ContentslistsavailableatScienceDirect
Neuroscience
and
Biobehavioral
Reviews
j o ur na l ho me p a g e :w w w . e l s e v i e r . c o m / l o c a t e / n e u b i o r e v
Review
article
Immobility
reactions
under
threat:
A
contribution
to
human
defensive
cascade
and
PTSD
E.
Volchan
a,∗,
V.
Rocha-Rego
a,b,
A.F.
Bastos
a,
J.M.
Oliveira
a,b,
C.
Franklin
b,
S.
Gleiser
b,
W.
Berger
b,
G.G.L.
Souza
d,
L.
Oliveira
c,
I.A.
David
c,
F.S.
Erthal
a,
M.G.
Pereira
c,
I.
Figueira
b aInstitutodeBiofisicaCarlosChagasFilho,UniversidadeFederaldoRiodeJaneiro,BrazilbInstitutodePsiquiatria,UniversidadeFederaldoRiodeJaneiro,Brazil cInstitutoBiomédico,UniversidadeFederalFluminense,Brazil
dInstitutodeCiênciasExataseBiológicas,UniversidadeFederaldeOuroPreto,Brazil
a
r
t
i
c
l
e
i
n
f
o
Articlehistory:Received27September2016
Receivedinrevisedform18January2017 Accepted21January2017
Availableonline25January2017 Keywords: Defensivecascade Stabilometry Posture Bodysway Heartrate Heartratevariability Motorreaction Pictures Traumascript Gunviolence Threat PTSD Tonicimmobility Attentiveimmobility Immobilityunderattack Freezing
Humans RDoC
a
b
s
t
r
a
c
t
Violenceexactsaburdenonpublichealth.Gunviolenceisamajortriggerformotordefensivereactions inhumansandpost-traumaticstressdisorder(PTSD)isitsmainpsychiatricsequela.However, stud-iesofthehumandefensivecascade,especiallythemotorreactions,areatanearlystage.Thisreview focusesonstudiesthatemploystabilometry,amethodologythatassesseswholebodymotorreactions, toaddressdefensivebehaviorstoviolence-relatedthreats.Specialattentionisgiventothreereactions: “attentiveimmobility”,“immobilityunderattack”and“tonicimmobility”,withemphasisonthelatter– aperitraumaticreactionwhichhasbeenstronglyassociatedwiththeseverityofPTSD.Thesereactions arecharacterizedbyreducedbodyswayandbradycardia,excepttonicimmobilitythatpresentsrobust tachycardia.Theadvancesmadebyinvestigationsintotheimmobilityreactionsofthehumandefensive cascadecontributetohelpingtobridgethegapbetweenhumanandnon-humanspecies.Furthermore, progressesinbasicresearchtoobjectivelymonitormotordefensivereactionsunderthreatcanhelpto developadimensional,trans-diagnosticapproachtoPTSD.
©2017ElsevierLtd.Allrightsreserved.
Contents
1. Introduction...30
1.1. Violence...30
1.2. Post-traumaticstressdisorder...30
1.3. TheResearchDomainCriteria ... 30
1.4. Defensivereactionstoviolence-relatedthreat...31
1.5. Stabilometry:abriefdescription ... 31
2. Immobilitydefensiveresponses...31
∗ Correspondingauthorat:InstituteofBiophysicsCarlosChagasFilho,FederalUniversityofRiodeJaneiro,Av.CarlosChagasFilho373,RiodeJaneiro21941-902,Brazil. E-mailaddresses:[email protected],[email protected](E.Volchan).
http://dx.doi.org/10.1016/j.neubiorev.2017.01.025 0149-7634/©2017ElsevierLtd.Allrightsreserved.
2.1. Attentiveimmobility...31
2.2. Immobilityunderattack...33
2.3. Tonicimmobility...34
2.3.1. Systematicretrospectivereports...34
2.3.2. BiologicalassessmentandimplicationsforPTSD...34
2.3.3. Thebenefitsofincreasedknowledge...35
3. DefensivereactionsandtheinvertedU-shapeprofile...35
4. Conclusions...37
Fundingacknowledgements...37
References...37
1. Introduction
1.1. Violence
In1996,theForty-NinthWorldHealthAssemblydeclared vio-lenceamajorandgrowingpublichealthproblemacrosstheworld (WorldHeathAssembly,1996).Sixyearslater,theWorldHealth Organizationlaunchedthefirstreportonviolenceandhealthaimed atraisingawarenessabouttheproblemofviolenceglobally,its pre-ventionandtheroleofpublichealthinaddressingitscausesand consequences(Krugetal.,2002).In2014,theWorldHealth Organi-zation,jointlywiththeUnitedNationsDevelopmentProgramand theUnitedNationsOfficeonDrugsandCrime,publishedtheGlobal StatusReportonViolencePrevention(WorldHealthOrganization, 2014)whichreviewedviolencepreventioneffortsincountries,and called,amongotherstrongrecommendations,fortheenhancement ofservicesforthevictimsofviolence.
Apartfrombeingacauseofdeath,violenceexactsanenormous burdenonpublichealthwithextremelydeleteriousconsequences, particularlyfromgunviolence(Websteretal.,2016).Thetollofgun violenceisnotjustprematuredeathbutaseriesofserioussnowball effectsoneducation,health,familyinstability,incarceration,and socialcapital(Winkeretal.,2016).
