Hemispheric speech lateralisation in the developing brain is related to motor praxis ability

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ContentslistsavailableatScienceDirect

Developmental

Cognitive

Neuroscience

jou rn a l h om ep ag e : h t t p : / / w w w . e l s e v i e r . c o m / l o c a t e / d c n

Hemispheric

speech

lateralisation

in

the

developing

brain

is

to

motor

praxis

ability

Jessica

C. Hodgson

a,∗,1

_,

_Rebecca

_J.

_Hirst

b

_,

_John

_M.

_Hudson

a

a_School_of_Psychology,_University_of_Lincoln,_Lincoln,_LN6_7TS,_UK b_School_of_Psychology,_University_of_Nottingham,_Nottingham,_UK

a

r

t

i

c

l

e

i

n

f

o

Articlehistory: Received29July2016 Receivedinrevisedform 27September2016 Accepted27September2016 Availableonline29September2016 Keywords: Speechproduction Lateralization TranscranialDoppler Motorcontrol Development

a

b

s

t

r

a

c

t

Commonlydisplayedfunctionalasymmetriessuchashanddominanceandhemisphericspeech later-alisationarewellresearchedinadults.Howeverthereisdebateaboutwhensuchfunctionsbecome lateralisedinthetypicallydevelopingbrain.Thisstudyexaminedwhetherpatternsofspeechlaterality andhanddominancewererelatedandwhethertheyvariedwithageintypicallydevelopingchildren. 148childrenaged3–10yearsperformedanelectronicpegboardtasktodeterminehanddominance;a subsetof38ofthesechildrenalsounderwentfunctionalTranscranialDoppler(fTCD)imagingtoderivea lateralisationindex(LI)forhemisphericactivationduringspeechproductionusingananimation descrip-tionparadigm.Therewasnomaineffectofageinthespeechlateralityscores,however,youngerchildren showedagreaterdifferenceinperformancebetweentheirhandsonthemotortask.Furthermore,this between-handperformancedifferencesigniﬁcantlyinteractedwithdirectionofspeechlaterality,witha smallerbetween-handdifferencerelatingtoincreasedlefthemisphereactivation.Thisdatashowsthat bothhandednessandspeechlateralisationappearrelativelydeterminedbyage3,butthatatypical cere-brallateralisationislinkedtogreaterperformancedifferencesinhandskill,irrespectiveofage.Resultsare discussedintermsofthecommonneuralsystemsunderpinninghandednessandspeechlateralisation.

1. Introduction

Functionalasymmetriesinhandskillandhemisphericspeech lateralisation are well researched in adults. However, there is debateaboutwhensuchfunctionsbecomelateralisedinthe typi-callydevelopingbrain.Themajorityofadultsdemonstrateatypical patternofrighthandednessandlefthemisphericdominancefor speechproduction(e.g.Knechtetal.,2000),butevidenceforthe neural development of motor skill and speechis more varied. Studiesoflanguagelateralisationinchildrenshowthatspeechis clearlylateralisedtothelefthemisphereataround6or7years of age (Groen et al., 2012; Gaillard et al., 2003) and evidence fromneuroimagingofpre-verbalinfantsdemonstratesanearlyleft hemispheredominanceforprocessingofspeechsounds( Dehaene-Lambertzetal.,2002).Howeverithasalsobeensuggestedthat

∗ Correspondingauthorat:NIHRHearingBiomedicalResearchUnit,Ropewalk House,NottinghamNG15DU,UK.

E-mailaddress:[email protected](J.C.Hodgson).

1 _Present_Address:_NIHR_Hearing_Biomedical_Research_Unit,_Nottingham,_NG1

5DU.

youngerchildrenexhibitmorebi-lateralactivationduringspeech production comparedtoadults (e.g.Holland etal.,2001). Simi-larly,researchhassuggestedhandpreferenceinadulthoodmay bepredictedfromlateralizedmotorbehaviourinearlygestation, comparingultrasoundobservationofthumbsucking(Hepperetal., 1991), and neonate palmargrasp reﬂexstrength (Tan and Tan, 1999).However,varyingobservationsofhandpreferenceinearly childhoodrevealthatnogeneralconsensusexistsforwhen adult-likehandedness occurs.Some studiesindicatethat directionof hand preference is attained by age 3 (e.g.Archer et al., 1988; McManusetal.,1988),withothersreportingshiftinghandusage andincreasedvariabilityonmanualtasksupuntilage6, suggest-ingthisisamorelikelyreﬂectionoflaterhandedness(Brydenetal., 2000).

Thereisevidencethattaskproﬁciencyisrelatedtoincreased laterality(Groenetal.,2012;SheehanandMills,2008), suggest-ingthatveryyoungchildren,whoarenotyetcompetentineither speech or motor control, may display more varied patterns of hemispheric lateralisation for these functions.Current thinking proposesthatwhilstthedirectionofcerebrallateralisationfor lan-guageandmotorfunctionsmaybegeneticallypredisposed,itis http://dx.doi.org/10.1016/j.dcn.2016.09.005

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infacta complexinteractionofenvironmentaland genetic fac-torswhichmediatetheindividualprofileofcerebrallateralisation duringdevelopment(e.g.Bishop,2013).Thereforeitiscrucialto understandtheextenttowhichanindividual’s lateralityprofile changesthroughdevelopment.Iflateralisationshiftswithageand taskproficiencythenitsuggeststhattheunderlyingfunctionaland structuralneuralarchitecturemayalsobechangingandshiftingin thisperiodandisthereforepotentiallyvulnerabletofactors affect-ingthisdevelopmentaltrajectory.

