Neurosciences Commons^™

Absence Of Endothelial Α5Β1 Integrin Triggers Early Onset Of Experimental Autoimmune Encephalomyelitis Due To Reduced Vascular Remodeling And Compromised Vascular Integrity, Ravi Kant, Sebok K. Halder, Gregory J. Bix, Richard Milner

Sanders-Brown Center on Aging Faculty Publications

Early in the development of multiple sclerosis (MS) and its mouse model experimental autoimmune encephalomyelitis (EAE), vascular integrity is compromised. This is accompanied by a marked vascular remodeling response, though it is currently unclear whether this is an adaptive vascular repair mechanism or is part of the pathogenic process. In light of the well-described angiogenic role for the α5β1 integrin, the goal of this study was to evaluate how genetic deletion of endothelial α5 integrin (α5-EC-KO mice) impacts vascular remodeling and repair following vascular disruption during EAE pathogenesis, and how this subsequently influences clinical progression and inflammatory demyelination. Immunofluorescence staining …

Dorsal Striatum Does Not Mediate Feedback-Based, Stimulus-Response Learning: An Event-Related Fmri Study In Patients With Parkinson's Disease Tested On And Off Dopaminergic Therapy, Nole M. Hiebert, Adrian M. Owen, Hooman Ganjavi, Daniel Mendonça, Mary E. Jenkins, Ken N. Seergobin, Penny A. Macdonald

Brain and Mind Institute Researchers' Publications

© 2018 Learning associations between stimuli and responses is essential to everyday life. Dorsal striatum (DS) has long been implicated in stimulus-response learning, though recent results challenge this contention. We have proposed that discrepant findings arise because stimulus-response learning methodology generally confounds learning and response selection processes. In 19 patients with Parkinson's disease (PD) and 18 age-matched controls, we found that dopaminergic therapy decreased the efficiency of stimulus-response learning, with corresponding attenuation of ventral striatum (VS) activation. In contrast, exogenous dopamine improved response selection accuracy related to enhanced DS BOLD signal. Contrasts between PD patients and controls fully support these …

White Matter Hyperintensities In Vascular Contributions To Cognitive Impairment And Dementia (Vcid): Knowledge Gaps And Opportunities, Jessica Alber, Suvarna Alladi, Hee-Joon Bae, David A. Barton, Laurel A. Beckett, Joanne M. Bell, Sara E. Berman, Geert Jan Biessels, Sandra E. Black, Isabelle Bos, Gene L. Bowman, Emanuele Brai, Adam M. Brickman, Brandy L. Callahan, Roderick A. Corriveau, Silvia Fossati, Rebecca F. Gottesman, Deborah R. Gustafson, Vladimir Hachinski, Kathleen M. Hayden, Alex M. Helman, Timothy M. Hughes, Jeremy D. Isaacs, Angela L. Jefferson, Sterling C. Johnson, Alifiya Kapasi, Silke Kern, Jay C. Kwon, Juraj Kukolja, Athene Lee, Brittani R. Price, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

White matter hyperintensities (WMHs) are frequently seen on brain magnetic resonance imaging scans of older people. Usually interpreted clinically as a surrogate for cerebral small vessel disease, WMHs are associated with increased likelihood of cognitive impairment and dementia (including Alzheimer's disease [AD]). WMHs are also seen in cognitively healthy people. In this collaboration of academic, clinical, and pharmaceutical industry perspectives, we identify outstanding questions about WMHs and their relation to cognition, dementia, and AD. What molecular and cellular changes underlie WMHs? What are the neuropathological correlates of WMHs? To what extent are demyelination and inflammation present? Is it helpful to …

Investigating The Visual Number Form Area: A Replication Study, Rebecca Merkley, Benjamin Conrad, Gavin Price, Daniel Ansari

Brain and Mind Institute Researchers' Publications

© 2019 The Authors. Published by the Royal Society The influential triple-code model of number representation proposed that there are three distinct brain regions for three different numerical representations: verbal words, visual digits and abstract magnitudes. It was hypothesized that the region for visual digits, known as the number form area, would be in ventral occipitotemporal cortex (vOTC), near other visual category-specific regions, such as the visual word form area. However, neuroimaging investigations searching for a region that responds in a category-specific manner to the visual presentation of number symbols have yielded inconsistent results. Price & Ansari (Price, Ansari 2011 …

