MEMORYMODIFICATIONSANDETHICALIMPLICATIONS

RossMichaelReul,Jr.

PlanIIHonorsProgramTheUniversityofTexasatAustin

Spring2018

__________________________________________LauraL.Colgin,Ph.D.

DepartmentofNeuroscienceSupervisingProfessor

__________________________________________RebeccaA.Wilcox,Ph.D.

Honors&Scholarships,CollegeofNaturalSciencesSecondReader

ABSTRACT

Author: Ross Michael Reul, Jr. Title: Memory Modifications and Ethical Implications Supervising Professors: Laura L. Colgin, Ph.D. and Rebecca A. Wilcox, Ph.D.

Memory is a complex mental phenomenon that connects us to our past. It allows us to

learn and better navigate our world on a day-to-day basis, but more importantly, it helps us to

form an idea of who we are as a person, a sense of self, or an identity. Still, we forget most of

what we perceive at any moment, and even that which we do remember is extremely fallible. The

complexity of memories is that they are stored in the brain in such a way that they are vulnerable

to new information and constantly reformed through a process known as reconsolidation. While

this happens naturally in the brain, there are methods of promoting memory reconsolidation such

that specific memories can be modified, suppressed, or enhanced. Three such instances of

memory modification are false memories, molecular memory modifications, and direct

stimulation of memory storing neurons. False memories are a psychological method of

implanting false childhood memories in test subjects through suggestible discourse, while

molecular memory modifications involve a similar process with the aid or manipulation of

molecules known to have a role in the reconsolidation process. This paper reviews the current

literature on memory modifications and memory neuroscience before a review of the current

ethical debate on memory research and modification. It then puts forth an ethical framework for

how to proceed with human memory research as neuroscientists and psychologists develop

increasingly precise methods of influencing the natural functions of the human brain.

ACKNOWLEDGEMENTS

I would like to thank my faculty mentor, Dr. Laura Colgin, and second reader, Dr.

Rebecca Wilcox, for their guidance and support throughout the research and writing process.

This project could not have been completed without the oversight and encouragement of my

advisors. I would also like to thank all involved in the Polymathic Scholars and Plan II honors

programs for providing me with the knowledge, skills, and freedom to pursue a rigorous and

interdisciplinary academic course load while at the University of Texas at Austin. Finally, I

would like to thank my parents for their continued support through all of my life endeavors.

Table of Contents

INTRODUCTION .......................................................................................................................................... 1

MEMORY FORMATION AND RECONSOLIDATION .......................................................................... 3

FALSE MEMORY RESEARCH ................................................................................................................ 15

MOLECULAR MEMORY MODIFICATION ......................................................................................... 24

MEMORY AND NEUROMODULATION TECHNOLOGIES .............................................................. 34

ETHICAL DEBATE .................................................................................................................................... 42

CONCLUSION ............................................................................................................................................. 62

REFERENCES ............................................................................................................................................. 65

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MEMORYMODIFICATIONSANDETHICALIMPLICATIONS

Introduction

Memoryisanessentialaspectofthehumanexperience.Ourmemoryactsasa

survivaladaptationinthatweremembernegativeorharmfulexperiencesandavoidthem

infuturesituations.Itstoresaspectsofourdailyperceptionsandlinksthemtosensoryand

emotionalcues.Inthiswaymemoryalsoplaysaroleinourmoraldevelopment,tying

feelingsofregretorsatisfactiontopastactions.Ourmemoryisalsointrinsicallytiedtoour

personalidentityandsenseofself.Itconnectsourpresentselftoourpastexperiences,

whileallowingustoimaginefuturescenarios.

Formanycenturies,philosophersandwritershavecommentedontheinadequacies

andfrailtiesofthehumanmemory.FromAugustineinhisConfessionstoDescartesinhis

Meditationstomodernautobiographers,thosewritingabouttheirlivesandexperiences

haveexpressedtheideathattheirmemoryofpasteventsisnotinfallible,butratherlimited

anduntrustworthy.Recently,vulnerabilitiesinmemoryhavebecomeafocusof

psychologicalandneuroscientificresearch.Asneuroscientistscontinuetounderstandthe

underlyingmechanismsofthemind,novelmethodsofartificiallyexploitingbrainfunctions

tendtofollow.Thesameistrueformemories,andrecentfindingsregardingtheprocesses

ofmemoryformation,storage,andretrievalhaveopeneduppossibilitiesformemory

interventions,whereinmemoriesmaybepurposefullyaltered,suppressed,orenhanced.

Tobetterunderstandmemorymodificationsandtheethicalconsiderationsrelatedtotheir

useinhumans,Ibeginwithanexplanationoftheneurosciencebehindmemoryformation

andrecall.Ithenaddressthesignificantresearchonfalsememories,apurelypsychological

methodofaltering,andevenimplanting,memoriesintestsubjects,thathasprovided

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substantialinsightsintothenatureofmodifiedmemoriesandtheirbehavioral

consequences.Inextdiscussvariousmethodsofmolecularmemorymodification,whereby

particularmemoriesareactivatedwhilepharmacologicalinterventionsareusedto

enhanceorsuppressthetargetedmemory.Ifinishwithexperimentalmemorymodification

technologiesinvolvinglightorelectricstimulationofthebrainandhowtoproceedwith

thepossibleintegrationofmemorymodifyingtechniquesintomedicalorjudicialpractice

inanethicallysoundmanner.

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MemoryFormationandReconsolidation

Memoryisacomplexmentalprocess,andtherearemanydifferenttypesof

memory.Theinitialstageofmemory,calledsensorymemory,istheautomaticresponseto

perceptualstimulithatdegradesveryquicklywhenwearenotattendedtowardthe

stimulus.Theinitialsensoryinputmemorythenentersshort-termmemory,orworking

memory,whichinvolvesholdingasmallsetofinformation,usually5-9things,inmindfora

shortperiodoftime,usuallynomorethanaminute(Bear,Connors,&Paradiso,2016).

Short-termmemoriesallowustoperformday-to-daytaskssuchasholdingaconversation,

buttheyarealsoquicklydegradedwhenattentionisdistracted.

Whilesensorymemoryandshort-termmemoryinvolvemanyunconscious

processes,long-termstorageofmemoriesinvolvesmoreconsciousprocessing.Long-term

memoryisfurtherdividedintoprocedural,semantic,andepisodicmemory(Bearetal.,

2016).Proceduralmemoriesofteninvolvewhatmaybecalled"musclememory"andare

involvedinourabilitytoperformactionssuchasthrowingabaseball.Semanticmemoryis

memoryforfacts.Episodicmemoryismemoryforautobiographicaldetailsofpast

experiences.Aspectsofmemoriesthatmakeitintolong-termmemorycanbestored

indefinitely.

Eachmemoryaboutourlifewasperceivedbyoursenses,senttoourshort-term

memorywhereitunderwentunconsciousprocessessuchasobjectrecognition,thensent

toourlong-termmemoryformoreconsciousprocessing,beforebeingarchived

somewhereinourmind.Eachsensoryperceptionthatwetakeinissenttothebrain

throughaseriesofneurons,ornervecells.Neuronssendelectricalsignalscalledaction

potentialsthatpropagatetothespinalcordandspecificbrainregions.Neuronsinthebrain

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thenreceiveandprocesstheincomingelectricalsignalsthroughtheirownconnections.

Memoriesare,therefore,productsofelectricalsignalssentthroughoutdifferentregionsof

thebrain.

Whilethebrainregionsinvolvedinmanynervousfunctionssuchasspeechand

motorcontrolhadbeenlocatedinthebrain,upuntilthemid1950smemorywasregarded

asamentaltaskthatwasnotspecifictoanyregion(Squire&Wixted,2011).ThenDr.

WilliamScoville,aneurosurgeon,treatedapatientknownasH.M.foruncontrollable

seizuresbybilateralresectionofhishippocampus.Followingthesurgery,H.M.wascured

ofhisseizures,andhisI.Q.improvedby8points;however,hehadlostallcapacityfor

short-termmemory.Apsychologicalexaminationwasgiventothe29-year-old19months

afterthesurgeryonApril26,1955,anda"memorydefectwasimmediatelyapparent.The

patientgavethedateasMarch,1953,andhisageas27....thispatientappearstohave

completelossofmemoryforeventssubsequentto[hissurgery]...butearlymemoriesare

seeminglynormalandthereisnoimpairmentofpersonalityorgeneralintelligence"

(Scoville&Milner,1957).

Otherstudieshaveshownthatpatientswithhippocampaldamagestillretain

memoriesforplacesfromtheirpast.ApatientknownasE.P.sufferedbilateralhippocampal

lesionsaswellasdamagetosomemedialtemporalloberegionsaftersufferingfromherpes

simplexencephalitis.TheresultsofstudiesonE.P.showedthathecouldnotanswer

questionsabouthiscurrentneighborhoodbasedonhismemory.E.P.wasthenaskedabout

hischildhoodneighborhood.Hewasfirstaskedtoprovidea“familiarnavigation,”aroute

fromhishometoafamiliarlandmark,suchasaschool.Hewasthenaskedtoprovidean

“alternativeroute”tothesamedestination,imaginingthefamiliarroutewasblockedin

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someway.Finally,hewasaskedtodescribea“novelnavigation,”aroutebetweentwo

otherlandmarksfromhischildhoodneighborhood.Giventheseprompts,hewasableto

provideinformationabouthischildhoodneighborhoodthatwascorrecttoadegreethat

wasconsistentwithcontrolsubjects(Squire&Teng,1999).

Consolidationistheprocessofstabilizationofmemoriesinthebrain.Psychological

studiesperformedonH.M.andE.P.showedthatthehippocampuswasrequiredfor

consolidationofshort-termmemoriesintolong-termmemories,asH.M.couldnolonger

formlong-termmemoriesforanyeventfollowinghissurgery.Theyalsoshowedthatafter

consolidation,long-termmemorieswerenolongersolelyencodedinthehippocampus,as

E.P.hadmemoriesofplacesthathadbeenconsolidatedintohislong-termmemorypriorto

hishippocampallesions.

Tounderstandmemoryformationandrecall,itisalsonecessarytounderstand

Hebb’spostulateaboutthesynapticplasticityofneurons.Inresponsetostimuli,cell

assembliesareactivatedandreverberateactivitythroughreciprocalconnectionsuntilthe

stimulusisremoved.Twoneuronsthatfireatthesametimeformconnectionsand

strengtheneachother.Asmemoriesareconsolidated,nervecellsareconnectedtogether

andstrengthenedinanetworkknownasamemorytrace,orengram.

Therearetwomodelsofmemoryconsolidation.Onemodel,knownas“thedual

tracemodel,”claimsthattherearemultiplememorytraces,orphysicalneuralnetworks

encodingamemory,withshort-termmemorytracesinthehippocampusandlong-term

memorytracesintheneocortex.Theothermodel,knownas“theconsolidationmodel,”

purportsthatmemoriesareconsolidatedbetweenthehippocampusandneocortex,but

thatthememorytraceinthehippocampusistemporary(Dudai,2011).Consolidationof

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thememoryintolong-termmakesitresistanttodegradation.Thetwomodelsare

interrelatedinthat"bothhypothesesembraceauniversalunifyingconceptinbiology:

Livingentitiesdevelopandgrow"(Dudai,2011).

Memoryengramsactlikeelectricalcircuitsinthesensethatactivationofapartial

setofthenetworkisenoughtoactivatetheentireengram.Possibly,activationofjustone

orafewneuronsinvolvedinamemoryengramisenoughtoactivatetheentirephysical

traceforthatmemory.Thisprovidesamechanismformemoryretrieval.Thus,aparticular

smellthatisperceivedmightbereminiscentofacertainflowerthatbringsbackanentire

memoryofplayingoutsideatachildhoodhomeonesummer.

Justasdevelopmentandgrowthinvolvephysicalchangesinanorganism,sodoes

memory.Asreferencedintheintroduction,"thatmemoryinvolvesenduringphysical

changesintheorganismhasbeenproposed,usingera-dependentmetaphors,since

antiquity"(Dudai,2011).Whenamemoryengramisactivated,thatengramisnotonly

rememberedbutalsosubjecttoreconstruction.Thisreconstructionofactivatedmemories

isaprocessknownasreconsolidation,anditisthebasisformanytypesofmemory

modification.

In1968,ananimalstudywaspublishedthatshowedthatinterferingwithbrain

processesusingelectroconvulsiveshockstimulationtherapyfollowingthereactivationofa

memoryledtosuppressionofthatmemory(Misanin,Miller,&Lewis,1968).

Electroconvulsiveshockstimulation(ECT)involvespassinganelectriccurrentthroughthe

braintoinduceaseizure.Atthistime,ECTwascommonlyknowntocauseretrograde

amnesiaofrecentlylearnedexperiencesbyinterferingwiththeconsolidationprocess.

Althoughtheauthorsdonotmentionthetermreconsolidation,theresearcherswere

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intendingtofindoutifECTcouldresultinretrogradeamnesialongafterthelearning

experience.Ratswerefearconditionedwithan80-dbwhitenoisefollowedbya3-second

footshock.24hoursafterthefearconditioning,onegroupofratswasgivenabrief

presentationoftheconditionedstimulusfollowedbyECT,whileanothergroupwasgiven

onlyECT.Basedontheirfearresponses,theratsthatwerepresentedwiththeconditioned

stimulusshowedmemorylossofthefearconditioning,whiletheratsthatreceivedonly

ECTshowednomemoryloss(Misaninetal.,1968).Thisexperimentwasoneofthefirstto

showthatactivationofpreviouslyconsolidatedmemorytracesleftthosetracessubjectto

disturbance.Itwouldbemanyyearsbeforescientistsunderstoodthatreactivated

memoriesenteranunstablestateuntiltheyarereconsolidatedandthatanymemory

interventionemployedduringthisperiodoftimecouldaffectthememory.

Inthe2000s,similaranimalexperimentswereperformedthatsuggestedthat

reactivationofmemoryengramsinducesatransientperiodofinstabilityfortheactivated

memory(Schwabe,Nader,&Pruessner,2014).Bythistime,theprocessofnewmemory

consolidationintolong-termmemorywasbetterunderstood.Itwasunderstoodthatuntil

consolidationintolong-termmemory,newmemoriesarelabile.Itwasalsounderstoodthat

proteinsynthesisinneuronsisrequiredforconsolidation.Agroupofresearchers,referring

totheresultsoftheelectroconvulsiveshockexperimentsofthe1960s,wantedtoknowif

retrievedorreactivatedmemoriesrequiredareconsolidationprocesstobecomestable

again(Nader,Schafe,&LeDoux,2000).Theyfearconditionedratswith30-secondtones

followedby1-secondfootshocks.Someoftheratsunderwentmemoryreactivationeither

24hoursor14daysafterconditioning.Theyinjectedsomeoftherats'lateralandbasal

nucleioftheamygdala,aregionbelievedtobethesiteoffearmemorystorage,with

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anisomycin.Anisomycinisaninhibitorofproteinsynthesisandhadbeenpreviouslyshown

topreventtheconsolidationofnewmemories.Theresultsshowedthatregardlessof

whetherreactivationwasperformed1or14daysafterconditioning,infusionof

anisomycinfollowingreactivationproducedamnesiaonlatertests,andthatwithout

memoryreactivation,anisomycinhadnoeffectonthefearmemory(Nader,etal.,2000).

Also,ifanisomycinwasinjectedsixhoursafterreactivation,therewasnomemoryloss.

Theseresultsareconsistentwithpreviousstudiesthatsuggestatime-sensitiveperiodof

memoryinstabilityfollowingreactivation.Byshowingthatstabilizingoftheretrieved

memoryisdependentononeofthesameprocessesinvolvedintheconsolidationofnew

memories,namelydenovoproteinsynthesis,theresultsalsosuggestedthatreactivated

memoriesgothroughaperiodofreconsolidationbeforestabilization.

Whilethesestudiesshowedthatconditionedfearmemoriesinratscouldbeerased

orsuppressedbydisruptingthereconsolidationprocess,itwasnotcertainthatthesame

resultswouldbefoundforhumanpatients.Propranololisabeta-blockeroftenusedto

treathighbloodpressureandothercardiovascularconditions.Itwasalsofoundthat

"propranololselectivelyactsontheβ-adrenergicreceptorsintheamygdaladuring

emotionalinformationprocessinginhumans"(Kindt,Soeter,&Vervliet,2009).β-

adrenergicreceptoractivationhasbeenknowntohavearoleinproteinsynthesis,

especiallyintheprocessoflong-termpotentiationofmemory.Thus,itwasbelievedthat

propranololcoulddisruptproteinsynthesisintheamygdala.Giventhattheamygdalaisthe

mainstoragelocationforemotionalandespeciallyfearmemories,propranolol

administrationduringreactivationofafearmemoryshoulddisruptthereconsolidation

processandresultinthelossofamygdalarmemoryforaspecificfearresponse.Withthis

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inmind,researchersfearconditionedagroupofhumantestsubjects.Fearresponseswere

measuredbyeyeblinkstartlereflexinresponsetoloudnoisesandpicturesofspiders.

