Neurosciences Commons^™

Factors And Behaviors Related To Successful Transition Of Care After Hospitalization For Ischemic Stroke, Chuanhui Dong, Hannah Gardener, Tatjana Rundek, Erika Marulanda, Carolina M Gutierrez, Iszet Campo-Bustillo, Gillian Gordon Perue, Karlon H Johnson, Ralph L Sacco, Jose G Romano, Transitions Of Care Stroke Disparities Study (Tcsd-S) Investigators

Faculty, Staff and Student Publications

BACKGROUND: Our objective is to describe adoption of the posthospitalization behaviors associated with successful transition of care and related baseline characteristics.

METHODS: This study includes 550 participants in the Transition of Care Stroke Disparities Study, a prospective observational cohort derived from the Florida Stroke Registry. Participants had an ischemic stroke (2018-2021), discharged home or to rehabilitation, with modified Rankin Scale score=0-3 (44% women, 24% Black, 48% White, 26% Hispanic, 35% foreign-born). We collected baseline sociodemographic and clinical characteristics. A structured telephone interview at 30-day postdischarge evaluated outcomes including medication adherence, medical appointment attendance, outpatient therapy, exercise, diet modification, toxic habit …

Monoclonal Antibody For The Prevention Of Respiratory Syncytial Virus In Infants And Children: A Systematic Review And Network Meta-Analysis, Mingyao Sun, Honghao Lai, Feiyang Na, Sheng Li, Xia Qiu, Jinhui Tian, Zhigang Zhang, Long Ge

Faculty, Staff and Student Publications

IMPORTANCE: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infection in children younger than 5 years; effective prevention strategies are urgently needed.

OBJECTIVE: To compare the efficacy and safety of monoclonal antibodies for the prevention of RSV infection in infants and children.

DATA SOURCES: In this systematic review and network meta-analysis, PubMed, Embase, CENTRAL, and ClinicalTrials.gov were searched from database inception to March 2022.

STUDY SELECTION: Randomized clinical trials that enrolled infants at high risk of RSV infection to receive a monoclonal antibody or placebo were included. Keywords and extensive vocabulary related to monoclonal antibodies, RSV, …

Loss-Of-Function KCa2.2 Mutations Abolish Channel Activity, Young-Woo Nam, Mohammad Asikur Rahman, Grace Yang, Razan Orfali, Meng Cui, Miao Zhang

Pharmacy Faculty Articles and Research

Small-conductance Ca²⁺-activated potassium channels subtype 2 (K_Ca2.2, also called SK2) are operated exclusively by a Ca²⁺-calmodulin gating mechanism. Heterozygous genetic mutations of K_Ca2.2 channels have been associated with autosomal dominant neurodevelopmental disorders including cerebellar ataxia and tremor in humans and rodents. Taking advantage of these pathogenic mutations, we performed structure-function studies of the rat K_Ca2.2 channel. No measurable current was detected from HEK293 cells heterologously expressing these pathogenic K_Ca2.2 mutants. When co-expressed with the K_Ca2.2_WT channel, mutations of the pore-lining amino acid residues (I360M, Y362C, G363S …

Cost-Effectiveness Analysis Of Overground Robotic Training Versus Conventional Locomotor Training In People With Spinal Cord Injury, Daniel Pinto, Allen W Heinemann, Shuo-Hsiu Chang, Susan Charlifue, Edelle C Field-Fote, Catherine L Furbish, Arun Jayaraman, Candace Tefertiller, Heather B Taylor, Dustin D French

Faculty, Staff and Student Publications

BACKGROUND: Few, if any estimates of cost-effectiveness for locomotor training strategies following spinal cord injury (SCI) are available. The purpose of this study was to estimate the cost-effectiveness of locomotor training strategies following spinal cord injury (overground robotic locomotor training versus conventional locomotor training) by injury status (complete versus incomplete) using a practice-based cohort.

