Neurosciences Commons^™

The Tenets Of Teneurin: Conserved Mechanisms Regulate Diverse Developmental Processes In The Drosophila Nervous System, Alison T. Depew, Michael A. Aimino, Timothy J. Mosca

Department of Neuroscience Faculty Papers

To successfully integrate a neuron into a circuit, a myriad of developmental events must occur correctly and in the correct order. Neurons must be born and grow out toward a destination, responding to guidance cues to direct their path. Once arrived, each neuron must segregate to the correct sub-region before sorting through a milieu of incorrect partners to identify the correct partner with which they can connect. Finally, the neuron must make a synaptic connection with their correct partner; a connection that needs to be broadly maintained throughout the life of the animal while remaining responsive to modes of plasticity …

Transdisciplinarity At The Boundaries: Exploring A Sylvan Metaphor For Health, Peter J. Whitehouse

Faculty Scholarship

Transdisciplinarity is an action oriented intellectual and ethical endeavor to address complex ecological, economic, and political challenges that humans face. Language is viewed as a powerful tool for necessary cultural change. Blending art and science looking for the difficult to define but critically important hidden spaces between apparently rigid conceptual structures is a core of transdisciplinarity. Metaphor is a particular powerful tool for examining boundaries and developing creative blends of structures and processes. Forests are biologically and culturally critical to life on the planet. In this paper we explore, a performance character named Sylvanus, the Tree Doctor, named after the …

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 …

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 …

Utilization Of A Parental Approach To Informed Consent In Intravenous Tissue Plasminogen Activator Administration Decision-Making: Patient Preference And Ethical Considerations, Ann M. Murray, Ashley B. Petrone, Amelia K. Adcock

Faculty & Staff Scholarship

Objective. While administration of intravenous tissue plasminogen activator (IV-tPA) is the standard of care in acute ischemic stroke and has been shown to have statistically significant benefit, there can also be potentially life-threatening complications; however, there is no standard informed consent approach. (e purpose of this study was to present a parental, technical, and general model of informed consent for IV-TPA and to determine which approach was preferred. Methods. Survey respondents were asked to hypothetically decide whether or not to provide consent for their family member to receive IV-tPA. Respondents were presented with 3 informed consent models: one emphasizing parental …

Micrornas And The Genetic Nexus Of Brain Aging, Neuroinflammation, Neurodegeneration, And Brain Trauma, Saumyendra N. Sarkar, Ashley E. Russell, Russell Elizabeth B. Engler-Chiurazzi, Keyana N. Porter, James W. Simpkins

Faculty & Staff Scholarship

ABSTRACT: Aging is a complex and integrated gradual deterioration of cellular activities in specific organs of the body, which is associated with increased mortality. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, neurovascular disorders, and neurodegenerative diseases. There are nine tentative hallmarks of aging. In addition, several of these hallmarks are increasingly being associated with acute brain injury conditions. In this review, we consider the genes and their functional pathways involved in brain aging as a means of developing new strategies for therapies targeted to the neuropathological processes themselves, but also as …

Neurogenesis In Neurodegenerative Diseases: Role Of Mfg-E8, Cletus Cheyuo, Monowar Aziz, Ping Wang

Faculty & Staff Scholarship

Neurodegenerative diseases are devastating medical conditions with no effective treatments. Restoration of impaired neurogenesis represents a promising therapeutic strategy for neurodegenerative diseases. Milk fat globule-epidermal growth factor-factor VIII (MFG-E8) is a secretory glycoprotein that plays a wide range of cellular functions including phagocytosis of apoptotic cells, anti-inflammation, tissue regeneration, and homeostasis. The beneficial role of MFG-E8 has been shown in cerebral ischemia (stroke), neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease, and traumatic brain injury. In stroke, MFG-E8 promotes neural stem cell proliferation and their migration toward the ischemic brain tissues. These novel functions of MFG-E8 are primarily mediated …

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 …

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 …

Translational Tests Involving Non-Reward: Methodological Considerations, Benjamin U. Phillips, Laura Lopez-Cruz, Lisa M. Saksida, Timothy J. Bussey

Brain and Mind Institute Researchers' Publications

© 2018, The Author(s). This review is concerned with methods for assessing the processing of unrewarded responses in experimental animals and the mechanisms underlying performance of these tasks. A number of clinical populations, including Parkinson’s disease, depression, compulsive disorders, and schizophrenia demonstrate either abnormal processing or learning from non-rewarded responses in laboratory-based reinforcement learning tasks. These effects are hypothesized to result from disturbances in modulatory neurotransmitter systems, including dopamine and serotonin. Parallel work in experimental animals has revealed consistent behavioral patterns associated with non-reward and, consistent with the human literature, modulatory roles for specific neurotransmitters. Classical tests involving an important …

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 …

Girls' Internalizing Symptoms And White Matter Tracts In Cortico-Limbic Circuitry, Ola Mohamed Ali, Matthew R.J. Vandermeer, Haroon I. Sheikh, Marc F. Joanisse, Elizabeth P. Hayden

