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Cited by 204Psychosomatic Disorders and Their TreatmentsTactile and Sensory InteractionsHeart Rate Variability and Autonomic Control

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Anterior insular cortex plays a critical role in interoceptive attention

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Wang, Xingchao, Wu, Qiong, Egan, Laura, Gu, Xiaosi, Liu, Pinan, Gu, Hong, Yang, Yihong, Luo, Jing, Wu, Yanhong, Gao, Zhixian, Fan, Jin·2019·eLife
DOI 10.7554/elife.42265PMC PMC6488299

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Abstract

Accumulating evidence indicates that the anterior insular cortex (AIC) mediates interoceptive attention which refers to attention towards physiological signals arising from the body. However, the necessity of the AIC in this process has not been demonstrated. Using a novel task that directs attention toward breathing rhythm, we assessed the involvement of the AIC in interoceptive attention in healthy participants using functional magnetic resonance imaging and examined the necessity of the AIC in interoceptive attention in patients with AIC lesions. Results showed that interoceptive attention was associated with increased AIC activation, as well as enhanced coupling between the AIC and somatosensory areas along with reduced coupling between the AIC and visual sensory areas. In addition, AIC activation was predictive of individual differences in interoceptive accuracy. Importantly, AIC lesion patients showed disrupted interoceptive discrimination accuracy and sensitivity. These results provide compelling evidence that the AIC plays a critical role in interoceptive attention.

