SoftwareforadvancedHRVanalysis
Juha-PekkaNiskanen,MikaP.Tarvainen,PerttuO.Ranta-aho,andPasiA.Karjalainen
4.9.2002
ReportNo.2/2002
ThismanuscripthasbeensubmittedtoComputerMethodsandProgramsinBiomedicine
UniversityofKuopio•DepartmentofAppliedPhysics
P.O.Box1627,FIN-70211Kuopio,Finland
SoftwareforadvancedHRVanalysis
Juha-PekkaNiskanen∗,MikaP.Tarvainen,PerttuO.Ranta-aho,
PasiA.Karjalainen
4.9.2002
AbstractAcomputerprogramforadvancedheartratevariability(HRV)analysisispresented.Thepro-gramcalculatesallthecommonlyusedtime-andfrequency-domainmeasuresofHRVaswellthenonlinearPoincar´eplotandbothparametricandnonparametricspectrumestimates.Theprogramgeneratesanin-formativeprintablereportsheetwhichcanbeexportedtovariousfileformatsincludingportabledocumentformat(PDF).ResultscanalsobesavedasanASCIIfilefromwhichtheycanbeimportedtoaspread-sheetprogramsuchasMicrosoftExcel.TogetherwithamodernheartratemonitorcapableofrecordingRRintervalsthisfreelydistributedprogramformsacompletelow-costHRVmeasuringandanalysissystem.Heartratevariability,Analysissoftware,Computerprogram,HRV
1Introduction
Heartratevariability(HRV)describesthevariationsbetweenconsecutiveheartbeats.Theregu-lationmechanismsofHRVoriginatefromsympatheticandparasympatheticnervoussystemsandthusHRVcanbeusedasaquantitativemarkerofautonomicnervoussystem[1].Stress,certaincardiacdiseases,andotherpathologicstatesaffectonHRV.AgoodreviewofphysiologicaloriginsandmechanismsofHRVcanbefoundin[2].
InHRVanalysiseithertheheartrateasafunctionoftimeortheintervalsbetweensuccessiveQRScomplexesneedtobedetermined.InthispaperwhenwetalkaboutHRVweactuallymeanthevariabilityofRRintervals(i.e.intervalsbetweenconsecutiveRpeaks).
HRVanalysismethodscanbedividedintotime-domain,frequency-domain,andnonlinearmethods.Inthefollowingthesemethodsarediscussedshortly.DenotionsanddefinitionsforHRVparametersinthispaperandinthedevelopedsoftwarefollowtheguidelinesgivenin[1].1.1
Time-domainmethods
Thetime-domainparametersarethemostsimpleonescalculateddirectlyfromtherawRRintervaltimeseries.ThesimplesttimedomainmeasuresarethemeanandstandarddeviationoftheRRintervals.ThestandarddeviationofRRintervals(SDNN)describestheoverallvariationintheRRintervalsignalwhilstthestandarddeviationofthedifferencesbetweenconsecutiveRRintervals(SDSD)describesshort-termvariation.ForastationarytimeseriesSDSDequalstotherootmeansquare(RMS)ofthedifferencesbetweenconsecutiveRRintervals(RMSSD).
TherearealsoothercommonlyusedparameterslikeNN50whichisthenumberofconsecutiveRRintervalsdifferingmorethan50ms.ThepNN50isthepercentagevalueofNN50intervals.TheprefixNNstandsfornormal-to-normalintervals(i.e.intervalsbetweenconsecutiveQRScomplexesresultingfromsinusnodedepolarizations).Inpractice,RRandNNintervalsusuallyappeartobesame.
Furthermore,therearesomegeometricmeasuresliketheHRVtriangularindexandTINNthataredeterminedfromthehistogramofRRintervals[1].
Niskanen,MikaP.Tarvainen,PerttuO.Ranta-aho,andPasiA.KarjalainenarewithUniversityof
Kuopio,DepartmentofAppliedPhysics,P.O.Box1627,FIN-70211Kuopio,Finland
∗Juha-Pekka
1
1.2Frequencydomainmethods
TheRRintervaltimeseriesisanirregularlytime-sampledsignal.Thisisnotanissueintime-domain,butinthefrequency-domainithastobetakenintoaccount.Ifthespectrumestimateiscalculatedfromthisirregularlytime-sampledsignal,implicitlyassumingittobeevenlysampled,additionalharmoniccomponentsaregeneratedinthespectrum.Therefore,theRRintervalsignalisusuallyinterpolatedbeforethespectralanalysistorecoveranevenlysampledsignalfromtheirregularlysampledeventseries.
