‘The thing about the brain is that everyone has one,” says Rob DeSalle, a curator at the American Museum of Natural History, when explaining the universal appeal of the exhibition Brain: The Inside Story.
Surely, the brain is an easy sell no matter where you are, but it’s especially fitting that the show, which was developed in New York, has now come to Toronto, a city where brain research is rather a big deal and lately getting bigger.
This may not be apparent to those outside the city’s scientific and medical research communities, in part because, unlike some cities – Montreal and Seattle come to mind – Toronto does not have one single institution that acts as a focal point for its brain science.
Instead, the local brain game is played in a range of hospital and academic labs. Many (though not all), are linked to the University of Toronto, which, in North America, ranks second only to Harvard University in publishing studies related to neuroscience and behaviour.
The distributed nature of the community means the city is not as well recognized for its neuroscience as it could be. But it also means there’s a diversity and a liveliness to the brain research going on here that invites interesting collaborations and sets the stage for genuine discoveries.
“The depth of the system makes it very rich,” says Donald Stuss, president and scientific director of the Ontario Brain Institute, which was created in 2009 in part to help connect and accelerate brain research across the city and the province.
And, as Brain: The Inside Story demonstrates, it’s a very interesting time to be working in the field.
A generation ago, scientists tended to resort to metaphors when describing what the brain might be doing. Now, parallel revolutions in genetics, computer science and neuroimaging have allowed researchers to lift the hood and examine the engine of our thoughts more directly. Increasingly, they are dealing directly with the molecules, cells and circuits that allow the brain to function. This, in turn, is shedding light on brain disorders and neurodegenerative diseases, and pointing the way to new treatments that are rooted in an understanding of our mental hardware.
Worldwide, the change has drawn more funding from governments and philanthropic groups who are sold on the idea of a brain revolution. It’s also drawing in a generation of researchers eager for a share of the scientific glory and the thrill that comes with being among the first to understand the brain in a new and deeper way.
As a global research hub, Toronto’s brain science is feeling the influence of new ideas, new methods and new money. To get a snapshot of the brain revolution in progress, here’s a quick tour of some of the most interesting neuroscience going on around town.
Before you can use your brain, it needs to be assembled, a remarkable feat of bioengineering that is the focus of research in Freda Miller’s lab at SickKids Hospital.
“Your brain starts as nothing more than a layer of little round stem cells,” Dr. Miller tells me as we look at images taken from embryonic mouse brains that trace how these generic stem cells grow and migrate out of that layer to become the vast interconnected network that is a working brain.
She has worked as a scientist in the U.S. and Montreal, among other places, but Dr. Miller says she finds Toronto particularly strong in the basic biology that relates to her own research, which links brain function and development to the fundamentals of cell growth.
By inserting genes to make stem cells light up when they are active, Dr. Miller can track the brain’s construction and renewal, a process known as neurogenesis. Her lab has been breaking new ground in connecting this process to genetic mutations and adverse effects in utero that can subtly divert brain development just as it’s getting under way.
Not only does this seem to account for developmental disorders, such as autism, conditions generally thought of as adult brain disorders may trace back to this very early stage in brain building.
Learning captivates Kenichi Okamoto, a Japanese neuroscientist who came to Mount Sinai hospital after a stint at the Massachusetts Institute of Technology. He was attracted here by the freedom to explore new methods of research without the intensely (and sometimes adversely) competitive atmosphere he found in the United States.
His work is directed at the question of how the brain acquires information, a fundamental process that allows us to function in the real world and adapt to new situations. “We still don’t know exactly how this happens,” Dr. Okamoto says.
To address the mystery of learning, he is making use of a set of nifty new tools that are currently transforming neuroscience. One is two-photon imaging, a kind of high-resolution microscope that allows him to zoom in on a single synapse – the connection point between two brain cells. Another is optogenetics, which involves genetically manipulating brain cells so that they can be switched on and off at will by exposing them to light.
Armed with these technologies, he is both observing and experimenting with synapses, working out how these microscopic triggers allow the brain to function something like a digital computer, but with far greater flexibility. The lab includes room-sized microscopes, where younger researchers can be found zooming in on the individual branches and synapses of a single brain cell with astounding clarity.
