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Environmental Enrichment as an Effective Treatment for Environmental Enrichment as an Effective Treatment for

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Environmental Enrichment as an Effective Treatment for - PPT Presentation

Woo and Michael Leon University of California Irvine Enriched sensorimotor environments enable rodents to compensate for a wide range of neurological challenges including those induced in animal models of autism Given the sensorimotor deficits in mo ID: 83628

Woo and Michael Leon

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EnvironmentalEnrichmentasanEffectiveTreatmentforAutism:ARandomizedControlledTrialCynthiaC.WooandMichaelLeonUniversityofCaliforniaIrvineEnrichedsensorimotorenvironmentsenablerodentstocompensateforawiderangeofneurologicalchallenges,includingthoseinducedinanimalmodelsofautism.Giventhesensorimotordeficitsinmostchildrenwithautism,weattemptedtotranslatethatapproachtotheirtreatment.Inarandomizedcontrolledtrial,3–12year-oldchildrenwithautismwereassignedtoeitherasensorimotorenrichmentgroup,whichreceiveddailyolfactory/tactilestimulationalongwithexercisesthatstimulatedotherpaired CynthiaC.WooandMichaelLeon,DepartmentofNeurobiologyand Jaber,2008;Nithianantharajah&Hannan,2006;Pang&Hannan,2013).Inanimalmodels,enrichedsensorimotorexperiencealsoamelioratesgeneticallybasedneurologicaldisorderssuchasDown’ssyndrome,Alzheimer’sdisease,Huntington’sdisease,Parkinson’sdisease,schizophrenia,andautism(Laviolaetal.,2008;Nithianantharajah&Hannan,2006;Pang&Hannan,2013).Inhumans,autismhasaclearbutcomplexgeneticbasis(Abra-hams&Geschwind,2008;Freitag,2007;Freitag,Staal,Klauck,Duketis,&Waltes,2010)andsomechildrenhaveautisticsymp-tomsthatareassociatedwithaknowngenemutationorchromo-somalaberration(Freitag,2007).Mousemodelshavebeengener-atedtomimicsomeofthesegeneticvariants(Ey,Leblond,&Bourgeron,2011)andasubsetofthesemousemodelsofautismhavehadtheirsymptomsreversedoramelioratedfollowingexpo-suretoanenrichedenvironment.Forexample,micehavebeengivenaMecp2(tm1Tam)-nullalleletomodelthegeneticabnormalityofRettsyndrome.Thisgeneticanomalyresultsinthedeteriorationofcognitiveandmotorskillsinearlychildhoodinhumans,similartosomebehavioralsymptomsseeninchildrenwithautism.Enrichedsensorimotorexperiencewasfoundtoimprovemotorcoordinationandanxiety-associatedtraitsinheterozygousMecp2mice(Kerr,Silva,Walz,&Young,2010;Kondoetal.,2008;Nagetal.,2009).Sensorimotorenrichmentforthesemiceproducedchangesinbothexcitatoryandinhibitorysynapticdensitiesincerebellumandcortex(Lonettietal.,2010).Additionally,itrestorednormallong-termpotentiationincortex,increasedcorticalBDNFlevels,improvedmemory,andalteredseveralsynapticmarkersinthesemice(Kerretal.,2010;Lonettietal.,2010).FragileXsyndrome,whichariseswithamutationofthegene,alsosharessymptomswithautism.Sensorimotorenrichmentsimilarlyrescues-knockoutmicefromcognitivedeficiencies(Restivoetal.,Potocki-Lupskisyndromeinvolvesthemicroduplicationofband11.2ontheshortarmofchromosome17and70–90%ofhumanswiththissyndromearediagnosedwithautism(Potockietal.,2007).Themousemodelofthissyndromehassocialabnormali-ties,abnormalultrasonicvocalizations,perseverativeandstereo-typicbehaviors,anxiety,deficitsinlearningandmemory,aswellasmotordeficits(Lacaria,Spencer,Gu,Paylor,&Lupski,2012).Rearingthesemiceinanenrichedenvironmentamelioratedthemotordeficits,improvedlearningandmemorydeficits,reducedaggressivebehavior,andrelievedanxiety,althoughitdidnotaffecttheirsocialabnormalitiesortheirabnormalvocalizations(Lacariaetal.,2012).Finally,Schneider,Turczak,andPrzewlocki(2006)exposedfetalratstovalproicacidtoproduceanotheranimalmodelofautism.Sensorimotorenrichmentdecreasedrepetitive/stereotypicactivityandanxiety,whileincreasingexploratoryactivityandsocialbehaviors.Similarenhancementsinsocialbehaviorwereobservedbetweencontrolratsgivenenrichedsensorimotorexpe-rienceandcontrolratsrearedinastandardboxcage.Theycon-cludedthatenvironmentalenrichmentcouldbeapotentialtreat-mentforautism.SensoryAbnormalitiesinAutismThepresenceofsensoryprocessingdysfunctioncontributestothedailychallengesofchildrenwithautism(Hiltonetal.,2010;Kernetal.,2007;Leekam,Nieto,Libby,Wing,&Gould,2007;Tomchek&Dunn,2007