Neurosciences Commons^™

Tdp-43 Gains Function Due To Perturbed Autoregulation In A Tardbp Knock-In Mouse Model Of Als-Ftd, Matthew A. White, Eosu Kim, Amanda Duffy, Robert Adalbert, Benjamin U. Phillips, Owen M. Peters, Jodie Stephenson, Sujeong Yang, Francesca Massenzio, Ziqiang Lin, Simon Andrews, Anne Segonds-Pichon, Jake Metterville, Lisa M. Saksida, Richard Mead, Richard R. Ribchester, Youssef Barhomi, Thomas Serre, Michael P. Coleman, Justin Fallon, Timothy J. Bussey, Robert H. Brown, Jemeen Sreedharan

Brain and Mind Institute Researchers' Publications

© 2018 The Author(s). Amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD) constitutes a devastating disease spectrum characterized by 43-kDa TAR DNA-binding protein (TDP-43) pathology. Understanding how TDP-43 contributes to neurodegeneration will help direct therapeutic efforts. Here we have created a TDP-43 knock-in mouse with a human-equivalent mutation in the endogenous mouse Tardbp gene. TDP-43Q331K mice demonstrate cognitive dysfunction and a paucity of parvalbumin interneurons. Critically, TDP-43 autoregulation is perturbed, leading to a gain of TDP-43 function and altered splicing of Mapt, another pivotal dementia-associated gene. Furthermore, a new approach to stratify transcriptomic data by phenotype in differentially affected mutant mice revealed 471 …

Advances In Understanding The Development Of The Mathematical Brain, Daniel C. Hyde, Daniel Ansari

Brain and Mind Institute Researchers' Publications

No abstract provided.

Differentiating Midbrain Structures In Parkinson’S Disease Using Magnetic Resonance Imaging, Erind Alushaj

Western Research Forum

Background: This study aims to differentiate two midbrain structures: substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) in patients with early-stage Parkinson’s Disease (PD) using magnetic resonance imaging (MRI). The SNc degenerates earlier in PD causing motor symptoms; whereas, VTA degeneration occurs later leading to non-motor symptoms. Conventionally, the SNc and VTA project to the dorsal and ventral striatum respectively. Evidence suggests this model may be overly simplistic since the dorsal striatum has uneven dopamine loss in PD. So, the dorsal striatum was segmented into six functional subregions and only the caudal motor subregion showed early changes …

Clarifying Dopaminergic Projections Of The Ventral Tegmental Area And Substantia Nigra In Humans Using Structural Magnetic Resonance Imaging, Nicholas Handfield-Jones

Western Research Forum

Background

Dopaminergic (DA) pathways from the human midbrain to the striatum mediate movement, decision making, learning, and reward processing. Classically, the scientific consensus has been that there are two main DA pathways: the nigrostriatal and the mesolimbic pathways. In the nigrostriatal pathway, the substantia nigra par compacta (SNc) sends DA to the dorsal striatum (DS), and in the mesolimbic pathway, the ventral tegmental area (VTA) sends DA to the ventral striatum (VS) as well as prefrontal and limbic cortices. Recent findings, however, cast doubt on the accuracy of this model. It seems likely these DA projections are more overlapping and …

Cortical And Thalamic Connectivity To The Second Auditory Cortex Of The Cat Is Resilient To The Onset Of Deafness., Blake E Butler, Alexandra De La Rua, Taylor Ward-Able, Stephen G Lomber

Brain and Mind Institute Researchers' Publications

It has been well established that following sensory loss, cortical areas that would normally be involved in perceiving stimuli in the absent modality are recruited to subserve the remaining senses. Despite this compensatory functional reorganization, there is little evidence to date for any substantial change in the patterns of anatomical connectivity between sensory cortices. However, while many auditory areas are contracted in the deaf, the second auditory cortex (A2) of the cat undergoes a volumetric expansion following hearing loss, suggesting this cortical area may demonstrate a region-specific pattern of structural reorganization. To address this hypothesis, and to complement existing literature …

Nutrient Intake In The First Two Weeks Of Life And Brain Growth In Preterm Neonates., Juliane Schneider, Céline J Fischer Fumeaux, Emma G Duerden, Ting Guo, Justin Foong, Myriam Bickle Graz, Patric Hagmann, M Mallar Chakravarty, Petra S Hüppi, Lydie Beauport, Anita C Truttmann, Steven P Miller

Brain and Mind Institute Researchers' Publications

BACKGROUND: Optimizing early nutritional intake in preterm neonates may promote brain health and neurodevelopment through enhanced brain maturation. Our objectives were (1) to determine the association of energy and macronutrient intake in the first 2 weeks of life with regional and total brain growth and white matter (WM) maturation, assessed by 3 serial MRI scans in preterm neonates; (2) to examine how critical illness modifies this association; and (3) to investigate the relationship with neurodevelopmental outcomes.

