Sensitive and critical periods in visual sensory deprivation

This observation of a critical period of susceptibility to deprivation was among the first to reveal the high degree of sensitivity of the ... ThisarticleispartoftheResearchTopic Whatwelearnandwhenwelearnit:sensitiveperiodsindevelopment Viewall 7 Articles Articles Abstract PlasticityintheVisualSystem ExtremeCircumstances:TheCaseofCompleteBlindness CrossmodalPlasticityinBlindness:BoundedbyCriticalorSensitivePeriods? ImplicationsforSightRestoration FutureConsiderations ConflictofInterestStatement References SuggestaResearchTopic> DownloadArticle DownloadPDF ReadCube EPUB XML(NLM) Supplementary Material Exportcitation EndNote ReferenceManager SimpleTEXTfile BibTex totalviews ViewArticleImpact SuggestaResearchTopic> SHAREON OpenSupplementalData REVIEWarticle Front.Psychol.,26September2013 |https://doi.org/10.3389/fpsyg.2013.00664 Sensitiveandcriticalperiodsinvisualsensorydeprivation PatriceVoss1,2* 1CognitiveNeuroscienceUnit,MontrealNeurologicalInstitute,McGillUniversity,Montreal,QC,Canada2InternationalLaboratoryforBrain,MusicandSoundResearch,Montreal,QC,Canada Whilethedemonstrationofcrossmodalplasticityiswellestablishedincongenitalandearlyblindindividuals,greatdebatestillsurroundswhetherthosewhoacquireblindnesslaterinlifecanalsobenefitfromsuchcompensatorychanges.Noproperconsensushasbeenreacheddespitethefactthataproperunderstandingofthedevelopmentaltimecourseofthesechanges,andwhethertheiroccurrenceislimitedto—orwithin—specifictimewindows,iscrucialtoourunderstandingofthecrossmodalphenomena.Anextensivereviewoftheliteraturerevealsthatwhilethemajorityofinvestigationstodatehaveexaminedthecrossmodalplasticityavailabletolateblindindividualsinquantitativeterms,recentfindingsrathersuggestthatthisreorganizationalsolikelychangesqualitativelycomparedtowhatisobservedinearlyblindness.Thisobviouslycouldhavesignificantrepercussionsnotonlyforthetrainingandrehabilitationofblindindividuals,butforthedevelopmentofappropriateneuroprosthesesdesignedtoaidandpotentiallyrestorevision.Importantparallelswillalsobedrawnwiththecurrentstateofresearchondeafness,whichisparticularlyrelevantgiveninthedevelopmentofsuccessfulneuroprostheses(e.g.,cochlearimplants)forprovidingauditoryinputtothecentralnervoussystemotherwiseaurallydeafferented.Lastly,thispaperwilladdressimportantinconsistenciesacrosstheliteratureconcerningthedefinitionofdistinctblindgroupsbasedontheageofblindnessonset,andproposeseveralalternativestousingsuchacategorization. Thescientificliteraturehasgrownrichinresearchillustratingtheremarkableabilityofthebraintoreorganizeitselffollowingsensoryloss.Inparticular,visuallydeafferentedregionswithintheoccipitalcortexofearlyblindindividualshavebeenrepeatedlyshowntobefunctionallyrecruitedtocarryoutawidevarietyofnon-visualtasks.Whilethedemonstrationofcrossmodalplasticityiswellestablishedincongenitally(CB)andearlyblind(EB)individuals,significantdebatesurroundswhetherthosewhobecomeblindlaterinlifecanalsobenefitfromsuchcompensatorychanges.Forinstance,severalinitialneuroimagingreports(e.g.,Cohenetal.,1999;Sadatoetal.,2002)suggestedthatthecrossmodalplasticphenomenaobservedintheblindarelikelyregulatedbyaparticularcriticalperiodbeyondwhichnoobservablechangesoccur.However,anumberofotherstudies(e.g.,Bücheletal.,1998;Burtonetal.,2002a,b;Vossetal.,2006)havedemonstratedthatsuchcrossmodalplasticphenomenamightinsteadberegulatedbyasensitiveperiod,asopposedtoamorerigidcriticalperiod,wheresensoryexperiencehasarelativelygreaterinfluenceonbehavioralandcorticaldevelopment,butisnotnecessarilyexclusivetothatperiod.Consequently,worktodatehasfocusedontheamountofmeasurablecrossmodalplasticityasafunctionoftheageofblindnessonset,thusmoreorlessassumingthatdifferencesobservedbetweengroupsofindividualswithdifferingonsetsarequantitativeinnature(i.e.,individualswithanearlierblindnessonsetwillshowmorecrossmodalrecruitmentofoccipitalcortexthanthosewithalateronset).Nonetheless,inlightofrecentfindings,onecouldarguethattheplasticchangesthatoccurfollowingblindnessdonotonlychangequantitativelywithincreasingageofblindnessonset,butalsoqualitativelyinthatcrossmodalrecruitmentofoccipitalcortexmightreflectdifferentprocessesandpurposesforEBandlateblind(LB)individuals.Forinstance,thefunctionalrelevanceofcrossmodalplasticityobservedinlate-onsetblindnesshasyettobeclearlyestablished,whereasithasbeenclearlylinkedtobehaviorinEB;thusevenifweweretoobservesimilarlevelsofcrossmodalrecruitmentofvisualareasinbothEBandLB,theobservedoccipitalactivationsmaynotsharethesamefunctionalorbehavioralrelevanceforbothblindgroups.Asaresult,weshouldperhapsnolongersimplyinvestigatethepresenceorabsenceofplasticityinearlyandlate-onsetblindness,butmoreimportantlyaskourselveshowtheplasticprocessesandmechanismschangewithincreasingageofonset.Evidencesupportingthisclaimwillbediscussedindetailbelow,followingabriefprimeronsomegeneralplasticpropertiesofthevisualsystemandanin-depthreviewoffindingsdepictingthecrossmodalplasticityphenomenonobservedinearlyblindness. PlasticityintheVisualSystem Muchofwhatweknowtodayonthebrainanditsplasticproperties,weoweingreatparttothepioneeringworkofNobellaureatesDavidH.HubelandTorstenN.Wieselperformedintheearly1960s.Theirinvestigationsontheeffectsofmonoculardeprivationrevealedbothanearlyinnateperiodofdevelopmentandalatercriticalperiodofexperience-dependantplasticity.Indeed,theirchoicetodepriveyoungkittensofvisioninonlyoneeyeallowedthemtodirectlycomparetheresponsesofbotheyes,thusactingasaninternalcontrolforvariationsinthedevelopmentalstageoftheanimal.Theyshowedthatmonocularlydeprivingnewbornkittensforaleastamonthinducedadramaticshiftintheprimaryvisualcortex(V1)responsesfromthedeprivedeyetothenon-deprivedeye(over98%oftherecordedneuronswereunresponsivetoinputtotheformerlydeprivedeye)(WieselandHubel,1963).Followupstudiesrevealedthatwhenkittenswerebinocularlydeprivedfrombirth,morethanhalfofthecellscontinuedtorespondtobotheyes(WieselandHubel,1965),andthatwheneyeswerekeptfromworkingtogetherbyalternatingocclusionofthetwoeyes,nearlyallofthecellsstoppedrespondingtobotheyesandwereinsteaddrivenbyoneeyeortheother(HubelandWiesel,1965).Thesefindingsledthemtohypothesizethatthelossofdeprived-eyeresponseswasaresultofcompetitiveprocesseswiththenon-deprivedeyeandnotsimplyfromdisuse. Ofgreaterrelevancetothecurrentspecialtopic,HubelandWiesel(1970)laterinvestigatedwhetherthesephysiologicaleffectsweregovernedbyaperiodofsusceptibility;thatiswhentheseeffectsweregreatestandhowlongtheylasted,thedurationofdeprivationnecessarytoproduceachange,aswellastherelationshipbetweenthetimingofdeprivationandtheabilitytorecovernormalfunction.Toaddresstheseissues,theydeprivedkittensforvariousperiodsoftimeatdifferentagesandcomparedneuralresponsesinthestriatecortexfrombothmonocularinputs.Importantly,theyfirstshowedthataperiodofsusceptibilitydidinfactexist,startingearlyinthe4thweekfollowingbirthandremaininghighforapproximatelythreeweeks,onlytoslowlydeclineuntiltheendofthethirdmonth.Whatreallyhighlightstheimportanceofthisperiodisthefactthatamonoculardeprivationoccurringduringthefirstthreemonths—evenoneasshortas3or4days—leadstoalastingandlargelyirreversibledeclineintheproportionofcellsrespondingtothedeprivedeye,whereasverylongperiodsofmonoculardeprivationintheadultcathasverylittletonophysiologicaleffects(HubelandWiesel,1970).Thisobservationofacriticalperiodofsusceptibilitytodeprivationwasamongthefirsttorevealthehighdegreeofsensitivityoftheimmaturebraintoanalteredsensorystateduringaveryrestrictedtimeperiodinlife. Itisprobablypertinentatthispointtomakeanimportantdistinctionbetweentworelatedconcepts;thatisthedifferencebetweenasensitiveperiodandacriticalperiod.Whilebothconceptshaveattimesbeeninterchangeabletoacertainextentintheliterature,theyarebestsegregatedtoexplaindistinctdevelopmentalphenomena.Sensitiveperiodsgenerallyrefertoalimitedtimewindowindevelopmentduringwhichtheeffectsofexperienceonthebrainareunusuallystrong,whereasacriticalperiodisdefinedasaspecialclassofsensitiveperiodswherebehaviorsandtheirneuralsubstratesdonotdevelopnormallyifappropriatestimulationisnotreceivedduringarestrictedperiodoftime(Knudsen,2004).Theabove-mentionedstudiesonmonoculardeprivationareperfectexamplesofcriticalperiods,wheretheabsenceofnormalsensoryinputduringaspecifictimewindowleadstoirreversiblechangesinbrainfunctionandconnectivity.Indeed,ifnormalbinocularinputisnotachievedbythreemonthsofageinkittens,nocellswilleverrespondtoinputfromtheoccludedeye,evenifvisualinputtotheoccludedeyeisrestoredafterthecriticalperiod. Sofarthefocushasbeenonananimalmodelofmonoculardeprivationtoillustratetheimportanceoftimewindowsindevelopmentduringwhichcompetitiveprocessesdeterminetheroleplayedbyindividualcellsintheprimaryvisualcortex.Animportantquestionthathasnotbeenraisedyetconcernswhathappenswhennovisualinputreachesthevisualprocessingcentersofthebrain(i.e.,binoculardeprivation).Doesthelackofsensoryexperienceleadtodisuse-relatedatrophicprocesseswithintheseregions?Oraretheirstillcompetitiveprocessesatplaytogaincontrolofoccipitalcorticalregionsdespitethelackofvisualinput?Suchquestionshaveledtomanyinvestigationsandrevealedthattheblindconstituteexcellentmodelsforstudyingtheplasticnatureofthebrain(BavelierandNeville,2002;Pascual-Leoneetal.,2005).Thefollowingsectionwilldescribeindetailwhatwecurrentlyknowabouttheconsequencesofcompleteblindnessinhumanadults,bothintermsofbrainandbehavioralchanges. ExtremeCircumstances:TheCaseofCompleteBlindness FunctionalandBehavioralAdaptations Wehaveaprettygoodunderstandingofhowthebrainprocessesvisualinformationandofthespecificrolesplayedbyvariousregionsthroughoutthevisualsystem.However,untilrecently,wehadverylittleknowledgeconcerningwhathappenedtotheseregionswhenanindividualwascutofffromthevisualworldduetoperipherallesionsofthevisualsystem(e.g.,damagetothelens,retinaoropticnerve)andthusleadingtocompleteblindness.Evidently,progresshasrapidlyincreasedwiththeadventofspecializedneuroimagingtoolsthatallowedforthein-vivoinvestigationofthebrain.Thefirstneuroimagingstudiesusedpositronemissiontomography(PET)tostudytheglucosemetabolismoftheoccipitalcortexatrestinbothEB—individualsthatbecomeblindduringthefirstfewyearsoflife(seeBox1)—andsightedindividuals(Wanet-Defalqueetal.,1988;Veraartetal.,1990).Itwasshownthattheglucosemetabolismobservedinoccipitalcortexofblindindividualswasgreaterthanthatobservedinblindfoldedsightedsubjects,butcomparabletowhatwasobservedwhentheblindfoldwasremoved.TheseinitialobservationsobviouslyraisedimportantquestionsonthefunctionalityoftheEB'svisualcortex.Subsequently,Uhletal.(1991,1993)wereamongthefirsttoshowtask-relatedactivationsinresponsetotactilestimulationwithinoccipitalcortexofEB,andshortlythereaftercameamultitudeofbrainimagingstudiesshowingthattheiroccipitalcortexcouldbecrossmodallyactivatedbyavarietyoftactile(Sadatoetal.,1996;Bücheletal.,1998;Burtonetal.,2002a)andauditory(Weeksetal.,2000;Arnoetal.,2001;Burtonetal.,2002b)tasks. BOX1 Box1. Despitetheimpressivenatureoftheobservedcrossmodalactivationsintheoccipitalcortex,importantquestionsstillremainedregardingtheirexactsignificance.Aretheytrulytask-relatedorsimplyanepiphenomenonassociatedwiththeabsenceofvisualinput?Severalfindingssuggestthattheoccipitalcortexdoesindeedplayafunctionalroleinprocessingnon-visualinformationfollowingearlyblindness.ThefirstlineofevidencestemsfromresearchdemonstratingstrongcorrelationsbetweenbrainactivityinoccipitalcortexofEBandbehavioralperformanceonavarietyoftasksincludingverbalmemory(Amedietal.,2003),episodicretrieval(Razetal.,2005)andsoundlocalization(Gougouxetal.,2005).ThisisperhapsnotsosurprisinggiventhewealthofevidencedocumentingthedevelopmentofheightenedcompensatoryperceptualandcognitiveabilitiesinEB(seeVossetal.,2010).Auditoryspatialabilitiesinparticularhavebeenheavilyinvestigatedinlightofsubstantialquestionsconcerningablindperson'sabilitytoformadequatespatialrepresentationsintheabsenceofvision;consequently,anabundanceofcompellingevidencelinkingoccipitalfunctioningandsoundlocalizationinearlyblindnesshasbeenbroughttolight(seeFigure1;seealsoCollignonetal.,2009). FIGURE1 Figure1.Functionalrelevanceofcrossmodalplasticity.Illustratedherearedemonstrationsofthefunctionalroleplayedbytheoccipitalcortexinspatialhearingtasksinearlyblindindividuals.Thetoprow(panelA)depictsthefindingthatoccipitalactivityinearlyblindindividuals(blackdots)waspredictiveoftheirperformanceinasoundlocalizationtask(Gougouxetal.,2005).Thebottomrow(panelB)illustratestheeffectthatTMShaswhenappliedtotheoccipitalcortex(blackbars)whenbothblindandsightedsubjectswereaskedtolocalizesounds(Collignonetal.,2007).ComparedtoSham-TMS(whitebars),TMSappliedoveroccipitalcortexreducedtheperformanceofearlyblindsubjectsonly,whichisindicativethatthisregionisfunctionallyrelevantforspatialprocessingintheearlyblind.AdaptedwithpermissionfromGougouxetal.(2005)andCollignonetal.(2007).