Exposure to subliminal arousing stimuli induces robust activation in the amygdala, hippocampus

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NeuroImage
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Review
Exposure to subliminal arousing stimuli induces robust activation
in the amygdala,hippocampus, anterior cingulate, insular cortex and
primary visual cortex: A systematic meta-analysis of fMRI studies
⁎
S.J. Brooks , V. Savov, E. Allzén, C. Benedict, R. Fredriksson, H.B. Schiöth
DepartmentofNeuroscience,UppsalaUniversity,75124Uppsala,Sweden
a r t i c l e i n f o a b s t r a c t
Articlehistory: FunctionalMagneticResonanceImaging(fMRI)demonstratesthatthesubliminalpresentationofarousing
Received14July2011 stimulicanactivatesubcorticalbrainregionsindependentlyofconsciousness-generatingtop-downcortical
Revised25September2011 modulationloops.Delineatingtheseprocessesmayelucidatemechanismsforarousal,aberrationinwhich
Accepted30September2011 mayunderliesomepsychiatricconditions.HerewearethefirsttoreviewanddiscussfourActivationLikeli-
Availableonline7October2011 hoodEstimation(ALE)meta-analysesoffMRIstudiesusingsubliminalparadigms.Wefindamaximumof9
outof12studiesusingsubliminalpresentationoffacescontributingtoactivationoftheamygdala,andalsoa
Keywords:
significantlyhighnumberofstudiesreportingactivationinthebilateralanteriorcingulate,bilateralinsular
Subliminal
Physiological cortex,hippocampusandprimaryvisualcortex.Subliminalfacesarethestrongestmodality,whereaslexical
Emotionalfaces stimuliaretheweakest.Meta-analysesindependentofstudiesusingRegionsofInterest(ROI)revealednobi-
Audio asingeffect.Coreneuronalarousalinthebrain,whichmaybeatfirstindependentofconsciousprocessing,
Words potentiallyinvolvesanetworkincorporatingprimaryvisualareas,somatosensory,implicitmemoryandcon-
Motivation flictmonitoringregions.Thesedatacouldprovidecandidatebrainregionsforthestudyofpsychiatricdisor-
fMRI dersassociatedwithaberrantautomaticemotionalprocessing.
Meta-analysis
©2011ElsevierInc.Open access under CC BY-NC-ND license.
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2963
Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2963
Definitionofsubliminal. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2963
Searching . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2963
Inclusionandexclusioncriteria. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2963
Selectedstudies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2964
fMRImethods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2966
WholeBrainversusRegionofInterestanalyses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2966
Quantitativedatasynthesis:ALEmeta-analyses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2966
Results. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2966
Meta-analysisone:significantALEclustersfromallstudies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2967
Meta-analysistwo:significantALEclustersfromstudiesemployingsubliminalphysiologicalparadigms . . . . . . . . . . . . . . . . . . 2968
Meta-analysisthree:significantALEclustersforstudiesemployingthesubliminalpresentationofemotionalfaces . . . . . . . . . . . . . 2968
Meta-analysisthree:significantALEclustersforstudiesemployingthesubliminalpresentationoflexical(words,lettersandnumbers)stimuli. . . . 2969
Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2969
Allsubliminalstimuli. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2970
Subliminalphysiologicalstimuli. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2970
Subliminalfacestimuli . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2970
Subliminallexicalstimuli . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2971
Subliminalaudiostimuli . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2971
Subliminalmiscellaneousstimuli . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2971
⁎ Correspondingauthorat:Box593,Husargatan3,DepartmentofNeuroscience,UniversityofUppsala,Uppsala,Sweden.Fax:[phone].
E-mailaddress:[email protected](S.J.Brooks).
1053-8119©2011ElsevierInc.Open access under CC BY-NC-ND license.
doi:10.1016/j.neuroimage.2011.09.077
S.J.Brooksetal./NeuroImage59(2012)2962–2973 2963
Strengthsandlimitations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2971
Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2972
Disclosures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2972
Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2972
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2972
Introduction consciouslyperceived.Sometasksdonotusesubliminalstimuli,butin-
steadpresentstimuliontheperipheryofawareness,sothatconscious
Subliminal paradigms using stimuli that are not consciously per- perceptioncanbeachievedifattentionisaltered(e.g.luminalorsupra-
ceivedhavebeenusedextensivelytotestarousalresponsesinpsychiat- liminalpresentation).Subliminalpresentationismostoftenachieved
ricpopulations,suchasthosesufferingfromanxiety,depressionand by a brief stimulus onset asyncrony (SOA) usually not more than
schizophrenia, and to evoke non-volitional brain mechanisms that 50ms, followed by a ‘masking’ procedure. Backward masking is the
may underlie such disorders. Subliminal stimuli in turn can evoke mostcommon,whereanotherstimulusispresenteddirectlyafterthe
arousingbehavioralresponses,whichhavebeenshowntobothposi- subliminalstimulus,causingtherelayoftheoriginalstimulusfromreti-
tivelyandnegativelyinfluencecognitiveprocessesinhealthypeople natovisualcortextobedisrupted.Subliminalstimulicanalsobeused
(Banse et al., 2001; Fazio and Olson, 2003; Gray, 2001; Hartikainen as‘primers’thatis,influencingfutureconsciousactionwithoutaware-
etal.,2000;MurphyandZajonc,1993).Ithasbeensuggestedthata nessoftheprime.Itisvitaltoensurethatstimuliwereindeedsublimi-
‘quickanddirty’neuralpathwayrelayssensoryinformationdirectlyto nalforeachparticipant,andthisisoftendonewithasubsequent‘forced
theamygdalaethenontoareaV1ofthevisualcortex(LeDoux,1996), choice’procedure.Thisusuallyinvolvespresentingtwostimulisimulta-
and that ‘somatic markers’, or bodily responses to arousing stimuli, neously,onenovelandonethatwasasubliminalprime,andinstructing
oftenoccuroutsideofconsciousawareness(Damasio,2010).However, theparticipanttochooseonethatfeelsfamiliar.Ifaparticipantper-
ithasnotbeenconfirmedwhichcorebrainregionsareactivatedinre- forms at chance level, it is deemed that the subliminal stimuli were
sponsetosubliminalstimuli.MostfunctionalMagneticResonanceIm- notconsciouslyperceived.Thus,inthepresentsearch,allstudiesad-
aging(fMRI)studiesusingsubliminalstimulipresentemotionalfaces heredtothestandarddefinitionofsubliminalpresentationofstimuli.
andshowactivationofsub-corticalregionssuchastheamygdalaand
fusiformgyrus(e.g.Phillipsetal.,2004).
fMRIstudiesarenotoriouslymulti-facetedintermsofthecontrasts Searching
appliedtomeasureneuronalactivation,participantpopulationsstud-
ied, stimulus presentation employed (e.g. event-related versus block Inclusionandexclusioncriteria
design),coordinatesystemsadopted(e.g.MNI,Talairach,AFNI),statis- PubMed,Medline,Ovid,Sciencedirect,WebofScienceandGoogle
ticalanalysesapplied,differencesinscannerequipmentandstrengthof Scholarweresearched,andhandsearchesthrougheachpaper'srefer-
thescannermagnet.Giventhisvariability,itisadvantageoustoconduct encelistuptoSeptember2011.Searchtermswere:(fMRIORMRI)
ameta-analysisoffMRIdata,togainconcordanceinthecorebrainre- AND(subliminal)AND(wordsORpictures)AND(facesORauditory).