METHODS: A probabilistic cost-effectiveness analysis was conducted using a prospective, practice-based cohort from four participating Spinal Cord Injury Model System sites. Conventional locomotor training strategies (conventional training) were compared to overground robotic locomotor training (overground robotic training). Conventional locomotor training included treadmill-based training with body weight …

Fast Blue And Cholera Toxin-B Survival Guide For Alpha-Motoneurons Labeling: Less Is Better In Young B6sjl Mice, But More Is Better In Aged C57bl/J Mice, Hasan Farid, Weston B. Gleford, Lori L. Goss, Teresa L. Garrett, Sherif M. Elbasiouny

Neuroscience, Cell Biology & Physiology Faculty Publications

Fast Blue (FB) and Cholera Toxin-B (CTB) are two retrograde tracers extensively used to label alpha-motoneurons (α-MNs). The overall goals of the present study were to (1) assess the effectiveness of different FB and CTB protocols in labeling α-MNs, (2) compare the labeling quality of these tracers at standard concentrations reported in the literature (FB 2% and CTB 0.1%) versus lower concentrations to overcome tracer leakage, and (3) determine an optimal protocol for labeling α-MNs in young B6SJL and aged C57Bl/J mice (when axonal transport is disrupted by aging). Hindlimb muscles of young B6SJL and aged C57Bl/J mice were intramuscularly …

Synthesize Heterogeneous Biological Knowledge Via Representation Learning For Alzheimer’S Disease Drug Repurposing, Kang-Lin Hsieh, German Plascencia-Villa, Ko-Hong Lin, George Perry, Xiaoqian Jiang, Yejin Kim

Faculty, Staff and Student Publications

Developing drugs for treating Alzheimer's disease has been extremely challenging and costly due to limited knowledge of underlying mechanisms and therapeutic targets. To address the challenge in AD drug development, we developed a multi-task deep learning pipeline that learns biological interactions and AD risk genes, then utilizes multi-level evidence on drug efficacy to identify repurposable drug candidates. Using the embedding derived from the model, we ranked drug candidates based on evidence from post-treatment transcriptomic patterns, efficacy in preclinical models, population-based treatment effects, and clinical trials. We mechanistically validated the top-ranked candidates in neuronal cells, identifying drug combinations with efficacy in …

Circadian Rhythms As Modulators Of Brain Health During Development And Throughout Aging, Rachel Van Drunen, Kristin Eckel-Mahan

Faculty, Staff and Student Publications

The circadian clock plays a prominent role in neurons during development and throughout aging. This review covers topics pertinent to the role of 24-h rhythms in neuronal development and function, and their tendency to decline with aging. Pharmacological or behavioral modification that augment the function of our internal clock may be central to decline of cognitive disease and to future chronotherapy for aging-related diseases of the central nervous system.

Ultrasound Assessment Of Spastic Muscles In Ambulatory Chronic Stroke Survivors Reveals Function-Dependent Changes, Javier González-Buonomo, Alexander H Pham, Jaskiran Ghuman, Aila Malik, Nuray Yozbatiran, Gerard E Francisco, Walter R Frontera, Sheng Li

Faculty, Staff and Student Publications

OBJECTIVE: To correlate ultrasound characteristics of spastic muscles with clinical and functional measurements in chronic stroke survivors.

METHODS: Ultrasound assessment and clinical and functional assessments were performed in 28 ambulatory stroke survivors (12 females, mean age 57.8 ± 11.8 years, 76 ± 45 months after stroke).

RESULTS: Muscle thickness in the affected side was decreased compared with the contralateral side (p < 0.001). The decrease was more evident in the upper limb muscles. On the affected side, the modified Heckmatt scale score was lowest (closer to normal) in the rectus femoris (RF) muscle compared with other muscles (biceps brachii (BB), flexor carpi ulnaris (FCU) and medial gastrocnemius (MG)). Muscle thickness and echogenicity of spastic muscles did not correlate with spasticity, as measured with the modified Ashworth scale (MAS), Fugl-Meyer motor assessment scores, age, or time since stroke. There was a significant negative correlation between grip strength and percentage decrease in muscle thickness for the spastic FCU muscle (r = -0.49, p = 0.008). RF muscle thickness correlated with ambulatory function (Timed Up and Go test (r = 0.44, p = 0.021) and 6-metre walk test (r = 0.41, p = 0.032)). There was no significant correlation between echogenicity and functional assessments Conclusion: Ambulatory chronic stroke survivors had function-dependent changes in muscle thickness on the affected side. Muscle thickness and echogenicity of spastic muscles did not correlate with spasticity, Fugl-Meyer motor assessment scores, age, or time since stroke.

