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  Developing a mechanistic understanding of crossmodal reorganization following sensory loss

  BrainsCAN, Western University; Blake E. Butler; Brian Allman; and Ravi Menon

  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.

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  Multi-area organization of saccade-evoked traveling waves

  BrainsCAN, Western University; Julio Martinez-Trujillo; Lyle Muller; and Adam Williamson

  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.

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  Detecting fine-grained population codes in human prefrontal cortex

  BrainsCAN, Western University; Marieke Mur; Julio Martinez-Trujillo; Ravi Menon; and Joe Gati

  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.

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  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; and Becky Horst

  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.

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  Developing and validating tools to assess higher level cognition in children and adolescents

  BrainsCAN, Western University; Bobby Stojanoski; Marc Joanisse; Ryan Stevenson; and Cambridge Brain Sciences Inc.

  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).

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  Uncovering the neural basis of cognitive impairment following hearing loss: an all-optical electrophysiology approach

  BrainsCAN, Western University; Brian Allman; and Wataru Inoue

  We have access to state-of-the-art equipment that will enable us to visualize specific neuron types in animal models. This is a new approach that combines several recent advances in the field of 'optogenetics', a technique that uses light to control neurons. This approach will allow us to explore how hearing loss induced by loud noise exposure leads to abnormal neural activity in areas of the brain that control learning, memory and higher cognitive function.

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  Development of a novel pharmaceutical to prevent noise-induced hearing loss

  BrainsCAN , Western University; Brian Allman; and Paul Walton

  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.

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  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; and Vania Prado

  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.

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  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; and Mark Daley

  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.

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  Integrating behavioural, imaging and transcriptional profiling to discover the impact of midlife stress in Alzheimer's disease

  BrainsCAN , Western University; Tim Bussey; Flavio Beraldo; Chakravarty Maller; Rosemary Bagot; Sylvain Williams; and Claudia Kleinman

  We will be integrating this cognitive assessment with imaging of brain structure and function to understand the mechanisms by which a risk factor, in this case modifiable life stress, influences Alzheimer's disease-related decline. The resultant data will be integrated and disseminated using a new open-access neuroinformatics platform developed at Western (MouseBytes.ca), which will become a unique resource for open science investigations and set the standard for sharing of behavioural data across the world.

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  The role of astrocytes in memory: focus on pattern separation

  BrainsCAN , Western University; Timothy Bussey; Vania Prado; Ceci Kramar; Marco Prado; and Lisa Saksida

  It has recently been shown that astrocytes play a leading role in a particular aspect of memory known as 'pattern separation' - differentiating between similar experiences or episodes in memory (say, recalling where you parked your car today compared to where you parked it yesterday). Pattern separation is disrupted in a wide variety of diseases of the brain so it is of considerable interest to memory researchers.

  We have already shown in a small pilot study that we can improve pattern separation with selective manipulation of astrocytes in a specific brain region. In this project, we will attempt to demonstrate a clear relationship between astrocyte signalling and performance at pattern separation, and propose the underlying mechanisms of this influence of astrocytes on pattern separation.

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  Imaging visually-evoked cortical activity

  BrainsCAN, Western University; Blake E. Butler; Stephen Lomber; Kyle Gilbert; and Mathias Dietz

  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.

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  Magneto-vestibular Stimulation (MVS): effects on behaviour and resting state networks

  BrainsCAN , Western University; Brian Corneil; Stefan Everling; Joe Gati; and Pieter Medendorp

  The MRI environment can stimulate the balance sensors within the inner ear. This is known as magnetovestibular stimulation (MVS), which occurs within the inner ear. It arises because of biophysical interactions between the fluids within our inner ear, the balance sensors and the magnetic field within an MRI machine.

  This vestibular system usually deteriorates with aging and is commonly dysfunctional in disorders like Parkinson's and Alzheimer's and following concussions and strokes.

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  Development of Virtual Gaming Environments for Functional Magnetic Resonance Imaging

  BrainsCAN, Western University; Jody Culham; Ingrid Johnsrude; and Julio Martinez-Trujillo

  The goal of this project is to develop, validate and test three aspects of a 3D video game environment for neuroscience.

