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Mapping neurotransmitter systems to the structural and functional organization of the human neocortex

View ORCID ProfileJustine Y. Hansen, View ORCID ProfileGolia Shafiei, View ORCID ProfileRoss D. Markello, View ORCID ProfileKelly Smart, Sylvia M. L. Cox, View ORCID ProfileMartin Nørgaard, View ORCID ProfileVincent Beliveau, Yanjun Wu, View ORCID ProfileJean-Dominique Gallezot, View ORCID ProfileÉtienne Aumont, Stijn Servaes, Stephanie G. Scala, View ORCID ProfileJonathan M. DuBois, View ORCID ProfileGabriel Wainstein, View ORCID ProfileGleb Bezgin, View ORCID ProfileThomas Funck, View ORCID ProfileTaylor W. Schmitz, View ORCID ProfileR. Nathan Spreng, View ORCID ProfileMarian Galovic, Matthias J. Koepp, View ORCID ProfileJohn S. Duncan, View ORCID ProfileJonathan P. Coles, Tim D. Fryer, View ORCID ProfileFranklin I. Aigbirhio, View ORCID ProfileColm J. McGinnity, View ORCID ProfileAlexander Hammers, View ORCID ProfileJean-Paul Soucy, View ORCID ProfileSylvain Baillet, View ORCID ProfileSynthia Guimond, View ORCID ProfileJarmo Hietala, Marc-André Bédard, View ORCID ProfileMarco Leyton, View ORCID ProfileEliane Kobayashi, View ORCID ProfilePedro Rosa-Neto, View ORCID ProfileMelanie Ganz, View ORCID ProfileGitte M. Knudsen, View ORCID ProfileNicola Palomero-Gallagher, View ORCID ProfileJames M. Shine, Richard E. Carson, View ORCID ProfileLauri Tuominen, View ORCID ProfileAlain Dagher, View ORCID ProfileBratislav Misic
doi: https://doi.org/10.1101/2021.10.28.466336
Justine Y. Hansen
1Montréal Neurological Institute, McGill University, Montréal, QC, Canada
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Golia Shafiei
1Montréal Neurological Institute, McGill University, Montréal, QC, Canada
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Ross D. Markello
1Montréal Neurological Institute, McGill University, Montréal, QC, Canada
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Kelly Smart
2Yale PET Center, Yale School of Medicine, New Haven, CT 06510, USA
3Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT 06520, USA
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Sylvia M. L. Cox
4Department of Psychiatry, McGill University, Montréal, QC, Canada
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Martin Nørgaard
5Center for Reproducible Neuroscience, Department of Psychology, Stanford University, Stanford, California, USA
6Neurobiology Research Unit & CIMBI, Copenhagen University Hospital, Copenhagen, Denmark
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Vincent Beliveau
6Neurobiology Research Unit & CIMBI, Copenhagen University Hospital, Copenhagen, Denmark
7Medical University of Innsbruck, Department of Neurology, Innsbruck, 6020, Austria
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  • ORCID record for Vincent Beliveau
Yanjun Wu
2Yale PET Center, Yale School of Medicine, New Haven, CT 06510, USA
3Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT 06520, USA
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Jean-Dominique Gallezot
2Yale PET Center, Yale School of Medicine, New Haven, CT 06510, USA
3Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT 06520, USA
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Étienne Aumont
8Cognitive Pharmacology Research Unit, UQAM, Montréal, QC, Canada
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Stijn Servaes
9The McGill University Research Centre for Studies in Aging, Douglas Hospital, McGill University, Montréal, QC, Canada
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Stephanie G. Scala
4Department of Psychiatry, McGill University, Montréal, QC, Canada
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Jonathan M. DuBois
10Biogen Inc., Cambridge, MA, USA
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Gabriel Wainstein
11Brain and Mind Centre, The University of Sydney, Sydney, NSW, Australia
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Gleb Bezgin
9The McGill University Research Centre for Studies in Aging, Douglas Hospital, McGill University, Montréal, QC, Canada
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Thomas Funck
12Julich Forschungszentrum, Julich, North Rhine-Westphalia
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Taylor W. Schmitz
13Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada
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R. Nathan Spreng
1Montréal Neurological Institute, McGill University, Montréal, QC, Canada
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Marian Galovic
14Department of Neurology, Clinical Neuroscience Center, University Hospital Zurich, Zurich, Switzerland
15Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK; MRI Unit, Chalfont Centre for Epilepsy, UK
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Matthias J. Koepp
15Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK; MRI Unit, Chalfont Centre for Epilepsy, UK
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John S. Duncan
15Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK; MRI Unit, Chalfont Centre for Epilepsy, UK
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Jonathan P. Coles
16Division of Anaesthesia, Department of Medicine, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK
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Tim D. Fryer
17Wolfson Brain Imaging Cantre, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK
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Franklin I. Aigbirhio
17Wolfson Brain Imaging Cantre, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK
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  • ORCID record for Franklin I. Aigbirhio
Colm J. McGinnity
18King’s College London and Guy’s and St Thomas’ PET Centre, Division of Imaging Sciences and Biomedical Engineering, King’s College London, London, UK
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Alexander Hammers
18King’s College London and Guy’s and St Thomas’ PET Centre, Division of Imaging Sciences and Biomedical Engineering, King’s College London, London, UK
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Jean-Paul Soucy
1Montréal Neurological Institute, McGill University, Montréal, QC, Canada
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Sylvain Baillet
1Montréal Neurological Institute, McGill University, Montréal, QC, Canada
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Synthia Guimond
19Department of Psychiatry, The Royal’s Institute of Mental Health Research, University of Ottawa, ON, Canada
20Department of Psychoeducation and Psychology, University of Quebec in Outaouais, Gatineau, QC, Canada
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Jarmo Hietala
21Department of Psychiatry, University of Turku and Turku University Hospital, Finland
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Marc-André Bédard
1Montréal Neurological Institute, McGill University, Montréal, QC, Canada
8Cognitive Pharmacology Research Unit, UQAM, Montréal, QC, Canada
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Marco Leyton
1Montréal Neurological Institute, McGill University, Montréal, QC, Canada
4Department of Psychiatry, McGill University, Montréal, QC, Canada
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Eliane Kobayashi
1Montréal Neurological Institute, McGill University, Montréal, QC, Canada
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  • ORCID record for Eliane Kobayashi
Pedro Rosa-Neto
1Montréal Neurological Institute, McGill University, Montréal, QC, Canada
9The McGill University Research Centre for Studies in Aging, Douglas Hospital, McGill University, Montréal, QC, Canada
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Melanie Ganz
6Neurobiology Research Unit & CIMBI, Copenhagen University Hospital, Copenhagen, Denmark
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Gitte M. Knudsen
6Neurobiology Research Unit & CIMBI, Copenhagen University Hospital, Copenhagen, Denmark
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  • ORCID record for Gitte M. Knudsen
Nicola Palomero-Gallagher
22Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany
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James M. Shine
11Brain and Mind Centre, The University of Sydney, Sydney, NSW, Australia
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Richard E. Carson
2Yale PET Center, Yale School of Medicine, New Haven, CT 06510, USA
3Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT 06520, USA
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Lauri Tuominen
19Department of Psychiatry, The Royal’s Institute of Mental Health Research, University of Ottawa, ON, Canada
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  • ORCID record for Lauri Tuominen
Alain Dagher
1Montréal Neurological Institute, McGill University, Montréal, QC, Canada
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Bratislav Misic
1Montréal Neurological Institute, McGill University, Montréal, QC, Canada
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  • ORCID record for Bratislav Misic
  • For correspondence: bratislav.misic@mcgill.ca
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Abstract

