Canada Brain Power

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  • Discovery of a new therapeutic avenue to protect vision in diabetic patients

    Discovery of a new therapeutic avenue to protect vision in diabetic patients

    This is a Brain Star Award feature of Dr. Sergio Crespo-Garcia, from the Maisonneuve-Rosemont Hospital Research Center. Dr. Crespo-Garcia he is first place winner of the 2024 competition and also the winner of the Marlene-Reimer Award for 2024. Congratulations!

    Diabetes is a silent epidemic with profound complications in the retina, including a profound visual impairment that robs individuals of their ability to connect with the world around them. Dr. Sergio Crespo-Garcia, working as a post-doctoral fellow in the laboratory of Dr. Przemyslaw (Mike) Sapieha at the Maisonneuve-Rosemont Hospital Research Center, has identified a novel therapeutic strategy aimed at reversing diabetic macular edema (DME), a pervasive blinding condition in diabetic patients. This new therapeutic approach has the potential to be applied to other neurodegenerative diseases.

    Specifically, Dr. Crespo-Garcia and his colleagues investigated the role of cell aging (senescence) in the development of diabetic macular edema (DME). They showed that senescent cells play a critical role in driving leakage from blood vessels and neuroinflammation of the retina leading to retinal damage in diabetes. Further, they identified a protein, called B-cell lymphoma extra-large (BCL-xL), as a potential target to selectively eliminate senescent cells. By employing foselutoclax (UBX1325), a small molecule drug, they demonstrated reduction in retinal neuroinflammation and improvement in vascular and neuronal function. Importantly, these preclinical data translated to human trials where patients enrolled in the Phase 1 trial showed a gain in visual acuity – these were patients for whom other treatments were no longer beneficial. Most excitingly, Phase 2 trials are currently underway, and could transform the way we protect vision in diabetic patients.

    Read the full story here: https://canadabrainpower.com/brain-star-award-winner-sergio-crespo-garcia/

    Read the full scientific publication here:

    Crespo-Garcia S, Fournier F, Diaz-Marin R, Klier S, Ragusa D, Masaki L, Cagnone G, Blot G, Hafiane I, Dejda A, Rizk R, Juneau R, Buscarlet M, Chorfi S, Patel P, Beltran PJ, Joyal JS, Rezende FA, Hata M, Nguyen A, Sullivan L, Damiano J, Wilson AM, Mallette FA, David NE, Ghosh A, Tsuruda PR, Dananberg J, Sapieha P. Therapeutic targeting of cellular senescence in diabetic macular edema: preclinical and phase 1 trial results. Nature Medicine 2024 Feb;30(2):443-454. doi: 10.1038/s41591-024-02802-4. Epub 2024 Feb 6. PMID: 38321220.

    https://www.nature.com/articles/s41591-024-02802-4

  • An optomapping approach to better understand connections in the visual cortex of the brain

    An optomapping approach to better understand connections in the visual cortex of the brain

    This is a Brain Star Award Feature: Christina You Chien Chou – McGill University, won this prize based on the excellence of the research and its potential benefits to the health of Canadians. Brain Star Awards are presented by the Canadian Association for Neuroscience (CAN) and the Canadian Institutes of Health’s Institute of Neurosciences, Mental Health and Addiction

    In the brain, information is passed from neuron to neuron via connections called synapses. Synaptic dysfunction unsurprisingly underlies many neurological diseases, such as autism, schizophrenia, and epilepsy. Understanding how synapses are wired up in a cell-type-specific way is fundamental to understanding brain function. In this publication, Christina Chou, working in Jesper Sjöström’s research group at McGill University, used a new technique called optomapping to reveal previously unknown circuit wiring principles for excitatory and inhibitory neurons in mouse visual cortex. She found that different cell types have distinct connectivity patterns and that excitatory synapses onto inhibitory neurons are stronger, denser, and farther reaching than onto excitatory neurons. In other words, inhibition may win over and temper excitation. She additionally found that short-term synaptic dynamics depend on both input neuron location and on target cell type. These findings are key to understanding how the diversity of synapses underlie cell-type-specific circuit functions.

    In the past, classic electrophysiology-based techniques have allowed researchers to precisely study synapses, but the low data yield of this technique has been a major obstacle towards comprehensive mapping of cell-type-specific connections in healthy and diseased states. As a result, there is a long-standing throughput problem in neuroscience research. In the lab of Prof. Jesper Sjöström, Christina Chou built a pipeline that combined electrophysiology and optogenetics for rapidly finding and studying synapses between different types of neurons without sacrificing precision and reliability. This method, which they called optomapping, is 100-fold faster than current electrophysiology-based techniques.