*P<0.05. Additionalevidencesupportingthefunctionalrelevanceofthecrossmodalrecruitmentofoccipitalcorticesinearlyblindnesscomesfromtheuseoftrans-magneticstimulation(TMS)whichenablesinferencesoncausalityviathetemporarydisruptionofcorticalfunctioningwithinveryspecificbrainareas.Indeed,theapplicationofTMStooccipitalareassignificantlyhamperstheperformanceofEBintasksassessingsoundlocalization(Collignonetal.,2007),verbalmemory(Amedietal.,2004)andBrailleidentification(Cohenetal.,1997),whileleavingtheperformancescoresofsightedindividualsunaffected.PerhapsthemoststrikingformofevidencecomesfromablindexpertBraillereader,whocompletelylosttheabilitytoreadBraillefollowinganischemicstrokecausingbilaterallesionstoheroccipitalcortex(Hamiltonetal.,2000).Similarly,amiddle-agedblindindividualwasreportedashavingtransientdifficultiesinreadingBraillewhileheexperiencedtemporaryvisualhallucinations(Maedaetal.,2003).ThefactthathisabilityreturnedtonormalfollowingthehallucinationssuggestsacausalrelationshipbetweenoccipitalfunctioningandBraillereadinginthisblindindividual.Takentogether,thesefindingssuggestthatoccipitalcortexmightstillservesomefunctionalpurposefollowingblindness.Whatisnotclearatthispoint,however,ishowthesecrossmodalplasticadaptationscometobe?Properlyunderstandinghownon-visualsensoryinputsareprocessedwithinoccipitalcortexisachallengingtaskandisdiscussedinthefollowingsection. CrossmodalPlasticity:UnderlyingMechanisms Ashighlightedearlier,manyneuralprocessesandconnectionsaretheresultofcompetitiveinteractionsbetweendifferentneuronsandsensoryinputs,andaspreviouslysuggestedbyPascual-LeoneandHamilton(2001),visualinputsmightactuallygainaccesstooccipitalregionsbymeansofsuchcompetitiveprocesseswiththeothersensesduringearlydevelopment.Onepopularhypothesisisthatoccipitalcortexmightbebydesignbestsuitedtocarryoutpredeterminedspecializedfunctionsforwhichthevisualsystemprovidesthemostadequatesensoryinput.However,inthecaseofblindness,othersensesprovidingpotentiallyrelevantsensoryinputcouldgainaccesstothe“visual”regionsofthebrainforfurtherprocessing.Suchaviewthereforeassumesthatthefunctionalspecializationof“visual”corticalregionsispreservedinblindness,andindeedthereareagrowingnumberoffindingsthatsupportit. Forinstance,regionsspecializinginthespatialprocessingofsoundsinblindindividualsappeartomapontoareasofthedorsalvisualstreamknownforsimilarprocessingofvisualstimuli(Collignonetal.,2009,2011).Anotherareawellknownforitsfunctionalspecializationisthelateral-occipitalcomplex(LOC),typicallyinvolvedinobject/formrecognitionprocesses,whichhasbeenshownonseveraloccasionstoberesponsivetonon-visualformprocessinginEB(Amedietal.,2007,2010).Similarly,thevisualwordformarea,which,asitsnameindicates,respondswelltothevisualpresentationofwords,hasbeenshowntobehighlyresponsivetotactuallypresentedBraillewordsinEBsubjects(Reichetal.,2011).Furthermore,Pietrinietal.(2004)hadpreviouslyshownthatthetactileexplorationoffacesactivateddifferentregionsthanthoseelicitedbytheexplorationofobjectsintheblind,suggestingthatthedevelopmentoftopographicallyorganized,category-relatedrepresentationsinextrastriatevisualcortexdoesnotrequirevisualexperience.Similarly,distinctregionswithintheventralvisualpathwayofblindindividualsshowneuralspecializationfornon-livingandlivingstimuliintheauditorymodality,suggestingthattheconceptualdomainorganizationintheventralvisualpathwaydoesnotrequirevisualexperiencetodevelop(Mahonetal.,2009).Lastly,anotherwellknownareaforitsfunctionalspecializationisthehumanextrastriatecorticalregionknownasthemiddletemporalcomplex(hMT+),whichishighlyresponsivetovisualmotion.Severalstudieshaveshownthatthisregioninblindindividualsbecomesresponsivetobothtactilemotiononthefingers(Ricciardietal.,2007)aswellastomovingsoundstimuli(Poirieretal.,2006).Thesefindings,takentogether,providecompellingevidencethatthefunctionalspecializationofoccipitalregionsispreservedinearlyblindness,andthattheoperationssubservedbyeachregionneednotdependonvisualinputtobesolicitedbyagiventask. Althoughmanyhighertiervisualareasseemtohavepreservedtherefunctionalspecializationfollowingblindness,itisstillundeterminedhowthenon-visualinputreachesoccipitalcortex.Twoobviouspossibilitiesareeitherviaalreadyexistingconnectionsorthroughtheestablishmentofnewconnectionsnotpresentinsightedindividuals.Theformercouldresultfromtheunmaskingorstrengtheningoflatentpre-existingpathwaysbetweensensory-specificcorticesand/orbetweenmultisensoryareasandoccipitalcortex.Thelatter,however,appearsunlikelyforatleasttworeasons.Thefirst,asdiscussedlateron,stemsfromagrowingbodyofevidencedemonstratingthatcrossmodalrecruitmentofoccipitalcortexispossibleinnormalsightedindividualsafterbrieftransientperiodsofvisualdeprivation,whichsuggeststhatalreadyexistingintermodalconnectionsareatplay[seereviewsonpotentialmultisensorypathwaysbySchroederetal.(2003);Cappeetal.(2009)].Thesecond,resultsfromanimalworkinvestigatingthedevelopmentalsynapticpruningperiodinearlyinfancy.Ithasbeenshownthatcorticocorticalprojectionsfromauditorytovisualcortexarepresentininfantkittensonlytobesoonafterprunedawayduetocompetitiveprocesses(InnocentiandClarke,1984;Innocentietal.,1988).However,inkittensdeprivedofvisionatbirth,theseextrinsicconnectionstotheoccipitalcortexseemtoremain(Berman,1991;Yakaetal.,1999).Thesefindingsrathersuggestthatitisthestrengtheningofnormallytransientintermodalconnections,andnottheformationofnewconnectionsfollowingblindness,thatislikelytoprovidethesubstrateforthecrossmodalinnervationofoccipitalcortexfollowingearlyblindness. Researchwithanimalmodelsofblindnesshasillustratedseveralsuchpathwaysthatcouldpotentiallymediatethecrossmodalprocessingofsoundinblindness.Forinstance,studieswithblindrodentshaveshowntheexistenceofconnectionsbetweentheinferiorcolliculus(animportantauditoryrelay)andthelateralgeniculatenucleus(LGN—animportantvisualrelay)(DoronandWollberg,1994;Izraelietal.,2002),suggestingthatauditoryinformationmayreachtheoccipitalcortexviatheopticradiationsascendingfromtheLGN.Alternatively,auditoryinformationcouldbefedviadirectconnectionsbetweenthemedialgeniculatenucleus(MGN—animportantauditoryrelay)andtheoccipitalcortex(Laemleetal.,2006).Furthermore,Karlenetal.(2006)haveshownthattheoccipitalcortexofCBoppossumsreceivesprojectionsfromnotonlytheauditory(MGN),butalsofromthesomatosensory(ventralposterior)nucleusofthethalamus,thussuggestingapossibleroutefortactileinformationtobeconveyedtowardtheoccipitalcortex.Morerecently,thefindingsofLaraméeetal.