Inthefrequency-domainanalysispowerspectraldensity(PSD)oftheRRseriesiscalculated.MethodsforcalculatingthePSDestimatemaybedividedintononparametric[e.g.fastFouriertransform(FFT)based]andparametric[e.g.basedonautoregressive(AR)models]methods[3].ThePSDisanalyzedbycalculatingpowersandpeakfrequenciesfordifferentfrequencybands.Thecommonlyusedfrequencybandsareverylowfrequency(VLF,0-0.04Hz),lowfrequency(LF,0.04-0.15Hz),andhighfrequency(HF,0.15-0.4Hz).Themostcommonfrequency-domainparametersincludethepowersofVLF,LF,andHFbandsinabsoluteandrelativevalues,thenormalizedpowerofLFandHFbands,andtheLFtoHFratio.Alsothepeakfrequenciesaredeterminedforeachfrequencyband.FortheFFTbasedspectrumpowersarecalculatedbyintegratingthespectrumoverthefrequencybands.Theparametricspectrum,ontheotherhand,canbedividedintocomponentsandthebandpowersareobtainedaspowersofthesecomponents.Adetaileddescriptionofthiscanbefounde.g.in[4].ThispropertyofparametricspectrumestimationhasmadeitpopularinHRVanalysis.1.3
Nonlinearmethods
ItisrealistictopresumethatHRValsocontainsnonlinearpropertiesbecauseofthecomplexregulationmechanismscontrollingit.Theinterpretationandunderstandingofmanynonlinearmethodsis,however,stillinsufficient.
OnesimpleandeasytocomprehendnonlinearmethodisthesocalledPoincar´eplot.ItisagraphicalpresentationofthecorrelationbetweenconsecutiveRRintervals.ThegeometryofthePoincar´eplotisessential.Acommonwaytodescribethegeometryistofitanellipsetothegraph[5].Theellipseisfittedontothesocalledline-of-identityat45◦tothenormalaxis.Thestandarddeviationofthepointsperpendiculartotheline-of-identitydenotedbySD1describesshort-termvariabilitywhichismainlycausedbyrespiratorysinusarrhythmia(RSA).Thestandarddeviationalongtheline-of-identitydenotedbySD2describeslong-termvariability.1.4
Aimofthisstudy
InthisstudywepresentacomputerprogramforadvancedHRVanalysisforWindowsoperatingsystems.Theprogramcalculatesallthecommonlyusedtime-andfrequency-domainparametersofHRVaswellthenonlinearPoincar´eplotandbothparametricandnonparametricspectrumestimates.ItalsofeaturesadvanceddetrendingoptionsforRRseriesandaninformativeprintablereportsheetwhichcanalsobeexportedtovariousfileformatsincludingportabledocumentformat(PDF).CombinedwithamodernheartratemonitorcapableofrecordingRRintervalsthisfreelydistributedprogramformsacompletelow-costHRVmeasuringandanalysissystem.
2Background
WehavebeendevelopingaMatlab1basedsoftwarepackageforevent-relatedbiosignalanalysisincollaborationwiththeKuopioUniversityHospitalandtheBrain@Work-LaboratoryoftheFinnishInstituteofOccupationalHealth.Thesoftwarepackageconsistsofamainbrowserfordifferentbiosignalsandofvariousanalysistools.ThepresentedHRVanalysissoftwareforWindowshasoriginatedfromtheHRVanalysistoolofthissoftwarepackage.
ThegrowinginterestinHRVandtheabsenceoffreeandprofessionalHRVanalysisprogramshaveledusontoportingtheexistingMatlabbasedprogramtoastandalonewindowsapplication.Ouraimhasbeentodevelopafreeandfull-featuredHRVanalysissoftwareforphysiciansand
1Matlab
isaregisteredtrademarkoftheMathworksInc.http://www.mathworks.com
2
othermedicalexpertsinresearchorclinicalfield.Therearesomecommercialprogramsavailableforthiskindofanalysis,suchastheNevrokardHRVSystem(MedistarInc.),buttheircostissometimestoohighformanyapplications.
