Methylphenidate and cognitive flexibility: dissociated dose effects in hyperactive children.

A randomized, double-blind, placebo-controlled trial was conducted to assess the acute effects of placebo and three doses of methylphenidate (MPH) (0.3, 0.6, 0.9 mg/kg) on cognitive flexibility and overt behavior in 28 children with a confirmed diagnosis of attention deficit-hyperactivity disorder. Two underlying cognitive processes (response inhibition and response reengagement) were assessed by measuring the probability and speed with which subjects could inhibit responses to a primary task (forced-choice letter discrimination) and immediately execute a response to a secondary task (simple reaction time) when given a signal to do so. Results indicated that MPH enhanced cognitive flexibility, although the high dose was less effective than lower doses in enhancing response inhibition. Dissociations of dose effects on cognitive function and behavior were demonstrated: Dose-response functions for changes in behavior were linear, whereas the function for response inhibition was U-shaped. Findings argue against the typical clinical practice of determining the response to stimulant treatment from a single measure such as parent report of child behavior.