gionsreported.Previousmethodswerequiterudimentary,forexample, Theinclusioncriteriawerethat:a)studieswerepublishedwithinthe
listingtheanatomicallabelsqualitativelyreportedineachstudy.How- lastdecade,betweenJanuary2001toSeptember2011,b)published
ever, for a more objective approach, we have applied the Activation inapeer-reviewedjournal,c)usedataskthatutilizedthesubliminal
Likelihood Estimation (ALE) meta-analysis method (Eickhoff et al., presentation of stimuli, d) were original articles written in English,
2009,2010;Lairdetal.,2005;Turkeltaubetal.,inpress).Thisisa3-D e) used functional Magnetic Resonance Imaging (fMRI) and not
voxel-basedstatisticalmethodthatcreatesprobabilitymapsofactiva- otherbrainimagingmodalities(e.g.PositronEmissionTomography,
tion based on the reported peak neuronal activation coordinates in [PET])sothatthedatacouldbebetteraggregatedformeta-analysis,
standard space (e.g. Talairach coordinates). Recent reviews of brain andf)reportedtheneuralactivationcoordinatesinMontrealNeuro-
imagingstudieshaveusedtheALEmethodtoillustratespecificbrainre- logical Institute (MNI) or Talairach space (Talairach and Tournoux,
gionsthatareactivatedtoemotionalstimuli(Costafredaetal.,2008) 1988). MNI coordinates were converted into Talairach for meta-
consciouslyperceivedimagesoffood(vanderLaanetal.,2011)and analyses.Studieswereexcluded(n=35)iftheywerenotwrittenin
rectaldistention(Tillischetal.,2011). English,if the stimuli werepresented above a subliminal threshold
Thus,hereweaimtousetheALE methodtosystematically and (e.g.liminalorsupraliminal),ifnodatawereavailableontheTalar-
quantitatively review neural responses to arousing stimuli derived aich(TalairachandTournoux,1988)orMontrealNeurologicalInsti-
bysubliminalfMRIparadigms.Thisisinordertosystematicallyquan- tute (MNI) activation foci coordinates (and if we were unable to
tifywhichbrainresponsesareassociatedwithnon-volitionalarousal contacttheauthor),ifthestudywasacasereportononeparticipant
thatmayunderliesomepsychiatricconditions.Tohighlightwhichare only,ifarticleswerereviewsordescribingtheorybutnotcontaining
thecoreregionsofneuronalactivation,weconducttoourknowledge original experiments. Studies examining patients with psychiatric
thefirstsystematicreviewandmeta-analysistodateonfMRIstudies conditions(e.g.acutedepressionandschizophrenia)wereexcluded
usingsubliminalparadigms.Theoutcome(dependent)variablesare from the meta-analyses, but patients with physiological conditions
coordinate-basedpeakneuronalactivation(“foci”). withoutdiagnosedpsychiatricorigin(IrritableBowelSyndrome,IBS,
Gastro-esophagealrefluxdisease,GERD)wereincluded.Wealsoin-
cludedfMRIstudiesderivedfrombothRegionofInterest(ROI)and
Methods Whole Brain (WB) analyses to increase the number of the foci and
thus the power of each individual meta-analysis, however, as de-
Definitionofsubliminal scribed below, we ran first level meta-analyses on all studies, then
secondlevelanalyseswithoutROIstudies.Studyselectionwasdone
Allofthestudiesweincludeinthisreviewhaveusedsubliminalpre- by three researchers and cross-checked between them. Thus, the
sentation of stimuli. According to recent definitions (Dehaene et al., aimofthisreviewistoprovide,forthefirsttime,basicinformation
2006;Pessiglioneetal.,2007;Pessiglioneetal.,2008)stimuliareren- about the main areas of activation to arousing subliminal stimuli.
dered subliminal if they are attended to by the brain, but not Foralistofexcludedstudies,seeSupplementaryTable1.
2964 S.J.Brooksetal./NeuroImage59(2012)2962–2973
Selectedstudies bothneutralfacesandagrayrectangle(Dannlowskietal.,2007),neu-
Wefound72studiesthatwereinitiallyscreenedforinclusionin tralfacesandnofaces(Degondaetal.,2005),neutralfacesandabase-
the systematic review and subsequent meta-analyses, but 20 of linefixationcross(KillgoreandYurgelun-Todd,2004),neutralfacesora
thesedidnotmeettheeligibilitycriteria,leavingatotalof52studies blankscreen(Sabatinietal.,2009;Suslowetal.,2010;Williamsetal.,
for inclusion in the meta-analyses. Of these 52 eligible studies, 15 2006).Whenthereweretwocontrastconditions,wechosetoreport
werenotincludedinthemeta-analysesbecausetheydidnotprovide neutralactivationtothesubliminalemotionalvs.neutralfaceasthis
detailsofTalairachorMNIpeakactivationcoordinates,anditwasnot wasthemostcommoncontrast(onlytwostudiesdidnotusesublimi-
possibletogaincontactwiththeauthors.Thus,therewere37studies nalneutralfacesasacontrastcondition:Kouideretal.,2009,unknown
that contributedto themeta-analyses. Four separatemeta-analyses faces,andPanneseandHirsch,2011ablankscreen).Additionally,two
were conducted, representing the different subliminal stimulus studiesusedsubliminalfacesthatcannotbedeemed‘emotional’;gray
modalities that studies employed: all stimulus types, physiological, scalefaces(Dannlowskietal.,2007)andprofessionalfaces(Degonda
visual emotional faces and lexical (visual words/letters/numbers). etal.,2005).Wehaveperformedmeta-analysesbothincludingandex-
Auditory stimuli or ‘miscellaneous’ were not separately meta- cludingthenon-emotionalfaces,andtheresultsarealmostidentical
analyzed because there were only 3 studies in auditory, and 5 andarediscussedbelow.
studies that used a variety of stimulus types in miscellaneous
(which are considered separately in the discussion). In all studies Lexical(words,letters,numbers)(n=10).Tenstudiesaimedtomea-
we only extracted neural activation data relating to contrasts sure brain activity evoked by subliminal lexical stimuli, e.g. words,
between the ‘subliminal stimulus presentation’ and the ‘control’ letters,andnumbers(Bianchi-DemicheliandOrtigue,2009;Dehaene
condition that was used for each study (see Table 1 for details of et al., 2003, 2004; Diaz and McCarthy, 2007; Heinzel et al., 2008;
thecontrolconditionsused).Wedidnotconsiderneuralactivation KouiderandDehaene,2007;Luoetal.,2004;NaccacheandDehaene,
associated with interaction data (e.g. case vs. control, which only 2001;Naccacheetal.,2005;Nakamuraetal.,2005;Nakamuraetal.,
appliedtoafewofthestudies,andweextractedonlywithin-group 2007; Ortigue et al., 2007; Ortigue et al., 2010; Qiao et al., 2010).
comparisons).Wedidthisbecausetheaimofthissystematicmeta- Theparadigmsincludedshowingwordsorletterstringsornumbers
analysis is only to report core neuronal responses to subliminal asprimesandtargetstimuli,subliminallyorsupraliminally.Tocreate
stimuli,andnottoconsiderdifferencesbetweengroups.SeeTable1 subliminalpresentationforwardandbackwardmaskswereusedin
fordetailsofincludedstudies. ordertohinderpotentialfutureperceptionorcamouflagepreviously
Thefollowingsectionsdescribethesestimulusmodalitiesforeach presentedsubliminalstimuli.
ofthemeta-analysesandthestudiesemployingthem. Thecontrastsusedtomeasureneuralresponsestosubliminallexi-
cal stimuli were mainly either a non-subliminal fixation cross
Physiologicalstimuli(n=7).Sevenstudiesusedsubliminalphysiolo- (Dehaeneetal.,2004;DiazandMcCarthy,2007;Qiaoetal.,2010),a
gicalstimuli.Infiveexperiments,researchersstudiedthesensitivity neutral name or noun (Bianchi-Demicheli et al., 2009), an empty
to subliminal rectal stimulation in IBS patients (Andresen et al., frame (Heinzel et al., 2008), a non-word (Kouider et al., 2007), a
2005;Lawaletal.,2005,2006;Sidhuetal.,2004)andhealthycontrols blankscreen(Luoetal.,2004;Ortigueetal.,2007a,2007b)ornon-
(Kernetal.,2004;Lawaletal.,2005;Smithetal.,2011).Acatheter- threateningwords(Naccacheetal.,2005).
affixedpolythenebagwasusedasasourceofthestimuli.Brainactiv-
ityinresponsetothisstimulation,whichwasdeemedsubliminalata Auditory stimuli (n=3). 3 studies examined unperceived auditory
distensionofbelow10mmHg,wasmeasuredwithfMRI,andnodis- stimulionthehealthyhumanbrain(Bijsterboschetal.,2011;Diekhof
tentionwasusedasacomparisoncondition.InthestudiesbyKern etal.,2009;Kouideretal.,2010).Inonestudy(Diekhofetal.,2009)
et al. (2004) and 2009 they used unperceived acid stimulation of subliminalstimuliconsistedofundetecteddevianttones.Inanother
thelowerpartoftheesophagustoelucidatesymptomssuchasheart- study (Kouider and Dehaene, 2007), subliminal words and pseudo
burninGERDpatients.Lawaletal.(2008)examinedbrainactivityin- words spoken by either male, or female voices were used. In the
duced by proximal esophageal distension before, after or without third study (Bijsterbosch et al., 2011), subjects were asked to tap
subliminalacidstimulation. his/her finger in synchrony with a repetitive pacing stimulus. The
The contrasts used to measure neural responses to subliminal pacingstimuluswasasimpleauditorysequenceconsistingofmetro-
physiologicalstimuliwere:restingphasewithoutrectalbaginflation nometonesatafrequencyof500Hzanddurationof50mspresented
(Andresenet al., 2005; Lawal et al., 2005, 2008; Sidhu et al., 2004; throughMRI-compatibleheadphones.Besideregularconditions,the
Smithetal.,2011),restingphasewithnoesophagealacidperfusion taskalsoincludedanirregulartonewithathreepercentperturbation,
(Kernetal.,2004);andrestingphasewithnoelectricalstimulation consideredsubliminal. In order to measurethe neuralresponses to
tothefinger(Taskinetal.,2008). subliminal auditory stimuli all studies used silence as a contrast
condition.