    Read the full story here: https://can-acn.org/brain-star-award-winner-christina-you-chien-chou/

    Read the original research article: Chou, C. Y. C., Wong, H. H. W., Guo, C., Boukoulou, K. E., Huang, C., Jannat, J., Klimenko, T., Li, V. Y., Liang, T. A., Wu, V. C., & Sjöström, P. J. (2024). Principles of visual cortex excitatory microcircuit organization. The Innovation, 6(1), 100735. DOI: 10.1016/j.xinn.2024.100735

    https://doi.org/10.1016/j.xinn.2024.100735

  • Studying how the deepest regions of the brain contribute to brain activity

    Studying how the deepest regions of the brain contribute to brain activity

    This is a Brain Star Award Feature: Justine Hansen, McGill University, won this prize based on the excellence of the research and its potential benefits to the health of Canadians. Brain Star Awards are presented by the Canadian Association for Neuroscience (CAN) and the Canadian Institutes of Health’s Institute of Neurosciences, Mental Health and Addiction

    The brainstem is a structure which is crucial for survival and consciousness, yet it is typically excluded from live human brain mapping efforts due to the difficulties in recording and analysing activity in this small region which sits deep at the base of the brain. In this study, Justine Hansen, working in the laboratory of Bratislav Misic at McGill University, used high-resolution 7-Tesla functional magnetic resonance imaging (fMRI) alongside new brainstem-specific processing and acquisition protocols to better understand connections in and with this essential brain region. This work identified a compact set of integrative hubs in the brainstem with widespread connectivity with the brain cortex. Specifically, they identified five modules of brainstem nuclei with distinct patterns of functional connectivity to the brain cortex related to memory, cognitive control, multisensory coordination, perception and movement, and emotion. These results push our understanding of brainstem functional neuroanatomy, such that the brainstem is no longer thought to simply be involved in basal functions but instead is recognized as an essential element of higher-order brain function.

    Read the full story here: https://can-acn.org/brain-star-award-winner-justine-hansen-2/

    Read the original research article here:

    Hansen, J. Y., Cauzzo, S., Singh, K., García-Gomar, M. G., Shine, J. M., Bianciardi, M., & Misic, B. (2024). Integrating brainstem and cortical functional architectures. Nature Neuroscience, 1-12.

    https://www.nature.com/articles/s41593-024-01787-0

  • A new framework to assess placement of electrodes in the brain for epilepsy surgery

    A new framework to assess placement of electrodes in the brain for epilepsy surgery

    Brain Star Award Feature: Kassem Jaber, Montreal Neurological Institute, won this prize based on the excellence of the research and its potential benefits to the health of Canadians. Brain Star Awards are presented by the Canadian Association for Neuroscience (CAN) and the Canadian Institutes of Health’s Institute of Neurosciences, Mental Health and Addiction

    Epilepsy is a chronic condition that is characterized by spontaneous recurring seizures. In clinical practice, the region which generates seizures is called the epileptic focus. The location of the focus can be localized by electrical measurement of brain activity, known as electroencephalography (EEG). This can be noninvasively placed on the scalp or invasively inserted into the brain for improved spatial accuracy. 30-40% of patients with epilepsy do not respond to antiseizure medication. For these patients a surgical intervention to remove the focus might be the only way to prevent seizures from occurring. However, currently only half of patients selected for surgery achieve post-operative seizure freedom. One reason may be due to the poor coverage of invasive electrodes in the brain tissue responsible for generating seizures. Research led by Kassem Jaber, working under the supervision of Dr. Birgit Frauscher at the Montreal Neurological Institute, resulted in the development of a spatial perturbation framework that evaluates whether invasive electrodes placed during pre-surgical evaluation adequately cover the epileptic focus.

    Read the full story: https://can-acn.org/brain-star-award-winner-kassem-jaber/

    Read the original scientific publication: Jaber, K., Avigdor, T., Mansilla, D., Ho, A., Thomas, J., Abdallah, C., Chabardes, S., Hall, J., Minotti, L., Kahane, P., Grova, C., Gotman, J. and Frauscher, B., 2024. A spatial perturbation framework to validate implantation of the epileptogenic zone. Nature Communications, 15(1), p.5253. https://rdcu.be/d6hnY

  • Discovery of differences in encoding threat discrimination in the brain of males and females

    Discovery of differences in encoding threat discrimination in the brain of males and females

    Brain Star Award Feature: Jessie Muir and Eshaan Sriram Iyer, McGill University, won this prize based on the excellence of the research and its potential benefits to the health of Canadians. Brain Star Awards are presented by the Canadian Association for Neuroscience (CAN) and the Canadian Institutes of Health’s Institute of Neurosciences, Mental Health and Addiction

    Learning to predict threat is essential, but equally important—yet often overlooked—is learning about the absence of threat. This study by Drs. Jessie Muir and Eshaan Sriram Iyer, working in the laboratory of Dr. Rosemary Bagot at McGill University, looks at mechanisms of threat encoding and discrimination in pathways relevant to depressive-like symptoms in mice. They identified sex differences in the circuits and mechanisms responsible for recognizing threats and suggest they may reflect differences in behavioral strategies that can be relevant for understanding sex differences in risk of psychiatric disorders.

