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

PersPectivesBox 1 | The co-activation of the AIC and the ACCIt is understandably mystifying that a region ofthe ventrolateral prefrontal cortex (the anteriorinsular cortex (AIC)) and a region of the medialprefrontal cortex (the anterior cingulate cortex(ACC)) are co-active in so many behaviours,because such widely separated regions in thecortex generally have distinct roles. Theinsular cortex was long regarded simply as avisceral sensory region, based on findings byPenfield, Mesulam and Saper 84–86 , whereas themedial prefrontal cortex has been associatedwith conflict responses, impulsive behaviourand autonomic activity. In an earlier article Isuggested that the insula and the ACC beregarded as limbic sensory and motor corticesthat respectively engender the feeling and themotivation (agency) that constitute anyemotion 1 . This suggestion was based on thedual lamina I spinothalamocortical projectionto both the insula and the ACC, theco-activation of these areas in virtually allstudies of emotion, their respective descendingprojections to sensory (parabrachial nucleus)and motor (periaqueductal grey) brainstemregions, the overall anatomical organization ofthe frontal cortex into sensory and motornetworks, and the evolutionarily ancient limbicrole of the cingulate cortex in integratedbehavioural control. I regarded the AIC as theprobable site for awareness on the basis of itsafferent representation of the ‘feelings’ fromthe body, and the ACC as the probable sitefor the initiation of behaviours. A recentreview 87 offered support for this view and anexplanation for the anatomical separation ofthe insula and the ACC. The ACC evolved firstas a motor-control region aligned with thesensory integration, in the hippocampus andthe amygdala, of olfactory-guided groupbehaviour in mammals. The insula evolved laterfor cortical processing of homeostatic sensoryactivity in the individual animal. The tworegions naturally became linked for integrativeautonomic control, and in mammalian evolutionthe insula grew as limbic behavioural activitybecame aligned more with autonomic activitythan with olfactory activity. This anatomicalperspective 87 is illustrated in the ventral view ofthe brain in the figure, which reveals thecommon relationship of these structures to theolfactory epithelium. Figure is reproduced, withpermission, from ReF. 87 © (1999) Elsevier.aCingulate sulcusRhinal sulcusbInsulaOlfactory cortexEntorhinal areaHippocampusCollateral sulcusLaterobasal cortical amygdalaOlfactorybulbOlfactorypeduncleOlfactory tractAnterior olfactory nucleusDiagonal bandBasolateral amygdalaHippocampusRisk, uncertainty and anticipation. Of thearticles listed in Supplementary informationS1 (table), I note particularly one report that‘emotional value’ in the immediate present,as specified in a second­order temporaldifferencemodel of learning, correlatedselectively with activity in the right AIC 24 ;another study (in which this learning modelwas adapted for neuroeconomic studies)reported that both the risk­prediction signalsand the risk­prediction error signals specifiedin the model were present only in thebilateral AIC 25 . No activation was observed inthe ACC in this study. Activation in the AICis also correlated with feelings of anticipatedvalue during purchase and sales decisions 26 .Visual and auditory awareness of themoment. Several reports that associated activationin the AIC with awareness of sensoryNature Reviews | Neurosciencebistable percepts must be explicitly notedhere 27–29 , but I highlight three additionalstudies. The first is a PET study which foundthat the right AIC and the ACC are sensitiveto cross­modal sensory time synchronizationand display a graded response to amismatch in timing between auditory andvisual stimuli that should normally be synchronous(for example, a speaking mouth) 30 .The second is an fMRI study that examined62 | JANuARy 2009 | VOLuME 10 www.nature.com/reviews/neuro© 2009 Macmillan Publishers Limited. All rights reserved