BrainsCAN Fellows

Research Information:
Anxiety disorders affect millions of Canadians, impairing their mental, physical, and social lives. Existing
pharmacotherapies used to treat anxiety disorders can have serious side-effects, including drug dependence and cognitive impairments. Recent research has suggested that cannabis derived compounds, particularly cannabidiol (CBD), may provide an alternative therapy for anxiety disorders. Using a model of general anxiety, this project aims to identify the neural systems associated with anxiety by employing neural recordings and advanced imaging techniques. Furthermore, we will assess the effectiveness of CBD, and other cannabis-derived substances, to treat anxiety and the associated cognitive impairment. These studies will improve our understanding of the mechanisms of anxiety disorders and the associated cognitive disorders. Additionally, this research will greatly aid in the development of safer and more effective pharmacotherapies.

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:
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:
The early life period sees rapid and fundamental maturational changes in the structure and function of the brain. These alterations include cortical reorganization, synaptic pruning and myelination, with varying time courses across development. This project will determine the impact of diet on functional brain network structure essential for cognition. The outcomes of this project will provide the basis for significantly reducing the impact of diet-induced cognitive decline through health recommendations in the clinic and public policy regarding diets.

 

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:
Oculomotor tasks have long been used as an index of cognitive control dysfunction in neuropsychiatric conditions (e.g., schizophrenia) in humans. Much of the understanding of this oculomotor circuitry has come from saccadic eye movement tasks – neuropsychiatric diseases, however, are difficult to model. With the advent of transgenic and optogenetic techniques, the use of saccadic tasks in preclinical NHP models of human brain diseases has tremendous potential for detecting the underlying disease-related pathophysiology of these debilitating brain disorders. To that end, this project involves the development of protocols for awake-behaving NHP functional magnetic resonance imaging at ultra-high field – by using saccadic tasks during fMRI acquisition, we can identify functional network topologies in NHPs that are homologous with the human brain. Understanding the functional organization of the NHP oculomotor circuitry will be important as researchers leverage the genetic similarity of NHPs to model human neuropsychiatric diseases.

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:
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:
The recognition of speech is fundamental for so many day-to-day activities that we often take this skill for granted, particularly in adverse listening conditions (e.g., maintaining a conversation in a crowded café). Reducing listening effort in these challenging environments is important for improving the quality of life for individuals across ages, and one promising means of achieving this goal is through developing perceptual expertise related to talker identity. Voices of friends or family members are substantially more intelligible than unfamiliar voices and are less susceptible to interference by competing sounds, indicating that they are less cognitively demanding and thus may reduce listening effort. Yet, a systematic understanding of how perceptual familiarity develops and leads to improved speech intelligibility is lacking. Thus, the overarching goal of this project is to determine how we develop familiarity with voices to realize maximal benefits to intelligibility. This goal will be informed by recent advances in our understanding of perceptual learning mechanisms as well as the neurobiology of sleep-dependent memory consolidation.

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. 

Research Information:
Affecting 10 million people worldwide, Parkinson’s disease (PD) is a complex neurological disorder that primarily affects movement, but can also be accompanied by psychiatric symptoms and cognitive impairment. Besides medication, deep brain stimulation, or DBS is an effective surgical therapy, where an electrode is implanted in the brain to electrically stimulate the designated nucleus (a cluster of neurons) to relieve the motor dysfunctions. Compared with sporadic Parkinson’s disease, the familial form due to inherited genetic mutations can have earlier and more aggressive disease progression, and are prone to post-surgical adverse effects in DBS treatment. However, the precise mechanisms are still unclear. Using diffusion and functional MRI that can reveal anatomical and functional connectivity of the brain, respectively, a map of brain network can be constructed to help us gain deeper insights into the working of the brain and the disease. By leveraging brain network information and computational models, I am interested to reveal the impacts of genetic mutations on PD symptoms and progression, as well as its interplay with DBS. The findings will allow better treatment plans and understanding of the disease.