How do you feel — now? The anterior insula and human awareness

PersPectivesin the representation of the sentient selfduring self­identification. Further, the demonstrationthat AIC activation is correlatedwith the “feeling of knowing” (ReF. 41) suggeststhat the AIC also engenders awarenessof feelings that are associated with mentalconstructs and operations 59,60 .The highlighted findings in the categories‘Risk, uncertainty and anticipation’,‘Time perception’ and ‘Cognitive controland performance monitoring’ are consistentwith the notion that the AIC contains arepresentation of the sentient self not only inthe immediate moment but at each momentacross a finite period of time. The AIC is acentral component of a neural substrate thatrepresents the passage of time 34 , it is sensitiveto time synchronization 30 and it is uniquelyinvolved in automatic comparisons of feelingsin the present moment with those inthe past and the future 25 . These findings alsoindicate that the AIC incorporates a ‘buffer’,or comparator, that is used for such comparisons.These observations suggest that theAIC fulfils a requirement of the proposed 49,53evaluative and predictive role of awarenessin the evolution of emotional communication,and that it affords an integral mechanismfor decision making. (Interestingly,a stable comparator might be perceivedintrospectively as an ephemeral observer, ora Cartesian theater, that nonetheless cannot‘see’ itself, as described 61 for ‘consciousness’.)Significantly, the evidence that the AIC isalso associated with predictions of futurefeelings can explain its involvement in thedistorted interoceptive predictions thatare associated with anxiety and functionalsomatic disorders 62,63 .The findings I highlighted on perceptualdecision making (“choice”) 40 and cognitivecontrol (“free won’t” (ReF. 45), preparation forerror commission 47 and attentional transitions48 ) imply that the AIC has a role in thesubjective guidance of mental and physicalbehaviour. This inference is consistent withthe introspective feeling that ‘I’ am not simplya passive observer (whether this is anillusion or not; see ReF. 64). Such involvementdoes not contradict the idea that the ACCsubserves volitional agency (BOX 1), an ideathat is supported by the ACC’s joint (with theAIC) activation in almost all of these studiesand by its association with action and thedescending limbic motor system 1,65 .Finally, the highlighted findings on theactivation of the AIC during musical enjoymentand ‘heightened awareness’ point tospecific characteristics of the AIC that needto be explained by any model of its role inawareness.Clinical observations. Clinical observationsoffer corroborative evidence for thehypothesis that the AIC engenders humanawareness. Supplementary information S1(table) lists clinical reports that indicateinvolvement of the AIC and the mid­insulawith conditions that include anosognosia,anergia, anxiety, alexithymia, depression,aphasia, amusia, ageusia, drug craving, eatingdisorders, conduct disorder, panic disorder,mood disorders, post­traumatic stressdisorder, schizophrenia, Smith–Magenissyndrome, cardiac arrhythmia, vertigo andfrontotemporal dementia (FTD). Many ofthese reports are quite narrowly focused anddo not describe comprehensive behaviouraltesting, whereas the evidence reviewedabove suggests that most patients with insulardamage could have several significantneurological deficits.Several clinical studies indicate thatdamage to or abnormal activation ordevelopment of the AIC is associated withaltered awareness. Two studies reportedthat anosognosia for hemiplegia is specificallyassociated with damage in the rightmid­insula 66,67 ; adolescents with conductdisorder were found to have a significantdecrease in grey matter volume in thebilateral AIC that correlated with a lack ofempathy and with aggressive behaviour 68 ;patients with borderline personality disorderwho are incapable of cooperatingdo not display the graded activation of theAIC that is associated with awareness ofsocial gestures in normal subjects 69 ; highfunctioningpeople with autism displayedincreased alexithymia and decreased empathy,both of which were correlated withreduced activation in the AIC (in a taskin which the subjects assessed their feelingsabout unpleasant images) 70 (however,see ReFs 71,72); hyperactivity in the rightAIC was selectively associated with anxiety62 ; infarcts of the AIC were reported toproduce anergia, or complete listlessness 73 ;and congenital malformation of the bilateralinsula (Smith–Magenis syndrome)produces childhood mental retardation andthe disruption of self­guided behaviour 74 .Most significantly, patients with FTD associatedwith degenerate fronto­insular andcingulate cortices display a selective lossof self­conscious behaviours and a loss ofemotional awareness of self and others 75 ;in fact, Seeley et al. reported the landmarkfinding that the loss of subjective emotionalawareness in patients with FTD is specificallyassociated with the degeneration ofVENs 76 . These reports are especially notablein light of the obvious difficulties indemonstrating deficits in emotionalawareness in adult humans who havewell­established behavioural patterns.Summary. Thus, the available data providecompelling support for the concept that theAIC contains the anatomical substrate forthe evolved capacity of humans to be awareof themselves, others and the environment.In my opinion, these data suggest that theAIC uniquely fulfils the requirements to bethe neural correlate of awareness. The brainis well organized into networks that distributefunctionality across multiple sites, andthe localization of awareness of feelingsand existence in a single substrate might seemunlikely 67,77 . Nevertheless, the evidence suggeststhat the AIC and the adjoining frontaloperculum (on both the left and right sides)contains an ultimate representation of thesentient self in humans (and perhaps hominoidprimates, elephants and whales; BOX 2).These data recommend a discussion of thepossibility that the AIC is a “neural correlate ofconsciousness” (ReF. 77) and of the questionof how the AIC might engender awareness.A model for awareness in the AICIn a recently published book chapter 78 , Iexpanded on the ideas presented in the 2002Perspective article 1 by outlining a theoreticalmodel for the structural instantiationof awareness in the AIC. The evidencedescribed above of a role for the AIC inawareness is consistent with this model,and thus I elaborate the model here andincorporate these recent findings.Briefly, in this model the cortical basisfor awareness is an ordered set of representationsof all feelings at each immediatemoment extending across a finite period oftime. The key to the cortical (that is, mental)representation of the sentient self is theintegration of salience across all relevantconditions at each moment. The salience ofany factor is determined by its significancefor the maintenance and advancement ofthe individual and the species. At the mostfundamental level, this means the energyefficientmaintenance of the health of thephysical body (and the brain) — in otherwords, homeostasis. In this view, the neuralbasis for awareness is the neural representationof the physiological condition of thebody, and the homeostatic neural constructfor a feeling from the body is thefoundation for the encoding of all feelings 1,78 .The phylogenetically new homeostaticafferent pathway from lamina I and thesolitary nucleus in primates providesthe basis for the sense of the physiological66 | JANuARy 2009 | VOLuME 10 www.nature.com/reviews/neuro© 2009 Macmillan Publishers Limited. All rights reserved