Fewstudies haveexaminedspeechlateralisation inchildren belowage6,predominatelyduetomethodologicaldifficultiesin measuringlanguageperformanceinpre-verbalchildren.Speech paradigms designed for adults tend not to produce a reliable enoughstreamofspeechinchildren,eitherduetotaskdifficulty, therequirement for literacyor complex instructions not easily understood,especiallybyveryyoungchildren.However,notable recentexceptions havebeenable todemonstratethat typically developing 4year old children show predominately left hemi-spherelateralisedspeech(Bishopet al.,2014), and thatnoage effects in overall lateralityprofile could befound in preschool childrenagedbetween1and 5years(Kohleretal.,2015).That studydidhoweverfindaneffectofageinvariabilityofthe later-alisationmeasurement,whichbecamemorereliablewithage.An emergingmethodologyknownasfunctionaltranscranialDoppler (fTCD)ultrasoundhasbeenshowntobeeffectiveinovercoming theissueof problematicmeasurement inchildren, asitis non-invasiveandcanbeperformedin relativecomfort,unlikeother neuro-imagingtechniques.Furthermore,specificspeech produc-tionparadigmshavebeendevelopedwhichallowassessmentof lateralisationinpre-literatechildren,andwhichhavebeen vali-datedagainststandardwordgenerationparadigmsusedinadult languagelateralisationresearch(e.g.Bishopetal.,2009).

Researchintothe useof handednessas anindirectmeasure forspeechlateralityhasformerlyprovedweakandinconclusive (Groenetal.,2013),predominatelyduetothevariabilityof method-ologies, and hand preference and skill definitions being highly dependenton themeasurement and classification used(Groen etal.,2013).However,speechandmotorcontrolaresaidtoshare acommondevelopmentaltrajectory(Iverson,2010),subserved byoverlappingneuralpathwayspredominantlysituatedintheleft hemisphere(see Binkofski and Buccino, 2004).Converging evi-denceunderlinestherelationshipbetweenlanguageand motor function.Forexample,ithasbeenshownthatbrainregions typi-callyassociatedwithmovement(pre-motorcortex,supplementary motorareaandcerebellum)arealsoactivatedbylanguagetasks (e.g.TremblayandGracco,2009;Petersen etal.,1989)andthat classicspeechproductionareas(i.e.Broca’sarea/Brodmannareas 44 and 45) show increased activation during the execution of sequencedhandmovements(Erhardetal.,1996).Inaddition, indi-vidualswithaphasia(Pedelty,1987)and children withspecific languageimpairments(Hill,2001)frequentlydisplayco-occurring motordeficits.

FlowersandHudson(2013)proposethatmotorandspeech lat-eralityarerelatedwheretheyinvolveacommonfeatureofmotor output,namelytheco-ordinationofsequencesofmovementsor utterancestoexecuteaplanorintentionsoastoachieveagoal, eitherlimbmovement orexpressionof anidea(Grimme etal., 2011).Thisrationalehasdemonstratedthatmeasuresof perfor-mance based hand skill are better at revealing theunderlying commonalitiesbetweenthetwofunctions,andthusaremore effec-tiveatinformingontheirneurologicalrelationship(Flowersand Hudson,2013;Groenetal.,2013).Thepresentstudyinvestigated thespeechandmotorlateralisationproﬁlesofchildrenaged3–10 yearstodeterminewhetherthetwofunctionsdevelopin paral-leland,speciﬁcally,whetheryoungerchildrenwouldshowmore variablelateralityacrossthesefunctions.Itfocussedona direct

measureoflanguagelateralisation(fTCD)andahandednesstask (electronicpegboard)whichreliesonthesameconceptofmotor sequencingsuggestedtounderliespeechandmotoraction. Specif-icallytheresearchquestionsposedwereasfollows:1.doesage affectmotorskillperformanceonthepegboardtask?2.Dospeech lateralisationproﬁlesvarywithage?3.Canskilledmotor perfor-mancepredictdirectionofhemisphericspeechlaterality? 2. Methodandmaterials

2.1. Participants

Participantswere153childrenagedbetween3yrsand10yrs (74males;meanage=5.9yrs,SDage=2.02yrs).Allchildrenwere reportedbyparentalreporttobetypicallydeveloping.Parentswere askedtoreportanyreading,languageormotorimpairmentsor concerns,aswellasanydevelopmentaldisorderssuchasAutism orADHD;anychildren withsuchconditionswereexcluded.All participatingchildrenhadnormal,orcorrectedtonormal,vision andnonehadahistoryofneurologicalinjuryordiseaseorwere onmedicationknowntoaffectthecentralnervoussystem,or car-diovascularsystem.AllparticipantswereBritishandhadEnglish asa ﬁrstand onlylanguage;4 ofthe153children testedwere ofAfrican ethnicity,and theremaining149children were Cau-casian,whichisrepresentativeofthelocalpopulation.Participants wererecruited throughlocalschools,parent/toddlergroupsand viatheUniversityofLincoln’sscienceoutreachevents.The inves-tigationwasapprovedbytheethicscommitteeoftheSchoolof Psychology,UniversityofLincoln.Parentalconsentwasobtainedin writingatleast48hpriortothetestingsessionfollowing acknowl-edgereceiptofdetailedstudyinformationsheetsandbrieﬁngon thestudyviaphone/emailcontact.Childrenwerealsorequiredto assenttoparticipationatthetimeoftesting.Failureonbehalfofthe childtoassentsupercededtheparentalconsent,suchthatthose childrendidnotcontinuewiththestudy.Duringtesting partici-pantswereaccompaniedbyafemaleexperimentersittingbeside themtoensuretheywerehappytocontinue.Childrenwerefreeto withdrawatanytimewithoutprejudice,andthisrightwasclearly explainedtothemand theywereaskedtopractise sayingthey wantedtostop.Inaddition,silence,lackofresponse,changesin demeanourandeyecontact,werealltakenassignsfromthechild ofdisinclinationtocontinue,thustriggeringthecessationof test-ing.Onlyoneinstanceoccurredofachildaskingtowithdrawbefore thetestinghadstarted.

2.2. Behaviouralassessments

Participantscompletedaseriesofassessmentstoascertaintheir levelsofmotorandlanguageabilities.

