Neurosciences & Mental Health
We are uncovering innovative solutions for mitigating and curing brain diseases in children.
The Neurosciences & Mental Health research program focus on the development and plasticity of complex neural systems in animal models and humans through a variety of approaches including molecular genetics, electrophysiology, behavior, cognition and neuroimaging. As a leader in paediatric neurosciences and mental health, and a hub of discovery for applied mental health research at SickKids, we’ve made a number of important research discoveries and published high-impact papers, translating our work into better health outcomes for children and youth.
We engage in a variety of research studies ranging from molecular genetics in various model organisms to human subjects.
We also conduct fundamental and translational research on neurodevelopmental disorders (e.g., autism. epilepsy, and ADHD), neurological and neurodegenerative diseases (e.g., pain, ALS, AD, etc.), and mental health (mood disorders).
We explore learning and memory, language acquisition, knowledge processes, and the way our brains normally digest and process information (in the context of specific cognitive disorders).
We utilize traditional psychophysical methods, behavioural and cognitive testing, advanced cellular and molecular biology techniques, and modern brain-scan technology in our mental health and neuroscience research.
By examining how the developing brain is influenced by early sensory experience, sensory system studies aim to promote sensory adaptation – ultimately allowing children to better perceive, comprehend, communicate, interact, and experience the world around them.
Brain injury and repair scientists’ goal is to develop better methods of predicting neurocognitive outcomes in children with acquired brain injury. Neuroimaging, neuroelectrophysiological, physiological measures and experimental techniques, including iPS cells and brain organoids, and other multimodal approaches drive studies in this area.
Neurodevelopment refers to how the nervous system and the pathways responsible for normal brain function are built during embryonic and postnatal life. We examine how stem cells build and sculpt the brain, the processes by which neurons and glia construct and shape the circuits that ensure proper cognitive and motor function, and how disruptions in genes and the environment result in neurodevelopmental disorders and developmental delay.
Unique to SickKids, the use of multimodal imaging of sensory and cognitive functions in children demands highly skilled, multidisciplinary collaborations among our expert team of physicists, neuroscientists, behavioural neuroscientists, and clinical scientists.
Clinical research is driven by brain imaging using structural and functional MRI, as well as MEG, localizing the nervous system injury sites and types, and defining their relationships to cognitive and behavioural abnormalities.
Currently, we’re investigating the normal development and disorders of the nervous system from a broad range of perspectives. Our teams examine the role of genes, proteins and other molecules in brain function, and use our findings to determine the causes of brain dysfunction. This helps us develop new and innovative forms of therapy for a variety of mental health disorders.
Studies of inherited and acquired disorders of the nervous system extend from early pre-natal life to the day-to-day functioning of children in their schools, homes and communities. Our current goals are to develop new therapies and prevention strategies, while still taking into account the child’s quality of life, and to integrate treatments that ensure children living with these disorders can live long and happy lives.
Research areas in which NMH investigators are currently making major advances include:
- Developmental and pathological neuroplasticity and neuron-glia interactions
- Development of sensory systems and pain
- Cognitive function and dysfunction research in model organisms and children
- Inherited and acquired disorders of the CNS in model organisms and children
- Functional neuroimaging and cognitive neuroscience in children
- Neurogenetics of complex disorders such as ADHD, autism and reading disabilities
A little bit of spit goes a long way for science
A team lead by Drs. Jennifer Crosbie and Russell Schachar are extracting DNA from the spit samples provided by 17,000 visitors, aged 6‐17, at the Ontario Science Centre to discover the way genetic and environmental risk factors cause mental illness.
The team showed that attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), and autism spectrum disorder (ASD) are genetically and cognitively similar to the extremes of widely distributed traits. The team found genetic markers for pediatric OCD (with Dr. Paul Arnold), copy number variants in ADHD (with Dr. Stephen Scherer), and cognitive deficits like the inability to stop a response in these disorders.
