HF-rTMS Over the Left and Right DLPFC Enhances Proactive Cognitive Control: An Antisaccade and Pupillometry Study

Proactive cognitive control enables individuals to anticipate and prepare for upcoming cognitive demands. Whereas prior research highlights the involvement of the dorsolateral prefrontal cortex (DLPFC) in proactive cognitive control, the lateralization of this function remains unclear. In this single-blind, sham-controlled, within-subject, randomized preregistered study, 31 healthy participants (mean age = 22.26, SD = 4.01; 18 women) received, in three separate sessions, sham and active high-frequency (20hz) repetitive transcranial magnetic stimulation (HF-rTMS) over the left and right DLPFC before performing a blocked version of the antisaccade task in combination with pupillometry to assess proactive cognitive control. Although preregistered analyses with saccade latency (i.e., time to initiate the first saccadic movement) did not show a significant effect of HF-rTMS, exploratory analyses with fixation latencies (i.e., time to fixate the gaze at the correct target location) in antisaccade trials were significantly shorter after both active left and right DLPFC stimulation compared to sham. Moreover, analyses accounting for tonic pupil size showed that the pupil size during the anticipatory phase (reflecting phasic resource allocation) was relatively larger after active left and right HF-rTMS (vs sham) on prosaccade trials, and that a larger pupil size during the anticipatory phase was associated with shorter fixation latencies in antisaccade trials. Tonic pupil size, reflecting sustained resource allocation, was larger after left DLPFC stimulation and was associated with longer saccade and fixation latencies after sham, but not active stimulation. These findings provide important evidence that helps reconcile mixed results in the field by supporting the involvement of both left and right DLPFC in proactive cognitive control via the regulation of anticipatory allocation of cognitive resources.