Theynotedthatthosesubjectswhowerefearconditionedtowardsthestimulihadstronger

eyeblinkresponsesascomparedtoacontrolgroup.Theyseparatedfear-conditioned

subjectsintogroupssimilartotheratstudies.Onegroupreceived40mgpropranololwith

memoryreactivation,onegroupreceivedadouble-blindplacebowithmemory

reactivation,andonegroupreceived40mgpropranololwithoutmemoryreactivation.The

resultsshowedasubstantialdecreaseinfearresponseforthegroupthatreceived

propranololwithmemoryreactivation,ascomparedtotheothergroups,whichshowed

littletonochangeinfearresponse(Kindtetal.,2009).Thus,eveninhumanfearmemories,

reactivationofamemoryisrequiredtoreturnthememorybacktoapre-consolidation-like

labilestate,duringwhichitissubjecttodisruptionbeforeitisreconsolidatedand

restabilized.

Thissuggeststhatpropranololdidindeeddisruptthereconsolidationofthefear

memoryintheamygdala.Importantly,thesubjectsdidnotloseepisodicmemoryforthe

fearconditioning.Thisisnotsurprisinggiventhatpropranololisspecifictoreceptorsin

theamygdala,andtheepisodicmemorytraceislikelystoredinthehippocampusor

neocortex.Theamygdalalikelyonlystoresthememorytracefortheemotionalfear

responsetotheconditionedstimuli.Theamygdalamaybethereasonthathighly

emotionalmemories,positiveornegative,aresowellremembered.Thebasolateral

amygdalaisassociatedwiththeemotionalcontentofourmemories,butithasalsobeen

showntoplayakeyroleinmodulatingmemoryconsolidationthroughstresshormones

andotherneuromodulatoryinfluences(McGaugh,2004).Thus,whiledisruptingthe

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reconsolidationofamemoryintheamygdalamaynoterasethecorrespondingepisodic

memorytracesinotherbrainregions,italsomaysuppressthememoriesasawholeby

blockingtheamygdala'sinfluenceonreconsolidationinthoseregions,anditcertainlymay

takeawaytheemotionsthatmakethememoryparticularlystrongtobeginwith.

Thestudiesdetailedabovehavefocusedonfearconditioning,forwhichthemeasure

ofthememoryhadbeenfearresponse.Whilethesestudieswerecrucialtounderstanding

theprocessofmemoryreactivationandreconsolidation,theymightonlyapplytofear

memoriesintheamygdalaasmeasuredbyunconsciousresponsestostimuli.Some

experimenterswantedtoknowifthesamereactivation-dependentmodificationsto

memorycouldbeaccomplishedinhumansforepisodicmemories.Althoughprevious

studiesfocusedonlyonerasingorsuppressingthereactivatedmemories,reactivation

opensatime-sensitivewindowforalltypesofmodifications-strengthening,altering,or

weakening-dependingonthetypeofmanipulationthataccompaniesthereactivationof

thememory.

Inordertotestwhetherornotthesameprinciplesofreconsolidationappliedto

humanepisodicmemories,researcherstested36universitystudents(Hupbach,Gomez,

Hardt,&Nadel,2007).Theywerebrokenupintothreegroupsof12andtoldtheywould

needtomemorizedifferentlistsofobjectsondifferentdaysofthestudy.Onthefirstdayof

thestudy,experimenterspulledrandomobjects(suchasaballoon,crayon,flower,key,or

sock)outofabagandplacedthemintoabluebasket.Thebasketwasthenhidden,andthe

subjectswereaskedtorecallalloftheitemsinthebasket.Thistaskwasrepeatedfour

timesoruntilthetestsubjectrecalledatleast17ofthe20itemscorrectly.Followingday1

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therewerenodifferencesbetweengroupsontheaveragenumberoftrialstakentoreach

17remembereditemsorfourtrials.

Onday2,onegroupof12,theremindergroup,wasshowntheemptybluebasket

fromday1bythesameexperimenterandasked,"Doyourememberthisbasketandwhat

wedidwithit?"Theywerenotaskedtorecallanyoftheitems,becausetheresearchers

werefocusedontheeffectsofanincidentalreminderratherthananexplicitreminder(i.e.

askingthesubjectstodescribetheprocessbutnottheactualitems).Foranothergroupof

12,theno-remindergroup,therewasnoreminderatallofday1.Individualsinthesetwo

groupswerethenpresentedwith20objectsandgiven30secondstomemorizethem.The

learningprocessdifferedfromday1astonotincidentallyremindtheparticipantsofthe

eventsofday1.Again,participantsrepeatedthememorizationtaskfourtimesoruntilat

least17objectswererememberedcorrectly.Therewasagainnodifferencebetweenthe

twogroupsontheaveragenumberoftrialstoreach17remembereditemsorfourtrials.

Thethirdgroupof12,thecontrolgroup,didnotparticipateinday2.

Onthethirdandfinaldayofthestudy,theexperimenteraskedallparticipantsto

recallalltheobjectstheycouldfromday1.Oncetheycouldnotnameanymoreobjects,

theyweregivenabreakwheretheexperimenterwouldengagetheminanunrelated

conversationbeforeaskingthemtorecalltheday1objectsagain.Allparticipantsrepeated

thisrecallatotaloffourtimes.

Theresultsofthestudyshowedthemeanpercentageofobjectscorrectlyrecalled

fromday1aswellasthemeanpercentageofintrusionsfromday2objectsthatwere

recalledasday1objectsduringtestingonday3.Theremindergrouphada36.3%recall

forlist1itemsand23.8%intrusions.Thiswascomparedto45.0%recalland4.9%

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intrusionsfortheno-remindergroupand49.5%recallwith0.5%intrusionsforthecontrol

groupthatdidnotparticipateinday2.Therewasnostatisticallysignificantdifferencein

thetotalnumberofobjectsrecalledfromday1;however,therewasasignificantdifference

betweenthereminderandno-remindergroupsonthenumberofintrusionsfromtheday2

list.Therewasnotasignificantdifferencebetweentheno-remindergroupandthecontrol

grouponnumberofintrusionsfromtheday2list(Hupbachetal.,2007).Thus,the

researchersshowedthatreactivationofepisodicmemoriesresultsinasimilarprocessto

fearmemoryreactivation,wherebythememorybecomeslabileandsubjecttomodification

untilitcanbereconsolidated.Inthestudy,theparticipantswhoweregivenanincidental

reminderofthefirstday'slistofobjectsincorporatedmoreoftheday2objectsintotheir

memoryfortheday1objects.Thislevelofincorporationofnewinformationwasonlyseen

inthegroupthathadrecentlyreactivatedthememoryofday1beforelearningnew

information.

Fromanevolutionarypointofview,itisnotentirelyclearwhyreconsolidation

exists.Atfirst,itmightseemthatwewouldbebetteroffifourmemoriesremainedstable

afterthefirstconsolidationfromshort-termtolong-termmemory.Giventhatwedonot

exactlyknowthebiologicalreasonforreconsolidationofmemories,itmayevenbetrue

thattheinstabilityofreactivatedmemoriesisabiologicalshortcoming.Morelikelyare

threepopularproposalsformoreadaptivepurposesforthelabilization-reconsolidation

process.Thefirstproposalisthatmemoryreconsolidationisbeneficialduetothenatureof

ourever-changingenvironments.Memoryupdating(ortheintegrationofnewinformation

intothebackgroundofdifferentmemories)allowsustoadapttonewenvironmentsand

storenewinformationwhileconnectingitwithrelevantpastinformation.AsYadinDudai

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stated,"updatingoutsidethetimewindowofreconsolidationmayfurtherfacilitatefast

incorporationofnewexperienceintoexistingassociativeknowledgeschemasinthe

absenceofsuperfluousactivationofindirectassociations"(Dudai,2011).Anotherproposal

holdsthatthelabilization-reconsolidationprocessiscrucialforthestrengtheningofthe

originalmemory.Inonesuchstudy,memorystrengtheninghasbeenshowntooccurasa

resultofthereactivationandreconsolidationofmemoriesratherthantheirretrievalalone.

Further,thesamestudyshowedthattheeffectsofstrengtheningwerenotpresentuntil

afterreconsolidationhasoccurredandthememoryisrestabilized(Forcato,Rodriguez,&

Pedreira,2011).Onelastproposedbenefitforthereconsolidationprocessisthat,atleast

forepisodicmemories,thereconsolidationprocessisactuallygoodforourimaginations.

Themalleabilityofmemoriesaddstothecreativityofourimaginations,for"toorigida

memorymayleadtopoorimagination,onethatplaysscenariosofthefuturethatareonly

similartothepast"(Dudai,2011).Itisconceivablethatupdatingourpastexperienceswith

newinformationfromthepresentwillallowustobetterimaginethefuture,because

withoutthecontextofthepresent,pastmemoriesmaybecomeirrelevant.

Whenactivated,memoryengramslosethestabilitythattheygainedthroughthe

originalconsolidationprocess.Whileinthissusceptiblestate,neuronsencodingthe

originalmemorycaninteractwithneuronscodingneweventsandinformation,and

connectionscanbemadeandstrengthenedbetweentheneurons.Theconnections

betweentheoriginalengramneuronscanalsobeweakened,strengthened,orassociated

withnewanddifferentepisodicmemoriesoremotionalstates.Thus,activatingmemory

tracesmakethememorysusceptibletonewinformationandinfluence.This

reconsolidationoflong-termmemoriesprovidesaneuroscientificmodelforthe

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inadequaciesofourmemoryandsusceptibilitytomisinformation.Italsoprovidesa

plausibleexplanationforhowmemoriesofpasteventscanbealtered,suppressed,or

enhancedbyactivatingamemorytraceandprovidinganindividualwithconflicting

informationoremotionswiththeaidofsuggestiblediscourseormoleculartargeting,or

evendirectneuronstimulationtechnologies.

Whilethestudiesmentionedabovehaveprovidedsignificantinformationaboutthe

roleandprocessofmemoryreactivationandreconsolidation,theyapplyonlytomemories

thathavebeenconditionedintestsubjectsinalabsetting.Whataboutlong-standing

episodicmemories?Doautobiographicalandpersonallyrelevantmemoriesundergothe

sameprocessofreconsolidationfollowingtheirreactivation?Ifso,manipulatingsuch

memoriescouldhavewide-rangingtherapeuticandjudicialusesaswellasarangeof

ethicalimplicationsthatdonotapplytolabconditionedmemories.

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FalseMemoryResearch

Onemethodofmodifyingpastmemoriesistheimplantationoffalsememories.The

processgenerallyinvolveshavingtestsubjectsthinkdeeplyaboutchildhoodenvironments

oreventsandfeedingthemfalseinformationalongsideothertruestoriesfromtheir

childhood.Theseexperimentswerenotinitiallyperformedinlightoftheneuroscience

researchonmemoryreactivationandreconsolidation,butratheraspsychological

examplesofthefallibilityofthehumanmemory.Regardless,themethodologyoffalse

memoryimplantationinvolvesactivationofmemoryengramsfromanindividuals’distant

pastfollowedbythepresentationofnewinformation;therefore,Iarguethatthesame

reactivation-reconsolidationprocessisatworkinthefollowingfalsememorystudies.

ElizabethLoftusandJacquelinePickrellfirstexploredtheformationoffalse

memoriesin1995(Loftus&Pickrell,1995).Knowingthatmemoriesofpasteventswere

subjecttointerferencebylaterexperiences,theysoughttoprovethatamemory,partialor

complete,ofaneventthatneveroccurredcouldbeimplantedinthemindofatestsubject.

Inordertodosotheycameupwithwhathascometobeknownasthe“lostinashopping

malltechnique.”Inthefirstcaseofasuccessfulfalsememoryimplantation,Loftusand

Pickrellfedfourstoriesofpasteventstoafourteen-year-oldtestsubjectnamedChris.With

thehelpoffamilymembers,theyconstructedstoriesofthreetrueeventsfromChris’

childhoodandonefalseeventwhereinChriswaslostinashoppingmallinhischildhood

homeofSpokane,Washington.Accordingtothestory,Chriswasfoundcryingbyanelderly

manafterlosinghisparents.Overfivedays,Chriswasaskedtowriteoutdetailsofallfour

eventswhileinstructedtowrite“Idon’tremember”foranydetailsthathewasunableto

recall.Overthefivedays,Chrisrememberedmoreandmoreabouttheeventthatnever

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occurred,includingdetailsabouttheelderlymanbeing“reallycool”andaboutbeing

scoldedbyhismother.Ratinghismemoriesofthefoureventsweekslater,Chrisgavea

ratingof8outof11fortheclarityofhismemoryforbeinglostinthemall,thesecond

highestratingoutofthefourevents.Whenlatertoldthatoneofthememorieswasfalse,

Chrisguessedoneofthetruememoriesastheeventthatneveractuallyoccurred(Loftus&

Pickrell,1995).

LoftusandPickrellthenusedthe“lostinashoppingmalltechnique”on24test

subjects.Studentresearchersrecruitedthesubjectsandarelativeofeachsubjectwhohad

detailedknowledgeofthesubjects’childhoodexperiences.Subjectswereunderthe

assumptionthattheywereparticipatinginastudyon“thekindsofthingsyoumaybeable

torememberfromyourchildhood.”Thesubjects’relativesprovidedaccountsofevents

fromthesubjects’childhood,andthesubjectreceivedabookletwithfourshortstoriesof

eventsfromtheirpast,includingthreetrueeventsandonefalsestoryaboutbeinglostina

shoppingmall,crying,andbeingrescuedbyanelderlyperson.Followingthecompletionof

thebookletandtwofollow-upinterviews,68%ofthetrueeventswereremembered

comparedto25%ofthefalsememories.Falsememorieswerealsorememberedwitha

lowerlevelofclarity,butofnote,theclarityratingofthememoriesincreasedbetweenthe

firstandsecondinterviews(Loftus&Pickrell,1995).Thisincreaseinclaritymaybethe

resultofincreasingconnectivitybetweendetailsofthefalseexperienceandtruedetails

andmemoriesfromthesubjects'childhoodshoppingmall.

Thefindingsofthefirstfalsememorystudyareremarkablenotforestablishing

somepercentageofpeoplethatcanbemadetobelievefalsememories,butratherfor

providingwhatLoftuscalls“existenceproofforthephenomenonoffalsememory

17

formation”(Loftus&Pickrell,1995).Priortofalsememoryformationresearch,Loftushad

spentyearsstudyingmemoryanditsassociationwitheyewitnesstestimony.Herresearch

onthemisinformationeffectinvestigatedwhethereyewitness’memoriescouldbealtered

byexposuretoincorrectinformationduringquestioning.Theformationofafalsememory

foracompletelyfabricatedevent,however,pavedthewayforalargerdebateinvolving

issuesbeyondthemisinformationeffectandincludingrealmsofpsychotherapy,criminal

testimonyandconfessions,andmedicine.

Follow-upstudiesshowedsimilarratesofrememberingforincreasinglyunlikely

falsechildhoodevents.IraHymanandcolleaguesimplantedmemoriesofanovernight

hospitalizationorabirthdaypartywithpizzaandaclownin20%ofsubjects(Hyman,

Husband,&Billings,1995).Theythenincreasedthepressureonsubjectstorecallafalse

memoryofspillingapunchbowlontheparentsofthebrideatawedding.Inseparate

studies,25-27%ofthesubjectsclaimedtorememberspillingthepunchbowl,some

relayingdetailsoftheappearanceandclothingofindividualsatthewedding(Hymanetal.,

1995).

Anotherinterestingsetofstudiesinvestigatedtheroleofadvertisinginfalse

memories.Afakeadvertisementwascreatedsuggestinganautobiographicalmemoryin

whichthesubjectshadshakenhandswithBugsBunnyasachildataDisneyresort(Braun,

Ellis,&Loftus,2002).Wellbeforetesting,participantsansweredalife-eventsinventory

questionnairethatcontainedaquestionaskingthemiftheyhadevershookhandswitha

cartooncharacteratathemepark.Theywereaskedtorespondwithanumberfrom1to

10,1being"definitelydidnothappen"and10being"definitelydidhappen".The

researchersremovedparticipantswhoratedthequestionas1-5ontheinitialtest.Onatest

18

afterpresentationofthead,78%oftheparticipantswhosawtheBugsBunnyad

respondedwithahigherconfidencelevelonthesamequestionforthelife-events

inventory.Also,whenaskedtowriteabouttheirmemoryoftheirchildhoodDisney

experience,participantswhowereshowntheBugsBunnyadreportedbetterclarity,

emotionalcontent,centralitytotheirchildhood,andimportancetotheirchildhood,as

comparedtoacontrolcondition.Additionally,16%ofparticipantswhowereshownthead

reportedtoremembershakinghandswithBugsBunnyduringachildhoodvisittoDisney

(Braunetal.,2002).

Inafollow-upstudyinElizabethLoftus'lab,researcherswereabletoget25-35%of

testsubjectstoremembermeetingBugsBunnyatDisneylandasachildaftershowingthem

fakeadvertisementswithsuggestibleautobiographicalmaterial.Evenmoreastounding,of

thosewhoclaimedtoremembermeetingBugsBunny,"62%rememberedshakinghishand

and46%rememberedhugginghim.Afewpeoplerememberedtouchinghisearsortail.

