Grey matter: making sense of the mind

Advances in brain science are allowing for once-unimaginable progress in understanding the mind and fighting against age-related diseases

In August 2013, researchers in Japan constructed the most complex simulation of the human brain in history. The man-made neuronal network, built on the world’s most powerful supercomputers, included 82,944 processors working together for 40 minutes. This represented 1.73 billion nerve cells connected among 10.4 trillion synapses. Yet for all the complexity, the undertaking amounted to just one second of activity in one per cent of the neurons in a human brain.

Recreating the brain’s exquisite complexity is still a major challenge, because scientists have so many questions about how this three-pound organ works: how it endows humans with the ability to walk, talk, see, think, love and remember. Perhaps the best summary of the problem comes from Emerson W Pugh, an inventor at IBM in the 1950s, who said, “If the human brain were so simple that we could understand it, we would be so simple that we couldn’t.”

New insights

Nevertheless, several international research groups are hard at work trying to do just that, studying brain regions at the macro and micro level to map trillions of neuronal connections. A team of cortical cartographers is looking for new insights into neurological diseases and injuries, the process of ageing, and the nature of human emotions and intelligence.

Neuroscientists have made tremendous strides in brain science in recent years, discovering that our senses and emotions – everything that makes a person human – are the result of cascading chemical exchanges between different brain cells. Improved diagnostic tools such as magnetic resonance imaging (MRI) machines, along with powerful computers, have yielded an explosion in neuroscience data in the past decade, explains Dr David Van Essen, Professor of Neurobiology at Washington University in St Louis and past President of the Society for Neuroscience.

But the network of connections among these cells is still largely uncharted territory. The brain contains dozens of types of cells, which send and receive messages among hundreds of thousands of their brethren. Each neuron responds to signals from each of its neighbours, leading to increasingly complex chains of responses. And each person’s brain is different, making the process of mapping them much more complex, says Van Essen. As the principal investigator of the Human Connectome Project, Van Essen is in the fourth year of a five-year project to chart the brain’s wiring and connections.

Like the Human Genome Project before it, the Connectome Project aims to create a basic blueprint that varies for each individual, yet is responsible for shaping our emotions, senses and character. The project aims to scan the brains of 1,200 individuals for four hours each, using four types of MRI machines. Neuroscientists are also studying the subjects’ behaviours, so they can match individual traits and differences with changes in the brain’s physical shape and structure. Individuals are asked to carry out a variety of tasks, including arithmetic, listening to stories, gambling and moving different parts of their body.

Two major publicly funded efforts in Europe and the US, both launched in 2013, will aim to map these mysterious regions. Europe’s 10 year Human Brain Project will cost €1bn and aims to stimulate a new neuroscience research community, with the ultimate goal of emulating the brain’s capabilities in a computer.

The BRAIN Initiative (Brain Research through Advancing Innovative Neurotechnologies) includes a more modest US$100m project to map the brain at all levels – from the individual nerve cells to complex neural circuits.

But Van Essen cautions that these efforts, while ambitious, are not likely to yield the neuroscience equivalent of satellite-view cartography. MRI scanners can see clusters of hundreds of thousands of neurons communicating across millions of synapses, but fine-grained, street-level detail is likely still many decades in the future. “These are exceedingly difficult problems,” he says.

Groundbreaking

Even without a detailed global map, neuroscientists are making new inroads. Researchers in the UAE are leading efforts to understand how the brain changes in the face of degenerative diseases such as Alzheimer’s and Parkinson’s.

In December 2013, Professor Omar El-Agnaf of the College of Medicine and Health Sciences at United Arab Emirates University was awarded an international patent for a new method for detecting Parkinson’s disease and other related illnesses. Parkinson’s is often characterised by the presence of abnormal protein deposits, called Lewy bodies. But these proteins are difficult to see without a microscope. That means Parkinson’s disease is difficult to diagnose. The new patent covers a chemical compound that binds to these abnormal protein deposits in the brain, making them easier to see in an MRI scan.

Milos R Ljubisavljevic, Professor of Physiology at United Arab Emirates University, studies what is known as brain plasticity – the tendency of the brain to rewire itself in patients with movement disorders. She says a method called transcranial magnetic stimulation (TMS) may be able to improve brain performance in patients experiencing normal ageing, Parkinson’s and Alzheimer’s. TMS uses a magnetic field to stimulate brain activity. Several studies using repetitive TMS have yielded improvement, Ljubisavljevic found.

Still, each person’s brain is remarkably different, from the folds in its grey matter to the connections among neurons. Future therapies – and mapping efforts –will have to account for individual variability, Van Essen cautions. And while he says he is “absolutely confident” that neuroscientists can build better maps in the future, it is less clear whether those maps will point the way towards diagnosing and treating diseases.

“That is a huge question, and I hope the answer is yes, but it is not guaranteed,” he says. “Even with imperfect maps, if the maps are good enough and our assessment of the wiring is good enough, we may be able to make a huge difference. But that’s a giant question mark.”