NAVIGATING THE MAPS OF THE MIND

The latest advancements in mind mapping will bring us closer to solving the age-old mysteries of the brain, reports Roger Dobson

Walter Freeman had an unusual method of guiding the knife during a lobotomy. Once through the newly drilled holes in the patient's skull, the knife would snap open like a helicopter blade and gouge out chunks of tissue from whatever part of the brain he thought responsible for the behavioural problems.

Guiding the knife to its target, however, was tricky because, in 1938, comparatively little was know about the higher workings of the brain, and nor were there scans or images that could monitor the progress of the knife. To overcome these seemingly major problems, Freeman, who was not qualified as a surgeon, employed a surgical colleague and used a special guidance technique. According to Robert Youngsom and Ian Schott, authors of Medical Blunders, Freeman, who chewed spruce gum throughout the operating sessions, would crouch in front of the patient, not unlike a baseball catcher, giving his surgical partner operating the knife navigational cues like, "up a bit", or "down a bit".

The surgeons who carried out thousands of now discredited lobotomies on patients around the world between the late Thirties and the early Fifties, knew their patients were malfunctioning because of a problem in the brain, but did not know which bit was to blame. Their shotgun approach often did irrevocable damage to perfectly healthy tissue.

At that time, knowledge of the interior of the functioning brain was sketchy and based largely on observations made during surgery, or culled from the dissection of corpses, or simply based on the intuition of Victorian physicians who had access to abundant experimental material in asylums.

"They never knew whether the region that had been damaged was where the malfunction was or whether they had stumbled across a pathway to it. Without knowing what you are doing you cannot know whether you have knocked out the railway station or the railway line," says Professor Bob Turner of the Wellcome Department of Cognitive Neurology at the Institute of Neurology, London.

It is only during the last decade that the remarkable functional ability and scope of the brain has been understood, and teams of scientists around the world are working on mapping the brain using new technology that will result in an A to Z of the brain comparable in scale and complexity to the human genome project. The knowledge provided will open up new treatments for mental illness, lead to better targeted rehabilitation for stroke victims and help neuro-surgeons navigate their way much more safely through the brain to tackle tumours. It will also assist in a better understanding of a range of necrological disorders, including Parkinson's disease, multiple sclerosis and motor neurone disease.

The target for all this effort, the human brain, is essentially made up of billions of nerve cells, the neurons, and nerve pathways. Latest estimates are that there are 10,000 million neurons in the brain distributed between several thousand modules, with each module responsible for a specific function.

The general roles of the major regions are already known. The cerebellum, for example, regulates the subconscious activities we take for granted, like movement and balance, with a separate region for conscious movement, while the brain stem holds the nerve centres that carry out automatic functions like heartbeat and breathing. What the new wave of brain mappers have been able to do is to harness and, in some cases, develop modern scanning technology to explore the secret, unchartered areas of the brain, to identity the individual sources of all our thoughts, actions and behaviour.

Two types of scanning are currently being used by the mappers. Positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) work by monitoring the blood-flow in different regions of the brain. A third technique which uses infra-red also works on the same principle that when a particular area of the brain is in use it uses more blood.

"When you look at me, part of your brain whirrs into action and tries to recognise my face. When it does, the blood supply to that area increases because the brain needs more fuel for that particular mental activity," says Dr John Wyatt, consultant neonatal paediatrician at University College Hospital, London, who has been working with non-invasive infra-red on babies.

PET and fMRI work in a similar way, monitoring the flow of blood and increased oxygen levels. By getting subjects to perform certain tasks and monitoring brain activity, scientists can match regions of the brain with their specific functions.

Professor Turner, who was one of the inventors of fMRI when he was working in the USA, says, "fMRI works by recognising that blood itself has magnetic properties and when you excite that part of the brain, the blood flows, there is more oxygen and you get a rise in fMRI signals."

The techniques have led to a huge increase in investigatory work by brain mappers. It's been found, for instance, that dyslectics have a much less well-defined area of the brain responsible for visual motion than normal subjects.

"We believe there are at least 10,000 different modules responsible for different functions, but there may be more. Out of that we have probably identified just a few hundred. We have identified the primary sensory areas which handle immediate input from vision, from hearing, touch, smell and taste. We also understand the primary motor area that sends out signals to make sure muscles move," says Professor Turner.

This area, the motor cortex, is a strip running across the top of the head down to just short of the top of the ear. The specific movement areas actually mirror the general structure of the body in that shoulder movement is on top of the cortex and arms to one side, and so on.

Beyond these primary areas, knowledge is still bitty and further complicated by the interactions between zones: taste, for instance, can impinge on memory.

Teams at the Wellcome Department, one of the world's leading centres for this kind of brain-function work, had demonstrated that one part of the brain is highly receptive to facial expressions of fear. Professor Ray Dolan and his team found that the amygdala, located in the left temporal lobe of the brain, responds selectively to fear.

"This is the most direct evidence we have yet had. We also know that people who had this area of the brian damaged may not experience fear," says Professor Turner.

The centre, where Professor Richard Frackowiak is director, is currently looking at systems involved in visual attention. "We have a searchlight inside ourselves which we can direct in whatever direction we intend. At a cocktail party, for example, we can tune into one conversation or another without turning our heads. That brain skill is both fascinating and mysterious."

Another mystery that might be solved by the mappers, is whether babies can recognise their mothers in the first year. Using invisible infra-red technology it's now possible to look into the brains of babies to see what parts of their brain are functioning in response to stimuli.

It's known that after the first year, a baby's eyesight is comparable in performance to an adult's but, before that, it is an unknown quantity. At University College Hospital, babies have been shown an image of the mother and a mixed-up image. Each time, the baby's reactions are measured.

The technique has been used on 10 babies, and further work is planned. If successful, Dr Wyatt and his team plan to look at the development and evolution of other senses in the baby brain, including hearing and touch.

At the Institute of Neurology, Professor Turner and his colleagues have no doubts about the value and implications of their work. He says it is a project on the same scale and importance as the human genome.

"Until we know how the whole system works we are just scratching around. There are a wide variety of psychiatric disorders which are the scourge of humanity but, at the moment, our treatments are pretty speculative ... lithium to treat depression when we really don't know what it does; ECT which is even more of a shotgun approach; and the treatments of schizophrenia are also broad spectrum. Until we understand what each area of the brain does and how it malfunctions we cannot target our treatment as well as we could."

He says that mapping will also give psychiatrists more of a scientific tool. "Until now they have been in the position of a car mechanic who is asked what is wrong with the car when he has only been able to listen to the engine and sniff the exhaust. We are now opening the bonnet for them."