Brain and Mind Institute Researchers' Publications

© 2019 The Authors Dysfunction in cortico-limbic circuitry is implicated in internalizing disorders (i.e., depressive and anxious disorders), but less is known about whether structural variations precede frank disorder and thus potentially mark risk. We therefore examined associations between white matter (WM) tract microstructure in cortico-limbic circuitry at age 7 and concurrent and longitudinal patterns of internalizing symptoms in 42 typically developing girls using Diffusion Tensor Imaging (DTI). Girls' internalizing symptoms were concurrently associated with reduced fractional anisotropy (FA) in segments of the cingulum bundle (CB) and the uncinate fasciculus (UF), bilaterally. Moreover, latent profile analysis showed that girls with …

The Benefit To Speech Intelligibility Of Hearing A Familiar Voice, Ysabel Domingo, Emma Holmes, Ingrid S. Johnsrude

Brain and Mind Institute Researchers' Publications

© 2019 American Psychological Association. Previous experience with a voice can help listeners understand speech when a competing talker is present. Using the coordinate-response measure task (Bolia, Nelson, Ericson, & Simpson, 2000), Johnsrude et al. (2013) demonstrated that speech is more intelligible when either the target or competing (masking) talker is a long-term spouse than when both talkers are unfamiliar (termed familiar-target and familiar-masker benefits, respectively). To better understand how familiarity improves intelligibility, we measured the familiar-target and familiar-masker benefits in older and younger spouses using a more challenging matrix task, and compared the benefits listeners gain from spouses' and …

Biomarkers Of Parkinson's Disease: Striatal Sub-Regional Structural Morphometry And Diffusion Mri, Ali R. Khan, Nole M. Hiebert, Andrew Vo, Brian T. Wang, Adrian M. Owen, Ken N. Seergobin, Penny A. Macdonald

Brain and Mind Institute Researchers' Publications

© 2018 The Authors Parkinson's disease (PD) is a progressive neurological disorder that has no reliable biomarkers. The aim of this study was to explore the potential of semi-automated sub-regional analysis of the striatum with magnetic resonance imaging (MRI) to distinguish PD patients from controls (i.e., as a diagnostic biomarker) and to compare PD patients at different stages of disease. With 3 Tesla MRI, diffusion- and T1-weighted scans were obtained on two occasions in 24 PD patients and 18 age-matched, healthy controls. PD patients completed one session on and the other session off dopaminergic medication. The striatum was parcellated into …

Linked Mri Signatures Of The Brain's Acute And Persistent Response To Concussion In Female Varsity Rugby Players, Kathryn Y. Manning, Alberto Llera, Gregory A. Dekaban, Robert Bartha, Christy Barreira, Arthur Brown, Lisa Fischer, Tatiana Jevremovic, Kevin Blackney, Timothy J. Doherty, Douglas D. Fraser, Jeff Holmes, Christian F. Beckmann, Ravi S. Menon

Brain and Mind Institute Researchers' Publications

Acute brain changes are expected after concussion, yet there is growing evidence of persistent abnormalities well beyond clinical recovery and clearance to return to play. Multiparametric MRI is a powerful approach to non-invasively study structure-function relationships in the brain, however it remains challenging to interpret the complex and heterogeneous cascade of brain changes that manifest after concussion. Emerging conjunctive, data-driven analysis approaches like linked independent component analysis can integrate structural and functional imaging data to produce linked components that describe the shared inter-subject variance across images. These linked components not only offer the potential of a more comprehensive understanding of …

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 …

Alive Inside, Andrew Peterson, Adrian M. Owen, Jason Karlawish

Brain and Mind Institute Researchers' Publications

This article provides an ethical analysis of the U.S. practice guideline update on disorders of consciousness. Our analysis focuses on the guideline’s recommendations regarding the use of investigational neuroimaging methods to assess brain-injured patients. Complex and multifaceted ethical issues have emerged because these methods alter the clinical understanding of consciousness. We address issues of false hope, patient suffering, and cost. We argue that, in spite of these concerns, there is significant benefit to using neuroimaging to assess brain-injured patients in most cases.

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 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.

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 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.

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.

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 …

Irreversible Chorea As The Initial Presentation Of Polycythemia Rubra Vera In An Elderly Woman, Shakya Bhattacharjee

Neurosciences

No abstract provided.

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 …

A Systems Thinking Approach For Eliciting Mental Models From Visual Boundary Objects In Hydropolitical Contexts: A Case Study From The Pilcomayo River Basin, Riveraine S. Walters, Erin S. Kenzie, Alexander E. Metzger, William Jesse Baltutis, Kakali B. Chakrabarti, Shana Lee Hirsch, Bethany Laursen

Complex Systems Faculty Publications and Presentations

Transboundary collaborations related to international freshwater are critical for ensuring equitable, efficient, and sustainable shared access to our planet’s most fundamental resources. Visual artifacts, such as knowledge maps, functioning as boundary objects, are used in hydropolitical contexts to convey understandings and facilitate discussion across scales about challenges and opportunities from multiple perspectives. Such focal points for discussion are valuable in creating shared, socially negotiated priorities and integrating diverse and often disparate cultural perspectives that naturally exist in the context of international transboundary water resources. Visual boundary objects can also represent the collective mental models of the actor countries and transboundary …