Abstract
Background and Objective: Generalized anxiety disorder (GAD) is a prevalent mental health condition affecting cognitive functions like response inhibition. The neural mechanisms underlying the interplay between inhibitory ability and anxiety regulation in GAD remain unclear. This study aimed to investigate the prefrontal cortex (PFC) alterations when anxiety regulation shares neural resources with response inhibition in patients with GAD compared to healthy controls and to explore the relationship between anxiety and PFC activity. Methods: The hemodynamic responses of bihemispheric PFC were measured in 19 GAD patients and 38 healthy controls using functional near-infrared spectroscopy (fNIRS) during the Go/No-Go task and were compared between the groups. The correlations between PFC activity and task performance and those between PFC activity and anxiety levels were analyzed. Results: The GAD group exhibited lower hemoglobin concentration across the PFC during both baseline and task sessions, with significant hypoactivity in the bihemispheric dorsomedial PFC (DMPFC) at baseline (p=0.035-0.049), and more widespread hypoactivity during the task in the bihemispheric DMPFC (p < 0.001-0.033) and dorsolateral PFC (DLPFC; p=0.012-0.042), as well as the right ventromedial PFC (VMPFC; p=0.019-0.037). Higher baseline prefrontal activity was associated with poorer task accuracy (r = -0.576 to -0.417) and greater trait anxiety (r = 0.441-0.514). When transitioning to the task, better accuracy correlated with increased activation in the left DMPFC (r = 0.405-0.593), whereas higher anxiety levels were linked to reduced activation in the left DMPFC (r = -0.512) and right DMPFC (r = -0.435). Conclusion: This study reveals that patients with GAD exhibit significant hypoactivity in the PFC during response inhibition, correlating with both task performance and anxiety levels. These findings emphasize the importance of targeting PFC dysfunction in the development of diagnostic tools and therapeutic interventions for GAD.