Curb your enthusiasm: Positive expectations negatively interact with prefrontal tDCS effects on attentional control, working memory, and emotion regulation in healthy individuals

INTRODUCTION: While prefrontal tDCS is an emerging antidepressant treatment, its efficacy shows considerable variability. Common prefrontal tDCS targets overlap with placebo/expectation-related brain networks and given that tDCS is thought to modulate ongoing neural activity, expectations may critically interact with its outcomes. This proof-of-concept study investigated in healthy individuals how positive expectations modulate prefrontal tDCS effects on depression-relevant cognitive-affective processes. METHODS: Using a preregistered, double-blind, 2 × 2 between-subjects design, 200 healthy participants underwent a positive expectation induction or a control procedure, crossed with either active (2 mA, 20 min, F3/Fp2) or sham tDCS. Assessed domains included attentional control (mixed-saccade task), working memory (dual 2-back task), and a multimodal assessment of emotion regulation (self-reports, skin conductance responses, cardiac reactivity, and pupillary responses). RESULTS: Positive tDCS beliefs were successfully induced. Importantly, combining positive expectations with active tDCS consistently yielded counterproductive interactions: it resulted in non-additive redundancy for anti-saccade accuracy costs, slowed working memory, increased emotional sensitivity, and disrupted cardiovascular markers of effective emotion regulation. Positive expectations alone also reduced pro-saccadic 'go' responses, sympathetic arousal, emotion regulation efficacy, and naturalistic autonomic orienting. CONCLUSION: Collectively, these findings suggest that expectations do interact with tDCS, and positive expectations in healthy individuals may foster a suboptimal, passive state, which possibly conflicts with activity-dependent tDCS mechanisms. Although positive expectations may enhance clinical outcomes in depressed patients because of higher baseline motivation or arousal, they appear detrimental on cognitive-affective performance based tasks in healthy individuals. Critically, these findings urge the need to systematically assess the influence of tDCS expectations in both experimental and clinical settings.