1.2. Post-traumaticstressdisorder
Post-traumaticstressdisorder(PTSD)isthemainpsychiatric sequelafromexposuretotraumaticeventssuchasgunviolence. Presently,thetriggerofPTSDisconsideredtobeexposuretoactual or threateneddeath, serious injury or sexual violation.For the diagnosisofPTSD,inadditiontotheexposuretooneormoreof thosepotentiallytraumaticevents,theDSM-5requiresthatagiven personpresents,foratleastonemonth,symptomsofintrusion, per-sistentavoidanceofstimuli,negativealterationsincognitionsand mood,andalterationsinarousalandreactivity,allofthemrelated tothetraumaticevent.SimilarlytootherDSM-5diagnosis, symp-tomsmustcreatedistressand/orfunctionalimpairment(American PsychiatricAssociation,2013).
However,sinceatitsconception,PTSDdiagnosishasbeen sur-roundedbycontroversy(Milleretal.,2014).Thiscontroversyhas furtherincreasedwiththerevisionofthePTSDcriteriainthe5th editionoftheDiagnosticandStatisticalManualofMentalDisorders (DSM-5), which has expanded the construct to include addi-tionalsymptompresentations(AmericanPsychiatricAssociation, 2013).InDSM-IV(AmericanPsychiatricAssociation,1994)there were17PTSDsymptoms,dividedinthreeclusters:intrusive re-experiencing,avoidance/numbing,andhyperarousal.Thisallowed variouscombinationsofrequiredsymptomstomeetthePTSD diag-nosis,resultinginatotalof79,794possiblesymptompresentations. DSM-5 increasedthenumber of symptomsfrom 17 to20, and thenumber ofclustersfromthree tofourwiththeaddition of alterationsinmoodandcognition,raisingthenumberofpossible symptompresentationsmeetingthePTSDdiagnosisfrom79,794
to636,120(Galatzer-Levyand Bryant,2013).Asaconsequence, thenewPTSDdefinitionismuchmoreheterogeneousthanbefore, andalsomoreheterogeneousthanthemajorityoftheotherDSM psychiatricdisordersuchaspanic,socialphobia,ormajor depres-sion.Infact,PTSDresearchhasbeenplaguedbylackofreplication, mixedfindings,andpoorspecificitydespitemassiveresearch fund-ingandintensiveinvestigativeefforts.Themainfactorthatmay explainthedisappointinglackofprogressinthisfieldisthe hetero-geneityderivedfromthedifferentclinicalmanifestationsofPTSD thatmayimpedeprogressintheidentificationofthebiological underpinningsofthisdisorder(Nemeroffetal.,2013).
1.3. TheResearchDomainCriteria
Theheterogeneity foundinPTSD diagnosisusing DSMis an exampleofaresearchobstaclethathasledtheNationalInstitutes of Mental Health (NIMH)to develop theResearch Domain Cri-teria (RDoC) (www.nimh.nih.gov/research-priorities/rdoc/index. shtml), a research framework which adopts a trans-diagnostic approach(Cuthbert,2014;Galatzer-LevyandBryant,2013;Insel etal.,2010).ThischangeinfocusbyNIMHreflectstheconcern thatresearchbasedonDSMdiagnosesarelimitedduetotheir pri-maryfocusonreliabilityattheexpenseofvalidity–leadingto scientificallyinconsistentfindings.TheRDoCprojectconsidersit fundamentaltocapturetheunderlyingmechanismsofdysfunction, openingnewpossibilitiesfortreatmentstargetedto pathophys-iologicalmechanisms.TheRDoCprojectextendsthecategorical viewof mental illness diagnosis,and suggests an dimensional-itytomentaldisorders, asaspectrum thatrangesfromnormal toabnormal.Italsofocusesontheunderlyingmechanisms (psy-chological,behavioral,physiological,theneuralcircuitframework, etc.)that cut across a wide array ofpsychiatry manifestations, operatingoutsidethetraditionaldiagnosticboundaries.Therefore, theRDoC takes a translational, dimensionalapproach to defin-ingpsychopathology,and aims topromote thedevelopmentof aninterdisciplinaryscience ofpsychopathologythat consistsof dimensionalconstructs integrating elements ofpsychology and biology(KozakandCuthbert,2016).Anobjectiveofthisapproach istodevelop,forresearchpurposes,newwaysofclassifyingmental disordersbasedondimensionsofobservablebehaviorand neuro-biologicalmeasures(NIMH,2016).
InlinewiththeRDoCinitiative,wedevelopedaresearchproject associatedwiththeoutpatientclinicoftheFederalUniversityofRio deJaneiro(Brazil)specializinginPTSDassessmentandthe treat-mentofvictimsofurbanviolence.Theresearchteamcomprisesa multi-disciplinarygroupofresearchersfromdifferentfields includ-ing:basicneuroscience,psychophysiology,psychiatry,psychology andepidemiology.Inthepresentmini-review,partoftheresults gatheredbythisnetworkwillbeconsidered.
TheRDoC projectidentified five researchdomains (negative valence,positivevalence,cognitive,socialprocesses,arousaland regulatorysystems)withinwhichthe“negativevalencesystems” domain is the one more closely related toour research focus.
Thisdomainwasclassifiedintoconstructsthatinvolveresponses toacutethreat,potentialharm,sustainedthreat,frustrative non-reward, and loss (see Kozakand Cuthbert(2016)).The studies reviewedhereareconnectedtodefensivereactionsto violence-related threatand mainlyrelateto theconstructs ofacute and sustainedthreat.
