Emo$onaldecision‐makingsystemsandtheirroleinaddic$on

AntoineBechara

Objec&ves:

1.Habit(Impulsive)system:Dopaminemediated(striatal).

2.Inhibitorycontrol(Reflec$ve)system:Prefrontalcortexdependent— a.Decision‐making b.Simpleinhibitorycontrol.

3.Insularcortexsystem:responsivetohomeosta$cimbalance(depriva$onstates),whichac$vity: a.Exacerbatestheac$vityofthehabit/impulsivesystem. b.Disable(or“hijack”)ac$vityoftheprefrontal(control/reflec$ve)system.

1.Thehabit(impulsive)system—rewardseeking

A.TheNatureofreward:

Theterm“reward”describesthepositivevalueanindividualascribestoanobject,behavioralactoraninternalphysicalstate.

Therearetwokindsofrewardsthatcanestablishaddictivebehaviors:

(1)NaturalrewardsarethosethatreachthebraincircuitryofmotivationviatheBivesenses.Therewardsoffoodforahungryperson,waterforathirstyperson,orcopulationforsexuallyreceptiveindividualreachthebrainviaperipheralsensorypathways(e.g.,vision,taste,olfaction,sensation,andaudition).

(2)“Unsensed”rewardsdenotethosewiththecapacitytoactivatethebrainsubstratesofmotivationdirectly,bypassingtheperipheralsensorypathways.Drugstakenorally,inhaled,orinjected,donothaveaparticulartaste,orsmell,thatmakesthemrewarding.Theyactdirectlyonthebraintoproducereward.

(3)“Money”isarewardtoo:Throughlearning,moneybecomesstronglyassociatedwithnaturalrewards,likefood,water,sex,andshelter.Becauselearningaboutmoneyissoextensiveandspansourentirelife,theselearningassociationswithnaturalrewardsbecomepowerful,automatic,andnon‐conscious.

Althoughthereareobviousdifferencesbetweenhownatural(e.g.,sex)andunsensed(e.g.,drugs),ormoneyrewardsreachtherewardsystemswithinthebrain,alargevolumeofstudies,datingbacktothe1980’s,haveimplicatedthe“mesolimbic”dopaminesystem,andseveralofitsafferents(inputs)andefferents(outputs),inmediatingthemotivationalfunctionsofbothtypesofreward.

Bothanimalandhumanstudieshavelinkednaturalrewardstothesamemesolimbicdopaminesystem.

Thusdrugsarerewardingbecausetheyhavethecapacitytoactivatedirectlyinthebraintheendogenousrewardmechanismssubservingnaturalorbiologicalrewards,whichexistedbeforetheinventionofdrugs.

B.Thedopaminesystemandreward:

Thereareseveralsystemsofdopaminergicneuronsorsystems(5intotal).However,thethreemostimportantoftheseoriginateinthemidbrain,speciBically:(1)Thesubstantianigra,whichprojectstothedorsalstriatumorneostriatum=mesostriatal(ornigrostriatal)dopaminesystem‐‐‐ParkinsonDisease.

Medications:predominantlyD2receptors—ParkinsonDAagonisttherapiestargetthesereceptors.

(2)Theventraltegmentalarea,whichprojectstothenucleusaccumbens=mesolimbicdopaminesystem‐‐‐‐reward.

Medications:predominantlyD3receptors—ParkinsonmedicationsthatareD3agonists(e.g.,Mirapex)havehighlikelihoodofinducingaddictivebehaviors(e.g.,pathologicalgambling)inindividualswhomotherwisenevergambledbefore.

(3)Anotheronefromtheventraltegmentalarea,whichprojectstotheprefrontalcortex=mesocorticaldopaminesystem—decision‐makingandinhibitorycontrol.

C.Thehistoryofresearchondopamineandreward.

Researchonthedifferencebetweenthenigrostriatalandmesolimbicsystemsintermsoftheircontributiontomovementversusrewardisoldanddatesbacktoatleasttheearly1980’s(itstartedinthelate70’s):

1.TheBirstproposalofauniquerelationshipbetweendopamineandrewardwasprovidedbyR.Wise:

Wise,R.A.,CatecholamineTheoriesofReward­Critical­Review.BrainResearch,1978.152(2):p.215­247.