    Depression is currently the leading cause of disability worldwide yet current antidepressant treatments remain ineffective in around 50% of the population. Women are twice as likely to develop depression compared to men. Given most pre-clinical studies have looked exclusively at males, there is a large gap in knowledge in the mechanisms underlying the disorder in females. Depression involves a disruption in many adaptive behavioral processes including discriminating aversive from neutral events.

    Read the full story here: https://can-acn.org/brain-star-award-winners-jessie-muir-and-eshaan-sriram-iyer/

    Featured scientific publication:

    Jessie Muir, Eshaan S. Iyer, Yiu-Chung Tse, Julian Sorensen, Serena Wu, Rand S. Eid, Vedrana Cvetkovska, Karen Wassef, Sarah Gostlin, Peter Vitaro, Nick J. Spencer & Rosemary C. Bagot Sex-biased neural encoding of threat discrimination in nucleus accumbens afferents drives suppression of reward behavior. Nature Neuroscience 27, 1966–1976 (2024). https://doi.org/10.1038/s41593-024-01748-7

    https://doi.org/10.1038/s41593-024-01748-7

  • A reduction in the number of connexions between brain cells is seen in the early stages of psychosis and is associated with negative symptoms.

    A reduction in the number of connexions between brain cells is seen in the early stages of psychosis and is associated with negative symptoms.

    Brain Star Award Feature: Maira Belen Blasco, Douglas Research Institute, McGill University, won this prize based on the excellence of the research and its potential benefits to the health of Canadians. Brain Star Awards are presented by the Canadian Association for Neuroscience (CAN) and the Canadian Institutes of Health’s Institute of Neurosciences, Mental Health and Addiction

    Schizophrenia is a complex psychiatric disorder typically emerging in adolescence or early adulthood. It is thought to occur because of alteration in the maturation or pruning of connexions between neurons called synapses. While this theory, called the synaptic theory is supported by genetic, stem cell and studies of brain of deceased patients, direct evidence to support this theory in living patients was doubtful. Maira Belen Blasco, working in the laboratory of Dr. Romina Mizrahi at the Douglas Research Centre, McGill University, investigated whether difference in the density of synapses could be seen in first-episode psychosis (FEP) and in clinical high risk (CHR) patients using positron emission tomography (PET). They found that synaptic density was reduced during the early stages of psychosis and its risk states and associated with negative symptoms.

    Read the full story here: https://canadabrainpower.com/brain-star-award-winner-maira-belen-blasco/

    Featured scientific articleMaira Belen Blasco

    Blasco MB, Nisha Aji K, Ramos-Jiménez C, Leppert IR, Tardif CL, Cohen J,  Pablo M Rusjan , Romina Mizrahi. Synaptic Density in Early Stages of Psychosis and Clinical High Risk. JAMA Psychiatry. 2024 Nov 13; Published online: https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2825648

    https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2825648

  • Better understanding the non-rhythmic components of Electroencephalography (EEG) can lead to better interpretation of brain activity

    Better understanding the non-rhythmic components of Electroencephalography (EEG) can lead to better interpretation of brain activity

    Brain Star Award Feature: Niklas Brake, McGill University, won this prize based on the excellence of the research and its potential benefits to the health of Canadians. Brain Star Awards are presented by the Canadian Association for Neuroscience (CAN) and the Canadian Institutes of Health’s Institute of Neurosciences, Mental Health and Addiction

    Article citation

    Brake, N., Duc, F., Rokos, A., Arseneau, F., Shahiri, S., Khadra, A., and Plourde, G. (2024) A neurophysiological basis for aperiodic EEG and the background spectral trend. Nature Communications 15(1514). https://www.nature.com/articles/s41467-024-45922-8

