Catecholaminergic neural transmission plays an important role during the inhibition of prepotent responses. Methylphenidate (MPH) is an important drug that modulates the catecholaminergic system. However, theoretical considerations suggest that the effects of drugs (e.g. MPH) on cognitive control may depend on prior learning effects. Here we investigate this in a conflict-modulated Go/Nogo task and evaluate neurophysiological processes associated with this dynamic using EEG signal decomposition methods and source localization analysis. The behavioral data show that prior learning experiences eliminate effects of MPH on response inhibition processes. On a neurophysiological level, we show that MPH modulates specific processes in medial frontal brain regions. Although MPH seems to consistently modulate neurophysiological processes associated with response inhibition, this is no longer sufficient to modulate behavioral performance once learning or task familiarization processes have taken place. An important consequence of this study finding is that it may be important to adjust MPH dosage depending on learning effects in a specific setting to constantly increase cognitive control functions in that setting. This has important implications for clinical practice, since MPH is the first-line pharmacological therapy in attention-deficit hyperactivity disorder (ADHD). Cross-over study designs with constant doses of MPH can mask effects on cognitive functions. The impact of learning needs careful consideration in cross-over study designs examining catecholaminergic drug effects.
Keywords: Catecholamines; EEG; Methylphenidate; Response inhibition; Study designs.
Copyright © 2020. Published by Elsevier B.V.