Onepersonrememberedthathewasholdingacarrot"(Loftus,2003).Notonlydoesthis

researchprovideevidencefortheabilityofadvertisingtochangepeoples'memories,but

moreimportantly,itgivesanexampleoftheimplantationofacompletelyimpossiblefalse

memory.Theresearchersknowwithoutadoubtthattheadvertisementsledtoafalse

memoryratherthanretrievalofatruememorybecauseBugsBunnyisaWarnerBros.

characterwhowouldhaveneverbeenpresentataDisneyresort.

Laterexperimentslookedtodeterminewhichpartsofthestandardfalsememory

implantationprocessweremostcriticaltoadoptionoffalsememories.AlanScoboriaand

hiscolleaguesidentifiedfivecomponentsoffalsememoryformationstudies:“(1)afalse

eventispresented;(2)anumberoftrueeventsobtainedfromfamilymembersare

19

presented;(3)participantsaretoldthatalloftheeventsoccurredpertheirfamily;(4)

participantsaretoldthatretrievalispossible;and(5)participantsengageinapurported

memoryretrievalprocedure,suchasguidedimageryand/orcontextreinstatement,over

repeatedtrials”(Scoboria,Wysman,&Otgaar,2012).Inseparatestudiestoisolate

individualcomponents,Scoboriaandhiscolleaguesconcludedthatattributingthefalse

eventsuggestionstoparentsresultedinstrongerfalsememories.Thisislikelydueto

subjectshavingaperceptionthattheinformationisfromatrustworthysource,andthus,

theyshouldrememberitandmightevenputmorepressureonthemselvestoremember

details.Theyalsofoundthatincludingtrueeventsalongsidethefalseeventinstudies

mightenhancethefalseeventsuggestionbecausethesubjectsknowthatacrediblesource

wasconsulted(Scoboriaetal.,2012).Again,thissuggestibilitylikelyresultsinmore

pressureforthesubjecttorememberdetailsofallevents,includingthefalsememory.Itis

importanttonotethatcomponents(1)and(2)fromtheaboveschemehappen

concurrently.Anotherimportantcomponentoffalsememorystudiesthatisnotmentioned

byScoboriaandcolleaguesisthatthefalseeventispersonalizedtothetestsubjectusing

informationprovidedbyfamilymembers,suchasspecificpeopleorplacesfromtheir

childhood.Thisincorporationofpersonallyrelevantpeopleorplacesmayservetoincrease

believabilityoftheaccountfromthebeginning,butmoreimportantly,itmayreactivate

memoryengramsassociatedwiththosedetails.Thiswouldallowtheinformationofthe

falseeventtobestoredandconnectedwiththeseactivatedmemorytraces,leadingtoa

falsememorythatfeelsastrueasanyoftheothertrueeventsrelayedtotheparticipant.

Whilethesestudiesdidnotseekouttodeterminewhattypesofindividualsare

susceptibletofalsememoryacceptance,thereweresomecorrelationsbetweenpersonality

20

traitsandfalsememoryacceptanceinthedata.Individualswhohadissueswithmemory,

attention,andawareness,basedontheDissociativeExperiencesScale,werefoundto

rememberfalsememoriesmore.Also,individualswhowereseentohavevividmental

imagery,basedontheCreativeImaginationScale,tendedtoadoptfalsememories(Loftus,

1997).Regardingthoseindividualswhohavememory,attention,orawarenessissues,this

resultisnotsurprising.Theymayhavelesstrustintheirownmemoriesfromthe

beginning,andthus,theywouldtendtorelyoninformationfromothersmoreoftento

supplementtheirmemory.Theyalsowouldbelessattentiveorawareofsignalsthatwould

normallyalertothersthatsomethingisnottrue,againresultinginaheightenedtrustfor

whattheyaretoldbyothers.Fortheindividualswithaheightenedcapacityforvivid

mentalimagery,theirtendencytoadoptfalsememoriesatagreaterratemaybemoredue

tothereactivation-reconsolidationprocessforlong-termmemories.Iftheyareableto

morevividlyimaginepasteventsandcues,theyarelikelyactivatingmoreoftheirdistant

memoryengramsandassociatingthosememoriestoagreaterextentwiththemisleading

suggestedinformationprovidedbytheexperimenter.

Falsememoryresearchersalsotestedtheroleofsleepdeprivationinfalsememory

implantation.Inoneexperiment,participantswerefirstgivenapassageaboutaplane

crashinPennsylvaniaonSeptember11,2001.Theyweretoldrepeatedlythatfootageof

thecrashwaswidelydistributedandaskediftheyhadseenthefootage.Theywerethen

shownaseriesofphotographsdepictingamanbreakingintoacarorawomanconfronting

athief.Theywerelatergivennarrativesthatincludedmisinformationaboutthephotosets.

Theresultsofthestudyshowedthatsubjectswhohadlesssleepthenightbeforewere

associatedwithincreasedfalsememories,andtestsubjectswho“reported5orfewer

21

hoursofsleepthenightbeforetheexperimentweremorelikelytoreportthattheyhad

witnessedanewseventthattheydidnotactuallysee….Therewasalsoatrendforthese

participantstoincorporatemoremisleadinginformationintotheirmemoryforvisual

materials”(Frenda,Patihis,Loftus,Lewis,&Fenn,2014).Theirsecondexperiment

addressedtheroleofsleepdeprivationatdifferentstagesofthemisinformationprocedure:

encoding,misinformation,andtest.Theresultsagainshowedthatthesleep-deprived

groupwasmoresusceptibletofalsememories,butthattheeffectwasonlyevidentwhen

participantsweresleep-deprivedatallstagesofthemisinformationprocedure(Frendaet

al.,2014).Theresultsofthesleepdeprivationstudymayalsobeduetothediminishing

effectsthatsleepdeprivationhasonmemory,attention,andawareness.

Having“existenceproof”offalsememoryimplantationinhumansaswellasa

plausibleneurologicalmodelfortheirformation,theroleoffalsememoriesinan

individual’slifemustbeaddressed.DanielBernsteinperformedtwoexperimentsto

examinewhetherornotfalsememoriescanhavelong-termeffects(Bernstein,Laney,

Morris&Loftus,2005).Inoneexperiment,237participantsfilledoutaFoodPreferences

Questionaire.Theywerethengivenafalsifiedprofileoftheirearlychildhoodfood

experiences,whichtheyweretoldwasindividualizedandbasedontheirresponses.One

thirdoftheparticipants’profilessaidtheyhadgottensickaftereatinghard-boiledeggs,

onethirdweretoldtheyhadgottensickaftereatingdillpickles,andtherestofthe

participantsmadeupthecontrolgroup.Theparticipantsinthepicklegroupreported

increasedconfidencethattheyhadgrownillfromeatingdillpickles,andtheyreported

higheravoidancescoreswithregardtopicklesthanothersinanimaginarybarbeque

scenariotest,butonlytheincreasedconfidencewasstatisticallysignificant(Bernsteinet

22

al.,2005).Inthesecondexperiment,180participantsfilledoutanidenticalquestionnaire

andreceivedsimilarfalsifiedfeedback.Halfwereplacedinthepicklefeedbackgroupand

halfintheeggfeedbackgroup.Theythenfilledoutfurtherquestionnairestodetermine

theirbeliefinthefalseinformationaboutthechildhoodfoodexperimentandtheirintentto

avoidcertainfoodsgoingforward.Theresultsshowedthatthosewhofalselybelievedthe

foodeventwereassociatedwithincreasedavoidanceoftheparticularfoodaswellas

closelyrelatedfoods.Bernsteinalsonotesthatsomeindividualsprovideddetailed

informationofthefalsememory(Bernsteinetal.,2005).Thesedetailedaccountswere

significantbecausethosewhoprovidedveryspecificanddetailedrecollectionsofabad

experiencewitheitherfoodhadpreviouslydeniedeverhavingsuchexperiencesinthe

originalquestionnaire.

Asimilarexperimentwasperformedlinkingfalsememoriesaboutalcoholto

changesinalcoholpreferences(Clifasefi,Bernstein,Mantonakis,&Loftus,2013).Usinga

similarmodeltothefood-preferencestudy,theresearcherssuggestedtosomeofthe

participantsthroughafalsifiedindividualizedfoodanddrinkprofilethattheyhadgotten

sickfromeitherrumorvodkaintheirearlyteenageyears.Non-controlparticipantswere

askedtoremembereventssurroundingthefalseautobiographicalepisodebefore

completingexitquestionnaires.Theresultsshowedthattheindividualswhoreceiveda

falsealcoholsuggestionweremoreconfidentthattheeventhadoccurredascompared

withthecontrolgroup.Thesamegroupalsoshowedacomparativelylowerpreference

towardthesuggestedalcohol(Clifasefietal.,2013).Thefoodandalcoholstudiesshowthat

adoptionoffalseautobiographicalmemoriescanaffectfuturebehavior.

23

Falsememoryimplantationprovesthatanindividuals'autobiographicalmemory

canbemanipulatedthroughmisinformationalone.Thereare,ofcourse,boundary

conditionsforthereliability,types,andextenttowhichtestsubjectsadoptfalsememories.

Inmoststudies,only20-30%ofparticipantsclaimedtohaveamemoryforthefalseevent.

Falsememorystudiesarealsolimitedtoincorporationofnewinformationintoasubjects'

memory.Entirelyfalsepasteventscanbeimplantedinasubjects'memory,orrealpast

experiencescanbereconsolidatedwithfalsedetails.Butratherthanenhancingor

suppressingspecificmemories,falsememoryresearchonlyprovidesevidencethatour

memoriesaresubjecttonewideasatlatertimes.Inordertoenhanceorsuppressspecific

memoriesofpasteventsthroughreactivationandreconsolidation,othermethodsmustbe

explored.

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MolecularMemoryModification

Molecularmemoryinterventionshaveshownpromisingresultsasmethodsfor

targetedandspecificenhancementorsuppressionofestablishedmemories.Molecular

memorymodificationsinvolvemanipulatingmoleculesknowntobeinvolvedinthe

formation,consolidation,orreconsolidationofmemory.Byinhibitingorupregulating

certainmoleculesthatarecriticalforproperfunctionofthesememoryprocesses,newor

pastmemoriescanbealteredinaveryspecificmanner.Ithasalreadybeenshownthat

amnesictechniquesandmoleculesdisruptthereconsolidationofmemoriesinanimal

models.Herewefocusonmolecularmemoryinterventionsthathavebeenproposedfor

humanuseandtreatment.

Themostcommonlycitedmethodofmolecularmemorymodificationistheoral

administrationofpropranolol.Aswasdescribedbefore,propranololisadrugcommonly

usedforcardiovascularconditions,butitalsohasaselectiveeffectontheamygdala.Inthe

studydescribedbefore,propranololwasshowntohaveadampeningeffectonthe

emotionalfearmemoryforaconditionedfearresponse(Kindt,Soeter,&Vervliet,2009).

HereIwilldiscusstheuseofpropranololtomodifynon-conditionedemotionalmemories,

thatis,memoriesofpastexperiencesofemotionalsignificancethatwerenotinducedina

labsetting.

Stressdisordersareaparticulartypeofanxietydisordercausedbytraumatic

experiences.Post-traumaticstressdisorder(PTSD)isaparticularlysevereformofstress

disorder.AccordingtotheNationalInstituteofMentalHealth,symptomsofPTSDinclude

nightmaresandflashbacks,difficultyconcentratingorfallingasleep,avoidanceofpeopleor

otherthingsrelatedtothetrauma,extremeresponsestobeingstartled,emotional

25

numbness,lossofenjoyment,anger,andguilt(NationalInstituteofMentalHealth,2016).

PTSDcanbeadebilitatingdisorderthattakesatollonone'sday-to-dayrelationships,

senseofself,andpeaceofmind.

Justaswithanyothermemory,traumaticmemoriesundergoconsolidationfrom

short-termtolong-termmemory,however,especiallytraumaticmemorieshave

considerableemotionalcontentbehindthemandtriggerthereleaseofadrenalineand

otherstresshormones.Theinfluenceoftheamygdalaandtheincreasedlevelsof

noradrenalineresultintheoverconsolidationofthetraumaticmemoryengram(Henry,

Fishman,&Youngner,2007).Thus,therootofpost-traumaticstressdisorderisan

overconsolidated,andthereforeeasilybroughtupandnoteasilyforgotten,traumatic

memory.

Itisbelievedthatpropranolol,becauseitisabeta-blocker,couldbeusefulin

blockingtheeffectsofnoradrenalineduringtheconsolidationoftraumaticmemories,

preventingthemfrombecomingoverconsolidated(Henryetal.,2007).Infact,propranolol

hasalreadyshownpromisingresultsfordecreasingtheinstanceofPTSDdevelopmentin

real-lifetraumapatients.Inclinicaltrialswhereinemergencyroomtraumapatientswere

giveneitherpropranololtreatmentsorplacebo(Pitmanetal.,2001)orgiventhechoiceof

takingpropranololornot(Vaivaetal.,2003),thosepatientswhoweretreatedwith

propranololsoonaftertraumaticexperienceshadmuchlowerratesofdevelopingPTSD.

Althoughtheseresultsarepromisingfortheuseofpropranololasapreventativemeasure

againstthedevelopmentofPTSD,itcanoftenbehardtopredictwhattypesofeventswill

resultinanindividualdevelopingPTSD.Disruptingtheinitialconsolidationoftraumatic

memoriesisatime-sensitivemeasure.Amoreuniversallyapplicablememorytreatment

26

forPTSDwouldhavetobeabletoaffectmemoriesforeventsthathappenedmonthsprior,

beforethesymptomsbegantomanifestanddiagnosiswaspossible.

Knowingthatinterventionsduringthereconsolidationphaseofarecently

reactivatedmemorycanhaveaneffectonpreviouslyconsolidatedmemories,agroupof

researcherssetouttodeterminewhetherpropranololusedduringreconsolidationwould

indeedhaveadampeningeffectonthetraumaticmemoryofPTSDpatients(Brunetetal.,

2008).Thestudyinvolved19individualswithchronicPTSD.Theywereaskedtodescribe

thetraumaticeventthatcausedtheirPTSDinordertoreactivatethememory.A

personalizedscriptwasmadeforeachpatient'sexperiencebytheexperimenters.The

patientswerethengiveneither40mgshort-actingpropranololfollowedhourslaterwitha

60mgdoseoflong-actingpropranololoraplaceboatbothinstances.9patientsreceived

propranololtreatments,while10receivedtheplacebo.Oneweeklater,subjectswere

calledbackinfortesting.Baselinemeasurementsweremadeforheartrate,skin

conductance,andleftcorrugatorelectromyogram.Subjectswerethenaskedtolistento

theirpersonalizedscriptswhileimaginingtheirtraumaticexperience,andthesame

measurementsweremade.Theresultsshowedthatthephysiologicalresponsetothe

mentalimagerywassignificantlysmallerforthoseindividualsinthepropranololtreatment

grouptheweekprior,ascomparedwiththosewhoreceivedtheplacebo(Brunetetal.,

2008).Follow-upstudiesbyBrunetandcolleaguesusedsixtreatmentsessionsratherthan

one,leadingtomoresignificantresultsabouttheclinicalpotentialandtheeffectonPTSD

symptoms(Brunetetal.,2011).Becausepropranololisspecifictotheamygdala,itshould

nothaveaneffectontheepisodicmemorytraceforPTSDpatients'traumaticmemories,

butitmaybeeffectiveindiminishingsomeoftheemotionalpainandreactionstothat

27

memory.Thesepreliminarystudiesarepromisingfortheefficacyofpropranololasa

treatmentforthephysiologicaleffectsandsymptomsofPTSD.

Propranololhasalsobeenusedinstudiestestingitseffectsonothertypesof

memories.Drugrewardmemoriesareonesuchtypeofmemorythatundergoes

reconsolidationafterreactivation.Inonetranslationalstudy,theeffectsofpropranolol

duringreconsolidationofnicotine-associatedmemoriesinratsandhumanswere

investigated(Xueetal.,2017).Fortheratstudy,ratsweresubjectedtoanicotine-

associatedunconditionedstimulusbeforetheywereinjectedwithpropranolol.Inthe

humanstudy,memorieswerereactivatedwithanunconditionedstimulusandpropranolol

orplacebowasadministeredorally.Inboththeratandhumanstudies,theresultssuggest

thatpropranololadministrationalongsidereactivationandreconsolidationofnicotine-

associatedmemories"maybeapromisingmethodfordecreasingnicotinecraving.

Additionally,tothedegreethattheresultsfromtheratmodelsgeneralizetodrugaddiction

amongpeople,thepotentialvalueoftheprocedureshouldbetestedforthepreventionof

relapsetosmoking"(Xueetal.,2017).