1.4. Defensivereactionstoviolence-relatedthreat
Assaultiveviolencewithagunisamajortriggerformotor defen-sivereactionsinhumans.Theimpactofgun-relatedviolenceonthe brainwasstudiedbyRocha-Regoetal.(2012)employingstructural magneticresonanceimaginginpatientsfromouruniversityclinic, whowerediagnosedwithPTSD.
Arobustreductionofgraymattervolumeintheventral premo-torcortexinvictimswithPTSDcomparedtovictimswithoutPTSD wasobserved.Electrophysiologicalstudiesinnon-humanprimates (GrazianoandCooke,2006)revealedaregionwithinthepremotor cortexwhichisinvolvedintherepresentationoftheperipersonal spaceandintheselectionandcoordinationofdefensivebehavior. Theperipersonalspacecanbedefinedasamarginofsafetyaround thebodyora flightzone(Hayduk,1978;Horowitzetal.,1964; Lloyd,2009),theshape ofwhichisplasticand dynamic, chang-ingindifferentsurroundingsandcontexts(Cléryetal.,2015;Holt etal.,2014).Abnormalitiesintheventralpremotorcortexofthe PTSDpatients(Rocha-Regoetal.,2012)mayberelatedtoa disrup-tioninthedynamicmodulationoftheperipersonalspaceandto inefficientselectionandcoordinationofmotordefensivereactions duringandintheaftermathoftheviolentevents.
Despite theirfundamental importanceto the understanding ofresilienceandvulnerabilityforPTSDassociatedwith violence-relatedtrauma,studiesofmotordefensivereactionsinhumans are still in the early stages. This is not the case in works on non-humanspecies,whichhaveshownthatthreatsfrom preda-tors orcon-specifics prompt a cascadeof hard-wireddefensive behaviors including overt actions and/or immobility. Potential threatevokesattentiveimmobility;predatorattackevokesflight, when escape is available; and aggressive defense, when prey-predator distanceshortens (Marks,1987; Ratner, 1967). When escaperoutes areblocked,and thepredatorapproaches, immo-bilityand/oraggressivethreatsensue(BlanchardandBlanchard, 1989,1971;Blanchardetal.,1986).Whensurvival isextremely threatened,tonicimmobilityisthelastanti-predatorresort(Marks, 1987;Ratner,1967).Itisworthmentioningthatexternalfactors, suchasthepredatorspecies,itsbehaviorandproximity,aswell astheparticularitiesofthesurroundingcontexts,allplayapartin triggeringaparticulardefensiveresponse.Internalfactorsarealso importantandincludespecies-relatedstrategies,individual vari-abilityindefensivepredispositionswithinspecies,pastexperiences undergonebyeachindividual(Eilam,2005;Korteetal.,2005).
Motorreactions,eitherovertactionsorimmobility,arethecore oftheobservabledefensivebehaviors.Wehavemadesuccessful attemptstoadvancetheknowledgeofthedefensivecascadein humansthroughstudiesofwholebodymotorreactionstothreats (Azevedoetal.,2005;Bastosetal.,2016;Facchinettietal.,2006; Volchanetal.,2011).Themethodologyusedtoaddressthisissue wasstabilometry,ausefultechniquetostudybodysway.
In the present mini-review, we will focus on studies that employed stabilometry to address the defensive reactions to violence-relatedthreats.Specialattentionwillbegivento immo-bility reactions1 with an emphasis on tonic immobility, a
peritraumaticreactionwhichhasbeenstronglyassociatedwiththe
1Otherdefensiverepertoiressuchasriskassessmentandaggressivedefensewill notbeaddressedhere.
severityofPTSDcausedbyviolenttraumaticevents(Fiszmanetal., 2008;Limaetal.,2010;Rocha-Regoetal.,2009).
1.5. Stabilometry:abriefdescription
Standingbalanceinvolvescontinuousandintermittentactivity ofmusclesdistributedoverthewholebodytomaintaindynamic equilibrium with respect to the environment. This is accom-plishedbytheresultingmotoroutputsofcomplexbrainprocesses involvinginformationfromseveralsensorialinputsincludingthe proprioceptive,visualandvestibularsystems(Balasubramaniam andWing,2002;Dieneretal.,1986).
Stabilometryisatechniqueemployedtostudythebodyswayof humanparticipantsinastandingpositionusingaforceplatform. Aforceplatformisadevicethatusesasetofforcetransducersto quantifytheground-reactionvectorforceanddetermineitspoint ofapplication,knownasthecenterofpressure.Usually,thedevice isconnectedtoacomputerwhichrecordsthedisplacementofthe centerofpressureforapresetperiodoftime.Astatokinesigramis thegraphicrepresentationofthisdisplacement,presentedinthe horizontalplane(Fig.1).Thedisplacementofthecenterof pres-surecanalsobevisualizedasastabilogram,arepresentationofthe statokinesigramprojectedinoneaxis,eitheranterior–posterioror lateral–lateral,asafunctionoftime.
Globalamplitudeofbodysway overaperiodoftime canbe extractedfromthestatokinesigram.Atypicalparameteristhesway areaestimatedbythecomputationofanellipseenclosingmostof thepointsonthecenterofpressurepath.Fromthestabilograms,it ispossibletoextract,forexample,amplitude(standarddeviation) andfrequencyparametersrelatedtotheprojectionofbodyswayin eithertheanterior-posteriororlateral-lateralaxes(Kapteyn,1972; Prietoetal.,1993).
Thestatokinesigramrepresentstheparticipant’smotor strate-giestokeephis/heruprightbodyinbalanceoveracertainperiod oftimeandunderacertaincondition.External(andinternal) chal-lenges add to this dynamic, preparing the body for behavioral (re)actions.
