The pathways of interoceptive awareness
Open accessAbstract
A network of cortical brain regions, including the insula and anterior cingulate cortex (ACC), has been proposed as the critical and sole substrate for interoceptive awareness. Combining lesion and pharmacological approaches in humans, we found that the insula and ACC were not critical for awareness of heartbeat sensations. Instead, this awareness was mediated by both somatosensory afferents from the skin and a network that included the insula and ACC. Together, these pathways enable the core human experience of the cardiovascular state of the body.
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Roger was unable to detect heart rate change at low doses of isoproterenol, had longer response lag than controls, and his interoceptive awareness worsened after anesthetic application.
“For instance, he was unable to detect heart rate change at low doses of isoproterenol infusion, his response lag was significantly longer than controls, and his interoceptive awareness was greatly worsened after anesthetic application (Khalsa et al., 2009).”
From Anterior insular cortex and emotional awareness (2013) · cites this paper as Khalsa et al., 2009
In the supplied passage labeled Abstract (page not provided), Roger's awareness ratings were somewhat delayed, and he reported no changes in cardiac sensation after topical anesthetic was applied. The copy does not say he could not detect changes at low isoproterenol doses or establish that his response lag was statistically significantly longer than controls'. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe insula is a key cortical structure for identifying interoceptive states and emotional awareness.
“Moreover, the insula is a key cortical structure for identifying interoceptive states and emotional awareness (Critchley et al., 2004; Khalsa et al., 2009; Khalsa et al., 2018); thus, aberrations at the level of the insula among individuals with PTSD may have negative cascading effects on the capacity for regulating emotion in higher-order prefrontal lobe structures of the brain.”
From How Processing of Sensory Information From the Internal and External Worlds Shape the Perception and Engagement With the World in the Aftermath of Trauma: Implications for PTSD (2021) · cites this paper as Khalsa et al., 2009
The Abstract describes the insula as important for representing bodily states and as typically considered a key structure for visceral sensation. But it says the insula is not necessary for heartbeat awareness and that its role in the experience of emotion remains to be determined. The claim overstates the paper’s support for the insula’s role in emotional awareness. (LLM, conf=0.84)
Experimental — accuracy not yet measuredDespite the variance, the brain tracks such changes in similar subregions, including the insula, somatosensory cortices, cingulate, amygdala, thalamus, and brainstem.
“Despite the variance, the brain tracks such changes in similar subregions, including the insula, somatosensory cortices, cingulate, amygdala, thalamus, and brainstem (42,43,51–53).”
From Interoception and Mental Health: A Roadmap. (2018) · cites this paper as [43]
The indexed paper (Abstract; page unavailable) links interoceptive awareness to the insula, anterior cingulate cortex, and somatosensory cortices. It mentions the amygdala as a damaged region in one patient, but does not establish that it tracks bodily changes; the passages also do not identify the thalamus or brainstem as tracking them. (LLM, conf=0.88)
Experimental — accuracy not yet measuredSeveral brainstem, subcortical, and cortical regions represent key afferent processing regions for interoception.
“Several brainstem (nucleus of the solitary tract, parabrachial nucleus, and periaqueductal gray), subcortical (thalamus, hypothalamus, hippocampus, and amygdala), and cortical regions (insula and somatosensory cortices) represent key afferent processing regions (22,42,43).”
From Interoception and Mental Health: A Roadmap. (2018) · cites this paper as [43]
The paper’s Abstract identifies the insula and somatosensory cortices as parts of interoceptive afferent pathways. It does not identify the listed brainstem regions, thalamus, or hypothalamus as key afferent processing regions; it mentions the hippocampus and amygdala as damaged in the patient but says such structures are less often implicated in interoceptive awareness. Page numbers are unavailable in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredOnce participants' chests were anesthetized, they were no longer able to detect their heartbeat at rest.
“In that study, once the participant’s chests were anesthetized, they were no longer able to detect their heartbeat at rest (Khalsa et al., 2009).”
From Mindfulness, Interoception, and the Body: A Contemporary Perspective (2019) · cites this paper as Khalsa et al., 2009
The anesthetic-challenge passage (section labeled Abstract; page not provided) reports that Roger no longer perceived changes in cardiac sensation after topical lidocaine was applied. It does not establish that participants generally could not detect their heartbeat at rest: the test repeated an isoproterenol challenge, and the healthy comparison participants’ sensations were unaffected. (LLM, conf=0.90)
Experimental — accuracy not yet measured
Three recent case studies reported intact interoceptive awareness and self-awareness after bilateral insular lesions.
“Three recent case studies specifically examined the effects of bilateral insular lesions on subjective awareness and reported intact interoceptive awareness (Khalsa et al., 2009) and self-awareness (Philippi et al., 2012; Damasio et al., 2013).”
From Anterior insular cortex and emotional awareness (2013) · cites this paper as Khalsa et al., 2009
Patient Roger exhibited deficits in certain aspects of interoceptive awareness.
“Third, patient Roger did exhibit deficits in certain aspects of interoceptive awareness, as reported in supplemental materials by Khalsa and colleagues (2009).”
From Anterior insular cortex and emotional awareness (2013) · cites this paper as Khalsa et al., 2009
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Feeling in Control: The Role of Cardiac Timing in the Sense of Agency
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- Authors
- Khalsa, S. S., Rudrauf, D., Feinstein, J. S., & Tranel, D.
- Affiliations
- University of Iowa (US)
- Corresponding author
- Khalsa, Sahib S
- Venue
- Nature Neuroscience
- Published
- 2009-11-01
- Volume
- 12
- Issue
- 12
- Pages
- 1494-1496
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC2787640
- OpenAlex
- W1964020740
- Cited by
- 387
- References
- 17
- Citations by year
- 2026: 21 · 2025: 27 · 2024: 37 · 2023: 29 · 2022: 35 · 2021: 36 · 2020: 32 · 2019: 23 · 2018: 21 · 2017: 26 · 2016: 26 · 2015: 15 · 2014: 19 · 2013: 14 · 2012: 13
- FWCI
- 5.34
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (R01DA022549)
- National Institute of General Medical Sciences (T32GM007337)
- National Center for Research Resources (M01RR000059, M01-RR59)
- National Center for Complementary and Integrative Health (F31AT003061)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Psychosomatic Disorders and Their Treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Life Sciences › Neuroscience › Cognitive Neuroscience › Tactile and Sensory Interactions
- Keywords
- interoceptive awareness, insula, anterior cingulate cortex, primary somatosensory cortex, somatosensory afferents, pharmacological manipulation
- MeSH terms
- Awareness, Brain Diseases, Cerebral Cortex, Gyrus Cinguli, Heart, Heart Rate, Humans, Magnetic Resonance Imaging, Male, Skin, Somatosensory Cortex, Visceral Afferents
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