(2011)suggestthatcorticocorticalpathwayscouldalsomediatethecrossmodalinputintodeafferentedvisualareasbyshowingindirectconnectionsbetweentheprimaryauditoryandtheprimaryvisualcortexinvisuallydeprivedmice. AnatomicaltracerstudiesinnormallyseeingprimateshaveshowntheexistenceofdirectconnectionsgoingfromcaudalauditoryareastoperipheralV1/V2(Falchieretal.,2002;RocklandandOjima,2003),suggestingthatthenecessarypathwaystomediatecrossmodalplasticitylikelyexistpriortovisualdeprivation.Evidenceinhumansisalittlesparser,butseveralrecentfindingsalsosupportcorticocorticalpathwaysbetweenauditoryandvisualareasasalikelysourceforstreamingauditoryinputintotheoccipitalcortex.Forinstance,arecentdiffusiontensorimaging(DTI)tractographystudyinnormalseeinghumanshasrevealedtheexistenceofconnectionsbetweenHeschl'sgyrusandthecalcarinesulcus(Beeretal.,2011).Whetherthispathwayisdifferentinblindindividualshasyettobeestablished,althoughitperhapsneednotbetosubservethecrossmodalrecruitmentofvisualareasbysound.Moreover,apairofrecentstudiesuseddynamiccausalmodeling(DCM)toinvestigatetheeffectiveconnectivitybetweenregionsunderlyingauditoryactivationsintheprimaryvisualcortexofEBindividuals.DCMisapowerfulhypothesis-driventoolthatallowsforinferencesonthecausalitybetweentheactivityobservedindifferentbrainareasand,analogously,tostudyhowinformationflowsinthebrain(Fristonetal.,2003).Itwasfoundthatauditory-drivenactivityinV1isbestexplainedbydirectconnectionswithA1(Collignonetal.,2013)andthattheconnectivitybetweenbothstructureswasstrongerintheblindcomparedtosightedindividuals(Klingeetal.,2010).Afinalargumentinfavorofcorticocorticalpathwaysunderlyingauditoryrecruitmentofoccipitalareasstemsfromneuroanatomicalinvestigationsshowingtheopticradiations(geniculocorticaltracts)ofEBhumanstobeseverelyatrophied(Noppeneyetal.,2005;Shimonyetal.,2006;Panetal.,2007;Parketal.,2007;Ptitoetal.,2008),renderingthemunlikelycandidatesforrelayingauditoryinformationtovisuallydeafferentedcorticalareas. CrossmodalPlasticityinBlindness:BoundedbyCriticalorSensitivePeriods? Sofaronlyresearchfindingsrelatingtoearlyorcongenitalblindnesshavebeencovered(seeBox1),moreorlessignoringthenotionofcriticalperiods.Thisispartlyduetothefactthatmostresearchhasprimarilyfocusedontheeffectsofearlyblindness,andalsobecause,thereislittleconsensusontheeffectsoflate-onsetvisualdeprivation.Thefollowingsectionsattempttodisentanglethedifferentfindingsrelatingtolateblindnessandtocontrastthemwiththoserelatingtoearlyblindness. OneofthefirstneuroimagingstudiestoinvestigatetheoccipitalbrainmetabolisminEBindividuals(Veraartetal.,1990)alsoexaminedagroupofLBindividuals.ItwasshownthatoccipitalfunctioninginLBwasdifferentfromthatofEB:whileEBwerefoundtohavehigheroccipitalglucosemetabolismrelativetosightedindividuals,LBshowedareduction.Thisfindingobviouslyservedasanearlyindicationthattheageofblindnessonsetwaspotentiallyadeterminingfactorinthechangesthatoccurinoccipitalcortexfollowingvisualdeprivation.Indeed,apairofearlyinvestigationsoftask-relatedactivationsshowedthatwhilecrossmodalrecruitmentwasobservedinEB,nosuchobservationwasmadeinLB(Cohenetal.,1999;Sadatoetal.,2002).Thisfindingsuggestedtheexistenceofastrictcriticalperiodforthedevelopmentofcrossmodalplasticitywithintheoccipitalcortex(14yearsofage:Cohenetal.,1999;16yearsofage:Sadatoetal.,2002),afterwhichnocrossmodalreorganizationwouldtakeplaceiftheonsetofblindnessoccurredbeyondthisperiod.However,findingsfromalargenumberofotherstudieshavesincechallengedthisview.Kujalaetal.(1997)firstsuggestedthepossibilityofcrossmodalreorganizationinLBindividualsbyshowingposteriorevent-relatedpotential(ERP)responsessimilartothoseobservedinEBwhentheyperformedsound-changedetectiontasks.Subsequently,aPETstudyrevealedactivationofvisualcortex,albeitmanifestingsomewhatdifferentpatterns,duringBraillereadingandauditorywordprocessinginbothEBandLBsubjects(Bücheletal.,1998).ThiswaslaterfollowedbyaseriesofstudiesbyBurtonetal.inwhichLBwereshowntoactivateoccipitalregionsinresponsetoavarietyoftactileandauditorytasks(Burtonetal.,2002a,b,2003,2004,2006;BurtonandMcLaren,2006).Similarly,severalauditoryspatialtaskselicitedoccipitalactivationsinlate-onsetblindindividuals(Vossetal.,2006,2008,2010).However,thesecrossmodalchangeswerenotaccompaniedbybehavioralenhancements,asisthecaseinEBindividuals,raisingquestionsconcerningthefunctionalrelevanceoftheobservedcrossmodalplasticityinLB. Despitesomeexceptions,therethusappearstobesomeagreementthatcrossmodalrecruitmentofdeafferentedvisualareasisnotexclusivetoEBandcanbeobservedincasesoflate-onsetblindnessaswell.Whilethisisthecase,thecrossmodalrecruitmentinLBappearstobenonethelessgenerallyreduced(bothintermsofintensityandspatialextent)relativetoEB,suggestingthatwhilethedevelopmentofcrossmodalplasticprocessesmightnotbeboundbyacriticalperiod,itisdefinitelymodulatedbyasensitiveperiodinearlydevelopmentduringwhichreorganizationislikelytobemorepronounced. CrossmodalChangesinSightedIndividuals Additionalevidencesupportingtheexistenceofadultcrossmodalplasticitystemsfromresearchinvestigatingtheeffectsoftemporaryvisualdeprivationinnormalsightedindividuals.Oneofthefirststudiestodocumentsucheffectsrevealedthatshort-termlightdeprivationenhancestheexcitabilityofvisualcortex.Indeed,abriefperiodofvisualdeprivationwasshowntonotonlyinduceareductionintheTMSthresholdsrequiredforelicitingphosphenesbutalsoleadtoanincreaseinvisualcortexactivationbyphoticstimulation(Boroojerdietal.,2000).Subsequently,usingapharmacologicalapproachincombinationwithTMS,itwasshownthatGABA,NMDA,andcholinergicreceptorslikelyplayanimportantroleinrapidexperience-dependentplasticityinvisualcortex,asadministeringappropriateagonists/antagonistseliminatedtheTMSphosphene-thresholddecreaseassociatedtotransientvisualdeprivation(Boroojerdietal.,2001). ThesefindingsweresoonfollowedbyresearchinspiredbyaschoolfortheblindinSpain,whichrequiredthatitsinstructorsexperiencedailylifewithoutsightforanentireweekduringtraining(Pascual-LeoneandHamilton,2001).Theinstructorsreportedhavingheightenedawarenessforsounds,beingabletobetterdistinguishdifferentspeakersandtobetterorientthemselvesinresponsetoincomingsounds.Tofollowuponthesereports,Pascual-LeoneandHamilton(2001)developedaprotocolinwhichsightedvolunteerswouldbeblindfoldedfor5days.PreliminaryfindingsrevealedanincreaseinBOLDsignalwithintheoccipitalcortexinresponsetotactilestimulationafter5daysofcompletevisualdeprivation,andthatthisincreasewasnolongerpresentthedayfollowingblindfoldremoval.Thesefindingsindicatedthatrapidcrossmodalchangescanoccurintheoccipitalcortexofadultswhentemporarilydeprivedofvision,andwerefurtherdocumentedinMerabetetal.