G Protein-Coupled Receptor Kinase-2 (Grk-2) Controls Exploration Through Neuropeptide Signaling In Caenorhabditis Elegans, Kristen Davis, Christo Mitchell, Olivia Weissenfels, Jihong Bai, David M. Raizen, Michael Ailion, Irini Topalidou

Department of Neuroscience Faculty Papers

Animals alter their behavior in manners that depend on environmental conditions as well as their developmental and metabolic states. For example, C. elegans is quiescent during larval molts or during conditions of satiety. By contrast, worms enter an exploration state when removed from food. Sensory perception influences movement quiescence (defined as a lack of body movement), as well as the expression of additional locomotor states in C. elegans that are associated with increased or reduced locomotion activity, such as roaming (exploration behavior) and dwelling (local search). Here we find that movement quiescence is enhanced, and exploration behavior is reduced in …

Discovery Of Associative Patterns Between Workplace Sound Level And Physiological Wellbeing Using Wearable Devices And Empirical Bayes Modeling, Karthik Srinivasan, Faiz Currim, Casey M Lindberg, Javad Razjouyan, Brian Gilligan, Hyoki Lee, Kelli J Canada, Nicole Goebel, Matthias R Mehl, Melissa M Lunden, Judith Heerwagen, Bijan Najafi, Esther M Sternberg, Kevin Kampschroer, Sudha Ram

Center on Aging Staff Publications

We conducted a field study using multiple wearable devices on 231 federal office workers to assess the impact of the indoor environment on individual wellbeing. Past research has established that the workplace environment is closely tied to an individual's wellbeing. Since sound is the most-reported environmental factor causing stress and discomfort, we focus on quantifying its association with physiological wellbeing. Physiological wellbeing is represented as a latent variable in an empirical Bayes model with heart rate variability measures-SDNN and normalized-HF as the observed outcomes and with exogenous factors including sound level as inputs. We find that an individual's physiological wellbeing …

Antagonistic Effect Of Cyclin-Dependent Kinases And A Calcium-Dependent Phosphatase On Polyglutamine-Expanded Androgen Receptor Toxic Gain Of Function, Diana Piol, Laura Tosatto, Emanuela Zuccaro, Eric N Anderson, Antonella Falconieri, Maria J Polanco, Caterina Marchioretti, Federica Lia, Joseph White, Elisa Bregolin, Giovanni Minervini, Sara Parodi, Xavier Salvatella, Giorgio Arrigoni, Andrea Ballabio, Albert R La Spada, Silvio C E Tosatto, Fabio Sambataro, Diego L Medina, Udai B Pandey, Manuela Basso, Maria Pennuto

Duncan NRI Faculty and Staff Publications

Spinal and bulbar muscular atrophy is caused by polyglutamine (polyQ) expansions in androgen receptor (AR), generating gain-of-function toxicity that may involve phosphorylation. Using cellular and animal models, we investigated what kinases and phosphatases target polyQ-expanded AR, whether polyQ expansions modify AR phosphorylation, and how this contributes to neurodegeneration. Mass spectrometry showed that polyQ expansions preserve native phosphorylation and increase phosphorylation at conserved sites controlling AR stability and transactivation. In small-molecule screening, we identified that CDC25/CDK2 signaling could enhance AR phosphorylation, and the calcium-sensitive phosphatase calcineurin had opposite effects. Pharmacologic and genetic manipulation of these kinases and phosphatases modified polyQ-expanded AR …

Impairment Of Attention Network Function In Posterior Circulation Ischemia-Evidence From The Attention Network Test, Na Li, Chuanjin Li, Xiaohui Xie, Gang Liu, Wendong Zhang, Jin Fan

Publications and Research

Objective:

This study aimed to investigate the effect of posterior circulation ischemia (PCI) on attention network function and to determine whether PCI is holistic or selective attention network deficit and which attention network is affected.