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Figure 1. Experimental setup, trial structure of the tasks, and stimulus conditions. (a) The respiratory effort is converted into electronic signal changes using a respiratory transducer, amplified by BIOPAC, digitized using an A/D converter, and sent to the test computer for the final visual display as a dynamic breath curve, with or without a 400 ms delay. (b) This panel shows two trials for the breath detection task (BDT) and flash dot detection task (DDT) runs, respectively. Each trial begins with a 3 s blank display, followed by a 12 s display of respiratory curve presented with or without a 400 ms delay and with or without a 30 ms red dot flashed at a random position on the curve, and ends with a 3 s response window during which participants make a forced-choice button-press response to two alternative choices depending on the block type (BDT or DDT) to indicate whether the feedback curve is synchronous or delayed (for the BDT run) or whether a dot has appeared (for the DDT run). (c) The task represents a 2 × 2 × 2 factorial design with the factors of attention to breath or dot (block design), presence or absence of breath curve delay, and presence or absence of a dot flashed. The dashed line represents the actual breath curve, while the solid line represents the feedback breath curve displayed on the screen.
Figure 1. Experimental setup, trial structure of the tasks, and stimulus conditions. (a) The respiratory effort is converted into electronic signal changes using a respiratory transducer, amplified by BIOPAC, digitized using an A/D converter, and sent to the test computer for the final visual display as a dynamic breath curve, with or without a 400 ms delay. (b) This panel shows two trials for the breath detection task (BDT) and flash dot detection task (DDT) runs, respectively. Each trial begins with a 3 s blank display, followed by a 12 s display of respiratory curve presented with or without a 400 ms delay and with or without a 30 ms red dot flashed at a random position on the curve, and ends with a 3 s response window during which participants make a forced-choice button-press response to two alternative choices depending on the block type (BDT or DDT) to indicate whether the feedback curve is synchronous or delayed (for the BDT run) or whether a dot has appeared (for the DDT run). (c) The task represents a 2 × 2 × 2 factorial design with the factors of attention to breath or dot (block design), presence or absence of breath curve delay, and presence or absence of a dot flashed. The dashed line represents the actual breath curve, while the solid line represents the feedback breath curve displayed on the screen.CC0 · PubMed Central
Figure 1—figure supplement 1. Raincloud plots visualizing the five-number summary (minimum, lower quartile, median, upper quartile, and maximum) for (a) accuracy, (b) reaction time, (c) d’, and (d) β for the BDT and DDT tasks in the first sample of the fMRI study.
Figure 1—figure supplement 1. Raincloud plots visualizing the five-number summary (minimum, lower quartile, median, upper quartile, and maximum) for (a) accuracy, (b) reaction time, (c) d’, and (d) β for the BDT and DDT tasks in the first sample of the fMRI study.CC0 · PubMed Central
Figure 1—figure supplement 2. Raincloud plots visualizing the five-number summary (minimum, lower quartile, median, upper quartile, and maximum) for (a) accuracy, (b) reaction time, (c) d’, and (d) β for the BDT and DDT tasks in the second sample of the fMRI study.
Figure 1—figure supplement 2. Raincloud plots visualizing the five-number summary (minimum, lower quartile, median, upper quartile, and maximum) for (a) accuracy, (b) reaction time, (c) d’, and (d) β for the BDT and DDT tasks in the second sample of the fMRI study.CC0 · PubMed Central
Figure 2. Main effects and the interaction effect of the whole brain analysis of the first sample. (a) Main effect of interoceptive vs. exteroceptive attention contrast (BDT vs. DDT). (b) Main effect of breath curve feedback condition (delayed curve vs. non-delayed curve). (c) Interaction between attention type and breath-curve feedback condition ([delayed – non-delayed] BDT – [delayed – non-delayed] DDT). Here we showed the left AIC for the visualization of the seed for the ROI analysis in the second fMRI sample, although the cluster with 210 voxels did not survive GRF correction. Red color represents an increased activation; Blue color represents a decreased activation. (d) Activation of the left and the right AIC under the four task conditions, and the pattern of the interaction.
Figure 2. Main effects and the interaction effect of the whole brain analysis of the first sample. (a) Main effect of interoceptive vs. exteroceptive attention contrast (BDT vs. DDT). (b) Main effect of breath curve feedback condition (delayed curve vs. non-delayed curve). (c) Interaction between attention type and breath-curve feedback condition ([delayed – non-delayed] BDT – [delayed – non-delayed] DDT). Here we showed the left AIC for the visualization of the seed for the ROI analysis in the second fMRI sample, although the cluster with 210 voxels did not survive GRF correction. Red color represents an increased activation; Blue color represents a decreased activation. (d) Activation of the left and the right AIC under the four task conditions, and the pattern of the interaction.CC0 · PubMed Central
Figure 3. Relationship between brain activation and behavioral performance across participants. (a) This was revealed in a regression analysis of contrast images for the interaction between interoceptive attention deployment (BDT vs. DDT) and breath curve feedback condition (delayed vs. no-delayed), with performance accuracy on interoceptive and exteroceptive tasks as regressor-of-interest and covariate, respectively. AIC, anterior insular cortex; MTG, middle temporal gyrus. (b) Correlational patterns between the interaction effect of bilateral AIC activation and relative interoceptive accuracy. Data were normalized as z-scores.