Neurotransmitter receptors support the propagation of signals in the human brain. How receptor systems are situated within macroscale neuroanatomy and how they shape emergent function remains poorly understood, and there exists no comprehensive atlas of receptors. Here we collate positron emission tomography data from >1 200 healthy individuals to construct a whole-brain 3-D normative atlas of 19 receptors and transporters across 9 different neurotransmitter systems. We find that receptor profiles align with structural connectivity and mediate function, including neurophysiological oscillatory dynamics and resting state hemodynamic functional connectivity. Using the Neurosynth cognitive atlas, we uncover a topographic gradient of overlapping receptor distributions that separates extrinsic and intrinsic psychological processes. Finally, we find both expected and novel associations between receptor distributions and cortical thinning patterns across 13 disorders. We replicate all findings in an independently collected autoradiography dataset. This work demonstrates how chemoarchitecture shapes brain structure and function, providing a new direction for studying multi-scale brain organization.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • The results have been updated to reflect the addition of an NMDA receptor (PET tracer [18F]GE-179) and the author list has been expanded.

  • https://github.com/netneurolab/hansen_receptors

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted January 11, 2022.
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Mapping neurotransmitter systems to the structural and functional organization of the human neocortex
Justine Y. Hansen, Golia Shafiei, Ross D. Markello, Kelly Smart, Sylvia M. L. Cox, Martin Nørgaard, Vincent Beliveau, Yanjun Wu, Jean-Dominique Gallezot, Étienne Aumont, Stijn Servaes, Stephanie G. Scala, Jonathan M. DuBois, Gabriel Wainstein, Gleb Bezgin, Thomas Funck, Taylor W. Schmitz, R. Nathan Spreng, Marian Galovic, Matthias J. Koepp, John S. Duncan, Jonathan P. Coles, Tim D. Fryer, Franklin I. Aigbirhio, Colm J. McGinnity, Alexander Hammers, Jean-Paul Soucy, Sylvain Baillet, Synthia Guimond, Jarmo Hietala, Marc-André Bédard, Marco Leyton, Eliane Kobayashi, Pedro Rosa-Neto, Melanie Ganz, Gitte M. Knudsen, Nicola Palomero-Gallagher, James M. Shine, Richard E. Carson, Lauri Tuominen, Alain Dagher, Bratislav Misic
bioRxiv 2021.10.28.466336; doi: https://doi.org/10.1101/2021.10.28.466336
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Mapping neurotransmitter systems to the structural and functional organization of the human neocortex
Justine Y. Hansen, Golia Shafiei, Ross D. Markello, Kelly Smart, Sylvia M. L. Cox, Martin Nørgaard, Vincent Beliveau, Yanjun Wu, Jean-Dominique Gallezot, Étienne Aumont, Stijn Servaes, Stephanie G. Scala, Jonathan M. DuBois, Gabriel Wainstein, Gleb Bezgin, Thomas Funck, Taylor W. Schmitz, R. Nathan Spreng, Marian Galovic, Matthias J. Koepp, John S. Duncan, Jonathan P. Coles, Tim D. Fryer, Franklin I. Aigbirhio, Colm J. McGinnity, Alexander Hammers, Jean-Paul Soucy, Sylvain Baillet, Synthia Guimond, Jarmo Hietala, Marc-André Bédard, Marco Leyton, Eliane Kobayashi, Pedro Rosa-Neto, Melanie Ganz, Gitte M. Knudsen, Nicola Palomero-Gallagher, James M. Shine, Richard E. Carson, Lauri Tuominen, Alain Dagher, Bratislav Misic
bioRxiv 2021.10.28.466336; doi: https://doi.org/10.1101/2021.10.28.466336

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