BrainsCAN Fellows

Research Information:
The recent legalization of cannabis for both medicinal and recreational purposes has altered the perception of risks, resulting in a sustained increase of cannabis use mainly among adolescents. This trend is concerning given that sustained consumption of marijuana during such vulnerable neurodevelopmental window has been associated with a wide range of long-lasting cognitive impairments and enhanced risks for neuropsychiatric diseases, such as schizophrenia, anxiety and mood disorders. In addition, emerging evidence has pointed out critical sex-related differences in neuropathological outcomes induced by marijuana consumption. In this study, the impairments in cognitive and affective processing will be investigated in a translational rodent model of adolescent cannabis exposure. Using a multi-level approach, cognitive performances, anxiety and psychiatric-like manifestations will be evaluated, concomitant with a detailed examination of molecular biomarkers and neural activity in selected brain regions relevant for cognition and neuropsychiatric disorders. The findings obtained by the proposed research will enhance our knowledge on the neurobiological mechanisms underlying the side effects of cannabis exposure on the adolescent brains in both genders and will aid in developing novel potential pharmacotherapeutic strategies to reverse the cannabis-related pathology. 

Research Information:
Hearing loss is one of the most prevalent chronic health conditions, affecting more than 1.2 billion people worldwide. It is well-recognized that excessive exposure to loud noise, resulting from environmental (e.g., city noise), recreational (e.g., loud music) and occupational (e.g., industry workers) insults, is a leading cause of permanent hearing loss. Beyond the devastating effects of hearing impairment itself, there is clear evidence that loud noise exposure also leads to pathology in brain regions both within and beyond the auditory pathway. For example, noise exposure can cause aberrant auditory perceptions such as tinnitus (i.e., “ringing in the ears”), as well as cognitive impairments in learning and memory tasks that do not depend on the auditory system. While the neural mechanisms contributing to noise-induced tinnitus and cognitive impairment remain elusive, accumulating evidence suggests that neuroinflammation plays an important role in mediating the brain plasticity thought to underlie these disorders. Using a combination of cell-specific in vivo neuroimaging and auditory/cognitive behavioural testing, my research aims to reveal how noise-induced neuroinflammation leads to aberrant neural activity in areas of the brain that control auditory perception, learning, memory and other higher-order cognitive functions. Ultimately, this work will address our crucial need to better understand the adverse effects of noise exposure on brain health.

Research Information:
The sustained and excessive consumption of calorie-dense foods is the leading cause of preventable chronic disease and premature death worldwide. Limiting the consumption of these foods is therefore essential to maintain optimal health. However, in the modern food-rich environment, maintaining a healthy diet has become a difficult endeavor. The environment is saturated with unhealthy ultra-processed calorie-dense foods (those high in saturated fats and sugar), and these foods are often cheaper than their healthier counterparts. This is coupled with omnipresent cues, in the form of media advertisements, to consume these foods. While some individuals find it really difficult to control calorie-dense food consumption in this environment, others are more adept. My research seeks to understand why some individuals are more prone to overconsumption than others. Specifically, my body of research seeks to understand the neural circuits underlying vulnerability to over consumption, with the particular focus on how the prefrontal cortex regulates reward circuits in the brain to modulate consumptive behaviours across developmental contexts. By delineating these neurobiological processes, we will be able to identify the subtle cognitive and neural markers that increase the propensity to overeat. This would enable researchers and clinicians to identify those individuals that may be more likely to respond to a given intervention and provide the foundational work necessary to develop novel evidence-based interventions.

 

Publications: 
Trends in Cognitive Sciences: Review suggests a reciprocal relationship between obesity and self-control
The Lancet: Adolescents prone to poor dietary choices, leading to changes in the brain 

Research Information:
Auditory cortex (AUD) is critical to our perception of spoken language, and the crossmodal plasticity that follows hearing impairment to improve visual perception impedes hearing restoration. Hearing impairment makes it impossible to functionally localize AUD with noninvasive magnetic resonance imaging (MRI) methods in order to understand the crossmodal plasticity that follows deafening. Structural MRI (sMRI) methods are thus needed to study the reorganization of AUD as it undergoes crossmodal plasticity following hearing impairment. Current imaging studies are increasingly using myelin to map the brain because MRI methods can measure how it restricts the movement of water. My previous work has shown that subregions of AUD differ markedly in quantitative myelin content, and recent imaging work confirms this agreement using structural and functional MRI in humans. This project establishes the precision of myelin as a structural marker of AUD in an animal model and then pilots the use of this method to study crossmodal reorganization in humans with hearing impairment. These results will fill a major gap in our understanding of the mechanisms of crossmodal plasticity by developing, validating, and applying the first structural marker of AUD to study the brain as it undergoes reorganization following hearing impairment.

Research Information:
Parkinson’s disease (PD) and Lewy body dementia (LBD) are neurodegenerative disorders characterized by accumulation of misfolded α-synuclein aggregates in the central nervous system. With improvements in the management of motor symptoms in recent decades, non-motor features of these synucleinopathies are now a major cause of morbidity, especially cognitive deficits. The molecular and cellular mechanisms underlying PD and LBD-associated cognitive decline remain to be fully revealed. Chaperones and co-chaperones assist protein folding, stability and degradation. Epichaperomes are maladaptive protein networks reflecting abnormal connectivity of chaperones with their interactomes. Multiple chaperones, including Hsp90, Hsp70 and their co-chaperone STIP1, interact with α-synuclein, supporting the notion that abnormal chaperone activity may contribute to the pathogenesis of synucleinopathies. Chaperones also influence the stability and the activation of several proteins related to signal transduction and immunity. For instance, the chaperone Hsp90 prevents the degradation of the NLRP3 inflammasome, a group of cytosolic multiprotein complexes mainly expressed in macrophages/microglia that recognize several stimuli, triggering innate inflammatory processes. Herein, by using transgenic mice expressing the mutant A53T human α-synuclein in neurons as a model of synucleinopathies and high-throughput touchscreen tests we aim to investigate whether epichaperome and NLRP3 inflammasome act synergistically to accelerate PD and LBD-associated cognitive decline.

