August 14, 2011
The Economic Times
Hari Pulakkat

New research is showing that ageing of the brain can be slowed down. The trick is to challenge your brain. Some clues on how to do it: physical exercise, a rich social life and an interest in the arts.

For nearly five decades, Michael Merzenich had been obsessed with one idea: plasticity of the adult brain. During the 1970s, he was the first in the world to show that the brain can rewire itself even at an advanced age, thus overturning a centuriesold notion that it is hardwired within a few years of birth.

Now 68 years old and professor emeritus at the University of California in San Francisco, Merzenich has not stopped thinking about the topic. His most recent research goes deep into the mechanism behind this rewiring, and is as fascinating as it was when he first announced adult brain plasticity to the world.

In his recent set of experiments, Merzenich took rats that had only a month left to die. Their brains were old and in a mess. His colleagues saw and documented 20 age-related deficits in their brain cortex known to be important for cognition. The rats were deficient neurologically, physiologically and chemically. They were slow, dim-witted and made frequent errors of judgement.

Merzenich and his colleagues then put them through a set of specially designed exercises for one hour every day for 30 days. “We found that every aspect of the brain that had been impaired was reversed with training,” says Merzenich. The rats were still old but their brains were made to look relatively young.

Training the Mind
Forget the rats for the moment. Neuroscientists around the world are now discovering that the human brain can be trained just as we train our bodies, and that our brains do not necessarily need to decline as rapidly as they do as we age. More interestingly, just as Merzenich showed with the rats, scientists have shown that mind training could reverse age-related cognitive decline of the brain.

They say that it can speed up our brains, improve our working memories, enhance our capacity to pay close attention and increases our fluid intelligence (the ability to solve new problems). Merzenich, however, goes beyond all this. He thinks that we can even treat diseases like schizophrenia through mind training, and is now in the middle of a clinical study to prove his claims. “The results so far strongly indicate a benefit,” he says.

Merzenich’s San Francisco-based company, Post Science, develops software that claims to train the mind intensely and partially reverse the effect of ageing on the brain. Posit Science was formally set up in 2003, but its genesis goes back at least a decade to the software that Merzenich haddeveloped to tackle childhood learning deficits (Merzenich had also developed the first cochlear implant).

The company has since been joined by a few others around the world. Lumosity in the Silicon Valley raised $32.5 million two months ago in venture capital funding; it has 15 million online users, including a few thousand in India. Cogmed in Sweden was set up by Pearson 10 years ago, based on research by Torkel Klingberg, professor at the Stockholmbased Karolinska Institute, one of Europe’s largest medical universities. The US market research firm SharpBrains estimates the market for mind training software at around $295 million in 2009 and growing at over 30% every year.

Scientists at the Karolinska Institute – not Klingberg’s group – last week published (in the journal Science) the results of a study that showed memory training to increase the production of dopamine, a chemical that is necessary for the modulation of several brain functions, including working memory. Brain imaging showed the dopamine production increasing just after the training, a hint that training can improve working memory, which was also borne out in tests.

Klingberg himself has published two years ago another study in Science that showed an increase of dopamine receptors after mind training. Says Klingberg: “There is now evidence to show that both young adults and older people can improve their working memory with training.” In both the studies, working memory was seen to improve for tasks that were not part of the training.

The Dopamine Factor
Working memory is the ability to hold bits of information briefly in the brain while performing a task. Poor working memory translates into several mental deficiencies like not being able to follow this sentence, the inability to remember names, or not being able to plan your next business strategy. Working memory capacity, as with several other aspects of the brain function, declines roughly at the rate of 10% a decade after the 20s. Which is why we become inefficient at many tasks as we age.

Scientists can now see this deterioration through imaging, which shows that the number of dopamine-producing neurons decreasing with age in the prefrontal cortex, an area of the brain that is involved in many complex mental activities. Mind training can slow down or reverse this process partly. “We can increase working memory capacity by 15% with training,” says Klingberg, “which corresponds to 15 years of loss.”

For a long time, psychologists and neuroscientists had recognised a critical period in the development of a human being. They thought that environmental stimuli during this period determined how a child’s brain was organised till the end of life. If you keep one eye of a child shut between three and eight months of age, it would remain blind forever even if opened later.

