Yet, despite their prevalence, we know remarkably little about how these drugs work, especially at lower doses that have been proven clinically to calm behavior and focus attention in ADHD patients, says Berridge. In 2006, his team reported that therapeutic doses of Ritalin boosted neurotransmitter levels primarily in the PFC, suggesting a selective targeting of this region of the brain. Since then, he and Devilbiss have focused on how Ritalin acts on PFC neurons to enhance cognition.
To answer this, the pair studied PFC neurons in rats under a variety of Ritalin doses, including one that improved the animals' performance in a working memory task of the type that ADHD patients have trouble completing. Using a sophisticated new system for monitoring many neurons at once through a set of microelectrodes, the scientists observed both the random, spontaneous firings of PFC neurons and their response to stimulation of an important pathway into the PFC, the hippocampus.
Much like tiny microphones, the electrodes record a pop every time a neuron fires, Devilbiss explains. Analyzing the complex patterns of "voices" that emerge is challenging but also powerful, because it allows study of neurons on many levels.
"Similar to listening to a choir, you can understand the music by listening to individual voices," says Devilbiss, "or you can listen to the interplay between the voices of the ensemble and how the different voices combine."
When they listened to individual PFC neurons, the scientists found that while cognition-enhancing doses of Ritalin had little effect on spontaneous activity, the neurons' sensitivity to signals coming from the hippocampus increased dramatically. Under higher, stimulatory doses, on the other hand, PFC neurons stopped responding to incoming information.
"This suggests that the
|Contact: David Devilbiss|
University of Wisconsin-Madison