Wise,R.A.andM.A.Bozarth,Apsychomotorstimulanttheoryofaddiction.PsychologicalReview,1987.94:p.469­492.

Theliteraturefromthatera(the80’s)clearlydemonstratesthatthedopaminergicprojectiontothenucleusaccumbens(themesolimbicdopaminesystem),butnotthedorsalstriatum(thedorsalpartoftheneostriatum,whichexcludestheventralstriatum,wherethenucleusaccumbensislocated),istheonethatplaysthemostsigniBicantroleintherewardderivedfromdrugsofabuse(e.g.,psychostimulants).

1.a.Itwasalsorecognizedinthelate1980’sandearly1990’sthattheabusepotentialofdrugsofabuse(e.g.,opiates,alcohol,nicotine,caffeine,barbiturates,benzodiazepines,cannabis,andphencyclidine)allarelinked,onewayoranother,tothismesolimbicdopaminesystem.Whilethesedifferentdrugsmayactinitiallyondifferentreceptorsitesinthebrain,ultimatelytheyallact(directlyorindirectly)onthemesolimbicdopaminesystemtoexertreward:Wise,R.A.,Theneurobiologyofcraving:Implicationsfortheunderstandingandtreatmentofaddiction.JournalofAbnormalPsychology,1988.97:p.118­132.

1.b.Itwasalsowellacceptedinthelate1980’sandearly1990’sthatmanipulationsofthesamemesolimbicdopaminesystem(withpharmacologicalblockadeofdopamineorwithselectivelesionsofthedopamineneuronsusing6‐hydroxydopamineor6‐OHDA)exertanimpactonnaturalrewards,suchasfood,sweetdrinks,andsex.Mostoftheseexperimentsshowedthatduringdopamineblockade,animalswouldnotbemotivatedtoeat,forexample,eventhoughfoodmaybereadilyavailable,andevenwhentheirmotorcapacitytowalk,chew,swallowandperformothermovementsarepreserved.Itwasalsorecognizedthatdopaminestimulationintheaccumbensincreasesthemotivationforfood.Microinjectionsofdopamineagonistsdirectlyintothenucleusaccumbensdoincreasethemotivationfornaturalrewards,suchasfood:

Wise,R.A.andP.P.Rompre,Braindopamineandreward.AnnualReviewsofPsychology,1989.40:p.191­225.

1.c.Morethan25yearshaspassed,andtheoriginalconclusionthatmanipulationsofthemesolimbicdopaminesysteminBluencesthemotivationtoseekrewardsremainsvalid:

‐Whenbraindopaminelevelsarelow,themotivationtoseekrewardbecomeshalted.Itisthestimulationofthedopaminesystem,orthepresenceofadrugthatactivatesthedopaminesystem,nottheabsenceofdopamine,thatenergizesandmotivatesbehaviorstowardstheseekingofrewards.

‐CellularphysiologyandpharmacologydemonstratesthattheactionofdopamineinthenucleusaccumbensistoinhibittheGABAneurons,whichareinhibitorytothenextneuronsinthechainthatinstigatemotivatedbehaviors.Inotherwords,dopamineintheaccumbensinhibitstheinhibitoryneurons,thusresultinginbehavioraldis­inhibition.

1.d.Therehasbeenmuchrecentfunctionalneuroimagingworkinhumansimplicatingtheventralstriatum(includingthenucleusaccumbens)inavarietyofrewardprocesses,includingmonetaryrewards.

Althoughfunctionalmagneticresonanceimaging(fMRI)approachescannottechnicallyaddressdopamine(oranyotherbrainchemicalforthatmatter),thefactthattheneuralregionreceivingthesedopamineprojections(i.e.,theventralstriatum)isimplicatedinavarietyofrewardprocesses(videogames,viewingofsexualmaterials,andmonetaryrewards,tonameafew)validatesthelargebodyofevidencethatemployedavarietyofelecrophysiological,microdialysis,orvoltammetrictechniques,whichaccumulatedover25yearsofresearch,andwhichconcludedthatthemesolimbicdopamineprojectiontonucleusaccumbensplaysakeyroleinrewardprocesses.

