Methylphenidate modulates interactions of anxiety with cognition.

While a large body of literature documents the impairing effect of anxiety on cognition, performing a demanding task was shown to be effective in reducing anxiety. Here we explored the mechanisms of this anxiolytic effect by examining how a pharmacological challenge designed to improve attentional processes influences the interplay between the neural networks engaged during anxiety and cognition. Using a double-blind between-subject design, we pharmacologically manipulated working memory (WM) using a single oral dose of 20 mg methylphenidate (MPH, cognitive enhancer) or placebo. Fifty healthy adults (25/drug group) performed two runs of a WM N-back task in a 3 T magnetic resonance imaging scanner. This task comprised a low (1-Back) and high (3-Back) WM load, which were performed in two contexts, safety or threat of shocks (induced-anxiety). Analyses revealed that (1) WM accuracy was overall improved by MPH and (2) MPH (vs. placebo) strengthened the engagement of regions within the fronto-parietal control network (FPCN) and reduced the default mode network (DMN) deactivation. These MPH effects predominated in the most difficult context, i.e., threat condition, first run (novelty of the task), and 3-Back task. The facilitation of neural activation can be interpreted as an expansion of cognitive resources, which could foster both the representation and integration of anxiety-provoking stimuli as well as the top-down regulatory processes to protect against the detrimental effect of anxiety. This mechanism might establish an optimal balance between FPCN (cognitive processing) and DMN (emotion regulation) recruitment.