Will we ever understand the human brain?

Will we ever get our minds around the brain? We know what it’s made of (77% water, for a start) and how much it weighs (about 3 pounds, generally). We also know that it has somewhere in excess of 80 billion neurons, each one connected chemically and electrically with 10,000 others, creating the world’s most complex network, with more interconnections (1,000 trillion synapses, give or take) than there are stars and planets in the Milky Way.

But how, exactly, does it all work? How does the brain cause our hearts to beat, or make us happy, breathe without thinking, fall in love, fear spiders, see, dream, learn, remember, taste, feel or smell?

And, perhaps most crucially, where in among all that neural spaghetti can we find our mind – our individual consciousness and sense of self?

Soul-searching
These are some of the big questions that philosophers and scientists have been grappling with ever since René Descartes proposed that mind and matter were not the same thing, and that human activity was the product of a dualism in which the mind – aka “the soul”, in the 17th century – controlled the body.

Since then, answers have been few, incomplete and far between. But at this year’s Annual Meeting of the New Champions in Tianjin, China, the spotlight will be shone on global developments in neuroscience. This highlights the fact that we may finally be on the cusp of what many believe is a revolution in our understanding of how our brains – and our minds – work.

The mission to understand the brain has suddenly taken centre stage globally on a scale reminiscent of the vast collaborative effort that in 1969 made it possible to land a man on the Moon. The final frontier, it turns out, is to be found in our own little understood internal space.

A year ago, scientists from more than 130 institutions began collaborating on the 10-year Human Brain Project. Funded by the European Union, its aim has been to develop new computer technology to distill all human knowledge about the brain into a full-scale computer model, in the hope that this unified picture of the brain will lead to a greater understanding of brain diseases.

Understanding Alzheimer’s
This is important work, socially and economically. As medicine improves and lifespans lengthen, age-related brain diseases such as Alzheimer’s are putting an increasingly intolerable strain on communities and their resources.

In the United States, meanwhile, the government has pledged $100 million for the first year alone of its BRAIN initiative – Brain Research through Advancing Innovative Neurotechnologies. This vastly ambitious project, launched by President Obama, aims to “give scientists the tools they need to get a dynamic picture of the brain and better understand how we think, learn and remember”.

So why now? And how come our understanding of the brain and the mind has lagged so woefully far behind our grasp of how all our other components function?

“We know much less about how the brain works than we do about the heart, liver or kidneys,” says Thomas Insel, a psychiatrist who heads the National Institute of Mental Health in the United States, and who will be at the Annual Meeting of the New Champions in September.

Why? The complexity of the brain dwarfs that of all our other parts “and we have not had the tools we have needed to be able to study the brain in the kind of detail that we’d like”, points out Insel.

In fact, the very first project in the BRAIN initiative is a stock-taking exercise – a cell census, designed to catalogue the number and different kinds of cells in the human brain. “Believe it or not,” says Insel, “we actually don’t even have that yet, though it’s something you’d think would be fundamental.”

Until recently, says Katerina Fotopoulou, a senior lecturer in the Psychoanalysis Unit at University College London and director of the International Neuropsychoanalysis Centre, brain science has been all about “studying the dead brain. It is only since the nineties that we have been able to study not only the brain alive, but functioning.

Falling in love
“You no longer look at a brain only for its anatomy, the kind of cells it has, the kind of chemistry it uses, but you are actually looking at it functioning – while a human being is falling in love, for instance, which we have never before had the ability to do.”

Marlene Behrmann, a professor of cognitive neuroscience at Carnegie Mellon University, who will join Insel and Fotopoulou in Tianjin, agrees that “despite decades and decades of research we still have only a rudimentary understanding about brain function”.

Science has, she says, “managed to get some traction on some issues”, such as how a single neuron works, so we have “some really clear understanding at a very basic level”. At the opposite end of the scale of complexity, “we’ve gotten really quite good at being able to describe human behaviour” – such as tracking brain activity related to hand and eye movements and understanding how people solve certain problems, like addition and subtraction.