The team is collecting 30,000 additional samples to learn more about the genetics of these disorders, and work out if environmental factors (e.g. exposure to NO2) interact with genes to impact mental health.
The team is translating what they learned about cognitive deficit into enjoyable, virtual reality games to strengthen cognition and improve behaviour (with the National Research Council). Samples will be stored in the Health Kids Biobank at SickKids, a legacy data set for researcher across all areas to access genetic and health data for primary analyses of disease-specific subgroups or as normal controls.
The invisible wounds of psychological injury
A team led by Drs. Margot Taylor, Liz Pang and Benjamin Dunkley discovered that psychological injuries lead to lingering brain dysfunction that is measurable using sophisticated functional brain imaging – magnetoencephalography (MEG).
Partnering with the Canadian Armed Forces, the team used MEG to assess brain function in soldiers with posttraumatic stress disorder and a matched group of soldiers exposed to trauma who did not develop PTSD. They found that the way in which brain areas communicate with one another - particularly in the frontal and temporal lobes, areas crucial for memory and emotions - were dysfunctional in PTSD. This disruption was directly related to the self-reported severity of the PTSD symptoms.
Subsequent analyses by Drs. Dunkley and Zhang, using deep learning algorithms, reliably distinguished individuals with PTSD from those without. They applied these approaches to longitudinal datasets, and can now predict the severity of disease from the MEG scan alone. Thus, integrated with advances in artificial intelligence algorithms, they are able to objectively recognize these conventionally invisible signatures from quick, well-tolerated brain scans. This approach holds tremendous promise for faster diagnostics in mental health challenges and predicting and/or monitoring the most effective treatment for psychiatric disorders.
Discovering precise molecular mechanisms that can influence memory
Learning and memory are crucial parts of human cognition, yet the biological processes that govern how we learn and store different types of memories are poorly understood.
Synaptic plasticity has long been thought to contribute to learning and memory, but many of the neural mechanisms behind synaptic plasticity remain unclear. In a study entitled The C-terminal tails of endogenous GluA1 and GluA2 differentially contribute to hippocampal synaptic plasticity and learning, Dr. Zhengping Jia and co-lead authors Celeste Leung and Zikai Zhou have discovered the precise neuronal mechanisms that can regulate synaptic plasticity to influence distinct forms of memory.
The study published in Nature Neuroscience is the first to identify a specific domain of native glutamate receptors that enables different forms of neuronal plasticity and memory. These findings could be important to provide a specific target for therapies meant to reverse memory deficit in brain disorders, such as Alzheimer’s disease and autism.
May 16, 2023
SickKids researchers discover that a matrix called the perineuronal net may be responsible for why human memories become more specific throughout childhood.
October 17, 2022
Dr. Sheena Josselyn, Senior Scientist in the Neurosciences & Mental Health research program, has been elected to the National Academy of Medicine.
August 16, 2021
Study finds cancer screening tool may help predict risk of developing a new cancer among childhood cancer survivors
Research led by SickKids and the Montreal Children’s Hospital of the McGill University Health Centre found that a novel cancer predisposition screening tool shows promise for helping doctors better predict which childhood cancer survivors may be at risk of developing future cancers.
The Miller/Kaplan Lab uses single cell and spatial transcriptomics, along with epigenomics and phosphoproteomics, in utero and post-natal electorporation with Crispr and shRNA knockdown vectors.
These three SickKids labs utilize magnetoencephalography (MEG). MEG accruately measures of brain function, with excellent temporal and spatial resolution. However, recordings in infants and toddlers, and young children with developmental disability, are difficult in conventional MEG systems, as those scanners are designed for adult-sized heads, and recordings are inaccurate with movement.
These labs have begun working with a new type of MEG brain imaging sensor – optically pumped magnetometers (OPMs). These sensors can be mounted in a flexible cap or customized helmet, specifically for a child’s head size, allowing for more organic experiments as participants can move and speak during their studies. OPM-MEG provides improved sensitivity over conventional neuroimaging systems, as the sensors are closer to the brain.
