Biography

    Tomas Paus , M.D. , Ph.D.

    Tomas Paus
    Research Axis
    Brain and Child Development Axis

    Title

    • Professor of Psychiatry, Department of Psychiatry and Addictology, Faculty of Medicine, University of Montreal
    • Research Scientist, CHU Sainte-Justine Research Centre

    Laboratory

    Population Neuroscience Laboratory

    Research Interests

    In the lab, we build on our expertise in multi-modal imaging of the human brain in large cohorts, as well as on our knowledge of the structural and functional organization of the developing human brain. We hope that our work would yield foundational knowledge about the variety of personal pathways of physical and mental health from childhood to adulthood. This is essential for developing personalized approaches to preventing a delayed impact of early adversities on mental and cognitive health later in life.

    Our program

    Our research program builds on a rich multi-modal database established over the past 20 years. This database contains detailed information about the brains, genes and environment of more than 5,000 typically developing adolescents. It is based on our collaborative work carried out in the context of several population-based cohorts from Canada, Europe and Brazil: the Saguenay Youth Study, IMAGEN, the Avon Longitudinal Study of Parents and Children, the Northern Finland Birth Cohort and the Brazil High Risk Cohort. We also work with large international consortia that pool together information about brain, behaviour and genes assessed in tens of thousands of individuals to provide a lifespan perspective on brain and behaviour: CHARGE, ENIGMA and International Cannabis Consortium.

    Working with these datasets, we have contributed to new knowledge about forces shaping the brain maturation during adolescence, from sex and stress hormones, through cannabis to income inequality, to name but a few. Our work is highly collaborative, spanning a number of disciplines, from physics and engineering, through genetics and epidemiology, to psychiatry, psychology and sociology. This is also reflected in the varied background of our trainees.

    Approach

    The workhorse in our research is multimodal Magnetic Resonance Imaging of brain structure and function (MRI). Insights about genetic underpinnings of various MR-derived phenotypes are gained through large Genome-wide Association Studies (GWAS). Dynamics of gene expression, as it relates to MRI-derived phenotypes, such as cortical thickness, is revealed by integrating data from the Allen Human Brain Atlas and the BrainSpan Atlas. Epigenetic signatures are explored via Epigenome-wide Association Studies. Influences of social and physical environment are studied through geo-spatial links between aggregate data (e.g., green space or income inequality in a neighbourhood) and health data obtained from our participants.

    Collaborators

    Trainees and Staff

    • Manon Bernard (Database architect; with Dr. Pausova)
    • Lassi Björnholm (MD/PhD student, Oulu University; with Prof. Veijola)
    • Zhijie Liao (PhD student, Psychology, University of Toronto)
    • Xavier Navarri (PhD student, University of Montreal)
    • Yash Patel (PhD student, Institute of Medical Science, University of Toronto)
    • Jean Shin (Research Associate; with Dr. Pausova)
    • Daniel Vosberg (Post-doctoral fellow)

    Career Summary

    Dr. Paus is a systems neuroscientist who extends his core expertise in structural and functional organization of the human brain to both the molecular level (omics), and population level (geospatial mapping of physical and social environments).

    His current work integrates epidemiology, neuroscience and genetics – through a new discipline of population neuroscience - in the pursuit of knowledge relevant for child and youth brain health. This research draws on data acquired in a number of cohorts based in North and South America and Europe.