2. Immobilitydefensiveresponses
Threeimmobilitydefensiveresponsesaredescribed:“attentive immobility”,“immobilityunderattack”and“tonicimmobility”.The word“freezing”iscommonlyusedinreferencetodefensive immo-bilityintheliterature(seeHagenaarsetal.(2014)).Freezinghas beenusedinterchangeablyinthedescriptionsofdifferentkindsof immobilityresponsestothreat,renderingitmisleadingand diffi-culttomakecomparisonsbetweenstudies.Forthatreason,wewill notadoptthisterminthepresentreview.
2.1. Attentiveimmobility
Thefast,effortlessprocessingofpotentiallythreatening stim-uliishighlyadvantageousandmaybecriticalforsurvival.When ananimaldetectsapredatorbuthasnotbeenspotted(a poten-tialthreat),attentiveimmobilityisacommonadaptivedefensive behavior (Fig. 2A). Being motionless increases the chances of goingunnoticedbya predator,and canbeanefficientstrategy if employedbeforethe preyis spotted by thepredator(Eilam, 2005;Marks,1987;Ratner,1967).Upondetectingcuesassociated withpotentialthreat,thealertedindividualcanbecomeabruptly motionless,monitoringthesourceofdanger,andreadytoswitch toanotherbehavioralstrategy.
Campbelletal.(1997),usingimplantedbiotelemetrydevices innon-humansspecies,observedimmobilityandbradycardiain responsetopotentialthreat.Takingthoseresultsinaccount,Lang etal.(1997)designedexperimentalparadigmstodrawananalogy
Fig.1. Statokinesigram:displacementofthecenterofpressure.Ontheleft,aschematictopviewofaforceplatformillustratingthefeetpositionofaparticipant.Inred,a depictionofthepathofhis/herrespectivecenterofpressure,representingbodyswayduringagivenperiodoftime.Thepathofthecenterofpressureisshownenlargedon theupperrightside.Anellipseshowninblack,enclosingmostofthepointsonthecenterofpressurepath,iscomputedforthecalculationoftheswayarea.Onthelower rightsideaschematichumanfigurestandingonaforceplatformisshown.Y:anterior-posteriordirection,X:lateral-lateraldirection.
Fig.2.Schematicrepresentationsofimmobilitydefensivereactionsinnon-humanmammal.(A)Attentiveimmobilityisatypicalreactionwhenananimaldetectsapotential threat,buthasnotbeenspottedbythepredator.(B)Immobilityunderattackmayoccurwhenthepreydetectssignsofimminentattackandanescaperouteisnotavailable. (C)Tonicimmobilityisthelastdefensiveresortwhenlifeisatriskandsurvivalisextremelythreatened.Notethatflightunderattackwhenanescaperouteisavailableis notrepresentedinthisfigure.
forattentiveimmobilityinhumans.Theauthorsusedaversive pic-turestorepresentpotentialthreat.Exposuretothemwasfound to prompt cardiac deceleration, as well as moderate increased skinconductance,potentiatedstartlereflexes,andreportsofhigh arousalandunpleasantness(Bradleyetal.,2001).Immobilityin humanswasnotprobed.
Theworkofourteam(Azevedoetal.,2005;Facchinettietal., 2006), using stabilometry, allowed immobility reaction during viewingofaversivepicturestobemorecloselycharacterizedforthe firsttime.Duringtheexperimentalsession,participantsstoodona forceplatformwiththeirfeettogetherandarmsalongtheirtrunk, andlookedatamonitorwhilebodyswaywasrecorded.Theyalso hadsensorsattachedtorecordtheelectrocardiogram.The statoki-nesigramsandstabilogramswereanalyzedtoextractamplitude parameters–areaandstandarddeviationsinlateral–lateraland anterior-posterioraxes.Meanpowerfrequencywasalsoanalyzed forbothaxes.Inthetwostudies(Azevedoetal.,2005;Facchinetti etal., 2006), mutilation pictures andneutral controloneswere presented, both categories in a separate full sequence without intervals.Picturesofinjuredhumansrepresentedcuesfor poten-tialthreats.Theresultsrevealedareducedareaofsway,signaling lessmobility.Inbothstudiesreducedamplitudewasmoreevident inthelateral–lateral axis;accompaniedby“rigidity”, character-izedbyaugmentedmeanpowerfrequencyinthesameaxis,and bybradycardia.
Takentogether,thesefindingsareobjectivesignsofa defen-sivereactionthatcouldbeanalogoustotheattentiveimmobility describedinotherspecies.Interestingly,individualvariabilitywas showntoinfluencethisdefensivereaction.Astudyfromanother group(Hagenaarsetal.,2012),usingaparadigmsimilartoAzevedo etal.(2005),showedthatthenumberofprioraversivelifeevents affectedthemagnitudeoftheimmobilityreaction.
Thisexperimentaldesign,thatallowedtherecordingofsubtle andautomaticchangesinwholebodymotorreactionsupon detect-ingthreateningcues,openedanavenueforfurtherexaminingthe defensecascadeinhumans.
2.2. Immobilityunderattack
Whenthepreydetectssignsofimminentattack,thedefensive strategyusuallyswitchestoflee.However,asdemonstratedina seriesofexperiments(BlanchardandBlanchard,1971;Blanchard etal.,1986);whenescapeisblocked,adifferenttypeofimmobility reaction,underattack,mayoccur(Fig.2B).