With continued development, OPM-MEG will allow brain imaging studies in children across the full spectrum of development and a wide range of disorders, from the beginning of symptom onset, and help monitor the effects of the earliest interventions.
The Mary Lou Smith Lab recently pinpointed, for the first time ever, the long-term effects of childhood treatments for epilepsy on cognition, behaviour and quality of life.
Combining patch-clamp electrophysiology and multiphoton real-time imaging in transgenic mouse models, the Wang Lab has done extensive work to conceptualize how sensory synapses remodel their morphology and function during the critical period of brain development to facilitate information transfer and coding. The work also explored how dysregulated excitation and inhibition (E/I) balance in the developing brain contributes to autism spectrum disorder and neonatal neurotoxicity.
The Josselyn/Frankland Lab uses a variety of methods (including 2-photon microscopy, 1-photon mini-endoscopes, optogenetics, gene transfer techniques and detailed behavioural analysis) to understand how information is acquired, stored, used and sometimes forgotten in the brain of rodents.
Research is driven by biological questions, and we use the most appropriate tool to try to answer these questions. We often engage with computational, theoretical and cognitive neuroscience to help guide our hypothesis and analysis.
The Steven Miller lab discovered that babies born early (preterm) or with congenital heart disease (CHD) share similar vulnerability to white matter injury (WMI), abnormal brain maturation, and developmental impairments in early childhood.
Using multimodal brain imaging, their team found that WMI underlies brain dysmaturation and early neurodevelopmental disability in both populations of neonates. Through these studies, they developed an innovative lesion mapping method that describes the likelihood of vulnerability for WMI in the baby brain, and reveals how WMI volume and spatial pattern are associated with neurodevelopmental outcomes. The Miller Lab also established the “importance of the everyday” for brain maturation in critically ill neonates: pain, nutrition, and common illness such as infection, significantly alter the trajectory of early brain maturation. These findings help us design and implement new strategies towards brain injury repair, and promote optimal brain maturation and neurodevelopmental outcome.
Spearheaded by program head Dr. Donald Mabbott, the multidisciplinary NMH team at SickKids has garnered international reputation for excellence in basic and clinical research.
NMH faculty have appointments in Critical Care Medicine, Diagnostic imaging, Neurology, Neurosurgery, Ophthalmology, Otolaryngology, Radiology, Rheumatology, Psychology, and Psychiatry. Additionally, NMH members hold primary academic appointments in 14 departments at the University of Toronto.
The program’s strength lies in the talented faculty, as evidenced by steady, successful applications for tri-council (especially Canadian Institutes of Health Research) funding, which is significantly higher than the national average. Program investigators produce stellar publications in both quantity and impact that have been featured in top journals and medical publications. Since our inception, the work of our Principal Investigators (PIs) has been recognized through numerous awards and grants. too.
Along with high-level scientists and investigators, students and trainees have universally praised the excellence of their mentors for the hands-on experience and opportunity to learn from the leading minds in neuroscience and mental health research.
- Dr. Donald Mabbott
- Dr. Cathy Barr
- Dr. Douglas Cheyne
- Dr. Paul Frankland
- Dr. Agnes Wong
- Dr. Karen Gordon
- Dr. Anne Marie Guerguerian
- Dr. Robert Harrison
- Dr. Jamie Hutchison
- Dr. Zhengping Jia
- Dr. Julie Lefebvre
- Dr. Sheena Josselyn
- Dr. David Kaplan
- Dr. Steven Miller
- Dr. Steven Prescott
- Dr. Michael Salter
- Dr. Russell Schachar
- Dr. Peter Szatmari
- Dr. Margot Taylor
- Dr. Lu-Yang Wang
- Dr. Joanne Rovet
- Dr. Carol Westall
- Dr. Rosemary Tannock
- Dr. Maureen Lovett
- Dr. Freda Miller
NMH scientists regularly feature in top journals, excel in increasingly competitive grant competitions, and receive national and international recognition. Our trainees have received some of the top awards in Canada to support their research projects.