(2008).Remarkably,suchcrossmodaldeprivation-relatedeffectswerelimitedtotheblindfoldingperiodandwererapidlyreversible. Subsequentworkhasimpressivelyshownthatveryshorttimeperiodsofvisualdeprivationaresufficienttoinducemarkedcrossmodalchangesinoccipitalcortex.Forinstance,Weisseretal.(2005)demonstratedthat2hofvisualdeprivationwasenoughtoinducetheneuralchangesfortheprocessingoftactileshapeswithintheoccipitalcortexofnormallysightedindividuals.Inarecentstudy,weusedanoveltechniquetodeterminewhetheroccipitalcortexprocessesauditoryinputinasimilarmannertoauditorycortex(Lazzounietal.,2012).Wedevelopedablindfoldingprotocoltoassesstheeffectsofshort-termvisualdeprivationontheauditorysteadystateresponse(ASSR).TheASSRcanbedefinedasanelectrophysiologicalresponsetorapidlychangingauditorystimuli,whereneuronalpopulationsrespondatthesamefrequencyasthemodulationrateofanamplitude-modulated(AM)toneand,importantly,forwhichthesourcesoftheactivitycanbeextractedusingdipoleanalyses.TheASSRthereforeconstitutesapowerfultoolasitevokesaresponsethatisintrinsicallylinkedtothestimulusandcanbetrackedwithinthebrain.Theresultsshowedthatthetwospectralpeaksassociatedwiththemodulationratesoftwodichoticallypresentedstimuli(39and41Hz)wereobservedonlywithinauditorycortexpriortoblindfolding.Following6hofvisualdeprivation,however,twopeakswerealsoobservedinoccipitalcortex(seeFigure2),thussheddinglightonthetimelineassociatedwithshort-termcrossmodalrecruitmentofinput-deprivedsensorycortices.Thisfindingalsodemonstratesthatvisualcortexcandisplayauditorycortex-likefunctioninginresponsetoauditoryinputduringperiodsofdeprivation. FIGURE2 Figure2.Crossmodalplasticityintemporarilydeprivedsightedindividuals.ThisfigureportraysarecentMEGfindingthattestifiestotheimpressivespeedatwhichthevisualcortexcandisplayauditorycortex-likefunctioningfollowingashortperiodofvisualdeprivation.Theleftgraphshowsthatpriortoblindfoldingthetwospectralpeaks(lefttemporalinred;righttemporalingreen)associatedwithmodulationrateoftheauditorystimulipresentedtobothears(39and41Hz)areclearlyrestrictedtothetemporalelectrodes(auditorycortex).However,asshownintherightgraph,thesamepeakscannowbefoundinvisualcortex(purplepeaks)followinga6hvisualdeprivationperiod.AdaptedwithpermissionfromLazzounietal.(2012). CrossmodalPlasticity:Early-vs.Late-OnsetBlindness Theprevioussectionsdocumentedmultipledemonstrationsofthecrossmodalprocessingthatoccursinthematureoccipitalcortex.However,animportantquestiontoaskconcernswhethertheplasticityobservedintheadultbrainissimilartowhatisobservedinthevisuallydeprivedimmaturebrain.AsidefromthetypicalobservationofreducedcrossmodalrecruitmentinLB(withtheexceptionofBücheletal.(1998)whoreportedgreateractivationinLB),thefollowingsectionswillhighlightfourmajordistinctionsbetweenthecrossmodalchangesobservedforearlyandlateonsetblindnessthatarguefortheexistenceofimportantunderlyingfunctionaldifferencesbetweenthetwo(seealsoFigure3).Indeedthesefindingspointnotonlytoquantitativedifferences(i.e.,theamountofcrossmodalrecruitmentobserved)betweenthecompensatoryreorganizationthatoccursfollowingearlyandlateonsetblindness,butalsotoqualitativeonesrelatingto,forinstance,theunderlyingmechanismsofcrossmodalrecruitmentanditsfunctionalrelevancetobehavior. FIGURE3 Figure3.Howearlyandlateblinddiffer.Illustratedherearetwoexamplesofhowthecrossmodalplasticityobservedinearlyandlateblindindividualsdiffers.Thetoprow(panelA)illustratesthedifferentialeffectTMShaswhenappliedovertheoccipitalcortex(blackbars)ofLB(firstbargraph)andEB(secondbargraph)ontheirperformanceinaBrailletask,whereonlytheearlyblindshowedanincreaseinerrorrate(Cohenetal.,1999).Thebottomrow(panelB)consistsinaschematicrepresentationofhowauditoryinformationflowstowardV1inthecongenitallyblindandlateblind,illustratingtheDCMfindingsofCollignonetal.(2013).AdaptedwithpermissionfromCohenetal.(1999)andCollignonetal.(2013).*p<0.001. Functionalrelevanceofcrossmodalprocessing Ashighlightedabove,thereisanabundanceofevidencedemonstratingthefunctionalrelevanceofthecrossmodalrecruitmentofoccipitalareasinEB.Severalstudieshaveshowedstrongcorrelationsbetweenbehavioralperformanceandoccipitalactivity(Amedietal.,2003;Gougouxetal.,2005;Razetal.,2005),whereasothershaveshownthatthetemporary(Cohenetal.,1997;Amedietal.,2004;Collignonetal.,2007)andpermanent(Hamiltonetal.,2000)dysfunctionofoccipitalneuronsinterfereswithperformanceinnon-visualtasks.Interestingly,thereislittletonoevidenceofthisinLB.ThisislikelyinpartduetothelimitedevidenceofenhancedperceptualabilitiesinLB,astheyareoftenfoundtobeindistinguishablefromsightedindividualsintermsofperformance.TheobservedcrossmodalrecruitmentinLBthereforeseeminglydoesn'tleadtoanybehavioralgainasitdoesintheEB.ThisassumptionissupportedbydataprovidedbyCohenetal.(1999),whereperformanceonaBraillereadingtaskwasunaffectedinLBbytheapplicationofTMSoveroccipitalcortex,whereasitreducedperformanceinEB.WhilethereareafewexceptionswhereLBhavedemonstratedheightenedperceptualabilitiescomparedtosightedindividuals(e.g.,Vossetal.,2004),suchinstanceshavegenerallynotbeenassociatedwithincreasedcrossmodalplasticity.Indeed,severalotherfactorscouldexplainincreasedperformance(e.g.,training,experience)withouttheinvolvementofoccipitalregions. Onepreviouslyproposedhypothesistoexplainoccipitalactivationsobservedinthelate-blindstatedthattheymightbetheresultofmentalimageryprocesses.ItwasreportedbyBücheletal.(1998)thattheirLBsubjectsimmediatelytransformedtactileandauditorycuesintoavisualrepresentation,implyingthatanyoccipitalactivationcouldbedueto“visualization”ofthetask.Whilesuchvisualimageryprocesseshavebeenshowntoactivatecomponentsofthevisualsysteminnormalsightedindividuals(Kosslynetal.,1995),morerecentparadigms,however,haveshownthatoccipitalrecruitmentnecessitatesmoreactivetasksthatexplicitlyrequiresubjectstousevisualimagery(Kosslynetal.,2001).Moreover,thevisualimageryhypothesislosestractionwhenconsideringthatoccipitalrecruitmentisseldomobservedinthesightedwhenperformingnon-visualtasksthatarealsoperformedbytheblind.ThiswouldimplythattheunlikelyscenariowhereLBresorttovisualimageryandnotsightedindividualstakesplace.Infact,itisoftenreportedthatwhensightedindividualsperformnon-visualtasks,cross-modalinhibitorymechanismsareengaged(e.g.,occipitaldeactivationisobserved)toreducethefunctioningofcorticessubservingtheunattended(andpotentiallydistracting)visualmodality(e.g.,Laurientietal.,2002;Gougouxetal.,2005). Attentionalmechanisms/processes