TableI:Variablescalculatedbytheprogramwithshortdescription
VariableMean&STDRRMean&STDHRRMSSDNN50pNN50
Unitss1/minmscount%
DescriptionStatisticalMeasuresMeanandstandarddeviationoftheselectedRRintervalseriesMeanandstandarddeviationoftheselectedheartrateseriesTherootmeansquareofdifferencesofsuccessiveRRintervalsNumberofconsecutiveRRintervalsthatdiffermorethan50ms
ThepercentagevalueofconsecutiveRRintervalsthatdiffermorethan50ms
GeometricMeasuresTheintegralofthesampledensitydistributionofRRintervalsdividedbythemaximumofthedensitydistribution
RRtriangularindexTINN
ms
SD1SD2
PeakfrequencyPower
Baselinewidthoftheminimumsquaredifferencetriangular
interpolationofthemaximumofthesampledensitydistributionofRRintervals
NonlinearMeasures(Poincar´eplot)msThestandarddeviationofpoincar´eplotperpendiculartotheline-of-identity
msThestandarddeviationofpoincar´eplotalongtheline-of-identitySpectralMeasures(parametricandnonparametric)HzPeakfrequenciesofthepowerspectraldensityestimateforVLF,LF,andHFfrequencybandsms2,%andn.u.
ThepowersforVLF,LF,andHFfrequencybandsinms2andinpercentagevalue.ForLFandHFbandsthepowerisalsorepresentedinnormalizedunits(n.u.).
RatioofLFandHFfrequencybandpowersin[ms2]
LF/HF%
3Programdescription
TheprogramwasoriginallydevelopedusingMatlab6.1(Release12.1).Thefinalversionoftheprogramhasbeencompiledtoastand-aloneC-languageapplicationusingtheMatlabCompilerSuite2.3andthefreeBorlandC-Builder5.5compiler.ThustheprogramisnowindependentfromMatlabanddoesnotrequireMatlabinstallationtorun.
ThepresentedHRVanalysissoftwarecalculatesallthecommonlyusedtime-andfrequency-domainmeasuresofheartratevariability.AllthecalculatedparametersaresummarizedinTableI.Theemphasisinthedevelopmentoftheprogramhasbeenoncompleteheartratevariabilityanalysiscombinedwitheaseofuse.Thuswehaveimplementedaneasy-to-usegraphicaluserinterfacefortheprogram(Fig.1).
Aftertheanalysistheprogramgeneratesaneasytointerpretprintableone-pagereportsheet(Fig.3)whichcanalsobeexportedtovariousfileformats.ThemostimportantresultsoftheanalysiscanalsobesavedasanASCIItextfilefromwhichtheyareeasytoimporttootherprogramsforlateranalysis.3.1
Inputformatfordata
Therearenumerousdifferentelectrocardiogram(ECG)measuringdeviceswithmanymoreorlessproprietaryfileformats.Thuswritingasupportforeveryprogramwouldbeanendlessjob.HowevermostoftheECGmeasuringprogramscanexporttheRRtimeseriesinsomecommonlyuseddataformat.OneoftheseuniversaldataformatsisasimpleASCIItextfile.HencewehavechosentohavetheRRintervaldataasacolumnvectorinASCIIformat.
SupportforASCIIfilesopensnewkindofpossibilitiessincethereexistssomeinexpensiveandeasilyavailableproductsforheartratemonitoring2.
2One
oftheseproductsisthePOLARS810heartratemonitorusedinthesamplerunsofthisarticle.
3
Fig.1:Theuserinterfaceoftheprogram.
3.2Theuserinterface
ThedevelopedHRVanalysissoftwareisoperatedwithagraphicaluserinterfaceconsistingofonlyonewindowshowninFig.1.
Theuserinterfaceisdividedintothreesegments:thedatabrowsersegmentonthetopoftheuserinterface,analysisoptionssegmentonthelowerleft-handside,andresultsviewsegmentonthelowerright-handsideoftheuserinterface.3.2.1
Databrowser
ThedatabrowsersegmentdisplaysthemeasuredRRintervaltimeseries.Theselectedpartorpartsofthedataareshownasapatchoverthedata.Anestimatefortrendintheselectedpartofthedataisshownoverthepatch.Thepatchismovableandresizablewithmouse.Thex-axislimitofthedataviewcanbechangedbymodifyingthevaluebesidetheRangetext.Thenameoftheselecteddata-fileisdisplayedoverthedatabrowser.