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  Genetic manipulation of lactate metabolism to regulate memory and Alzheimer's disease pathogenesis

  BrainsCAN , Western University; Robert Cumming; Robert Bartha; and Tim Scholl

  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.

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  Imaging fetal brain connectivity in high risk pregnancy

  BrainsCAN, Western University; Sandrine de Ribaupierre; Barbara de Vrijer; Charles McKenzie; Roy Eagleson; Simon Levin; and Jacqueline Olgivie

  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.

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  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; and Andrew Pruszynski

  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.

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  Single-photon calcium imaging for interrogating the circuitry of the frontoparietal cognitive control network

  BrainsCAN , Western University; Stefan Everling; Ravi Menon; and Liya Ma

  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.

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  Dissecting the architecture of prefrontal cortical circuits

  BrainsCAN, Western University; Stephan Everling; Susheel Vijayraghaven; Kevin Johnston; and Wataru Inoue

  In this project, we will develop a technique for recording and simultaneously manipulating this input activity with drugs in awake subjects engaged in cognitive tasks. Recording and modifying this input activity with neurochemicals is a difficult technical challenge.

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  OMMABA: the open multimodal music and auditory brain archive

  BrainsCAN , Western University; Jessica Grahn; Jorn Diedrichsen; Joe Gati; Molly Henry; Robert Zatorre; Jean-Baptiste Poline; Bratislav Misic; Estrid Jakobsen; Mor Regev; Marcel Farrés Franch; Virginia Penhune; and Emily Coffey

  We will create a specific neuroimaging database focused on the auditory domain. It will allow researchers to ask questions about the neural circuitry underlying auditory behaviour in the healthy brain and to understand the sources of individual variability. We will include detailed information about experiential factors, such as musicianship and bilingualism that are not documented in any existing databases, so that it will be possible to investigate plasticity-related effects. It will also provide baseline data for clinical studies.

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  Validating methods for using noninvasive brain stimulation to influence auditory perception

  BrainsCAN, Western University; Jessica Grahn; Molly Henry; Blake Butler; Marc Joanisse; and Stefan Everling

  We will be exploring the influence of a weak alternating current on neural activity at different frequencies to build a more complete picture of tACS. We will also incorporate EEG measurements to help us predict how the synchronization varies across individuals, to determine when to provide stimulation for each individual. Finally, we will vary the tACS stimulation and use participant behaviour as the measure to understand what stimulation timing produces the largest behavioural changes.

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  Attention bias modification training as a potential preventative tool

  BrainsCAN, Western University; Elizabeth Hayden; Marc Joanisse; Pan Liu; Koraly Perez-Edgar; and Thomas Olino

  We will use eye-tracking techniques to understand more about attentional bias and how it changes through ABM training.

  Through neuroimaging, we will look at 'resting state functional connectivity', which is the activity and communication in the brain when a person is not engaging in any activity themselves. There are resting-state patterns of brain activity that have been identified in the brains of youth with depression, anxiety and related disorders, but we do not know if these brain patterns can be used to identify those at risk for these disorders. We also don't know if preventative approaches to depression and anxiety, such as ABM, can change these patterns in the brain.

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  Assessing listening with engaging, real-world auditory signals

  BrainsCAN , Western University; Björn Herrmann; and Ingrid Johnsrude 6612111

  Our project will develop and evaluate a novel way (using functional imaging, fMRI, and electrophysiology, EEG) to assess this cognitive impact of hearing loss with engaging, real‐world auditory stimuli. We will try to assess listening effort in more realistic listening situations among healthy listeners, comparing detected effort in degraded and clear acoustic conditions.

  Using EEG, we will then develop measures that are sensitive to the cognitive demands imposed by degraded speech, using these features to assess hearing function with engaging narratives in natural listening conditions.

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  Developing optogenetics/electrophysiology applications for studying cognitive impairment during stress

  BrainsCAN, Western University; Wataru Inoue; Brian Allman; and Julio Martinez-Trujillo

  We will develop cutting-edge techniques to:

  • precisely measure and artificially manipulate the activity of CRH neurons in the PFC, and
  • measure small and local releases of CRH by these neurons.

  The success of our project will open the door to understand the neural mechanisms for how stress impairs cognitive functions and how it may contribute to mental disorders.

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  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; and Jeffrey Gruen

  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.