Emotionalfaces(n=12).12studiesexaminedtheeffectsofsublimi-
nalpresentationoffacialimages(Dannlowskietal.,2007;Degonda Miscellaneous(n=5).Fivestudiesusedsubliminalstimulitomeasure
et al., 2005; Duan et al., 2010; Killgore and Yurgelun-Todd, 2004; spatial memory, reward-related motivational responses, cognitive
Kouideretal.,2009;Liddelletal.,2005;Morrisetal.,2007;Nomura control of effects caused by subliminal conflicting stimuli and re-
etal.,2004;PanneseandHirsch,2011;Phillipsetal.,2004;Sabatini sponsestosubliminalphobicstimuli(Janzenand Weststeijn,2007;
etal.,2009;Suslowetal.,2010;Williamsetal.,2006). Lipka et al., 2011; Pessiglione et al., 2007, 2008; Wolbers et al.,
Studiesfirstsetthediscriminationthresholdbypresentingtheim- 2006). In the study by Janzen et al. subjectswatcheda short video
agesatdifferenttimedurationsbeforethemaskordetectionthresh- leadingthemthroughavirtualmazecontainingrecognizableobjects
oldwherethesubjectswereunabletotellwhetherthestimulusisa placed at decision points and non-decision points within the maze
pictureofafaceorablankscreen.Thetargetstimuliacrossstudies (e.g. crossroads). They were afterwards asked in the MR scanner to
consisted of angry faces, surprised faces, happy and sad faces or recognizeobjectsshowninthemazethatwerecombinedwithnovel
familiar and unfamiliar faces. In Killgore et al. subjects were also objectsnotpreviouslyshowninthemaze.Pessiglioneetal.(2007)con-
askedtocompleteataskwheretheymadeagenderdiscrimination. ducted an fMRI study combined with a skin conductance test and a
Thecontrastsusedtomeasureneuralresponsestosubliminalemo- hand-grip force measurement made during an incentive force task
tionalfacesweremostly‘neutral’faceswithnoemotionalexpression, withamonetaryreward.Pessiglioneetal.(2008)usedinstrumental
butinasmallnumberofstudiesthereweretwocontrastconditions: conditioningtoshowhowsmallpunishmentsalteredtheincentiveto
S.J.Brooksetal./NeuroImage59(2012)2962–2973 2965
engage in rewarding subliminal monetary stimuli. Pessiglione et al. tolinkwitheitheragoodorabadoutcome.Thisstudytestedthedegree
(2007) compared alterations in grip force to no grip force (“just do towhichparticipantsaltertheirresponsesfollowingtheunperceived
nothing”),inordertomeasurethedegreetowhichthepresentation prime.Wolbersetal.(2006)examinedcognitivecontrolovertheinter-
of a subliminal reward stimulus (monetary) alters motivational re- feringeffectscausedbyarousingsubliminalconflictingstimuli.Theydid
sponses(thelevel of gripforce).Inafollow-upstudy by Pessiglione this by presenting two stimuli adjacently on a screen (a complete
et al. (2008), subjects were asked to choose either a risky or a safe squarevs.asquarewithahole)bothsubliminallyandafterwardsastar-
choice for monetary reward. Backward masked behind some of the getstimuli andtheparticipantrespondedtothesquarewitha hole.
riskychoiceswasaprimethattheparticipantswerepreviouslytrained Subliminalconflictingstimuliwerethosewhenthesquareswiththe
Table1
fMRIstudiesincludedintotalandseparateALEmeta-analysesforeachsubliminalmodality(n=37).
Study Subliminal Control n Foci fMRI
name stimuli condition analysis
a)Physiological
1 Andresenetal.,2005 Rectalstimulation(baginflated) Restingphaseswithoutinflation 16 45 ROIb
2 Kernetal.,2004 Esophagealacid(acidperfusion) Noacidperfusion(restingphase) 11 6 WBe
3 Lawaletal.,2005 Rectalstimulation(baginflated,musclecontraction) Nostimulation(musclerelaxation) 18 16 WBb
4 Lawaletal.,2008 Rectalstimulation(phasesofproximalesophageal nodistention 20 28 WBe
distention)
5 Sidhuetal.,2004 Rectalstimulation(baginflated) Nostimulation(pressureinbagwasatatmospheric 16 62 WBb
pressure)
6 Taskinetal.,2008 Electricalfingerstimulation Noelectricalstimulation(restingphase) 12 5 ROIb
7 Smithetal.,2011 Rectalstimulation(ballooninflation) Balloondeflation 14 9 WBb
107 171
b)Faces
1 Dannlowskietal.,2007 Grayscalefaces Neutralfaces(ornofaceblockjustagrayrectangle) 23 9 ROIb
2 Degondaetal.,2005 Professionalfaces Neutralfaces/nofaces 16 45 WBb
3 Duanetal.,2010 Surprised,happyfaces Neutralfaces 18 39 WBb
4 KillgoreandYurgelun-Todd, Sad,happyfaces Neutralfaces(orbaselinewithfixationcross) 12 26 ROIb
2004
5 Kouideretal.,2009 Familiar/famousfaces Unknownfaces 16 36 ROIb
6 Liddelletal.,2005 Fearfulfaces Neutralfaces 22 18 ROIb
7 Nomuraetal.,2004 Angryfaces Neutralfaces 9 9 WBb
8 PanneseandHirsch,2011 Participant'sownface Blankscreen 12 8 WBand
ROIb
9 Phillipsetal.,2004 Angry,disgustedfaces Neutralfaces 8 55 WBb
10 Sabatinietal.,2009 Angryfaces Neutralfaces(orblankscreen) 10 15 ROIb
11 Suslowetal.,2010 Happy,sadfaces Neutralfaces(orblankscreen) 56 6 WBe
12 Williamsetal.,2006 Fearfulfaces Neutralfaces(orblankstimuli) 15 8 ROIb
217 274
c)Lexical
1 Bianchi-Demicheliand Sexualpartner'sname Neutralperson'snameandnoundescribingtheir 29 6 WBb
Ortigue,2009 favoritehobby
2 Dehaeneetal.,2004 ClassifyingA,E,I,O,andUlettersinwords Fixationpoint 26 17 ROIb
3 DiazandMcCarthy,2007 Wordsandnon-words Fixationcross/non-wordbaseline 14 4 WBand
ROIb
4 Heinzeletal.,2008 IdentifyingAorB Emptyframecondition 12 18 ROIb
5 Kouideretal.,2007 Pseudowordsdifferingby1letter Blankscreen 15 24 WBb
6 Luoetal.,2004 Wordrepetitionvsunrelatedwords Blankscreen 9 12 WBb
7 Naccacheetal.,2005 Threateningwords Nonthreateningwords 3 10 ROIb
8 Ortigueetal.,2007a Lover,acquaintanceandhobbyprimes Blankscreen 29 30 WBe
9 Ortigueetal.,2007b Beloved,friend,passionname Blankscreen 36 30 WBe
10 Qiauetal.,2010 Easyvsdifficulthandwriting Fixationcross 14 19 WBb
187 170
d)Audio
1 Bijsterboschetal.,2011 Perturbationofauditorytone Silence 16 15 ROIb
2 Diekhofetal.,2009 Subtlechangesinaudiofrequency Silence 9 6 WBe
3 Kouideretal.,2010 Words/pseudowords,differentvoices Silence 16 4 WBb
41 25
e)Miscellaneous
1 JanzenandWeststeijn,2007 Objectlocation,routeinfilmclip Scrambledobjects 15 18 ROIb
2 Lipkaetal.(2011) Spiderpictures Neutralpictures 18 2 ROIb
3 Pessiglioneetal.(2007) Gripforcewithmonetaryreward Nogripforce,“justdonothing” 18 3 ROIand
WBe
4 Pessiglioneetal.(2008) Riskyresponsecombinedwitharewardingorpunishing Riskyversussaferesponses 20 2 WBe
subliminalcue
5 Wolbersetal.,2006 Strategiccontrol,locationprediction Blankscreen 14 28 ROIb
67 51
Grandtotal 619 691
bBlockdesignfMRI,eEvent-relatedfMRI,n=numberofparticipants,foci=numberofseparateTalairachcoordinatescontributingtothemeta-analysis,ROI=RegionofInterest
analysis;WB=WholeBrainanalysis.Bolditemsrepresenttotalparticipantsandtotalfociperseparatemeta-analysis,andgrandtotal.