Methods:

Thirty-six PCI patients aged 30 to 75 were assessed using the Attention Network Test and the Mini-Mental State Examination (MMSE). There were no significant differences in age, sex, and education between PCI group and the control group (n = 32). All data were statistically analyzed by SPSS 23.0 software.

Result:

There were no significant difference in the MMSE scores between the two groups. …

The Lysosomal Ragulator Complex Activates Nlrp3 Inflammasome In Vivo Via Hdac6, Kohei Tsujimoto, Tatsunori Jo, Daiki Nagira, Hachiro Konaka, Jeong Hoon Park, Shin-Ichiro Yoshimura, Akinori Ninomiya, Fuminori Sugihara, Takehiro Hirayama, Eri Itotagawa, Yusei Matsuzaki, Yuki Takaichi, Wataru Aoki, Shotaro Saita, Shuhei Nakamura, Andrea Ballabio, Shigeyuki Nada, Masato Okada, Hyota Takamatsu, Atsushi Kumanogoh

Duncan NRI Faculty and Staff Publications

The cellular activation of the NLRP3 inflammasome is spatiotemporally orchestrated by various organelles, but whether lysosomes contribute to this process remains unclear. Here, we show the vital role of the lysosomal membrane-tethered Ragulator complex in NLRP3 inflammasome activation. Deficiency of Lamtor1, an essential component of the Ragulator complex, abrogated NLRP3 inflammasome activation in murine macrophages and human monocytic cells. Myeloid-specific Lamtor1-deficient mice showed marked attenuation of NLRP3-associated inflammatory disease severity, including LPS-induced sepsis, alum-induced peritonitis, and monosodium urate (MSU)-induced arthritis. Mechanistically, Lamtor1 interacted with both NLRP3 and histone deacetylase 6 (HDAC6). HDAC6 enhances the interaction between Lamtor1 and NLRP3, resulting …

Investigating The Role Of Vasopressin Receptor 1a Expressing Neurons In Mouse Dorsal Raphe, Tirth Nimishbhai Patel

Theses and Dissertations

Human social interactions heavily impact our physical and mental wellbeing. Arginine-vasopressin (Avp) and serotonin have both been implicated in modulation of social behaviors ranging from affiliation to aggression. In male mice, Avp neurons in the bed nucleus of stria terminalis (BNST) show increased activity during prosocial behavior. BNST sends Avp afferents to the dorsal raphe (DR) in the midbrain, a home to a large portion of serotonin neurons in the mouse brain. Previous data suggests that DR is activated during male prosocial behavior with a female stimulus, and Avp indirectly excites serotonin neurons. We hypothesized that DR contains a population …

Ticagrelor Plus Aspirin Vs Clopidogrel Plus Aspirin In Mild Non-Cardioembolic Ischemic Stroke: A Protocol Of A Randomized, Controlled, Active Comparator Arm, Outcome Assessor Blind, Feasibility Study, Athena Sharifi-Razavi, Amir Moghadam Ahmadi, Nasim Tabrizi, Razieh Daz

Farber Institute for Neuroscience Staff Papers and Presentations

Background & Objectives: The risk of recurrence after a transient ischemic attack (TIA) or minor stroke is high especially within three months after first event. The aim of study is assessing the efficacy of ticagrelor plus aspirin in reduction of mild non-cardioembolic ischemic stroke or high risk TIA recurrence during first 3 months.