    Electroencephalography (EEG) has been in use for almost a century to study brain activity, during which time its rhythmic oscillations in signal, seen as waves of activity, have shaped a unique lens through which many researchers view the nervous system. Recently, interest has shifted toward seemingly non-rhythmic (i.e., aperiodic) EEG signals, which have been linked to various neurological conditions and states of consciousness. However, these findings have been primarily descriptive, leaving interpretations of these aperiodic signals elusive.
    In this study, Niklas Brake, in the research group of Professor Anmar Khadra at McGill University and collaborating with anesthesiologist Dr. Gilles Plourde at the Montreal Neurological Institute, used biophysical modeling to show that large aperiodic fluctuations in the brain’s electric field arise from cortical circuits synchronizing with aperiodic dynamics. These fluctuations, in turn, can significantly bias traditional EEG interpretations. Additionally, the model predicted that both periodic and aperiodic EEG signals are shaped by the molecular timescales of the brain’s inhibitory pathways. To test this, they collected EEG data from individuals undergoing general anesthesia with propofol, a drug that alters the molecules underlying neural inhibition. The observed signal changes matched their model predictions. Using insights from the modeling, they developed an analysis method for identifying and removing aperiodic EEG signals, both to extract aperiodic features and to improve brain rhythm characterization. Applying this method to EEG data revealed that loss of consciousness from propofol was uniquely associated with an increase in delta rhythms, an observation that had previously been masked by propofol’s molecular effects.
    Overall, this study extends EEG theory beyond neural oscillations, illustrating how EEG signals are shaped by neural mechanisms other than brain rhythms and revealing how these signals can undermine traditional analysis methods.

    Read more: https://can-acn.org/brain-star-award-winner-niklas-brake/

  • Understanding how the brain’s network architecture shapes its capacity to transition between different states

    Understanding how the brain’s network architecture shapes its capacity to transition between different states

    This is a Brain Star Award feature: Andrea Luppi, McGill University, won this prize based on the excellence of the research and its potential benefits to the health of Canadians. Brain Star Awards are presented by the Canadian Association for Neuroscience (CAN) and the Canadian Institutes of Health’s Institute of Neurosciences, Mental Health and Addiction

    To support the diversity of human cognitive functions, such as learning, thinking, reasoning, remembering, problem solving, decision making, and attention, brain regions flexibly form and dissolve connections on the fly. How is the brain’s capacity to transition between different functional configurations shaped by brain network architecture? Andrea Luppi, working in Bratislav Misic’s lab at McGill University and the Montreal Neurological Institute, investigated this question using engineering principles of network control to simulate transitions between behaviourally derived brain states. They identified >100 cognitively relevant brain states in a data-driven manner, corresponding to activation patterns aggregated over 14,000 fMRI studies from a large collaborative database called NeuroSynth, and effectively mapped how brain network organization and chemoarchitecture interact to manifest these brain states. By leveraging large-scale databases of network structure, functional activation and neurotransmitter systems, the present work provides an integrative framework for the systematic exploration of the full range of possible transitions between experimentally defined brain states. This systematic approach allowed the researchers to discover the key role of the brain’s wiring diagram in supporting flexible transitions with high energetic efficiency, and how this efficiency can be disrupted by disease and restored by targeted pharmacology.

    Read the full story here: https://can-acn.org/brain-star-award-winner-andrea-luppi/

    View the original research article here:

    Andrea I. Luppi, S. Parker Singleton, Justine Y. Hansen, Keith W. Jamison, Danilo Bzdok, Amy Kuceyeski, Richard F. Betzel & Bratislav Misic. Contributions of network structure, chemoarchitecture and diagnostic categories to transitions between cognitive topographies. Nature Biomedical Engineering 8, 1142–1161 (2024).

    https://doi.org/10.1038/s41551-024-01242-2

  • Study linking depression to specific altered brain cells opens door to new treatments

    Study linking depression to specific altered brain cells opens door to new treatments

    Research on rare post-mortem brain samples reveals altered gene activity, shedding light on depression’s biological roots

    Researchers at McGill University and the Douglas Institute have identified two specific types of brain cells that are altered in people with depression.

    The study, published in Nature Genetics, opens the door to developing new treatments that target these cells and deepens our understanding of depression, a leading cause of disability worldwide that affects more than 264 million people.

    “This is the first time we’ve been able to identify what specific brain cell types are affected in depression by mapping gene activity together with mechanisms that regulate the DNA code,” said senior author Dr. Gustavo Turecki, a professor at McGill, clinician-scientist at the Douglas Institute and Canada Research Chair in Major Depressive Disorder and Suicide. “It gives us a much clearer picture of where disruptions are happening, and which cells are involved.”

    Rare brain bank enables breakthrough

    The researchers used post-mortem brain tissue from the Douglas-Bell Canada Brain Bank, one of the few collections in the world with donated tissue from people who had psychiatric conditions.