2.2.1. Handednessassessment

Allparticipantsunderwentassessmentsoftheirhand prefer-enceviacompletionof5manualtasksselectedasreliableindicators ofmanual preference. Thetaskswere selectedfroma groupof manualactionsusuallyfoundonhandednessquestionnaires(e.g FlowersandHudson,2013;Annett,2002).Thisapproachwastaken duetotherangeofagesinthesample,whereitwasconsidereda standardhandednessinventorywouldbeinappropriateduetothe literacyskillsrequiredtocompletesuchaquestionnaire.Similarly relianceonself-reportedwritinghandwasnotconsideredarobust enoughapproachgiventheagerangeoftheyoungestparticipants. The5manualtasksusedtoassesshandpreferencewereas fol-lows:1.Underarmthrowofasoftballtotheexperimenter;2.Eat withaspoonfromabowlofimaginarycereal;3.Sharpenapencil; 4.Unscrewalidfromajar;5.Drawacirclewithapencil.Eachtask wasperformed3timesbythechildandthehandusedwasrecorded

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bytheexperimenter.Thecircledrawingtaskalwayswentlast,as researchhasshowntheactofwritingcaninﬂuencesubsequent handuse(Annett,2002).Thetaskswerenotdemonstratedbythe experimenter,onlydescribedverbally,toavoiddirectcopying.The numberofitemsperformedwitheachhandwascalculatedintoa handednessquotientusingthefollowingformula:

[(R-L)/(R+L)]∗100, (1)

wherepositivevaluesindicaterighthandpreferenceandnegative valueslefthandedness.

This5-itemhandpreferencescaleappearedtohavegood inter-nalconsistency,␣=0.93.Allitemsappearedworthyofretentionin thismeasure,withthebiggestincreaseinalphacomingfromthe deletionofthe‘lidunscrewing’task,howeverremovalofthisitem onlyincreasedalphaby0.03.

2.2.2. Motorassessment

Asubsetof65participantscompletedtheMovement Assess-mentBatteryofChildren2ndEdition(MABC-2;Hendersonetal., 2007).Thistestbatteryassessesarangeofgrossandﬁnemotor skills,includingbalance,dexterityandhand-eyecoordination,and providesastandardisedscoreofmotordevelopment.Thesescores can then be measured against sets of normalised performance scoreswhichdeterminewhetherachildistypicallydevelopingin motorskillsfortheirage.TheMABC-2wasincludedtoensureall childrenmetthecriteriaofhavingtypicalmotordevelopmentfor theirage.

2.2.3. Vocabularyassessment

Inadditiontothemotorassessments83oftheparticipantsalso completedtheBritishPictureVocabularyScale-II(BPVS-II;Dunn &Dunn,2009)toassesslanguageability.TheBPVS-IIisatestof receptivevocabularyconsistingof168itemsarrangedin14setsof 12items,eachbecomingprogressivelymoredifﬁcult.The BPVS-IIrequireschildren toselectwhich pictureout offourpossible optionsbestﬁtsthewordreadaloudbytheexperimenter.Thistest wasselectedasithasnormalisedscoresforchildrenaged3and above,andbecauseitdoesnotrequirereadingandliteracyskills tocomplete,bothfactorswhichsuitedoursampleofparticipants. TheBPVS-IIproducesarawscore,which,followingconversionto astandardisedscore,canthenbecomparedtonormalisedscores byage.Split-halfanalysiswereusedtoassessinternalconsistency oftheitemspresentedandtheresultsshowedtheseitemswere highlyreliable(r=0.93,p<0.001).

2.3. Experimentalprocedure 2.3.1. Motorskillassessment

Togiveamoreaccuratemeasureofhandskillandmotor dexter-ity,alltheparticipantscarriedoutanelectronic,4trialversionofthe pegboardtaskdescribedbyFlowersandHudson(2013).Brieﬂy,this consistedofa280×100×20mmboardwithtworowsof20holes (7mmdiameter)drilled13mmapartalongthelength.Thedistance betweenthetwolinesofholeswas70mm.TheFitts’(1954)Index ofDifﬁculty(Id)measurementforthisboardwasId=7.6,makingit unlikelythatthetaskcanbeperformedbypre-programmedaimed movements,andmustinvolvesome“online”movementcontrol wherehandednessdifferencesaremostconsistentlyfound(Annett etal.,1979;FlowersandHudson,2013).Toimprovetiming accu-racytheboardwasconstructedtoallowdetectionofpegliftingand placingviaanelectricalcircuitintheboard.Thiswasconnectedto thePC’sParallelPort,whereaVisualBasicprogrammecontinuously monitoredandrecordedthetimesatwhichpegswereremoved fromorinsertedintotheholes.Cloakedstandardelectricalfuses (6mmdiameter×24mmlong)wereusedaspegs,themetalcaps

ofwhichallowedconductionbetweenthewirecontactswhenthe pegswereinsertedintheholes.

Pegsweremovedeitherawayfromthebody,thatis,fromthe nearrowofholestothefarone(‘Out’condition)orinreverse direc-tiontowardthebody (‘In’condition)onsuccessivetrials,which wereorderedasfollows:1.PreferredHandOut;2.Non-Preferred HandOut;3.Non-PreferredHandIn;4.PreferredHandIn.Scores onthistaskwerealsousedtoconﬁrmhandpreferenceasmeasured bythe5itemtask.