2.Theconditionedcuesevidence:Accordingtothe“psychostimulant”anaylsis,themesolimbicdopaminesystemplaysakeyroleinmediatingthe“approach”responseelicitedbydrugsaswellasnaturalrewards.Mesolimbicdopaminestrengthenstheapproachresponseandmotivationalarousalelicitedbyrewards,whichareassociatedwithpleasure.Themesolimbicdopaminesystem,whichisclearlycriticalforrewardfunctions,becomesincreasinglyresponsivetostimuliandcuesthatpredictthedeliveryoftheactualreward(e.g.,food):

Stewart,J.,H.Dewit,andR.Eikelboom,RoleofUnconditionedandConditionedDrugEffectsintheSelf­AdministrationofOpiatesandStimulants.PsychologicalReview,1984.91(2):p.251­268.

Schultz,W.,P.Dayan,andP.R.Montague,Aneuralsubstrateofpredictionandreward.Science,1997.275:p.1593­1599.

3.The“liking”versus“wanting”:Laterresearchersassertthattheprocessofrewardcanbefurthersub‐dividedinto(1)a“wanting”component,whichmakesrewardsattractiveand“wanted”,andwhichtriggers“approach”andpursuitofthereward;and(2)a“liking”component,whichinvolvesfeelingofpleasure.Althoughthereseemtobeadditionalsystemsinthebrain(whichremainunidentiBied)thatmediatethe“liking”orpleasurecomponent,themesolimbicdopaminesystemiscriticalforspeciBicallythis“wanting”componentofthereward:Berridge,K.C.andT.E.Robinson,Whatistheroleofdopamineinreward:hedonicimpact,rewardlearning,orincentivesalience?BrainResearchReviews,1998.28:p.309­369.

Robinson,T.E.andK.C.Berridge,Theneuralbasisofdrugcraving:anincentive­sensitizationtheoryofaddiction.BrainResearchReviews,1993.18:p.247­291.

Withrepeateddruguse,themesolimbicdopamineprojectionstothenucleusaccumbensbecomesensitized,andeventuallyleadtoexcessiveincentivesalienceattributiontothedrugsanddrug‐relatedstimuli,whichactivatethisneuralcircuitry,thusmakingthemhighlyattractiveandpathologically“wanted”orcraved.Thismesolimbicdopaminesensitizationphenomenondoesnotapplytoonlydrugs,buttoalltypesofrewards.Whenthemesolimbicdopaminesystemisactivatedinthepresenceofarewardintheenvironment,theincentivesalienceofthatrewardisincreased,andtherewardbecomesmoreattractiveandpathologically“wanted”.

4.Thenotionsofpleasureanddopamine:TheevidencethatblockadeofdopaminenerotransmissioninthencleusaccumbensinterferedwiththemotivationtoseekrewardspromptedWise(1982)toproposethe“anhedonia”hypothesis,thatdopaminemediatesthepleasureproducedbyfood,sex,ordrugsthatcompulsivedrugusersseek.

‐However,Wisehimselfretracted,shortlyafter,thenotionthatdopamineblockadereducespleasure(Wise1985),andhereplacedtheanhedoniahypothesiswithanincentive‐basedtheoryofmotivation,the“psychostimulant”theory(WiseandBozarth,1987).

‐Thekeyaspectofthattheoryisthatthemesolimbicdopaminesystemplaysakeyroleinmediatingthe“approach”responseelicitedbydrugsaswellasnaturalrewards.Inotherwords,afeelingofpleasureisnotnecessarilyexperiencedwhendopamineisreleased;mesolimbicdopaminestrengthenstheapproachresponseandmotivationalarousalelicitedbyrewards,whichtheyareclearlyassociatedwithpleasure.