OneexceptionthathaslinkedsuperiorperformanceinLBtobrainchangeshasdonesousinganauditoryspatialchange-detectiontaskandERPmeasurements(Fiegeretal.,2006).LBparticipantsweresignificantlymoreaccuratethansightedparticipantsatlocalizing/detectingdeviantauditorystimuliinperipheralauditoryspace(performanceforbothgroupswasidenticalforcentralauditorypositions).ThiswasalsoataskforwhichtheCBhadbeenshownpreviouslytoexcelat(Röderetal.,1999),andimportantdifferenceswereobservedwhencomparingtheERPresultsfrombothstudies.TheN1ERPcomponentdisplayedamoresharplytunedspatialgradientduringperipheralattentioninCBthaninthesightedgroup,whereastheP3componentwasidenticalinbothgroups(Röderetal.,1999).Conversely,theearlyN1amplitudetoperipheralstandardstimulidisplayednosignificantspatialtuningineithertheLBorthesightedcontrols,whereastheamplitudeofthelaterP3elicitedbytargets/deviantsdisplayedamoresharplytunedspatialgradientduringperipheralattentioninLBcomparedtocontrols(Fiegeretal.,2006).Assuch,itappearsthatCBpersonspossessamoresharplytunedearlyattentionalfiltering,manifestedintheN1component,whileLBshowsuperiorityatdeployinglateattentionalprocessesoftargetdiscriminationandrecognition,indexedbytheP3component.ThesefindingsthereforestronglysuggestthatevenwhenbothCBandLBindividualsshowabehavioraladvantageoversightedsubjectsonagiventask,theseenhancementsarepotentiallymediatedbydifferentunderlyingcerebralmechanisms. Sourceofauditoryinputintotheoccipitalcortex Thepotentialroleplayedbycorticocorticalconnectionsinmediatingthecrossmodalrecruitmentofoccipitalcortexwasspecificallyunderlinedinprevioussections.Forinstance,aDTItractographyanalysishasshowntheexistenceofdirectconnectionsbetweenprimaryauditoryandvisualareasinnormalseeingindividuals(Beeretal.,2011),whereastheuseofDCMenabledresearcherstoestablishthatthefunctionalconnectivitybetweenbothstructuresisstrongerinEBthaninsightedindividuals(Klingeetal.,2010).ToaddressesthepossibledifferencesbetweenEBandLBindividuals,wehaverecentlyshownthattheflowofauditoryinformationintotheoccipitalcortexmightbemediatedbyadifferentpathwayinLBusingDCManalyses(Collignonetal.,2013).Sinceitwasrecentlydemonstrated,usingDCM,thatcrossmodalplasticityobservedinCBindividualsismorelikelytobesupportedbycorticocorticalconnectionsratherthanthalamocorticalconnections(Klingeetal.,2010),weincludedonlycorticocorticalconnectionsinourmodels.OurfindingsindicatedthattheauditoryactivityobservedinoccipitalcortexofCBindividualswasbestexplainedbydirectfeed-forwardconnectionsfromprimaryauditorytoprimaryvisualcortex,whereasinLB,auditoryinformationappearstorelymoreonanindirectfeedbackrouteusingparietalregionsasarelaybetweenbothprimarysensoryareas(Collignonetal.,2013).ThisstronglysuggeststhatthecrossmodalrecruitmentofvisuallydeafferentedareasislikelymediatedbydifferentpathwaysinEBandLB. Indeed,itishighlylikelythatEBindividualshaveaccesstodifferentpathwaysgiventheexcessiveconnectivitybetweenregionsinearlydevelopment.Indeed,thesynapticdensityofvisualcortexreacheslevelsgreaterthanthatofadultsinearlyinfancythroughsynaptogeneticprocesses,andthengraduallydecreasestoadultlevelsbyapproximately5yearsofagethroughthepruningofexuberantconnections(Johnson,1997),aprocessthatisinterruptedbyvisualdeprivation(StrykerandHarris,1986).Moreover,ashighlightedabove,theexistenceofsuchcorticocorticalconnectionsbetweenauditoryandvisualareashasbeenshowninyounginfantanimals,onlyforthemajorityoftheseconnectionstobeprunedawayduringnormaldevelopment(InnocentiandClarke,1984;Innocentietal.,1988).Whethersimilarcorticocorticalconnectionsarealsomoreprominentduringearlydevelopmentinhumansisunclear,butifpresent,EBmayutilizeandstrengthenthesenormallytransientexuberantconnectionstocompensateforthelossofsightthroughexperience-dependentstabilizationprocesses,whereasLBmustrelyonconnectionsthatdevelopwithinthenormalvisualbrain. Preservedfunctionalspecialization Morerecentresearchhasbeguntoexaminewhetherthecrossmodaltakeoverofoccipitalcortexduetoblindnessfollowssomesortoforganizationalprinciple.Therearenowseverallinesofevidencestemmingfromneuroimagingstudies[reviewedinVossandZatorre(2012)]thatillustratehowthepre-existingfunctionalspecializationofspecificcorticalregionsappearstobepreservedfollowingvisualdeprivation.Asdiscussedearlier,awelldocumentedexampleofthisconcernstheLOC,notablyinvolvedinobject/formrecognitionprocesses.Amedietal.(2007,2010)haveshownonmultipleoccasionsthatthisregionisalsorecruitedbyauditoryandtactileformrecognitiontasksinEBindividuals.Similarly,thevisualmotionprocessingcenter(areaMT)hasbeenshowntoberecruitedbybothtactile(Ricciardietal.,2007)andauditory(Poirieretal.,2006)motionstimuli.Bothoftheseexamplesconvincinglysuggestthatvisualdeprivationdoesnotalterthespecializedmodularorganizationofthevisuallydeafferentedoccipitalareasofthebrain,andthattheoperationssubservedbyeachregionneednotdependonvisualinputtobesolicitedbyagiventask.Importantly,withrespecttotheobjectivesofthispaper,tworecentinvestigationshavecomparativelyinvestigatedthistopicinbothCBandLBindividuals.First,wehaverecentlyshownthatwhilebothrecruitoccipitalregionsforsoundprocessing,thepreferentialactivationoftherightdorsalstreamforthespatialprocessingofsounds(comparedtospectralprocessingofsounds)wasonlyobservedinCB(Collignonetal.,2013).Thissuggeststhattheseoccipitalregionsmaintainafunctionalspecializationforspatialprocessinginothersensesonlyifvisionislostearlyinlife.AsecondexamplesupportingsuchaclaimwasprovidedbyBednyetal.