Category: Awards

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

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.

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://can-acn.org/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

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/

Development of a functional atlas of the human cerebellum

The human cerebellum is a brain region that is activated during many behaviours, including movement, language and cognitive tasks. However, the cerebellum’s contribution to these processes remained poorly understood because of a lack of a comprehensive functional map of this brain region. To address this, Caroline Nettekoven, working in the laboratory of Jorn Diedrichsen at Western University, fused 7 large-scale brain activity imaging (fMRI) datasets into the first comprehensive functional atlas of the cerebellum. The authors developed a computational model that learns brain organization across many datasets and derived a consensus atlas based on 111 subjects and 417 task conditions. This new atlas predicts functional boundaries better than previous atlases and any atlas based on a single dataset only – even on new, unseen data. It therefore provides the most detailed characterization of the functional organization of the human cerebellum so far.

The new atlas provides several novel important features. For example, the atlas and the computational model are designed for precision functional mapping in individuals. Existing atlases simply present a group map, ignoring the large inter-individual variability of functional organisation. The model can integrate the new atlas with a short 10-minute localizer scan to adapt to an individual’s brain, resulting in a much better prediction of individual boundaries. This unprecedented precision will enable detailed investigations into the cerebellum’s contribution to human behaviour.

Read the full story here

Uncovering the role of cilia in astrocyte development and function

Astrocytes are a type of cells that act as crucial regulators of nearly all aspects of the brain. Different types of astrocytes exist; however, little is known about how different subtypes of astrocytes are created during development to differentially support their local neural circuits. Lizheng Wang, working in the laboratory of Jiami Guo at the University of Calgary, has discovered that a structure called the primary cilia acts as a small signaling antennae to transmit local cues and drive the region-specific diversification of astrocytes within the developing brain, and plays important roles in brain development.

Discovered over 100 years ago, primary cilia are only beginning to be appreciated for their significance in the brain. Researchers have recently demonstrated that primary cilia of neurons are indispensable in regulating major neuronal development and functions, while the presence and function of cilia in astrocytes remained unexplored. This study shows that perturbation of astrocytic cilia leads to disruption of neuronal development and connections in the brain. Mice with primary ciliary deficient astrocytes show behavioral deficits in sensorimotor function, sociability, learning and memory.

Read the full story here

Phase 2a clinical trial reveals a small molecule called LM11A-31 is safe and slows progression of many features of Alzheimer’s Disease

Alzheimer’s disease (AD) is a debilitating neurodegenerative disorder for which there is no cure. Therapeutics available to the approximately 734,000 Canadians living with AD provide symptom management without slowing disease progression. Hayley Renee Christine Shanks, working in the laboratory of Dr. Taylor Schmitz at Western University, adopted a novel approach to AD therapeutics by targeting “deep biology” — that is, receptors that control multiple fundamental cellular pathways and may therefore normalize multiple pathological processes underlying AD. This “deep biology” target, called the p75 neurotrophin receptor (p75NTR), plays a critical role in determining  whether cells degenerate or survive. This receptor was discovered approximately 30 years ago and is widely studied in the fields of developmental neuroscience and neurology.

In AD, p75NTR is a key receptor that mediates neuronal dysfunction, neurodegeneration, and glial reactivity. Research in AD mouse models indicates that modulation of p75NTR with a small molecule called LM11A-31 promotes neuronal resilience and reduces neuroinflammation. Building on this work, Shanks et al. (2024), Nature Medicine, was the first publication to examine selective modulation of p75NTR in individuals with AD.

Read the full story here: https://can-acn.org/brain-star-award-winner-hayley-renee-christine-shanks/

Read the original research article here:

Shanks, HRC, Chen, K, Reiman, EM, Blennow, K, Cummings, JL, Massa, SM, Longo, FM, Börjesson-Hanson, A, Windisch, M, Schmitz, TW. p75 neurotrophin receptor modulation in mild to moderate Alzheimer disease: a randomized, placebo-controlled phase 2a trial. Nat Med 30, 1761–1770 (2024).  https://doi.org/10.1038/s41591-024-02977-w

https://www.nature.com/articles/s41591-024-02977-w