Significantly, the project will produce maps not for one brain but for those of 1,200 healthy participants, some of them siblings, including twins. The strategy is designed to tease out how genes and life experience can act to make each human brain – and therefore each human being – unique.
“There is a fair amount of variability,” Dr. Toga says, in the way different brains are wired. “We have to understand the origins of that variability.” That, in turn, will help researchers make sense of what is going on in brains that are not working properly, and look for ways to effect repairs.
The fine-scale mapping of the Human Connectome Project will complement other emerging techniques that can reveal both the activation of brain cells under various circumstances and the underlying connections between them. The result gives researchers a better sense not only of how the brain looks as a giant circuit, but can expose which neural pathways are used and for what purpose – the property known as functional connectivity.
“Just because there’s a wire between two areas doesn’t mean it’s used,” says Tim Murphy at the Brain Research Centre, based in Vancouver. “By looking at functional connectivity, we’re reflecting the strength of connections.”
Researchers in Dr. Murphy’s lab are exploiting a powerful new way of mapping functional connectivity called “optogenetics.” It involves using the methods of genetic research to coax different classes of brain cells to make proteins that are sensitive to light. Then, they can be triggered simply by being exposed to a light source, giving scientists a direct way to see what role the cells play in different brain functions, from motor control to sleep.
Previously, “we were more or less spectators, with respect to brain activity,” Dr. Murphy says.
Researchers have also manipulated the DNA of brain cells to create fluorescing proteins that can glow, depending on the cells’ changing conditions, allowing researchers to observe the cells with high-powered microscopes. In the past, says Yves De Koninck, who specializes in the method at Laval University, neuroscientists were reduced to guesswork – cutting away bits of research animal brains to see what happens.
Now they can watch cells in action, which has “revolutionized our ability to probe the brain and understand how it works.”
The genetic revolution is pushing brain science forward in many avenues, exemplified by work at the Allen Brain Institute in Seattle, supported to the tune of $500-million by Microsoft co-founder Paul Allen. The institute has shouldered what Dr. Murphy calls the “grunt work” of developing a massive atlas of the mouse brain that can be linked to specific genetic mutations and serve as a crucial reference for work on neurological disorders in humans.
Of equal importance to researchers is the revolution in bioinformatics, which brings the power of 21st-century computing to the massive amounts of data needed to comprehend the inner workings of the brain. Looking still further, some neuroscientists continue to pursue the elusive goal of simulating the brain in its entirely as a computer program. The task is daunting, says Chris Eliasmith, director of the Centre for Theoretical Neuroscience at the University of Waterloo, in part because with 100 billion neurons capable of forming thousands of connections, the complexity of the brain dwarfs its would-be digital mimics. “The single biggest challenge is trying to reproduce the amount of communication that there is in the brain,” he says.
That has not held back Henry Markram at the Swiss Federal Institute of Technology in Lausanne from proposing the Human Brain Project, a massive effort to incorporate everything known about the brain in a massive computer simulation. Some experts question what it will show, but the project is shortlisted for as much as a billion euros from the European Commission over the next decade.
Even if Dr. Markram doesn’t succeed, the number and scale of brain-related projects now emerging suggests a turning point for the field, a sort of “Galileo moment” that could open the workings of the human mind as never before.
Funding here remains modest, but opportunities for Canadian researchers abound, Dr. Kaplan says, in part because what the field needs most is not just big money, but fresh thinking.
“What we’re best at in Canada is coming up with new ideas.”
With Brain Canada and others providing a push, he hopes that enough of those ideas will come to fruition to turn the brain’s inner space into a universe of discovery.