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Unlocking the enigma of brain disorders

Computational neuroscientists like Dr. Alan Evans are taking the next giant step towards understanding brain disorders thanks to a major gift from alumnus Marc Sievers.

Alan Evans standing in front of a screen

Dr. Alan Evans

Credit: Alex Tran

As you read this article, your brain is working hard on multiple fronts, interpreting the characters on the screen, accessing stored information to aid comprehension, archiving data for later use and much, much more.  Traditional research can tell you where this activity occurs in the brain but, in terms of understanding how different regions of the brain talk to each other, computational neuroscience provides one of the most promising and fast-developing areas of research.

Now, thanks to a major gift from McGill alumnus Marc Sievers, BSc’69, computational neuroscience is taking a big step forward with the launch of the Marc and Susie Sievers Computational Neuroscience Initiative at the Ludmer Centre for Neuroinformatics & Mental Health. The Initiative builds on McGill’s leadership in the field and the ground breaking work of Dr. Alan Evans. As Scientific Director of the Sievers Initiative, Evans will lead the project through his lab, the McGill Centre for Integrative Neuroscience, under the auspices of the Ludmer Centre.

Computational neuroscience uses advanced computer modelling to simulate brain circuitry in normal and disordered brains (so-called “in silico” modelling) to better understand normal brain function, brain development and brain disorders.

New insights into brain illnesses, disorders and diseases

This innovative research can yield important discoveries and insight into illnesses like depression, developmental disorders such as autism spectrum, or neurodegenerative diseases like Alzheimer’s disease and Parkinson’s disease.

“It’s an exciting and fast evolving field of research which leverages the advances being made in artificial intelligence, big data and neuroinformatics,” says Sievers. “I’m pleased to support McGill’s work in this area.”

Diagnosing brain disorders has always been one of the most challenging areas of medicine.

“When somebody visits a doctor’s office and describes symptoms, the doctor tries to infer what's going on inside the brain and selects an intervention to deal with it,” says Evans, who is the James McGill Professor in Neurology and Neuroscience at The Neuro, co-Director of the Ludmer Centre, and Victor Dahdaleh Chair in Neurosciences. “What you really need to do is get inside the brain and see what's going on with its internal circuitry. We can do this nowadays because we have technologies like brain imaging. We then seek to relate circuitry measures to cognitive performance and to genetic signatures so as to reveal the origins of the brain pathology.”

The major challenge here is exactly how to combine different types of data in a way which allows neuroscientists to understand the connections, and disconnections, that take place within the human brain. That’s where computational neuroscience, and support from donors like Marc Sievers, comes in.

Sievers gift supports collaboration and training

The Sievers gift will bolster efforts, in particular, in two critical areas: promoting cross-disciplinary scientific collaboration and training a new generation of scientists with the skills and experience to advance knowledge across different fields.

“We are bringing together people with backgrounds in mathematics, physics and engineering, along with researchers in psychiatry, neurology and cognitive neuroscience – and all these people will work together,” says Evans.

The gift will provide the infrastructure needed to support cutting-edge computational science by funding computer programmers and IT experts. Funds will also support outreach initiatives such as an annual international Sievers Symposium on Computational Neuroscience.

“It’s wonderful to work with a donor like Marc [Sievers] who cares about this work,” says Evans. “He’s very knowledgeable about the science, the methods and what we’re trying to accomplish. He gets it.”

The work of McGill’s computational neuroscientists has already led to some notable accomplishments.

New findings in autism and Alzheimer’s disease

A case in point is the work done on autism by Dr. John Lewis, a researcher working in Evans’ lab. He looked at existing data indicating that the earliest signals – or biomarkers – for autism could only be detected once a child was two years old. However, using large sets of data, his research subsequently showed the same biomarker could be identified in the brain at the age of six months – an important breakthrough for early clinical diagnosis of autism and the possibility of timely intervention and therapies.

Another example relates to Alzheimer’s disease, typically associated with a build-up of amyloid plaques (clumps of misfolded protein) in the brain. A member of Evans’ lab, Dr. Yasser Iturria-Medina, now an Assistant Professor in the Department of Neurology and Neurosurgery, used a large, open database to build a model of amyloid propagation through the brain’s connections. Using this model, he was able to show that the buildup of these toxic proteins was not due to amyloid overproduction but rather to a failure of the glymphatic system, the brain’s garbage removal system that clears away amyloid and other detritus clogging up neuronal pathways. 

Those kinds of discoveries are essential for the development of early interventions to mitigate – or even prevent – brain disorders and can speed the development of drug discovery, therapies and treatments for patients. 

Open Science opens new opportunities for discovery

One of the key catalysts driving the development of computational neuroscience is Open Science, the practice of data sharing with the global research community and aggregating complementary global expertise to accelerate the pace of discovery.

“With modern digital technologies and a greater willingness to share their hard won data, brain researchers around the world now have access to huge amounts of data. They can run their own analyses and come up with new findings, so we can get a lot more mileage out of the same data, which is good for society,” said Evans.

Marc Sievers has long demonstrated a keen interest in McGill’s work in neuroscience. In 2011, he established the Ann and Richard Sievers Award in Neuroscience, in honour of his parents. The annual award provides a $25,000 fellowship to a PhD student in the fifth or sixth year of study in the Integrated Program in Neuroscience, supporting young researchers doing innovative research as part of their thesis work and providing additional financial “runway” to complete or extend that work. To date, the awards have supported the work of 10 students who have gone on to apply their expertise to areas that include the discovery of drugs to treat neurodegenerative diseases and the development of highly detailed 3D brain models. 

A history of donor support for neuroscience

The gift from Marc Sievers is indicative of the remarkable commitment of donors to neuroscience research at McGill over many years, which has generated key learnings and understanding of mental health and neurodegenerative disorders. The Ludmer Centre, a partnership between The Neuro (Montreal Neurological Institute-Hospital), the Douglas Mental Health University Institute, and the Jewish General Hospital’s Lady Davis Institute for Medical Research, was established in 2013 through a foundational gift from McGill alumnus Irving Ludmer to improve the prevention, diagnosis and treatment of mental disorders through innovative research.

Three years later, the federal government granted the University $84 million in funding to set up the Healthy Brains, Healthy Lives program to further advance our understanding of the human brain and ease the burden of neurological and brain disorders. The Sievers initiative continues the growth of this booming field at the interface between neuroscience, mathematics and artificial intelligence.

It’s a legacy of excellence in neuroscience at McGill that is not lost on Evans, and he remains in awe of pioneers in the field like Dr. Wilder Penfield, one of Canada's foremost neurosurgeons, and Brenda Milner, a legendary neuropsychologist still going strong at the age of 102.

“Working alongside Brenda Milner is a constant source of amazement and inspiration for me,” says Evans. “I often wonder how I was so fortunate to end up here.”