A Touchscreen Motivation Assessment Evaluated In Huntington's Disease Patients And R6/1 Model Mice, Christopher J. Heath, Claire O'Callaghan, Sarah L. Mason, Benjamin U. Phillips, Lisa M. Saksida, Trevor W. Robbins, Roger A. Barker, Timothy J. Bussey, Barbara J. Sahakian

Brain and Mind Institute Researchers' Publications

Copyright © 2019 Heath, O'Callaghan, Mason, Phillips, Saksida, Robbins, Barker, Bussey and Sahakian. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Apathy is pervasive across many neuropsychiatric disorders but is poorly characterized mechanistically, so targeted therapeutic interventions remain elusive. A key …

White Matter Injury Predicts Disrupted Functional Connectivity And Microstructure In Very Preterm Born Neonates, Emma G. Duerden, Sheliza Halani, Karin Ng, Ting Guo, Justin Foong, Torin J.A. Glass, Vann Chau, Helen M. Branson, John G. Sled, Hilary E. Whyte, Edmond N. Kelly, Steven P. Miller

Brain and Mind Institute Researchers' Publications

© 2018 The Authors Objective: To determine whether the spatial extent and location of early-identified punctate white matter injury (WMI) is associated with regionally-specific disruptions in thalamocortical-connectivity in very-preterm born neonates. Methods: 37 very-preterm born neonates (median gestational age: 28.1 weeks; interquartile range [IQR]: 27–30) underwent early MRI (median age 32.9 weeks; IQR: 32–35), and WMI was identified in 13 (35%) neonates. Structural T1-weighted, resting-state functional Magnetic Resonance Imaging (rs-fMRI, n = 34) and Diffusion Tensor Imaging (DTI, n = 31) sequences were acquired using 3 T-MRI. A probabilistic map of WMI was developed for the 13 neonates demonstrating brain …

Brain Activation Time-Locked To Sleep Spindles Associated With Human Cognitive Abilities, Zhuo Fang, Laura B. Ray, Adrian M. Owen, Stuart M. Fogel

Brain and Mind Institute Researchers' Publications

Simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) studies have revealed brain activations time-locked to spindles. Yet, the functional significance of these spindle-related brain activations is not understood. EEG studies have shown that inter-individual differences in the electrophysiological characteristics of spindles (e.g., density, amplitude, duration) are highly correlated with "Reasoning" abilities (i.e., "fluid intelligence"; problem solving skills, the ability to employ logic, identify complex patterns), but not short-term memory (STM) or verbal abilities. Spindle-dependent reactivation of brain areas recruited during new learning suggests night-to-night variations reflect offline memory processing. However, the functional significance of stable, trait-like inter-individual differences in brain …

The Neural Basis Of External Responsiveness In Prolonged Disorders Of Consciousness, Clara A. Stafford, Adrian M. Owen, Davinia Fernández-Espejo

Brain and Mind Institute Researchers' Publications

Objective: To investigate the structural integrity of fibre tracts underlying overt motor behaviour in PDOC. Methods: This cross-sectional study examined 15 PDOC patients and 22 healthy participants. Eight PDOC patients met the criteria for the vegetative state, 5 met the criteria for the minimally conscious state and 2 met the criteria for emerging from the minimally conscious state. We used fibre tractography to reconstruct the white matter fibres known to be involved in voluntary motor execution (i.e., those connecting thalamus with M1, M1 with cerebellum, and cerebellum with thalamus) and used fractional anisotropy (FA) as a measure of their integrity. …

Developing A Mechanistic Understanding Of Crossmodal Reorganization Following Sensory Loss, Brainscan, Western University, Blake E. Butler, Brian Allman, Ravi Menon

Project Summaries

Our long-term goal is to understand how plasticity reshapes circuits in the brain in response to atypical early experiences. This will allow us to better understand how the Deaf brain processes the world around us, and will make clear the challenges that must be overcome to optimize the function of cochlear implants and prostheses designed to restore sensory functions more broadly.

