Stimulation of the dorsolateral prefrontal cortex modulates brain cue reactivity to reward (un)availability

Brain imaging studies have shown that stimulation of the left dorsolateral prefrontal cortex (dlPFC), which plays a pivotal role in high-order cognitive control processes, modulates brain reactivity to reward-related cues. Nevertheless, the impact of contextual factors such as reward availability (the reward that is depicted in the cue exposure task) on such modulation effect remains unclear. Here we tested whether a single session of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) over the left dlPFC differently impacts brain reactivity to cues signalling either availability or unavailability of a sports betting opportunity. Employing a within-subject design (verum versus sham HF-rTMS) among thirty-two frequent sports bettors, we first observed that, as compared to the sham condition, verum HF-rTMS modulated brain reactivity to game cues prior to being made (un)available for betting, through simultaneous increases (posterior insula and caudate nucleus) and decreases (occipital pole) in brain activation. Second, verum HF-rTMS led to increased ventral striatal activity towards cues available for betting but did not modulate brain response to cues unavailable for betting. Third, exploratory functional connectivity analyses revealed increased negative coupling in the verum condition between the left dlPFC and the right and left superior frontal gyrus toward available and non-available betting cues, respectively. Taken together, these findings demonstrate that transient stimulation of the left dlPFC led to a general modulation in brain activity and functional connectivity in responses to cues, and that this effect is only partly dependent on cues signalling for reward (un)availability.