Bonaz, Lane, Oshinsky, Kenny, Sinha, Mayer & Critchley (2021) — Diseases, Disorders, and Comorbidities of Interoception
The third paper the wiki has read from the Trends in Neurosciences January 2021 interoception special issue, and the one that takes the field furthest from where the rest of this wiki lives. Almost everything here is about emotion, self, and mental health. This review is about gastroenterology, urology, rheumatology and neurology — IBS, bladder pain, hypermobile joints, multiple sclerosis, Parkinson’s, Alzheimer’s — argued to be interoceptive conditions in the same sense that panic and depression are.
It contradicts nothing in the wiki. Its value is coverage: it is the first source here to treat interoception as a medical rather than psychological subject, and the first to make the whole neuraxis, not just cortex, the site where interoception can fail.
The organizing claim: dysfunction at any level, expressed at every level
The frame is worth stating precisely because it is what licenses the review’s range. Interoception is a bidirectional predictive system running from receptor to cortex; therefore:
Perturbed interoceptive representation, integration, and predictive control can originate at any level of the neuraxis and impact distinct component processes or affect the whole bidirectional system.
Downward: “higher-order cognitive ‘beliefs’ or emotional dysfunction can drive maladaptive responses expressed through endocrine, immune, inflammatory, somatic, cardiovascular, and neurological channels.” Upward: peripheral pathology propagates into representation. The review’s Figure 1 is Stephan, Petzschner and colleagues’ allostatic self-efficacy circuit reproduced directly (adapted from their Figure 7), with a lightning bolt drawn onto it marking where interoceptive dysfunction strikes — and arrows radiating out to psychiatric disorders, neurological disorders, addiction, chronic visceral pain, neurodegenerative disease, autism, pelvic disorders, arthritis and comorbid conditions.
That is a strong architectural commitment and the wiki should record it as such: the same diagram the computational-psychiatry page holds as a theory of fatigue and depression is here made the general theory of psychosomatic medicine. See allostasis, where allostatic self-efficacy already sits, and central-autonomic-network, the anatomical layer the review adds beneath it.
Three clinical features are proposed as the shared surface expression across these disorders: anticipatory symptom-related anxiety, central sensory amplification, and aberrant autonomic activation. If the unifying claim has empirical content, it is here.
The neurological section: interoception dissociated by lesion
The most evidentially solid material in the paper, and new to the wiki, because it is the one place where interoceptive dimensions come apart through damage rather than through psychometrics.
- Viscerosensory vs somatosensory heartbeat experience dissociate. Patients with bilateral ischemic damage to insula and ACC may retain residual somatosensory but not viscerosensory experience of their own heartbeats, tested under pharmacologically induced tachycardia (García-Cordero et al. 2016; Khalsa et al. 2009’s isoproterenol method). The felt heartbeat is not one thing.
- Cardiac interoception, emotion recognition and theory of mind fall together. After fronto-insular-temporal ischemic stroke, heartbeat-detection deficits are linked to deficits in emotion recognition and mentalizing — read as confirming that network’s role in integrating interoceptive information into emotional and social representation.
- Focal insular lesions produce specific affective losses: disgust insensitivity, acquired alexithymia, psychopathy, and loss of drug-craving — the last being a striking convergence with the addiction material later in the same paper.
- Alzheimer’s disease shows a four-way interoceptive deficit that maps cleanly onto the wiki’s taxonomy: impaired accuracy (imprecise fingertap tracking of own heartbeats), abnormal heartbeat-evoked potential modulation, impaired interoceptive learning (negligible gain from feedback), and impaired metacognitive awareness (confidence-accuracy mismatch). Prolonged vagus somatosensory evoked-potential latencies distinguish AD from major depression.
- Tourette syndrome: interoceptive deficits linked to the premonitory urge-to-tic — an interoceptive account of a symptom usually described motorically.
- Multiple sclerosis and Parkinson’s: structural insula abnormality and altered cardiac-interoception responses; interoceptive processing deficit proposed as a behavioural marker for subtyping Parkinson’s.
Also here: functional (psychogenic) neurological disorders — functional motor disorders and functional seizures — where interoceptive abnormalities predict dissociative symptoms and seizure frequency. See functional-disorders.
The caution the wiki should attach: nearly all of this rests on the resting cardiac tasks, and Critchley co-authored both the review that flags those tasks’ generalizability problem and this one, which uses them without the flag. See is-the-heartbeat-counting-task-valid.
The somatic-visceral sections: medicine as interoception
This is the review’s distinctive payload, and none of it existed in the wiki before.
IBS — the most common disorder of brain-gut interaction, 5–20% of people worldwide, still diagnosed on symptom criteria in the absence of agreed biomarkers or organic pathology. IBS patients score high on interoceptive sensibility (subjective self-report), consistent with a strong focus on gut symptoms, while deficits in interoceptive processing increase risk. That accuracy-low/sensibility-high shape is the same signature the ITPE literature reports for autism and anxiety, reached independently in gastroenterology — the wiki’s best evidence that the discrepancy profile is not an artefact of one measurement tradition.
The microbiota-gut-brain axis — an interoceptive channel the wiki did not have, and one that does not run through neurons at the periphery at all. Bacterial metabolites reach the CNS via systemic circulation or via enteroendocrine cells relaying luminal signals to vagal afferents; short-chain fatty acids stimulate EECs to release neurotransmitters activating those afferents; bacterial lipopolysaccharides directly activate toll-like receptors (TLR4) on vagal afferents. This is the humoral channel Quadt et al. flagged, extended to a signalling source that is not the body’s own.
chronic-pain — deficits in objective interoceptive accuracy predict symptom severity; sensibility and metacognitive awareness data are “less conclusive.”
