Tue, 29 Nov 2005 12:00 CST
Our brains form a million new connections for every second of our lives. It is a mind-blowing statistic, and one that highlights the amazing flexibility of our most enigmatic organ. While the figure emphasises how much we still have to learn about brain structure, it also reveals the huge importance of our everyday experiences in making our brains what they are.
Anatomy, neural networks and genes are yesterday's hot topics. Today, neuroscientists are increasingly concentrating on how the way we live our lives creates profound and often long-lasting changes in the structure and connectivity of our brains. They are focusing on how influences as diverse as our emotions, environment, social interactions and even our spiritual lives help make us tick.
To reflect this shift, the Society for Neuroscience in Washington DC last week invited a leading religious figure to open its annual meeting for the first time. The Dalai Lama spoke of ethics and responsibility in scientific research, but he was ostensibly there to tell how meditation, a mainstay of Buddhist practice, could influence our minds and change the structure and activity of our brains, perhaps permanently. Buddhist traditions have developed techniques training people to think compassionately, he told thousands of assembled researchers. And these may be reflected in observable synaptic and neural changes in the brain.
Sara Lazar of Massachusetts General Hospital in Charlestown presented the details of one such study. Certain brain regions were thicker in experienced meditators, notably the prefrontal cortex, important in higher thought and planning, and the insula on the right side, a region that integrates emotions, thought and senses. The thickening may be caused by new connections, support cells, branches or blood vessels, she says, but whatever the cause, the effect seems to reverse the usual cortical thinning that occurs with age. "It is a real effect to do with meditation experience," says Lazar.
Nature and nurture influence each other, but there is growing interest in finding the details of exactly how our brains can be permanently altered by our experiences. In part, this resurgence has arisen with the ability to make quantitative measures, as opposed to the subjective reports of people's experiences we once relied on, says Lazar. The completion of the human genome project and the decade of the brain initiative -designated by the US Congress in the 1990s - have also made people realise the huge complexity involved in the interaction between genes and experiences.
"Experience modulates gene expression, which leads to substantial behavioural differences," says Charles Nemeroff, a psychiatrist from Emory University in Atlanta. It's quite a new idea, he says, and we are at last describing some of the mechanisms, such as epigenitics, through which environmental factors - whether birth trauma, bad parenting or toxins - can have a long-lasting effect.
His study of 681 people who had suffered major depression for an average of eight years highlighted how significant early life events could be on later mental health. "If you look at measures such as loss of a parent through death, divorce or separation; abuse, either physical or sexual; or neglect, only one-third of patients had no trauma," he reports. "Two-thirds suffered early life trauma. We have to consider this as a risk factor."
Several studies have also linked early trauma to substance abuse, personality disorders and anxiety disorders. Nemeroff suggests the origins may be physical changes in the way people respond to stress. His studies have shown women with depression who also suffered an early trauma responded differently to a stress test, such as speaking to a hostile audience, or perform a taxing serial arithmetical calculation. "It took their cortisol levels sky high," says Nemeroff. Those with depression but no trauma, however, responded normally: their levels were raised but not as high or for as long. A study in men, which is being prepared for publication, shows the same result.
Early trauma seems to cause changes in the brain too. In imaging studies of the emotion centres, the response of people to positive and negative images was analysed. Those who had been through an early life trauma had a blunted response to positive stimuli and heightened reactions to the negative. There were also structural changes in the hippocampus, an area important for learning and memory. Some of these changes have been reported in depression before, Nemeroff points out. "But I am beginning to wonder whether other findings about depression are actually about early trauma. I have no doubt that this is a totally different pathological sub-type."
On the flip side, if experiences can trigger the problem, then perhaps experiences can also treat it. In a study that would have made Sigmund Freud proud, Nemeroff compared antidepressant drug treatment with psychotherapy. His preliminary analysis showed that the techniques had roughly equal effectiveness and a slightly better outcome in combination. But looking at just those people with depression who had been through early trauma, psychotherapy was significantly more effective than drug treatment, and led to remission in 45 per cent of people, even though they had suffered the condition for as long as eight years.
The placebo effect is another area in which we are beginning to understand the brain's response to environmental influences. Tor Wager of Columbia University in New York has shown that prefrontal brain regions, linked with expectation and reward, are active when a placebo is given, and that pain regions, by contrast, become less active. "Placebo changes how your brain processes pain while it is happening," says Wager. "Your expectations can have profound impacts on the brain and the body. The responses are neurobiologically real responses. They are not just how you say you felt." The placebo response is part of the process of getting well.
An interesting implication is that if you no longer respond to your surroundings in such a way as to create any expectation, you will not experience the placebo effect, and may need higher doses of drugs. Fabrizio Benedetti from the University of Turin Medical School in Italy showed that Alzheimer's patients, who have damage to the frontal circuits that mediate expectations, show no placebo effect for pain. "We may have to revise the therapies in mental patients to compensate for the loss in these expectation mechanisms," says Benedetti.
Changes in the brain that depend on experiences can affect many more aspects of brain function as well. Helen Fisher of Rutgers University in New Brunswick, New Jersey, reported brain activity in regions that control physical pain in people who had just been left by a lover, showing how emotions can trigger real physical effects.
And diet and exercise affect our brains just as much as our bodies, with bad diets having several deleterious effects on memory, and good diets bringing benefits. A large proteomic analysis described by Fernando Gómez-Pinilla of the University of California at Los Angeles showed that many proteins associated with synaptic structures are produced in response to energy metabolism, including the growth factor BDNF and an important memory protein, CREB. Junk diets reduce the levels of these in rats, he says, while exercise restores them. "Exercise probably exerts its effect on the brain by altering energy metabolism," he says. "It's a nice example of how diet and exercise could combine in people."
"We are moving from the excitement of the human genome to a new complexity," concludes Colin Blakemore, a neuroscientist at the University of Oxford and chief executive of the UK Medical Research Council. He should know: he's the one who reported how many neural connections our brains form every second.