Figure 3. Relationship between brain activation and behavioral performance across participants. (a) This was revealed in a regression analysis of contrast images for the interaction between interoceptive attention deployment (BDT vs. DDT) and breath curve feedback condition (delayed vs. no-delayed), with performance accuracy on interoceptive and exteroceptive tasks as regressor-of-interest and covariate, respectively. AIC, anterior insular cortex; MTG, middle temporal gyrus. (b) Correlational patterns between the interaction effect of bilateral AIC activation and relative interoceptive accuracy. Data were normalized as z-scores.CC0 · PubMed Central
Figure 4. PPI and DCM results of the first fMRI sample. (a) Regions showing positive (red) and negative (blue) associations with AIC activation modulated by interoceptive attention relative to exteroceptive attention (BDT vs. DDT). (b) An increase in activation in the right AIC was associated with an increase in activation in the postcentral gyrus (PoCG) and a decrease in activation in the visual cortex (VC, V2/3) under the condition of interoceptive attention compared with exteroceptive attention. (c) Five base models generated by specifying possible modulations of interoceptive and exteroceptive attention (BDT and DDT) on the four endogenous connections between ROIs. The model surrounded by a rectangle in dashed-line indicates the winning model out of 52 variant models revealed by random-effects Bayesian model selection (BMS). (d) Intrinsic efferent connection from the AIC to the PoCG was significant. The modulatory effect of interoceptive attention (BDT) on the connection from the AIC to the PoCG was significant. The modulatory effect of exteroceptive attention (DDT) on the connection from AIC to V2/3 was significant (uncorrected).
Figure 4. PPI and DCM results of the first fMRI sample. (a) Regions showing positive (red) and negative (blue) associations with AIC activation modulated by interoceptive attention relative to exteroceptive attention (BDT vs. DDT). (b) An increase in activation in the right AIC was associated with an increase in activation in the postcentral gyrus (PoCG) and a decrease in activation in the visual cortex (VC, V2/3) under the condition of interoceptive attention compared with exteroceptive attention. (c) Five base models generated by specifying possible modulations of interoceptive and exteroceptive attention (BDT and DDT) on the four endogenous connections between ROIs. The model surrounded by a rectangle in dashed-line indicates the winning model out of 52 variant models revealed by random-effects Bayesian model selection (BMS). (d) Intrinsic efferent connection from the AIC to the PoCG was significant. The modulatory effect of interoceptive attention (BDT) on the connection from the AIC to the PoCG was significant. The modulatory effect of exteroceptive attention (DDT) on the connection from AIC to V2/3 was significant (uncorrected).CC0 · PubMed Central
Figure 4—figure supplement 1. Regions showed positive (red) and negative (blue) association with the left AIC (as the seed) modulated by interoceptive attention relative to exteroceptive attention (BDT vs DDT) for the first fMRI sample.
Figure 4—figure supplement 1. Regions showed positive (red) and negative (blue) association with the left AIC (as the seed) modulated by interoceptive attention relative to exteroceptive attention (BDT vs DDT) for the first fMRI sample.CC0 · PubMed Central
Figure 4—figure supplement 2. Exceedance probability of RFX BMS for the first fMRI sample. Across all 52 models, M20 outperformed the other models and thus was identified as the optimal model. M20 denotes the model with the modulatory effects of interoceptive and exteroceptive attention (BDT and DDT) exerting on the connection from the AIC to the PoCG and to the V2/3.
Figure 4—figure supplement 2. Exceedance probability of RFX BMS for the first fMRI sample. Across all 52 models, M20 outperformed the other models and thus was identified as the optimal model. M20 denotes the model with the modulatory effects of interoceptive and exteroceptive attention (BDT and DDT) exerting on the connection from the AIC to the PoCG and to the V2/3.CC0 · PubMed Central
Figure 5. ROI results of the second fMRI sample. (a) ROI analysis of the parameter estimates of the left and the right AIC under the four experimental conditions. Raincloud plots were used for visualization. (b) Correlation between the interaction effect of bilateral AIC and relative interoceptive accuracy. The values of the variable in b were normalized as z-scores.
Figure 5. ROI results of the second fMRI sample. (a) ROI analysis of the parameter estimates of the left and the right AIC under the four experimental conditions. Raincloud plots were used for visualization. (b) Correlation between the interaction effect of bilateral AIC and relative interoceptive accuracy. The values of the variable in b were normalized as z-scores.CC0 · PubMed Central
Figure 5—figure supplement 1. Raincloud plot visualization of respiratory volumes under the four experimental conditions from the second fMRI sample.
Figure 5—figure supplement 1. Raincloud plot visualization of respiratory volumes under the four experimental conditions from the second fMRI sample.CC0 · PubMed Central
Figure 5—figure supplement 2. Activation maps without and with RETROICOR +RVHRCOR correction for the second fMRI sample. (a) Main effect of interoceptive vs. exteroceptive attention (BDT vs. DDT). (b) Main effect of breath curve feedback condition (delayed vs. non-delayed). (c) Interaction between attention type and breath-curve feedback condition ([delayed – non-delayed] BDT – [delayed – non-delayed] DDT). Pink purple contours indicate corresponding activation in the first sample. We used an extremely liberal threshold of voxelwise p<0.05 for visualization.
Figure 5—figure supplement 2. Activation maps without and with RETROICOR +RVHRCOR correction for the second fMRI sample. (a) Main effect of interoceptive vs. exteroceptive attention (BDT vs. DDT). (b) Main effect of breath curve feedback condition (delayed vs. non-delayed). (c) Interaction between attention type and breath-curve feedback condition ([delayed – non-delayed] BDT – [delayed – non-delayed] DDT). Pink purple contours indicate corresponding activation in the first sample. We used an extremely liberal threshold of voxelwise p<0.05 for visualization.CC0 · PubMed Central