METHODS: Forty-nine preterm neonates (21 boys, median [interquartile range] gestational age: 27.6 [2.3] weeks) were scanned serially at the following median postmenstrual weeks: 29.4, …

Acute Inhibition Of Estradiol Synthesis Impacts Vestibulo-Ocular Reflex Adaptation And Cerebellar Long-Term Potentiation In Male Rats, Cristina V. Dieni, Aldo Ferraresi, Jacqueline A. Sullivan, Sivarosa Grassi, Vito E. Pettorossi, Roberto Panichi

Brain and Mind Institute Researchers' Publications

© 2017, The Author(s). The vestibulo-ocular reflex (VOR) adaptation is an ideal model for investigating how the neurosteroid 17 beta-estradiol (E2) contributes to the modification of behavior by regulating synaptic activities. We hypothesized that E2 impacts VOR adaptation by affecting cerebellar synaptic plasticity at the parallel fiber–Purkinje cell (PF) synapse. To verify this hypothesis, we investigated the acute effect of blocking E2 synthesis on gain increases and decreases in adaptation of the VOR in male rats using an oral dose (2.5 mg/kg) of the aromatase inhibitor letrozole. We also assessed the effect of letrozole on synaptic plasticity at the PF …

Early Procedural Pain Is Associated With Regionally-Specific Alterations In Thalamic Development In Preterm Neonates., Emma G Duerden, Ruth E Grunau, Ting Guo, Justin Foong, Alexander Pearson, Stephanie Au-Young, Raphael Lavoie, M Mallar Chakravarty, Vann Chau, Anne Synnes, Steven P Miller

Brain and Mind Institute Researchers' Publications

Very preterm human neonates are exposed to numerous invasive procedures as part of life-saving care. Evidence suggests that repetitive neonatal procedural pain precedes long-term alterations in brain development. However, to date the link between pain and brain development has limited temporal and anatomic specificity. We hypothesized that early exposure to painful stimuli during a period of rapid brain development, before pain modulatory systems reach maturity, will predict pronounced changes in thalamic development, and thereby cognitive and motor function. In a prospective cohort study, 155 very preterm neonates (82 males, 73 females) born 24-32 weeks' gestation underwent two MRIs at median …

A Supramodal Role Of The Basal Ganglia In Memory And Motor Inhibition: Meta-Analytic Evidence, Yuhua Guo, Taylor W. Schmitz, Marieke Mur, Catarina S. Ferreira, Michael C. Anderson

Brain and Mind Institute Researchers' Publications

© 2017 The Authors The ability to stop actions and thoughts is essential for goal-directed behaviour. Neuroimaging research has revealed that stopping actions and thoughts engage similar cortical mechanisms, including the ventro- and dorso-lateral prefrontal cortex. However, whether and how these abilities require similar subcortical mechanisms remains unexplored. Specifically of interest are the basal ganglia, subcortical structures long-known for their motor functions, but less so for their role in cognition. To investigate the potential common mechanisms in the basal ganglia underlying action and thought stopping, we conducted meta-analyses using fMRI data from the Go/No-Go, Stop-signal, and Think/No-Think tasks. All three …

Human Neuroimaging Reveals The Subcomponents Of Grasping, Reaching And Pointing Actions., Cristiana Cavina-Pratesi, Jason D Connolly, Simona Monaco, Teresa D Figley, A David Milner, Thomas Schenk, Jody C Culham

Brain and Mind Institute Researchers' Publications

Although the neural underpinnings of visually guided grasping and reaching have been well delineated within lateral and medial fronto-parietal networks (respectively), the contributions of subcomponents of visuomotor actions have not been explored in detail. Using careful subtraction logic, here we investigated which aspects of grasping, reaching, and pointing movements drive activation across key areas within visuomotor networks implicated in hand actions. For grasping tasks, we find activation differences based on the precision required (fine > coarse grip: anterior intraparietal sulcus, aIPS), the requirement to lift the object (grip + lift > grip: aIPS; dorsal premotor cortex, PMd; and supplementary motor area, SMA), …

Cross-Script Orthographic And Phonological Preview Benefits, Olessia Jouravlev, Debra Jared

Brain and Mind Institute Researchers' Publications

The present experiment examined the use of parafoveally presented first-language (LI) orthographic and phonological codes during reading of second-language (L2) sentences in proficient Russian-English bilinguals. Participants read English sentences containing a Russian preview word that was replaced by the English target word when the participant’s eyes crossed an invisible boundary located before the preview word. The use of English and Russian allowed us to manipulate orthographic and phonological preview effects independently of one another. The Russian preview words overlapped with English target words in (a) orthography (ВЕЛЮР [vʲɪˈlʲʉr]–BERRY), (b) phonology (БЛАНК [blank]–BLOOD), or (c) had no orthographic or phonological overlap …

Registered Reports: Introducing A New Article Format In Developmental Science, Daniel Ansari, Judit Gervain

Brain and Mind Institute Researchers' Publications

No abstract provided.

