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

PersPectivesAPSacasmsSPSpsalIPSplHin well­known melodies were mis­timed) 16 .A recent fMRI study compared activationinduced by listening to pleasant and unpleasantmusic that the subjects selected individuallyand found that subjectively pleasantmusic induced activation of the AIC that wasgreater on the left than on the right side 17 .One review presented evidence that the AICis activated bilaterally during overt speechand singing and, strikingly, that the AIC activationis asymmetric during covert singing:activity in the right AIC was higher duringslow tempos (3 Hz) 18 .Figure 1 | Anatomy of the insula. A photograph of the left insular cortex of a human patient. For acomparison with the insulae of other patients, see ReF. 114. The human insular cortex is a distinct buthidden lobe of the brain. It is disproportionately (~30%) enlarged in the human Nature relative Reviews to | Neurosciencethe macaquemonkey 109 . It has 5–7 oblique gyri, but its morphology is quite variable, even between the two sides 114–118 .A comprehensive hodological description in the macaque is lacking, and few connectivity analyses ofthe insula have been made in humans. Primary interoceptive representations are located in the dorsalposterior insula and re-represented in a polymodal integrative zone in the mid-insula and again in theanterior insular cortex (AIC) 2,7,119,120 . The primary interoceptive, gustatory and vagal representationsextend to the anterior limit of the insula in macaques but only to the middle of the insula in humans 98,121–124 ,which suggests that the AIC of humans has no equivalent in the monkey. The most anterior and ventral(inferior) portion of the human insula that adjoins the frontal operculum is probably the most recentlyevolved, because this part (as well as the anterior cingulate cortex; BOX 1) contains von Economo neurons(BOX 2). as, anterior short insular gyrus; al, anterior long insular gyrus; ac, accessory gyrus; APs, anteriorperi-insular sulcus; H, Heschl’s gyrus; IPs, inferior peri-insular sulcus; ms, middle short insular gyrus; ps,posterior short insular gyrus; pl, posterior long insular gyrus; sPs, superior peri-insular sulcus. Photographis courtesy of Professor Thomas P. Naidich, Mount sinai Medical Center, New York.in the bilateral mid­insula. Another studyreported activation in the right mid­insuladuring the rubber­hand illusion, in whichthe subject was not actually moving but feltlike the moving hand was their own 13 . Theauthors suggested that the mid­insula activationduring movement might represent asense of body ownership rather than agency.No activation was observed in the ACC inthese studies. Finally, a recent study reportedthat simply hearing the piano notes that asubject has just learned to play activates thesame mid­insular region 14 . Based on a metaanalysisthat they performed of prior studies,the authors proposed that the insula containsa sensorimotor map that represents movements.My interpretation of these studies isthat the insular cortex contains a somatotopicrepresentation of the subjective feelings ofone’s current movements as part of arepresentation of all feelings from the body.Self-recognition. The imaging studies citedin Supplementary information S1 (table)reported that the act of seeing one’s ownimage produced activation in the AIC. Themost recent study 15 contrasted brain activationin subjects viewing photos of their ownface or body with activation when thesesubjects viewed photos of a close colleagueor scrambled images. During both types ofvisual self­recognition the authors foundselective activation of the AIC and the adjacentIFG and ACC, all on the right side.They suggested that the right AIC and ACC“could give rise to an abstract representationof oneself that could possibly participate inmaintaining a sense of self ”.Vocalization and music. There are differingviews on the involvement of the insula inspeech (some authors include the insulain Broca’s area), as summarized in thereviews cited in Supplementary informationS1 (table), but there is consistent evidence forthe involvement of the AIC in music. Of note,a PET study reported findings that differentiatedbrain regions associated with familiarity,pitch, rhythm and timbre in music listening;the authors reported robust activation specificallyin the left AIC (not the ACC) duringthe rhythm task (in which occasional notesEmotional awareness. Almost all recentimaging studies of emotion report joint activationof the AIC and the ACC in subjectsexperiencing emotional feelings, includingmaternal and romantic love, anger, fear,sadness, happiness, sexual arousal, disgust,aversion, unfairness, inequity, indignation,uncertainty, disbelief, social exclusion,trust, empathy, sculptural beauty, a ‘state ofunion with God’, and a hallucinogenic state(induced by ayahuasca). Thus, the AIC isactivated not just in association with subjectivefeelings from the body, but apparentlywith all subjective feelings. One noteworthystudy examined resting­state functionalconnectivity and found two networks: an‘executive control’ network that includedthe dorsolateral prefrontal cortex (DLPFC)and parietal areas, and an emotional ‘salience’network that included the bilateralAIC, the ACC, the amygdala and the hypothalamus19 . Significantly, small regions inthe left AIC and the medial prefrontal cortex(MPFC) near the ACC were included inboth networks, suggesting a basis for bothemotional awareness of cognitive functionsand the influence of emotion on cognition.In addition, several studies (for example,ReFs 20,21) found selective activation inoverlapping regions in the AIC during anempathic feeling and a comparable subjectivefeeling (for example, seeing disgustexpressed on another’s face and smellinga disgusting odour, respectively), with theformer located anterior to the latter (consistentwith the posterior­to­anterior gradienttowards greater behavioural complexity inthe frontal cortex 22 ). Notably, similar locationsin the AIC may be active during quitedifferent emotions and behaviours 20,21,23 ;across all studies, a main determinant oflocation in the AIC seems to be the regionof somatic association, with face representationslocated most anterior and hand andfoot representations located more posterior(see also ReF. 14).60 | JANuARy 2009 | VOLuME 10 www.nature.com/reviews/neuro© 2009 Macmillan Publishers Limited. All rights reserved