Anotherstudyinvestigatedwhetherornotthesametypeofpost-retrieval

propranololadministrationwouldhaveaneffectoncravingandcuereactivityforcocaine

addicts(Saladinetal.,2013).50cocaine-dependentindividualsatanin-patientfacility

participatedinthestudy.Allweregivencocainecueexposuretoreactivatecocaine-

associatedmemories.Immediatelyafterthecueexposure,26weregiven40mg

propranololand24weregivenaplacebo.24hourslater,theyunderwentanotherroundof

cocainecueexposure.Cravings,heartrate,skinconductance,andbloodpressurewere

measuredbefore,during,andafterbothcueexposuresessions.Theresultsshowedthatthe

28

propranololgrouphadagreaterreductionincravingsandphysiologicalmarkers24hours

afterthepost-retrievalpropranololtreatmentascomparedtotheplacebogroup(Saladin

etal.,2013).Theresearchersfoundnoevidenceoftreatmenteffectsatafollow-upaweek

later,butgiventhe24hourresultsandkeepinginmindtheBrunetetal.studieswithPTSD,

thereispromisingevidencethatfurtherstudiesthatemploymorethanonetreatment

couldhavetherapeuticeffectsthatpersistovertime.

Propranololhasbeenshowntimeandtimeagaintohaveasuppressingeffecton

emotionalmemories.Whereaspropranololhasaninhibitoryeffectonthereconsolidation

process,othermoleculesknowntobeinvolvedinreconsolidationmayenhancethe

process.Itisknownthatintraumaticmemoryconsolidationandreconsolidation,stress

hormonescanleadtotheoverconsolidationofmemories.Inastudyinvestigatingthe

effectsofcortisoladministrationduringreconsolidationofaconditionedfearmemory,

cortisolwasshowntoenhancethereactivatedmemories(Drexler,Merz,Hamacher-Dang,

Tegenthoff,&Wolf,2015).Thistypeofexperimentprovidesamodelforhowmemories

couldbespecificallytargetedthroughreactivationandenhancedwithpharmaceutical

interventions.Whilethistypeofeffectwouldbeconsideredlessthanidealforpatientswith

PTSDordrugaddictswithdrug-associatedmemories,suchmemorymodificationscould

beofuseinscenariossuchaseyewitnesstestimony.

Anotherstudysoughttodeterminetheeffectofstressorsduringreconsolidationof

humandeclarative(episodic)memories(Larrosaetal.,2017).Participantswereaskedto

memorizecuesandresponses.Experimentersusedacoldpressorstresstreatment(CPS)

asastressor,andsalivatestsshowedthatCPSledtoraisedcortisollevels.Theresults

showedthatapplyingstressorsbeforereactivationofdeclarativememoriesledtoshort

29

andlong-termdecreasesinmemoryexpressionforthedeclarativememories(Larrosaet

al.,2017).Otherstudieshaveshownthatstressorsduringreconsolidationcanhave

enhancingorimpairingeffectsonthememoriesthatarereactivated.Asmoreinformation

isgathered,theadministrationofstresshormonesduringreactivationofmemoriescould

becomeaminimallyinvasivemethodforpreciselyenhancingorsuppressingvarioustypes

ofmemories.

AnothermoleculecalledproteinkinaseM-zeta(PKMζ)hasbeenshowntohavea

roleinmaintaininglong-termmemoriesinthebrainbywayoflong-termpotentiation(Hui

&Fisher,2015).Long-termpotentiation,orLTP,referstothestrengtheningofneural

synapsesinvolvedinlearningandmemoryandcanlastformonthsorlongerafterinitial

learning.PKMζisanaturalproteinencodedbythePRKCZgene.Thebrainmustcontinually

producePKMζinordertopreservelong-termmemory,asitisslowlydegradedovertime.

"Bymanipulating[PKMζproduction]inrodents,researchershavebeenabletobotherase

andenhancememoryunderlaboratoryconditions,"becausePKMζcanbeeitherinhibited

orupregulateddependingonthedesiredeffect(Hui&Fisher,2015).Interventionswith

PKMζduringthereconsolidationprocesscouldleadtoextremelyspecificmemory

alterationsineitherdirection.Also,incontrasttopropranololandcortisol,"PKMζappears

tobecommontoallmemoriesregardlessofwhethertheyaredeclarative(ie,explicitand

conscious,suchasfacts)orprocedural(ie,implicitandunconscious,suchasmuscle

memory)"(Hui&Fisher,2015).Thus,amoleculesuchasPKMζcouldbeauniversaltarget

fortheerasure,enhancement,andmodificationofalltypesofmemories.

OneofthefirstexperimentsinmanipulatingtheroleofPKMζinvolvederasureof

long-termmemoryassociations(Shema,Sacktor,&Dudai,2007).Theresearchers

30

understoodthatPKMζmustbepersistentlyphosphorylatedtomaintainlong-term

potentiationofmemories.Theychosetomanipulatethisprocessintheratinsularcortex,a

regionofthebraincontainingthegustatorycortex.Thetargetfortheirmemory

interventionwastherattastememoryprocess.Theyconditionedatasteaversionfor

saccharininrats.Threedayslater,theybeganinfusinganinhibitorofPKMζ,myristoylated

zeta-pseudosubstrateinhibitorypeptide,orZIP,intotherats'insularcortex.Ratsreceiving

ZIPadministrationswereinfused3,7,or25daysfollowingtheinitialconditionedtaste

aversion.Aversionwaslatermeasuredthroughapre-establishedaversionindex.Allthree

ZIPgroupsdifferedsignificantlyfromthecontrolgroupintasteaversion,(Shemaetal.,

2007)andZIPinfusionsintotheICappearedtoselectivelyerasetheconditionedtaste

aversionmemory.Interestingly,therewasnosignificantdifferencebetweenthethreeZIP

groupsontasteaversionindex,(Shemaetal.,2007)implyingthatZIPeffectivenessisnot

extremelytimesensitive.Anotherimportantfindingcamefromafollow-upstudybythe

sameresearchers,inwhichtheyreactivatedthememorytracepriortoZIPinfusion.While

similarresultswereobtainedwithreactivationofthetasteaversionpriortoZIPinfusion,

"noreactivationisneededtorenderthetracesusceptibletoZIP"(Shemaetal.,2007).This

findingseemslimitedtoZIPanditseffectsonPKMζproduction,asotherclassicalamnesic

agentsdonothaveaneffectonlong-termconditionedtasteaversionunlessthememoryis

reactivatedpriortoadministration.Thismayhaveimportantimplicationsforthe

specificityofPKMζinhibitorssuchasZIP,becauseitwouldseemthatareactivation-

dependentsystemwouldbemoreaccuratefortargetedmemories.Withnonecessityforor

specificitytowardscue-reactivatedmemorytraces,itwouldappearthatZIPinfusionsare

limitedinspecificitytothespatialbrainareathattheyareinfusedinto,meaningtheycould

31

easilymisstheirmemorytargetorhaveeffectsonunintendedmemories.

AverysimilarexperimentwithPKMζwasperformedtotesttheeffectsof

overexpressionoftheproteinonlong-termmemory(Shemaetal.,2011).The

experimentersdesignedlentivirusesthatexpressedPKMζandinfusedthemintothe

insularcortexofratsthathadbeentasteaversionconditioned.Theyusedgreenfluorescent

protein(GFP)asamarkertoassuretransformation,and"overexpressionofthePKMζ

protein[intheinsularcortex]wasevident"(Shemaetal.,2011).Memoryforthe

conditionedtasteaversionwassignificantlyenhancedforthoseratsinfectedwithPKMζ

expressinglentiviruses,ascomparedtootherratsinfectedwithlentivirusesexpressinga

dominantnegative(mutated,inactiveform)ofPKMζandthoseexpressingonlyGFP

(control).Also,theresultsshowedthattheextentof"memoryenhancementwaspositively

correlatedwiththeextentofLVPKMζinfectioninthe[insularcortex]"(Shemaetal.,2011).

ThisexperimentshowedhowtheupregulationofPKMζcouldeffectivelyenhancelong-

termmemories.Moreresearchshouldbeperformedandnovelmethodsofcausing

overexpressionofPKMζshouldbeexplored,asviralvectorsarenotanidealtechniquefor

possibleinterventioninhumans.

WhilePKMζseemslikeapromisingtargetformolecularmemoryinterventions,J.L.

KwapisandF.J.Helmstetterhaveraisedcaveats(Kwapis&Helmstetter,2013).WhileZIP

wasbelievedtobindsolelytoPKMζ,thereisevidencethatZIPtargetsotherPKCisoforms

inthebrainthatmayhaveaneffectonitsroleinmemorymaintenance.Also,therehave

beenconflictingfindingsontheuniversalityofPKMζformemorymaintenance,assome

studiessuggestthatPKMζdoesnotmaintainsomespecifictypesofmemoriesindifferent

regionsofthebrain.Finally,althoughthememoryerasurestudydescribedabove(Shema

32

etal.,2007)suggestedthatreactivationisnotrequiredforZIPtoeffectivelyerasetargeted

memories,otherworkhasbeendonethatmakesacaseforthenecessityofreactivation

withZIPinfusion.Still,thefindingsofthesestudies“donotconclusivelyruleoutthe

possibilitythatPKMζnormallyactstomaintainmemory"(Kwapis&Helmstetter,2013).I

wouldarguethattheinconsistencywithfindingsaboutPKMζservesnottodiminishitsrole

inthemaintenanceofmemory,butrather,servesasatestamenttothecomplexityof

memorysystemsandtheinabilitytosimplifysuchprocessestotheeffectofsingle

molecules.

Multitudesofmoleculesanddrugshavebeenshowntoaffectthememoryprocess

throughouttheyears.Inlightoftherelativelyrecentresearchontheneuroscienceof

reconsolidation,manyofthesedrugsmaybereconsideredaspossiblememory

interventionsduringthereconsolidationprocess.Examplesincludescopolamineand

benzodiazepines.Scopolamineisananticholinergicdrugthataffectstheneurotransmitter

acetylcholine,andit"impairsaspectsofinitialmemoryacquisition(e.g.encodingand

consolidation)andspontaneousmemoryretrieval"(Caine,Weingartner,Ludlow,Cudahy,

&Wehry,1981).Benzodiazepinesareaclassofpsychoactivedrugstheenhancegamma-

aminobutyricacid(GABA)receptorsinthebrain,and"allbenzodiazepinescanbeshownto

causeanterogradeamnesia"(King,1992).Thesetypesofmoleculesandothermolecules

withknownrolesinmemoryformation,consolidation,maintenance,andreconsolidation

mustbeinvestigatedaspossibleinterventionsforsaferandbetter-targetedmolecular

memorymodifications.

Becausethephysicalprocessesandmechanismsofreconsolidationarestilllargely

unknown,thereisconsiderableroomforadvancementwithmolecularinterventions.

33

Knowingthatproteinsynthesisisrequiredforreconsolidation,thenextstepinfinding

effective,targeted,andreliablemolecularinterventionsistoidentifyspecifictranscription

factors,kinases,andotherproteinsandenzymesinvolvedintheprocessandexploretheir

role.Thereisstillmuchtobelearnedbecause“studiesofreconsolidationhavetakenthe

manipulationsthatareknowntoaffectconsolidationasastartingpoint,andexamined

theireffectsonreconsolidation”(Tronson&Taylor,2007).Whiletheseprocessesarevery

similar,theyarenotentirelythesame.Thus,notallmoleculesknowntoaffect

consolidationwillhavethesameeffectsduringreconsolidation,andtherearelikely

mechanismsandmoleculesinvolvedinreconsolidationthathavenoroleinconsolidation.

Asmoreisunderstoodaboutthemolecularprocessesinvolvedinmemory,itisalso

importanttolookattechnologiesthathavethecapabilitytoinfluencememoryinaless

invasivemannerthanmolecularmanipulations.

34

MemoryandNeuromodulationTechnologies

Neuromodulationtechnologiesaretechnologiesthatcanalternerveactivity

throughvariousmeansofstimulation.Asadvancesinneurosciencecontinuetolead

towardsamorerefinedunderstandingofbrainfunctionsandprocesses,neuromodulation

technologiesbecomemoretargetedanduseful.Forexample,technologiessuchasbrain-

computerinterfaceshaveprogressedfromEEGcontrolofcursorsonacomputerscreento

brain-implanttechnologiessuchasBrainGate,whichhaveallowedparalyzedpatientsto

moverobotarmswithenoughprecisiontogrababottleandtakeasipofcoffee(Robson&

Davenport,2014).Neuromodulationtechnologiesaffectingmemoryhavebeenusedsince

thelate1930s,beginningwiththeuseofelectroconvulsiveshocktherapy(ECT)for

patientsexperiencingschizophreniaanddepression(Impastato,1960).Althoughstillused

todayinsomecasesofseveredepression,theuseofECTisunderasignificantamountof

controversy.Therearefewotherneuromodulationtechnologiesdirectedtowardhuman

memoryinpracticetoday,buttherehavebeenplentyofinstancesofpromising

technologiesdevelopedforlaboratoryuse.Itisnotbeyondthescopeofreasonthatasour

understandingofmemoryprocessescontinuestodevelop,moreneuromodulation

technologieswiththepowertoenhance,suppress,oralterhumanmemorieswillcomeinto

practice.

Ashasbeenalreadydiscussed,electroconvulsiveshocktherapywasemployedasa

methodofinducingretrogradeamnesiainratsinoneofthefirststudiestoidentifya

reconsolidationprocessforlong-termmemories(Misaninetal.,1968).A2014studyonthe

effectsofECTondepressedhumanpatientsfoundsimilarresults,namelythatECTapplied

duringreconsolidationofanemotionalepisodicmemoryresultedinadecreaseinthe

35

reactivatedmemory(Kroesetal.,2014).42patientswithunipolardepressionparticipated

intheclinicalstudyandwererandomlyassignedtothreegroups.Allpatientswereasked

tolearntwoemotionallyaversiveslideshowstories.Oneweeklater,thepatientswere

shownapartialversionofthefirstslideofoneoftheslideshowsinordertocue

reactivationofthatstory.PatientsingroupsAandBwerethenanesthetizedand

underwentECTimmediatelyfollowingreactivationofthefirststory.GroupCpatientswere

inthecontrolgroupanddidnotreceiveECT.GroupBpatientsweretestedonthetwo

storiesabout90minutesafterreactivationandECT,whilegroupAandCpatientswere

testedonthestories24hoursafterreactivationandECT.Theresultsshoweddisruptionof

thememoryforthereactivatedstoryingroupA.Forthenon-reactivatedstory,memory

performancewascomparableingroupsAandB,andgroupBshowednodifferencein

performancebetweenthereactivatedandnon-reactivatedstory.GroupChadbetter

memoryperformanceonthereactivatedstorythanthenon-reactivatedstory(Kroesetal.,

2014).TheseresultsprovidemanyinsightsintothepotentialofECTandreconsolidation.

First,ECTresultedindisruptionofthereactivatedmemorybutnotthenon-reactivated

memoryforgroupA,suggestingthatECTinandofitselfdoesnotresultingeneralmemory

disruptionandreactivationisnecessary.Secondly,ECTdidnotresultinachangein

memoryperformanceforareactivatedmemorywhentested90minutesafterthetherapy

(groupB),suggestingthatreconsolidationofthereactivatedmemorymustbecompleted

beforeresultsareobserved.Lastly,groupC,whodidnotundergoECT,hadimproved

memoryperformanceforthereactivatedmemory,suggestingthatmemoryreconsolidation

isbeneficialwhennomanipulationisinvolvedintheprocess.Unfortunately,becauseECT

issuchacontroversialneuromodulationtechnique,therearelimitedapplicationsfor

36

humanuseandotherneuromodulationtechnologiesshouldbeconsidered.

Onesuchneuromodulationtechnologywithawiderangeofusesinhumansis

transcranialdirectcurrentstimulation(tDCS).tDCSisanon-invasiveneuromodulation

techniquethatinvolvesplacingananodeandcathodeoverthescalpinordertopassa

weakelectriccurrentthroughthebrain.Thisregion-specifictechniquecaneitherenhance

neuronalfiringthroughanodalstimulationordampenneuronalfiringintheregion

throughcathodalfiring.Variousstudieshaveshownpromisingresultsofbothformsof

tDCSinprocessessuchasinitialmemoryconsolidationandworking-memoryfunction

(Javadi&Cheng,2013).FewstudieshaveexaminedtheeffectsoftDCSonlong-term

memoryreconsolidationinhumans.

A2013studyexaminedtheeffectsofdifferenttypesoftDCSstimulationduring

memoryreconsolidation(Javadi&Cheng,2013).Theexperimentinvolved30participants

whowereseparatedintoareconsolidationgroupandacontrolgroup.Participants

underwentanencodingsessionwheretheywerepresentedwithwordsandaskedto

imagineandmemorizethem.Afterathree-hour"consolidation"window,participantsin

thereconsolidationgroupreceivedtDCSstimulationfor20minuteswhileperformingan

old-newwordrecognitiontask.ParticipantsinthecontrolgroupreceivedtDCSstimulation

whileplayingcomputergamesunassociatedwiththewords.Participantswerethengivena

five-hour"reconsolidation"window.Thenbothsetsofparticipantsperformedtheold-new

wordrecognitiontask.Theexperimentwasperformedoverthreedaysemployinganodal,

cathodal,orshamstimulationondifferentdays.Theresultsshowedanincreasein

performanceforthereconsolidationgroupwithanodalstimulationcomparedtothatofthe

controlgroup.However,therewasnotasignificantdecreaseinperformanceforthe

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reconsolidationgrouponthecathodestimulationday.Theresearcherssuggestthatitmay

beeasiertoenhancememoryreconsolidationusinganodaltDCSthanitistodisruptthe

reconsolidationprocesswithcathodaltDCS(Javadi&Cheng,2013).Whiletheresearchers

failedtoshowhowtDCSmightdampenthereconsolidationprocessinthesamemanner

thatithadforpreviousstudiesonothermemoryprocesses,theydidprovideevidencethat

itispossibletoinfluencehumanmemorywithanodaltDCS.