(2012)whoinvestigatedtheroleofthevisualcortexinlanguageprocessinginbothCBandLBindividuals.Again,whiletheyobservedthatoccipitalcortexwasrecruitedbygeneralauditoryinputinbothgroups,apreferentialresponsetospeechstimuliinthelefthemisphere(comparedtonon-speech)wasonlyobservedinCB,suggestingthatearlyvisualexperiencemightbedetrimentaltotheoccipitalcortexacquiringaroleinlanguageprocessingfollowingblindness. Theabove-mentionedpointsraiseinterestingquestionsconcerningtheroleplayedbysensitive/criticalperiods.WhilethegeneralobservationofcrossmodalrecruitmentinLBindividualssuggeststhatitissubjecttotheinfluenceofasensitiveperiod,thehighlighteddifferencesindicatethatdifferentprocessesmightbemediatingtheobservedcrossmodalrecruitmentinbothearlyandLBindividuals.Ifthisisindeedthecase,itrathersuggeststhatcriticalperiodsmayplayaroleafterall,withperhapsvaryingcutoffpointswithregardstothedifferentprocessesinplay.Consequently,futureworkwouldbenefitfromattemptingtotargettheseissuesbyrelatingtheageofblindnessonsetwiththedevelopmentofspecificparticularitiesthatsofarhaveonlybeenobservedinearlyblindness(e.g.,functionalrelevanceofrecruitment,corticocorticalconnectivity). ImplicationsforSightRestoration Whathappenstotheabilityofthe“visual”braintoprocessvisualinformationonceit“goesauditory?”Suchaquestionhasimportantrepercussionswhenconsideringthepotentialoutcomesofsightrestorationproceduresandprostheses.Overthreecenturiesago,theIrishphilosopherWilliamMolyneuxposedananalogousquestiontooneofhiscontemporaries,JohnLocke,onhowlongtermblindnesswouldaffectone'sabilitytoseeshouldsightberestored(Degenaar,1996):“Supposeamanbornblind,andnowadult,andthentaughtbyhistouchtodistinguishbetweenacubeandasphereofthesamemetal,andthesamebigness,soastotell,whenhefeltoneandtheother,whichisthecube,whichisthesphere.Supposethen,thecubeandthesphereplacedonatable,andtheblindmantobemadetosee.Query,whetherbysight,beforehetouchedthem,hecoulddistinguish,andtell,whichistheglobe,whichisthecube?”Whilethismatterhassincebeendebatedfordecadesonendbetweenvarioushistoricalfigures,therehavebeenseveralcasestudiesthathaveprovidedsomeinsightintothematter,demonstratingforinstancethatvisualacuityisseverelyreducedaftercataractremovalsurgeryfollowingprolongedperiodsofdeprivation(vonSenden,1960;GregoryandWallace,1963;Fineetal.,2003).Additionally,recentneuroimagingdataallowsfortheinvestigationofpotentialunderlyingmechanisms.Asalreadynoted,thevisualbraingoesthroughdrasticchangesthatmightsignificantlyalteranindividuals'abilitytoprocessvisualinformationshouldsightberestored.Thenextsectionwill,however,firstexamineresearchwithdeafindividuals,astechnologicaladvancesforrestoringhearinginprofoundlydeafindividualshaveachievedafairdealofsuccesswiththedevelopmentofsophisticatedcochlearimplants(CI).SuchprogresshasallowedresearcherstoascertaintheconsequencesofcrossmodalplasticityinthedeafpopulationonthesuccessrateofCIs,andwillthereforeprovideinsightintohowtoapproachthesameissuesinblindness. InsightsfromtheDeaf Oncetheyhavebecomeresponsivetoanewinputmodality,cantheauditorycorticesstillprocesstotheiroriginalsourceofinput?Thisquestionbearsspecialimportancegiventhatprofounddeafnesscansometimesbereversedbyauditorystimulationviaacochlearimplant(CI)(Pontonetal.,1996).Putsimply,thedevicereplacesnormalcochlearfunctionbyconvertingauditorysignalsintoelectricalimpulsesdeliveredtotheauditorynerve(seeMens,2007forfurtherdetails).Severalstudieshaveshowntheexistenceofacriticalperiodthatcannotbeexceededforrecoveryofauditoryfunctionsfollowingauraldeprivation(Kraletal.,2005;Sharmaetal.,2005).Thistimewindowisgenerallylimitedtothefirstfewyearsoflife,withevidencesuggestingthatifimplantedbeforetheageof2,childrencanacquirespokenlanguageinacomparabletime-frametonormalhearingchildren(WaltzmanandCohen,1998;Hammesetal.,2002). Althoughitwasinitiallythoughtthatthedurationofauditorydeprivationshouldaccountformostofthevarianceoftheimplantationoutcome,severallinesofevidenceclearlysuggestothermodulatingfactors(O'Donoghueetal.,2000;Leeetal.,2001;Sarantetal.,2001).Infact,aretrospectivecasereviewshowedthatthedurationofdeprivationonlyaccountedfor9%ofthevariabilityinimplantoutcome(Greenetal.,2007).Analternatepredictorcanbefound,forinstance,inpreoperativemeasuresofcerebralmetabolism.Leeetal.(2001)forinstance,showedthatthetemporalcortexbecomeshypometabolicfollowingauditorydeprivation,andthatthelevelofhypometabolismiscorrelatedtospeechcomprehensionscoresobtainedpost-implantation.Inotherwords,thelongerapersonhasbeendeaf,thelesslikelyitisthattheirtemporalcortexwillbehypometabolicandthemorelikelytheirspeechperceptioncapacitywillbecompromised.Inthesamevein,itwaslatershownthatspeechperceptionperformancewasnegativelyassociatedwithactivityinoccipito-temporalnetworks(Leeetal.,2005),evenwhenfactoringouttheconfoundingeffectofageofimplantation(Leeetal.,2007).Furthermore,otherimportantprocessesmaybealsoatplay,suchasthelevelofcrossmodalreorganizationoftheauditorycortex(seeGiraudandLee,2007).Forinstance,onestudycomparedcorticalevokedpotentialsinvolvedintheprocessingofvisualstimuliinimplantedsubjects(Doucetetal.,2006).Afterevaluatingthespeechperceptionabilitiesoftheimplantedsubjects,theyweresubsequentlydividedintotwogroupsbasedontheirperformance.Itturnedoutthatthegroupwiththepoorestperformersforspeechperceptionwasalsotheonewhereimplantedindividualsshowedbroaderandmoreanteriorscalpdistributionswhenprocessingvisualstimuli(i.e.,likelytheresultofcrossmodalprocessingofthevisualstimuliintemporalauditoryareas),andvice-versa.Itthusappearsthatseveralinteractingfactorsinfluencetheoutcomeofcochlearimplantation,ofwhichimportantlyiscrossmodalreorganization.Awarenessofthisimportantfactwillevidentlyhaveanimportantimpactonhowsimilarconcernswillbeaddressedinblindness. IstheVisualSystemStillVisualFollowingBlindness? Knowingwhethercrossmodalplasticchangesarereversibleiscrucialtotheproperdevelopmentofneuroprosthesesdesignedtorestorevisioninblindindividuals.Althoughsignificantprogresshasbeenmadetowardachievingsuchagoal,futureresearchisextremelydependantonourunderstandingofhowblindnessaffectsthebrain,andonhowtheseeffectsaredrivenormodulatedbytheageofblindnessonset.Indeed,thebrainofaLBindividualmaybemoreapttoprocessvisualinputfollowingaprolongedperiodofvisualdeprivation,whereasthebrainofanEBindividualhaslikelyunderwentpermanentplasticchangesrenderingitunabletoprocessvisualinformation.Forinstance,thefindingthattheoptictractsandradiationsareatrophiedinEB(Noppeneyetal.,2005;Shimonyetal.,2006;Panetal.,2007;Parketal.,2007;Ptitoetal.,2008)raisesseriousquestionsabouttheintegrityofthepathwaysandwhetherornottheycouldconveyelectricalinformationstemmingfromretinal,subretinal,orepiretinalimplants(seeMerabetetal.,2005),oreventransmitretinalimagesobtainedfollowingcataractremovalinindividualswithcongenitalcataracts.Furthermore,thenumerousreportsofsignificantreductionofcorticalgraymatterinoccipitalcortexraisesseriousquestionsregardingthearea'sabilitytoprocessvisualinput(Panetal.,2007;Ptitoetal.,2008;Leporeetal.,2010).AcompensatoryapproachmorelikelytoprovideasuccessfuloutcomeinEBistheuseofsensory-substitutiondevices,whereonesensorymodalityisusedtosupplyinformationnormallygatheredbythedeprivedsense.PerhapsthemostwellknownexampleofthisisBraille,whichofcoursehasbeenhighlysuccessfulinprovidinginformationnormallyacquiredthroughvision(e.g.,readingmaterial)viathetactilemodality.Severalmoresophisticateddevices-thattransformvisualinformationcapturedviacamerasintospatiallyrelevanttactileorauditorystimulation-havesincebeenimplemented(Meijer,1992;Bach-y-Ritaetal.,1998;Capelleetal.,1998)andhaveallowedblindindividuals“tosee”complextwo-dimensionalobjectsandshapes(e.g.,Arnoetal.,1999;RenierandDeVolder,2010),andmorerecentlytoevennavigatearoundobstaclesinahighlycontrolledenvironment(Chebatetal.,2011).Whilethesedevicesarenotatapointwheretheycanbereliedupontosuccessfullynavigateintherealworld,theyprovidenonethelessaverypromisingavenueforfutureresearchdesignedtoaidvisuallydeprivedindividuals. Visualrestoration,however,mightstillbepossibleforLBindividuals.Forinstance,Panetal.