2.3.2. Speechlaterality

Allchildrenwereinvitedtotakepartintheimagingsectionof thestudy,withdeliberatefocusonencouragingthelefthanded participants(asdefinedbythe5-itempreferencetest)toincrease thelikelihoodofrecruitingatypicallylateralisedindividuals.Thirty eight of the children (22 males; aged between 3 and 10 yrs, meanage=6.5yrs,SD age=1.92yrs)respondedtothis invitation andunderwentfunctionaltranscranialDoppler(fTCD)imagingto determinetheirlanguagelateralisationprofile.Language lateralisa-tionwasdeterminedbymeasuringhemisphericchangesincerebral bloodflowvolume(CBFV)withfTCDduringananimation descrip-tiontask.TheAnimationdescription(AD)taskwasdevelopedasan effectiveneuroimagingparadigmtoelicitspeechlateralisationin pre-literatechildren(Bishopetal.,2009).Todatetheparadigmhas beenusedspecificallywithinfTCDandithasbeenvalidatedagainst thestandardwordgenerationparadigmusedinadultparticipants todeterminespeechlaterality.Theparadigmisdescribedindetail byBishopetal.(2010).Inbrief,participantswereseatedinfrontofa computerscreenwiththefTCDheadsetfitted.Eachtrialconsisted ofawatchphase,areportphaseandrestphase.Initiallyasilent animationwaspresentedinthecentreofacomputerscreenfor 12s,duringthistimeparticipantswererequiredtositsilentlyand watch;the‘watch’phase.Attheonsetofthetriala500msepoch markerwassimultaneouslysenttotheDoppler.Participantswere thenrequiredtodescribealouddetailsofthecartoonfor10s;the ‘report’phase.Thetrialconcludedwiththe‘rest’phase,whichwas an8speriodofrelaxationtoallowCBFVtoreturntobaselinebefore theonsetofthenexttrial.TheADparadigmconsistedof20trials intotal,eachlasting30s.Animationpresentationwasrandomised andnonewerepresentedmorethanoncetoanygivenparticipant. Althoughtheclips dohaveachronologicalsequence,the‘story’ theytellisverybasic,consistingmainlyofcharactersplaying/doing activitieseitherinsideoroutside.Thereforerandomisationofthe clipswouldnotcauseconfusionbyputtingeventsoutoforder; asthere wasnoobvioussequential element.The ‘watch’phase alsoservedasthepre-speakingbaselineperiod,followingprevious researchshowingnoevidenceoflateralisedactivationwhile par-ticipantspassivelywatchedthesevideoclips(Bishopetal.,2009). Theresponsestoeachanimationwereaudiorecordedtoenable subsequentanalysisoffluency.

2.4. Dataanalysis

2.4.1. Pegboardperformance

Performance ontheelectronic Pegboard taskwas measured by the speed with which the rows of pegs were completed. Mean movement times were calculated for the preferred and non-preferredhands,andameasurementofbetween-hand perfor-mancedifferencewascalculatedbysubtractingthenon-preferred handmeantimefromthepreferredhandmeantime.Toallowfor morereliablecomparisonbetweenindividualsthebetween-hand differencemeasurementwastransposedintoanadaptedversion ofthelateralityquotientscore,asdescribedbyAnnett(2002).In thisstudythequotientscorewasderivedtoindicatethedegree ofrelativehandskillonthistask,ratherthanhandedness direc-tion,andwascalculatedbythefollowingformula:[(preferredhand

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Table1

Pearson’srvaluesforthebehaviouralassessmentsacrossthewholesample(n=148).*_indicates_p_<_0.05;**_indicates_p_<_0.001.

Age HandednessQuotient BPVS-II MABC-2 PegboardPHmean WholeSample(n=148) HandednessQuotient −0.01

BPVS-II −0.09 −0.08 MABC-2 −0.07 0.07 0.23 PegboardPHmean −0.83** _−0.06 _−0.06 _−0.12 PegboardNPHmean −0.82** _−0.03 _−0.02 _−0.13 _0.95** SpeechLaterality sub-group(n=38) HandednessQuotient −0.04 BPVS-II 0.39* _−0.32 MABC-2 −0.003 −0.03 0.15 PegboardPHmean −0.82** _−0.08 _−0.32 _−0.12 PegboardNPHmean −0.87** _−0.01 _−0.41* _−0.15 _0.91**

meanscore− nonpreferred handmeanscore)/(preferredhand meanscore+nonpreferredhandmeanscore)]*100.Higher posi-tivequotientscoresindicategreaterproﬁciencywiththepreferred hand,andhighernegativequotientscoresindicategrater proﬁ-ciencywiththenon-preferredhand.Handpreferencewasusedas opposedtorightvsleftasthehypothesisconcernstherelative per-formancedifferencesbetweenthehands,andnotthedirectionof preferenceperse(seeFlowersandHudson,2013).

2.4.2. fTCD

RelativechangesinCBFVwithintheleftandrightMiddle Cere-bralArteries(MCAs)wereassessedusingbilateralfTCDmonitoring from a commercially available system (DWL Doppler-BoxTM_X: manufacturer, DWL Compumedics Germany GmbH). A 2-MHz transducerprobeattachedtoanadjustableheadsetwaspositioned overeachtemporalacousticwindowbilaterally.PsychoPySoftware (Peirce,2007)controlledtheanimationdescriptionexperimentand sentmarkerpulsestotheDopplersystemtodenotetheonsetofa trial.Datawereanalysedoff-linewithaMATLAB(MathworksInc., Sherborn,MA,USA)basedsoftwarepackagecalleddopOSCCI(see Badcocketal.,2012foradetaileddescription).DopOSCCImakesa numberofcomputationsinordertosummarizethefTCDdataand advancethevalidityofmeasuringhemisphericdifferencesinCBFV. First,thenumbersofsampleswerereducedbydownsamplingthe datafrom∼100Hz to25Hz. Second,variations incardiac cycle whichmaycontaminatetask-relatedsignalswerecorrectedusinga cardiaccycleintegrationtechnique(Deppeetal.,1997).Third,data contaminatedbymovementor‘drift’wereremovedpriorto nor-malisation,usingthe‘activationrejection’(wherebyepochswith activationoflessthan70%orgreaterthan130%oftheaverageblood flowvelocitywereexcludedfromtheanalysis)and‘epoch normal-isation’settingsindopOSCCIrespectively(Badcocketal.,2012). Trialswheretheexperimenterhadnotedoccurrenceoflargebody movements,talkingduringthebaselineorcoughingweremanually excludedfromtheanalysis.Normalisedepochsweresubsequently screenedandexcludedasmeasurementartefactsifactivation val-uesexceededtheacceptablerange(±40%meanCBFV).Fourth,to controlforphysiologicalprocesses thatcaninfluenceCBFV(e.g. breathingrate;arousal),themeanactivationofthebaselineperiod (takenfromthe‘watch’phase,between0–10s)wassubtractedfrom eachindividualepoch.Deviationsinleftversusrightactivitywere thereforebaselinecorrectedandreflectrelativechangesinCBFV.A lateralityindex(LI)wasderivedforeachparticipantbasedonthe differencebetweenleftandrightsidedactivitywithina2swindow. Theactivationwindowwascentralisedtothetimepointatwhich theleft-rightdeviationwasgreatestwithintheperiodofinterest (POI).InthepresentparadigmthePOIwastakenfromthe‘report’ phaseoftheparadigmandrangedfrom12to22sfollowingonset ofthetrial(Bishopetal.,2009).