    Funding

    1. Canadian Institutes of Health Research
      Paus T (PI) 2020-2025
      Social Environment and Functioning of Adolescents Born Preterm
      • This project is aimed at identifying features of social environment that may modify long-term outcomes of preterm birth vis-à-vis mental health, cognition and brain maturation of adolescents & youth (~12 to 22 years).
      • Role: PI; Co-investigators: Ballantyne, Belik, Hatzopoulou, Lindsey, Pausova
    2. Canadian Institutes of Health Research
      Conrod, P (PI) 2020-2025
      Canadian Cannabis and Psychosis Research Team
      • This is a team grant that brings together clinical and pre-clinical researchers to answer questions about the relationship between (early) cannabis use and psychosis. I am contributing to the following work packages: (1) Measurement harmonization and data pooling; and (2) MicroRNAs as markers of risk for cannabis-related abnormalities in human brain maturation.
      • Role: Co-PI; Co-investigators: Bourque, Crocker, Flores, Potvin, Tibbo, Sylvestre, Amirali, Rossignol, Afzali, Castellanos Ryan, Cote, Esmaeilzadeh, Pausova, Stewart
    3. The Research Council of Norway
      Walhovd, K (PI) 2020-2023
      The Oslo-Toronto Alliance in Lifespan Changes in Brain and Cognition
      • This is a continuation of the Oslo-Toronto alliance, funded initially in 2017, to develop world-class research and education through collaborative research between the research group in Norway and our research groups in Canada.
      • Role: Co-PI; Other co-PIs: Fjell, Pausova
    4. National Institutes of Health (USA)
      Pausova, Z (PI) 2018-2023
      Visceral fat, neuroinflammation and brain health: towards early detection and prevention of preclinical dementia
      • The major goals of this project are to investigate whether systemic inflammation induced by excess body fat (and visceral fat in particular) may be a risk factor for Alzheimer’s Disease, and whether its impact on the brain can be monitored by newly identified lipid biomarkers.
      • Role: Co-investigator; Other co-investigators: Bennett, Lerch, Post, Strug, Seshadri, Black, Sung, Mapstone, Syme
    5. Canadian Institutes of Health Research
      Paus T (PI) 2017-2022
      Cannabis and Brain Maturation: A population-based study
      • This research project applies a prospective longitudinal approach in a community-based sample, namely the Saguenay Youth Study (n=1,024), in order to understand possible impact of cannabis use on the brain and mental health in young adulthood.
      • Role: PI; Co-investigators: Pausova, Abrahamowicz, Richer, Pike, Seguin, Selby

    Publications

    The work of Dr. Paus, his trainees and collaborators has been well received by peers, being cited in over 55,000 publications (h-index: 112).

    This body of work, carried out over the past 30+ years, has focused on structural and functional organization of the human brain, and factors that shape its development and maturation during adolescence. In a number of collaborative projects, they relate this knowledge, and their expertise in studying the human brain, to investigations of life-long risks of mental illness and addiction.

    In the early 1990s, Dr. Paus and his colleagues studied one particular region of the human frontal lobe, the anterior cingulate cortex. Based on a number of lesion and imaging studies, they put forward a novel view of its functioning as an interface between motor and cognitive processes, modulated by drive. A series of original papers has been (collectively) cited ~ 2,000 times. Their review paper on this topic (Nature Reviews Neuroscience 2001) has been cited 1,897 times.

    • Paus T et al. Role of the human anterior cingulate cortex in the control of oculomotor, manual, and speech responses: A positron emission tomography study. Journal of Neurophysiology 70:453-469, 1993. 988 citations
    • Paus T. Primate anterior cingulate cortex: Where motor control, drive and cognition interface. Nature Reviews Neuroscience 2:417-424, 2001. 1,897 citations

    In the late 1990s, Dr. Paus and his colleagues developed a new technique for measuring in vivo functional connectivity in the human brain. This technique combined – for the first time - transcranial magnetic stimulation with neuroimaging. The initial paper has been cited 824 times. Collectively, this body of our work has been cited over 4,000 times. Dr. Paus has authored a number of chapters and reviews on this topic, and co-edited The Oxford Handbook of Transcranial Stimulation (2008).

    • Paus T et al. Transcranial magnetic stimulation during positron emission tomography: a new method for studying connectivity of the human cerebral cortex. Journal of Neuroscience 17:3178-3184, 1997. 824 citations
    • Paus T et al. Synchronization of neuronal activity in the human sensori-motor cortex by transcranial magnetic stimulation: a combined TMS/EEG study. Journal of Neurophysiology 86:1983-1990, 2001. 332 citations
    • Strafella AP et al. Striatal dopamine release induced by repetitive transcranial magnetic stimulation of the human motor cortex. Brain 126:2609-2615, 2003. 999 citations

    Also in the late 90s, Dr. Paus returned to his interest in brain development. Together with his colleagues at NIH, they used novel techniques for analyzing magnetic resonance images to gain new insights into structural maturation of the human brain. The first two publications reporting this work (Science 1999, Nature Neuroscience 1999) have been cited over 8,000 times. Dr. Paus has summarized our work in this area in a number of chapters and reviews, including the following three papers published in Brain Research Bulletin (2001; 900 citations), Trends in Cognitive Science (2005; 1,400 citations) and Nature Reviews Neuroscience (2008; 2,000+ citations).

