Memory Training May Readjust Neurotransmitter Systems

by Elizabeth Norton Lasley

April 10, 2009

Memory-training exercises may do more than just improve recall: They may also help correct biochemical imbalances that underlie certain memory problems, a new study suggests. The research might lead to a time when mental exercises could augment medication and other treatment approaches for brain disorders such as attention-deficit/hyperactivity disorder (ADHD) and schizophrenia.

Using a cognitive training program backed up with imaging techniques, researchers have shown that improvements in working memory are accompanied by changes in the pattern of key dopamine receptors in the parts of the brain involved.

Working memory is the ability to retain information for short periods of time—for example, keeping relevant facts in mind while focusing on a particular problem. Impairments in working memory can be a part of normal aging; more severe deficits occur in ADHD and schizophrenia and are linked to disruptions in brain circuits that use dopamine.

Brain training

Torkel Klingberg and colleagues at the Karolinska Institute, Stockholm, had previously devised a cognitive training regimen to improve working memory in people with ADHD. Their success led them to wonder whether the training had a distinct, measurable effect on brain biochemistry.

The resulting study appeared online Feb. 6 in Science (pdf). The investigators recruited 13 healthy volunteers to undergo half an hour of working-memory training daily for five weeks. The computer-based tasks included visual-spatial exercises, such as viewing a screen full of cubes, some of which lit up in sequence; participants had to click on the same cubes in the original, then the reverse, order. In verbal-memory tests, subjects heard lists of letters, syllables or numbers—some presented visually and some aloud—then repeated them, again in the original and the reverse order. Results from each session were automatically sent to a psychologist who monitored progress and provided feedback.

To pinpoint the brain areas involved, the team conducted functional magnetic resonance imaging of each individual before and after the training period. The scans revealed five “regions of interest,” including parts of the frontal and parietal cortex. “These regions, which are activated by working memory, overlap with cortical regions implicated in both ADHD and schizophrenia,” Klingberg says.

The researchers also used positron emission tomography scans—again, before and after the five-week training period—to investigate the effects on dopamine receptors. Most participants showed a negative correlation, meaning that improvements in working memory led to a decrease in the density of the so-called D1 dopamine receptors. Working-memory training produced no change in D2 receptors, which function differently, suggesting that the effect on the brain is quite specific.

“Our findings emphasize the reciprocal interplay between behavior and the underlying brain biochemistry,” Klingberg says. “But we don’t yet know the mechanism through which working-memory training alters levels of D1 receptors.”

One possibility, he says, is that activity in receptors for other neurotransmitters, such as glutamate, might be affecting the D1 receptors. Another scenario might be that memory training increases the brain’s production of dopamine, and the D1 receptors retreat within the neurons to maintain the proper balance between the amount of neurotransmitter and the available receptors. “The effect would be a kind of fine-tuning of the dopamine system,” Klingberg says.

Klingberg predicts that as the mechanisms become better understood, targeted memory training might be used to help fine-tune the system not only for those with memory impairments but for people with ADHD and schizophrenia as well—in conjunction with pharmacological treatment and other approaches. “If cognitive training affects the receptor systems, one could consider that it might at least partially compensate for disturbances of these systems,” he says.

The software program used in the study, provided by Cogmed America Inc., is available in clinics in the United States, though not yet to individual patients.

Working on memory

“The study is both novel and exciting,” says Rosemary Tannock, an associate professor of psychiatry at the University of Toronto, who was not involved with the research. “It’s conducted well and provides converging evidence that working-memory training shows neuroplasticity even in adulthood,” she says. She notes that the gradually increasing difficulty level and continuous feedback are essential components of working-memory training, especially for patients with conditions such as ADHD.

But she cautions that the study did not use a control group of subjects doing another type of computer task—one that was merely repetitive, for example, without increasing in difficulty or specifically challenging working memory.

“We don’t yet know for sure that the changes in dopamine receptor density are related to working memory,” she says. “But the finding is an important first step.” Tannock adds that since medication for disorders such as ADHD leads to only a modest improvement in working memory while the medication is active, the training of memory processes may turn out to be an important component of treatment.