2966 S.J.Brooksetal./NeuroImage59(2012)2962–2973
holeswerepresentedontheoppositesideofthescreentothetarget. Quantitativedatasynthesis:ALEmeta-analyses
Finally,Lipkaetal.(2011)examinedhowthebrainsofpeoplewitha
spiderphobiarespondedtosubliminalphobic(e.g.spiders)andnon- To examine consensus in reported clusters of neural activation
phobicimages. across studies, we conducted four meta-analyses using BrainMap
GingerALEversion2.0software(Lairdetal.,2005;Turkeltaubetal.,
fMRImethods in press). We applied the updated version of the ALE approach
(Eickhoffetal.,2009)toconductthemeta-analysesusingTalairach
FunctionalMagneticResonanceImaging(fMRI)isabrainimaging or Montreal Neurological Institute (MNI) coordinates (“foci”) from
techniquethatindirectlymeasuresneuralactivationrepresentedby neuroimagingresults.Thefirstmeta-analysisconsistedofcoordinates
Blood Oxygen Level Dependency (BOLD). This is a signal derived taken from all subliminal stimulus modalities (physiological, faces,
fromtheratioofdeoxygenatedtooxygenatedbloodinlocalizedvas- lexical, auditory, and miscellaneous). For the second meta-analysis,
culatureofaspecificbrainregion.Thepremiseisthatthemoreactive we examined coordinates taken only from fMRI studies using
the neuronal population, the greater the level of oxygen extracted subliminal physiological stimuli. For the third meta-analysis we
fromlocalvasculature. used coordinates only for subliminally presented emotional faces.
Wefoundinthisreview,thattomeasuretheBOLDresponse,stud- Thefourthmeta-analysisweusedonlycoordinatestakenfromstud-
iesadoptedeitherablockdesignoranevent-relatedmethod;8outof ies presenting subliminal lexical stimuli. Foci from other stimulus
the37fMRIstudiesusedevent-relateddesign.Event-relateddesign modalitieswerenotmeta-analyzed(auditoryandmiscellaneous)be-
is a technique to measure neuronal responses to briefly presented causethenumberofcontributingstudieswastoosmall(n=3and5
stimuli.Contrastsofneuronalactivationarecalculatedbetweenthe respectively),andalsothestimuliusedweretoodiffusetoconducta
baselineandtheevent.Event-relatedparadigmsinthisreviewused single meta-analysis. Papers that reported coordinates in standard
devianttones,deviantmotion,briefesophagealacidinfusion,esopha- MNIspacewereconvertedintoTalairachspaceusingtheGingerALE
gealdistention,rectaldistention,odd-ballnumberpresentation,writ- software.Textfileswerethencreated,listingthestudynames,their
ten name of a loved one, image of a penny or pound, reward or number of subjects and a list of the foci (Talairach coordinates)
punishmentwordsandanincongruentemotionalface. associatedwithneuralactivation(butnotdeactivation)tosubliminal
Incontrast,ablockdesign,whichaimstomaintaincognitiveen- stimuli. Text files of foci were cross-checked by three
gagement during a task, presents similar images together in blocks researchersindependently.
andalternatesbetweendifferentblocks(torepresentdifferentcondi- ALEisastatisticalmodelingtechnique,specificallydesignedtoad-
tions,usuallyaneutralcontrolandactiveexperimentalcondition).It dressthevariancebetweenandwithinfMRIstudies.Thistechnique
isthemostpopularfMRImethodmainlybecauseitincreasesthesta- uses the total foci coordinates reported in each study to build a 3-
tisticalpowerwheninterpretingthe‘signal-to-noise’ratioinneural dimensional Gaussiankernelto provide a modeledactivation (MA)
activation. Furthermore, statistical analyses can be quite simple, map for each study. The position of foci can be a consequence of
ofteninvolvingthesubtractionofneuralactivationdatainthecontrol between-study variances, such as the different templates used, or
conditionfromtheexperimentalcondition,andfittingtheresulting thedifferencesbetweenparticipants,andassuchthesetwomainis-
datatoaGeneralLinearModel(GLM)ofpredictedBOLDactivation. suesareconsideredintheparametersofthekernel.Thisisdoneby
Block design studies identified in this review (of which there were weighting the foci reported by the number of participants in each
29)usedspokenwords,sexualpartner'sname,electrical fingersti- study. Finally, the MA maps for each study are combined for each
mulation, and presentation of arrows, numbers, word primes, ana- separate meta-analysis, creating an experimental ALE map. This is
grams,emotionalorrecognizablefacesandimagesofspiders.Inall testedagainstthenullhypothesisthatthereisrandomvariationin
cases,thestimulicouldberegardedas‘emotionallyarousing’(apart relationtothespatialorientationofneuralactivationforthespecific
fromtwostudiesusinggrayscaleandprofessionalfaces,althougha meta-analysis (e.g. subliminal presentation of faces), but that the
facepersecouldbedeemedanarousingstimulus). within-studyvariationisfixed.Arandomeffectmodelisemployed
ForthepurposesofthisreviewwetookdataonlyfromfMRIcon- bytheALEanalysistechnique,whichassumesahigherthanchance
trasts that were done between subliminally arousing and sublimi- likelihood of consensus between different experiments, but not in
nallynon-arousingconditions(seeTable1),andfociwerereported relationtoactivationvariancewithineachstudy.Thenulldistribution
on specific neural activation that was greater in the subliminally mapispermutedbythenumberofstudiesthatconstituteeachmeta-
arousingcomparedtothesubliminallynon-arousingcondition(e.g. analysis.Tocorrectformultiplecomparisons,weusedathresholdof
wedidnotreportdeactivationtosubliminalstimuli,nordidwere- pb0.05FalseDiscoveryRate(FDR),andchoseaminimumclustersize
portinteractionsifastudydidthem). of100mm3inlinewitharecentlypublishedfMRIALEmeta-analysis
(vanderLaanLN,2011).Weusedananatomicalimageoverlaypro-
WholeBrainversusRegionofInterestanalyses gram called Mango (Creators, Jack Lancaster, Michael Martinez:
Additionally,fMRIstudiesgenerallyanalyzecontrastseitherusing http://ric.uthscsa.edu/mango) to illustrate the results of our meta-
a Whole Brain (WB) or a Region of Interest (ROI) approach. A WB analyses.
analysismeansthatreportedsignificantclustersofactivationarede- GingerALE employs the term “contributing studies”, to describe
rived by comparing areas of activation globally across the whole studiesthatarelocatedwithintheboundariesofALEcluster.However,
brain,andisnotsubjecttoapriorithresholdsettings.Conversely,a thisdoesnotdiscountotherstudiesthatmightbelocatednearthese
ROIanalysismeansthatamaskorsmallvolumecorrectionisused, boundariesbutoutsideofthecluster,whichcouldhavealsocontributed
to either include or exclude a region of the brain during statistical toit.