Speechlateralitywasassumedtobeclearinallcasesinwhich the LI deviated by>2 SE from 0 (Knecht et al., 2001; Hudson

andHodgson,2016).Left-hemisphereorright-hemispherespeech dominancewasindicatedbypositiveornegativeindices respec-tively.CaseswithanLI<2SEfrom0werecategorisedashaving bilateralspeechrepresentation. Individualswerecategorisedas having‘Typical’speechrepresentationiftheydisplayedaclearLI scorewhichwaspositive,alternativelyindividualswithabilateral LIscoreoraclearLIscorewhichwasnegativewerecategorised ashaving‘Atypical’speechrepresentation.Participantsrequireda minimumof10acceptabletrialsfromthetotalof20presentedto beincludedintheanalysis(i.e.50%);all38participantsreachedthis threshold,and23ofthemachieved100%acceptabletrials(mean numberoftrialsaccepted=18.44;SD=2.3).

ToensurehighreliabilitywithintheLIscoresderivedfromthe speechtask, splithalfreliabilityestimates werecalculatedfrom Pearsoncorrelationsoftheoddandevenepochsforeachindividual. Forthegroupasawholecorrelationsindicateahighlevelofinternal consistencybetweenthereadings(r=0.62,p=0.001),meaningthat thefTCDmeasurementswerereliable.

2.4.3. Statisticalanalysis

The research questions outlined in the introduction were assessedbyaseriesofregressionanalyses.Firstly,toassesswhether skilledmotor performance changes with age,a multiple linear regressionwasconductedwiththetimedifference(ins)between thenon-preferredhandmeantimeandthepreferredhandmean time derived from the pegboard trials as the dependent vari-able,andage(inyearsandwholemonths)and thebehavioural assessmentscores(MABC-2,BPVS-IIandhandpreferencequotients derivedfromthe5-itemtask)aspredictorvariables.Toprobethe pegboardperformancemorecloselyaseriesofpairedsamples t-testswereusedtodeterminedifferencesbetweenthe4trialson thepegboard.

Asecondmultiplelinearregressionwasconductedonthe sub-groupofchildrenwhounderwentfTCDduringspeechproduction, toassesswhetherspeechlateralityproﬁlevariedsigniﬁcantlywith ageandmotorskill.ThemodeltreatedspeechLIasthe depen-dent variableand had 6 predictorvariables asfollows: Age (in yearsandmonths);thebehaviouralassessmentscores(MABC-2, BPVS-IIandhandpreference quotientsderived fromthe5-item task);thenumberofwordsproducedduringthespeechtaskand meanbetween-handdifferencescoresfromthepegboardtrials. Bootstrappingwasappliedtothis analysistoaccommodatethe increasednumberofpredictorvariablesandthereducedsample sizearisingfromthesub-group.

Finallyabinarylogisticregressionwasperformedtotestthe assumptionthatatypicalspeechlateralisationcouldbepredicted frommotorperformance,bytreatinglateralitygroup(typicalvs. atypical)asthedependentvariableandmeanbetween-hand dif-ferencescoresfromthepegboardtrialsasanindependentpredictor variable.

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Table2

Performancescoresonthebehaviouralassessmentsforthemotorlateralityanalysisandthespeechlateralitysub-group.

MotorLaterality (wholesample)

SpeechLaterality(sub-group,n=38)

Atypicalspeech Typicalspeech

n 148 13 25

Sex:M:F 73:75 7:6 15:10

Age:mean(SD) 6.41(2.05) 7.1(2.02) 6.9(1.9)

5-itemtaskscore(max=5):mean(SD) Right Left Either 4.02(1.77) 0.97(1.76) 0.02(0.14) 3.54(2.29) 1.5(2.29) n/a 4.4(1.44) 0.6(1.44) n/a

HandednessQuotient:mean(SE) 61.1(5.71) 41.5(25.4) 76.0(11.54)

BPVS-IIScore:mean(SD) n=83 98.3(13.5) 97.2(10.9) 96.5(14.4)

MABC-2Score:mean(SD) n=65 8.4(1.8) 7.8(2.3) 8.7(1.7)

LI:mean(SE) n/a −2.01(0.40) 2.8(1.9)

Wordsproduced:mean(SD) n/a 17.3(4.3) 14.5(3.3)

3. Results

Table1showsthecorrelationmatrixoftheparticipant’s perfor-manceacrosseachofthebehaviouraltestsbyage.Thisindicates thatthere werenosigniﬁcantrelationshipsbetweenageofthe participantsandanyofthebehaviouralmeasures,meaningthat participantsweresimilarlymatchedfor handpreference,motor and vocabulary ability; furthermore all participants fell within normalrangesfortheirageonthesemeasures(seeTable2). Par-ticipantsdidnotdiffersigniﬁcantlyonhandednessquotientsas derived fromthe5-itempreferencetask;there were26 partic-ipants with a handedness quotientat or below zero, denoting left-handedness.

