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Meta-analysis of amygdala connectivity in anxiety disorders versus healthy controlsBrain scans show altered connections in anxiety disorder patients

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Key Takeaway
Consider the altered amygdala connectivity patterns as a potential biomarker target in anxiety disorders.

This is a coordinate-based meta-analysis of resting-state functional MRI studies comparing amygdala-based whole-brain functional connectivity in patients with anxiety disorders versus healthy controls. The analysis included 378 patients and 405 controls. The authors synthesized pooled effect sizes for several connectivity metrics.

The meta-analysis found decreased amygdala-anterior cingulate cortex connectivity (effect size -0.54, 95% CI: -0.73 to -0.35). It also found increased connectivity between the amygdala and the left superior temporal gyrus (effect size 0.46, 95% CI: 0.27-0.65), middle temporal gyrus (effect size 0.38, 95% CI: 0.19-0.57), and cuneus (effect size 0.35, 95% CI: 0.17-0.53).

The authors note heterogeneous findings in resting-state functional MRI studies as a key limitation. They also clarify that this is a meta-analysis of coordinate-based data, not a primary trial, and results are based on voxel-wise tests with multiple corrections to minimize false positives.

The authors suggest this work provides a potential primary target for biomarker development and novel interventions. However, the practice relevance is restrained, as the evidence is preliminary and requires further validation in clinical contexts.

This review combined data from multiple studies to look at brain activity in people with anxiety disorders versus healthy controls. The researchers focused on resting-state functional connectivity, which measures how different parts of the brain communicate while at rest. The study included 378 patients with anxiety disorders and 405 healthy controls. No specific setting or intervention was reported for this analysis.

The analysis found that connectivity between the amygdala and the anterior cingulate cortex was decreased in patients. In contrast, connections between the amygdala and the left superior temporal gyrus, middle temporal gyrus, and cuneus were increased. These differences suggest distinct patterns of brain communication in anxiety disorders.

The study notes that findings in resting-state functional MRI can be heterogeneous. Because the data comes from a meta-analysis of coordinate-based studies rather than a single primary trial, results are based on voxel-wise tests with corrections to minimize false positives. This work provides a potential primary target for biomarker development and novel interventions. Readers should view these findings as a step toward understanding brain mechanisms rather than a definitive cause of anxiety.

What this means for you:
Brain scans show altered connections in anxiety patients compared to healthy controls, offering potential targets for future research.

Study Details

Study typeMeta analysis
Sample sizen = 378
EvidenceLevel 1
PublishedMay 2026
View Original Abstract ↓
BACKGROUND: 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. METHODS: 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. RESULTS: Fifteen datasets (378 patients, 405 controls) were included. Compared to healthy controls, patients with anxiety disorders had decreased amygdala-anterior cingulate cortex (ACC,  = -0.54, 95% confidence interval [CI]: -0.73 to -0.35) connectivity and increased connectivity with the left superior temporal gyrus ( = 0.46, 95% CI: 0.27-0.65), middle temporal gyrus ( = 0.38, 95% CI: 0.19-0.57), and cuneus ( = 0.35, 95% CI: 0.17-0.53). After threshold-free cluster enhancement correction, only reduced amygdala-ACC connectivity remained significant ( = -0.54, 95% CI: -0.73 to -0.35). Subgroup analyses confirmed this effect was driven mainly by adult patients and the left amygdala. CONCLUSIONS: 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.
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