‐Despitethisconsensusintheliteraturemorethanadecadeagothatdopamineisnotsynonymouswithpleasure,thisnotionthatdopamineisthe“pleasure”neurotransmitterofthebrainhashadaninsurmountableappeal;itseemstocontinuetolingeruntiltodayinvariousmediareports;eventhemorerecentfunctionalneuroimagingworkinhumansthataddressestherewardmechanismsmediatedbythenucleusaccumbensoftendiscusstheroleofdopamineinthisregioninamannerthatishardlydistinguishablefromthenotionsofpleasure.

5.Dopaminedepletionviews:DeBicienciesinneurotransmitteractivationofdopamineinthemesolimbicrewardpathwaysaretheinstigatorsofrewardseekingbehaviors:‐Thisistrueincasesofdrug‐induceddopaminedepletions:e.g.,cocainecrash.‐Itisverycontroversialastowhetherthiswouldbetrueforsomeonebornwithlowdopaminebaselinelevels.

6.Habits(implicit)mechanismsofdrugrewardseeking:Whileaddictedbehaviorsallstartoutundersome“conscious”controlthroughtheseventralstriatalmotivationalneuralcircuitries,prolongeddruguseresultsinthestrengtheningofmotivation‐relevantassociativememories,whichpromotecontinueduse,andanimplicit,orrelativelyspontaneous(automatic)processbeginstogovernbehavior.

‐Neutralstimuliassociatedwithappetitivebehaviorssuchasdrugusecometorepresentandcuethebehavior.Ascue‐behavior‐outcomeassociationsarestrengthened,patternsofassociationssignalanddrivebehaviorwithoutthenecessaryinvolvementofconsciouscontrolprocesses.

‐Onceastronghabitisformed,cueselicitthehabitregardlessofanticipatedoutcomes.‐ Habits become automatic and difficult to change. Another pivotal feature of habit

systems is that participants do not necessarily know what triggers their habits.

-At the neural level, there have been numerous neuroscientific demonstrations as what starts out as reward seeking mediated through the ventral striatum can end up as a “habit” automatic behavior and shifts to the dorsal striatum:

Everitt, B.J., A. Dickinson, and T.W. Robbins, The neuropsychological basis of addictive behaviour. Brain Research Reviews, 2001. 36: p. 129-138.

Everitt, B.J., K.A. Morris, A. Obrien, and T.W. Robbins, The Basolateral Amygdala Ventral Striatal System and Conditioned Place Preference - Further Evidence of Limbic Striatal Interactions Underlying Reward-Related Processes. Neuroscience, 1991. 42(1): p. 1-18.

Everitt, B.J., J.A. Parkinson, M.C. Olmstead, M. Arroyo, P. Robledo, and T.W. Robbins, Associative processes in addiction and reward: the role of amygdala and ventral striatal subsystems., in Advancing from the ventral striatum to the extended amygdala, J.F. McGinty, Editor. 1999, Annals of the New York Academy of Science: New York. p. 412-438.

Everitt, B. and T.W. Robbins, Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nature Neuroscience, 2005. 8: p. 1481-1489.

2.Inhibitorycontrol(Reflec&ve)system:Prefrontalcortexdependent— a.Decision‐making b.Simpleinhibitorycontrol.

Dual‐processmodelsofdecision‐making,cognition,andassociativememoryhavegainedsubstantialmomentuminbehavioralresearch.Incharacterizingthedistinctionsbetweenthesetwocognitivesystems,Kahnemansummarizedthat:“…theoperationsofSystem1aretypicallyfast,automatic,effortless,associative,implicit(notavailabletointrospection),andoftenemotionallycharged;theyarealsogovernedbyhabitandarethereforedifBiculttocontrolormodify…”

“…OperationsofSystem2areslower,serial,effortful,morelikelytobeconsciouslymonitoredanddeliberatelycontrolled;theyarealsorelativelyBlexibleandpotentiallyrulegoverned…”.

AccordingtoKahneman(2003),theimplicitorautomaticcognitivesystem(System1)isthesystemgoverningthemajorityofhumandecisionmaking,whereasSystem2monitorstheoperationsofSystem1.

