Altered amygdala resting-state functional connectivity in anxiety disorders: a coordinate-based meta-analysis

Anxiety disorders are associated with disrupted amygdala connectivity; however, resting-state functional MRI studies have reported heterogeneous findings. To clarify these inconsistencies, we conducted a meta-analysis of amygdala-based connectivity studies.

A systematic search of Embase, PubMed, and Web of Science was performed through December 26, 2025. Studies comparing amygdala-based whole-brain resting-state functional connectivity in patients with anxiety disorders versus healthy controls were included. Meta-analysis was conducted with the latest software - Seed-based d Mapping with Permutation of Subject Images (SDM-PSI), which employs voxel-wise tests and multiple corrections to minimize false positives. Subgroup analyses were performed to examine differences by age and hemisphere.

Fifteen datasets (378 patients, 405 controls) were included. Compared to healthy controls, patients with anxiety disorders had decreased amygdala-anterior cingulate cortex (ACC, g = -0.54, 95% confidence interval [CI]: -0.73 to -0.35) connectivity and increased connectivity with the left superior temporal gyrus (g = 0.46, 95% CI: 0.27-0.65), middle temporal gyrus (g = 0.38, 95% CI: 0.19-0.57), and cuneus (g = 0.35, 95% CI: 0.17-0.53). After threshold-free cluster enhancement correction, only reduced amygdala-ACC connectivity remained significant (g = -0.54, 95% CI: -0.73 to -0.35). Subgroup analyses confirmed this effect was driven mainly by adult patients and the left amygdala.

Reduced connectivity between the left amygdala and the ipsilateral ACC was the most robust neuroimaging marker of anxiety disorders, which suggests a lateralized vulnerability. By applying updated analytic methods, this study refines our understanding of the neuropathology of anxiety disorders and provides a potential primary target for biomarker development and novel interventions.