analysis.InclusionROIanalyseswerefoundinsomestudiesreported
here,wherebyanalyseswereonlydoneinasmallbrainregionthat Results
wasexpected,basedonpreviousstudies,toshowdifferentialneural
activation. This of course can alter the strength of results obtained, Ofthe72fMRIstudiesinoursearching,thatwerefoundtousesub-
sowedecidedtorunmeta-analyseswithineachmodality,forboth liminalstimuli,20didnotmeetthesearchinclusioncriteria.Thus,52
total studies, and then after excluding those studies that only used studiesremainedandwereincludedinthereview.Ofthese52studies,
ROI analyses. This meant that in the second level meta-analyses 15wereexcludedfromthemeta-analysesbecausetheydidnotade-
(resultsreportedbelow)weexcluded2studiesfromthephysiologi- quatelyreportpeakactivationcoordinatesineitherMNIorTalairach
calmodality,6fromfacesand3fromaudio. space(andwewereunabletocontacttheauthors).Thus,therewere
S.J.Brooksetal./NeuroImage59(2012)2962–2973 2967
37 remaining studies that contributed to the four meta-analyses Meta-analysisone:significantALEclustersfromallstudies
reportedhere.Inthefirstmeta-analysis,all37studieswereincluded;
thesecondmeta-analysiscontained7studiesusingsubliminalphysio- From691foci,619subjectsand37separateexperiments,14clusters
logicalstimuli;thethirdmeta-analysisused12studieswithsubliminal werefoundthatsurvivedtheFDRcorrectionthreshold,threeofthese
faces;thefourthexamined10studieswithsubliminallexical(words, passed the predefined cluster criterion (see Methods). Cluster one
letters,numbers)stimuli.Therewerenotenoughcontributingstudies wasfoundintheleftfusiformgyrus(x=−48,y=−58,z=−6),clus-
to conduct meta-analyses on auditory (n=3) or miscellaneous tertwowasfoundintheleftinsularcortex(x=−26,y=20,z=−4)
(n=5)stimuli.SeeTable1fordetailsofincludedstudies,andsupple- andclusterthreewasfoundintherighthippocampus(x=28,y=2,
mentarymaterialfordetailsofexcludedstudies. z=−18). It must be noted that the data obtained from this meta-
Thesignificantclusters(seeMethodssectionforcontributingstudy analysis includes foci from all stimulus modalities, and so caution
criteria),alongwiththeremainingclustersthatweresignificantatthe mustbeappliedwheninterpretingthesedata.SeeFig.1.
FalseDiscoveryRate(FDR)and100mm3voxelthresholdsarereported We excluded 15 studies that only conducted ROI analyses and
inTable2andSupplementaryTable2fornon-ROIstudies. there were no surviving clusters. This could simply be a power
Table2
LocationsofcentredTalairachpeakcoordinateswithsignificantALEvaluesforthesubliminalfMRIstudiesincludedinthemeta-analysis.
Clustera Anatomicallabelb Peakvoxelcoordinatesc Cluster ALE No.of
size value contributing
(mm3) (×10−2) experiments
x y z %
Allmodalities(n=37)
1 Lfusiformgyrus −48 −58 −6 5280 4.59 15 43
2 Linsularcortex −26 20 −4 3656 3.53 13 37
3 Rhippocampus 28 2 −18 3648 5.55 12 34
4 Rinsularcortex 42 10 12 3200 4.56 10 29
5 Lanteriorcingulate −6 36 22 1440 3.47 5 14
6 Rsuperiortemporalgyrus 46 −42 20 1168 4.61 3 9
7 Lhippocampus −16 −8 −16 768 3.44 4 11
8 Rthalamus 8 −14 12 736 3.14 5 14
9 Rinferiortemporalgyrus 50 −72 2 640 4.67 4 11
10 Ranteriorcingulate 2 18 40 592 2.75 3 9
11 Ranteriorcingulate 6 48 0 376 2.50 1 3
12 Lthalamus −16 −22 10 280 2.97 3 9
13 Rmidfrontalgyrus 36 42 16 280 2.95 3 9
14 Rfusiformgyrus 34 −62 −14 256 2.67 1 3
Physiological(n=7)
1 Rinsularcortex 36 10 4 2688 2.21 4 67
2 Lanteriorcingulate −2 36 18 2232 2.35 4 67
3 Ranteriorcingulate 2 16 32 2168 2.62 4 67
4 Ranteriorcingulate 2 36 0 1408 1.90 3 50
5 Linsularcortex −42 14 10 1160 2.50 2 33
6 Linsularcortex −42 2 −4 600 2.07 2 33
7 Lthalamus −8 −34 4 432 1.94 1 17
8 Lposteriorcingulate 0 −46 22 312 1.84 1 17
9 Rorbitofrontalgyrus 6 54 12 1352 2.00 1 17
Allfaces(n=12)
1 Ramygdala 28 2 −18 5576 5.07 9 75
2 Lhippocampus −16 −8 −16 3352 3.43 7 58
3 Lfusiformgyrus −48 −76 2 1680 2.70 4 33
4 Rfusiformgyrus 44 −78 −4 792 3.61 2 17
5 Lfusiformgyrus −42 −62 −14 680 2.03 3 25
6 Rdorsolateralprefrontalcortex 34 12 36 384 1.94 3 25
7 Lanteriorcingulate −12 34 18 344 2.13 1 8
8 Linferiorparietallobe −34 −42 46 240 1.98 2 17
9 Rcerebellum 22 −56 −14 208 1.73 2 17
10 Rhippocampus 28 −18 −12 208 1.57 1 8
Onlyemotionalfaces(n=10)
1 Ramygdala 25 −1 −17 4528 4.57 7 70
2 Lfusiformgyrus −49 −72 2 1536 2.69 3 30
3 Lamygdala −18 −3 −15 1224 2.34 5 50
4 Rfusiformgyrus 49 −72 2 928 3.61 2 20
5 Lfusiformgyrus −38 −55 −9 912 2.03 4 40
6 Rcerebellum 26 −52 −12 376 1.73 2 20
7 Lanteriorcingulate −9 38 21 312 1.99 1 10
Lexical—words,letters,numbers(n=10)
0 – – – – – – –
Numbersinboldtyperepresentstudycontributionsoverthe33%thresholdasreportedbyvanderLaanetal.(2011).
a ALEclustersatpb0.05(FDRthresholdcorrectionformultiplecomparisons,clustersizeN100mm3.
b L,lefthemisphereandR,righthemisphere.
c VoxelcoordinatesareinTalairachspace.
2968 S.J.Brooksetal./NeuroImage59(2012)2962–2973
Fig.1.SignificantALEclustermaximaofneuralactivationtostimuliofallmodalitiessurvivingFDRcorrection,pb0.05formultiplecomparisons,clustersizeN100mm3,Talairach
coordinatesaregivenfortherespectiveslices;leftfusiformgyrus(43%ofstudiescontributed;ALE=4.59,foci=40,clustersize=5280mm3),leftinsularcortex(37%ofstudies
contributed;ALE=3.53,foci=29,clustersize=3656mm3),righthippocampus(34%ofstudiescontributed;ALE=5.55,foci=26,clustersize=3648mm3).
issue, in that the variation in stimulus modalities combined with a predefined cluster criterion (see Methods). These were in the right
smallernumberofstudiespreventedanysignificantclustersofacti- amygdala (x=−49, y=−72, z=2), the left amygdala (x=−18,
vation.However,itcannotberuledoutthattheROIstudiesdidnot y=−3, z=−15) and the left fusiform gyrus (x=−38, y=−55,
biasourinitialfindings.Wewillbeabletomoreaccuratelymeasure z=−9).
the effect that ROI studies have on the results, by excluding them Additionally, we ran a separate meta-analysis after removing
fromtheindividualmeta-analysesbelow. those studies that only used ROI analysis (n=7). For all faces we
The next meta-analyses are done on the separate subliminal found7clustersthatsurvivedFDRcorrection,5passedthepredefined
stimulimodalities. clustercriterion(seeMethods).Theclusterswerealmostidenticalto
those found in the previous meta-analysis, suggesting that the ROI
Meta-analysis two: significant ALE clusters from studies employing studies did not cause much bias to the results. The clusters were
subliminalphysiologicalparadigms found in the rightamygdala (x=25, y=−3, z=−17), left hippo-
campus(x=−16,y=−9,z=−16),leftfusiformgyrus,rightdorso-
From 171 foci, 107 subjects and 7 studies, the ALE analysis lateralprefrontalcortex(x=37,y=14,z=39)andrightcerebellum
revealed 9 significant clusters that survived the FDR threshold, six (x=25, y=−52, z=−12). For faces, excluding non-emotional
of these clusters passed the predefined cluster criterion (see faces, we found two clusters that survived all thresholds, in the
Methods).Clusteronewasfoundintherightinsularcortex(x=36, right amygdala (x=26, y=0, z=−18) and right cerebellum
y=10, z=4), cluster two was in the left anterior cingulate cortex (x=25, y=−52, z=−12). All clusters are listed in Table 2 and
(x=−2,y=36,z=18),clusterthree,intherightanteriorcingulate SupplementaryTable2.SeeFig.3foranillustrationofthesignificant
cortex(x=2,y=16,z=32),clusterfourwasfoundintherightante- clustersofneuralactivationtoemotionalfaces.
riorcingulate(x=2,y=36,z=0),clusterfivewasfoundintheleft
insular cortex (x=−42, y=2, z=−4) and cluster six was also in
theleftinsularcortex(x=−42,y=2,z=−4).Theremainingclus-
ters reported in the ALE (that did not pass the predefined cluster
criterion,seeMethods)arepresentedinTable2.SeeFig.2.