Neuroscientists discovered in the 1960s that, although one eye is blind, its processing area in the brain is quickly taken over by the other eye. But even those who discovered this plasticity – and won a Nobel Prize in the bargain – initially denied its existence in adult brains. Merzenich, through a series of ingeniously constructed experiments, showed that the brain reorganises its structure even in adult life.

New Neurons
By the 1980s and certainly by the 1990s, neuroscientists had accepted adult brain plasticity. But its effect on cognition still remained in doubt. They knew that cognition declined with age; they were not sure how much plasticity could compensate for this decline. How profusely can the brain grow new connections in later life? How can we increase the production of neurotransmitters, which determine brain health and decline with age?

Neuroscientists seemed sure – many still are – that the adult brain would not produce new neurons. This notion has been shown to be wrong for the hippocampus, which is involved in the consolidation of short-term memory into long term. Generation of neurons in the adult cortex is still a matter of debate. But we do know that neurons in the cortex grow new connections abundantly. And that we can stimulate this growth with the right kind of exercise.

Our early years are a period of intense learning. The brain cells respond to this learning by growing connections luxuriantly. After the 20s most people set their learning on cruise mode, and try to confine their knowledge acquisition to narrow ranges. Economists stick to economics, linguists stick to languages, musicians stick to music, businessmen stick to business.

Few people keep learning new things the way they did till their 20s. Our brains then settle into a rut from which it is difficult to extricate. Neuroscientists now think that the brain would respond well even in later life if challenged sufficiently, and that this response can partially compensate for age-related cognitive decline.

“The non-diseased brain is far more likely to waste away with underuse than it is to wear away with overuse in later life,” says Norman Doidge, Toronto-based psychiatrist and author of the international bestseller The Brain that Changes Itself. So we could keep our brains in shape by constantly learning new things in new areas, but mind training might do better.

Brain Plasticity
Good brain exercises are cleverly designed to concentrate long periods of mental activity into short periods of intense training. Companies like Posit Science, Lumosity and Cogmed have teams of scientists developing training programmes that are designed to stimulate the brain just the right amount for an individual. “When we try to enhance cognitive performance,” says Joe Hardy, vice-president of research at Lumosity, “we try to improve the brain’s ability to do every day things that we really care about.”

This list would include working memory, visual perception and fluid intelligence, among other things. Over 30,000 research papers now document brain plasticity; a few recent studies show the impact of mind training on brain function. A Mayo Clinic study in 2009 – funded by Posit Science – showed a doubling of speed and accuracy of brain processing when compared to a control group.

Another study by University of Michigan scientist Susanne Jaeggi and her colleagues, published in the journal PNAS in 2008, showed an increase in fluid intelligence that was carried over to tasks quite unlike those in the training module. Yet one study by the BBC, published in the journal Nature last year, served a note of caution.

It showed no improvement in brain capacity, but neuroscientists have widely criticised this study as flawed. It had taken young and motivated students at their peak and trained them only for 10 minutes, three times a week, for six weeks. “We know that mind training works when done intensely for a long time,” says Klingberg.

Scientists involved in mind training focus their attention on the cortex, which is the part of the brain involved in higher learning. Academic neurologists in their research look at other parts of the brain as well, and find often surprising responses to training. At the National Centre for BiologicalSciences (NCBS) in Bangalore, Sumantra

Chattarji has been investigating plasticity in the amygdala and the hippocampus.

The amygdala is involved in emotional response and the hippocampus in the consolidation of short-term memory into long term. Growth of nerve connections in the amygdala produces strong emotional memories and fear, while similar growth in the hippocampus consolidates memory faster.

Magic Drug
Chattarji put his rats in enriched environments that stimulated their brains. These rats developed more connections in the hippocampus, but growth was suppressed in the amygdala. “This is exactly what is required for cognitive enhancement,” says Chattarji, who has presented this finding last week at the Gordon Research Conference in Maine, US.

An enriched environment for humans would include physical activity, continuous learning, strong social life and a deep interest in the arts. There is an Indian twist to this story as well. Chattarji thinks that cognitive enhancement drugs should work this way too, if they work at all.

Specifically, the plant Brahmi is supposed to enhance memory, and Chattarji thinks it should have the same effect on brains that enriched environments have. He is in the middle of experiments to prove this hypothesis, but is not yet ready to discuss the findings.