Canada Brain Power

Tag: Brain Imaging

  • Revealing how division of labour occurs in the brain

    Revealing how division of labour occurs in the brain

    Humans have evolved large, costly brains which enable the many cognitive tasks behind everything we think, feel, and do. The division of the brain into two hemispheres is probably one of the brain’s key organizational principles with left and right hemispheres anchoring specific cognitive processes, such as specialization for spatial and facial processing in the right hemisphere and the dominance of the left hemisphere in language comprehension and production. Yet there remains a vague understanding of how the physical structure of the brain relates to the functional division of labor between hemispheres. A study led by PhD student Karin Saltoun at McGill University looked at grey- and white-matter structural imaging of over 37,000 UK Biobank participants and revealed that brain asymmetry is a more complex phenomena than previously believed. Rather than one or two areas of the brain with pronounced asymmetry, they discovered that all levels of the brain meaningfully deviated from symmetry in systematic ways.

    Karin Saltoun won a CAN-CIHR-INMHA Brain Star award for these discoveries.

    Using a statistical analysis approach that reveals how much two variables vary or “move” together, the researchers revealed that commonly studied brain regions had one or multiple spatially-disperse brain features with interrelated asymmetry. In other words, brain features do not spontaneously deviate from symmetry but rather shift in conjunction with other brain features. Their analysis further revealed that these asymmetric partners spanned all regions of the brain.

    The UK Biobank is a large-scale epidemiological initiative that offers behaviour, lifestyle and mental health indicators in addition to the uniform structural brain-scanning for over 37,000 individuals used in the first leg of the study. The researchers were therefore able to compare the newly discovered asymmetry patterns with a broad portfolio of ~1,000 real-world lifestyle indicators.

    This analysis revealed a breadth of asymmetry-linked behaviours and traits that have been discussed only rarely in the context of asymmetry. For example, they revealed associations with socioeconomic status, immune system markers and depression to specific asymmetry patterns. They further found unique combinations of phenotypic links, such as cognition but not mental health in one pattern, while handedness and cognition characterized another.

    The researchers uncovered a sequence of unique brain asymmetry patterns that spatially overlap in the human brain, and each relate to a unique constellation of measurable behavioural and lifestyle indicators. The researchers have made these brain asymmetry patterns freely available through a public database to enable others in the community to peruse and use the full set of results.

    About Karin Saltoun

    Karin Saltoun performed this research as a Master’s student in the laboratory of Dr. Danilo Bzdok at the McConnell Brain Imaging Centre, Montreal Neurological Institute (MNI). As the lead author, Karin Saltoun contributed to all aspects of the paper, including data analysis, code development, figure preparation, and manuscript writing.

    Sources of funding

    This study was supported by the Brain Canada Foundation, through the Canada Brain Research Fund, with the financial support of Health Canada, National Institutes of Health (grant nos. NIH R01 AG068563A and NIH R01 R01DA053301-01A1 to D.B.), the Canadian Institute of Health Research (grant nos. CIHR 438531 and CIHR 470425 to D.B.), the Healthy Brains Healthy Lives initiative (Canada First Research Excellence fund to D.B.), Google (Research Award, Teaching Award to D.B.) and by the CIFAR Artificial Intelligence Chairs programme (Canada Institute for Advanced Research to D.B.). Karin Saltoun was supported by a Canada Graduate Scholarship at the Master’s level awarded by the Canadian Institutes of Health Research.

    Scientific publication

    Saltoun K, Adolphs R, Paul LK, Sharma V, Diedrichsen J, Yeo BTT, Bzdok D. Dissociable brain structural asymmetry patterns reveal unique phenome-wide profiles. Nat Hum Behav. 2023 Feb;7(2):251-268. doi: 10.1038/s41562-022-01461-0.

    https://doi.org/10.1038/s41562-022-01461-0

  • The role of neurotransmitter receptors in the structure and function of the human brain

    The role of neurotransmitter receptors in the structure and function of the human brain

    Neurons in the brain transmit signals to other cells through the release of molecules called neurotransmitters which bind to specific receptors. These receptors effectively mediate the transfer and propagation of electrical impulse from neuron to neuron, which is how brain cells communicate. A new study led by Justine Hansen at McGill University used advanced computational approaches to collate data from brain scans (Positive Emission Tomography, or PET) from more than 1,200 healthy individuals to construct a whole-brain 3D atlas of 19 receptors and transporters across nine different neurotransmitter systems.  This impressive endeavour shows the map of receptors is a key layer in the multiscale organization of the brain, and reveals how the chemical signals (neurotransmitters) help shape brain architecture and function.