3.2. Doesageaffectmotorskillperformance?

Datafrom5oftheoriginal153participantswasincomplete, duetotoofewtrialsperformedorfailuretocompletethetaskat all,meaningthatadequatedatawasavailableforatotalof148 chil-dren.Theexcludedchildrenwereagedasfollows:2×3yrs,1×4yrs, 1×5yrsand1×8yrs.

A multiple linear regression was conducted with mean between-handdifference scorefrom thepegboard trials asthe dependentvariable.Age,BPVS-IIscore,MABC-2scoreand hand-edness quotient derived from the5-item preference test were allenteredaspredictorvariables. Intercorrelationsbetweenthe regressionvariableswerereportedinTable1andtheregression statisticsareinTable3a).TheanalysisrevealedthatAgewasthe onlyvariablethatcontributedsigniﬁcantlytotheregressionmodel, anditaccountedfor49%ofthevariationinbetween-hand differ-encescoresonthepegboard.Thisindicatesthatyoungerchildren hadgreaterperformancedifferencesbetweentheirpreferredand non-preferredhands,whereasolderchildrenperformedsimilarly withbothoftheirhands.

Pairedsamplest-tests wereusedtodeterminedifferencesin preferredandnon-preferredhandperformanceonthepegboard acrossallparticipantsirrespectiveofage;asigniﬁcantdifference wasfound,wherethemeanpreferredhand(PH)movementtimes werelower,thusindicatingfasterperformance,thannon-preferred hand (NPH) movement times, t (147)=−14.49, p<0.001 (PH meantime=38.94s,SD=11.1;NPHmeantime=44.13s,SD=13.4, d=0.42).T-testsrevealedpractiseeffectswithinthepegboardtask, withlatertrialsbeingperformedsigniﬁcantlyfasterthanearlier trials,t(147)=4.76,p<0.001(Trial1meantime=41.91s,SD=14.3; Trial4meantime=38.52s,SD=11.9,d=.25,seeTable4).

Table3

Summaryofregressionanalysisforvariablespredictinga)between-handdifference scoresandb)speechlateralisationindices.

(a) B SEB ␤ Constant 15.34 4.93 Age −1.13 0.32 −0.49* HandednessQuotient −0.01 0.01 −0.06 BPVS-IIscore −0.01 0.05 −0.03 MABC-2score −0.14 0.34 −0.05 Note:R2_=.₂₇_(ps_<_0.001). *_p_<_0.001. (b) B. SEB. ␤ Constant 7.26. 2.36. Age −0.35. 0.26. −0.26. HandednessQuotient 0.01. 0.01. .07. MeanWordsProduced −0.15. 0.13. −0.22. Between-handdifference −0.31 0.11 −0.48*

Note:Bootstrappingapplied,R2₌_0.28_(ps_<_0.01).

*_p_<_0.01._Excluded_variables₌_MABC-2_scores_and_BPVS-II_scores.

3.3. Dospeechlateralisationproﬁlesvarywithage?

Asexpected,acrossthewholesampletherewasanoverallbias towardsactivationinthelefthemisphereduringspeech produc-tion,withthecombinedmeanLI=1.17(SD=2.59). Thirtyseven oftheparticipantshadLIs>2SEfrom0,denotingclear laterali-sation.TwelveofthecaseshadanegativeLIscoredenotingright hemispherebiasedactivation,and25 caseshad lefthemisphere dominantactivation.Theremainingcasewasclassedasbi-lateral duetoLI<2SEfrom0,(meanLIscore=0.56).

Abootstrappedmultiplelinearregressionwasconductedwith meanspeechlateralisationindexasthedependentvariable.Age, mean between-hand difference score, mean number of words produced,BPVS-IIscore,MABC-2scoreandhandednessquotient derivedfromthe5-itempreferencetestwereallenteredas pre-dictorvariables.Intercorrelationsbetweentheregressionvariables werereportedinTable1andtheregressionstatisticsareinTable3 b).Theanalysisrevealedthatmeanbetween-handdifferenceon thepegboardwastheonlyvariablethatcontributedsigniﬁcantly totheregressionmodel,anditaccountedfor48%ofthevariation inmeanspeechLIscores.Notably,agedidnotsigniﬁcantlypredict speechLIscore(seeFig.3),indicatingthatyoungerchildrenhada similarpatternoflefthemisphericspeechrepresentationasolder children.

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Table4

Pegboardperformanceforpreferred(PH)andnon-preferredhands(NPH),classifedbyhandpreferencecategory(derivedfromthe5-itemtaskscore),acrossthewhole sampleandforthespeechlateralitysub-group.

Mean(SD)pegboardmovementtimespertrial(seconds)

WholeGroup(n=148) n 1stPHout 2ndNPHout 3rdNPHin 4thPHin

Right-handed 123 41.6(14.4) 42.4(13.1) 44.4(13.3) 38.1(12.1)

Left-handed 25 44.2(13.5) 43.6(12.7) 45.8(17.6) 40.5(11.1)

p 0.403 0.690 0.656 0.386

SpeechLateralitysub-group(n=38) n 1stPHout 2ndNPHout 3rdNPHin 4thPHin

Right-handed 31 36.6(9.4) 39.4(9.9) 43.3(14.4) 35.6(10.7)

Left-handed 7 42.2(12.5) 40.7(14.0) 43.5(15.5) 41.1(16.4)

p 0.194 0.774 0.980 0.272

Fig.1. Between-handdifferencescoresonthepegboardtaskbyageforthewhole sample,withregressionlineﬁtted.