Figure 5—figure supplement 3. Paired t-test of beta maps obtained without and with RETROICOR + RVHRCOR correction for the second fMRI sample. The difference of the signals of the AIC between the analyses with and without physiological corrections was only evident under the main effect of interoceptive vs. exteroceptive attention (BDT vs. DDT), but not under the interaction contrast, confirming that the interaction effect of the AIC was not significantly impacted by the physiological noises. (a) Main effect of interoceptive vs. exteroceptive attention (BDT vs. DDT). (b) Main effect of breath curve feedback condition (delayed vs. non-delayed). (c) Interaction between attention type and breath-curve feedback condition ([delayed – non-delayed] BDT – [delayed – non-delayed] DDT). Pink purple contours indicate corresponding activation in the first sample. We used an extremely liberal threshold of voxelwise p<0.05 for visualization.
Figure 5—figure supplement 3. Paired t-test of beta maps obtained without and with RETROICOR + RVHRCOR correction for the second fMRI sample. The difference of the signals of the AIC between the analyses with and without physiological corrections was only evident under the main effect of interoceptive vs. exteroceptive attention (BDT vs. DDT), but not under the interaction contrast, confirming that the interaction effect of the AIC was not significantly impacted by the physiological noises. (a) Main effect of interoceptive vs. exteroceptive attention (BDT vs. DDT). (b) Main effect of breath curve feedback condition (delayed vs. non-delayed). (c) Interaction between attention type and breath-curve feedback condition ([delayed – non-delayed] BDT – [delayed – non-delayed] DDT). Pink purple contours indicate corresponding activation in the first sample. We used an extremely liberal threshold of voxelwise p<0.05 for visualization.CC0 · PubMed Central
Figure 6. Reconstruction of anterior insular cortex lesions of six patients. Red color indicates 100% overlap. Left lesions were flipped to the right side to map the lesion overlap.
Figure 6. Reconstruction of anterior insular cortex lesions of six patients. Red color indicates 100% overlap. Left lesions were flipped to the right side to map the lesion overlap.CC0 · PubMed Central
Figure 7. Behavioral results of the lesion study. (a, b, c) the interoceptive performance on the BDT, and (d, e, f) the exteroceptive performance on the DDT. On the BDT, patients with AIC lesions had significantly lower performance in accuracy and dʹ compared with the NC and BDC groups but did not show significant alteration in β during the BDT. On the DDT, patients with AIC lesions did not show significant abnormality in performance in accuracy, dʹ, and β compared with either the NC or BDC groups. NC, normal control; BDC, brain damage control. Dashed line: chance level. * p < 0.05; ** p < 0.01; *** p < 0.001.
Figure 7. Behavioral results of the lesion study. (a, b, c) the interoceptive performance on the BDT, and (d, e, f) the exteroceptive performance on the DDT. On the BDT, patients with AIC lesions had significantly lower performance in accuracy and dʹ compared with the NC and BDC groups but did not show significant alteration in β during the BDT. On the DDT, patients with AIC lesions did not show significant abnormality in performance in accuracy, dʹ, and β compared with either the NC or BDC groups. NC, normal control; BDC, brain damage control. Dashed line: chance level. * p < 0.05; ** p < 0.01; *** p < 0.001.CC0 · PubMed Central
Author response image 1. Activation maps with and without including individual heart rate and respiratory volume as covariates in the 2nd GLM. (a) Main effect of interoceptive attention (interoceptive task vs. exteroceptive task). (b) Interaction between attention type and breath-curve feedback condition ([delayed – non-delayed]interoceptive task – [delayed – non-delayed]exteroceptive task).
Author response image 1. Activation maps with and without including individual heart rate and respiratory volume as covariates in the 2nd GLM. (a) Main effect of interoceptive attention (interoceptive task vs. exteroceptive task). (b) Interaction between attention type and breath-curve feedback condition ([delayed – non-delayed]interoceptive task – [delayed – non-delayed]exteroceptive task).CC0 · PubMed Central
Author response image 2. The pattern of respiratory parameters under different task conditions.
Author response image 2. The pattern of respiratory parameters under different task conditions.CC0 · PubMed Central
Author response image 3. Activation maps with and without physiological correction for the 1st level GLM. (a) Main effect of interoceptive attention (interoceptive task vs. exteroceptive task). (b) Interaction between attention type and breath-curve feedback condition ([delayed – non-delayed]interoceptive task – [delayed – non-delayed]exteroceptive task). (c) The interaction patterns of the left and right anterior insular cortex (AIC) activity without physiological correction. (d) The interaction patterns of the left and right AIC activity with physiological correction.
Author response image 3. Activation maps with and without physiological correction for the 1st level GLM. (a) Main effect of interoceptive attention (interoceptive task vs. exteroceptive task). (b) Interaction between attention type and breath-curve feedback condition ([delayed – non-delayed]interoceptive task – [delayed – non-delayed]exteroceptive task). (c) The interaction patterns of the left and right anterior insular cortex (AIC) activity without physiological correction. (d) The interaction patterns of the left and right AIC activity with physiological correction.CC0 · PubMed Central
Author response image 4. Paired t-test on beta maps obtained without and with physiological correction. (a) using interoceptive vs. exteroceptive contrast maps. (b) using interaction effect beta maps.
Author response image 4. Paired t-test on beta maps obtained without and with physiological correction. (a) using interoceptive vs. exteroceptive contrast maps. (b) using interaction effect beta maps.CC0 · PubMed Central
Author response image 5.
Author response image 5. CC0 · PubMed Central
Author response image 6. The F-test across all RETROICOR regressors. Voxelwise p < 0.001.
Author response image 6. The F-test across all RETROICOR regressors. Voxelwise p < 0.001.CC0 · PubMed Central

