the other two. We identified such variants in the APOE region with a predicted moderate impact based on the SnpEff tool. We tested their interaction with APOE-ɛ4 on MCI in …


Acupuncture Treatment For Post-Stroke Depression: Intestinal Microbiota And Its Role, Hailun Jiang, Shizhe Deng, Jieying Zhang, Junjie Chen, Boxuan Li, Weiming Zhu, Menglong Zhang, Chao Zhang, Zhihong Meng Mar 2023

Acupuncture Treatment For Post-Stroke Depression: Intestinal Microbiota And Its Role, Hailun Jiang, Shizhe Deng, Jieying Zhang, Junjie Chen, Boxuan Li, Weiming Zhu, Menglong Zhang, Chao Zhang, Zhihong Meng

Faculty, Staff and Student Publications

Stroke-induced depression is a common complication and an important risk factor for disability. Besides psychiatric symptoms, depressed patients may also exhibit a variety of gastrointestinal symptoms, and even take gastrointestinal symptoms as the primary reason for medical treatment. It is well documented that stress may disrupt the balance of the gut microbiome in patients suffering from post-stroke depression (PSD), and that disruption of the gut microbiome is closely related to the severity of the condition in depressed patients. Therefore, maintaining the balance of intestinal microbiota can be the focus of research on the mechanism of acupuncture in the treatment of …


Properties Of A Combined Measure Of Reading And Writing: The Assessment Of Writing, Self-Monitoring And Reading (Awsm Reader), Anthony R Gioia, Yusra Ahmed, Steven P Woods, Paul T Cirino Mar 2023

Properties Of A Combined Measure Of Reading And Writing: The Assessment Of Writing, Self-Monitoring And Reading (Awsm Reader), Anthony R Gioia, Yusra Ahmed, Steven P Woods, Paul T Cirino

Faculty, Staff and Student Publications

There is significant overlap between reading and writing, but no known standardized measure assesses these jointly. The goal of the present study is to evaluate the properties of a novel measure, the Assessment of Writing, Self-Monitoring, and Reading (AWSM Reader), that simultaneously evaluates both reading comprehension and writing. In doing so, we evaluate reliability (Cronbach’s alpha) and various aspects of construct-related validity, including separate criterion measures of reading and writing, and the AWSM Reader’s relations with other variables, including language and executive function (EF), both of which are implicated for both reading and writing. Participants were 377 3rd, 4th, and …


Impact Of Time To Treatment On Endovascular Thrombectomy Outcomes In The Early Versus Late Treatment Time Windows, Negar Asdaghi, Kefeng Wang, Hannah Gardener, Angus Jameson, David Z Rose, Ayham Alkhachroum, Carolina M Gutierrez, Hao Ying, Nils Mueller-Kronast, Nicole B Sur, Chuanhui Dong, Gillian Gordon Perue, Marissa Lepain, Sebastian Koch, Nastajjia Krementz, Erika Marulanda-Londoño, Ricardo Hanel, Brijesh Mehta, Dileep R Yavagal, Tatjana Rundek, Ralph L Sacco, Jose G Romano Mar 2023

Impact Of Time To Treatment On Endovascular Thrombectomy Outcomes In The Early Versus Late Treatment Time Windows, Negar Asdaghi, Kefeng Wang, Hannah Gardener, Angus Jameson, David Z Rose, Ayham Alkhachroum, Carolina M Gutierrez, Hao Ying, Nils Mueller-Kronast, Nicole B Sur, Chuanhui Dong, Gillian Gordon Perue, Marissa Lepain, Sebastian Koch, Nastajjia Krementz, Erika Marulanda-Londoño, Ricardo Hanel, Brijesh Mehta, Dileep R Yavagal, Tatjana Rundek, Ralph L Sacco, Jose G Romano

Faculty, Staff and Student Publications

BACKGROUND: The impact of time to treatment on outcomes of endovascular thrombectomy (EVT) especially in patients presenting after 6 hours from symptom onset is not well characterized. We studied the differences in characteristics and treatment timelines of EVT-treated patients participating in the Florida Stroke Registry and aimed to characterize the extent to which time impacts EVT outcomes in the early and late time windows.

METHODS: Prospectively collected data from Get With the Guidelines-Stroke hospitals participating in the Florida Stroke Registry from January 2010 to April 2020 were reviewed. Participants were EVT patients with onset-to-puncture time (OTP) of ≤24 hours and …