What causes schizophrenia? : Nature News Findings from a 'brain training' study challenge theory.

Researchers in Sweden have revealed a surprising change in brain biochemistry that occurs during the training of working memory, a buffer that stores information for the few second required to solve problems or even to understand what we are reading. The discovery may have implications for understanding disorders in which working memory is deficient ” such as schizophrenia and attention deficit hyperactivity disorder (ADHD).

Working memory depends on the transmission of signals in certain parts of the brain by the chemical dopamine and one of its receptors, the D1 receptor, particularly in the parietal and frontal regions of the cortex.

The efficiency of working memory drops off as people age. But the 'use-it-or-lose-it' adage holds true ” working memory can be improved through training. Torkel Klingberg, a neurologist at the Karolinska Institute in Stockholm, and his colleagues studied what happened to D1 receptors in the brains of healthy young men during such training1.

In particular, the researchers wanted to see whether the density of the receptors changes, because when dopamine is plentiful, dopamine receptors 'downregulate' ” that is, move from the nerve-cell membrane to the inside of the cell, where they cannot be activated. This is a normal 'tune-down' mechanism to avoid overstimulation.
Brain training

Klingberg's team organized a five-week training programme for 13 volunteers aged between 20 and 28. Every day, they spent around half an hour in total on five computer-based tests designed to stretch their working memories. In one, for example, participants would hear a string of numbers that they then had to remember the sequence of and repeat backwards, reporting results by clicking on relevant numbers in a grid on the screen.

Using brain-imaging techniques, the scientists measured levels and locations of dopamine receptors in brain areas of interest in each participant before and after training. They found that the density of D1 receptors in the parietal and frontal cortices fell as working memory improved.

"The density of neurotransmitter receptors is known to change in psychiatric disorders like schizophrenia, and this has been considered a cause of the diseases," says Klingberg. "But now we see that cognitive activity also affects receptor density." In the future, researchers will need to consider whether changes in receptor density in certain brain regions are simply the result of changes in behaviour or part of the disease process itself, he says.
Calming effect?

"This is an important consideration that applies to many findings of purported brain changes in mental disease," comments Sol Snyder, a neuroscientist at Johns Hopkins University in Baltimore, Maryland. "The research implies that alterations observed in schizophrenics may reflect altered attention or other behavioural features." Many findings of altered brain biochemistry may simply reflect the patients' inattentiveness, he says.

Klingberg says that his team's results may also have practical implications for training working memory. Children diagnosed with ADHD are frequently treated with drugs such as Ritalin that affect the dopamine system. In some centres, children undergo working-memory training programmes. "We are now interested to see if a combination of cognitive training and pharmacological intervention could be more effective than either alone," he says.