Lijuan YANG, Fang HE, Danfeng YUAN, Ting YANG, Liyang ZHANG, Yu CHEN, Jia LUO, Ying LI, Xiangyun YANG, Zhanjiang LI
Alpha Psychiatry - 2026;27(5):51187-0
Background: The dorsolateral prefrontal cortex (dLPFC) is a key brain region involved in cognitive control and emotional regulation and has been implicated in the pathophysiology of generalized anxiety disorder (GAD). This study used resting-state functional magnetic resonance imaging (rs-fMRI) to investigate functional connectivity (FC) and effective connectivity (EC) patterns of the bilateral dLPFC in drug-naïve patients with GAD. In addition, the relationships between abnormal connectivity patterns, anxiety symptoms, and attentional bias (AB) were examined. Methods: A total of 40 patients with GAD and 40 healthy controls (HCs) were recruited. Clinical symptoms in the GAD group were assessed using the Hamilton Anxiety Rating Scale (HAMA), the 17-item Hamilton Depression Rating Scale (HAMD-17), and the Generalized Anxiety Disorder-7 (GAD-7) scale. Attentional bias toward negative stimuli was evaluated using the dot-probe task and the emotional Stroop task. Independent-samples t-tests were performed to compare whole-brain voxel-wise FC and EC differences based on bilateral dLPFC regions of interest (ROIs) between the two groups. Partial correlation analyses, controlling for the duration of the current episode, were conducted to examine associations between aberrant FC/EC values and clinical symptoms or attentional bias in patients with GAD. Results: Compared with healthy controls, patients with GAD exhibited increased FC between the dLPFC and the medial superior frontal gyrus, inferior parietal gyrus, and left precentral gyrus. In addition, patients with GAD showed reduced directional (Granger-causal) connectivity from the dLPFC to the caudate nucleus, thalamus, and BA37, as well as from the left postcentral gyrus to the dLPFC (voxel-level p < 0.01; cluster-level Gaussian random field [GRF]-corrected p < 0.05). Correlation analyses revealed that dLPFC-based FC and EC values were significantly associated with anxiety symptom severity and attentional bias to varying degrees (r = -0.515 to 0.584, p < 0.05). Conclusions: This study identified widespread abnormalities in resting-state FC and EC involving the bilateral dLPFC in patients with GAD. Aberrant FC and EC patterns were closely associated with anxiety symptoms and attentional bias, further supporting the anxiety network hypothesis and highlighting the central role of the dLPFC within anxiety-related neural circuits. These findings provide preliminary neuroimaging evidence for the cognitive model of GAD and suggest that attentional bias toward threat-related stimuli may play a critical role in the pathogenesis of the disorder.