;Watling,Deitz,&White,2001).Indeed,morethan90%ofthosewithautismhavesensoryabnormalities,expressedasoversensitivity,unresponsiveness,orsensory-seekingbehaviors,whichpersistacrossallagesandIQlevels(Ben-Sassonetal.,2009;Hiltonetal.,2010;Kernetal.,2007;Leekametal.,2007;Tomchek&Dunn,2007;Watlingetal.,2001).Themostcommonlyobservedsensoryissuesinautisminvolveolfactionandtouchsensitivity(Hiltonetal.,2010;Lane,Young,Baker,&Angley,2010;Leekametal.,2007;Schoen,Miller,Brett-Green,&Nielsen,2009).Notonlyissensoryprocessingdysfunctioncorrelatedwithbothmaladaptivebehaviorsandau-tismseverity(Kernetal.,2007;Laneetal.,2010),buttouchandolfactoryissuesarestrongpredictorsofbothatypicalsocialbe-haviorsandpoorsocialcommunicationskillsinchildrenwithautism(Bennetto,Kuschner,&Hyman,2007;Hiltonetal.,2010).SensorimotorDeprivationIncreasesAutismSymptomsIfsensorimotorexperiencescanaltertheprobabilityofexpress-ingautisticsymptoms,aswasobservedinanimalmodelsofautism,thenreducingtheamountofenvironmentalstimulationshouldincreasetheirexpression.Conversely,increasingsuchstim-ulationshoulddecreasetheexpressionofthesesymptoms.AnaturalexperimentofthiskindoccurredwhenimpoverishedRo-manianssentlargenumbersofchildrentoorphanages,wheretheyhadlittleenvironmentalstimulation.Consequently,onethirdofthemdevelopedwhathasbeencalledpostinstitutionalautisticsyndrome(Hoksbergen,terLaak,Rijk,vanDijkum,&Stoutjes-dijk,2005).Thissyndromeincludesstereotypicbehaviors,aninabilitytoidentifyhumanemotions,aswellasdisorderedcom-munication,language,cognition,andattachment(Ellis,Fisher,&Zaharie,2004;Hoksbergenetal.,2005;Johnson,Browne,&Hamilton-Giachritsis,2006;Miller,Chan,Comfort,&Tirella,2005;WismerFries,Ziegler,Kurian,Jacoris,&Pollak,2005).Importantly,whentheseorphansweremovedtoanenrichedenvironmentprovidedbyfosterparents,theirintelligencetestscores,languagedevelopment,socialengagementandmentalhealthimproved(Nelsonetal.,2007).Therefore,environmentaldeprivationcanincreasetheprobabilityofexpressingasyndromethatisquitesimilartoautism,andenvironmentalstimulationcanamelioratethosesymptoms.Olfactory/TactilePairingsAlterNeurobehavioralThecombinationofolfactoryandtactilestimulationmaybeparticularlycompellingforthedevelopingbrain.Whenwegaveolfactory/tactilestimulationtohumaninfantsonthefirstdayoflife,theydevelopedanattractiontothatodor,whileodorexposurealonewasineffectiveinthatregard(Sullivanetal.,1991).Wealsofoundstrikingbehavioral,neuroanatomical,neurophysiologicalandneuropharmacologicalchangesinthebrainsofyoungratswhentheywereexposedtosimultaneousolfactory/tactilestimu-lation(Coopersmith&Leon,1984;Rangel&Leon,1995;Sulli-van,Wilson,&Leon,1989;Wilson,Sullivan,&Leon,1987;Woo&Leon,1991;Woo,Coopersmith,&Leon,1987).Again,olfac-torystimulationalonedidnotevokeneurobehavioralplasticityindevelopingrats.ThisdocumentiscopyrightedbytheAmericanPsychologicalAssociationoroneofitsalliedpublishers.Thisarticleisintendedsolelyforthepersonaluseoftheindividualuserandisnottobedisseminatedbroadly.WOOANDLEON Sincethecombinationofolfactoryandtactilestimuliwaspar-ticularlyeffectiveinproducingneurobehavioralchangesinyoungrats,weusedasensorimotorregimenthatinvolvedolfactoryandtactilestimulation,aswellasvariouscombinationsofvisual,thermal,motor,balance,auditorystimuli,andcognitivetasks,inanattempttomaximizesensorimotorstimulationinhumans.Wealsowantedtoaddnoveltyintotheirsensorimotorexperiencebothbycyclingthroughasetofsevenodorantsandbyintroducingnewenrichmentactivitiesatregularintervals.Indeed,noveltyappearstobeacriticalaspectoftheenvironmentalenrichment.Veyracetal.(2009)foundthatexposingmicetodifferentodorantsonadailybasisincreasedmemoryandneurogenesis,whereasexposingthemtoacomplexcombinationofodorantsthatdidnotvaryovertheexposureperiodwasnoteffective.Wethereforehadparentsgivenovelsensorimotorenrichmentwithsimultaneousstimulationofdifferentsensorysystemstochildrenwithautismeachdayfor6months,inadditiontotheirongoingstandardcare,andwethendeterminedwhethertheirsymptomsimprovedcomparedtostan-dardcarecontrols.Weconductedarandomizedcontrolledtrialinvolving28malechildrendiagnosedwithautism,3–12yearsold(mean2.5years).TheInstitutionalReviewBoardattheUni-versityofCalifornia,Irvineapprovedallproceduresusedinthisstudy.Childrenwereexcludedfromthestudyiftheyhadsyn-dromicformsofautism,suchasRett’sDisorder,FragileXsyn-drome,orChildhoodDisintegrativeDisorder.Nopsychotropicmedicationswereallowedthroughoutthestudyandanticonvulsantmedicationwasonlyallowedifthechildhadbeenonastabledoselongerthan3monthspriortotheinitiationofthestudy.Childrencouldnothaveinitiatedanewin-schoolbehavioraltherapywithinonemonthbeforethestartofthestudyortwomonthsbeforethestudyforaprivateprogram.Nosensoryintegrationtherapywaspermittedatanytimeduringthestudy.Wealsodidnotallowconcurrenttherapiesthatinvolvedphysicalrestraint.Behavioraltherapiesweresowidelyutilizedbythechildrenthatwereferredtotheirusageas“standardcare,”andthefrequencyofuseforthedifferentbehavioraltherapiesdidnotdifferstatisticallyacrossgroups(seeTable1).DiagnosesofautismwereconfirmedusingtheAutismDiagnosticObservationSchedule(ADOS).Thecom-municationandsocialinteractionsADOSscoreswerecombined,andtoqualifyforourstudy,thetotalscorehadtobewithintheADOSautismclassificationandnotsimplywithintheautismspectrumclassification.Thechildrenwerethenrandomlyassignedtoeitherasensorimotorenrichmentgroupstandardcare(13children),oragroupreceivingstandardcarealone(15children),matchingforageandautismseverity,asassessedbytheirChild-hoodAutismRatingScale(CARS)score.Thechildreninboththesensorimotorenrichmentgroupandthecontrolgroupallwerereceivingvariouscombinationsofstandardtreatments,whichwerecontinuedthroughouttheclinicaltrial(seeTable1).Mostchildrenwerereceivingappliedbehavioranalysis,whichinvolveddifferentialreinforcementforadaptivebehavior.Somechildreninbothgroupsalsoreceivedconcurrentspeechtherapytoimprovetheirlanguageskills,occupationaltherapytohelpdeveloptheskillsneededforindependentliving,orsocialskillstherapyinanefforttodeveloptheabilitytoexperiencetypicalsocialinteractions.Adaptedphysicaleducationprovidedmotoractivitiesthatweremodifiedforchildrenwithautism.Physicaltherapywasusedtoimprovebothfinemotorskillsandgrossmotorskills.Theenrichmentgroupreceiveddailyexposuretomultiplesen-sorimotorstimuli,distributedthroughouttheday.Parentsinthisgroupweresuppliedwithakitthatcontainedmostofthesuppliesneededforthesensorimotorexercises.Forolfactoryenrichment,eachkitincludedsevenvialscontainingscentedessentialoils(anise,apple,hibiscus,lavender,lemon,sweetorange,andvanilla;EssentialOils,Portland,OR),sevenemptyvialswithcaps,andcottonballs.Fordifferenttextures,thekitcontainedsquaresofplasticdoormat,smoothfoam,arubbersinkmat,aluminumfoil,finesandpaper,felt,andsponges.Fordifferentobjectstomanip-ulate,theyweregivenasmallpiggybankwithplasticcoins,miniatureplasticfruits,coloredbeads,asmallfishingpolewithamagnetic“hook,”colorfulpaperclips,alargebutton,and20smalltoysofvaryingshapes/colors/textures.Inaddition,thekitcontainedstraws,coloredconstructionpaper,fourbowlsforwater,picturesofwell-knownpaintings,picturesoffruits,andacanofPlay-Doh.Formusicenrichment,theywereprovidedwithaclas-sicalmusicCD(ClassicalMusicForPeopleWhoHateClassicalMusic,Vol.1;DirectSource)andaportableCDplayerwithheadphones.Theparentsprovidedawoodenplank(2)forawalkingexercise,scentedbathsoapandbodyoilsforthespatreatmentexercise,andmiscellaneousotherhouseholditemsfortheexercises,includingalargesaladbowlforwateratdifferenttemperatures,metalspoons,ice,blindfold,noisemaker(e.g.,abellorbuzzer),picturebook,cookiesheet,ovendish,mirror,ballorpillow,pillowcase,felt-tipmarkers,andmusicthatmatchedpic-tures(e.g.,Hawaiianmusicandabeachpicture).Theyalsopro-Table1StandardTreatmentsReceivedbyChildreninBothSensorimotorEnrichmentGroupandControlGroup StandardcareSensoryenrichmentConcurrentInterventions15)(Speechtherapy12/1510/130.84Occupationaltherapy9/157/130.75Appliedbehavioralanalysis10/1510/130.60Socialskills2/152/130.86Adaptedphysicaleducation,physicaltherapy,other.8/154/130.25Two-sampletestofproportionsThisdocumentiscopyrightedbytheAmericanPsychologicalAssociationoroneofitsalliedpublishers.Thisarticleisintendedsolelyforthepersonaluseoftheindividualuserandisnottobedisseminatedbroadly.ENVIRONMENTALENRICHMENTANDAUTISM