3.4. Canmotorskillperformancepredictspeechlateralisation? Finally,a suggestionfromresearchintoneurodevelopmental disordersaffectingspeechandmotorcontrolindicatethatatypical

Fig.3.Scatterplotofthemeanspeechlateralisationindicesacrossageofthe partici-pants.Thedottedlinedenotestheseparationbetweenlefthemispherelateralisation (denotedbypositiveLIvalues)andrighthemispherelateralisation(denotedby negativeLIvalues).

hemisphericspeechactivationcouldberepresentativeofan imma-ture,orimpaired,neuralspeechnetwork(HodgsonandHudson, 2016;HsuandBishop,2014;Bishop,2013).Toexaminewhether atypicalspeechrepresentationwasreﬂectedinthemotor perfor-mancescores,thedatawasdividedintotwogroupstorepresent;

Fig.2.Meanmovementtimesforallpegboardtrialscombined,splitbypreferredhand(PH)andnon-preferredhand(NPH),acrossparticipantage.Thesolidregressionline representstheNPHﬁtandthedashedlineisthepHﬁt.

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Fig.4. Scatterplotofthebetween-handdifferencelateralityquotientscoresacross twoclassiﬁcationsofspeechlaterality;typicalandatypical.Higherhandlaterality quotientsreﬂectgreaterdiscrepancyinperformancebetweenthedominantandthe non-dominanthands.Thegreycircledenotestheonebi-lateralcase.

1.Typicallefthemisphereactivationprofilesand2.Atypical activa-tionprofiles,denotedbyrighthemisphereorbi-lateralactivation. Thirteenchildrenwereclassedashavingatypicallateralisationand 25withtypical.Astepwisebinarylogisticregressionmodelwas usedtoassesswhetherpegboardperformancewasanaccurate pre-dictorofspeechlaterality.Group(typicaloratypical)wasentered asthedependentvariableandtheindependentpredictorwasthe timedifference(ins)betweenthenon-preferredhandmeantime andthepreferredhandmeantimederivedfromthepegboard tri-als.Themodelshowedthatbetweenhanddifferenceonthemean pegboardperformancescoresisasignificant,albeitweak,indicator ofspeechlateralisation,R2=0.16(Nagelkerke)[␹2(1)=4.61,Exp ␤=1.171](95%CI=1.003–1.386,p<0.05;seeFig.4).Thisindicates thatgreaterperformancedifferencesbetweenthehands signifi-cantlypredictsatypicalspeechlateralisationprofiles.

4. Discussion

4.1. Doesspeechlateralisationvarywithage?

Theaimofthisstudywastoassessthespeechandmotor later-alisationprofilesofchildrenaged3–10yearstodeterminewhether thetwofunctionsdevelopedinparallelandwhetheryounger chil-drenwoulddemonstratemorevariablelaterality.Resultsshowed thatmeanspeechlateralisationscoresshowedasignificant left-wardsbiasacrossallagestested,givingclearindicationthatspeech lateralisationisbiasedtothelefthemisphereby3years ofage. Thisisinlinewithotherrecentneuroimagingdatashowingthat evenveryyoungchildrendisplaytheexpectedpatternofleft hemi-spherelanguagedominance(Bishopetal.,2014;Kohleretal.,2015). Thedata alsorevealedthat handpreference wassimilarly well establishedbyage3,withallthechildreninthisstudyshowing aclearhanddominanceeffectonthe5-itempreferencescoreand themotorskilltask.Thisprovidesconfirmatoryevidence,froma largesample,inlinewithpreviousresearchsuggestingthat direc-tionofhandednessisestablishedearlyoninmotordevelopment (forreviewseeScharounandBryden,2014).

4.2. Doesageaffectmotorskillperformance?

Motor performance was significantly affected by age, with youngerchildrenshowingastrongerperformancepreferencefor theirdominanthandonthepegboardtask,adifferencewhich nar-rowedduringdevelopment.Thisfindingisrelativelyrare,buthas beenobservedpreviouslyinstudiesalsousingapegboardparadigm (e.g.KilshawandAnnett,1983;Royetal.,2003),andrepresentsthe developmentaltrajectoryofbi-manualproficiency.Italso demon-stratesthataskillbasedperformancemeasureismoresensitiveto assessinghandednessdevelopment,thaninventoriesbased prefer-encetools.Themotorskilldataalsoindicatesthattheperformance differencesyounger childrendisplayare mediatedbythe profi-ciency,orlackthereof,ofthenon-preferredhand(NPH).Thisis confirmedwithinourtestingbythefindingthatchildrenshowed significantlylongerlatenciesforpegboardtrialsrequiringachange indirectionwhenmovingtheNPH.Thisissomethingnotseenin previousadultpegboarddata(e.g.FlowersandHudson,2013),but isinaccordancewithpreviousevidencethatchildrenfindit eas-iertoperformaway-frombodymanualactions,ratherthanthose towardsthebody(e.g.Boessenkooletal.,1999).Evidenceshows thatspecialistareasofthelefthemisphereplayagreaterroleinthe controlofcomplex,finemotortasksforcontrolofboththeright andlefthand.Thisipsilateralcontrolnetworkforthelefthandisin contrasttothetypicalcontralateralcortico-motorcontrolnetworks whichgovernmotoractions(Serrienetal.,2006;Haarlandetal., 2004).ThereforethefindingthatNPHproficiencyunderliesthis differenceinpegboardperformancesuggeststhatitisspecifically thedevelopmentofipsilateralpathway,fromlefthemispheretoleft hand,whichiskeytounderstandingtheneuralprofileofmotorskill development.Thisfindingisinlinewithrecentworkshowingthat adultswithdevelopmentalmotorcoordinationimpairments,such asDevelopmentalCoordinationDisorder,performmorepoorlyon finemotortaskswiththeirnon-dominanthand(Debrabantetal., 2013;HodgsonandHudson,2016)andthatapraxicpatientswith lefthemispheredamageshowdeficitsperformingheterogeneous motorsequences.Takentogetherthesefindingsindicatethatthe ipsilateralpathwaycontrollingthenon-dominanthandfromthe languagedominanthemisphere(typicallytheleft),maytakelonger todeveloptofunctionalmaturity,andthatindividualswithdeficits inmotorcoordinationareactuallydisplayingperformanceofan immatureipsilateralcontrolpathway.