Blanchardetal.(2001) devisedaparadigmin which human participantsshouldselectfromalistofchoicesthedefensive behav-iortheywouldadoptiffacedwithdifferentthreateningscenarios (seealsoPerkinsandCorr,2006;Shuhamaetal.,2008).Escaping waschosenasthemostlikelyresponsetoscenariosevaluatedas unambiguousandhighlythreatening,whenanescaperoutewas available;andbecomeimmobilizedwaschoseninaninescapable threateningsituation.
To measure these reactions through body sway recording, ourteamconceivedanexperimentaldesignemployingclear-cut threateningpictorialstimuli,inwhichcluesofanescaperoutewere eitherpresentorabsent(Bastosetal.,2016).Tosimulate attack-likethreat,pictures depictingaman carrying agunwereused. Moreover,themajorityoftheparticipantsreportedhavingbeen previouslyexposeddirectlyorindirectlytoviolentcrime,which madethepicturesevenmorerelevanttothesample.Inpictures simulatingpossibilityofescape,thegunwasdirectedawayfrom theparticipant;in thosesimulatinghigher riskand lesschance ofescape,thegunwasdirectedtowardtheparticipant.Matched controlpicturesdepictedsimilarlayouts,butwiththegun sub-stitutedfor a non-lethal object (e.g.a camera). Pictureswithin each categorywerepresented ina fullsequence without
inter-Fig.3.Schematicstatokinesigramsrepresentingtheareaofbodyswayduringthe viewingofcontrolpicturesandthreatpictures.(A)Cuesforthepresenceofanescape route(pointedaway).Non-lethalobjectpointedawayfromtheobserver(control) andgunpointedawayfromtheobserver(threat).Amplitudeofbodyswayarea isincreasedforthreatcomparedtocontrolpictures,conceivablyrepresentinga transitionintoamoreactivemotoricstateinpreparationtoescape.(B)Cuesfor theabsenceofanescaperoute(pointedtoward).Non-lethalobjectpointedtoward theobserver(control)andgunpointedtowardtheobserver(threat).Amplitudeof bodyswayisreducedintheanterior-posterioraxisforthreatcomparedtocontrol pictures.Thereductioninback-and-forthswayinresponsetopicturesofapointed gun(lesspossibilityofescape)evokesan“immobilityunderattack”reaction.
vals.Participantsstooduprightontheforceplatformandlookedat amonitor.Stabilometryandelectrocardiographywererecorded. Aftertherecordingsession,participantsevaluatedtheemotional impactofeachsetofpictures.
Bastos et al. (2016) observed that pictures depicting a man carryingaguncomparedtomatchedcontrolpictures(non-lethal objects) wereevaluatedasmore intenseandwithmore riskof death,andtriggeredmoredesiretoescape.Comparedtothe pic-turesin whichthegunwaspointedaway fromtheparticipant, thepicturesinwhichthegunwasdirectedtowardtheparticipant wereevaluatedasmorethreatening,closer,withlesschanceof escapingandwithless chanceofhiding.Also,pictureswiththe gundirectedattheparticipantwereperceivedaslessambiguous andpresentingincreasedriskofdeathwithparticipantsreporting feelingimmobilized,andwithmoredesiretoescape.
Forthepicturesthatsimulatethreatwithmorepossibilityof escape,withthegundirectedawayfromtheparticipant,postural reactivitywascharacterizedbya generalincrease inthe ampli-tudeofbodysway,comparedtomatchedcontrolpictures(Fig.3A). Exposuretogundirected-awaypicturesdidnotevokeabradycardic
effectasitdidwhenparticipantswereexposedtopicturesof muti-lation(Azevedoetal.,2005;Facchinettietal.,2006),infact,there wassomeindicationsofheartratedrifttowardacceleration(Bastos etal.,2016).Inthecaseofpicturesdepictinggunsdirectedaway fromtheparticipantpresentedtoasamplewithahistoryofprior exposuretoviolence,insteadofyieldingattentiveimmobilitythey seemedtotriggerapredispositiontoamoreactivemotoricstate, possiblyanescape-likedefensiveresponse.
Exposuretopictures portrayingthegundirectedtowardthe participant,whichwereevaluatedasthemostthreateningand pre-sentingtheleastchanceofescaping,resultedindifferentpostural andcardiacreactions(Bastosetal.,2016).Comparedtothe pre-sentationofmatchedpictures ofnon-lethalobjects,therewasa significantreductionoftheamplitudeofbodyswayinthe anterior-posterioraxis(Fig.3B)andbradycardia.Thisreactionresemblesthe immobilityunderattackdescribedinnon-humananimalsunder exposuretoapredatorandwithescaperoutesblocked(Fig.2B).
Inconclusion,theresultsfromBastosetal.(2016)indicatethat whenexposedtothreatinacontextindicatingapossibleescape route,humans,asinnon-humanspecies,engageinactiveescape (increasedbodysway),resemblingtheflightstageofthe defen-sivecascade.Whenfacingthreatwithlesspossibility ofescape, resultsindicatethathumanspresentimmobilityunderattack–a specificimmobileresponse(reducedback-and-forthsway)with bradycardia.
Althoughtherearesomaticandautonomicsimilaritiesbetween “attentiveimmobility”and“immobilityunderattack”,thecontexts thatevokeeachoftheseevolutionaryadaptivestrategiesareclearly distinct.Intheformer,thereisnosignofcurrentattack;whilein thelatter,theattackisongoingandanescaperouteisnotreadily accessible.