    • Paus T et al. Structural maturation of neural pathways in children and adolescents: in vivo study. Science 283:1908-1911, 1999. 1,581 citations
    • Giedd JN et al. Brain development during childhood and adolescence: a longitudinal MRI study. Nature Neuroscience 2:861-863, 1999. 5,855 citations
    • Paus T et al. Why do many psychiatric disorders emerge during adolescence? Nature Reviews Neuroscience 9:947-57, 2008. 2,246 citations

    Since the early 2000s, the work on brain maturation during adolescence continues in the context of several large-scale community based cohorts, including the Saguenay Youth Study and IMAGEN. Two topics stand out in this context. Dr. Paus and his colleagues have put forward a new framework for the role of testosterone in shaping white matter during male adolescence, emphasizing radial growth of the axon and axonal transport. This work has been reported in a number of their publications, cited collectively over 1,200 times. The other area is that of brain maturation and cannabis use during adolescence. Their initial work was based on data from three adolescent cohorts, and revealed an interaction between polygenic risk score for schizophrenia and cannabis use vis-à-vis thickness of the cerebral cortex (JAMA Psychiatry 2015; 134 citations).

    • Perrin JS et al. Growth of White Matter in the Adolescent Brain: Role of Testosterone and Androgen Receptor. Journal of Neuroscience 28:9519-9524, 2008. 348 citations
    • Paus T. Growth of White Matter in the Adolescent Brain: Myelin or Axon. Brain and Cognition 72:26-35, 2010. 426 citations
    • French L et al. Early cannabis use, polygenic risk score for schizophrenia and brain maturation in adolescence. JAMA Psychiatry 72:1002-11, 2015. 134 citations

    In the most recent work, Dr. Paus and his trainees use a new method developed in his laboratory, so-called virtual histology, to facilitate interpretation of neuroimaging-based findings with regards to their neurobiological underpinnings; to do so, they use open-access sources of gene-expression data and link these with in vivo datasets via spatial correlations across the human cerebral cortex. They have reported their findings in a number of recent publications in Cerebral Cortex (2018, 2019, 2021), NeuroImage (2020), Scientific Reports (2020) and JAMA Psychiatry (2020, 2021). The virtual-histology approach has attracted interest of colleagues working in two international consortia, CHARGE and ENIGMA, sparking a number of collaborative projects currently under way.

    • Shin J et al. Cell-specific gene-expression profiles and cortical thickness in the human brain. Cerebral Cortex 8:3267-3277, 2018.
    • Patel Y et al. Maturation of the Human Cerebral Cortex During Adolescence: Myelin or Dendritic Arbor? Cerebral Cortex 29:3351-3362, 2019.
    • Parker N et al. Neurobiological Correlates of Cortical Thinning During Childhood and Adolescence: Relevance for Psychiatric Disorders. JAMA Psychiatry 77:1127-36, 2020.
    • Patel Y, Shin J, Drakesmith M, Evans J, Pausova Z, Paus T. Virtual histology of multi-modal magnetic resonance imaging of cerebral cortex in young men. NeuroImage Sep;218:116968, 2020.
    • Vidal-Pineiro D et al.  Cellular correlates of cortical thinning throughout the lifespan. Scientific Reports 10: 1-14, 2020.
    • Liao Z, Patel Y, Khairullah A, Parker N, Paus T. Pubertal testosterone and the structure of the cerebral cortex in young men. Cerebral Cortex Jan 12:bhaa389, 2021.
    • Patel Y, et al. Virtual histology of cortical thickness reveals shared neurobiology underlying six psychiatric disorders. JAMA Psychiatry 78:47-63, 2021.
 

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