Advancing Knowledge

Sleep is a pivotal behaviour for health and well-being. We know how important sleep is for brain health, and appreciate how brain disorders can impact quality and quantity of sleep, especially in children. This common concern among parents and family members was recently addressed by a team of researchers spanning three of OBI’s Integrated Discovery Programs.

Researchers from the Province of Ontario Neurodevelopmental Disorders Network (POND), the Childhood Cerebral Palsy Integrated Neuroscience Discovery Network (CP-NET), and OBI’s Epilepsy Research Program (EpLink) patient data from children with neurodevelopmental disorders (NDDS) such as autism spectrum disorder, obsessive compulsive disorder, attention deficit hyperactivity disorder, cerebral palsy, and epilepsy collected, curated, and stored on Brain-CODE, OBI’s neuroinformatics platform.

The results of their work were recently published in the Journal Frontiers in Sleep as a part of the Journal’s ‘current issues in sleep in children with neurodisability’ research topic.

The study found that sleep disturbances in children with NDDs were significantly greater that neurotypical or typically developing children. Furthermore, children with NDDs with greater sleep disturbances were more likely to have greater symptom severity for their disorder, lower quality of life, and experience greater symptoms of anxiety and depression (referred to as internalizing symptoms). The researchers concluded that sleep monitoring and management were needed to improve the quality of life of children impacted by any of the brain disorders. Additionally, the research team suggested that commonalities in sleep disturbances for children should inform treatments to support sleep across the board, regardless of a child’s condition or disorder.

“Sleep is a critical biological function that is important to a person’s recovery, energy conservation, and survival. And for children, it’s especially important for growth and development,” said Dr. Patrick McPhee, a faculty member at McMaster University and researcher affiliated with CP-NET during a panel discussion about the study.

“Sleep problems in children with NDDs have been reported to be as high as 86%. However [prior to this study], knowledge gaps really limited our ability to understand and to treat sleep problems in children both within and across disorders. Particularly, our knowledge of these sleep problems in children with NDDs has been largely limited to studying one diagnostic group or condition at a time, which leads to small sample sizes. What this really means is that we haven’t known for certain if sleep issues apply to all children or children only with a particular condition.”

Dr. McPhee explained that key takeaways from the sleep study were that researchers and clinicians need to look beyond a diagnosis to truly understand and treat sleep problems. The results of the study underscore the notion that there are many commonalities among pediatric brain disorders in terms of sleep problems. “What we’ve done here is identify a common starting point or foundation for treating sleep in children with NDDs, who are particularly impacted by sleep disturbances,” he noted.

Moreover, the success of the study’s methodology, which looked at common data elements – including sleep, anxiety level and quality of life – collected across conditions, will pave the way for future collaborative investigations by IDP researchers, uniquely set up to answer questions from the data stored in Brain-CODE. Learn more about sleep and brain health in children with neurodevelopmental disorders by watching this companion webinar.

‘Nothing about us without us’ is a common refrain from patients when talking about their engagement in research. And this is not just a saying. Embedding patients and families early on in the design and conduct of research yields findings that are more relevant to the needs of the patient community. And these findings are more likely to be carried forward along the translational process that brings lab to life.

Results from a recent study led by the Province of Ontario Neurodevelopmental Disorders Network (POND), add more support for this approach to research. Input from POND’s patient partners and biological observations from researchers converged on the idea that there are likely more commonalities between neurodevelopmental disorders than the diagnostic labels currently suggest. Allison Chang, a parent of a child in POND supports this approach saying, “Only through engagement in research can high quality findings be discovered, and assumptions be challenged.”

A study designed to challenge the current assumptions that treatment should be based on diagnostic criteria was led by Dr. Azadeh Kushki, a member of POND as well as a senior scientist at the Holland Bloorview Kids Rehabilitation Hospital. Titled, Identifying Replicable Subgroups in Neurodevelopmental Conditions Using Resting-State Functional Magnetic Resonance Imaging Data, the research team looked at two independent datasets – one from POND and a second from New York’s Healthy Brain Network.

The team examined data from a total of 551 individuals – both male and female, and all between the ages of 5 and 19 – with neurodevelopmental conditions including attention-deficit/hyperactivity disorder, obsessive compulsive disorder, and autism spectrum disorder. They also considered health information from neurotypical children and youth. By looking at the brain scans in the data, the research team was able to identify patterns of brain function to group together. From there, they investigated the relationship between brain function and behavioural traits from clinical and parental reports.

Further analysis of the data indicated that treatments for children and adolescents living with neurodevelopmental conditions can be better tailored to each individual by analyzing brain patterns instead of relying on diagnostic labels provided to them. As Dr. Kushki notes: “The results of this study tell us that we need to consider the unique strengths and needs of each child, beyond broad diagnostic labels.”