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3.2.2Analysisoptions
Theanalysisoptionssegmentoftheprogramuserinterfacehasbeendividedintofivesubcategories.TheleftsideofthesegmentcontainsFrequencyBands,DetrendingofRRseries,andInterpolationofRRseriesoptions.TherightsidecontainsRRSampleSelectionandSpectrumEstimationoptions.Eachoftheseoptionsaredescribedbelow.
FrequencyBands:Thefrequencylimitsforverylowfrequency(VLF),lowfrequency(LF),andhighfrequency(HF)bandsarealterable.TheUseDefaultsbuttonrestoresthefrequencybandsintotheirdefaultvalueswhichare0-0.04HzforVLF,0.04-0.15HzforLF,and0.15-0.4HzforHFband.
DetrendingofRRSeries:SometimestheRRintervaltimeseriesincludesadisturbinglow
ntrendcomponent.nfrequencynbaselineDetrendingoptionscanbeusedtoremovethiskindoftrend
components.Detrendingoptionsincluderemovalofthefirstorsecondorderlineartrendorthetrendcanberemovedusingthesocalledsmoothnesspriorsmethodpresentedin[6].
InterpolationofRRSeries:RRintervaltimeseriesisanirregularlytime-sampledseriesandshouldthereforebeinterpolatedpriortospectrumestimation.Theprogramusescubicinterpola-tionatthedefaultrateof4Hz.
RRSampleSelection:ThepartoftheRRseriestobeanalyzedcanbeselectedbyeditingtheStartandEndvaluesorbyjustmoving/resizingthepatchovertheRRseries.Theanalyzedsegmentcanalsobeformedbymergingtwoormoresmallersegments.Thenumberofsegmentsislimitedto20segments.
SpectrumEstimation:Thissubcategoryisdividedintotwoparts:Welch’sPeriodogram(FFTbasedspectrum)andARSpectrum(autoregressivemodelingbasedspectrum).Thenumberofpointsinfrequencydomaincanbechangedforbothspectrumestimates.ForWelch’speriodogramalsothewidthandoverlapoftheHanningwindowcanbeadjustedinpoints[3],andforARspectrumtheorderofthemodelcanbechanged.ThesocalledFBLS-method(forward-backwardlinearleastsquaresmethod)isusedforthecalculationoftheAR-modelparameters[3].ThedefaultvaluesoftheseoptionsaresetfortheRRinterpolationrateof4Hz.
Allthedefaultvaluesfordifferenttunableparametersintheanalysisoptionssegmentcanbecustomized,byeditingacommentedASCIIconfigurationfile(namedhrvparam.dat)locatedintheinstalldirectoryoftheprogram.3.2.3
Resultsview
Theresultsviewsectionisforviewingcalculatedparametersandspectrumsforprevailingoptions.Itcontainsfourbuttonswhichcontrolthedisplayedresults(Fig.2).ChoosingtheARSpectrumoption,theautoregressivespectrumestimateisdisplayedalongwithtableofcalculatedparametersforthespectrum(Fig.2(a)).ThepowersandpeakfrequenciesfortheARspectrumarecalculatedfromthedistinctcomponents.TheFFTSpectrumbuttondisplaystheWelch’speriodogramand,correspondingly,atableofparameterscalculatedfromtheperiodogram(Fig.2(b)).TheStatisticsbuttondisplaysatableofcalculatedtime-domainparameters(Fig.2(c)).UnderthetableRRintervalandheartratehistogramsaredisplayed.ChoosingthePoincareplotoption,thenonlinearPoincar´eplotalongwithcalculatedparametersisdisplayed(Fig.2(d)).3.2.4Meusadtoolbarbuttos
Therearethreeusermenusandsixtoolbarbuttonslocatedintheupperleft-handcorneroftheprograminterfacewindow(Fig.1).TheFilemenuincludesOpen,Save,SaveAs,andQuitcommands.TheSavecommandsavesthenumericresultsoftheanalysistoafileinASCIIformat.Columnsofthefileareseparatedwithcommassothattheresultscouldeasilybeimportedtoe.g.aspreadsheetprogramsuchasMicrosoftExcelforfurtherinspection.Open,Save,andQuitcommandsarealsoavailableastoolbarbuttons.