Methods: This is a randomized, controlled, active comparator arm, outcome assessor blind, parallel group, feasibility study design on 90 patients with diagnosis of non-cardioembolic minor ischemic stroke or high risk TIA admitted in Bou-Ali Sina Hospital, Sari, Iran. After meeting all inclusion and exclusion criteria, patients will …

Dentate Gyrus Integrity Is Necessary For Behavioral Pattern Separation But Not Statistical Learning, Helena Shizhe Wang, R. Shayna Rosenbaum, Stevenson Baker, Claire Lauzon, Laura Batterink, Stefan Köhler

Brain and Mind Institute Researchers' Publications

Pattern separation, the creation of distinct representations of similar inputs, and statistical learning, the rapid extraction of regularities across multiple inputs, have both been linked to hippocampal processing. It has been proposed that there may be functional differentiation within the hippocampus, such that the trisynaptic pathway (entorhinal cortex > dentate gyrus > CA3 > CA1) supports pattern separation, whereas the monosynaptic pathway (entorhinal cortex > CA1) supports statistical learning. To test this hypothesis, we investigated the behavioral expression of these two processes in BL, an individual with highly selective bilateral lesions in the dentate gyrus that presumably disrupts the trisynaptic pathway. We tested pattern …

The Neuroscience Of Trauma Supports Diminished Capacity As A Nuanced Approach To The Icc Case Of An Ex-Child Soldier, Lee Hiromoto, Ramail Siddiqui, Landy F. Sparr

JCLC Online

The 2021 conviction of former child soldier Dominic Ongwen by the International Criminal Court (ICC) for war crimes committed as an adult commander in the Lord’s Resistance Army in Uganda raises questions about the ICC’s approach to mental illness.  During his trial, the defendant unsuccessfully raised defenses of insanity and duress, based on his kidnapping into the militant group as a child.  The court rejected not only those defenses, but also the claim that he had mental illness at all, in spite of his traumatic childhood.  Integrating scientific research, we argue that both the ICC and the defense failed to …

Water And Brain Function: Effects Of Hydration Status On Neurostimulation And Neurorecording, Sam Critzer

Dissertations and Theses

Introduction: TMS and EEG are used to study normal neurophysiology, diagnose, and treat clinical neuropsychiatric conditions, but can produce variable results or fail. Both techniques depend on electrical volume conduction, and thus brain volumes. Hydration status can affect brain volumes and functions (including cognition), but effects on these techniques are unknown. We aimed to characterize the effects of hydration on TMS, EEG, and cognitive tasks. Methods: EEG and EMG were recorded during single-pulse TMS, paired-pulse TMS, and cognitive tasks from 32 human participants on dehydrated (12-hour fast/thirst) and rehydrated (1 Liter oral water ingestion in 1 hour) testing days. Hydration …

Automated Detection Of Hippocampal Sclerosis Using Real-World Clinical Mri Images, Jingwen Jiang, Jiajun Qiu, Jin Yin, Junren Wang, Xinyue Jiang, Zuo Yi, Yang Chen, Xiaobo Zhou, Xiutian Sima

Faculty, Staff and Student Publications

BACKGROUND: Hippocampal sclerosis (HS) is the most common pathological type of temporal lobe epilepsy (TLE) and one of the important surgical markers. Currently, HS is mainly diagnosed manually by radiologists based on visual inspection of MRI, which greatly relies on MRI quality and physician experience. In clinical practice, non-thin MRI scans are often used due to the time and efficiency needed for the acquisition. However, these scans can be difficult for junior physicians to interpret accurately. Thus, the rapid and accurate diagnosis of HS using real-world MRI images in clinical settings is a challenging task.

OBJECTIVE: Our aim was to …

Characterizing Performance Gaps Of A Code-Based Dementia Algorithm In A Population-Based Cohort Of Cognitive Aging, Maria Vassilaki, Sunyang Fu, Luke R Christenson, Muskan Garg, Ronald C Petersen, Jennifer St Sauver, Sunghwan Sohn

Faculty, Staff and Student Publications

BACKGROUND: Multiple algorithms with variable performance have been developed to identify dementia using combinations of billing codes and medication data that are widely available from electronic health records (EHR). If the characteristics of misclassified patients are clearly identified, modifying existing algorithms to improve performance may be possible.

OBJECTIVE: To examine the performance of a code-based algorithm to identify dementia cases in the population-based Mayo Clinic Study of Aging (MCSA) where dementia diagnosis (i.e., reference standard) is actively assessed through routine follow-up and describe the characteristics of persons incorrectly categorized.

METHODS: There were 5,316 participants (age at baseline (mean (SD)): 73.3 …