Abstract
<title>Abstract</title> <p>Stress-induced arousal disrupts prefrontal control and can impair working memory (WM), a feature shared across stress-related psychiatric conditions for which non-invasive, non-pharmacological interventions are needed. Transcranial direct current stimulation (tDCS) targeting the ventromedial prefrontal cortex (vmPFC) may support performance under such conditions by modulating prefrontal control networks. Using a randomized, single-blind, sham-controlled mixed design, we examined whether focal anodal vmPFC stimulation modulates WM performance and task-related neural activity under elevated arousal during concurrent functional MRI (fMRI). Arousal was manipulated using emotionally aversive and neutral clips, and the MRI environment elevated baseline arousal across sessions. Forty-eight participants performed a verbal n-back task (2-, 3-, and 4-back) during fMRI acquisition, with subjective affect, heart rate (HR), cortisol, task performance, and task-related functional connectivity assessed. Active stimulation improved WM performance relative to sham, selectively at the 2-back load. Aversive clips increased negative affect and HR relative to neutral clips, confirming arousal induction, whereas cortisol was elevated before clip presentation in both sessions. Task-based connectivity analyses showed that active stimulation was associated with reduced connectivity between prefrontal attention-regulatory regions and sensory-processing regions, and increased connectivity between superior temporal and cerebellar regions, and these changes correlated with task performance. These findings suggest that vmPFC stimulation may support WM performance under elevated arousal by altering task-related functional connectivity, consistent with the role of the vmPFC in the attentional processes required for efficient performance rather than in WM maintenance itself and identify the vmPFC as a candidate stimulation target for stress- and arousal-related disorders.</p>