Pelvic disorders — urological chronic pelvic pain syndrome as chronic idiopathic visceral (i.e. interoceptive) pain, with functional abnormality in a bladder–pontine micturition centre–locus coeruleus–forebrain pathway, linked to EALs and exacerbated by stress. ~60% of women with pelvic floor disorders have overlapping bladder and bowel symptoms, and experimental bladder filling and rectal distension both activate the insula — offered as a partial account of the overlap.
joint-hypermobility — Critchley’s own line, and the most surprising item in the review. Variant connective tissue (the Ehlers-Danlos spectrum) is associated with higher interoceptive sensitivity, heightened insula reactivity, and anxiety symptoms; postural orthostatic tachycardia syndrome is a common comorbidity mediating affective symptoms; and both hypermobility and PoTS are increasingly recognized in autism and ADHD. A connective-tissue variant with an interoceptive and psychiatric phenotype is the strongest single case for the review’s bottom-up limb.
Comorbidity, adversity, and the addiction thread
The review’s account of why these conditions cluster is early adverse life events. The animal evidence is specific — maternal deprivation in rats produces long-term central CRF changes and predisposes adults to stress-induced visceral hypersensitivity, with increased defecation, intestinal mucosal dysfunction under stress, greater colitis sensitivity, raised HPA response and heightened anxiety in the same animal — which is the clearest demonstration in the paper that one early perturbation can express across organ systems. The human side is correlational: childhood trauma negatively correlates with interoceptive ability (heartbeat detection after cold pressor), and maltreatment is associated with lower cardiovascular and HPA responses alongside higher subjective distress. Maternal nurture is named as the protective factor, with a mother’s reading of her child’s bodily needs laying the foundation for mentalization — Fotopoulou & Tsakiris’s “mentalizing homeostasis,” which is social-origins-of-interoception arriving from a second direction. Compare oldroyd-2019-attachment-interoception.
On addiction, craving is framed as an interoceptive motivational feeling that varies with drug state (intoxication, tolerance, withdrawal, abstinence, recovery), with alcohol acting partly through a humoral interoceptive route (HPA stress-hormone release, glucocorticoid receptor upregulation in limbic forebrain and mPFC), and stress hormones themselves serving as conditioned interoceptive cues motivating consumption. The eating sections run the same logic through satiety: reduced interoceptive sensitivity in obesity, distorted interoceptive prediction in anorexia, leptin resistance of vagal afferents accompanying hyperphagia.
Kenny’s molecular section is the finest-grained mechanism in the paper — nicotine activating GLP-1 neurons in the NTS, exciting medial habenular projections to the interpeduncular nucleus, attenuating nicotine reward and hyperglycemia in mice — and also the furthest from anything else in the wiki. Recorded as mouse circuit work with an interoceptive framing, not as a human finding.
The translational close
Two deliverables are proposed. Interoceptive biomarkers — questionnaires, heartbeat-detection performance, autonomic measures (baroreflex sensitivity, HRV), neuroendocrine response (salivary cortisol, NPY), neuroimaging, M/EEG — with the concession that “few of these measures have yet found broad clinical application in this role.” That is the same empty cupboard the roadmap reported in 2018 and Petzschner et al. report in the same issue, now stated a third time.
And bioelectronic-medicine — VNS, spinal cord stimulation, TMS, tDCS, DBS as “electroceutical” intervention on brain-body communication, alongside the psychological route (biofeedback, interoceptive exposure of panic). This is the wiki’s first translational thread that treats the interoceptive pathway rather than interoceptive attention as the target — a genuinely different intervention logic from the contemplative and exposure material the wiki otherwise holds. Bonaz’s own VNS/anti-inflammatory work is the evidence base cited.
Sex and gender differences in interoceptive sensitivity and neural reactivity are flagged as an under-handled consideration for biomarker development.
Placement, and the vagus
A fourth quadrant joined the issue with the Quigley et al. (2021) ingest — the functional one, asking what interoception is for. Two direct points of contact: their lower-urinary-tract physiology is the normal-function counterpart to this review’s pelvic-pain section, and their reading of homeostasis as retaining local autonomy sits against this paper’s “enslaved” reflex arcs (recorded on homeostasis).
Read as the clinical-medicine quadrant, standing beside Quadt et al. (2018) (psychiatric conditions, same Critchley lineage, more careful about measurement) and Petzschner et al. (2021) (the computational quadrant, cited here as reference 118). Where Quadt et al. work six psychiatric conditions through one inferential mechanism, Bonaz et al. work twenty-odd conditions across all of medicine through one architectural diagram — broader, shallower, and more useful for knowing that the claim has been made than for knowing it is true.
One structural note. The vagus nerve carries this paper: immune-to-brain signalling, the microbiota axis, VNS as therapy, vagal SEP latencies in Alzheimer’s. The wiki’s only vagus page is polyvagal-theory, held at one remove through Somatic Experiencing and flagged as contested. Bonaz is a vagus researcher writing about the vagus, and nothing here depends on or endorses Porges’s three-branch scheme — so the wiki now holds mainstream vagal-interoceptive material that is entirely independent of the polyvagal framework. Worth keeping separate.