    Justine Hansen, from the Montreal Neurological Institute, won a CAN-CIHR-INMHA Brain Star award for these discoveries.

    Indeed, the researchers found a strong link between neurotransmitter receptor distribution and both brain structure and function, which highlights the important role of neurotransmitters in shaping the brain. Using diffusion-weighted MRI and fMRI, they show that neurotransmitter receptors densities follow the organizational principles of the brain’s structural and functional connectomes. Moreover, they find that neurotransmitter receptor densities shape magnetoencephalography (MEG)-derived oscillatory neural dynamics.

    To determine how neurotransmitter receptor distributions affect cognition and disease, they analysed receptor distributions across 13 neurological, psychiatric, and neurodevelopmental disorders (for N=21,000 patients against N=26,000 controls), uncovering specific receptor-disorder links. They validated these findings and extended the scope of the investigation to additional receptors using an independently collected receptor dataset. Altogether, this study used data from multiple experimental methods, across a range of scales to build a robust characterization of how neurotransmitter receptors shape brain structure and function in both health and disease.

    This work also maps receptors to disease-specific structural changes across a wide range of disorders. A key step toward developing therapies for specific syndromes is to reliably map them onto underlying neural systems. This goal is challenging because psychiatric and neurological classification is built around clinical features, rather than neurobiological mechanisms. These results complement some previously established associations between disorders and neurotransmitter systems, and reveal new associations, which will help to identify novel targets for pharmacotherapy.

    The data generated in this study has been made available publicly as part of a large and international open science effort to map the human brain, to better understand how it works. The comprehensive approach of this study showcases novel associations that may not have been considered before. This large-scale characterization of receptor systems will hopefully inspire future studies, driving the cycle of discovery. Altogether, these data and analyses provide a framework for testing predictions from the wider literature and consolidating knowledge about neurotransmitter systems.

    About Justine Hansen

    Justine Hansen performed this study as a PhD student in the Network Neuroscience Laboratory, led by Dr. Bratislav Misic at the Montreal Neurological Institute. She is interested in how neurotransmitter receptors shape brain structure and function but at the time there was no comprehensive multi-receptor dataset. Justine Hansen and Dr. Misic therefore began reaching out to researchers who study neurotransmitter receptor systems to collate data across multiple sites and individuals. This effort began locally (e.g. McGill University, Universite de Quebec a Montreal), spread to other provinces (e.g. Western University, University of Ottawa), across the American border (Yale University), and finally across the ocean (Te.g. urku University Hospital, University of Cambridge, King’s College London). Justine led this data sharing collaboration that resulted in an open-source multi-receptor human atlas of receptor distributions. She then mapped receptors to brain structure, function, dynamics, cognition, and disease. Altogether, with the support from her supervisor and collaborators, Justine Hansen spearheaded a comprehensive characterization of how receptor systems fit in with the rest of the brain.  

    Sources of funding

    Natural Sciences and Engineering Research Council of Canada (NSERC)

    Fonds de reserches de Quebec (FRQ-NT)

    Helmholtz International BigBrain Analytics & Learning Laboratory (HIBALL)

    Scientific publication

    Hansen, J. Y., Shafiei, G., Markello, R. D., Smart, K., Cox, S. M., Nørgaard, M., Beliveau, V., Wu, Y., Gallezot, J., Aumont, E., Servaes, S., Scala, S. G., DuBois, J. M., Wainsten, G., Bezgin, G., Funck, T., Schmitz, T. W., Spreng, R. N., Galovic, M., Koepp, M. J., Duncan, J. S., Coles, J. P., Fryer, T. D., Aigbirhio, F. I., McGinnity, C. J., Hammers, A., Soucy, J., Baillet, S, Guimond, S., Hietala, J., Bedard, M., Leyton, M., Kobayashi, E., Rosa-Neto, P., Ganz, M., Knudsen, G. M., Palomero-Gallagher, N., Shine, J. M., Carson, R. E., Tuominen, L., Dagher, A., & Misic, B. (2022). Mapping neurotransmitter systems to the structural and functional organization of the human neocortex. Nature Neuroscience, 25(11), 1569-1581.

    https://www.nature.com/articles/s41593-022-01186-3

  • Live brain imaging techniques reveal how the primary motor cortex responds to reward to optimize learning.

