Methylphenidate effects on neural activity during response inhibition in healthy humans

Methylphenidate (MPH) is a stimulant drug that blocks the dopamine transporter, which results in increased extracellular levels of dopamine, a neurotransmitter involved in motor control and reward. The ability to suppress automatic or contextually inappropriate motor responses is referred to as response inhibition, a function improved by MPH in patients with attention-deficit/hyperactivity disorder. However, little is known about the effects of MPH on response inhibition and underlying brain function in healthy individuals. Therefore, this study employed functional magnetic resonance imaging (fMRI) and two response inhibition tasks in a sample of 50 healthy males. Participants underwent fMRI during the go/no-go and stop-signal tasks after administration of 40 mg MPH and placebo in a double-blind, placebo-controlled, repeated-measures design. Results revealed task-specific neural effects of MPH: The drug increased neural activity in the striatum during errors on the go/no-go task, but not the stop-signal task. We speculate that this pattern might be due to differences in the type of errors that occur in the two tasks; whereas errors can be avoided on the go/no-go task and thus likely have high salience, they are inevitable on approximately 50% of trials on the stop-signal task. The study thus provides further evidence that MPH effects interact with the salience of the behaviour under investigation.