Can Self-Efficacy Training Improve Memory And Functional Activation In Older Adults With Mild Cognitive Impairment? A Proof-Of-Concept Intervention Study, Brainscan, Western University, Lindsay Nagamatsu, Derek Mitchell, Paul Minda, Amer Burhan, Becky Horst

Project Summaries

The goal of this study is to examine the changes in brain activity after a memory self-efficacy training program to better understand the mechanisms of memory self-efficacy. We will conduct a proof-of-concept six-week memory self-efficacy intervention in older adults with MCI, in order to demonstrate that self-efficacy impacts brain function. This will allow us to determine whether self-efficacy interventions may be a potential strategy for combating AD in the future.

Developing And Validating Tools To Assess Higher Level Cognition In Children And Adolescents, Brainscan, Western University, Bobby Stojanoski, Marc Joanisse, Ryan Stevenson, Cambridge Brain Sciences Inc.

Project Summaries

Collaborating with CBS, we will create a unique platform for understanding, detecting and predicting delays in cognition during the formative period from childhood to adolescence. The aim of this project is to develop and validate a battery of tests specifically for children and adolescents between the ages of 7 and 15 to measure various aspects of higher-level cognitive abilities. These include short-term and episodic memory, planning, reasoning, verbal abilities and executive functioning (those processes necessary to control behaviour, such as controlling attention and inhibition, working memory, reasoning and problem solving).

Multi-Area Organization Of Saccade-Evoked Traveling Waves, Brainscan, Western University, Julio Martinez-Trujillo, Lyle Muller, Adam Williamson

Project Summaries

In this project, we will employ new, large-scale electrophysiological recording techniques to sample widely across the visual system. It will allow us to test our hypothesis that neural traveling waves coordinated across multiple areas contribute to perceptual stability during eye movements. Using our newly developed signal processing technique to track traveling waves moment-by-moment in noisy multichannel data, we will detect and quantify them across multiple visual areas.

Detecting Fine-Grained Population Codes In Human Prefrontal Cortex, Brainscan, Western University, Marieke Mur, Julio Martinez-Trujillo, Ravi Menon, Joe Gati

Project Summaries

In this project, we will develop techniques for improving our measurement resolution so that we can gain access to prefrontal population codes. We will combine high-field fMRI with pattern analysis techniques to unlock population coding in the prefrontal cortex. This is essential for understanding how the brain supports higher-order cognition, and ultimately, for treating dysfunctions of cognitive flexibility in the clinic.

The Risk Of New-Onset Epilepsy And Refractory Epilepsy In Older Adult Stroke Survivors, Jorge G. Burneo, Tresah C. Antaya, Britney N. Allen, Andrea Belisle, Salimah Z. Shariff, Gustavo Saposnik

Neuroepidemiology Research Unit Project Summaries

Research Summary: Key Findings

• Stroke is a common cause of epilepsy in older adults, but little is known about stroke-related epilepsy or its outcomes in this population.
• 1.1% of older adult stroke survivors developed epilepsy in this study, of whom 12.9% developed refractory epilepsy, indicating that this population is particularly responsive to treatment.
• Over 85% of deaths in this population are not due to stroke or epilepsy.

Determinants Of Occupational Injuries Among Building Construction Workers In Kampala City, Uganda, Arthur Kiconco, Nathan Ruhinda, Abdullah Ali Halage, Stephen Watya, William Bazeyo, John C. Ssempebwa, Joseph Byonanebye

Biomedical Sciences Faculty Research and Publications

Background

Globally, about 1000 people die and close to 860,000 people sustain injury at work daily. Injury prevention and control require contextual evidence, although most studies in Uganda have focused on general causes. Factors associated with occupational injuries among building construction workers were assessed in this study.