Understanding The Effects Of Education Through The Lens Of Biology, H Moriah Sokolowski, Daniel Ansari

Brain and Mind Institute Researchers' Publications

Early educational interventions aim to close gaps in achievement levels between children. However, early interventions do not eliminate individual differences in populations and the effects of early interventions often fade-out over time, despite changes of the mean of the population immediately following the intervention. Here, we discuss biological factors that help to better understand why early educational interventions do not eliminate achievement gaps. Children experience and respond to educational interventions differently. These stable individual differences are a consequence of biological mechanisms that support the interplay between genetic predispositions and the embedding of experience into our biology. Accordingly, we argue that …

Recording Neuronal Activity Using Miniscopes, Brainscan , Western University, Marco Prado, Sylvian Williams, Vania Prado, Salah El Mestikawy

Project Summaries

Our overarching goal is to understand how the striatum can select between competing options to favor goal-directed behaviors or the establishment of habitual control. This will provide fundamental and transformational insights into the regulation of cognitive functions by co-transmission.

Investigating Vta, Snc And Dopamine Projections In The Brain Using Mri, Brainscan , Western University, Penny Macdonald, Ali Khan, Adrian Owen, Ravi Menon

Project Summaries

By using a multi-modal imaging approach - combining a number of different imaging techniques - we will seek to understand the dopaminergic pathways of the brain. While all neurons depend on neurotransmitters such as dopamine to communicate (since neurotransmitters are responsible for transmitting signals between neurons in the brain), very few neurons actually produce dopamine.

Characterizing Auditory Cortical Receptive Fields, Brainscan , Western University, Ingrid Johnsrude, Alex Billig, Matthew A. Howard Iii, David Steven, Jorge Burneo

Project Summaries

Through this research we have a unique opportunity to explore how auditory cortices respond to naturalistic stimuli and how that response changes with different tasks. This foundational work is critical if we are to understand abnormality in auditory cortices in disorders such as autism, specific language impairment, auditory processing disorders and prolonged auditory deprivation (due to hearing loss).

State-Of-The-Art Clinical Assessment Of Hand Function, Brainscan , Western University, Joern Diedrichsen, Naveed Ejaz, John W. Krakauer, Kevin Olds, Robert Teasell, Neil Duggal, Andrew Pruszynski

Project Summaries

We have assembled a multi-disciplinary team of engineers, surgeons, clinicians and neuroscientists from Johns Hopkins School of Medicine and Western University to develop a new device for assessing hand function. It will be capable of sensitively measuring fingertip forces across all five fingers and along all movement directions. Then we can use this device to develop and validate a clinical hand assessment for patients with brain injuries.

Single-Photon Calcium Imaging For Interrogating The Circuitry Of The Frontoparietal Cognitive Control Network, Brainscan , Western University, Stefan Everling, Ravi Menon, Liya Ma

Project Summaries

We will use miniscopes to detect activities in the frontal eye field, a brain region responsible for voluntary eye movements and perception and awareness in the field of vision. The detection of neuronal activity with calcium imaging can then be compared with the visual stimuli and eye movements expected. If successful, this project will show the feasibility of calcium imaging using miniscopes in this way and open the door for future work to expand our understanding of frontoparietal cortical circuits.

Development Of Fmri Compatible Reversible Deactivation To Examine Cerebral Networks, Brainscan , Western University, Stephen Lomber, Blake Butler, Stefan Everling, Blaine Chronik

Project Summaries

This study will permit us, for the first time, to examine the effects of deactivation of one cortical site on large-scale neural networks. It will permit neural networks to be functionally disassembled and the consequences of 'reversible' lesions, strokes or tumors to be assessed and modeled before they occur.

Using Automated Touchscreen Tasks For Cognitive Assessment In A Novel Model Of Parkinson's Disease, Brainscan, Western University, Flavio Henrique Beraldo De Paiva, Marco Prado, Vania Prado

Project Summaries

This research will focus specifically on evaluating cognitive flexibility (the ability to respond and adapt behaviours to changes in the environment), cognitive dysfunction (changes in the intellectual processing and reasoning that impact daily functions, to a greater severity than what might be expected from typical age-related decline) and long-term memory in a PD model using touchscreens.

Imaging Visually-Evoked Cortical Activity, Brainscan, Western University, Blake E. Butler, Stephen Lomber, Kyle Gilbert, Mathias Dietz

Project Summaries

This work will significantly inform our understanding of 'neural plasticity', the ability of the brain to respond and reorganize to environmental changes or following an injury or disorder. It is also our hope that the results of this program will inform the design of devices to restore hearing - it might enable tuning of those devices to restore sensory representations in the brain in a patient-specific manner. We believe this will significantly reduce the impact of cognitive disorders that arise as a result of abnormal perception both in children and in older adults.