Each brain cell can have thousands of synapses; Dr. Okamoto and his team are exploring how the activity in one synapse can boost or inhibit the activity of others nearby. This cross-communication, he suspects, is key to understanding how some neural circuits are boosted at the expense of others, enabling the brain to adjust its responses to new inputs and, ultimately, allowing us to learn everything from nursery rhymes to calculus.
SEEING IS PREDICTING
There are many ways to image the brain. For Aristotle Voineskos, a neuroscientist at the Centre for Addiction and Mental Health (CAMH) and a Toronto native, one relatively new approach has proved especially revealing. It’s called “diffusion magnetic resonance imaging,” a kind of MRI that shows, among other things, how water molecules are moving around in the bundles of nerve fibres that connect brain regions to one another.
Dr. Voineskos has become an expert in probing those connections down to individual brain circuits. When connections are well formed, he says, water tends to flow in the same direction as neural signals, allowing researchers to see how the brain talks to itself in real time.
This kind of imaging may reveal how the brain malfunctions in mental disorders that are not tied to one specific brain region. For example, it’s relatively easy to
see where the brain has been damaged by a stroke and work out how that may affect cognition. But where in the brain is schizophrenia?
At CAMH, Dr. Voineskos wants to put the technique to use in new ways, by using it to chart and predict pre-existing vulnerabilities to mental illness. To that end, he is now leading a $5-million project funded by the U.S. government’s National Institute of Mental Health for a study of social cognitive impairment, a condition that can prevent individuals from properly reading a range of emotional cues communicated by others, from a parent’s smile to a sarcastic remark. The study will use imaging to help get at what happens in the brains of people who lack that ability.
“The key point is that once we identify the impaired circuitry, then we can target it through treatment,” he says.
At the University Health Network, Andres Lozano is not just looking at neural circuits in the brain, he’s manipulating them. The technique is called deep brain stimulation (DBS), a therapy in which Dr. Lozano is a world leader.
“We can choose any circuit in the brain and we can adjust the activity in that circuit,” says Dr. Lozano, who was born in Spain but immigrated to Canada as a child.
The method involves inserting a small electrode through the skull and placing its narrow tip adjacent to the desired circuit. The activity of the circuit can then be boosted or diminished by applying a small electric charge.
DBS has gained attention as a way of forestalling the tremors associated with Parkinson’s disease, a situation caused by a malfunction in the circuits controlling movement. It has also been applied to mood circuits that are related to depression, or to boost activity in circuits that are deteriorating as a result of the onset of Alzheimer’s disease.
But what is equally fascinating to Dr. Lozano is the use of the method to probe circuits whose roles are not yet understood. In one instance, he was able to identify a brain region that, when stimulated by DBS, causes patients to recall childhood memories.
“It’s like exploring a new galaxy or a new planet, where you go to someplace in the brain where no one has ever been before.”
As we learn more about how the brain works, it seems inevitable that we will try to build one from scratch. One Toronto researcher at the forefront of this quest is Randy McIntosh, director of the Rotman Research Institute at North York’s Baycrest Centre.
Dr. McIntosh leads an international project called The Virtual Brain, which he describes as “a platform that allows you to simulate the human brain using real data.”
At its heart the project is a computer program, a virtual network that can be adjusted to mimic the responses of a particular individual’s brain to various inputs. If the person is suffering from a brain disorder, the idea is that the simulation can be used to recreate this and then provide a way to test different approaches to treatment.
It can also be used to create art. Dr. McIntosh is bringing a version of his project called “My Virtual Dream” to the Ontario Science Centre this weekend, where it will harness the brain waves of visitors to drive a dream-like visual sequence. He previously has brought the experience to Nuit Blanche, where he found the results intriguing.
“It’s the individual differences that make the whole thing quite interesting,” Dr. McIntosh says. “In a large public installation, you can really get a handle on that in a way that you can’t really do in a lab.”
Brain: The Inside Story is at the Ontario Science Centre until March 29. This weekend, the centre is hosting BRAINFest, featuring local neuroscience experts discussing current research along with brain-related activities for all ages.