Thisperspectiveofrelativelyautomaticprocessesbeingasortof‘default’modeguidingbehavior,unlessoverriddenbydeliberatecognitiveprocesses,hasbeenexpressedinsocialpsychologicaltheories,andmemoryresearchforoveradecade.

Thedistinctionbetweenautomaticandcontrolledprocesses(andsimilardistinctions)isreinforcedfurtherthroughseveralindependentlinesofresearchinneuroscience,includingmyown(theimpulsiveversusreBlectivesystemsforaddictivebehaviors,Bechara,NatureNeuroscience,2005).

AcriticalneuralregioninthereBlectivesystemistheventromedialprefrontalcortexregion(whichwehaveconsideredasinclusiveofthemedialorbitofrontalcortex).However,otherneuralcomponents,includingthedorsolateralprefrontalcortex(forworkingmemory)andthecingulatecortexarealsoapartofthisneuralcircuitry,andareessentialforthenormaloperationoftheventromedialprefrontalcortex:

Active vs control (all 10 subjects, all 4 tasks), p(bonf)<0.001

Left hemisphere Right hemisphere

Memory Systems : DorsoLatPrefCtx (DLPC) Hippocampus

Emotion Systems : Insula Posterior Cingulate

OrbitFrontCtx/VMPC

Striatum AntCingCtx/SupMotArea Motor/Behavioral Systems

Amygdala

Outline of the Somatic Marker Theory

HypothalamusPAGBrainstemautonomiccenters

Computa$on:Inthebody‐‐‐Bodyloop

InSensorynucleiandneurotransmiTercellbodiesofbrainstem‐‐‐‐Asifbodyloop

DopamineSerotoninAchNE

Decision‐makingversusinhibitorycontrol:Thereisadistinctionbetweenthemechanismsofaffectivedecision‐makingandthoseofsimpleinhibitoryorimpulsecontrol.Wehavearguedthat,withinthe“reBlective”system,thereisadistinctioninfunctioningbetween1)simpleinhibitoryandimpulsecontrolprocesses(somearemediatedbythelateralorbitofrontalandinferiorfrontalgyrusregions,andsomearemediatedbythemoreposteriorsectorsofthemedialprefrontalregion,i.e.,theanteriorcingulatecortex,bothdorsalandventral),and2)affectivedecisionmaking(mediatedbymoreanteriorregionsofmedialprefrontalcortex,includingthefrontalpole),whicharehighlyrelevanttobehavioralcontrolabilityandtothedecisionsindividualsmakefrequentlyonadailybasis(Bechara,2005).

Bothinhibitory/impulsecontrolfunctionandaffectivedecision‐makingareimportant,speciBicaspectsofhigherorderexecutivecontrolfunctioning(Winstanleyetal.,2006).

1.GoodinhibitoryfunctioningreBlectstheabilitytoactivelystopapre‐potentbehavioralresponse(e.g.,drinkingoreatinginexcess)afterithasbeentriggered(Loganetal.,1997;BraverandRuge,2006).

IndividualswithdeBicitsorfailuresinthesesystemshaveatendencytoactmoreimpulsively.

2.Adequateaffectivedecision‐makingreBlectsanintegrationofcognitiveandaffectivesystemsandtheabilitytomoreoptimallyweighshorttermgainsagainstlongtermlossesorprobableoutcomesofanaction(Bechara,2005).Forexample,excessivedrinkingoreatingknowntohaveshort‐term“reinforcingeffects”(butlong‐termnegativeconsequences)shouldbelesslikelyorproblematicforindividualsscoringhigherontasksthatassessthisability.

Thefunctionaldistinctionbetweensimpleinhibitory/impulsecontrolandaffectivedecisionmakingprocessescomesfromextensiveclinicalresearchwithpatientpopulationswithdamageinfrontalloberegions(see(Bechara,2005)forreviews).

However,thesetwosetsoffunctionsareasymmetricallyrelated,i.e.,oneway(notdouble)dissociation:DamagethatleadstobasicinhibitorycontroldeBicitsinevitablyleadstoaffectivedecision‐makingdeBicits.However,damagetoareasimportantforaffectivedecision‐making(e.g.,anteriorventromedialregion)canleadtopureaffectivedecision‐makingdeBicits,independentofanyothersimpleinhibitorycontroldeBicits.