Given to just 55 out of 1,500 co-op supervisors, Dr. Elizabeth Pang received the UBC Science Co-op Supervisor Recognition Award, which recognizes “super” supervisors who provide exceptional mentorship, demonstrate excellent leadership/managerial skills, and go above and beyond to provide a meaningful and quality work experience for their students.
Dr. George Ibrahim was recently named a recipient of Canada's Top 40 Under 40 award, a celebration of the top up-and-coming leaders in the country.
Dr. Ibrahim is a paediatric neurosurgeon and Associate Scientist in the Neurosciences & Mental Health program at SickKids Research Institute. He is also an Assistant Professor in the Department of Surgery, Institute of Biomaterials and Biomedical Engineering at the University of Toronto.
At SickKids, he treats children with medically-intractable epilepsy, spasticity and functional disorders. His lab has yielded insights into personalized treatments for children with epilepsy and functional disorders by targeting specific network impairments and developing novel devices and treatment strategies. He was part of the team that performed the first deep brain stimulation to treat drug-resistant paediatric epilepsy in Canada.
Dr. Mary Lou Smith is the recipient of the 2020 Fritz Dreifuss Award from the America Epilepsy Society!
She's the Senior Associate Scientist in the Neurosciences & Mental Health Program, and a professor in the Department of Psychology at the University of Toronto Mississauga.
For more than 30 years, Dr. Smith has dedicated her career to cognitive and behavioural co-morbidities associated with epilepsy. Her work has addressed these topics from a number of perspectives, including the clinical nature of intractable epilepsy, and theoretical issues for understanding early brain dysfunction. This award recognizes her significant accomplishments and impact in the field of epilepsy research.
Dr. Freda Miller captured the 2019 Till & McCulloch Award for a new research discovery in tissue repair and regeneration that holds potential for future therapies.
The Award is presented annually to one researcher in Canada who has made an exceptional contribution to global stem cell research in that year. Dr. Miller presented the Award lecture on November 5 at the Till & McCulloch Meetings (TMM) in Montréal, Québec, based on her Cell Stem Cell paper entitled, “Mesenchymal Precursor Cells in Adult Nerves Contribute to Mammalian Tissue Repair and Regeneration.”
- Investigators: Dunkley, BT, Zhang, J & Richardson, JD.
- Grant: $977K, Innovation for Defence Excellence and Security (IDEaS) Program, Department of National Defence.
- Primary Investigator: Gordon, K.A.
- Co-investigators: Papsin, B.C., Cushing, S.L.
- Collaborators: Scollie, S., Papaioannou, V.
- CIHR Project Grant, Fall 2019 competition.
- Primary Investigator: Freda Miller
- Co-investigators: Gary Bader, David Kaplan, Cindi Morshead, Yun Li, Penny Gilbert, Alison McGuigan, Sid Goyal
- Canada First Research Excellence Fund - Medicine by Design 9/1/2019-8/31/2022
- Primary Investigator: Steven Miller
- CIHR Fall 2019 Competition
- Investigators: Mabbott DJ, Bouffet E , Laughlin S, Willan A, Larouche V, Beattie T, Cheng S, Girgis R, Sinha R, Khan N, Halverson M, Lafay-Cousin L, Hukin J, Erker C, Johnston D, Crooks B, Wilson V, Haas K, Haas T.
- Canadian Cancer Society/CIHR Cancer Survivorship Team Grant. ($2,500,000 2019-2024).
Julie Lefebvre is a co-PI on a Medicine by Design Cycle 2 Team Grant aimed to improve outcomes of cell-based retinal therapy for preserving and restoring sight (lead PI Molly Shoichet).
Giulia Longoni received a Feiga Bresver Catalyst grant for Quantitative Perfusion Imaging for Autoimmune Encephalitis Diagnosis and Monitoring. From the Centre for Brain & Mental Health, $98,694.