In order to provide the best treatments and supports for children and youth living with neurodevelopmental conditions, understanding neurodiverse brain similarities and differences is crucial.

“This study will hopefully change how neurodevelopmental disorders are diagnosed, as the current process differs for ADHD and autism. This will lead to more appropriate and effective treatment,” says Ms. Chang.

This impactful study from POND is another example of the kind of positive change that happens when the concept of ‘nothing about us without us’ becomes the way research is done. In POND’s case, this work is part of their ongoing effort to redefine how we think about and provide care for individuals with neurodevelopmental disorders. Read the study

In December 2022, researchers with the Childhood Cerebral Palsy Integrated Neuroscience Discovery Network (CP-NET), one of OBI’s Integrated Discovery Programs, published a paper on a lesser-investigated area of cerebral palsy. Their study explored the intersection of brain function and motor skill improvement in children with diplegic cerebral palsy (DCP), a condition characterized by challenges moving both legs.

The six-week study was rolled out with a group of 17 participants between the ages of 8 and 16 years and aimed to identify the correlation between changes in functional neuroplasticity – a process by which the brain adapts to change – and changes in how their bodies moved. The research team, led by Dr. Alicia Hilderley of the Kids Brain Health Network, concluded that brain function in young people with DCP does change after gross motor training. As a next step, the team recommended further investigation in a larger population of children.

“The children in this study completed a gross motor intervention, and we looked at brain activity before and after the intervention,” explained Dr. Hilderley. “We found three different patterns of change in brain activity. We need to continue investigating these patterns to better understand the characteristics of children with each pattern of change. This information may help optimize intervention [or treatment] selection and dose for each child.”

For Dr. Hilderley, this research emphasizes that children with diplegic cerebral palsy have the potential for improvements in movement, and that improvements may be accompanied by different changes in brain function. “Our findings suggest that there is not one "right" way for their brains to function and change.”

This is the first known study to specifically focus on task-based functional brain plasticity in association with gross motor skill improvements for independently ambulatory children with DCP. However, as the largest translational network in Canada dedicated to cerebral palsy, CP-NET is uniquely positioned in the world to undertake this work.

“This research project is a great example where the necessary expertise existed in the network to do a deep dive into understanding neural mechanisms supporting intervention change for children with CP,” Dr. Darcy Fehlings, a senior clinician scientist the Holland Bloorview Kids Rehabilitation Hospital and CP-NET's program lead. Read the paper

The work of three of OBI’s Integrated Discovery Programs came to an end in 2023. However, the impact of the Ontario Neurodegenerative Disease Research Initiative (ONDRI), the Epilepsy Research Program (EpLink), and the Concussion Ontario Network: Neuroinformatics to Enhance Clinical Care and Translation (CONNECT) on research, commercialization, and care will live on.

ONDRI was created in 2013 with a mission to catalyze advances in dementia and motor disorders to improve the diagnosis, prognosis, care, and outcomes for persons living with these conditions as well as those who support them. The ONDRI team released a rich dataset to help further scientific investigation into these disorders and contributed to amplifying the patient experience through their Patient & Community Advisory Committee.

EpLink was established in 2011 with the aim of reducing seizures and improving the quality of life for people with epilepsy through research. Driven by the vision of a world without epilepsy, EpLink's research focused on developing more effective drug therapies, improving diet therapies and surgical procedures, uncovering new treatment options with gene therapy and brain stimulation, and creating new programs to improve cognition, mood, and quality of life for individuals living with uncontrolled seizures. With OBI, the EpLink team ran Canada’s first research priority setting partner with patients and contributed to the development of Ontario’s epilepsy guidelines.

The goal of the CONNECT program was for clinicians and researchers in Ontario to establish themselves as leaders in achieving the most rapid and complete recovery from concussion and its complications. Focused on three main priorities to guide this mission, CONNECT conducted research, personalized data collection, and uncovered holistic findings that not only improved recovery, but prevented re- injury and the long-term implications from concussion. By bringing together ten expert centres across the province, the CONNECT team worked to ensure that new knowledge was translated into better diagnoses and care for the benefit of all Ontarians.

“We remain grateful for the work of ONDRI, EpLink, and CONNECT to advance brain research, commercialization, and care,” said Dr. Tom Mikkelsen, OBI’s President and Scientific Director. “The datasets that each of these programs brought to Brain-CODE, as well as tools they each created to understand neurodegenerative diseases, epilepsy, and concussion, ensures that their legacy remains and that they continue to impact research within the province and beyond.”

Learn more about the legacies of ONDRI, EpLink and CONNECT.