Basedonanatomicalconnec$ons:Anteriorinsula:roleinintegra$onofautonomicandvisceralinforma$on.

Posteriorinsula:roleinsomatosensory,ves$bular,andmotorintegra$on.

In1947,BoninandBaileysaidthat“thefunc$onsandaffini$esoftheinsulaaretotallyunknown”.

Sincethen,althoughmuchhasbeenlearnedaboutthismysteriouslobe,s$ll(withtheexcep$onofafew)contemporarytextbooksofneuroanatomyandfunc$onalneuroimagingresearchtendtooverlookthefunc$onalimportanceofthisstructure:

3.Insularcortexsystem:responsivetohomeosta&cimbalance(depriva&onstates),whichac&vity: a.Exacerbatestheac&vityofthehabit/impulsivesystem.

b.Disable(or“hijack”)ac&vityoftheprefrontal(control/reflec&ve)system.

1.Earlierstudies(mid80’s),mostlyinanimals,ascribedarolefortheinsulaincondi$onedaversivelearning(e.g.condi$onedtasteaversionparadigm).

2.Laterstudies(late80’s;e.gBerthier):insulaandasymboliaforpainin6pa$ents;noemo$onalresponsetopainfuls$muli.

3.Fewstudiesthroughouttheseyearssuggestedarolefortheinsulainlanguage.

4.Intheearlytomid1990’s,someneuroscien$sts(e.g.,Damasio;Craig)begantosaythattheinsulaisa“plaaormforfeelingsandemo$on.”Morespecifically,theideaisthattheinsularcortexplaysanimportantroleinthemappingofbodilystatesandtheirtransla$onintowhatwesubjec$velyandconsciouslyexperienceasemo$onalfeelings.Perhapsrelatedtoconsciousfeelingsofurgetotakedrugs,includingtheurgetosmoke.

I. Case Report: Nathan is a right-handed male who lost interest in smoking after suffering from an ischemic stroke at the age of 28.

He was 38 years old when we interviewed him, and he was articulate and insightful about his medical and smoking history.

He started smoking at the age of 14. At the time of his stroke he was smoking more than 40 unfiltered cigarettes per day.

-Before his stroke, he used to enjoy smoking , experience frequent urges to smoke, and he often found it difficult to abstain from smoking in situations where it was inappropriate, such as at work, or when he was so sick and in the hospital.

-Hewasawareofthenega$vehealthconsequencesofsmokingbeforehisstroke,thoughhewasnotpar$cularlyconcernedabouttheseconsequences;hehadnevertriedtoquitandhehadnointen$onof

quiengatthe$meofhisstroke.

Nathan smoked his last cigarette on the evening before his stroke. When asked about his reason for quitting smoking, he stated: “[his] body forgot the urge to smoke.”

-He reported that he felt no urge to smoke during his hospital stay, even though he had the opportunity to smoke.

-While he came to believe that his stroke was caused in some way by smoking, this was not the reason why he quit; he never actually tried to quit smoking, but spontaneously, he had completely lost interest in smoking.

-Hehasnotfeltanyurgetosmokesincehequit.

2 1 3 4

A B C

1

2

3

4

A

B

C

High-resolution structural magnetic resonance images of his brain revealed:

• This suggested that the insula plays a critical role in psychological processes, such as conscious urge, that make it difficult to quit smoking and that promote relapse.

Conclusion: -What Hilke said yesterday:

We speak different languages! We must translate those languages…How different is what I said about urges and homeostatic signals in relation to the insula from that of “loss aversion” for example?

-What I say: you need a “translational” branch for this neuro field to survive in marketing and economics and the social sciences:

BasicNeuroscience

BasicNeuromarke$ng??Neuroeconomics??

Transla$onal‐‐‐‐‐‐‐‐ClinicalNeurosecience

Transla$onalMarke$ngorEconomics