2.3. Tonicimmobility
Whenlifeisatextremerisk,tonicimmobilityisthelast defen-siveresort.Itisareflexiveandinvoluntaryreaction,elicitedunder theperceptionofoverwhelmingdanger,andischaracterizedby reversibleprofoundmotorinhibition(Fig.2C)andrelative unre-sponsivenesstoexternalstimuli(Ratner,1967).Tonicimmobility isofadaptivevalueunderpredationattack(Rüttingetal.,2007; SargeantandEberhardt,1975),sinceapredatormayloosenitsgrip tohidethepreyortofendoffotherpredators.
2.3.1. Systematicretrospectivereports
Althoughdescribedinnon-humananimalsformorethanthree centuries(Maser and Gallup, 1977), it was notuntil 1979 that Suarezand Gallup(Suarezand Gallup, 1979)arguedthat there weresimilaritiesbetweentonicimmobilityandstillnessreactions inwomenvictimsofrape–“rape-inducedparalysis”.
Gallianoetal.(1993)conductedthefirstsystematicstudyon tonicimmobility in femalerapesurvivors. More recent studies assessedthis phenomenon throughretrospectivereports ofthe traumatic events in a more systematic way using psychomet-ricinstrumentsinfemalevictimsofsexualassault(Bovinetal., 2008;Fuséetal.,2007;Heidtetal.,2005;Humphreysetal.,2010; TeBockhorstetal.,2015).Otherstudiesexpandedthescopetoother traumaticeventsandtomenaswellaswomenindifferent conve-niencesamples:students(Abramsetal.,2009;Badosetal.,2008; Portugaletal.,2012),policeofficers(Maiaetal.,2015)andPTSD patients(Fiszmanetal.,2008;Limaetal.,2010;Rocha-Regoetal., 2009).
Recently, peritraumatictonic immobilitywasdescribed in a largerepresentativesampleofthegeneralpopulationthrough ret-rospectivereports(Kalafetal.,2015).Theauthorsobservedthat quantifiedscoresoftonicimmobilityweremorethandoublefor thesubsamplewhometthecriteriaforPTSD.Thisisnot
surpris-inggiventhat thediagnosticcriteriafor PTSDinclude exposure toactualor threateneddeath,seriousinjury orsexualviolation (AmericanPsychiatricAssociation,2013),whicharealsotriggers fortonicimmobility.
InaseriesofstudiesexaminingPTSDpatientsexposedto gun-relatedviolencefromouruniversityoutpatientclinic,retrospective reportsofperitraumatictonicimmobilitywereobservedto cor-relatewiththeseverityofPTSDsymptomsandrefractorinessto pharmacologicaltreatment(Fiszmanetal.,2008;Limaetal.,2010; Rocha-Regoetal.,2009).
2.3.2. BiologicalassessmentandimplicationsforPTSD
The first human study to successfully report biological evi-dencefortonicimmobilitywasperformedinourlaboratorysetting employing stabilometry recordings (Volchan et al., 2011).This studywasconductedwithPTSDpatientsfromtheuniversity out-patientclinic.
Tosimulateexposuretolife-threateningeventsinthelab,PTSD patientsandtrauma-exposedparticipantswithoutPTSDpassively listenedtothescriptoftheirpersonalviolence-relatedtrauma.2
Participantsstooduprightontheforceplatform,had electrocardio-gramelectrodesattachedandworeearphones.Immediatelyafter therecordingsession,participantsratedthescript-inducedtonic immobilitythroughaspecificquestionnaire.Stabilometryresults fromVolchanetal.(2011)revealedthatparticipantswhorated thehighestscoresoftonicimmobilityafterlisteningtothe per-sonaltrauma-scriptpresentedthelowestamplitudesofbodysway. Furthermore,thoseparticipantsalsoexhibitedrobusttachycardia andverylowheartratevariabilityafterlisteningtothepersonal trauma-script.ItisworthnotingthatamongthePTSDpatients,40% hadveryhighscoresoftonicimmobilityafterlisteningtothescript, whilelessthan7%oftrauma-exposedparticipantswithoutPTSD scoredabovethemedianvalueoftonicimmobilityquestionnaire (Franklin, 2010). Not unexpectedly, thebiological indicators of tonicimmobilityinthelaboratorysettingwerepresentedexpressly bythePTSDpatients,whoaremoresusceptibletore-experiencing thetraumaticevent,eveninanotherwisesafeenvironment.
Insummary,thestudybyVolchanetal.(2011)revealedthat animportantproportionofPTSDpatients,triggeredbylistening totheirpersonalviolence-relatedtraumascript,reactedwith sus-tainedtachycardiaaccompaniedbyreducedheartratevariability andreducedbodysway;which,togetherwiththequestionnaire ratings,characterizedtonicimmobilityinhumans.