AnotherverysimilarstudyshowedpromisingresultsforthelastingeffectsoftDCS

onepisodicmemoryinolderadults(Manentietal.,2017).Inthisstudy,22subjectslearned

alistofwordsandwereseparatedintotDCSandcontrolgroups.24hourslater,

participantsweregivenacontextualreminderofthewordslearnedwhiletheexperimental

groupreceivedtDCSoverthelateralprefrontalcortex.Theytestedmemoryperformance

48hoursand30daysafterthecontextualreminder,andinbothcases,theexperimental

grouphadhigherperformancethantheplacebogroup.Theresearcherssuggestedthat

tDCSmighthaveapotentialuseinthepreventionofold-agememorydisorderssuchas

Alzheimer’s(Manentietal.,2017).

AnothersignificantstudyshowedthattDCShadenhancingeffectsonconditioned

fearmemoriesinhumans(Mungeeetal.,2014).74individualsunderwentfear

conditioninginvolvinglow-intensitywristshocks.Skinconductanceresponseswere

measuredthroughouttheprocess.Onedaylater,allparticipantswereremindedofthefear

conditioningwithasinglepresentationofthestimulusandshock.Theexperimentalgroup

thenreceivedanodaltDCSoverthelateralprefrontalcortexwhilethecontrolgroup

receivedshamstimulation.Onthefollowingday,fearresponsesweremeasuredin

responsetostimuli,andtheresultsshowedincreasedfearresponseaftermemoryretrieval

38

withtDCSanodalstimulationascomparedtothecontrol(Mungeeetal.,2014).An

importantfollow-upstudyfortheseresultswouldneedtoexaminetheeffectsofcathodal

tDCSstimulationforfearmemories,becauseanon-invasivedampeningprocedurecouldbe

ofusefordampeningreconsolidationoftraumaticoraddiction-associatedmemories.

Transcranialmagneticstimulation(TMS)isanothermethodforinducing

neuromodulationofspecificbrainregionsinanon-invasivemanner.TMSinvolvestheuse

ofamagneticfieldratherthanelectriccurrentsforstimulationofneurons.Dependingon

thecoilsusedintreatment,TMScanbeusedforstimulationfrom1-4cmbelowthescalp.

Isserlesandcolleaguesexploredtheuseofdeeptranscranialmagneticstimulation

(DTMS)ofthemedialprefrontalcortexinpatientswithPTSDwhowereresistantto

standardtreatmentmethods(Isserlesetal.,2013).30resistantPTSDpatientswere

randomlyassignedtothreetreatmentgroups.GroupAreceivedDTMSafterexposuretoa

traumaticexperienceimageryscript.GroupBreceivedDTMSafterexposuretoapositive

experienceimageryscript.GroupCreceivedshamDTMSafterexposuretoatraumatic

experienceimageryscript.Eachgroupreceived12treatmentsoverfourweeks.Weekly

psychiatricstatusevaluationsandassessmentswereperformedusingvariousclinicalPTSD

anddepressionscales.TheresultsshowedthatDTMSstimulationofthemedialprefrontal

cortexcouldbeeffectiveintreatingresistantPTSDpatients(Isserlesetal.,2013).This

studyshowedthatTMScanbeaneffectivetherapyforPTSDpatients,butitdidnotprovide

amechanismforthetherapeuticeffect.FurtherstudiesonPTSDpatientsshouldbe

performedwithappropriateexperimentalconditionsandcontrolstodetermineifTMS

stimulationhadadampeningeffectonthereconsolidationofthetraumaticmemoryorifit

hadanenhancingeffectonanextinctionprocessforthememory.

39

OtherstudieshavelookedintotheeffectsofTMSonothermemoryprocesses.In

onesuchexperiment,TMSwasshowntoimproveworkingmemoryinhealthyindividuals,

expandingondataofthesameeffectsinschizophrenicanddepressivepatients

(Bagherzadeh,Khorrami,Zarrindast,Shariat,&Pantazis,2016).TMSappliedtothe

primarymotorcortexduringreactivationofaspecificmotormemorysuggestedthatTMS

haddampeningeffectsonthereconsolidationprocessforexistingmotormemories

followingreactivation(Censor,Dimyan,&Cohen,2010).Thus,TMSinterventionscouldbe

therapeuticformemoryenhancementforindividualswithworkingmemorydisordersor

formemorysuppressionwithreactivationofunhealthymemories.

tDCS,TMS,andothernon-invasivebrainstimulationtechnologiesareespecially

usefulbecause,asopposedtoneuroimagingtechniquessuchasfMRI,whichcanonly

providecorrelationaldata,thesebrainstimulationtechniquesprovideacausallink

betweenneuralprocessinginspecificbrainregionsandmemoryfunctioninthoseareas.

Also,tDCSandTMSonlyaffectstimulationforaboutanhouraftertreatments,but

especiallyformemoryprocesses,theycan"inducelong-lastingeffects...[and]canbealso

usedasadjuvantstrategiesfortherehabilitationofneurobiologicaldeficitsandthe

treatmentofpsychiatricdisorders"(Sandrini,Cohen,&Censor,2015).Unfortunately,due

tothenatureofthestimulationtechniques,thereispotentialforremoteeffectsof

treatmentinuntargetedbrainregions.Still,thesenon-invasivetechniquescanprovide

muchmoreimmediateresultsandtargetedeffectscomparedtobehavioralor

pharmacologicalinterventions.

Therearemanyothertypesofmemorydirectedneuromodulationtechnologiesthat

arenotcurrentlyfeasibleforuseonhumans.Nonetheless,theyhavehelpedprovidecausal

40

datafortheroleofvarioussystemsinmemoryfunctionthroughanimalmodels.Theyhave

alsohelpedpeaktheinterestofthepopularmediaintothecapacityformemory

modificationtechniquesandtheirfutureinthefieldofmemoryresearch.

Optogeneticsisarapidlyevolvingbiologicaltechniqueforstimulatingtargetedcells

withtheuseoflight.Whileelectrical,magnetic,andpharmacologicalmethodslackthetype

ofspecificityforcontrollingindividualneuronsinthebrain,transformingcellstohavea

light-dependentswitchforactivationcanresultinalevelofspatialspecificitypreviously

unimaginedaswellasactivationofcellswithgreaterspeed.Inregardstomemory,one

optogeneticstudybecamewidelypopularin2013.SteveRamirezandcolleaguescreated

anexperimenttoshowthatfalsememoriescouldbeimplantedbyactivatingcertain

neuronsinmemory-engramregions(Ramirezetal.,2013).Knowingthatthehippocampus

playsacriticalroleinmemoryformationandconsolidation,theresearchersidentifiedcells

inthedentategyrus(DG)ofthemousehippocampusthatcodedcontextualmemories,or

memoriesforparticularenvironments.Theyusedtransgenicmicewhosedentategyrus

(DG,aregionofthehippocampus)neuronswerelabeledtoexpresschannelrhodopsin-2,a

light-sensitiveionchannel.Whencellsexpressingchannelrhodopsin-2areexposedtoblue

light,theionchannelsareopenedandsodiumionsenterthecell,inducinganaction

potentialinthetransformedcells.Ondayoneoftheexperiment,amousewasplacedinbox

A,andtheDGneuronsthatrespondedtothecontextofboxAwereidentifiedand

transformedwithviralvectorstoexpresschannelrhodopsin-2.Thenextday,themouse

wasplacedinboxB,whereadifferentsetofDGneuronswouldfireinresponsetothenew

context.Theresearchersthensimultaneouslyshockedthemouse,whileactivatingthe

channelrhodopsin-2expressingcellsfromcontextA.Onday3,themousewasplacedback

41

inboxAandshowedafearresponse,thoughthemousehadneverbeenshockedinboxA.

Toshowthatageneralizedfearmemoryhadnotbeendeveloped,themousewasnext

placedinanewcontext,boxC,whereitdidnotdemonstrateafearresponse(Ramirezet

al.,2013).Thestudyprovidesananimalmodelforwhichfalseandrealmemoriescanbe

studieddowntothelevelofaspecificmemoryengram,andshowedaninteractionbetween

agenuineandfalsememoryinthecells.Althoughnospecificmemoryengramshavebeen

identifiedduringhumanfalsememoryexperiments,Ramirezandhiscolleaguesprovideda

solidmodelforhowfalsememoriesinhumansmaybecausedbythesametypeof

interactionbetweenconcurrentactivationofmemoryengramsfromtheretrievalof

genuinememoriesandassociationwithnewinformationthroughreconsolidation.

42

EthicalDebate

Neuroethicsisarelativelynewconceptfocusedontheethicaldilemmasinvolvedin

ourincreasingunderstandingofandabilitytocontrolandmanipulatebrainfunctionsand

processes.Neuroethiciststhereforeseektodelineatehowtoproceedwhenneuroscientific

advancementsyieldquestionsabouttheimpactofsuchinformation,ifandhowitshouldbe

used,andwhohastherighttodevelopandadministertheproductsandmethodsthat

follow.Whilewithinthefieldofbioethics,neuroethicsisespeciallyimportantbecauseit

dealswithissuesofthebrain,andchangesmadewithinthebrainhavewide-ranging

consequencesimpactingthemind.

Becausememoryisanessentialcomponentofourlearning,moraldevelopment,

senseofnarrativeandpersonalidentity,andoverallsurvival,theneuroethicsofmemoryis

anespeciallycomplicatedsubfield.Accordingly,thereisconsiderableroomfordebate

aboutifandtheextenttowhichweshouldallowcertaintechniquesandtechnologiesthat

havetheabilitytomodifyhumanmemories.Inthispaper,Ihavedescribedvariousmeans

ofenhancing,suppressing,orotherwisealteringhumanmemoriesthatarecurrentlyused

forresearch.Ihavealsodescribedmemorymodificationtechniquesnotcurrentlydeemed

safeforhumanexperimentation.Thisresearchintomemoryinterventionshasprovided

significantfindingsaboutthenatureofmemoryasawholeaswellasthephysical

mechanismsofconsolidationandreconsolidation.Manyhavehelpedtoidentifyspecific

brainregions,interactions,andmoleculescrucialtonumerousanddiversememory

functions.Theseandfurtherstudiescontinuetoaddtotheunderstandingofthehuman

memory,buttheyalsoraisequestionsaboutthepotentialfutureusesformethodsof

memorymodification.Memoryinterventionssuchasthesecouldhavemanybeneficial

43

rolesinrealmssuchasmedicine,therapy,andcriminaljustice,amongmanyotherfields.

Unfortunately,anyartificialmodificationofthehumanmemory,whetherthrough

behavioral,pharmacological,ortechnologicalintervention,alsocarriessignificant

concerns.Whiletheinterventionscurrentlyinuseforresearchpurposesmaynot

necessarilymakeitintohumanpracticeinanyrealcapacity,theyallprovideexistence

prooffortargetedmemorymodifications.Inlightoftherecentadvancementsand

developmentsinthefieldsofpsychologyandneuroscience,ourknowledgeofthehuman

brainwillpropagatemorepreciseandlessriskymethodsofmemorymodifications,and

thus,theintentionalmodificationofhumanmemoriesmeritsanethicalframeworkforhow

andwhenitshouldbeemployed.

Someofthepotentialtherapeuticeffectsofmemorymodificationshavealready

beendiscussedthroughresearchonpatientswithPTSD,depression,andaddiction

problems.Whiletheseeffectshavebeenrealizedinlimitedresearchstudiesandclinical

trials,inthecaseofpropranololasapotentialtreatmentforPTSDpatients,physiciansmay

soonemploythedrugasanoff-labeltreatmentduetothepromisingresults.Whetherithas

ofyetbeenproveneffectiveornot,memorymodificationscouldhavetherapeuticeffects

fornumerousconditionsanddisordersrangingfromgeneralmemorydisorders,suchas

dementiaandAlzheimer's,toanxietydisordersanddepression.Theycouldfurtherbeused

astreatmentoptionsforobesityandaddiction,orevenastherapeuticmethodsof

promotingagenerallyhealthybehaviorormindset.

Themainethicalconcernfortherapeuticmemorytreatmentsissafety.Most

availabletreatmentsformedicalorpsychiatricproblemscomewithrisksandsideeffects.

Ideally,thebenefitofthetreatmentoutweighsthepotentialrisksinvolved.Acurrentissue

44

withmemorymodifications,andmanyinterventionaltreatmentsofthebrain,isthatthe

risksandsideeffectsarenotlargelyknown.Becauseoftheinterconnectivityofthebrain,

treatmentstargetedatspecificregionsorevenforspecificmemoriescouldhave

unforeseendownstreameffects.Similarly,memoriesarenothousedinasinglecell,but

acrossnetworksofinterconnectedcellsallthroughoutthebrain.Itisnotcertainhow

alteringonecellorgroupofcellswillaffectothermemoryfunctions.Hereexiststhe

potentialforunintentionalreinforcementofpathologicalmemories,wherebyan

enhancementinoneareamayresultinanunintendedeffectsuchasanincreased

sensitivitytopain(Hui&Fisher,2014).Thiscouldbeduetoenhancedactivityofmemory-

engramneuronsthathaveothernervoussystemrolesbesidestheconnectiontothat

particularmemory.

Evenifwecouldsomehowsubvertthesafetyproblemsthatarisefromthebrain's

intricateinterconnectivity,therearestillsubstantialsideeffectsthatcanarisefrom

alteringmemories.Themainargumentformolecularlytargetedmemoryinterventions,

especiallythosethatworkwithoragainsttheconsolidationorreconsolidationprocess,is

thattheyarehighlyspecific,donotaffectshort-termmemoryorlearning,anddoso

withoutchangingthebraincircuitry.MolecularmemorymodificationwithPKMζor

propranolol,whichhasbeenshowntointerferewithhighlyemotionalmemories,then

shouldtheoreticallyalterveryspecificmemorieswithlittlesideeffects.Othermolecular

enhancementstomemorycurrentlyinuse,suchasstimulantsthataffectattention,donot

affectlong-termmemoryreconsolidationandhaveawiderangeofhealthconcerns.

However,inusingPKMζtostrengthentaste-aversionmemoriesinrats,non-targetedtaste-

relatedbehaviorswerechanged(Shemaetal.,2011).Thisexampleshowshowchanginga

45

memorymighthaveeffectsthatarenotimmediatelyapparent.Becauseourmemoryofthe

pastshapesourpresentexperiences,memorieshavethecapacitytoshapeourfuture

behavior.Thisconnectionbetweenmemoryandfuturebehaviorwasalsoexploredthrough

falsememoryexperiments(Bernsteinetal.,2005;Clifasefietal.,2013).Itisextremely

hardtopredictthebehavioralconsequencesofenhancingorsuppressingmemories,

especiallyforemotionalmemories.

Behavioralchangesandotherchangesthatoccurasaresultofmemorymodification

inhumansmaybehardtoresearchorobserve.Ifchangingamemoryalsochangedan

individual’sbehaviorand/oremotions,itwouldbehardtodeterminebecausethealtered

memorywouldfeelgenuinetotheindividual(Hui&Fisher,2014).Thisisbecausethereis

nowayforindividualstodiscernbetweenrealandmodifiedmemories.Because

reconsolidationisanaturalprocessfollowingreactivationofamemory,reconsolidated

memoriesshouldappearnomoredifferentthanmemoriesrecentlyconsolidatedfrom

short-termmemory,exceptthattheymaybestrengthenedasaresultoftheprocess.Thus,

theonlywayofapersonknowingthatamemoryinterventionhadoccurredwouldbethe

episodicmemoryoftheinterventiontechnique,assumingtheywereconsciousandthat

memorywasnotdampenedalongsideotherreactivatedmemories.

Anotherconcernisthateventhoughmolecularmemorymodificationsmaynot

changethebraincircuitryasfaraschangingpatternsofsynapses,theycanstillhaveeffects

atindividualsynapsesthroughoutthebrain.Morestraightforwardly,HuiandFisherclaim

“floodingthebrainwithPKMζorarelatedmoleculemightgiverisetotoomanyreceptors,

eliminatingmeaningfuldifferencesbetweenneurons…[and]couldcausewider,network-

levelimbalancesbydisproportionatelyoveremphasizingcertainmemories,possibly

46

leadingtointrusivethoughtsortriggeringamnesiabyinterferingwiththerecallof

unenhancedmemories”(Hui&Fisher,2014).Whilemolecularmemorymodifications

shouldtheoreticallybespecificandhaveminimalsideeffects,itishardtoknowtheextent

tohowtheneuronsinthebrainwilladapttoartificiallyheightenedorloweredlevelsofa

particularmolecule.