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Cites

Research works printed but not linked: 3

  1. Hamilton, 1976, Sourcebook of Adult Assessment: Applied Clinical Psychology, 154
  2. Porges, 1993, Body perception questionnaire, Laboratory of Developmental Assessment, University of Maryland
  3. Tranel, 1991, Somatic Markers and the Guidance of Behaviour: Theory and Preliminary Testing

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Metadata

Authors
Wang, X., Wu, Q., Egan, L., Gu, X., Liu, P., Gu, H., Yang, Y., Luo, J., Wu, Y., Gao, Z., & Fan, J.
Affiliations
  • Capital Medical University (CN)
  • Peking University (CN)
  • Queens College, CUNY (US)
  • James J. Peters VA Medical Center (US)
  • National Institute on Drug Abuse (US)
  • Capital Normal University (CN)
Corresponding author
Fan, Jin
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2019-04-15
Volume
8
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.42265
PMC
PMC6488299
OpenAlex
W2899948248
Cited by
204
References
131
Citations by year
2026: 31 · 2025: 37 · 2024: 31 · 2023: 40 · 2022: 28 · 2021: 17 · 2020: 18 · 2019: 2
FWCI
12.95
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, public-domain)
  • PubMed Central (publishedVersion, public-domain)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Greater South Information System
Funders
  • Beijing Municipal Administration of Hospitals (Youth Program QML20170503)
  • National Natural Science Foundation of China (81600931, 31771205, 61690205, 81328008, 81729001)
  • Capital Health Development Research Project of Beijing (2016-4-1074)
  • Brain Research Project of Beijing (Z16110002616014)
  • China Postdoctoral Science Foundation (2016M600835)
  • National Institute on Drug Abuse (1R01DA043695, Intramul Research Program)
  • The Mental Illness Research, Education, and Clinical Center, James J. Peter Veterans Affairs Medical Center (MIRECC VISN 2)
  • National Basic Research Program of China (973-2015CB351800)
  • National Institute of Mental Health (R01MH094305)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Psychosomatic Disorders and Their Treatments
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Tactile and Sensory Interactions
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
Keywords
anterior insula, interoceptive attention, interoception, respiratory rhythm, interoceptive accuracy, interoceptive sensitivity, somatosensory cortex, individual differences
MeSH terms
Attention, Brain Mapping, Cerebral Cortex, Humans, Magnetic Resonance Imaging, Healthy Volunteers, Interoception

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