Neurosciences Commons^™

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.

Thermal Block Of Action Potentials Is Primarily Due To Voltage-Dependent Potassium Currents: A Modeling Study, Michael W. Jenkins, Hillel J. Chiel

Faculty Scholarship

Objective. Thermal block of action potential conduction using infrared lasers is a new modality for manipulating neural activity. It could be used for analysis of the nervous system and for therapeutic applications. We sought to understand the mechanisms of thermal block. Approach. To analyze the mechanisms of thermal block, we studied both the original Hodgkin/Huxley model, and a version modified to more accurately match experimental data on thermal responses in the squid giant axon. Main results. Both the original and modified models suggested that thermal block, especially at higher temperatures, is primarily due to a depolarization-activated hyperpolarization as increased temperature …

Soft-Surface Grasping: Radular Opening In Aplysia Californica, Catherine E. Kehl, Joey Wu, Sisi Lu, Richard F. Drushel, Rebekah K. Smoldt, Hillel J. Chiel

Faculty Scholarship

Grasping soft, irregular material is challenging both for animals and robots. The feeding systems of many animals have adapted to this challenge. In particular, the feeding system of the marine mollusk Aplysia californica, a generalist herbivore, allows it to grasp and ingest seaweeds of varying shape, texture and toughness. On the surface of the grasper of A. californica is a structure known as the radula, a thin flexible cartilaginous sheet with fine teeth. Previous in vitro studies suggested that intrinsic muscles, I7, are responsible for opening the radula. Lesioning I7 in vivo does not prevent animals from grasping and ingesting …

Targeting The Blood-Brain Barrier To Prevent Sepsis-Associated Cognitive Impairment, Divine C. Nwafor, Allison L. Brichacek, Afroz S. Mohammad, Jessica Griffith, Brandon P. Lucke-Wold, Stanley A. Benkovic, Werner J. Geldenhuys, Paul R. Lockman, Candice M. Brown

Faculty & Staff Scholarship

Sepsis is a systemic inflammatory disease resulting from an infection. This disorder affects 750 000 people annually in the United States and has a 62% rehospitalization rate. Septic symptoms range from typical flu-like symptoms (eg, headache, fever) to a multifactorial syndrome known as sepsis-associated encephalopathy (SAE). Patients with SAE exhibit an acute altered mental status and often have higher mortality and morbidity. In addition, many sepsis survivors are also burdened with long-term cognitive impairment. The mechanisms through which sepsis initiates SAE and promotes long-term cognitive impairment in septic survivors are poorly understood. Due to its unique role as an interface …

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 …

Decrease In P3-Alcb37 And P3-Alcb40, Products Of Alcadein B Generated By G-Secretase Cleavages, In Aged Monkeys And Patients With Alzheimer’S Disease, Saori Hata, Chiori Omori, Ayano Kimura, Haruka Saito, Nobuyuki Kimura, Veer Gupta, Steve Pedrini, Eugene Hone, Pratishtha Chatterjee, Kevin Taddei, Kensaku Kasuga, Takeshi Ikeuchi, Masaaki Waragai, Masaki Nishimura, Anqi Hu, Tadashi Nakaya, Laurent Meijer, Masahiro Maeda, Tohru Yamamoto, Colin L. Masters, Chris C. Rowe, David Ames, Kazuo Yamamoto, Ralph N. Martins, Sam Gandy, Toshiharu Suzuki

Research outputs 2014 to 2021

Introduction Neuronal p3-Alcβ peptides are generated from the precursor protein Alcadein β (Alcβ) through cleavage by α- and γ-secretases of the amyloid β (Aβ) protein precursor (APP). To reveal whether p3-Alcβ is involved in Alzheimer's disease (AD) contributes for the development of novel therapy and/or drug targets. Methods We developed new sandwich enzyme-linked immunosorbent assay (sELISA) systems to quantitate levels of p3-Alcβ in the cerebrospinal fluid (CSF). Results In monkeys, CSF p3-Alcβ decreases with age, and the aging is also accompanied by decreased brain expression of Alcβ. In humans, CSF p3-Alcβ levels decrease to a greater extent in those with …