Alongthesamenote,therehasnotbeenenoughresearchonthelong-term

neurologicaleffectsofmanyofthesemolecules.Withoutlong-termexperimentation,

possiblelate-onsetsideeffectssuchasaconnectiontoadegenerativebraindiseasecannot

beknown.Metabolicandothernon-neurologicalsideeffectsofsuchmoleculesshouldalso

betakenintoaccount.

Propranololhasbeenusedforyearsasanoralmedicationforcardiovascular

conditions.Consequently,theeffectsoforalpropranololtreatmentarewellknown.The

sideeffectsaregenerallyminorincomparisontotheeffectsofhighbloodpressureand

irregularheartbeats.Assuch,thepotentialbenefitsasatreatmentforPTSDshouldalso

outweighthemetabolicsideeffects.Propranololhasbeenshowneffectiveindampening

theemotionalcontentofmemoriesforPTSDpatientsinmultipleclinicaltrials(Pitmanet

al.,2001;Vaivaetal.,2003)andlaboratoryresearchexperiments(Brunetetal.,2008;

Brunetetal.,2011).Alargeissuewiththeuseofpropranololisthepossibilityofit

interferingwithepisodicmemoriesratherthanjusttheemotionalcontentofthose

memoriesintheamygdala.Thisisalegitimateconcern,however"noseverememory

problemshavesurfacedamongthetensofmillionsofindividualswhohavetaken

propranololforheartconditionsandhighbloodpressure"(Henryetal.,2007).Butevenif

propranololdoesonlyaffecttheemotionalcontentofmemories,therearestillreasonsto

47

proceedwithcautioninusingitfortargetedmemorydampening.Overuseofpropranolol

couldresultinanindividual'sreducedabilitytorespondtoemotionalstimuli.Walter

Glannonwritesthatthistypeof"chronicmanipulationofneuralmechanismsmediating

emotionalresponsestothenaturalandsocialenvironmentmightweakenorevendestroy

inhibitorymechanismscontrollingharmfulbehaviorandthusalsothecapacitytoconform

tosocialnorms"(Glannon,2011).Notonlycouldthisdiminishanindividual'ssocial

functioning,butalso,itcouldleadtoalessenedabilitytoassociatefearingivensettings,

whichisabasicsurvivalmechanismtoavoidharmfulorotherwisepainfulscenarios.

Further,eventhoughpropranololonlyactsontheemotionalcontentofmemories,thereis

notenoughevidencetosupportthetypesofemotionalmemoriesthatitwilltargetwhen

administered.Propranololtreatmentcouldthereforeinadvertentlyacttodampensomeof

thepositiveemotionalaspectsofuntargetedepisodicmemories,resultinginalossofthe

positiveemotionsassociatedwithpastlifeexperiences(Glannon,2011).Assumingthatthe

negativeemotionalmemoriesthatwillbetargetedthroughpropranololtreatmentare

sufficientlydetrimentaltoanindividual'sfurtherwellbeing,thebenefitsoftreatmentmay

evenstilloutweighthesepossibleunintendedeffects;however,muchofthecurrentclinical

useofpropranololasatreatmentoptionfortraumaticexperiencesisimmediately

followingthetrauma.Inthesesituations,itcanoftenbehardtotellhowtheexperiencewill

eventuallyaffectthepersonwithorwithouttreatment.Amoreidealtreatmentwould

involvedampeningofthereconsolidationofthesetypesofemotionalmemoriesaftera

patienthasalreadybeendiagnosedwithPTSD,butclinicaltrialsforthistypeof

interventionusingpropranololarenotascommon.Nonetheless,propranololisadrugthat

isreadilyavailableandmuchcheaperthanpsychotherapyandotherantidepressantdrugs,

48

soitsefficacyasatreatmentorpreventiontherapyforPTSDshouldcontinuetobe

explored.

Thereareotherproposedmethodsfortherapeuticmemorymodificationwithout

manyofthesafetyconcernsinvolvedwithmolecularinterventions.Transcranialdirect

currentstimulation(tDCS)anddeeptranscranialmagneticstimulation(dTMS)aretwo

examplesofnon-invasiveneuromodulationtechnologiesthathaveshownpromising

resultsasinterventionsduringtheconsolidationandreconsolidationofmemory.Theycan

betargetedtospecificbrainregionsinordertoaffectdifferenttypesofmemories,andthey

havethepowertoenhancememory,byaidingconsolidationorreconsolidation,or

suppressmemory,bydisturbingthenormalconsolidationandreconsolidationprocesses.I

wouldalsoproposethattheycouldbeusedintandemwithsuggestivemisinformationto

alterthecontentofmemories.Theireffectsonmemory,however,areunderstudied,limited

tolaboratoryresearchsettings,andoftenhardtoreproduce.Becauseoftheminimalrisk

involvedintDCSanddTMSduetotheirnon-invasivenature,theirclinicalusefor

depressionandschizophrenicpatients,andtheirabilitytoaffectmemoryinresearch

settings,theseandothernon-invasiveneuromodulationtechnologiesshouldbeexamined

fortherapeuticefficacyinclinicaltrials.Otherneuromodulationtechniquesusedin

animals,suchasoptogeneticinterventions,mightbeavoidedforfuturehumanusedueto

theirrelianceonviralvectorsandalterationsofcellgenomes.

Falsememoryimplantationsimilarlydoesnotrelyonfloodingthebrainwith

molecules,andtherefore,shouldnothavemanyofthesameneurologicalrisksinvolved

withmolecularmemorymodifications.Rather,itisapurelybehavioralintervention,

dependentontheincorporationofmisleadingorotherwisefalseinformationintopast

49

episodicmemoryengrams.Atheoreticalfalsememorytherapyinterventioncouldthenbe

employed,whereinapsychologist,therapist,orevenparentmightmakeuseoffalse

memoryimplantationtechniquestoimplantfalsememoriesthatpromotehealthyfuture

behaviors.

Hereinliesadifferentethicaldilemma,namely:cantheendseverjustifyan

inherentlydeceptivesetofmeans?Whilenoethicalframeworkhasbeendevelopedto

specificallyaddressfalsememories,RobertNashandcolleaguessurveyedalargepoolof

participantsintheirarticle,“PublicAttitudesontheEthicsofDeceptivelyPlantingFalse

MemoriestoMotivateHealthyBehavior.”Theynotethepossibilitythatplantingfalse

memoriescouldbeofbenefittobothindividualsandsociety.Theydrewoffofstudies

involvingfalsememoriesthataffectedfuturebehaviorandfoundthatthelargestresearch

programsofaronthetopicinvolvedfoodstudies.WhileBernsteinandcolleagueshad

shownthatanegativefalsememorycouldleadtofoodavoidancewiththeirexperiment

involvingmemoriesoffallingillfromeitheradillpickleorhard-boiledegg,otherstudies

showedfoodpreferencesalsochangedasaresultofpositivefalsechildhoodmemoriesfor

foodssuchasasparagus(Nashetal.,2016).Theauthorslookedatthespeculationabout

suchdata,suchasthemedia’scoiningoftheterm‘False-MemoryDiet,’andnotionsthat

falsememoriescouldbeusedto“makepeoplelessscaredofvisitingthedentistormake

lazypeoplelovetoexercise”(Nashetal.,2016).Regardlessoftheactuallegitimacyofsuch

techniques,theauthorsbelieve“thesemoralandethicalquestions…areimportanttotackle

asneuroethicalandneurophilosophicalperspectivesassumeincreasinglycrucialrolesin

thescienceofmemorymodification"(Nashetal.,2016).

Nashandhiscolleagueshadtheparticipantsintheirstudyreadandrespondtoa

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hypotheticalscenariowheredeceptivefalsememorytherapywasusedtoalterunhealthy

behavior.Participantsinthefirststudywerethenaskedtorespondwithwritten

statementsabouttheacceptabilityoftherapistsusingthetechniquetoimproveeating

habitsintheirpatientsandtheplausibilityofitssuccess.Participantsofasecondstudy

wereaskedtorespondaboutwhetherthetreatmentwasacceptable,moral,andethicaland

whatfactorstheymightconsiderintheirjudgment.Resultsofthefirststudyshowedthat

peopletendedtobelievemorestronglythatdeceptivefalsememorytherapywouldbe

acceptableforuseonthemselvesthanonotherobesepeople.Participantswerelesssure

thatthetherapycouldbeconsideredmoralandethical.Also,participantsoverallwere

fairlyconvincedofthepossibilityofplantingfalsechildhoodmemories,buttheywereless

convincedthatthosetypesofmemoriescouldaffectfutureeatingbehavior(Nashetal.,

2016).

Theresultsofstudytwoaremoreinterestinginthattheyprovidedspecificreasons

whyparticipantsfounddeceptivefalsememorytherapyacceptableorunacceptable.37%

oftheargumentsagainstfalsememorytherapywerebasedonthepotentialconsequences

ordangersofitsuse.Theargumentswerefurtherdividedintoargumentsabout

psychologicalconsequencesandthepatients’wellbeing,authenticityconsequencesand

thepatients’personalidentity,andsocialconsequencesaffectingthepatients’relationships

afteralteringamemory.32%oftheargumentsagainstfalsememorytherapyclaimedthat

theendsdonotjustifythemeans.Thesestudyparticipantsweremostlyconcernedwith

theintegrityofhealthcareprofessionals,andtheyexpressedaperceivedimmoralityin

lyinganddistastewithmodifyingpeoples’minds.Another14%claimedthatfalsememory

therapywasunacceptableforitspotentialforabuse.Individualresponsesinthisgroup

51

voicedconcernsthatthetherapycouldpotentiallybeusedforalternativemotivesother

thanhealthybehavior,suchaspersuadinggaypeoplethattheyshouldbeheterosexual,or

pushingsomeonetoconverttoterrorismorcommitviolentacts.Interestingly,36%ofthe

argumentsmadefortheacceptabilityoffalsememorytherapyindicatedthattheendsdoin

factjustifythemeans.Theseindividualsfeltthatthepossibleindividualorsocietalbenefit

outweighedintegrityintermsofethicalpractice.Otherargumentsfortheacceptability

includedincreasingtreatmentoptionsandthatsomepeopleneedhelpanddonotknow

howtogetit(Nashetal.,2016).Itisimportanttorealizethattheseargumentsarepublic

opinionaboutahypotheticalscenario,butpublicopinioncanbeagoodmeasureofthings

toconsiderwhenmakinganethicalframeworkforanewtreatment.

Onelastconcernabouttheideaoffalsememorytherapynotmentionedbythe

surveyrespondentsisthefactthatoncefalsememoriesareimplantedinasubject,they

oftenevolvewithdetailsthatwerenotsuggestedduringtheimplantation.Inalmostevery

falsememorystudy,subjectstendtorecalldetailssuchaswhatotherpeoplewerewearing

ordoing.Thus,itwillneverbecertainwhatanindividualmightdowithsuggested

informationorhowexactlythefalsememorywillresult.Whilefalsememorytherapycan

comewiththesesideeffects,anotherinterestingethicalconsiderationaboutfalsememory

ariseswhenthefalsememoryisitselfasideeffectofadifferenttypeoftherapy.

Duetoourstilllimitedunderstandingofnormalmemoryprocesses,wemust

proceedwithextremecautionwithanyandallmethodsofdisruptingmemory’snatural

reconsolidationprocess.Theissuewithfalsememoryimplantation,however,isthatitdoes

notsolelyoccurunderspecificandtargetedresearchtrials.Rather,falsememoriesarisein

everydaylifewhenindividualsarerecallingpastevents.Thismeansthatprofessionalsin

52

fieldssuchascriminaljusticeandpsychotherapy,whereindividualsareplacedunder

pressuretoremembereventsfromtheirpast,mustbeextremelycautioustoavoid

providingfalseorleadinginformationthatcanbeincorporatedintotheirsubjects’memory

andbelievedtobetrue.

Dr.JohnCannellandcolleaguesexploredthistypeofincidentalfalsememory

implantationthroughmalpracticesuitsfiledagainsttherapistsinvolvedinrecovered

memorytherapy.Cannell,Hudson,andPopedefinerecoveredmemorytherapyas

includingthefollowing:“(1)Anassumptionthatpatientsmayharbor‘repressed’memories

oftraumaticexperiences;(2)anassumptionthattheserepressedmemoriesmaybe

recoveredafteraprolongedperiodofamnesia;and(3)anassumptionthatpatientsmay

gainrelieffrompsychologicaldisordersbyattemptingtorecover,explore,andunderstand

thesememorieswiththeassistanceofatherapist”(Cannell,Hudson,&Pope,2001).While

psychotherapistsmaynothavebeenintentionallyimplantingfalsememoriesintotheir

patients,thistechniqueisverysimilartothetechniquesusedinfalsememoryresearch.

Therapistsbelievedthatbyhavingtheirpatientsdigdeeperanddeeperintotheir

memories,theywouldbeabletodiscovermemoriesforpasttraumaticexperiencesthat

hadbeenrepressedbysomesortofnaturaldefensemechanism.Thisideawasapopular

beliefduetoastudyonwomenwhohadamedicalhistoryofapriorsexualassault

(Williams,1994).Thestudyfoundthat38%ofthewomendidnotrecallordidnotreport

thepriorabuseininterviews.Whilecertainprofessionalsviewedthisasevidenceof

repressedmemories,therewereissueswiththemannerinwhichthestudywasperformed.

AccordingtoLoftusandPolage,“thewomenwereneveraskeddirectlyabouttheabuse.In

otherstudiesinwhichindividualshavebeenaskeddirectly,theyadmitthattheirfailureto

53

reportwasnotduetolackofmemory”(Loftus&Polage,1999).Despitethepopularityof

theWilliamsstudy,DanielSchacterwritesinhisbooktwoyearslaterthatthereis“asyet

littleornoscientificallycredibleevidencethatpeoplewhohavesufferedyearsofviolentor

horrificabuseaftertheyearsofinfancyandearlychildhoodcanimmediatelyand

indefinitelyforgetabouttheabuse”andthat“theideathatforgettinginabusesurvivorsis

causedbyaspecialrepressionmechanism–somethingmorepowerfulthanconscious

suppression–isstillwithoutascientificbasis”(Schacter,1996).Inotherwords,rather

thanresurfacingmemoriesofrepressedtraumaticexperiences,thesetherapistswere

guidingpatientsintothecreationoffalsememories.

Manyofthesefalse“recovered”memoriespaintedhorrifyingpicturesofabuse.

Someevenledtocriminalconvictionsforthefalselyaccused“perpetrators”(Loftus&

Polage,1999).Inoneinstance,“thetherapistimplantedmemoriesofincestin[afamily’s]

eldestdaughter,includingmemoriesofgivingbirthtoherfather’sbaby.Thedaughter’s

gynecologicalexaminationshowedhertobeavirgin”(Canneletal.,2001).Anotherwoman

“formedfalsememoriesofsatanicritualabuseinthecourseoftherapywithaWisconsin

psychiatrist”(Canneletal.,2001).Withtheseincreasinglyunlikelymemoriesbeingformed,

psychotherapistsbegantobesuedonthechargethattheydidnotprovideinformed

consentpriortotherapybystatingthatfalsememoriescouldbeformed.WhileLoftusand

Pickrell’spaperonfalsememorieswaspublishedaboutthesametimeastheWilliams

studyonrepressedsexualabuse,manydidnotconsiderthepossibilitiesoffalsememories

arisingthroughtherapy.

Settlementsintheearlycasesawardedpatientsupto10.6milliondollarsonthe

basisofthefailureoftherapiststoobtaininformedconsentpriortorecoveredmemory

54

therapy.Thesettlementsmainlyconcludedthatthepatients,manyofwhomwereledto

believeoutrageousfalsememoriesofsexualabuse,werenotproperlyinformedoftherisks

offalsememoryimplantation.Manytherapistswerefoundtohavehadalegalobligationto

informpatientsoftheriskoffalsememories.TheAmericanPsychologicalAssociation

eventuallyreachedfourconclusionsontheissue:“mostpeoplewhoweresexuallyabused

aschildrenrememberall,orpart,ofwhathappenedtothem;itispossibletoremember

abusethathasbeenforgottenforalongtime;itisalsopossibletoconstructconvincing

pseudo-memoriesforaneventthatneveroccurred;andtherearegapsinourknowledge”

(Merskey,1996).WhiletheAPAstatesthatitispossibletorememberabusethathasbeen

forgottenforalongtime,theyarelikelyreferringtoisolatedinstancesofabusethatwere

forgottenbynaturalmemoryprocessesratherthansomesortofrepressionmechanism.

Thesecasespointouttheimportanceofthistypeofmemoryresearch,andtheimplications

thatithasoneverydaylife.

Averysimilareffectcanoccurintheprocessofeyewitnesstestimonies.Criminal

trialsrelyveryheavilyontheaccountsofeyewitnesstestimonies,butitisimportantto

understandthattheirmemoriesmaybeheavilyinfluencedandskewedbythetimethey

takethestand.Eyewitnessesmayfacemanyroundsofinterrogationandinterviews

followingthecriminalevent.Ineachinstancetheyareaskedtorecalltheirexperience,

reactivatingthememoryengramintheprocess.Assuch,throughmultiplereactivations

followedsubsequentlybyleadingquestionsandprobes,misinformationandsuggested

evidencecouldbereconsolidatedintotheoriginalmemory.Worryingly,this

reconsolidatedmemorywillnotappeartobealteredinanywaytotheeyewitnesses

themselves.

