Sickness behaviors
The response that makes interoception a two-way street with the immune system. Quadt et al. (2018) use sickness behaviours (SBs) to make a point the wiki’s mostly-neural, mostly-cardiac interoception material underweights: a large part of the body-to-brain traffic is humoral (blood-borne cytokines, hormones) and immune, not electrical, and it drives a specific, evolutionarily conserved behavioural syndrome.
The syndrome and its channels
Peripheral infection/inflammation is signalled to the brain through three routes: vagal afferents, humoral cytokines reaching the brain via the circumventricular organs (area postrema, OVLT, subfornical organ) and the NTS, and microglial transduction (inflammatory mediators propagating waves of microglial activation across the brain). The output is a narrow, stereotyped repertoire — fatigue, reduced calorie/fluid intake, social isolation, anhedonia, fever — evoked by a wide range of insults. That mismatch (many causes, one behavioural pattern) is the argument that SBs are a coordinated physiological/motivational reaction to a class of interoceptive challenge, not an incidental byproduct: fatigue motivates rest, social withdrawal reduces onward infection, fever fights pathogens.
Experimentally the syndrome is induced with typhoid vaccine, endotoxin infusion, or inhaled antigens, which let the interoceptive pathway be imaged: typhoid vaccination recruits basal/posterior ventromedial thalamus and dorsal mid/posterior insula, and specific SB components map to specific regions — mid-insula (fatigue), subgenual cingulate (mood change), substantia nigra (psychomotor slowing).
The insula mediates the experience
The load-bearing claim for the wiki is that the insula carries the experiential side of being sick: right anterior insula metabolism tracks loss of interest in social interaction, and AI–middle-cingulate connectivity predicts subjective malaise and discomfort after an inflammatory challenge. So the same interoceptive cortex that re-represents cardiac and homeostatic state also renders “I feel ill, I want to withdraw” — inflammation entering conscious feeling through the interoceptive hierarchy, exactly as the IPP account of feeling would predict.
The bridge to depression
Because SBs and major depression share their hallmark — changed motivation, anhedonia, social withdrawal, fatigue — and the same regions (insula, ventral striatum, subgenual cingulate) carry both, SBs are Quadt et al.’s proposed mechanistic bridge from inflammation to mood disorder. Endotoxin reduces ventral-striatum reward reactivity and raises anhedonia (Eisenberger et al. 2010); prolonged or severe inflammation can convert adaptive energy-conserving withdrawal into a depressive episode. Depression’s raised inflammatory markers (IL-6, CRP) sit on the same axis. See interoceptive-psychopathology for the transdiagnostic frame and computational-psychiatry for the “locked-in” EPIC reading in which downweighted, chronically unresolved interoceptive error enlists SBs to conserve energy.
Fatigue as the paradigmatic SB
Fatigue is both a component of SBs and a chronic condition in its own right (chronic fatigue syndrome; a symptom in ~50% of immune-compromised conditions — cancer, MS, fibromyalgia — and a core DSM-5/ICD-10 depression criterion). Its neurobiology is the frontostriatal reward network (ventral striatum) plus insula, reached by immune-to-brain microglial signalling. The newer, top-down reading (Stephan et al. 2016) casts fatigue not only as a bottom-up inflammatory effect but as a metacognitive verdict — aberrant beliefs about the brain’s capacity to predictively control the body (low allostatic self-efficacy), possibly sustained by chronic stress, cortisol, and HPA-axis disturbance feeding back into belief-updating. This is the computational-psychiatry account; the shared point is that fatigue is an interoceptive-regulatory failure, not merely peripheral tiredness.
Where it touches the debates
SBs are a clean case for is-more-interoceptive-awareness-better in reverse: here the adaptive response is to feel the body’s inflammatory state and act on it (rest, withdraw), so blunted interoception of sickness would be maladaptive — but the same machinery, over-run in chronic inflammation, produces the depressive lock-in. More contact is protective acutely and pathological chronically, which is the debate’s recurring shape.