Differential Prefrontal Hypoactivity in Generalized Anxiety Disorder: The Influence of Nonemotional and Emotional...

Generalized anxiety disorder (GAD) is marked by emotional dysregulation and impaired inhibitory control, often linked to atypical prefrontal cortex (PFC) function. However, how emotional context influences PFC engagement during inhibition remains unclear. This study aimed to examine how emotional versus nonemotional contexts modulate PFC activity in GAD compared to healthy controls (HCs).

Functional near-infrared spectroscopy (fNIRS) assessed bilateral PFC activity in 23 individuals with GAD and 42 HC during emotional and nonemotional Go/No-Go tasks. Two-way repeated-measures ANOVAs (group × condition) were conducted per channel with false discovery rate (FDR) correction. Effect sizes are reported as partial eta squared.

A significant group × condition interaction was found for No-Go accuracy (p = 0.032, η _p ² = 0.074), with GAD showing a larger decline from nonemotional to emotional conditions (87.70% vs. 47.17%) than HC (79.49% vs. 48.54%). For PFC activity, group × condition interactions reached uncorrected significance in the left dorsolateral PFC (DLPFC) and right dorsomedial PFC (DMPFC) (p = 0.013-0.047, η _p ² = 0.061-0.094), and the group main effect was uncorrected significant across bilateral dorsomedial and dorsolateral PFC (DLPFC, p = 0.005-0.039, η _p ² = 0.066-0.130); neither survived FDR correction. Significant condition main effect in the right dorsomedial and right ventromedial PFC (VMPFC, η _p ² = 0.120-0.159) were revealed after FDR correction.

Both groups showed PFC deactivation under emotional load, most prominently in the right medial PFC. HC exhibited context-dependent modulation of the left dorsolateral and right DMPFC, whereas GAD showed a flat, unmodulated response and broadly lower PFC activation, alongside selective impairment of response inhibition. These preliminary findings suggest prefrontal inflexibility as a core neural feature of GAD and underscore the role of left dorsolateral and DMPFC in emotion-cognition integration.