TheReportmenuhasReportSheetoptionwhichopenstheprintablereportsheetwindow(Fig.3).Reportsheetwindowoptionisalsoincludedasatoolbarbutton.
TheHelpmenuhasAboutoptionwhichopenstheaboutdialog.Theaboutdialogcontainstheversionnumberoftheprogramandcontactinformation.Theaboutdialogcanalsobeinvoked
5
(a)(b)
(c)(d)
Fig.2:Differentoptionsoftheresultsviewsegmentoftheprogramsuserinterface.(a)ARspectrumestimationresults,(b)FFTbasedspectrumestimationresults,(c)time-domainparametersanddistributionhistograms,(d)Poincar´eplotresults.
withatoolbarbutton.Thereisalsoatoolbarbuttonforshowing/hidingtheRRintervaldatamarkers.3.3
Thereportsheet
Theprogramgeneratesaninformativeprintablereportsheetaftertheanalysishasbeenmade.Thereportincludesinonepagealltheparameterscalculatedbytheprogram.AscreenshotofthereportsheetispresentedinFig3.
Therearesevenbuttonsinthereportpagetoolbar.Inorderfromlefttoright:Export,Print,ZoomIn,ZoomOut,Restoreoriginalview,Moveviewablearea,andClose.ThePrintbuttonopenstheprintdialogoftheoperatingsystemandtheClosebuttonclosesthereportwindow.TheExportbuttonopensaspecificexportdialog.SupportedfileformatsintheexportdialogaresummarizedinTableII.Version6.53oftheGNUGhostscriptisusedforexportingthereportsheettosomeofthefileformatsanditisincludedintheprogramdistribution.GNUGhostscript
6
Fig.3:Reportsheetgeneratedbytheprogram.
7
isdistributedwiththeGNUGeneralPublicLicense.
TableII:Supportedfileformatstoexportthereportsheet
FileFormatExtensionPortableDocumentFormat.pdfEnhancedMetafile.emfBitmapfile.bmpEncapsulatedPostscript.epsJPEGimagefile.jpgTIFFimagefile.tifPortableNetworkGraphicsfile.pngPaintbrush24-bitfile.pcxPortableBitmapfile.pbmPortableGraymapfile.pgmPortablePixmapfile.ppm
3.4Hardwarespecifications
HRVanalysissoftwarewillrunonall32-bitwindowsoperatingsystems(thatis,windows
98/Me/NT/2000/XP).Itshouldworkalsoinwindows95environmentalthoughithasnotbeentested.TheprogramrequiresaPCsystemwithabout30MBofharddiskspace,aPentiumclassorhigherprocessorwithx86architecture,minimumof32MBRAManddesktopresolutionof800x600(although1024x768orhigherisrecommendedforusability).ForcomputationsitusesmainlyMatlablibrarieswhichareincludedintheprogramdistribution.
4Sampleruns
AsatestcasewemeasuredHRVfromahealthyyoungfemaleatrestinalyingposition.AsameasuringdeviceaPOLARS810heartratemonitorwasused.ItiscapableofautomaticallystoringconsecutiveRRintervalsanditisveryinexpensivecomparedtoothercommercialECGorRRintervalmeasuringdevices.TheresolutionofPOLARVantageNVheartratemonitor,whichisanalogoustoS810butwithlowermemorycapacity,wasstudiedin[7].TheinaccuracyoftheRRintervalmeasurementswasshowntobelessthan3mswhichissufficientforHRVanalysis.Thetimingaccuracyofthebuild-inQRSdetectionsystemwasstudiedin[8].
PriortoHRVanalysis,themeasuredRRintervaldatawaspreprocessedforartifactsusingthePolarPrecisionPerformanceTMsoftwarethatcamewiththeheartratemonitor.ThemeasuredpreprocessedRRintervaldatacanbeseeninthedatabrowsersegmentoftheuserinterfaceinFig.1.Foranalysisasegmentfrom140to340secondswasselected.ObtainedresultsfortheselectedRRepocharepresentedinthereportsheetinFig.3.ThelowfrequencytrendcomponentintheRRserieswasremovedusingthesmoothnesspriorsbasedapproach.Thesmoothnesspriorsmethod[9]operateslikeatime-varyingfiniteimpulseresponse(FIR)high-passfilteranditiseasytoapplytodifferentoccasions,sinceithasonlyoneadjustableparameter.