55

WrongfulconvictionsareaseriousissueintheUnitedStates.Accordingtothe

NationalRegistryofExonerations,therewere139exonerationsin2017(NationalRegistry

ofExonerations,2017).Theindividualswhowereexoneratedin2017spentanaverageof

10.6yearsincarceratedforacrimetheydidnotcommit,foratotalof1,478yearslostinthe

system.Ofthose139exonerations,mistakeneyewitnesstestimonywasaleadingfactorin

37ofthecases.Thisreportincludesonlythosewhowereexoneratedthatyear,butitis

extremelydifficulttoestimatetheamountofpeopleconvictedofseriouscrimeswhoare

currentlyincarceratedduetowrongfulconvictionsandespeciallythoseduetofalse

memoriesofeyewitnesses.

Thepossibilityofmisinformationbeingincorporatedintoeyewitnesstestimonies

needstobeacknowledgedineverycourtroom.Butwhatifitwereindeedpossibleto

enhanceaneyewitness’memoryofanevent,throughmolecularorothermeans,insteadof

possiblyalteringthememory?HuiandFisherwonder,“ifthiswerepossible,wouldthere

beamoralobligationtopreservecertainmemories?”(Hui&Fisher,2014).Eyewitnesses

couldtheoreticallytakedosesofPKMζfollowingtheeventtoenhanceconsolidationor

undergocue-drivenreactivationofthememorywiththeaidoftDCSordTMSinorderto

strengthenthereconsolidationoftheirmemoryfortheevent.Eventhoughfalsememories

mayariseinthedaysinbetweenwitnessingacrimeandtheeyewitness’dayincourt,

intentionallymodifyinganindividual’smemorythroughenhancementmethodsseemsto

betoomuchofanoverstep,and“advocatesforautonomywouldlikelyarguethat

pressuringindividualstoaltersomethingasdeeplypersonalastheirmemorywouldbetoo

muchofaninfringement”(Hui&Fisher,2014).Further,giventhenatureofmanyviolent

crimesthatpeoplewitness,otherswouldarguethatenhancingsuchmemoriescouldbe

56

cruelortorturoustowitnesses.

Whileitmaynotbeacceptabletoforcepeopletoaltertheirmemoriesforthe

purposeofeyewitnesstestimony,manyneuroethicistshaveconsideredwhetherornot

individualsevenhavetherighttoaltertheirownmemories.Manyclaimthatwhile

memoriesmayseeminherentlypersonal,wehavea“dutytoremember”tosociety.The

mainideahereisthatpersonalmemoriesareofvaluenotonlytotheindividualwho

possessesthem,butalsotosocietyasawhole.AdamKolberconsidersahypothetical

scenariowhereinanindividualunexpectedlyregainsconsciousnessduringaninvasive

surgery(Kolber,2014).Shouldthepatienthavetherighttoerasetheirmemoryofthe

experienceinordertoavoidfuturetrauma?Itseemsasifthatrightshouldbeuptothe

patient,butifthepatienthadbecomeconsciouslyawareofacrimeduringtheprocess,can

hisorherowndesiretoavoidlatertraumaoutweighthemoraldutytorememberand

reportsaidcrime?WalterGlannondisagreeswiththeideaofa“dutytoremember.”His

viewpointisthatmemoriesareinherentlyinaccurateandfallible,andthus,evenifapatient

doesholdontotheirmemoryoutofduty,itisnotlikelytobeaccurateinthefirstplace

(Glannon,2014).Itseemsastretchtosaythatthefallibilityofmemoriesmakesthem

completelyinvaluableasasourceineyewitnesstestimonies.Tomakesuchaclaimwould

betoundermineeveryeyewitnessaccountevergiven,andwhenwecanonlyrelyonthose

involvedorpresenttocorroborateastory,therewouldbenomeansofreachingany

conclusionsbeyondareasonabledoubt.Themainpointhereisthatwemustbewearyof

theeffectsofmisinformationandsuggestiblediscourseonmemorywhenconsideringany

accountbasedoffofanindividual’smemory.Weshouldalsobecautiousinallowingpeople

totamperwiththeirownmemories.Evenaftertraumaticexperienceswhereanindividual

57

mayelecttotakepropranololtodampentheemotionalcontentofhisorhermemoryand

avoidthepotentialofdevelopingPTSDinthefuture,treatmentprovidersshouldconsider

thepotentialobstructionofjusticethatsuchmemorymodificationscanhaveonfuture

prosecutions.

Memorymodificationtechniqueshavealsobeenproposedasafutureintervention

fordefendantsandcriminals.Whilenoneofthemethodsofmemorymodificationthathave

beendiscussedarecurrentlyatalevelofspecificitytoachievereliableresultsinthisfield,

theystillraisequestionsaboutwhatthefuturecouldbringandwhattypesofinterventions

shouldbeallowed.Substancessuchasalcoholandthiopentalhavebeenusedinthepastto

gaintestimonyfromcriminaldefendants(Cabrera&Elger,2016),butanyuseofmemory

modificationtechniquesincriminalinterrogationscouldbedeemedasbothcoerciveand

illegal.CabreraandElgerproposetwousesformemorymodificationtechniquesinthe

criminaljusticesystemthatcouldserveasanaidtomakeincarcerationandtherapyof

criminalsmoreeconomicallyviableandefficient.Thefirstusewouldbeindampeningthe

emotionalcontentofanoffenders’criminalmemory.Manycriminals,forexamplerapists

orpedophiles,mightrelishinthememoriesoftheircrimes.Bydampeningthoseassociated

memories,retributioncouldbeachieved“viathelossofenjoymenttheoffenderwould

suffer,”andcrimedeterrencecouldbeachieved“ifsuchoffendersweremotivatedbythe

anticipationofsavouringthesememoriesandcametoknowthatiftheywerecaughtthey

wouldlosethem”(Cabrera&Elger,2016).Aninterventionforothertypesofcriminals

wouldinvolveenhancingtheemotionalcontentofcriminalmemories.Thiswouldleadto

heightenedfeelingsofremorseandshameandcouldholdcriminalsmoreaccountablefor

theiractions(Cabrera&Elger,2016).Ofcourse,theethicalissuesinvolvedhereareno

58

differentthanthosealreadydiscussed.Enhancingmemoriesforaterribleactionthat

someonecommittedcouldbecrueloreventorturous.Also,criminalsstillmaintain

treatmentrights,meaningthattheywouldhavetoagreetoanytypeofmemorytreatment

inthesamewayasthosewhowouldundergotreatmentfortherapeuticreasons.

Theuseofmemorymodificationsinthecriminaljusticesystemalsoraisesthe

questionofwhetherornotthesetypesofinterventionsshouldbeinthehandsofthestate.

Ifmemoryinterventionsareinthehandsofthestate,theywouldthenhavetheabilityto

shapepeoples’mindstoanextenttowhichwedonotcurrentlyknow.Thiscouldineffect

takeawayourabilitytokeepchecksandbalancesonthesystemiftheybegantoshape

criminals’civilandmoralconstitutionstowardsplacidobedience.

Guidelinesforethicalpracticeswillhelptherapistsandotherprofessionalstoassess

andinformtheirpatientsorsubjectsoftherisksinvolvedinmemorymodification

techniquesaswellastherisksoffalsememoriesdevelopingthrougheverydaypractice,

especiallywiththecontinuingresearchdevotedtothetopic;however,therecouldbe

scenarioswherememorymodificationsareusedasatool,suchasinCIAandmilitary

contractingofpsychiatristsandpsychologists.TheCIAandU.S.militaryhavebeenknown

touseformsofpsychologicalexperimentationandwarfareinthepast.Examplesinclude

interrogationsinanIraqiprisonandGuantanamoBay,experimentswithLSDandbrain

electrodes,andcreatingartificialmultiplepersonalitydisorderusinghypnosis(Ross,

2007).Knowingthatmodifiedmemoriescanhaveaneffectonfuturebehaviorand

emotions,itisimperativethatthesetechniquesarenotusedforevilends.

Afinalethicalconsiderationformemorymodificationsisinvolvedineverytypeof

memorymodificationandinterventionscenarioimaginable,namely,theconnection

59

betweenmemoryandpersonalidentity.Ingeneral,whoweareasapersonisseatedinthe

brain.Memoryisoneofthemostimportantpartsofwhoweare,becauseitallowsusto

connectwithourpastselves.However,personalidentityishardtodefine.Philosophical

argumentsforwhatconstitutespersonalidentityarevaried,butmostrelyonsometypeof

numericalidentityornarrativeorpsychologicalcontinuity.Itisnotclearthatmemory

modificationscouldaffectanindividual’snumericalidentitytohisorherpastself,but

modificationstomemorycertainlyhavethepotentialtodisruptanindividual’s

psychologicalcontinuity.Still,accordingtoHuiandFisher,thispsychologicalcontinuity

includesmainlyourbeliefs,intentions,preferences,andcapacityforrationalthought(Hui

&Fisher,2014),forwhicherasureofevencriticallyimportantmemoriesmaynotalter.

Ourepisodicmemoriesarecrucialtoourpersonalidentity,forwithoutthememory

ofapastexperience,thereisnosenseofhavingexistedatthattime.Thus,ourmemory

impliesourpastandcontinualexistenceasaperson.Butourbeliefsaboutourselves,orour

dispositionalcharacteristics,arenotrootedinourepisodicmemories.Rather,our

“dispositionalsenseoftheselfturnsouttoberesilientacrossdramaticdamagetomemory

systems.Therenowexistsanextensivedatabaseshowingthatevenpatientssufferingtotal

anterogradeandretrogradeepisodicamnesiacandescribetheirownpersonal

characteristicsbothreliablyandaccurately”(Klein&Nichols,2012).Ifpsychological

continuitywereallthatwasrequiredformaintenanceofpersonalidentity,thenweshould

havenoworriesaboutmessingwithanyandallmemories,becauseepisodicmemoriesare

notrequiredforthisself-traitmemory.However,Iarguethatself-traitmemoriesarenot

sufficientforpersonalidentity,becausewithoutepisodicmemories,thereisnoabilityfor

anindividualtoplacehimorherselfinthepast.Forexample,H.M.,whounderwenta

60

bilateralhippocampallesionsurgeryandlosttheabilitytoformnewmemories,wasstill

abletoidentifywithhischildhoodself.Althoughhecouldnotrememberhowoldhewas

currentlyorwhatyearitwas,hewasabletoprovidedetailedaccountsofmemoriesfrom

hischildhoodandidentifythechildinhismemoriesasayoungversionofhimself.Thereis

somethingremarkableabouthavingsuchaconnectiontothedistantpastwhilenot

knowingwhatoccurred15minutesprior.

Anotherwaytoframememory’sconnectiontoanindividual’spersonalidentityisas

follows:“apersonPattimetisidenticaltoapersonP1atalatertimet1ifP1att1

remembersP’sexperiencesatt.Sinceidentityistransitive,itcanalsoarisefrom

overlappingstrandsofsuchmemorylinks:ifP2att2doesnotrememberP’sexperiencesat

t,P2att2andPattareneverthelessidenticalifP2att2remembersP1’sexperiencesatt1,

andifP1att1remembersP’sexperiencesatt”(Roache,2015).Thisinterpretationposes

identityintermsofapersonatagiventime.Toeraseamemoryofaparticulartimeisto

dissociatefromthatperson,suchthatthatpersonatthattimeisnolongeridenticalwith

thecurrentindividual.

Thosewhoargueagainstmemorymodificationfromtheviewofpersonalidentity

believethatourmemoriesaresocrucialtooursenseofselfthattheyarethebasisofwho

weareasindividuals.Regardingmemoryerasure,LeonKassargues“…todepriveoneself

ofone’smemory–initstruthfulnessalsooffeeling–istodepriveoneselfofone’sownlife

andidentity”(Kass,2003).Thosewhoobjecttothepersonalidentityargumentclaimthat

becausememoriesarenaturallyandinherentlyreconsolidatedandaltered,changesin

memorycannotbeathreattoidentity.Whilethereisadifferencebetweenactivelyand

intentionallyalteringmemoriesandthepassive,naturalprocessthatoccursinthebrain,

61

theriskstopersonalidentitycanbelookedatinthesamewayasrisksofsafetyin

treatment.Inotherwords,forthosewhoareinseriousneedofsomesortofmemory

modification,theissueislikelyaffectingtheirtruepersonalidentitymuchmorethanany

memoryenhancementorsuppressionwould.Whilememorymodificationscansurelybe

thecauseofsomepersonalidentityissues,theycanalsoacttocombatthesameproblems

intherightscenarios.

62

Conclusion

Muchaboutthehumanmemoryisyettobediscovered.Fortunately,thescientific

communityhasmadegreatstridesinthepast50yearsorsoinunderstandingthemind.

Overtime,ourperceptionofmemoryhasevolvedfromablankslatewrittenuponthrough

experiencetoaprocessingsystem,involvingcountlessfunctions,mechanisms,andbrain

regions.Wehaveabetterunderstandingforwhyweremembersomethingsandforget

others,howmemoriesarephysicallystored,andwhymemoriesofthepastarepainted

overwithanewandupdatedpaletteeachtimetheyareretrieved.

Researchintoreconsolidationhasprovideduswithaneuralmechanismforhowwe

makenewconnectionswithinandbetweenpastmemories.Ithasledtobetter

understandingsabouttheevolutionaryadaptationsinvolvedinourmemorysystem,

namelythatwehavebiologicalprocessesinplacetostrengthenourmemorieswhile

makingnewassociationsbetweenthemovertime,allowingustomakethemostofever-

changingenvironments.Ithasalsoprovidedcriticalinformationforaprocessthatcanbe

manipulatedinordertoenhance,alter,orsuppressmemoriesofmanydifferenttypesand

contents.

Falsememoryresearchhasopenedpeople’seyestothefallibilityofourmemories.

Inprovidingexistenceproofforapsychologicalphenomenonwhereinpeopleadoptand

believecompletelyfabricatedstoriestobeproductsoftheirownmemory,ithasshedlight

onimportantconcernsaboutcommonpracticessuchaspsychotherapyandeyewitness

testimony.Ithasalsoprovidedinsightintoourownmemoriesofthepast,notablythe

knowledgethatpastmemoriesarenotanexactaccountofpastexperiencesbutratherare

compoundedwithnewandpossiblymisleadinginformationwitheachretrieval.

63

Molecularmemorymodificationresearchhashelpedtoidentifyspecificmolecules

involvedinvariousmemoryprocesses.Bymanipulatingtheamountsofthesemoleculesor

theeffectsoftheprocessestheyareinvolvedin,wecontinuetoaddtoourknowledgeof

thephysicalmechanismsbehindmemoryformation,storage,andretrieval.Withthis

knowledgecomesnovelwaysofenhancing,suppressing,oralteringmemoriesthrough

pharmacologicalinterventions,whichcanbeusedtotreatcountlessissuesstemmingfrom

memorydisordersortheeffectsofdeleteriousmemories.

Neuromodulationtechnologieshavegivenresearchersthecapabilityofmaking

causalconnectionsbetweenspecificbrainregionsandtheirfunctions.Theyhavealso

servedasmethodsfornon-invasiveinterventionsfornotonlymemoryfunctions,butalsoa

wholerangeofotherproblemsfromdepressiontoschizophrenia.Technologiessuchas

thosediscussedherewillcontinuetorelyonaswellasguidefutureneuroscienceresearch.

Thepastandcurrentusesoftheresearchonmemorymodificationspalesin

comparisontowhattheymeanforthefuture.Ofcourse,itisimportanttounderstandthe

currentstateofpsychologyandneuroscienceresearchinordertobegintolookforward,

buttherealissuestoaddressarethewaysinwhichthisresearchwillbeputintopractice.

Themostcrucialcomponentsoftheresearchcouldbeaselementaryassimply

understandingthatacertainphenomenonexists,aswasthecasewithfalsememoriesand

recoveredmemorytherapyoreyewitnesstestimony.Inothercases,suchasmolecular

modificationofmemories,therearewiderangesofethicalissuestoconsiderfromsafetyto

autonomyandpersonalidentity.Inanycase,itisimportanttostayaheadoftheresearch

andtechnologies,becauseourunderstandingofandabilitytomanipulatebrainfunctionsis

evolvingatanexponentialrate.

64

Inregardstoanytypeofmemorymodificationusedinhumans,thereisnosimple

answerforitsethicalprogressionintopractice.Rather,eachshouldbeconsideredona

case-by-casebasis,becausethevariablesinvolvenotonlytheparticulartypeof

interventionathand,butalsothestateoftheindividual.Sometypesofmemory

modificationsshowpromiseaspotentiallyeffectiveandlow-costtreatmentsforindividuals

withdebilitatingconditionsrootedintraumaticorotherwiseinjuriousmemories.When

consideringthesetreatmentoptions,providersmustalwaysconsidertheirefficacyover

othertreatments,thepossibleneurologicalandmetabolicsideeffects,theeffectsonother

memoriesandqualityoflife,effectsonanindividual’spersonalidentity,andmostofall,the

individual’sinformedconsenttotreatment.Becauseofthepotentialviabilityofsuch

interventions,Ibelievetheyshouldbesubjecttocautiousbutsteadyfurtherresearchin

clinicalsettings.