Theseresultssuggestthatunderexternaland/orinternalcues, in daily-life a significant proportion of PTSD patientsprobably presentrepeatedepisodesoftonicimmobility-likereactions.This canhaveharmfuleffects.Forinstance,prolongedreducedheart rate variability has been associated with immune dysfunction, inflammation,cardiovascular disease,and mortality(Kempand Quintana,2013).In fact,Ratner(1967)had already observedin experimentalanimalsthatrepeatedinductionsoftonicimmobility potentiatethisreactionandhaveharmfullong-termconsequences, whicharesometimeslethal(Libersonetal.,1961).Indeed,PTSD patientsreportingperitraumatictonicimmobilityfrom violence-relatedtraumaticeventwerefoundtobethemostseverelyaffected
2Thisisnotthesameasthe“personaltraumascript-drivenimageryprotocol” (seeLangetal.,1980;Pitman,1987)inwhichparticipantsareinstructedtomentally relivetheeventasvividlyaspossibleduringandafterlisteningtothescript.Inthe paradigmthatweapply,thereisnosuchinstructionandparticipantspassivelylisten tothescripts.Weshowed(Norteetal.,2013)thatPTSDpatientsrobustlyincreased theheartratewhenpassivelylisteningtotheirpersonaltraumascript,andhad sustainedorevenaugmentedheartratesafterlisteningtothescript.Furthermore, sustainedtachycardiawascorrelatedwithre-experiencingsymptoms.Ontheother hand,participantswithoutPTSDslightlyincreasedtheheartrateduringlisteningto thescriptandreturnedtobasallevelthereafter.
Fig.4. Immobilitydefensivereactionsinhumans-schematicrepresentationsofexperimentalparadigms.(A)Attentiveimmobility:picturesofmutilation(potentialthreat) presentedonascreenevokebradycardiaandreducedareaofbodysway–mainlyinthelateral–lateral(X)axis.(B)Immobilityunderattack:picturesofapointedgundirected attheparticipant(attackwithlesspossibilityofescape)presentedonascreenevokebradycardiaandareducedareaofbodysway–mainlyintheanterior-posterior(Y)axis. (C)Tonicimmobility:scriptofapersonalviolencetrauma(lifeatrisk)listenedtothroughearphonesevokestachycardiaandareducedareaofbodysway.
(Fiszmanetal.,2008;Limaetal.,2010;Rocha-Regoetal.,2009). Repeatedepisodesoftonicimmobilitymayunderpintheseverity ofthedisorderinthesepatientsbyrenderingthemmore suscepti-bletotheknownhazardouseffectsofrepeatedactivationofstress mediatorsondysregulationofbrainandbodyallostasis(Karioetal., 2003;McEwenandGianaros,2010).
Predispositionstoreactwithtonicimmobilitymaybea spe-cificcharacteristicofsomeindividuals.AsdiscussedbyKorteetal. (2005),within-speciesdifferencesintypicalbehavioraldefensive strategies(supportedbyparticularphysiological,neurobiological andneuroendocrinologicalunderpinnings)areevolutionary adap-tive.In the face of changes in thesurrounding environment, a balancebetweendifferenttraitscanbeadvantageousforaspecies’ survival.However,foragivenindividual,his/herdefensivetraitcan sometimesbemaladaptive.Thismayhavetherapeuticimplications forthosePTSDpatientswhoarepronetotonicimmobilityreaction. ThepharmacologicaltreatmentofchoiceforPTSDpatientsisthe antidepressantsknownasselectiveserotoninreuptakeinhibitors (SSRIs).Asmentionedbefore,ithasbeenfoundthatPTSDpatients whoexperiencedthehighestlevelsofperitraumatictonic immobil-ity,weretheleastresponsivetoPTSDpharmacologicaltreatment (Fiszmanetal.,2008;Limaetal.,2010),raisingtheneedfor alter-nativepharmacological agents. In fact,there is evidence that a neglectedclassofmedicationsinthetreatmentofSSRI-resistant PTSD–namelydopaminergicagonists–shouldreceivemore atten-tionfromresearchersandclinicians(Bergeretal.,2009;Houlihan, 2010;Nayloretal.,2015).Anincreasedfocusonidentifyingthe occurrenceofperitraumatictonicimmobilitymayopenthefield fortheuseofmorespecificpharmacologicalagentsinPTSD.
2.3.3. Thebenefitsofincreasedknowledge
The occurrence of tonicimmobility in humans still remains largely unrecognized. This automatic and involuntary reaction underextremelifethreateningcontextsmayelicitthefeelingof terrorofbeingimmobilized,addingtothefearevokedbythe trau-maticeventitself(Volchanetal.,2011).Additionally,victimsoften feelguiltyandashamedbynothavingbeenabletoreact,and some-timesnotevenscream,particularlyvictimsofsexualabuse(Marx etal.,2008).Professionalslikerescuers,policeandsoldiersmay bestigmatized iftheyundergotonicimmobilitywhen enrolled inamissiontosaveandprotectotherpeople(Maiaetal.,2015). Thus,it isessentialthatstepsaretakentoalleviatethe entrap-mentsymptoms,guiltandprejudicefoundintheaftermathoftonic immobility,andthatinformationaboutthisinvoluntaryreactionis morewidelydisseminatedtohealthprofessionalsandthegeneral public.
3. DefensivereactionsandtheinvertedU-shapeprofile
Thepresentreviewfocusedonthehumandefensivecascade– morepreciselyonimmobilityreactionstoviolence-relatedthreats ofincreasingintensity.Wehighlightedstudiesonimmobility reac-tionstodangercuesrelatedtohumanco-specificviolencethreats, nottacklingthecontextofpredatorattacks.Interestingly, stud-iesinrodentshaveshownthatalthoughdifferentneuralcircuits areinvolvedwhenanimalsfacesocial(co-specific)versuspredator threats,behaviorallytheimmobilityreactionswereshowntobe verysimilar(Silvaetal.,2013).
