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

PersPectivesBox 3 | Forebrain asymmetry of emotionThere are two sides of the brain, and so if there are separate time-based representations of thesentient self that subserve awareness in the anterior insular cortex (AIC) (one in each side), howare they coordinated to generate one unified self? The homeostatic model of awarenesspresented in this and prior articles 1,78 suggests that there is an energy efficiency-optimal processthat is based on the coordinated opponency of the autonomic system — that activity in the rightside of the forebrain is associated with energy expenditure, sympathetic activity, arousal,withdrawal (aversive) behaviour and individual-oriented (survival) emotions, and activity in theleft side is associated with energy nourishment, parasympathetic activity, relaxation, approach(appetitive) behaviour and group-oriented (affiliative) emotions. This proposal is described indetail in prior articles 78,95 . Briefly, the origin of this asymmetry can be related to the asymmetricautonomic innervation of the heart, and its evolutionary development would have beencompelled by the need for energy optimization in the brain (which consumes 25% of the body’senergy). This model fits with an accumulating body of psychophysical literature which indicatesthat the left and right forebrain halves are differentially associated with positive and negativeaffect 96 and, importantly, with the anatomical and functional asymmetry in the homeostaticafferent input to the insular cortex 5,97,98 and in forebrain cardiac control 99 . It can explain whyunder particular conditions the AIC is more active on one side (FIG. 2) but also why in mostconditions the two sides display joint activity, which mirrors the coordinated sympathetic andparasympathetic control of the heart. The model offers explanations for why positive emotionscan reduce or block negative emotions (and vice versa), why the left (affiliative, vagal) sidecontrols deictic pointing and verbal communication, and how increased parasympathetic activity(for example, activation of vagal afferents by gastric distension, slow breathing or elecricalstimulation) can reduce negative emotions (for example, pain). Given the many asymmetries inthe activations of the AIC noted in this article, investigations addressing this model in split-brainpatients could be enlightening, particularly if performed with those rare patients in whom boththe corpus callosum and the anterior commissure are sectioned 100,101 .“feeling of knowing”, which is the subjectivesense of knowing a word before recalling it.(The “feeling of knowing” has been interpretedas a subjective feeling that representsthe retrievability, accessibility or familiarityof the particular target word, which correlateswith the subsequent ease of recall 41,42 .)using a well­tested set of general­knowledgequestions without prior exposure or priming,they found pronounced activation inthe bilateral AIC/IFG and the ACC that correlatedparametrically with the strength ofthe “feeling of knowing”. The bilateral AIC/IFG was not recruited during the successfulrecall process itself, which implied to theauthors a “particular role in meta­memoryprocessing” for this area.Cognitive control and performance monitoring.Several reports in this major fieldof study described strong activation in theAIC. One described functional­connectivityanalyses that were performed on brain activationduring a combined working­memoryand target­switching task; a “cognitivecontrolnetwork” was identified thatincludes the bilateral AIC and the ACC 43 .In another report, brain activation was analysedduring various cognitive­control tasksand the authors concluded that the bilateralAIC and the ACC form a highly interconnected“core” system for task­dependentcontrol of goal­directed behaviour andsensory processing 44 . A study that used astop­signal paradigm in which the subjectsvoluntarily initiated a hand movement buton signalled trials inhibited the movementat the last possible subjective instant foundthat the bilateral AIC (L>R) and a smallregion in the MPFC near the ACC regionwere specifically involved in the active,willed inhibition of a motor act (which theauthors called “free won’t”, as opposed tofree will) 45 . The authors associated the AICactivation with the affective consequence ofcancelling a motor intention (frustration),and other investigators in similar studiesassociated such activation with autonomicarousal 46 . However, an alternative interpretationis that the occurrence of the stopsignal naturally elicited an immediatelyheightened awareness — such heightenedawareness would certainly have increasedwith the rarity of the stop signal, as theinvestigators found for the AIC 46 andthe MPFC region 45 . In another study, performanceerrors were examined in subjectsengaged in a demanding repetitive task,similar to that used in the lapse­of­attentionstudy described above 37 , and thenindependent component analyses and backwarddeconvolutions were performed toidentify brain­activation patterns that precedederrors 47 . The authors found four setsof brain regions in which activity patternspredicted the commission of an error; thefirst set consisted of the bilateral AIC and theACC, which they suggested act as a performancemonitor. Another set of brain regionsthey identified consisted of the right AIC/IFGand an MPFC region near the ACC, whichthey associated with the evaluation of taskcosts and the maintenance of task effort. Inthe latter regions, activation declined justbefore an error occurred and increased afteran error had occurred, similar to the patternof attention­related activity in the study oflapses of attention described above 37 . Theseresults are therefore also consistent with thealternative interpretation that the AIC activityrepresents awareness and that the ACCactivity represents the control of directedeffort. A recent study performed severalsophisticated connectivity and correlationanalyses of attentional transitions and confirmedthat the AIC and the ACC act as acognitive­control network and, further, thatthe right AIC in particular “plays a criticaland causal role in switching between thecentral executive network and thedefault­mode” or self­reflective network 48 .Finally, a study by Klein et al. 23 may providedirect evidence that the AIC engendersawareness. The authors used an antisaccadetask with a distractor (in which subjects wereinstructed to shift their gaze in the oppositedirection to a briefly displayed indicator butwere occasionally misdirected by an interveningcue that indicated the other direction),which produced occasional erroneoussaccades that the subjects were either awareof (and signalled with a button press) orunaware of. The subjects’ error­awarenessreports were corroborated by slowed reactiontimes and improved performance (formost subjects) on trials following ‘aware’errors but not following ‘unaware’ errors.The fMRI data on error trials revealed activationof the bilateral AIC and three smallMPFC regions near the ACC. By contrastingbrain activity during aware errors with thatduring unaware errors, the authors foundactivation only in the left inferior AIC (similaractivation in the right AIC was just subthreshold).Significantly, activation near theACC was not associated with error awareness.The authors suggested that the activityof the AIC during aware errors might beexplained by interoceptive awareness ofgreater autonomic responses to aware errors(which have been documented previously),but they also recognized that the AIC activityand error awareness might precede theautonomic response 23 . They recommendedthe use of electroencephalographic recordingsto resolve this uncertainty, because thetemporal resolution of fMRI is too low.64 | JANuARy 2009 | VOLuME 10 www.nature.com/reviews/neuro© 2009 Macmillan Publishers Limited. All rights reserved