Theeffectofthedetrendingprocedureonthespectrumestimatesandonfewpopulartime-domainparametersispresentedinFig.4andTableIII.ThespectrumestimatesoftheoriginalanddetrendedRRseriesarecomparedinFig.4(b).FortheWelch’speriodogrammethod,theVLFcomponentisproperlyremovedwhilethehigherfrequencycomponentsarenotsignificantlyalteredbythedetrending.ButwhenARmodelsofrelativelyloworderareused,whichisusuallydesirableinHRVanalysisinordertoenabledistinctdivisionofthespectrumintoVLF,LF,andHFcomponents,theeffectofdetrendingisremarkable.IntheARspectrumoftheoriginalRRseriestheLFandHFcomponentsarealmostentirelyobscuredbythestrongVLFcomponent.However,fromthedetrendedRRseriesspectrumtheLFandHFcomponentsareclearlyevidentandmorecongruentwiththeWelch’speriodogram.
Theeffectofthedetrendingprocedureonafewcommonlyusedtime-domainparametersisshowninTableIII.ThedetrendinghasnaturallyastrongeffectonSDNNandonlyasmalleffectonRMSSDandpNN50whichdescribetheshort-termRRvariability.Finallyitshouldbeemphasizedthatwhenusinganydetrendingmethodoneshouldmakesurethatthedetrendingdoesnotloseanyusefulinformationfromthelowerfrequencycomponents.
8
1.2RRI (s)10.80.60.20DetrendedRRI−0.2140240Time (s)3400.050.040.030.020.01PSD (s/Hz)200.050.040.030.020.01000.25Frequency (Hz)0.5VariableSDNNRMSSDpNN50Units(ms)(ms)(%)Original82.1271.9040.71Detrended68.5371.4041.59
5Futureplans
Infutureversionsweintendtoaddread-supportforNeuroScancontinuousCNTfiles(NeuroScanInc.),BiopacAcqKnowledgefiles(BiopacSystemsInc.),andpossiblyforsomeotherfileformats.ThiswillalsoincludesupportforviewingrawECGdataandautomaticdetectionofQRS-complexesforcalculatingRRintervals.ThesefeaturesarealreadyimplementedintheMatlabversionofthesoftware.
WearealsoplanningtoporttheapplicationtoLinuxandotherUnixbasedsystems.
9
6Discussion
WehavepresentedacomputerprogramforadvancedHRVanalysisforWindowsoperatingsys-tems.Theprogramcalculatesallthecommonlyusedtime-andfrequency-domainparametersandthenonlinearPoincar´eplot.Advancedspectrumestimationmethodsanddetrendingoptionsareincludedaswell.Theprogramgeneratesaninformativeandeasytointerpretprintableone-pagereportsheetthatcanbeexportedtovariousdifferentfileformatsincludingtheportabledocumentformat(PDF).ThemostimportantresultsoftheanalysiscanalsobesavedasanASCIItextfilefromwhichtheyareeasytoimporttoaspreadsheetprogramsuchasMicrosoftExcelforlateranalysis.Theuserinterfaceoftheprogramfunctionswithonlyonewindowwhichsimplifiestheuseoftheprogramconsiderably.Thissoftwareisaimedatphysiciansandothermedicalexpertsforclinicalorresearchuseanditisavailablefreeofchargeuponrequest.
HRVanalysishasalongtimebeenconsideredonlyasa”researchtoy”,butnowadaysithasalsogainedgrowinginterestintheclinicalfieldaswell.ThishasraisedaneedforinexpensivemethodsforadvancedHRVanalysis.ThepresentedHRVanalysissoftwareforwindowstogetherwithmodernheartratemonitorabletorecordRRintervalscreatesacompletelow-costHRVmeasuringandanalysissystem.
7Availability
TheHRVanalysissoftwareforWindowsisavailablefreeofchargeuponrequest.Ifyouareinterestedindownloadingandusingthesoftwarepleasevisithttp://venda.uku.fi/research/biosignaloremailtoPasi.Karjalainen@uku.fiforfurtherinstructions.
Acknowledgments
ThisworkhasbeendoneincollaborationwithKuopioUniversityHospitalandtheBrain@Work-LaboratoryoftheFinnishInstituteofOccupationalHealth.
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