Catecholaminergic modulation of indices of cognitive flexibility:a pharmaco-tDCS study

Background: Dopaminergic activity within the dorsolateral prefrontal cortex (dlPFC) has been implicated in the control of cognitive flexibility. Much of the evidence for a causative relationship between cognitive flexibility and dopamine has come from animal studies, whilst human data have largely been correlational. Objective/Hypothesis:The current study examines whether changes in dopamine levels through tyrosine administration and suppression of dlPFC activity via cathodal tDCS could be causally related to cognitive flexibility as measured by task switching and reversal learning. Methods: Using a crossover, double-blind, sham controlled, counterbalanced, randomized trial, we tested the effects of combining cathodal tDCS with tyrosine, a catecholaminergic precursor, with appropriate drug and tDCS placebo controls, on two measures of cognitive flexibility: probabilistic reversal learning, and task switching. Results: While none of the manipulations had an effect on task switching, there was a significant main effect of cathodal tDCS and tyrosine on reversal learning. Reversal learning performance was significantly worsened by cathodal tDCS compared with sham tDCS, whilst tyrosine significantly improved performance compared with placebo. However, there was no significant tDCS × drugs interaction. Interestingly, and as predicted by our model, the combined administration of tyrosine with cathodal tDCS resulted in performance that was equivalent to the control condition (i.e. tDCS sham + placebo). Conclusions: Our results suggest a causative role for dopamine signalling and dorsolateral prefrontal cortex activity in regulating indices of cognitive flexibility in humans.