Wealsoranaseparatemeta-analysisafterexcludingthestudiesthat
usedROIanalysis(n=2).Bydoingthis,wealsofound9clustersurviv-
ingFDRthresholdcorrection,sixoftheseclusterspassedthepredefined
clustercriterion(seeMethods).Theclusterswerefromthesamere-
gionsasdescribedabove,exceptinthiscasewealsofoundactivation
in the left orbitofrontal cortex (−3, 57, 16), created from 2 studies.
SeeSupplementaryTable2formoredetails.
Meta-analysis three: significant ALE clusters for studies employing the
subliminalpresentationofemotionalfaces
AnALEanalysisof274fociand217subjectsrevealedthat10clusters
survivedFDRmultiplecomparisoncorrections,butoftheseonlythree
passed the predefined cluster criterion (see Methods). Cluster one
wasintherightamygdala(x=28,y=2,z=−18),clustertwowasin Fig.2.SignificantALEclustermaximaofneuralactivationtosubliminalphysiological
thelefthippocampus(x=−16,y=−8,z=−16)andclusterthree stimuli surviving FDR correction, pb0.05 for multiple comparisons, cluster
wasintheleftfusiformgyrus(x=−48,y=−76,z=2).Additionally, sizeN100mm3).Talairachcoordinatesaregivenfortherespectiveslices:bilateralan-
terior cingulate cortex (67% of studies contributed; ALE=2.35, foci=9, cluster
weremovedfromthisinitialmeta-analysistwostudiesthatusednon-
size=2232mm3;ALE=2.62,foci=10,clustersize=2168mm3),andbilateralinsular
emotionalfacesandre-rantheanalysis.Thisresultedinsevenclusters cortex;(left:33%ofstudiescontributed,ALE=2.50,foci=7,clustersize=1160mm3;
that survived FDR correction; three of these clusters passed the right:67%ofstudiescontributed,ALE=2.20,foci=15,clustersize=2688mm3).
S.J.Brooksetal./NeuroImage59(2012)2962–2973 2969
Meta-analysis three: significant ALE clusters for studies employing the feeling”(LeDoux,1996).Suchnon-conscioussomato-sensoryactiva-
subliminalpresentationoflexical(words,lettersandnumbers)stimuli tionsmaycauseanunderlyingsenseofconflict(e.g.reflectedbyacti-
vation of the anterior cingulate cortex) and altered motivation
NosignificantclusterswerereportedbytheALEanalysis,andthis towardssubconsciouslyrewardingstimuli,assuggestedbysomere-
could be due to vast differences in the subliminal paradigms used. searchersinthefield(e.g.Pessiglioneetal.,2007,2008).Additionally,
Due to the variance between paradigms and the relatively small thepregenualACCishighlyactivatedduringtheanticipationofpain,
studynumbers(n=10),itwasnotpossibletoseparatethestudies andcanbemodulatedwhenpainisconsciouslyperceived(Straube
intofurthermeta-analyses. etal.,2009),thus,itishighlyplausibleforthepregenualACCtoacti-
vate during subliminal physiological stimulation of the rectum, and
Discussion esophagus. Othersalso proposethatactivation of bottom-up arousal
systems (e.g. involving the striatum, amygdala, hippocampus) likely
Wehaveshowninthefirstmeta-analysisofitskind,thatintheab- guideoursubsequentdecision-makingbehaviorviaimpingementon
senceofawarenesssubliminallypresentedarousingstimuliactivate top-down processes (Damasio, 2010; Dehaene et al., 2006; Diekhof
corebrainregionsassociatedwithsomatosensory,emotional,memo- etal.,2009).Wefoundnosignificantactivationsintherangeofstudies
ryandvisualbrainregions.Ourmostrobustfindingswerethat9of12 presentingsubliminallexicalstimuli(words,letters),whichmightsug-
studies presenting subliminal faces contributed to activation in the gestthattherewashugevarianceinthesemanticsoftheparadigms
rightamygdala.Tocheckthevalidityofthisresult,weremovedfrom employed.Itcouldalso bethatforwordsto beadequatelyencoded,
the meta-analysis, fMRI studies that employed ROI analysis, and conscious,higherorderprocessingmightbeneeded.However,wedid
found similar results. Additionally, subliminal physiological stimuli find that subliminal audio stimulus deviancy activated bottom-up
producedactivation,asrepresentedby4of6studiesinthebilateral somato-sensory responses, perhaps as a gut-feeling of discrepancy
anteriorcingulateandbilateralinsularcortices.Similarclustersofac- (Diekhofetal.,2009),buttherewerenotenoughstudiestocontribute
tivationwerealsoconfirmedbyremovingtheROIfMRIstudiesfrom to a meta-analysis. Thus, the basis of neural activation to subliminal
the analysis. However, no significant clusters of activation were arousingstimuliisseeminglyembeddedinsomato-sensoryaffectivere-
foundtolexicalstimuli.Thesemeta-analysessuggestthatsubliminal sponses,whichlikelyimpinge on prefrontalcortex systemsenabling
arousingstimuliofdifferentmodalitieshavedistinctpatternsofneu- eventualconsciousprocessing.
ralactivation.Wedonotcomparesubliminalstimuliseparatelybe- Thesemeta-analyseshaveseparatelyshownthatsubliminalemo-
cause the modalities differ greatly, however, we speculate on what tionalstimuliofdifferentmodalitieshavedistinctpatternsofneural
thedifferencesmightmeaninresponsetospecificstimuli.Withacti- activation.Itcouldbethatdifferentneuralsystemsaremoresensitive
vationoftheamygdala,hippocampus,bilateralanteriorcingulatecor- to subliminal stimuli of different modalities. However, we did not
tex,insularcortexandprimaryvisualcortexbeingmostconsistently deem it possible, given the variability between stimuli to explicitly
activated across studies, these data provide specific regions in the testthecomparativeeffects,andsocautionmustbeexercisedwhen
brainthatarehighlyresponsivetostimuliwhenawarenessisabsent. makingcomparisonsbetweenstimuli.Itisalsoimportanttoempha-
In comparison to other meta-analyses and in conjunction with sizethatthevarianceinfMRIparadigmdesigncouldhavehadanin-
views on the reproducibility of fMRI data (e.g. Turkeltaub et al., in fluenceonthedataobtained,althoughapreviousALEmeta-analysis
press;Wieneretal.,2010;BennettandMiller,2010),ourmostsigni- also found no significant difference between event-related and
ficant finding that 9 of 12 studies using subliminal emotional faces blockdesignparadigms(vanderLaanetal.,2011).Nevertheless,it
contributetoactivationisextremelyrobust.Itcouldbethattheevo- isdefinitelythecasethat,althoughtheALEmethodsolvesmanyis-
lutionaryadvantageinhumans,torecognizetheemotionalcontentof suesfrompreviousattemptstometa-analyzefMRIdata,thereisstill
afaceandadjustbehavioraccordingly,issodeeplyembeddedinneu- aneedformoresophisticatedmeta-analyses(e.g.bytakingintoac-
ralsystemsthatitisrenderedquickandautomatic,withouttheinitial countstrengthoftheBOLDsignalineachstudy).Furthermore,itis
needofhigherorderevaluation.Subliminalphysiologicalstimulialso apparentthatthereisaneedforstudiespresentingsubliminalfood
producedahighrateofstudyconcurrencewith4of6studiescontrib- stimuli, in order to assess the origin of appetitive responses in the
utingtoclustersofactivation.Subliminalphysiologicalstimulilikely brain,asnofMRIstudieshaveyetusedthesubliminalpresentation
evoke somato-sensory responses that are the foundation of a “gut- offoodstimuli.
Fig.3.SignificantALEclustermaximaofneuralactivationtosubliminalfacesstimulisurvivingFDRcorrection,pb0.05formultiplecomparisons,clustersizeN100mm3.Talairach
coordinatesaregivenfortherespectiveslices;leftfusiformgyrus(33%ofstudiescontributed;ALE=2.70,foci=8,clustersize=1680mm3);lefthippocampus(58%ofstudiescon-
tributed;ALE=3.43,foci=16,clustersize=3352mm3);andrightamygdala(75%ofstudiescontributed;ALE=5.07,foci=24,clustersize=5576mm3).