videdmaterialtocreateamultitexturedwalkingpath,suchascarpet,ahardfloor,pillows,cardboard,orbubblewrap.Thechildrenwereexposedtofourdifferentfragrances,atdifferenttimesduringtheday.Theparentplacedonedropofodorantonacottonballthattheyhadplacedinaglassvialandtheythenallowedthechildtosniffitrepeatedlyforaminute.Thisolfactorystimulationwaspairedwithgentletactilestimulation,givenbyrubbingtheirbackswithaclosedhand.Theyalsowereexposedtoafragrancethroughoutthenightbyplacingascentedcottonballintheirpillow-casebeforebedtime.Parentswereaskedtocyclethrougheachofthesevenodorants,whichwerechosensolelybasedontheirpleasantfragrance.Onlyoccasionallydidchildrendislikeanodorant,andinthosecases,weprovidedthemwithanotherpleasantodorant(bananaorappleblossom;EssentialOils,Portland,OR).ThechildrenlistenedtoclassicalmusiconceadayandtheparentswereaskedtousetheportableCDplayerandthehead-phonesthatwereincludedintheirkittopairauditoryandtactilestimulation.However,thechildrentypicallywouldnotusetheheadphonesandparentsusedspeakersystemstoexposetheirchildtothemusic.Inaddition,theparentsweregivenwritteninstruc-tionsfor34sensorimotorenrichmentexercises,andafterabrieftrainingsession,theyengagedtheirchildwith4–7exercises,twiceaday.Theseexercisesinvolvedsomewhatarbitrarycombinationsofsensorystimulisuchastactile,thermal,visual,andmotoractivities.Weinstructedtheparentstoengageinadifferentsetofexercisesevery2weeksandtheexercisesbecameincreasinglychallengingoverthecourseof6months.Thedailyexercisestookapproximately15–30minutestocomplete,twiceaday:1.Thechildplaceshisorherhandsorfeetinwaterofdifferenttemper-atures(thermal,motor),2.Thechildsqueezesobjectsofdifferentshapesandtextures(tactile,motor),3.Theparentdrawslinesonthechild’shandwithobjectsofdifferenttexturewhilethechildwatches(tactile,visual),4.Theblindfoldedchildwalksonapathwayofdifferenttextures(tactile,motor),5.Theparentdrawsimaginarylinesonthechild’sface,arms,andlegswithobjectshavingdifferenttextureswhilemusicplays(tactile,auditory),6.Thechildselectsthetwinofobjectsinapillowcaseafterseeingitonthetable(tactile,cognitive),7.Thechildisgivenascentedbathandamassagewithscentedoil(thermal,tactile,olfactory),8.Theparenttouchesthechildonhisorherarmsandlegswithacooledspoonorwarmedspoonwhiletheparentspeaksorsings(thermal,auditory,tactile),9.Linesaredrawnonthechild’sarmsandlegswithcooledorwarmedspoons(thermal,tactile),10.Thechildisshownapictureofanobjectandpicksouttherealobjectonatableamongotherobjects(visual,cognitive,motor),11.Thechildisaskedtowalkona2board,thenheorsheisaskedtodothattaskblindfolded(motor,balance),12.Thechildpicksoutacoloredbeadamongaplatefulloficecubes(thermal,motor,visual),13.Thechildisshownaphotoandhisorherattentionisdrawnawayfromthephotousinganauditorycue(visual,audi-tory),14.Thechildliftsanobjectoutofacoolbowlofwaterandthenawarmbowlofwater(motor,thermal,visual),15.Thechildpullsabuttonfrombetweentheparent’sfingers(motor,tactile,visual),16.Thechildwalkseitheronasheetoffoamoronlargepillows,eventuallyblindfolded(tactile,balance,motor),17.Thechildpointstoobjectsinabookandsaysthenameoftheobject(language,cognitive,motor),18.Thechild’sfingerisplacedonacoolobjectandthenawarmobject(thermal,tactile),19.ThechildpokesaholeinPlay-Dohandthenplacesgrainsofriceinit(motor,tactile,visual),20.Thechildselectsatexturesquarethatmatchesthetextureofanobjectinaphoto(tactile,cognitive,visual),21.Differentobjectsareusedtodrawimaginarycirclesonthechild’sface(tactile,cognitive),22.ThechildplacescoldstrawsfilledwithiceinPlay-Dohusingeachhand(motor,thermal,visual),23.Thechildwalksona2boardwhileholdingacooledtray(thermal,balance,motor),24.Theparentrubseachofthechild’sfingersandtoesinturn,whilethechildwatches(tactile,visual),25.Thechildplacescoinsinapiggybankusingonlyhisorherreflectioninamirror(motor,cognitive,visual),26.Thechildusesamagnetontheendofasmallfishinglinetopickuppaperclips(motor,visual),27.Thechildtracksaredobjectthatismovedaroundaphotoofapainting(visual,cognitive),28.Thechildwalksupanddownstairswhileholdingabigballorpillow(motor,tactile,balance),29.Thechilddrawsshapesusingpenandpaperwhiletheparentdrawsimaginaryshapesonthechild’sbackusingatoy(motor,tactile,visual),30.Thechilddrawslinesusingbothhandssimulta-neously(motor,cognitive,visual),31.Thechildmatchesthecolorofobjectsinaphotowithcoloredbeads(visual,cognitive,motor),32.Thechildblowsasmallpieceofaluminumfoilonthefloorasfaraspossible(motor,visual),33.Thechildviewsapicturemovingfirstbehindandtheninfrontofanotherpicture(visual,cognitive),34.Thechildviewsaphotowithmusicassociatedwiththatscene(auditory,Trainedpsychometriciansconductedallassessmentsblindwithrespecttogroupassignment,bothatthebeginningofthestudyandafter6months.AllindividualsweretestedwiththeLeiterInter-nationalPerformanceScaleRevised(Leiter-R),anonverbaltestofcognitiveabilities,whichisrecommendedfortestingchildrenwithautism(Tsatsanisetal.,2003).Thistestcanevaluatechangesinnonverbalcognitiveability.TheLeiter-Rdoesnotrequireaspokenorwrittenwordfromtheexaminerorthechild,allowingthestudyofcognitiveperformanceinchildrenwithandwithoutlanguageissues.SincetheLeiter-Rscoresdonotchangesignifi-cantlywithincreasingage,thetestcanbeusedeffectivelywithchildrenfrom2–21years.Thetestcanmeasurecognitiveabilityoverawiderangeanditalsoallowsexperimenterstoobserveimprovementincognitivecapacitiesovertime.WeusedtheExpressiveOne-WordPictureVocabularyTesttoassessverbalintelligenceandauditory-visual-verbalassociationskills.Thechildrenwereshownapictureofanitemandwerethenrequestedtonametheitemusingoneword.TheCARSprovidesqualitativemeasuresofalargerangeofissuesforchildrenwithautism(Schopler,Reichler,DeVellis,&Daly,1980).Thetestassesses:relatingtopeople,imitation,emo-tionalresponse,emotionalexpression,bodyuse,objectuse,adap-tationtochange,visualresponse,listeningresponse,taste,smell,andtouchresponses,fearornervousness,verbalcommunication,nonverbalcommunication,activitylevel,levelandconsistencyofintellectualresponse,andgeneralimpressions.TheCARStestcombinestotalscorestoplaceindividualsinnonautistic,mildly/moderatelyautistic,orseverelyautisticclassifications.Thistesthasveryhighinternalconsistency,indicatingthattheindividualscorestogetherconstituteaneffectivetoolfortheidentificationofdifferentlevelsofautismseverity(Schopleretal.,1980).TheCARShas100%accuracyindiscriminatingchildrenwithautismfromchildrenwithintellectualdisabilities(Teal&Wiebe,1986).Changesintestscoresover6monthswerecomparedbetweenthesensorimotorenrichmentandstandardcaregroupsusingananalysisThisdocumentiscopyrightedbytheAmericanPsychologicalAssociationoroneofitsalliedpublishers.Thisarticleisintendedsolelyforthepersonaluseoftheindividualuserandisnottobedisseminatedbroadly.WOOANDLEON ofcovariance(ANCOVA,one-tailed),controllingforbaseline.Avalueoflessthanorequalto0.05wasconsideredstatisticallysignif-icant.Weusedparametricstatistics,asresidualanalysisshowedthedataforallmeasureswasbalanced.Inaddition,withregardtoclinicalimprovement,Perryetal.,(2008)demonstratedaclinicallysignificantimprovementusinga5-pointorgreaterdecreaseontheCARSscore.Weusedthesamecriteriontodeterminewhetheraclinicallysignif-icantimprovementoccurredinourstudy.Statistically,baselinevaluesforthetwogroupsdidnotdiffersignificantlyonage,ADOSscores,CARSscores,Leiter-Rscores,orExpressiveOne-WordPictureVocabularyTestscores.After6months,however,themeanchangeinLeiter-R(VisualizationandReasoning)rawscoresinthesensorimotorenrichmentgroupwas11.3pointshigherthanthatinthestandardcaregroup(Figure1;.008;meanLeiter-RtestscoreS.E.M,sensorimotorenrichment:48.465.52(baseline),5.50(6months);standardcare:46.20(baseline),43.706.89(6months).Comparisonbetweengroupsrevealedthatafter6months,thechangeinmeanautismseverityscores,assessedbytheCARS,differedbetweengroupsby2.8points(ANCOVA,.03;meanCARSscoreS.E.M.,sensorimotorenrich-ment:34.380.72(baseline),31.121.46(6months);standardcare:38.071.71(baseline),37.611.67(6months).Moreover,42%oftheenrichedgroupand7%ofthestandardcaregrouphadwhatweconsideredtobeaclinicallysignificantimprovementofatleast5pointsonthatscale(Figure2;two-sampletestforproportions,Parentswereaskedwhethertheoverallautismsymptomsoftheirchildhadimproved,worsened,orstayedthesameoverthe6-monthperiod.Statisticalanalysiswasperformedusingthetwo-sampletestforproportionsandthenumberofindividualsreportingtheirchild’sautismsymptomshadimprovedwascomparedtothenumberofindividualsreportingtheirchild’ssymptomshadwors-enedorhadnotchange.Astatisticallysignificantincreaseinthenumberofparentsreportinganimprovementinautismsymptomswasobservedinthesensoryenrichmentgroupcomparedtothestandardcaregroup(Figure3,Twosampletestforproportions,.03).Specifically,69%inthesensoryenrichmentgroupreportedimprovement,while31%inthestandardcaregroupreportedimprovement.WefurtheranalyzedtheCARSscorestoevaluatechangesinspecificbehavioralresponses.AlthoughthechangeinoveralltotalCARSscorewasstatisticallysignificantacrossthetwogroups,theaveragechangeinCARSscoresforindividualitemsdidnotreachstatisticalsignificance.However,greaterimprovementinbehav-ioralresponseswasobservedintheenrichedgrouprelativetothecontrolgroupin11outofthe15itemsexaminedonthetest:relatingtopeople;emotionalresponses;bodyuse;objectuse;adaptationtochange;visualresponse;listeningresponse;taste,smell,andtouchresponseanduse;fearornervousness;levelofconsistencyofintellectualresponse;andgeneralimpressions.Forexample,wecalculatedthedifferenceforthetouch/smell/tastesubtestoftheCARSbetweentheinitialtestandthe6-monthassessment.Wefoundadecreaseinatypicalresponsivenesstothesestimuliforthesensorimotorenrichmentgroup(mean0.29),relativetostandardcarealone(mean0.07),butthatdifferencedidnotreachstatisticalsignificance(.07).Notethatadecreaseinthisscoredenotesadecreaseinautismseverity.TheExpressiveOne-WordPictureVocabularyTestrevealednodifferenceinoutcomesbetweenthegroupsonthistest(ANCOVA,.44;meanchange4.77forsensorimotorenrichmentgroup;meanchange4.67forstandardcaregroup),withbothgroupsimprovinginthismeasureoverthe6-monthWefoundthatanin-home6-monthsensorimotorenrichmenttherapyproducedimprovementsincognitionandsymptomsever-ityinchildrenwithautismacrossarangeofages.Specifically,wehavefoundthatenvironmentalenrichmentamelioratedautismsymptomsformanychildrenbothintermsofoverallseverityandtheircognitiveperformance.IntheExpressiveOne-WordPictureVocabularyTest,bothgroupsimproved,withnostatisticaldiffer-enceobservedwhenthetwogroupswerecompared.Therewereanumberoffactorsthatwouldbeexpectedtoincreasethevariabilityintheoutcomesofthisstudy.Forexample,weimaginethatparentsvariedintheirfaithfulnessinadminister-ingthestimulation.Somechildrenvariedintheirmoodfromtesttoretest.Thebehavioraloutcomemeasurescouldbeinexact.The Figure1.ChangeinmeanLeiter-Rscore.Sensoryenrichmentresultsinimprovementsincognitivefunctioninchildrenwithfullautismasmea-suredusingtheLeiterInternationalPerformanceScale-Revised.Astatis-ticallysignificantimprovementinthemeanchangeinscoreswasobservedinthesensorimotorenrichmentgroupfollowing6monthsoftherapy,whilethemeanchangeinscoresforthestandardcaregroupdecreasedoverthesameperiodoftime.ThisdocumentiscopyrightedbytheAmericanPsychologicalAssociationoroneofitsalliedpublishers.Thisarticleisintendedsolelyforthepersonaluseoftheindividualuserandisnottobedisseminatedbroadly.ENVIRONMENTALENRICHMENTANDAUTISM childrenhadawideagerange,theirsymptomsvariedwidely,andwetestedarelativelysmallnumberofsubjectswhohadavarietyofconcurrentstandardtherapies.Thefactthatwewereabletorevealconsistentsignificantdifferencesbetweenthegroupsde-spitethesesourcesofvariability,suggeststhatthereisastrongeffectofenvironmentalenrichmentonthesechildren.ComparisontoOtherAutismTreatmentsSensoryintegrationtherapyisoftenusedbyoccupationalther-apiststotreatchildrenwithautism(Ayres&Tickle,1980).Thetreatmenttypicallyinvolvesvestibular,proprioceptive,auditory,andtactileinputsusingbrushes,swings,andballs,althoughothersensesmaybeengagedatthediscretionofthetherapist.Whileattemptstousesensoryintegrationtherapyforautismhavetypi-callynotbeensuccessful(Baranek,2002;Dawson&Watling,2000),arecentpilotstudyfoundsomeimprovementsin“autisticmannerisms”usingthatapproachforchildrenwithautism(Pfe-iffer,Koenig,Kinnealey,Sheppard,&Henderson,2011).Appliedbehavioranalysisisawidelyusedtreatmentforautism.Thisapproachusesdiscretetrialteaching,inwhichtherapistsbreakdownbehaviorsintotheirbasiccomponents,rewardingpositiveperformance,andthengeneralizingskillstoothersitua-tions(Lovaas,1987).Typically,achildwillreceivethistherapyfromatrainedprofessionalfor25–40hours/weekforanumberofyears.Meta-analysesregardingitsefficacy,however,arenotinfullagreement(Ospinaetal.,2008;Smith,Groen,&Wynn,2000;Spreckley&Boyd,2009;Rogers&Vismara,2008).TheEarlyStartDenverModelusesappliedbehavioranalysistechniques,butalsoencouragespositiveaffectandsharedengagementbetweenthetherapistandchild(Dawsonetal.,2010).TheAgencyforHealthCareResearchandQualityrecentlyevaluatedthedatasupportingbothappliedbehavioranalysisandtheDenverModel,andconcludedthat“...