InstabilometrystudiesbyAzevedoetal.(2005)andFacchinetti etal.(2006),picturesofmutilatedhumanbodies,acueforpotential
Fig.5.Schematicrepresentationsofbodyswayarea(red)andheartrate(blue)valuesafterpassivelisteningtoapersonaltraumascript(basedonVolchanetal.,2011). Controls:violence-exposedparticipantswithoutPTSD.PTSDwithouttonicimmobility(TI):violence-exposedpatientsdiagnosedwithPTSD,notreportingtonicimmobility afterlisteningtotheirpersonaltraumascript.PTSDwithtonicimmobility(TI):violence-exposedpatientsdiagnosedwithPTSD,reportingtonicimmobilityafterlistening totheirpersonaltraumascript.Notethatastheseverityofsymptomsincreases,theprofileoftheareaofbodyswayacrosstheparticipantspresentsaninvertedU-shape.In thisparadigm,heartrateincreasessteadily.(Forinterpretationofthereferencestocolourinthisfigurelegend,thereaderisreferredtothewebversionofthisarticle.)
threat,havebeenshowntoinduceattentiveimmobility charac-terizedbyareductioninbodysway,mainlyinthelateral–lateral axis,andbradycardia(Fig.4A).Acutethreatcued bypictures of agundirectedawayfromtheparticipantevokedincreasedbody sway,compatible witha predisposition toactive escape.When thepictures portrayeda gundirected atthe participant, evalu-atedasmorethreatening,closerandwithlesschanceofescape; therewasareductioninanterior-posteriorbodyswayand brady-cardia;characterizingimmobilityunderattack(Bastosetal.,2016) (Fig.4B).Overwhelmingthreat,cuedbytheaudio-playofthe per-sonaltraumascript, especiallyinPTSDpatients, canleadtothe mostextremedefensivereaction−tonicimmobility,characterized byreducedbodysway,robusttachycardiaandreducedheartrate variability(Volchanetal.,2011)(Fig.4C).
The presence of points of disjunction and non-linear func-tions,likeinvertedU-shaperesponsivitycurvesinstudiesofstress andmentaldisordershasbeenrecentlyhighlighted(e.g.Cuthbert (2014);Sapolsky(2015)).Itisimportanttohaveinmindthatan invertedU-shapedprofilemight beobservedwhen analyzing a parameterassociatedwiththreatintensityorsymptomsseverity. Thisfindingis consistentwiththepossibility ofmore thanone dimensionunderlyingtheresponsivitycurve,aswediscussbelow inconnectionwithdefensivereactivity.
For instance, the response profile to pictures representing increasingdanger:frompotential(mutilation),tomorethreatening but escapable (gun pointed away), to even more threaten-ing but less escapable (gun pointed toward) contexts; led to an inverted U-shaped responsiveness profile characterized by “reduced-increased-reduced”bodysway(andtosomeextentheart rate).Thatis,agunpointingtoward(comparedtopointingaway) additionally to being more threatening, is more unescapable, bringinginto play anadaptive switchtoimmobility,instead of continuallyincreasing“mobility”.
AninvertedU-shaped profilewasalso foundwhen the pos-turalreactions,afterpassivelylisteningtotheirpersonaltrauma script,werecomparedamongparticipantswithincreasing sever-ityPTSDsymptoms(Fig.5).Almostnomodulationwasshownby participantswithoutPTSD (controls);anincreasedareaof body swaywaspresentedbyparticipantswithPTSDreportingnotonic immobility;andalowerareaofbodyswaywaspresentedby par-ticipantswithPTSDreportingtonicimmobility.Inthiscase,the analysisofanotherphysiologicalparameter–heartrate–revealed aseeminglylinearincreasingtrendacrossthesethreegroupsof participants(seeFig.5).
Anothergroupof researchers(McTeagueet al.,2010), tested heartratereactivityusingthepersonalthreatimageryparadigm inthreegroupsofparticipantswithincreasingsymptomseverity: controls,single-traumaPTSDpatientsandmultiple-traumaPTSD patients.Bodyswayandtonicimmobilitywerenotassessed.They foundthatheartreactivityincreasedfromcontrolstosingle-trauma PTSDpatients,andfelltocontrollevelsinthemoreseverelyaffected PTSDpatientswithmultipletraumahistory,resemblinganinverted U-shapedprofile.
AnotherstudycalledattentiontoaninvertedU-shapeintheir proposalofdifferentstagesofdefensivereactivityinPTSDpatients (SchauerandElbert,2010–Fig.1,p.111).Intheirframework,they hypothesizedthatinresponsetoatraumaticevent,some individu-alswouldpresentafight/flightreaction,otherswouldpresenttonic immobilitywithintensetachycardia, andstill others, especially thoseindividualswithhistoryofmultipletraumas,wouldpresent a“shutdown”effectandfaint(bradycardiaandhypotension).
In conclusion,it is essential tohavein mind theinvertedU frameworkwhenanalyzingdifferentparametersandacross dif-ferentsubjects.
4. Conclusions
Thepresentmini-reviewsynthesizedrecentadvancesregarding immobilityreactionsofthehumandefensivecascadethatseemto haveparallelswiththoseproposedfornon-humanspecies, bridg-ingthegapbetweenthem.
InlinewiththeResearchDomainCriteria(RDoC)project(NIMH, 2016), the progresses in basic research to objectively monitor motor defensive reactionsunder threat can help to develop a dimensionaltrans-diagnosticapproachtoPTSD,potentiallyleading tonewavenuesofpreventionandtreatment.
Fundingacknowledgements
This work was supported by National Council for Scientific andTechnologicalDevelopment(CNPq),CarlosChagasFilho Foun-dation of Research Support in Rio de Janeiro (FAPERJ), and CoordinationfortheImprovementofHigherEducationPersonnel (CAPES).
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