4.3. Canmotorskillperformancepredictspeechlateralisation? A further key finding from this data was the relationship between direction of hemispheric speech representation and extent ofperformance difference betweenthe hands, a finding which was independentof age or hand preference. Individuals who displayatypical speechlateralisation showgreater perfor-mancedifferencesbetweentheirhandsonthemotorskilltask. Theseresultssupportthetheorythatactioninvolvingfinemotor sequencingandspeechproductionengageacommon cognitive-motorneuralnetwork,andthatthesenetworksdevelopinparallel forthedominanthand/hemisphere mapping.Thedataindicates that thisrelationship betweenspeechlateralityand motor skill wasirrespectiveofdirectionofhandpreference,andthusgiven thelefthemisphere’sspecialismforsequentialresponseordering inboththeleftandrighthands(SerrienandSovijarvi-Spape,2015; KotzandSchwartze,2016),itispossibletoconcludethatrelative performance differences betweenthehands are more informa-tive about therelationship between cerebral lateralisation and handedness,thanisthedirectionofhandpreferenceperse. Fur-thermore,thisdatasuggestthattheperformanceofnon-dominant handthroughoutdevelopment,andparticularlywhetherthis per-formancedifferencereduceswithage,maybekeytoidentifying

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thosewithatypicalspeechlateralisation,whoaretherefore poten-tiallymorelikelytohavedifficultieswithmotor/languagetasks. Although,itshouldbestressedthatatypicallateralisationdoesnot necessitatelanguage/motor deficits,infactlittleevidenceexists tosupportthis(Bishop,2013),butratherthatthosewhodohave developmentaldifficultiesmaybedetectedthroughsimplemotor skilltasks.Causalitycannotbeinferredfromthisdata,butthe find-ingthatatypicalspeechrepresentationislinkedtohandskillisin linewithevidencefromneurodevelopmentaldisordersshowing atypicalpatternsofspeechlateralityinindividualswith develop-mentalmotor coordinationimpairments(Hodgsonand Hudson, 2016), indicating shiftingfunctional organisationinspeech net-worksasaresultofimpairedmotorpathways.

Oneunexpectedoutcomefromthisstudywasthatperformance onthebehaviouralassessmentsofvocabularyandmotorabilitydid notcorrelatewithpegboardperformanceorspeechlaterality.It hasbeenshownpreviouslythattherearelinksbetweentask profi-ciencyanddegreeoflateralisation(Groenetal.,2012),butourdata didnotreplicatethis.Apossibleexplanationforthatfailureisthat thetypesofbehaviouralassessmentweused(BPVS-IIand MABC-2)lackedsensitivitytotheparticularfunctionswewereassessing. TheBPVS-IIdoesnotcontaintasksorperformancemeasurements relatedtosequencingormotorresponsetiming,andsocould eas-ilybearguednottotapintothetypeofphonologicalprocessing. Furthermore,thetestbatterydoesnotrequireaverbalresponseto bemade,butmerelyprovidesascoreofvocabularyabilitybased uponrecognitiononly,neverthelessduetotheagerangesinour sample,itwasnecessarytouseanassessmenttoolwhichdidnot relyonliteracyability.Futureworkshouldinvestigatethe compo-nentprocessesinvolvedinspeechproductionandmeasurerelative lateralisationprofilesacrossdevelopment.Thelackofsensitivityin theMABC-2wasmoresurprising,asthistestbatterydoesindeed containseveraltasksdirectlyrelatedtosequencing,motortiming andco-ordination,allcomponentsthoughttoformthebasisofthe speech-motorsystem(KotzandSchwartze,2016).Howeverthe scoringsystememployedbythisbatterymakesitdifficulttodetect subtleandnuancedmotordeficitsasresultsaredrawnfrom sub-sectionsofgroupedtests,wheresomemayhavebeenperformed wellbutotherslesswell,resultinginanaveragescoreindicating typicaldevelopment,butnotanin-depthprofileofdifferingaspects ofmotordevelopment.However,aswiththeBPVS-II,theMABC-2 wasusefulinconfirmingtypicalityofoursample,althoughfuture workrelatingspeechandmotorabilityshouldfocusonarangeof behaviouralproficiencymeasures.

5. Conclusions

Thisstudysetouttoanswerthreespecificresearchquestions regardingtheeffectofageonmotorskillperformanceandspeech lateralisationindices,aswellasontheinteractionbetweenmotor performanceandspeechlateralisation.Thedatashowedthat,1) motorskilldoesvarywithage,wherebyyoungerchildrenshow sig-nificantlylargerperformancedifferencesbetweentheirpreferred andnon-preferredhands;2)Speechlateralisationindicesdonot varywithageinasample of3–10yearoldtypically developing children;3)greaterperformancedifferencesbetweenthehands significantlypredictsatypicalspeechlateralisation,regardlessof participantageorhandpreference.

Inconclusionthesedatasuggestthatlateralisationoflanguage andmotorcontrolisaprocesswhichbeginsveryearlyin devel-opment,beforethechildisproﬁcientatmanualcoordinationor speech.Evidencefromearlylateralisationofauditoryprocessing

(Dehaene-Lambertzetal.,2002)mayindicatethestartofthis hemi-sphericspecialisationseeninlaterchildhood;perhapsmostcritical istheperiodinwhichspeechsoundandmotoroutputmappings arebeginningtobeformedandrehearsed.Thespecialisationof thelefthemispherefor controlofresponse sequencesand tim-ingintegrationalsoaccountsforthepatternsobservedbetween speechlateralityandmotorperformance(Serrienand Sovijarvi-Spape,2015).Futureworkneedstofocusonisolatingthecommon componentsofthespeechandmotortaskswhichmaybedriving thisrelationshipandwillalsolookattheperformanceofindividuals withmotorimpairments.

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