Multi-scale, multi-species neuroimaging: Translational perspectives for neuroscience

Mallar Chakravarty, PhD Organizer
McGill University
Psychiatry
Montréal, QC 
Canada
 
Gemma Modinos Co Organizer
King's College London
London
United Kingdom
 
3721 
Symposium 
New approaches that enable bridging knowledge across scales in neuroscience, from the level of genes and proteins to cells to whole-brain networks and to behaviour, are beginning to transform our understanding of how the brain works in health and disease. Magnetic resonance imaging (MRI) is a widely available technique for mapping brain structure, function and neurochemistry safely and non-invasively. However, a key barrier for translation of MRI-based metrics into the clinic is that we do not know how they are linked to dysfunction at the cellular and molecular levels. Such knowledge is critical for a more logical, mechanism-based discovery of new druggable targets. This symposium will provide an in-depth view into the state-of-the-art of novel tools and approaches bridging the gap between the structural and functional organization of the brain and the underlying cellular and molecular mechanisms. The symposium will also illustrate how these approaches, along with pharmacological manipulation, can be applied across humans and experimental animals.

Overall, this interdisciplinary symposium will offer new insights and tools to investigate brain complexity at multiple spatial and temporal scales, to advance our understanding of the mechanisms underlying major neuropsychiatric disorders and contribute to unlocking the discovery of new pharmacological targets.

Objective

* Understand how translational imaging methods that can be applied to model organisms; for example, to understand the role of dysfunction in specific cell-types to macroscopic non-invasive neuroimaging readouts.

* Understand how integrating data across scales—from genes and cells to whole-brain imaging and behaviour in model systems—can inform on genetic, neurobiological and neuropharmacological sources of neuropsychiatric disease.
 

Target Audience

The target audience for this symposium will be individuals working in neuroimaging studies seeking to connect neural signatures to the neurobiological underpinning of these findings (transcriptomics, cell-types, or the function of specific brain circuits).
 

Presentations

Biological decoding of functional dysconnectivity via cross-species fMRI

Alessandro Gozzi (Italy) will present recent cross-species investigations of the molecular and physiological mechanisms underlying fMRI dysconnectivity in brain disorders. Specifically, he will show how genetic manipulations across multiple murine models of brain disorders can be used to uncover the molecular pathways underpinning fMRI hyper- and hypo-connectivity patterns identified in clinical populations. He will then illustrate chemogenetic work showing how fMRI hyper- and hypoconnectivity may counterintuitively reflect reduced and increased cortical excitability, respectively. A discussion of how this framework may offer novel opportunities to biologically decode fMRI dysconnectivity in human disorders will follow.
 

Presenter

Alessandro Gozzi, PhD, Istituto Italiano di Tecnologia Rovereto
Italy

Longitudinal brain and behavioural studies in models of psychiatric and neurodegenerative disorders.

Mallar Chakravarty (Canada) will demonstrate new findings regarding how we can causally examine the role of pathology in models of neurodegeneration and how we can map the spread of pathological proteins in the brain. We further demonstrate how we can connect neurodegenerative phenotypes to better understand neurodegenerative patterns and how they may impact behaviours. We further demonstrate how these findings may be relevant to the human condition and may provide important information in the realm of drug discovery.
 

Presenter

Mallar Chakravarty, PhD, McGill University
Psychiatry
Montréal, QC 
Canada

Multi-scale approaches to brain vulnerability for psychosis

Gemma Modinos (UK), will present new data linking MRI-based markers of brain function in individuals with early- and chronic-stage schizophrenia spectrum disorders to specific cell-types and neuroreceptor systems, by using available gene expression and neuroreceptor atlases. She will also show new data on the effects of pharmacological modulation of excitation-inhibition balance on multi-modal MRI profiles in individuals at clinical high-risk for psychosis and relevant animal models.
 

Presenter

Gemma Modinos, King's College London London
United Kingdom

Development of an Integrative Eco-Platform for Knowledge-Driven Brain Imaging Across Multiple Primate Species

Tomoko Sakai (Japan) will introduce 'The Japan Monkey Centre Primates Brain Imaging Repository,' a repository developed based on high-resolution postmortem magnetic resonance imaging. Furthermore, our group is currently engaged in the innovative project 'Integrative Eco-Platform for Knowledge-Driven Brain Imaging Across Multiple Primate Species.' This platform utilizes an unparalleled collection of primate brain specimens among the world's most extensive collections, providing highly detailed anatomical images scanned using ultra-high field MRI. These images are integrated with brain information and metadata using hierarchical ontology techniques, forming the foundation of a knowledge-based database. This initiative will accelerate data-driven brain science research beyond national and academic disciplines. It is expected to elucidate the evolutionary similarities and diversities in the human brain, enhance our understanding of human higher brain functions, and provide insights foundational to mental and neurological diseases.
 

Presenter

Tomoko Sakai, PhD, Keio University School of Medicine Tokyo
Japan