    They used single-cell genomic techniques to analyze RNA and DNA from thousands of brain cells, identifying which cells worked differently in depression and what DNA sequences could explain those differences. They studied samples from 59 people who had depression and 41 people without it.

    The results revealed altered gene activity in a certain type of excitatory neuron involved in mood and stress regulation, and in a subtype of microglia cells, which help manage inflammation. In both cell types, many genes were functioning differently in people with depression, suggesting potential disruptions in these key brain systems.

    By pinpointing brain cells affected in depression, the study adds new insight into its biological basis and, more broadly, challenges lingering misconceptions about the disorder.

    “This research reinforces what neuroscience has been telling us for years,” Turecki said. “Depression isn’t just emotional, it reflects real, measurable changes in the brain.”

    As a next step, the researchers plan to study how these cellular changes affect brain function and whether targeting them could lead to better therapies.

    About the study

    “Single-nucleus chromatin accessibility profiling identifies cell types and functional variants contributing to major depression” by Anjali Chawla and Gustavo Turecki et al., was published in Nature Genetics.

    The study was funded by Canadian Institutes of Health Research, Brain Canada Foundation, Fonds de recherche du Québec – Santé and Healthy Brains, Healthy Lives initiative at McGill University.

    This study was published in the Journal Nature Genetics

    10.1038/s41588-025-02249-4 

  • Scientists reveal how the brain uses objects to find direction

    Scientists reveal how the brain uses objects to find direction

    Study shows how visual landmarks tune the brain’s internal compass

    We take our understanding of where we are for granted, until we lose it. When we get lost in nature or a new city, our eyes and brains kick into gear, seeking familiar objects that tell us where we are.

    How our brains distinguish objects from background when finding direction, however, was largely a mystery. A new study provides valuable insight into this process, with possible implications for disorientation-causing conditions such as Alzheimer’s.

    The scientists, based at The Neuro (Montreal Neurological Institute-Hospital) of McGill University and the University Medical Center Göttingen, ran an experiment with mice using ultrasound imaging to measure and record brain activity. The mice were shown visual stimuli, either an object or a scrambled image showing no distinct object.

    They found a small number of brain areas that fired especially when the mouse looked at objects. These areas were found in a brain region called the postsubiculum which specializes in keeping track of where the animal is facing at any given time. Each direction activates a specific cell in the postsubiculum. Objects in the mice’s vision increased the firing of the cell responsible for the direction in which the mouse was looking. They also inhibited cells responsible for directions where the mouse was not looking. Together, this activity reinforced the mouse’s perception of where it was relative to the object.

    While the postsubiculum was particularly sensitive to the presence of objects in the mouse’s vision, other brain regions were not, suggesting that object recognition is particularly important to the brain’s understanding of where it is and where the animal is looking.

    This finding offers clues as to why humans with diseases such as dementia and Alzheimer’s often lose track of where they are. A recent study from Oxford University has shown that the accumulation of tau protein-a hallmark of Alzheimer’s-happens first in the brain regions responsible for spatial orientation.

    “A very useful aspect of our study is it presents a very high-level understanding of two systems that interact together-the visual and spatial recognition systems,” says Stuart Trenholm, a researcher at The Neuro and the paper’s co-senior author. “We have a decent understanding now of how they modulate each other. They are both very high-level brain functions and lot of these neurodegenerative disorders lead to disconnections between these states, so that will be interesting to look into in the future.”

    “Our results are incredibly surprising,” says Adrien Peyrache, a researcher at The Neuro and the paper’s co-senior author. “Nobody would have predicted that object processing would occur in the navigation system and not in the visual cortex. For the first time, we have an inside-the-brain perspective of what an object is, and how we use an object to get a sense of the world around us.”

    Their results were published in the journal Science on Sept. 11, 2025.

    About The Neuro

    The Neuro – The Montreal Neurological Institute-Hospital – is a bilingual, world-leading destination for brain research and advanced patient care. Since its founding in 1934 by renowned neurosurgeon Dr. Wilder Penfield, it has grown to be the largest specialized neuroscience research and clinical center in Canada, and one of the largest in the world. The seamless integration of research, patient care, and training of the world’s top minds make The Neuro uniquely positioned to have a significant impact on the understanding and treatment of nervous system disorders. It was the first academic institute in the world to fully adopt Open Science, to help accelerate the generation of knowledge and discovery of novel effective treatments for brain disorders. The Neuro is a McGill University research and teaching institute and part of the Neuroscience Mission of the McGill University Health Centre. For more information, please visit www.theneuro.ca 

    This study was published in the Journal Science

    DOI: 10.1126/science.adu9828