improvementsoccurinsomeaspectsoflanguage,cognitiveability,adaptivebehavior,challengingbehav-iors,andpotentially,educationalattainment,forsomechildren”(Warrenetal.,2011).ChildrengiventheDenverModeltreatmenthaveshowngainsincognitiveperformanceofabout10IQpoints,comparabletowhatwehavefound,alongwithgainsinautismseverity,alsoaswehavefound.Theyalsoreportedimprovementsinadaptivebehav-ior,communication,andmotorskills,althoughtheydidnotfinddifferencesinrepetitivebehaviorandADOSscores(Dawsonetal.,2010).DifferencesbetweentheDenverModelandtheenvironmentalenrichmenttherapydescribedhereincludethefactthatthechil-drenintheDenvertreatmentstartedtheirintensivetherapybe-tween18and30months,whilethechildreninourstudyaveraged6.6yearsold.Earlydetectionofautismisstillnotcommon(Pringle,Colpe,Blumberg,Avila,&Kogan,2012),despitethecallbytheAmericanAcademyofPediatricsforphysicianstoscreen18-month-oldchildrenforautism(Johnson&Myers,2007).Infact,themedianageatwhichchildrenarediagnosedwithautismintheU.S.is5yearsold(Pringleetal.,2012).Thissituationmaylimittheefficacyoftheintensivebehavioralapproaches,becausesuchbehavioraltreatmentsdonotseemtobeveryeffectiveforeven4–7-year-oldchildren(Eikeseth,Smith,Jahr,&Eldevik,TheDenverModelalsotook20.4hours/weekofprofessionaltreatmentand16.3hours/weekofparentaltreatmentoverthecourseof2years,whiletheenvironmentalenrichmentusedinour Figure2.PercentofindividualswithclinicalimprovementontheChild-hoodAutismRatingScale(CARS).Sensoryenrichmentresultsinim-provementsinmaladaptivebehaviorscharacteristicofindividualswithautism.AutismseveritywasassessedusingtheChildhoodAutismRatingScale.Aclinicallysignificantimprovementofatleast5pointsonthatscalewasobservedin42%ofthesensorimotorenrichmentgroupandonly7%ofthestandardcaregroup.Two-sampletestforproportions, Figure3.Parentalassessmentofautismbehaviors.Parentswereaskedtocharacterizeautismbehaviorsoverthecourseofthestudyashavingimproved,worsened,orhadnochange.Inthesensorimotorenrichmentgroup,69%ofparentsexpressedanimprovementinoverallautismsymp-toms,comparedto31%inthestandardcaregroup,corroboratingthestatisticallysignificantimprovementinoverallChildhoodAutismRatingScalescoresintheenrichmenttherapygrouprelativetothestandardcarecontrolgroup.Two-sampletestforproportions,ThisdocumentiscopyrightedbytheAmericanPsychologicalAssociationoroneofitsalliedpublishers.Thisarticleisintendedsolelyforthepersonaluseoftheindividualuserandisnottobedisseminatedbroadly.WOOANDLEON studytookabout5–9hours/weekofparentaltreatmentfor6months.ThetotalcostintimeandmoneyoftheDenverModelisthereforehighrelativetothecostoftheenvironmentalenrichmentprogrampresentedinthisreport.Appliedbehavioranalysisisalsoquiteexpensive;theoriginalLovaasstudyscheduled40hoursofprofessionaltreatment/week,althoughlessintensiveprogramsalsohavereportedimprovementsinchildrenwithautism(Smithetal.,2000;Fernelletal.,2011).DevelopmentalTrajectoriesThedevelopmentaltrajectoriesof6,975childrenwithautism,aged2–14,weredeterminedoverrepeatedassessmentsusinggroup-basedlatenttrajectorymodelingandmultinomiallogisticregressionmodels(Fountain,Winter,&Bearman,2012).Theresearchersfoundthatthechildrenclusteredintoseveralgroups.Thosewithalowinitialautismseveritytendedtohavethegreatestimprovementsovertime.Mostchildrenwhowereinitiallyas-sessedwithintellectualdisabilitiesdidnotseemuchimprovement,althoughabout10%ofchildrenimprovedfromhavingasevereautismassessmenttobeinghighfunctioning.Althoughtheout-comesofthisenvironmentalenrichmenttrialcannotbecompareddirectlytotheFountainetal.,developmentaltrajectoryreport,enrichedsensorimotorexperiencesappeartohaveimprovedthedevelopmentaltrajectoryforasignificantproportionofchildrenwithautisminourstudy.NeuralPathwaysOlfactorydysfunctionisassociatedwithneuralatrophyinspe-cificbrainareas(Bitteretal.,2010,2011).Theaffectedareasincludethenucleusaccumbens,medialanddorsolateralprefrontalcortex,piriformcortex,insularcortex,orbitofrontalcortex,hip-pocampus,parahippocampalgyrus,supramarginalgyrus,andcer-ebellum.Olfactorysystemdysgenesishasbeensuggestedtoun-derliethedevelopmentofautism(Brang&Ramachandran,2010),andremarkably,everyareaofthebrainthatisaffectedfollowingolfactorydeprivationisalsoadverselyaffectedintheautisticbrain(Allen&Courchesne,2003;Andersonetal.,2010;Baron-Cohenetal.,1999;Courchesne,1997;Gilbert,Bird,Brindley,Frith,&Burgess,2008;Gilbert,Meuwese,Towgood,Frith,&Burgess,2009;Hadjikhani,Joseph,Snyder,&Tager-Flusberg,2006;Hasan,Walimuni,&Frye,2012;Richeyetal.,2012;Schumannetal.,2004;Yu,Cheung,Chua,&McAlonan,2011).Itthereforeseemspossiblethatlimitedolfactoryexperiencesduringdevelop-mentmaycontributetotheinabilityofindividualstocompensatefortheneuralandbehavioralanomaliesproducedbyautism,oritmayevencontributedirectlytotheirneuralanomalies.Whileneitherolfactorystimulationnortactilestimulationevokedmuchofanoradrenergicresponseinyoungrats,thecombinationofthosestimulievokeda300%increaseinnorepi-nephrinethatdidnotreturntobaselinelevelsfor2hours(Rangel&Leon,1995).Thisriseinnorepinephrineiscriticalforboththeneuralandthebehavioralconsequencesofearlyolfactorylearninginrats(Sullivanetal.,1989;Sullivan,Wilson,Lemon,&Ger-hardt,1994;Sullivan,Stackenwalt,Nasr,Lemon,&Wilson,2000).Micehousedinanenrichedenvironmentalsohaveelevatednorepinephrinelevelsintheirbrains(Naka,Shiga,Yaguchi,&Okado,2002)andtheeffectsofenvironmentalenrichmentalsodependonthisriseinnorepinephrine(Mohammed,Jonsson,&Archer,1986;Veyracetal.,2009;Lietal.,2013).Somechildrenwithautismmayhavesystemicdeficientnorad-renergicresponsesthatmayimpairtheirabilitytocompensatefortheirneurologicalissues.Time-averagedmeasuresofnorepineph-rineinurine,whicharenotaffectedbythestressofablooddraw,foundchronicallydepressedlevelsofthatneurotransmitterinchildrenwithautism(Barthelemy,etal.,1988;Young,Cohen,Brown,&Caparulo,1978).Themothersofautisticchildrenalsohavedepresseddopaminebeta-hydroxylasethatresultsinde-pressedmaternalnorepinephrinelevelsduringpregnancythatcouldaffecttheneuraldevelopmentoftheirchild(Robinson,Schutz,Macciardi,White,&Holden,2001).Otherstudiessuggestanincreaseinnorepinephrineinchildrenwithautism(Anderson,Colombo,&Unruh,2012).SincetheeffectsofnorepinephrineonlearningdescribeaninvertedU-shapedfunction(Baldi&Bucha-relli,2005),witheitherloworhighlevelspreventingneurobehav-ioralplasticity,itseemspossiblethatenrichedsensorystimulationmayhavenormalizedthenorepinephrineresponseinthesechil-dren,therebyallowingneuralplasticitytoproceed.Howmightnorepinephrinefacilitatefunctionalcompensationinthebrainsofchildrenwithautism?NorepinephrinestimulatesBDNFproduction(Chen,Nguyen,Pike,&Russo-Neustadt,2007;Mannarietal.,2008),whichislowinautisticindividuals(Sheikhetal.,2010),increasesneurogenesis,(Jhaverietal.,2010;Masudaetal.,2012),increasesbrainglutamateanddopamine(Grinberg,Rueb,&Heinsen,2011),anddownregulatesinflammatorygenes(Feinsteinetal.,2002;Henekaetal.,2003).Italsopreventsneuronaldeath(Counts&Mufson,2010;Patel,Chen,&Russo-Neustadt,2010),inpartbydecreasingoxidativestress(Traveretal.,2005;Troadecetal.,2001).Robertson(2013)hassuggestedthatrepeatednoradrenergicpulsesoverthecourseofalifetimebuildupacompensatorymechanismthatprotectsagedindividualsfromthedementiaassociatedwithAlzheimer’sdisease,evenwhentheyexpressitscharacteristicneuropathology.Thisconceptissimilartowhatweareproposingforautism,exceptthatthecompensatorymechanismswoulddeveloptoimprovepreexistingautismsymptoms.FutureStudiesWehopetodetermineinfuturestudieswhetherthereisanameliorationofthesensoryprocessingdysfunctionthatcommonlyaffectschildrenwithautismandwhetherthereisacorrelationbetweenthecognitiveandbehaviorimprovementsandchangesinsensoryprocessingdysfunctionusingamoresophisticatedmea-sureforthoseresponses.Wealsopredictthatregulartreatmentinschoolbyatrainedtherapistwouldimprovetheoutcomesforthechildrenbyassuringthattheyreceivedthetreatmentreliably.Itwillbeimportanttodeterminewhetherthesensorimotorenrich-menttherapycanbeusedonlyinanadjunctiveway,orwhetheritcanbeusedsuccessfullyonitsown.Ifsensoryenrichmentcanbeeffectiveonitsown,itwouldbealessexpensiveandlesstime-consumingtherapeuticoptionthatcanbeusedsuccessfullyforolderchildren.Suchamonotherapywouldbebeneficialtochil-dren,parents,insurers,andsociety(Ganz,2007).Indeed,individ-ThisdocumentiscopyrightedbytheAmericanPsychologicalAssociationoroneofitsalliedpublishers.Thisarticleisintendedsolelyforthepersonaluseoftheindividualuserandisnottobedisseminatedbroadly.ENVIRONMENTALENRICHMENTANDAUTISM 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