    Live brain imaging techniques reveal how the primary motor cortex responds to reward to optimize learning.

    A region of the brain called the primary motor cortex (M1) is a critical site for learning motor skills (such as riding a bicycle). Moreover, reward is known to accelerate and enhance motor learning, however, it is not understood how reward exerts these effects. While reward has previously been shown to activate neurons in M1 of primates, the cell-types exhibiting this activity were unknown. Candice Lee, a PhD student at the University of Ottawa led a study using live brain imaging techniques in mice while they were learning a task and demonstrated that different cell-types do indeed have distinct responses to reward and reward-predicting cues and these responses evolve differentially with learning.

    Candice Lee, who was at the time of this work a PhD student at the University of Ottawa, won a CAN-CIHR-INMHA Brain Star award for these discoveries.

    In this experiment, a specific sound cue was linked to a reward, and researcher knew the mice had learned the association when they observed anticipatory licking for the reward when the sound was heard. This allowed the researchers to use a live imaging technique, called in vivo two-photon calcium imaging, to investigate which specific neuron types were activated during this classical conditioning task. They demonstrated that excitatory neurons and the inhibitory GABAergic interneuron subtypes, PV-, SST- and VIP-expressing interneurons all have distinct responses to both reward and reward-related cues. Moreover, different neuronal cell-types underwent differential changes as the animal progressed through reward-based associative learning. While excitatory neurons were initially responsive to reward, reward responses were reduced after associative learning occurred. Remarkably, PV-interneurons were preferentially responsive to reward-related cues rather than the reward itself, and became more responsive with associative learning, suggesting that PV-interneurons could have a specialized role in preparatory activity during reward-expectation. In contrast, VIP-interneurons, which specialize in inhibiting other inhibitory interneurons and are thereby disinhibitory, were preferentially responsive to reward itself and became more responsive to reward with learning. Changes in PV- and VIP-interneuron activity were not seen in the absence of reward or if reward was given randomly, denoting specificity to associative learning. Together, these findings demonstrate that reward is faithfully represented within M1, despite being outside of canonical reward-processing regions. This suggests that during reward-based associative learning, VIP-interneurons act as a gate, whereby reward activates VIP-interneurons to disinhibit pyramidal neurons and enable plastic changes.

    This publication connects and expands on multiple findings within the fields of reward processing and motor learning. Since the activation of different cell-types exert opposing and precise effects on local circuitry, elucidating cell-type specific activity is a critical step in understanding how reward affects motor cortex activity. There is hope that mechanisms discovered in this study can be leveraged to enhance motor learning following the loss of motor skills such as after stroke or traumatic brain injury, potentially through VIP-interneuron targeted therapies.

    About Candice Lee

    Dr. Candice Lee joined Dr. Simon Chen’s lab as a doctoral student and was the first member of the newly minted lab. During this time, she established two-photon calcium imaging, and imaged the activity of hundreds of cells in the brains of behaving animals, as described in this study. Candice and Dr. Chen conceived the project. Candice performed the experiments and data analysis, with the exception of figure 3, which was contributed by collaborators from Dr. Richard Naud’s lab. She also took the lead on writing the manuscript with Dr. Chen. Candice completed her PhD in 2022 and is now a postdoctoral fellow at the University of Oxford in the UK.

    Sources of funding

    This work was supported by grants for Dr. Simon Chen from Canada Research Chair (CRC) (grant no. 950-231274) and Natural Sciences and Engineering Research Council of Canada (NSERC) (grant no. 05308), and a grant for Dr. Richard Naud from NSERC (grant no. 06972). Emerson Harkin was supported by a NSERC graduate scholarship. Candice Lee was supported by Ontario Graduate Scholarship and Queen Elizabeth II Graduate Scholarship.

    Original research article

    Candice Lee, Emerson F Harkin, Xuming Yin, Richard Naud, Simon Chen, (2022). Cell-type-specific responses to associative learning in the primary motor cortex. eLife 11:e72549.

    https://doi.org/10.7554/eLife.72549