65

References

Bagherzadeh,Y.,Khorrami,A.,Zarrindast,M.R.,Shariat,S.V.,&Pantazis,D.(2016).

Repetitivetranscranialmagneticstimulationofthedorsolateralprefrontalcortex

enhancesworkingmemory.ExperimentalBrainResearch,234(7),1807-1818.

doi:10.1007/s00221-016-4580-1

Bear,M.F.,Connors,B.W.,&Paradiso,M.A.(2016).Neuroscience:Exploringthebrain.

Philadelphia:WoltersKluwer.

Bernstein,D.,Laney,C.,Morris,E.,&Loftus,E.(2005).Falsememoriesaboutfoodcanlead

tofoodavoidance.SocialCognition,23,11-34.doi:10.1521/soco.23.1.11.59195

Braun,K.A.,Ellis,R.,&Loftus,E.F.(2002).Makemymemory:Howadvertisingcanchange

ourmemoriesofthepast.Psychology&Marketing,19(1),1-23.

doi:10.1002/mar.1000

Brunet,A.,Orr,S.P.,Tremblay,J.,Robertson,K.,Nader,K.,&Pitman,R.K.(2008).Effectof

post-retrievalpropranololonpsychophysiologicrespondingduringsubsequent

script-driventraumaticimageryinpost-traumaticstress.JournalofPsychiatric

Research,42(6),503-506.doi:10.1016/j.jpsychires.2007.05.006

Brunet,A.,Poundja,J.,Tremblay,J.,Bui,E.,Thomas,E.,Orr,S.P.,&...Pitman,R.K.(2011).

Traumareactivationundertheinfluenceofpropranololdecreasesposttraumatic

stresssymptomsanddisorder:3open-labeltrials.JournalOfClinical

Psychopharmacology,31(4),547-550.doi:10.1097/JCP.0b013e318222f360

Cabrera,L.Y.,&Elger,B.S.(2016).Memoryinterventionsinthecriminaljusticesystem:

Somepracticalethicalconsiderations.JournalofBioethicalInquiry,13(1),95-103.

doi:10.1007/s11673-015-9680-2

66

Caine,E.D.,Weingartner,H.,Ludlow,C.L.,Cudahy,E.A.,&Wehry,S.(1981).Qualitative

analysisofscopolamine-inducedamnesia.Psychopharmacology,74(1),74-80.

doi:10.1007/BF00431761

Cannell,J.,Hudson,J.I.,&Pope,H.J.(2001).Standardsforinformedconsentinrecovered

memorytherapy.JournalOfTheAmericanAcademyOfPsychiatryAndTheLaw,

29(2),138-147.

Censor,N.,Dimyan,M.A.,Cohen,L.G.(2010).Modificationofexistinghumanmotor

memoriesisenabledbyprimarycorticalprocessingduringmemoryreactivation.

CurrentBiology,20(17),1545-1549.doi:10.1016/j.cub.2010.07.047

Clifasefi,S.L.,Bernstein,D.M.,Mantonakis,A.,&Loftus,E.F.(2013)."QueasyDoesIt":False

alcoholbeliefsandmemoriesmayleadtodiminishedalcoholpreferences.Acta

Psychologica,143(1),14.doi:10.1016/j.actpsy.2013.01.017

Drexler,S.M.,Merz,C.J.,Hamacher-Dang,T.C.,Tegenthoff,M.,&Wolf,O.T.(2015).Effects

ofcortisolonreconsolidationofreactivatedfearmemories.

Neuropsychopharmacology,40(13),3036-3043.doi:10.1038/npp.2015.160

DudaiY.(2011).TheEngramrevisited:Ontheelusivepermanenceofmemory.InS.

Nalbantian,P.M.Matthews,J.L.McClelland,S.Nalbantian,P.M.Matthews,J.L.

McClelland(Eds.),Thememoryprocess:Neuroscientificandhumanisticperspectives

(pp.29-40).Cambridge,MA,US:MITPress.

ForcatoC.,RodrıguezM.L.C.,PedreiraM.E.(2011)Repeatedlabilization-reconsolidation

processesstrengthendeclarativememoryinhumans.PLoSONE,6(8),e23305.

doi:10.1371/journal.pone.0023305

67

Frenda,S.J.,Patihis,L.,Loftus,E.F.,Lewis,H.C.,&Fenn,K.M.(2014).Sleepdeprivationand

falsememories.PsychologicalScience,25(9),1674-1681.

doi:10.1177/0956797614534694

Glannon,W.(2011).Theneuroethicsofmemory.InS.Nalbantian,P.M.Matthews,J.L.

McClelland,S.Nalbantian,P.M.Matthews,J.L.McClelland(Eds.),Thememory

process:Neuroscientificandhumanisticperspectives(pp.233-251).Cambridge,MA,

US:MITPress.

Glannon,W.(2014).Anaesthesia,amnesiaandharm.JournalofMedicalEthics,40(10),651-

657.doi:10.1136/medethics-2013-101543

HenryM.,FishmanJ.R.,&YoungnerS.J.(2007)Propranololandthepreventionofpost-

traumaticstressdisorder:isitwrongtoerasethe“sting”ofbadmemories?.The

AmericanJournalofBioethics,7(9),12-20,doi:10.1080/15265160701518474

HuiK.&FisherC.E.(2015)Theethicsofmolecularmemorymodification.JournalofMedical

Ethics,41,515-520.doi:10.1136/medethics-2013-101891

Hupbach,A.,Gomez,R.,Hardt,O.,&Nadel,L.(2007).Reconsolidationofepisodicmemories:

Asubtleremindertriggersintegrationofnewinformation.Learning&Memory,

14(1-2),47-53.doi:10.1101/lm.365707

Hyman,I.E.,Husband,T.H.andBillings,F.J.(1995),Falsememoriesofchildhood

experiences.AppliedCognitivePsychology,9,181-197.doi:10.1002/acp.2350090302

Impastato,D.J.(1960).Thestoryofthefirstelectroshocktreatment.TheAmericanJournal

OfPsychiatry,116,1113-1114.

Isserles,M.,Shalev,A.Y.,Roth,Y.,Peri,T.,Kutz,I.,Zlotnick,E.,&Zangen,A.(2013).

Effectivenessofdeeptranscranialmagneticstimulationcombinedwithabrief

68

exposureprocedureinpost-traumaticstressdisorder—Apilotstudy.Brain

Stimulation,6(3),377-383.doi:10.1016/j.brs.2012.07.008

Javadi,A.H.,&Cheng,P.(2013).Transcranialdirectcurrentstimulation(tDCS)enhances

reconsolidationoflong-termmemory.BrainStimulation,6(4),668-674.

doi:10.1016/j.brs.2012.10.007

Kass,L.,&President'sCouncilonBioethics(U.S.).(2003).Beyondtherapy:Biotechnology

andthepursuitofhappiness.NewYork:DanaPress.

Kindt,M.,Soeter,M.,&Vervliet,B.(2009).Beyondextinction:Erasinghumanfear

responsesandpreventingthereturnoffear.NatureNeuroscience,12(3),256-258.

doi:10.1038/nn.2271

King,D.J.(1992).Benzodiazepines,amnesiaandsedation:Theoreticalandclinicalissues

andcontroversies.HumanPsychopharmacology:ClinicalAndExperimental,7(2),79-

87.doi:10.1002/hup.470070202

Klein,S.B.,&Nichols,S.(2012).Memoryandthesenseofpersonalidentity.Mind,121(483),

677-702.doi:10.1093/mind/fzs080

Kolber,A.J.(2014).Thelimitedrighttoaltermemory.JournalOfMedicalEthics,40(10),

658-659.doi:10.1136/medethics-2013-101972

Kroes,M.C.W.,Tendolkar,I.,VanWingen,G.A.,VanWaarde,J.A.,Strange,B.A.,&

Fernandez,G.(2014).Anelectroconvulsivetherapyprocedureimpairs

reconsolidationofepisodicmemoriesinhumans.NatureNeuroscience,17,204-206.

doi:10.1038/nn.3609

Kwapis,J.L.,&Helmstetter,F.J.(2014).DoesPKM(zeta)maintainmemory?.BrainResearch

Bulletin,105,36-45.doi:10.1016/j.brainresbull.2013.09.005

69

Larrosa,P.F.,Ojea,A.,Ojea,I.,Molina,V.A.,Zorrilla-Zubilete,M.A.,&Delorenzi,A.(2017).

Retrievalunderstressdecreasesthelong-termexpressionofahumandeclarative

memoryviareconsolidation.NeurobiologyOfLearningAndMemory,142(PartA),

135-145.doi:10.1016/j.nlm.2017.03.005

Loftus,E.&Pickrell,J.(1995).Theformationoffalsememories.PsychiatricAnnals,25,720-

725.

Loftus,E.&Polage,D.(1999).Repressedmemories:Whenaretheyreal?Howarethey

false?.ForensicPsychiatry,22(1),61-70.doi:10.1016/S0193-953X(05)70059-9

Loftus,E.(1997).Memoryforapastthatneverwas.CurrentDirectionsinPsychological

Science,6(3),60-65.doi:10.1111/1467-8721.ep11512654

Loftus,E.(2003).Ourchangeablememories:legalandpracticalimplications.Nature

ReviewsNeuroscience,4,231-234.doi:10.1038/nrn1054

Manenti,R.,Sandrini,M.,Gobbi,E.,Cobelli,C.,Brambilla,M.,Binetti,G.,&Cotelli,M.(2017).

Strengtheningofexistingepisodicmemoriesthroughnon-invasivestimulationof

prefrontalcortexinolderadultswithsubjectivememorycomplaints.FrontiersIn

AgingNeuroscience,9.doi:10.3389/fnagi.2017.00401

McGaugh,J.L.(2004).Theamygdalamodulatestheconsolidationofmemoriesof

emotionallyarousingexperiences.AnnualReviewOfNeuroscience,27,1-28.

doi:10.1146/annurev.neuro.27.070203.144157

Merskey,H.(1996).Ethicalissuesinthesearchforrepressedmemories.AmericanJournal

ofPsychotherapy,50(3),323-335.

70

Misanin,J.,Miller,R.,&Lewis,D.(1968).Retrogradeamnesiaproducedby

electroconvulsiveshockafterreactivationofaconsolidatedmemorytrace.Science,

160(3827),554-555.http://www.jstor.org/stable/1723988

Mungee,A.,Kazzer,P.,Feeser,M.,Nitsche,M.A.,Schiller,D.,&Bajbouj,M.(2014).

Transcranialdirectcurrentstimulationoftheprefrontalcortex:Ameansto

modulatefearmemories.Neuroreport:ForRapidCommunicationOfNeuroscience

Research,25(7),480-484.

Nader,K.,Schafe,G.E.,&LeDoux,J.E.(2000).Fearmemoriesrequireproteinsynthesisin

theamygdalaforreconsolidationafterretrieval.Nature,406(6797),722-726.

doi:10.1038/35021052

Nash,R.,Berkowits,S.,&Roche,S.(2016).Publicattitudesontheethicsofdeceptively

plantingfalsememoriestomotivatehealthybehavior.AppliedCognitivePsychology,

30(6),885-897.doi:10.1002/acp.3274

NationalInstituteofMentalHealth.(2016).Post-TraumaticStressDisorder.Retrieved

fromhttps://www.nimh.nih.gov/health/topics/post-traumatic-stress-disorder-

ptsd/index.shtml

NationalRegistryofExonerations.(2017).Exonerationsin2017.Retrievedfrom

https://www.law.umich.edu/special/exoneration/Documents/2017_Exonerations-

Report_1000x3962.pdf

Pitman,R.K.,Sanders,K.M.,Zusman,R.M.,Healy,A.R.,Cheema,F.,Lasko,N.B.,&...Orr,S.

P.(2002).Pilotstudyofsecondarypreventionofposttraumaticstressdisorderwith

propranolol.BiologicalPsychiatry,51(2),189-192.doi:10.1016/S0006-

3223(01)01279-3

71

Ramirez,S.,Liu,X.,Lin,P.,Suh,J.,Pignatelli,M.,Redondo,R….&Tonegawa,S.(2013).

Creatingafalsememoryinthehippocampus.Science,341(6144),387-391.

doi:10.1126/science.1239073

Roache,R.(2016).Memoryandminenessinpersonalidentity.PhilosophicalPsychology,

29(4),479-489.doi:10.1080/09515089.2015.1102216

Robson,J.A.,&Davenport,R.J.(2014).Neurotechnology:Anewapproachfortreating

braindisorders.RhodeIslandMedicalJournal,97(5),18-21.

Ross,C.A.(2007).EthicsofCIAandmilitarycontractingbypsychiatristsandpsychologists.

EthicalHumanPsychologyAndPsychiatry:AnInternationalJournalOfCritical

Inquiry,9(1),25-34.doi:10.1891/152315007780493799

Saladin,M.E.,Gray,K.M.,McRae-Clark,A.L.,LaRowe,S.D.,Yeatts,S.D.,Baker,N.L.,&...

Brady,K.T.(2013).Adoubleblind,placebo-controlledstudyoftheeffectsofpost-

retrievalpropranololonreconsolidationofmemoryforcravingandcuereactivityin

cocainedependenthumans.Psychopharmacology,226(4),721-737.

doi:10.1007/s00213-013-3039-3

Sandrini,M.,Cohen,L.G.,&Censor,N.(2015).Modulatingreconsolidation:Alinktocausal

systems-leveldynamicsofhumanmemories.TrendsInCognitiveSciences,19(8),

475-482.doi:10.1016/j.tics.2015.06.002

Schacter,D.L.(1996).Searchingformemory:Thebrain,themind,andthepast(1sted.).

NewYork,NY:BasicBooks.

Schwabe,L.,Nader,K.,&Pruessner,J.C.(2014).Reconsolidationofhumanmemory:Brain

mechanismsandclinicalrelevance.BiologicalPsychiatry,76(4),274-280.

doi:10.1016/j.biopsych.2014.03.008

72

Scoboria,A.,Wysman,L.,&Otgaar,H.(2012).Crediblesuggestionsaffectfalse

autobiographicalbeliefs.Memory,20(5),429-442.

doi:10.1080/09658211.2012.677449

Scoville,W.B.,&Milner,B.(1957).Lossofrecentmemoryafterbilateralhippocampal

lesions.JournalOfNeurology,Neurosurgery&Psychiatry,20,11-21.

doi:10.1136/jnnp.20.1.11

Shema,R.,Haramati,S.,Ron,S.,Hazvi,S.,Chen,A.,Sacktor,T.C.,&Dudai,Y.(2011).

Enhancementofconsolidatedlong-termmemorybyoverexpressionofprotein

kinaseM[zeta]intheneocortex.Science,331(6021),1207-1210.

doi:10.1126/science.1200215

Shema,R.,Sacktor,T.C.,&Dudai,Y.(2007).Rapiderasureoflong-termmemory

associationsinthecortexbyaninhibitorofPKMζ.Science,317(5840),951-953.

doi:10.1126/science.1144334

Squire,L.R.,&Teng,E.(1999).Memoryforplaceslearnedlongagoisintactafter

hippocampaldamage.Nature,400(6745),675-677.doi:10.1038/23276

Squire,L.R.,&Wixted,J.T.(2011).Thecognitiveneuroscienceofhumanmemorysince

H.M.AnnualReviewOfNeuroscience,34,259-288.doi:10.1146/annurev-neuro-

061010-113720

Taylor,J.R.,&Tronson,N.C.(2007).Molecularmechanismsofmemoryreconsolidation.

NatureReviewsNeuroscience,8(4),262-275.doi:10.1038/nrn2090

Vaiva,G.,Ducrocq,F.,Jezequel,K.,Averland,B.,Lestavel,P.,Brunet,A.,&Marmar,C.R.

(2003).Immediatetreatmentwithpropranololdecreasesposttraumaticstress

disordertwomonthsaftertrauma.BiologicalPsychiatry,54(9),947-949.

73

Williams,L.M.(1994).Recallofchildhoodtrauma:Aprospectivestudyofwomen's

memoriesofchildsexualabuse.JournalOfConsultingAndClinicalPsychology,62(6),

1167-1176.doi:10.1037/0022-006X.62.6.1167

Xue,Y.,Deng,J.,Chen,Y.,Zhang,L.,Wu,P.,Huang,G.,&...Lu,L.(2017).Effectofselective

inhibitionofreactivatednicotine-associatedmemorieswithpropranololonnicotine

craving.JAMAPsychiatry,74(3),224-232.doi:10.1001/jamapsychiatry.2016.3907

Biography

MichaelReulisagraduatingseniorattheUniversityofTexasatAustinpursuing

dualdegreesinthePlanIIHonorsProgramandBiologyHonorsthroughthePolymathic

ScholarsHonorsProgram.MichaelwillattendBaylorCollegeofMedicinebeginningin

Augustof2018.