The Impact Of Maternal Immune Activation On Fetal Brain Development, Brainscan , Western University, Stephen Renaud, Susanne Schmid

Project Summaries

We will be studying the contribution of two distinct immune cell subtypes to fetal brain development: the mother's main immune cells present in the uterus (known as uterine natural killer cells), and the fetal brain's main immune cells (fetal microglial cells).

Evaluating Cognitive Impairment, Imaging And Blood Biomarkers In A Pre-Clinical Model Of Concussion, Brainscan, Western University, Arthur Brown, Marco Prado, Rob Bartha, Ravi Menon, Mark Daley

Project Summaries

The foundational milestone for the research, that we are addressing in this project, is to demonstrate that cognitive impairments in mouse models and humans are similar by using touchscreen technology. We will also be applying fMRI and MRS analyses to mouse models since they are analogous to that used in human studies - it will help us establish relevant endpoints for the studies as part of understanding the underlying characteristics, pathways and effects of concussion.

Genetic Manipulation Of Lactate Metabolism To Regulate Memory And Alzheimer's Disease Pathogenesis, Brainscan , Western University, Robert Cumming, Robert Bartha, Tim Scholl

Project Summaries

Our project will attempt to determine the relative importance of astrocyte or neuronal directed lactate generation on memory by modifying mouse models to either suppress or overexpress the lactate producing enzyme in either cell type. Using these newly created transgenic mouse models, we aim to understand the processes of production and utilization of lactate and its effect on memory and cognition in health and in AD across the lifespan. The outcome of our study may lead to entirely new clinical approaches to treating cognitive and neurodegenerative disorders via drugs which alter lactate metabolism.

Diffusion Mri Modelling Of The Cortex Informed By Macro- And Myelo-Architecture, Brainscan , Western University, Ali Khan, Corey Baron

Project Summaries

The overall goal of this transformative program is to develop novel imaging and analysis techniques for evaluating cortical architecture, providing a means to characterize and quantify structural features that have been invisible to MRI until now.

The Role Of The Basolateral Amygdala In Gaze Avoidance Behaviour, Brainscan , Western University, Julio Martinez-Trujillo, Lena Palaniyappan, Robert Nicolson

Project Summaries

We are researching the neural circuits involved in human social interactions and how they are affected during mental disease, in particular the circuits involved in the pattern of eye movements (known as gaze behaviour) in social settings.

System-Wide Electrophysiological Assessment Of Hearing, Brainscan , Western University, Ingrid Johnsrude, Björn Herrman, Chris Allen

Project Summaries

The current work proposes to develop and evaluate an electrophysiological recording setup capable of assessing neural function at all levels of the auditory neural pathway, including hair cells, auditory nerve fibers, brainstem and cortex. We will then test the neural responses across those levels of the auditory pathway in younger and older people.

Neurocognitive, Genetic And Environmental Risk Factors Of Learning Disorders In Children, Brainscan , Western University, Marc Joanisse, Daniel Ansari, Lisa Archibald, Elizabeth Hayden, Janis Oram Cardy, Ryan Stevenson, Jeffrey Gruen

Project Summaries

Our research has already uncovered a range of behavioural and neural factors that can differentiate between children whose development is impaired and those whose development is progressing typically. Intriguingly, our recent findings have also suggested that multiple learning disorders are often present in children with general cognitive difficulties like autism spectrum disorder and ADHD. However, a common feature of research in this area is that of a ‘distinct syndrome’ approach, only studying childhood disabilities separately.

Imaging Fetal Brain Connectivity In High Risk Pregnancy, Brainscan, Western University, Sandrine De Ribaupierre, Barbara De Vrijer, Charles Mckenzie, Roy Eagleson, Simon Levin, Jacqueline Olgivie

Project Summaries

Our hypothesis is that differences in the regional connectivity within the fetal brain (the structural and functional connections between regions of the brain) can be observed with fetal fMRI as early as in the second trimester of pregnancy.

If we can detect differences in an at-risk fetal brain and associate that with plancental and maternal data, we could recommend interventions, such as diet or medication changes, and then monitor the impact of treatment on the fetal brain.

Development Of A Novel Pharmaceutical To Prevent Noise-Induced Hearing Loss, Brainscan , Western University, Brian Allman, Paul Walton

Project Summaries

To limit the damage caused by noise-induced oxidative stress, we intend to determine the most effective way to deliver a customized version of catalase to the vulnerable sensory hair cells in the cochlea. We will conduct experiments to explore how best to 'package' and deliver catalase to the subject.