2970 S.J.Brooksetal./NeuroImage59(2012)2962–2973
Inthenextsection,wereviewthemostsignificantregionsofneu- Subliminalfacestimuli
ralactivationfoundinourmeta-analyses,inrelationtothesubliminal
stimulus modality in which they were found; 1) all subliminal sti- Presentationofsubliminalfacesactivatedtherightamygdala,left
muli, 2) subliminal physiological stimuli, and 3) subliminal faces. hippocampus and left fusiform gyrus. The most robust neural re-
Wealsobrieflydiscusstheindividualfindingsofstudiesemploying sponseacrossstudiestothesubliminalpresentationoffaceswasin
4)subliminalaudiostimuliand5)miscellaneousstimuli. therightamygdala.Itiswellknownthattheamygdalaisresponsive
to affective stimuli, particularly negative emotion such as fear and
Allsubliminalstimuli disgust,andarecentmeta-analysisof385neuroimaging(fMRIand
PET)studiesconfirmedthis(Costafredaetal.,2008).Inourreview,
Subliminalstimuliofallmodalitiesmostsignificantlyactivatedthe studies contributing to the surviving cluster in the amygdala used
leftfusiformgyrus,leftinsularcortexandrighthippocampus.Inare- subliminalfacesdepictingthenegativeemotions:fear,sadness,dis-
centmeta-analysisoffMRIstudiesusingexplicitlypresentedappeti- gustoranger(Dannlowskietal.,2007;KillgoreandYurgelun-Todd,
tivestimuli,itwasshownthatthebilateralfusiformgyri,whichform 2004;Liddelletal.,2005;Nomuraetal.,2004;Phillipsetal.,2004;
part of the primary visual cortex, were consistently activated (van Suslow et al., 2010; Williams et al., 2006). Rapid activation of the
der Laan et al., 2011). The fusiform gyri are seemingly involved in amygdala,whichbypassesconsciousperception,occursinresponse
therapidrecognitionofhighlysalientstimuli,evenintheabsenceof tostimulithathavebeenpreviouslyassociatedwithanegativeemo-
consciousperception(Littetal.,2011).Sucharapidresponsemaybe tion,forexample,stimuliassociatedwithapsychiatriccondition(e.g.
drivenbyaninitial‘quickanddirty’activationofapathwayfromthe excessive fear responses to social stimuli). It is plausible that rapid
amygdalatothevisualcortex(LeDoux,1996).Theinsularcortexisas- activationoftheamygdalainresponsetonegativeemotion(particu-
sociatedwithfeelingstatesandinteroceptiveawarenessofthebody larly depicted in faces) escapes prefrontal cortex modulation, and
andprobablyachievesthisfunctionviadenseconnectionsbetween couldbethebasisofovergeneralizationoffear,leadingtoanxietydis-
the cortex and sub-cortex, aiding somatosensory processing (Craig, orders(Dunsmooretal.,2011).Giventhattheamygdalaealsoform
2009;ShelleyandTrimble,2004).Oneofthemainfunctionsofthein- partofthehippocampalcomplex,aregionassociatedwithmemory
sularcortexisintheorchestrationofsomato-sensoryresponsesfrom formation and also found to be highly activated to faces in this
theinternalmileu(e.g.bodytemperature,hunger,pain,discomfort, meta-analysis,itisplausiblethattheemotionalcontextassignedto
sensorychanges)forfutureinteroceptiveawareness(Critchleyetal., a face aids future recognition and the necessary behavioral adjust-
2004).Thus,itisplausiblethattheinsularcortexwouldbeactivated ments needed to maintain effective social status quo (Conty and
inresponsetosubliminalarousingstimuli,assuchstimuliwouldlikely Grezes,inpress).Thereissomeevidencetosuggestthatdifferentre-
causesomatosensorychangespriortohigherordercognitiveproces- gionsoftheamygdalaactivatetodifferenttypesofsubliminalemo-
sing,andbeabasisforagutfeeling.Finally,thehippocampi,partof tional faces (e.g. negative vs. positive emotion), particularly those
the subcortical entorhinal complex with the amygdalae, were also scoring high on anxiety measures (Vizueta et al., 2012). However,
mostsignificantlyactivatedacrossallsubliminalstimuli.Thehippo- there were not enough studies of separate emotional categories to
campiareknowntobeinvolvedintheconsolidationoflong-termim- comparetheeffectofpositiveandnegativefaces.
plicit memory and spatial navigation, e.g. episodic and semantic Thehippocampuswasthenextmostrobustfindingacrossstudies
recollections of familiar objects and locations (Squire and Wixted, inresponsetosubliminalfaces.Thehippocampi,partoftheentorhi-
2011;Cowelletal.,2010).Thus,implicitmemorysystemswerealso nal complex with the amygdalae, are known to be involved in the
likelyengaged in responseto subliminalstimuli, particularly highly consolidation of long-term implicit memory and spatial navigation,
salientstimulisuchassubliminalemotionalfaces. e.g. episodic and semantic recollections of familiar objects and
locations(SquireandWixted,2011;Cowelletal.,2010).Subliminal
Subliminalphysiologicalstimuli faces are able to activate the hippocampus, likely because they are
consolidated in long-term memory, aiding in the recognition of fa-
Subliminalphysiologicalstimulationactivatedthebilateralante- miliarfacesandalsotorapidlyrecognizefaciallyexpressedemotion.
riorcingulatecortex(ACC)includingthepregenualarea,andthebi- Additionally,sincetheamygdalaeformpartofhippocampalcomplex,
lateral insular cortex. The ACC is known for its involvement in itisplausiblethathigharousal,attributedtoactivationoftheamyg-
predicting and detecting conflict and error, particularly during the dala,helpstoconsolidatehighlysalientstimuli,suchasfaces,parti-
presentationofunexpectedstimuli(e.g.Botvinick,2007;Kimetal., cularlyemotionalfaces.Forexample,ifapersonwemeetwasangry
2010; Yeung and Nieuwenhuis, 2009). Furthermore, it is suggested andelicitedthreattowardsusinthepast,itisadvantageoustoour
that motor control, drive and cognition interface at the ACC (Paus, survivaltorememberthisperson'sfaceinthefuture,sothatwecan
2001).Itisplausiblethatsignalsderivedfromsubliminalphysiologi- avoidthem,oralterourbehaviorinanattempttolowerthechances
calstimulationareprocessedbythisregion,duetotheunexpected ofarepeatthreat.Perhapsthisautomatic,non-consciousactivationof
nature of such stimulation, or because they may cause future pain. arousalmechanismsinthebraintoafaceunderliesthehigherlevels
SometheoriesonthefunctionoftheACCpurportthatitsignalsthe of interpersonal stress in urban areas, as we are constantly bom-
needforcognitivecontrolinthepresenceofconflict,tootherprefron- bardedwithemotionalfacesthatwetrytoencodeforfuturesurvival.
talcortexregions,suchasthedorsolateralprefrontalcortex(DLPFC) Overstimulation of the hippocampal–amygdala complex, indepen-
(e.g.Kernetal.,2004).ThepregenualACC,oneoftheregionswere- dentoftop-downcorticalregulatoryprocesses,mightbeanunderly-
porthere,isinvolvedintheanticipationofpain(Straubeetal.,2009), ing factor in many psychiatric diseases prevalent in developed
andsothisbrainregionmaybeinvolvedintranslatinginitiallyun- societiestoday(e.g.anxiety,depression,schizophrenia).
