Reshaping Brain Theory

By Chris Rogers

neuroscientist randy Macintosh is driving urgently needed innovation around brain health

With Ontario’s population getting older, innovations in the CNS (central nervous system) fi eld, which deals primarily with diseases and repercussions of the aging brain are becoming more important than ever.

Located at Baycrest, a world leading academic health science centre, RRI (Rotman Research Institute) is at the forefront of this fi ght to understand how the brain ages and mitigating the factors surrounding the development of diseases such as Alzheimer’s and problems such as stroke. By bringing together world-renowned researchers in a broad spectrum of disciplines, from cognitive neuro-psychologists to computer scientists, RRI is able to tackle its goal of comprehending the workings of memory and the executive functions of the brain.

“The focus of the research institute at Baycrest is to understand both the aging brain as well as age related diseases and disorders,” said Dr. Randy McIntosh, senior scientist and director of RRI.

Dr. McIntosh is a leader in the CNS fi eld. His own research is geared to the development of a unifi ed theory of brain operation that emphasizes the integrative capacity of the brain.

“The idea is to understand how different kinds of mental functions change as we age, how they can be worse if there is accompanying disease but also understand ways to try to stave off that change,” he explains.

Part of his research focus is to understand the neuro-basis of those changes in terms of cognitive theories for memory and attention.

“The main component of that, using modern neuro-imaging technology [is] to then use that information to develop more effective ways of staving off the declines, that’s with cognitive rehabilitation strategies as well as remediating it if there is a more protracted kind of decline that comes with things with mild cognitive impairment, dementia and/or stroke, and then tracking the effi cacy of those therapies again going back and using the neuro-imaging technology as a way to validate that these therapies have direct benefi t.”

The benefi t of working at an institution such as RRI is that it brings together a group of researchers from a diverse range of disciplines, all devoted to solving a common problem. The varied backgrounds of the scientifi c staff at RRI allows for unique solutions to be engineered.

“If you address that problem from a number of different perspectives, the solutions to that problem end up being much more innovative then they would be if they were addressed with a typical kind of constrained focus from a given discipline,” says MacIntosh.

In trying to understand memory, he explains that the typical approach is to let psychologists address it in a traditional environment such as a university. But the idea behind RRI has a much broader scope. A diverse group of psychologists, engineers, neurologists, physiologists and computer scientists, all approach memory from different avenues with their contrasting backgrounds allowing them to foster new solutions.

“What you do is have the same problem but address it from different perspectives and that brings different ideas to the table, and you end up coming up with solutions that would not be possible if you focued on only one particular way of looking at the world,” said McIntosh. “It’s the idea of bringing different perspectives to the same problem and coming up with innovative solutions, I think it’s what differentiates the kind of work that we do with some other places.”

He is quick to point out that this approach is also true for other research institutes across Ontario.

“There is this idea of plasticity or adaptability that’s in brain function throughout life, and what that does is it actually provides the potential, I guess you could almost say hope that you can make use of that flexibility, then potentially remediate cognitive function.” — Dr. Randy McIntosh

At RRI, perhaps the best example of this process incorporates a combination of strong cognitive theory and modern neuro-imaging technologies while looking at the computational or informatics aspects and trying to merge theory with data to develop large-scale computational models of the brain and how it changes as we age.

“One of the next focuses is developing what’s been called the virtual brain which is actually a model of the human brain that allows us to understand not only how the brain functions in a normal state but also how the brain functions as we age,” said McIntosh. “You can make a virtual brain that actually ages, a virtual brain that gets Alzheimer’s disease, a virtual brain that gets a stroke, and develop the algorithms that help explain how the brain tries to adapt to age and adapt to damage and disease.”

McIntosh explains that the brain is designed based on the structural information they are collecting from neuroimaging at RRI in combination with functional information and brought together with high-level mathematics to model the brain in action.

“We’re really merging the math with the ‘wet-brain’ as it were, architecture would then put the necessary dynamics in that are captured in the math that drive the model,” said McIntosh.

Trying to explain the way the model works to someone not in the know can be a trying experience but McIntosh breaks it down.

“You get a structural MRI, for example, that you can use to image the connections in the brain. Then you use that as your architecture and then impose the dynamics on top of that using the neuro-network theory.”

“The virtual brain actually ends up being an amalgamation of both normative data but also the clinical that we have access to as well,” he said.

Bringing the research back to its real-world applications and the looming concerns of an aging population, the end-goal of the research, at least in terms of clinical research, is prediction. People generally associate Alzheimer’s disease with the aging brain but what about those who develop these diseases in their 40’s?

“The idea would be to use the virtual brain as a way of testing whether that person is showing some kind of random abnormality, over and above what you can see with the regular clinical imaging.”

He explains that using the information gathered from the neuro-imaging technologies and apply a specific persons characteristics to the virtual brain. From this, researchers can then compare brain functions in the virtual environment to see how the virtual brain’s patterns show similarities to someone who has, for example, dementia.

“It ends up being a sort of diagnostic tool and a prognostic tool,” said McIntosh. “Because in theory, you could use that virtual brain to help guide the course of therapy to help decide what potential pathways you could try and invoke. In a stroke for instance, to facilitate those pathways to help the brain recover. “

And don’t take those comments the wrong way, recovery is definitely what they’re after.

Previously, it was thought that the brain didn’t change after the first 20 to 25 years of life. RRI is leading the charge to reshape that theory.

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