Insula shows abnormal task‐evoked and resting‐state activity in first‐episode drug‐naïve generalized anxiety disorder
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BACKGROUND: Interoception is associated with neural activity in the insula of healthy humans. On the basis of the somatic symptoms in generalized anxiety disorder (GAD), especially abnormal heartbeat perception, we hypothesized that abnormal activity in the insula was associated with interoceptive awareness in patients with GAD. METHODS: We investigated the psychological correlates of interoceptive awareness in a sample of 34 patients with first-onset, drug-naïve GAD and 30 healthy controls (HCs). Furthermore, we compared blood oxygenation level-dependent responses between the two groups during a heartbeat perception task to assess task-evoked activity and its relationship with psychological measures. We also examined between-group differences in insular subregions resting-state functional connectivity (rsFC), and its relationship with anxiety severity. RESULTS: Patients with GAD had significantly higher body perception scores than HCs. They also exhibited greater task-evoked activity in the left anterior insula, left posterior insula, and right anterior insula during interoceptive awareness than HCs. Left anterior insula activity was positively correlated with body awareness in patients with GAD, and rsFC between the left anterior insula and left medial prefrontal gyrus was negatively correlated with somatic anxiety severity. CONCLUSIONS: Investigating a sample of first-episode, drug-naïve patients, our study demonstrated abnormal interoceptive awareness in patients with GAD and that this was related to abnormal anterior insular activity during both rest and task. These results shed new light on the psychological and neural substrates of somatic symptoms in GAD, and they may serve to establish abnormal interoceptive awareness as a neural and psychological marker of GAD.
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Qualitative synthesis suggested that anxiety disorders may exhibit increased activation in the anterior and mid-insula during interoceptive tasks.
“Qualitative synthesis suggested potential insula hyperactivation in anxiety, aligning with theories of interoceptive hypervigilance.”
From Neural correlates of altered interoception in depressive and anxiety disorders: a systematic review and meta-analysis (2026) · cites this paper as [39]
The Results (§3.2, page unavailable) report greater anterior-insula activity during heartbeat-focused tasks in patients with GAD than in healthy controls, supporting potential insula hyperactivation during interoception. This is a single GAD study, not a qualitative synthesis across anxiety disorders, and its reported regions are anterior and posterior—not mid-insula. (LLM, conf=0.87)
Experimental — accuracy not yet measuredLarger effects were observed for comparisons between interoceptive and exteroceptive processing than for comparisons between interoceptive processing and rest.
“Generally, larger effects were observed for comparisons between interoceptive and exteroceptive processing, in contrast to comparison between interoceptive processing and rest [39].”
From Neural correlates of altered interoception in depressive and anxiety disorders: a systematic review and meta-analysis (2026) · cites this paper as [39]
Section 3.2 (page unavailable) reports group differences in four regions for heartbeats versus pure tones, compared with one region for heartbeats versus fixation. That supports a greater extent of reported differences, but the paper does not establish that the effects themselves were larger in the interoceptive-versus-exteroceptive comparison. (LLM, conf=0.78)
Experimental — accuracy not yet measuredCui et al. reported increased activation in the right precentral cortex and both the anterior and posterior insula in generalized anxiety disorder.
“Cui et al. studied GAD and reported increased activation in the right precentral cortex and both the anterior and posterior insula in the clinical group [39].”
From Neural correlates of altered interoception in depressive and anxiety disorders: a systematic review and meta-analysis (2026) · cites this paper as [39]
Anterior insula can be activated in interoceptive awareness, emotion perception, and pain perception tasks.
“The anterior insula could be activated both in interoceptive awareness (Cui et al., 2020) and emotion perception task (Lamm et al., 2010) including pain perception (Farb et al., 2013).”
From Enhanced Resting-State Functional Connectivity With Decreased Amplitude of Low-Frequency Fluctuations of the Salience Network in Mindfulness Novices (2022) · cites this paper as Cui et al., 2020
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References 55 · Cited by 38
Research works printed but not linked: 5
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- Authors
- Cui, H., Zhang, B., Li, W., Li, H., Pang, J., Hu, Q., Zhang, L., Tang, Y., Yang, Z., Wang, J., Li, C., & Northoff, G.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Guangzhou Medical University (CN)
- Suzhou Guangji Hospital (CN)
- University of Ottawa (CA)
- Corresponding author
- Wang, Jijun
- Li, Chunbo
- ORCID
- Venue
- Depression and Anxiety
- Publisher
- Wiley
- Published
- 2020-03-20
- Volume
- 37
- Issue
- 7
- Pages
- 632-644
- ISSN
- 1091-4269 (ISSN-L)
- 1520-6394
- OpenAlex
- W3011965540
- Cited by
- 38
- References
- 55
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 3 · 2023: 13 · 2022: 10 · 2021: 4 · 2020: 2
- FWCI
- 5.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Depression and Anxiety (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81801345, 81071098, 81971251)
- Natural Science Foundation of Shanghai (18ZR1432600, 17ZR1424700)
- Canadian Institutes of Health Research
- Physicians' Services Incorporated Foundation
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Psychosomatic Disorders and Their Treatments
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Keywords
- generalized anxiety disorder, insula, interoceptive awareness, interoception, heartbeat perception, anterior insula, resting-state functional connectivity, somatic anxiety, body awareness, medial prefrontal cortex, first-episode drug-naive patients, neural markers
- MeSH terms
- Anxiety Disorders, Awareness, Cerebral Cortex, Humans, Magnetic Resonance Imaging, Interoception
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