consciouslyprocessedbodilysensationsintocognitionsaboutpain. Finally,thesubliminalpresentationoffacesalsoshowedaconsis-
This is particularly plausible given that the bilateral insular cortex tentpatternofactivationacrossfMRIstudiesinthefusiformgyrus,
were also most significantly activated in response to subliminal strongestfortheleftthantheright.Arecentmeta-analysissuggests
physiologicalstimuli.Interoceptiveawareness,whichisthebasisof that the affective representation of a face is largely encoded at the
perceivinghowthebody‘feels’,isstronglyassociatedwiththeinsular level of the fusiform gyrus, with dense connections to subcortical
cortex(Craig,2009;Critchleyetal.,2004;ShelleyandTrimble,2004). emotionalregions(Saidetal.,2011).Ifsubcorticalresponses,e.g.in
Furthermore,physiologicalchangesinthebody,whichunderlieagut theamygdala,arelargelyassociatedwithunconsciousemotionalper-
feelingcaninformfuturedecisionmakingandarepossiblynotatfirst ception(LeDoux,2003),ourfindingofincreasedfusiformgyrusacti-
perceivedconsciously(Damasio,2010). vationtosubliminalemotionalfacessuggeststhatprocessingoutside
S.J.Brooksetal./NeuroImage59(2012)2962–2973 2971
of awareness can infiltrate and influence visual processing. Such a Subliminalaudiostimuli
rapidresponsemaybedrivenbyaninitial‘quickanddirty’activation
fromtheamygdalatothevisualcortex(LeDoux,1996).Recognizing There were too few studies to completea meta-analysis on this
theemotionalcontextofafaceisofhighsocialvalue,giventhataper- sub-category(n=3),however,allstudiesweresimilarinthatthey
sonmustadjustbehavioraccordinglyforsuccessfulsocialinteraction examinedhowthebrainrespondstochangesinasubliminalauditory
withanotherhumanbeing.Anothermeta-analysisrecognizesthefu- stimulus.Theleftlateralcerebellum,leftsuperiortemporalgyrusand
siformgyrus,knownalsoasthe‘fusiformfacearea(FFA)’,tobehighly left insular cortex were most significantly activated in response to
activatespecificallyandrapidlytothepresentationoffacesandim- subliminalauditorychanges.However,inonestudy,repetitionofa
portant for social interaction (Kanwisher and Yovel, 2006). Thus, voicewasshowntoreduceinsularcortexactivation(Kouideretal.,
combinedwithourfindingsonhippocampal–amygdalaactivationto 2010). Thus, regions associated with speech production (Broca's
emotional faces, and with knowledge that these structures connect area),speechcomprehension(Wernicke'sarea)andsomatosensory
tothevisualcortex,hypervigilancetowardsthevisualprocessingof responses seem to be activated independently of conscious aware-
facescouldensueinsomepeople.Thismaycauseparanoiaandhy- ness.These regions might be particularlysusceptible to heightened
persensitivity to another person's facial expressions, particularly in activationduringauditoryhallucinationsthatareperceivedtobein-
social situations, as observed in people with schizophrenia, and dependent of conscious volition, as experienced by, for example,
couldbeminimizedwithbettertop-downregulationofthesesubcor- thosewithschizophrenia.
ticalsystems.
Subliminalmiscellaneousstimuli
Subliminallexicalstimuli
In this final subcategory of fMRI studies employing subliminal
We did not observe any significant clusters of neural activation paradigms, it was impossible to find a common corollary in tech-
acrossstudiesinresponsetogeneralsubliminallexical(words,letters) nique, thus we briefly discuss their separate findings. One study
stimuli.Thiscouldbebecausethesemanticsofthestimuliweretoodif- asked participants to remember objects located on a virtual 3-D
fuse,orthatactivationofhigherordercognitionsisneededinorderto route in the scanner (Janzen and Weststeijn, 2007). By doing this
fullyprocesssuchstimuli.Further,perhapsitisanecessitythatsub- the authors found significant activations in the parahippocampal
liminalstimuliareofanemotionallyarousingnature,otherwisethey gyrus, inferior parietal gyrus, ACC and right caudate. These regions
are not salient enough to provoke strong subcortical responses. This areallinvolvedinsomatosensoryactivationandmotivation,thusit
also highlights the importance of limbic and paralimbic structures, seems plausible that such arousal mechanisms are activated when
suchasthehippocampus,amygdalaandinsularcortex,intheproces- weviewfamiliarlandmarksthathelptoguideusthroughourenvi-
singofsubliminalstimulithatareofanarousingnature.Thenullresult rons.Anotherstudyexaminedneuralresponsestosubliminalspider
forsubliminallexicalstimulipotentiallyhighlightsthedistinctionbe- images,inthosewithaspiderphobia(Lipkaetal.,2011),andfound
tween semantic and emotional processing, in terms of brain regions greateractivationintherightamygdala.Thisisexpected,giventhat
thatareengaged.Somestudiesidentifiedinthisreviewdiduseemo- theamygdala,particularlytheright,isassociatedwithfearprocessing
tionalwords,forexample,asexualpartner'sname(Bianchi-Demicheli (e.g.Costafredaetal.,2008).Anotherstudyexaminedalterationsin
and Ortigue, 2009; Ortigue et al., 2007a), a friend's name (Ortigue gripforce,indicativeofhowmuchapersonispreparedtoworkfor
etal.,2007b),orthreateningwords(Naccacheetal.,2005).Aleftlater- an unconscious monetary reward (Pessiglione et al., 2007), and
alized insular cortex response was most prevalent to sexual experi- foundsignificantactivationsinthebasalganglia.Theseauthorsalso
ences, whereas the name of a beloved was mostly associated with examined the effects of reward and punishment on motivation for
activation of the fusiform gyrus. These results fit with our meta- monetaryrewardinrelationtomaskedcontextualcues(Pessiglione
analysesdescribedabove,inthatstatesofhigharousalandbodilysen- etal.,2008).Subliminalcuesassociatedwithrewardwerestillable
sationsareassociatedwithactivationoftheinsularcortex.Theleftinsu- toactivatethestriatum,aregionofthebrainassociatedwithuncon-
larcortexhasbeen associatedmorewithpleasantbodily sensations, scious reward encoding and motivation. A final study examined
whereas the right with negative bodily states such as pain (Craig, how strategic control over subliminal stimuli influences neural
2011).Additionally,wehavediscussedhowconnectionsbetweenemo- activity (Wolbers et al., 2006). They found activation in the pre-
tionalcentersinthebrain(e.g.hippocampus,amygdala)andthefusi- supplementarymotorarea,occipitalregionandthestriatum,suggest-
formgyrusmayformthebasisoftheperceptionofsaliencyinvisual ingthatmotorregionsofthebrainareabletointeractwithuncon-
stimuli.Thus, seeing a beloved person's namewrittenislikely to be sciousprocessingduringdeliberatecontrol.
moresalientthanotherwords.
The other lexical studies identified in this review used ‘cognitive’ Strengthsandlimitations
subliminalparadigms,suchasdetectingdifferencesbetweenrecogniz-
able versus unrecognizable words and letters (Dehaene et al., 2004; Thisisthefirstmeta-analysistodateusingtheALEstatisticalap-
DiazandMcCarthy,2007;Heinzeletal.,2008;Kouideretal.,2007;Luo proach to illustrate the core brain regions activated to subliminal
etal.,2004;Qiaoetal.,2010).Ingeneral,wordsthatwouldbedeemed emotionalstimuliduringfMRI.ThemainadvantageofusingtheALE
recognizable,incontrasttounrecognizable,whentheywerepresented methodisthatitisamorescientificallyrobustmeasurethancounting
subliminally, activated the fusiform gyrus. This finding complements theanatomicalcoordinatesreportedinstudies(e.g.Lairdetal.,2005).
ourotherfindingsaboutthefusiformgyrusanditsroleinsaliencyper- Furthermore, our combined analysis incorporated 691 separate foci
ception. Other studies showed that despite an absence of awareness, and 619 subjects, with maximum concordance between reported
maskedwordsarestillabletoactivatelefthemispherelanguageregions, neuronalactivationin9of12studies.DataderivedfromfMRIstudies
suchasBroca'sarea.Thus,inlinewiththetheoriesofsomeresearchers arenotoriouslydifficulttosystematicallymeta-analyze,duetohigh
inthefield(e.g.KouiderandDehaene,2007),theremaybetwolevels variabilityinthestatisticalcontrastsusedtocreateimagesofneuro-
of non-perceived cognitive processing: subliminal and preconscious, nalactivation.Inthisreview,weanalyzedonlyreportedneuralacti-
the second being able to infiltrate top-down attention mechanisms vation, and not deactivation relative to a subliminal ‘baseline’. The
without necessarily being aware of them. Such a neural mechanism relative subliminal baselines included: neutralfaces, neutral words,
mightunderliethehugeimpactthatimplicitadvertisinghasinourcur- resting periods where no physiological stimulation was given,
rentsociety,forexample,theabundanceoffoodadvertisingthatmaybe thesame(asopposedtodeviant)tones,andimagesofmoney.Thus,
causinganobesityepidemic. the reader must also consider these unavoidable variances when