Research Information:
Up to 20% of pregnant women self-report using cannabis during pregnancy. With recent decriminalization and progressive legalization of recreational cannabis in North America, this figure is projected to increase. While the THC component of cannabis has been shown to impair fetal growth in clinical populations and animal models, our understanding of the developmental effects, and associated neural pathways, of maternal cannabis consumption is currently lacking. This project will address this knowledge gap in a model of prenatal cannabis exposure. Specifically, the effects of cannabis constituents on cognition (e.g. learning and memory) will be investigated at the levels of behaviour, neural pathways, and brain structures. The goal of this project is to improve postnatal developmental outcomes and inform public awareness of the risks associated with prenatal cannabis consumption.

Research Information:
Intrauterine growth restriction (IUGR) is a serious condition where the placenta stops growing late in pregnancy, limiting oxygen to the fetal brain. In the early stages of IUGR, blood flow is still being directed to the frontal lobes. Later, however, blood is directed to midbrain areas important for keeping the fetus alive. This redistribution referred to as ‘brain sparing’. Brain sparing can result in severe brain injury, with adverse consequences for cognitive function, including language. For these fetuses, early delivery can prevent death; however premature birth also comes at a cost. The neonatal ICU is a stressful environment, and preterm babies are at risk of both short- and long-term health issues. Objective measures to guide decisions regarding delivery time to maximize developmental outcomes are crucial to neonatal care in this population. My research aims to evaluate whether brain sparing is associated with decreased functional and structural connectivity in the language network in utero, and if connectivity measures are associated with language outcomes at 12- and 24-months. By using MRI-based methods to monitor fetuses at risk for IUGR, and following the developmental trajectory of the newborns, I aim to improve newborn brain health and cognitive outcomes, specifically later language development.

Research Information:
Speech is arguably the most important form of human communication. Since the goal of speech production is the transfer of information, speech production must be carefully regulated to ensure the desired information is conveyed. During speech production sensory feedback, such as auditory feedback, plays an important role in maintaining the fluidity of speech, as it allows speech motor movements to be monitored and production errors to be detected and corrected. A major focus of my research program is investigating how the role of sensory feedback in the control of speech changes throughout development in individuals with and without autism spectrum disorder. I am also interested in how the ability to extract and utilize the information contained in sensory feedback influences the development of higher-order cognitive processes such as speech communication, emotion regulation, and social competence.

Research Information:
To form a coherent perception of the world around us, we are constantly processing and integrating sensory information from multiple modalities. In fact, when auditory and visual stimuli occur within ~100 ms of each other, individuals tend to perceive the stimuli as a single event, even though they occurred at separately. Although this integration of closely-timed audiovisual stimuli can offer certain behavioral advantages, an overly broad window of temporal integration can be problematic (e.g., in autism and schizophrenia), as information from truly separate events may not be perceived correctly. While recent studies in humans have suggested that the binding of audiovisual stimuli is regulated by neural oscillations, the brain circuits and cellular mechanisms that regulate the putative oscillatory activity subserving audiovisual perceptual binding remains unknown. Using our translational behavioural task in combination with optogenetics and in vivo electrophysiology, my research aims to uncover the mechanisms by which inhibitory neurotransmission finely controls audiovisual perception. Ultimately, these studies will significantly advance our understanding of the neuronal circuitry underlying audiovisual temporal perception, and will be the first to establish the role of interneurons in regulating the synchronized neural activity that is thought to contribute to the precise binding of audiovisual stimuli.

Research Information:
One of the most critical quests of developmental and cognitive neuroscientists is the discovery of the origin of human knowledge. One type of knowledge, which is the most important basis of academic achievement, is symbolic number knowledge: children understand each number word is associated with a respective quantity. Children initially develop this understanding of the meaning of the numbers around 2-3 years old. Uncovering the underlying mechanism of symbolic number knowledge leads to better insights about cognitive development and individual differences in humans. In a longer perspective, this understanding might help for earlier diagnoses and more effective interventions in children at risk for learning disorders, particularly developmental dyscalculia (i.e., mathematical disability). In a longitudinal project, neural correlates of acquisition of symbolic number knowledge will be tracked in preschoolers from age 3 to 5 years. Functional organization of particular brain regions such as intraparietal sulci and functional connectivity between these brain regions will be measured using functional near-infrared spectroscopy (fNIRS), as one of the most appropriate neuroimaging techniques in young children.

Research Information:
One quarter of the population has such difficulty learning mathematics that it impairs their ability to use information effectively in adult life. What causes some students to struggle with math? Brain imaging research has begun to shed light on how the brain processes numerical information. However, little is known about how this information is integrated across the brain systems important for math learning, such as memory and attention. With this fellowship, I will conduct a series of studies that provide detailed information about the brain mechanisms that support math skills. First, using ultra-high field 7T magnetic resonance imaging (MRI), I will begin to answer questions about how the brain solves math problems at the individual level. This is an important advance because behavioural research shows that children with math learning difficulties are very different from one another. Second, I will investigate the possibility of subtypes of math learning disability with children who have been identified to need math remediation. To do this, I will identify subgroups of individuals with similar cognitive profiles and compare neural signatures of these cognitive profiles. Research in this area will pave the way to improved pedagogical techniques, diagnosis of learning disabilities, and remediation of deficits.