(2007)showedthatwhitematter(WM)lossintheoptictractandradiationofEBindividualswasmodulatedbytheageofblindnessonset,suggestingthatalateronsetwouldhavelesseffectontheanatomicalintegrityofthevisualpathways.Moreover,Schothetal.(2006)foundnoevidenceofWMlossineithervisualcortexorinvisualtractsinsubjectsthatcouldbecategorizedasLB(withameanageofblindnessonsetoftwelve),suggestingthatthevisualpathwaysmaystillbeabletocommunicatesignalstowardoccipitalcortex.Consequently,approachesthatinvolvecataractremovalandretinalimplantsarelikelytobeconsiderablymoreviableinindividualsthatbenefittedfromthenormaldevelopmentofthevisualsystem. FutureConsiderations Giventheinfluenceearlydevelopmenthasontheemergenceofcrossmodalplasticphenomenainblindindividuals,whatstepsneedtobetakentofurtherourunderstandingofthedifferentprocessesatplay?Acrucialfirststepwillbetoaddressinconsistenciesacrosstheliteratureregardinghowblindindividualsaresegregatedintodifferentgroupsbasedontheirageattheonsetofblindness(e.g.,EBandLBindividuals).Thissegregationisoftendoneinaveryarbitrarymanner,asveryfewstudiesusethesamedefinitionstoclassifyandcircumscribeearlyandlateonsetblindgroups,andinfactoccasionallyoverlapacrosspublishedreports.Thisisofcoursequitetroublesomewhenwantingtocomparefindingsacrossstudies,andwillrequiregreatercareandcooperationbetweenresearchgroupsinorderforfutureworktoyieldfruitfulresults. AsfirsthighlightedinBox1,thecurrentlackofuniformityacrossstudiesindefiningtherangeofonsetsofblindnessforEBandLBgroupshasyieldedatleasttwosubstantialissues.Thefirstrelatestotheoftennon-inclusionofalargegroupofblindindividualswithagesofblindnessonsetsthatliebetweenchosencut-offsforbothforearlyandlateonsetblindgroups.Thispracticenotonlyintroducesastrongsamplingbias,butalsoremovespotentiallyimportantdatawheninvestigatingblindness-inducedcrossmodalplasticity.Indeed,importantdevelopmentalsensitiveperiodsmaytakeplaceduringthisgapintheagesofonset.Theadditionofoneormoredistinctblindgroupscoveringthisgapcouldhelpalleviatethelossofpotentiallyimportantinformation.Inthisvein,Lietal.(2013)veryrecentlyaddressedthisissuebydefiningfourdistinctgroupsininvestigatingbrainanatomicalconnectivitynetworks:CB,EB(onsetafterbirthbutpriortotheageof12),adolescentblind(onsetbetween12and15yearsofageinclusively)andLB(onsetafter15yearsofage).Whilethechosenrangescouldbedebated,thisnonethelessrepresentsanimportantfirststepindirectingfutureresearch.ThisworkalsohighlightsthefactthatitmightalsobewisetodivideCBandEBindividualsintoseparategroups(whichseveralgroupshavestarteddoing),asevenafewyearsofvisualexperiencecouldhaveasignificantimpactonthefunctionalarchitectureofthevisualsystemandonthemanneritiscrossmodallyrecruitedfollowingblindness.Indeedtheuseofacontinuumofonsetsofblindnesswillbetterallowforthedirectinvestigationofthedevelopmentaltime-courseofprocessesthatgoverntheemergenceofcrossmodalplasticity. Thesecond,potentiallymoreseriousissuearisingfromtheinconsistentdefinitions,concernstheoftenoverlappingofgroupsacrossdifferentstudies;i.e.,agivenblindindividualcouldbecategorizedasanEBindividualinonestudyandasaLBindividual.Forinstance,Burtonetal.(2002b,2003,2004,2006)haveoftenconsideredindividualswithonsetsofblindnessoccurringaftertheageof7asaLBindividual;sohasFiegeretal.(2006)andBednyetal.(2012)forindividualswithonsetsoccurringaftertheageofthe9.Thisisinstarkcontrastwithotherreportsthathaveconsideredindividualswithanonsetoccurringpriorto13yearsofageasEB(e.g.,Cohenetal.,1999;Sadatoetal.,2002;Vossetal.,2008).Thisisaclearindicationthatgreatereffortandcareshouldbeputintohomogenizingblindgroupdefinitionsinordertobetterunderstandtheeffectssensitiveandcriticalperiodsinsensorydeprivation. Lastly,theabove-mentionedconcernscouldalsobesignificantlyalleviatedbysimplymovingawayfromcreatinggroupsaltogether.Certainly,itcouldbearguedthatweshouldbelookingtousetheageofblindnessonsetmoreasacontinuousvariableandsearchfornon-linearitiesintheresultingfunctionslinkingtheageofonsetwithvariousdependantvariables,whichwouldbeindicativeofsuddenchangesintheoccurrenceofcrossmodalplasticityandpossiblyresultingfromimportantcriticalorsensitiveperiods.Forinstance,ifcrossmodalplasticitychangesonlyquantitativelyovertime,thantherelationshipbetweentheageofblindnessonsetandvariousdependantvariableswouldbealinearone.However,asdiscussedabove,thereareseverallinesofworksuggestingthatthecrossmodalplasticprocessalsoundergoessomequalitativechangeswithlateronsets,suggestingthattherelationshipcouldinfactbenon-linear.Suchanapproachwouldhavemultiplebenefits,perhapsnonegreaterthantheremovalofthegroupdefinitionswhichareoftenhighlyarbitraryandthecauseofdiscrepanciesbetweenstudies.Moreover,treatingtheageofblindnessonsetasacontinuousvariableshouldallowfortheextractionofimportanttime-pointsduringthedevelopmentofcrossmodalplasticphenomenainadata-drivenway,ratherthanbytheuseofa-prioridefinitionsofparticularsubgroupsbasedontheageatblindnessonset. 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Editedby:VirginiaPenhune,ConcordiaUniversity,Canada Reviewedby:CatherineY.Wan,BethIsraelDeaconessMedicalCenterandHarvardMedicalSchool,USAHaroldBurton,WashingtonUniversitySchoolofMedicine,USA Copyright©2013Voss.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense(CCBY).Theuse,distributionorreproductioninotherforumsispermitted,providedtheoriginalauthor(s)orlicensorarecreditedandthattheoriginalpublicationinthisjournaliscited,inaccordancewithacceptedacademicpractice.Nouse,distributionorreproductionispermittedwhichdoesnotcomplywiththeseterms. *Correspondence:PatriceVoss,Neuropsychology/CognitiveNeuroscienceUnit,MontrealNeurologicalInstitute,McGillUniversity,Room276,3801UniversityStreet,Montreal,QCH3A2B4,Canadae-mail:[email protected] COMMENTARY ORIGINALARTICLE Peoplealsolookedat SuggestaResearchTopic>