Methods

A cross-sectional study among building construction workers was conducted in Kampala, Uganda. A standardized semi-structured questionnaire was used to collect data. Three hundred nineteen (319) participants were randomly and proportionately selected from 57 construction sites. Descriptive statistics were used to describe the variables while generalized linear modeling was used to estimate the …

Stress-Dependent Regulation Of A Major Node Of The Insulin-Like Peptide Network That Modulates Survival, Rashmi Chandra

Wayne State University Dissertations

Chronic stress disrupts insulin signaling, predisposing human populations to diabetes, cardiovascular disease, Alzheimer’s Disease, and other metabolic and neurological disorders, including post-traumatic disorders (PTSD). Thus, efficient recovery from stress optimizes survival. However, stress recovery in humans is difficult to study, but is much easier to dissect in model organisms. The worm genetic model Caenorhabditis elegans can switch between stressed and non-stressed states, and this switch is largely regulated by insulin signaling. Previously, the Alcedo lab proposed that insulin-like peptides (ILPs), which exist as multiple members of a protein family in both C. elegans and humans, implements a combinatorial coding strategy …

Characterizing The Development Of Episodic Memory And Assessing The Reliability Of Fmri Measures, Lingfei Tang

Wayne State University Dissertations

The ability to remember past events is critical for everyday life and showed robust improvement over development from childhood to adulthood. With advances in noninvasive neuroimaging methods such as functional MRI in recent years, research efforts have been focused on identifying neural correlates underpinning developmental gains in memory performance. In my dissertation work, using a widely-validated subsequent memory paradigm, I aim to characterize functional MRI correlates of memory development. Specifically, I focused my investigation on identifying age differences in the functional patterns of two brain regions critical for memory, the prefrontal cortex and the hippocampus. Focusing on the prefrontal cortex …

A Synthetic Agonist To Vasoactive Intestinal Peptide Receptor-2 Induces Regulatory T Cell Neuroprotective Activities In Models Of Parkinson's Disease, R. Lee Mosley, Yaman Lu, Katherine E. Olson, Jatin Machhi, Wenhui Yan, Krista L. Namminga, Jenell R. Smith, Scott J. Shandler, Howard Gendelman

Journal Articles: Pharmacology & Experimental Neuroscience

A paradigm shift has emerged in Parkinson's disease (PD) highlighting the prominent role of CD4⁺ Tregs in pathogenesis and treatment. Bench to bedside research, conducted by others and our own laboratories, advanced a neuroprotective role for Tregs making pharmacologic transformation of immediate need. Herein, a vasoactive intestinal peptide receptor-2 (VIPR2) peptide agonist, LBT-3627, was developed as a neuroprotectant for PD-associated dopaminergic neurodegeneration. Employing both 6-hydroxydopamine (6-OHDA) and α-synuclein (α-Syn) overexpression models in rats, the sequential administration of LBT-3627 increased Treg activity without altering cell numbers both in naïve animals and during progressive nigrostriatal degeneration. LBT-3627 administration was linked to …

Ca2+ Sensor Synaptotagmin-1 Mediates Exocytosis In Mammalian Photoreceptors, Justin J. Grassmeyer, Asia L. Cahill, Cassandra L. Hays, Cody Barta, Rolen M. Quadros, Channabasavaiah B. Gurumurthy, Wallace B. Thoreson

Journal Articles: Pharmacology & Experimental Neuroscience

To encode light-dependent changes in membrane potential, rod and cone photoreceptors utilize synaptic ribbons to sustain continuous exocytosis while making rapid, fine adjustments to release rate. Release kinetics are shaped by vesicle delivery down ribbons and by properties of exocytotic Ca²⁺ sensors. We tested the role for synaptotagmin-1 (Syt1) in photoreceptor exocytosis by using novel mouse lines in which Syt1 was conditionally removed from rods or cones. Photoreceptors lacking Syt1 exhibited marked reductions in exocytosis as measured by electroretinography and single-cell recordings. Syt1 mediated all evoked release in cones, whereas rods appeared capable of some slow Syt1-independent release. Spontaneous …

Mice, Acorns, And Lyme Disease: A Case Study To Teach The Ecology Of Emerging Infectious Diseases, Laurieann Klockow

Biomedical Sciences Faculty Research and Publications

Ebola, Zika, the recall of contaminated lettuce - these are just a few recent outbreaks making headlines. Students should be able to connect what they learn in their biology courses to explain these events happening around them. Unfortunately, students do not necessarily make those connections. Therefore, it is important, as instructors, to provide opportunities where students engage with societal issues and problems related to course content and case studies, using headlines from the news are one way to do this.

Here I describe a case study about Lyme disease that engages students in learning about the ecology of infectious disease. …