But the big question now, she says, “is the rest of the continuum between those two extremes” – and scientists are finally ready to exploit technological developments that began in the nineties and are now coming of age.

“We’ve had windows opened to us that have offered really unprecedented opportunities to delve into the human brain and it’s taken 10 years for people to be able to utilize these methodologies and approaches to begin to make progress.”

For the top slot in a hit parade of most significant technological developments, she says, most in the field would nominate brain imaging in humans. But while functional MRI “has opened up new vistas, it’s a little bit arbitrary to say that it alone is the harbinger of all good because it would not have been possible without developments in computer science, statistics, physics and biomedical engineering”.

Thorny questions
Scientists shy away from words like “revolution” but, if we are not exactly on the cusp of one in neuroscience, says Behrmann, “we are certainly on the ramp. We have a long way to go but I think we’re making really good progress. The questions are deep, the questions are really thorny, but it’s an extremely exciting time to be in this field”.

And, she believes, it is cross-disciplinary cooperation that is going to make all the difference.

“There has been a real shift in approaching this problem from an interdisciplinary perspective. So we have engineers, and clinicians and neurobiologists all working together and bringing their own expertise to the problem and there’s a non-linearity – a kind of super additivity – in having the conjoined input from these different disciplines.”

There is no shortage of dramatic examples of the progress that is already being made. Last year scientists at MIT reported that they had successfully implanted a false memory of fear in mice, while at the University of Pittsburgh’s Motor Lab, research in the field of brain-computer interfaces has seen patients operating complex prosthetic arms solely with the power of their minds.

For Insel, one of the best examples of cross-disciplinary cooperation is the CLARITY project at Stanford University. By taking brains that have been donated for medical research and replacing the fat with a clear gel, it has bypassed the traditional need to “slice” the organ – either electronically or literally for microscopic examination – allowing transparent brains and their connections to be studied in their entirety.

As he noted in his NIMH blog, Insel believes CLARITY will “revolutionize neuropathology, opening a new era for studying the neural basis of mental disorders”, and already, the technique has identified previously unseen unusual connections in the brain of someone with autism who died.

The breakthrough was possible, he says, “only because of a materials scientist, somebody who works on hydrogels, getting together with people who have been doing neuroanatomy”.

For Morten Overgaard, a professor in cognitive neuroscience at Aarhus University, Denmark, who is working on theoretical models to better understand the relationship between the brain and the mind, “lots of good things” will doubtless come out of the increased interest in the brain.

Who are we?
But, while “we may be able to get better at discovering serious diseases in the brain and maybe better at helping people with various brain injuries”, he believes part of the refreshed interest in the field is because “we desperately need some sort of explanation about who we really are” – and that greater understanding of the structures of the brain is unlikely to provide the answers for which human beings have been searching for centuries.

“If you open up a skull and look really hard you won’t suddenly see subjective experience down there,” he says. “So in a sense it’s very obvious that you don’t make progress on the mind-brain problem just by looking at the brain at a more detailed level.”

There might, he thinks, be a chance for progress “if we dare to come up with some theoretical models different to those that simply claim that consciousness is created by the brain, because there seems to be no logical way for us to really understand what that would mean”.

Ultimately, though, we should be prepared to accept what for some is blasphemy – that even with all the investment and cross-disciplinary cooperation in the world, science might not be able to provide all the answers.

“When it comes to the essential question of the mind-brain problem, very little has happened in the sense that the question of consciousness and why we have subjective experience seems to be just as mysterious now, even with all this progress, as it was 100 years ago,” says Overgaard.

“We have assumed that physical science can do everything, that it is stupid even to argue that there might be something beyond that reach. Maybe what we need to do now is look at those assumptions a little bit closer.”

Author: Jonathan Gornall is a writer who specializes in health.

Image: A laser-etched lead crystal glass artwork by Katherine Dowson entitled Memory of a Brain Malformation is seen at an exhibition at the Wellcome Collection in London March 27, 2012. REUTERS/Chris Helgren