DifferentNeuralManifestationsofTwoSlowFrequencyBandsinRestingFunctionalMagneticResonanceImaging:ASystemicSurveyatRegional,Interregional,andNetworkLevels

Shao-WeiXue,1,2DaLi,1,2Xu-ChuWeng,1,2GeorgNorthoff,1,3andDian-WenLi1,2AbstractTemporalandspectralperspectivesaretwofundamentalfacetsindecipheringfluctuatingsignals.Inrestingstate,thedynamicsofbloodoxygenlevel-dependent(BOLD)signalsrecordedbyfunctionalmagneticresonanceim-aging(fMRI)havebeenproventobestrikinglyinformative(0.01–0.1Hz).Thedistinctionbetweenslow-4(0.027–0.073Hz)andslow-5(0.01–0.027Hz)hasbeendescribed,butthepertinentdatahaveneverbeensystem-aticallyinvestigated.ThisstudyusedfMRItomeasurespontaneousbrainactivityandtoexplorethedifferentspectralcharacteristicsofslow-4andslow-5atregional,interregional,andnetworklevels,respectivelyassessedbyregionalhomogeneity(ReHo)andmeanamplitudeoflow-frequencyfluctuation(mALFF),functionalcon-nectivity(FC)patterns,andgraphtheory.Resultsofpairedt-testssupported/replicatedrecentresearchdividinglow-frequencyBOLDfluctuationintoslow-4andslow-5forReHoandmALFF.Interregionalanalysesshowedthatforbrainregionsreachingstatisticalsignificance,FCstrengthsatslow-4werealwaysweakerthanthoseatslow-5.CommunitydetectionalgorithmwasappliedtoFCdataandunveiledtwomodulessensitivetofrequencyeffects:onecomprisedsensorimotorstructure,andtheotherencompassedlimbic/paralimbicsystem.Graphthe-oreticalanalysisverifiedthatslow-4andslow-5differedinlocalsegregationmeasures.Althoughthemanifes-tationoffrequencydifferencesseemedcomplicated,theassociatedbrainregionscanbegrosslycategorizedintolimbic/paralimbic,midline,andsensorimotorsystems.OurresultssuggestthatfuturerestingfMRIresearchaddressingthethreeabovesystemseitherfromneuropsychiatricorpsychologicalperspectivesmayconsiderusingspectrum-specificanalyticalstrategies.

Keywords:communitydetection;functionalconnectivity;functionalmagneticresonanceimaging;graphtheory;meanamplitudeoflowerfrequencyfluctuation;regionalhomogeneity

IntroductionThehumanbrainisalargeandcomplexnetworkor-

ganizedbyspatial,temporal,andspectralprinciples.Inactivementaloperation,frequencyeffectsaretasksensitiveinatopographicalmanner.Forexample,electroencepha-lography(EEG)studiesrevealthatshort-termmemorypro-cessesarereflectedbythetaoscillationintheanteriorlimbicsystem,whereaslong-termmemoryprocessesarereflectedbyupperalphaoscillationsintheposteriorthalamicsystem(Klimesch,1996).Synchronizationingammaspec-trumcanenableobjectrepresentationandcontributetothe

maintenanceofinformationinmemory(BertrandandTallon-Baudry,2000).Inrestingstate,neuralcharacteristicsalsoconferphysiologicalandneuropsychologicalsignificance.Neuronaloscillationprovidessupportingcontextforvariousfunctions,includinginputselection,plasticity,perceptualbinding,psychologicalrepresentation,andlearning(BuzsakiandDraguhn,2004).Frontalalphaasymmetryhaslongbeenregardedasapotentialindicatoroftemperamentandaffec-tivereactivity(Davidson,1992;Hagemannetal.,1998),andconnectivitystrengthsoverseveralbrainregionsmayhaveimplicationsindepressivedisorder(Fingelkurtsetal.,2007;Leeetal.,2011a).

1CenterforCognitionandBrainDisorders,HangzhouNormalUniversity,Hangzhou,China.

2ZhejiangKeyLaboratoryforResearchinAssessmentofCognitiveImpairments,Hangzhou,China.

3Mind,BrainImagingandNeuroethics,InstituteofMentalHealthResearch,UniversityofOttawa,Ontario,Canada.

BRAINCONNECTIVITYVolume4,Number4,2014ªMaryAnnLiebert,Inc.DOI:10.1089/brain.2013.0182

242Theuseoffunctionalmagneticresonanceimaging

(fMRI)toinvestigateneuralfeaturesinrestingstateisre-ceivingincreasedattention.IncontrasttoEEG,themajordistributionofbloodoxygenlevel-dependent(BOLD)dy-namicsandthetemporalresolutionoffMRIaresituatedatmuchlowerrange.TheseinnatepropertiesrenderfMRIsuitableforinvestigatingslowerbrainoscillation,whichhasbeenproventobesurprisinglyinformative.Anearlyre-portbyBiswalandassociates(1995)revealedthatsponta-neouslow-frequencyfluctuations(0.01–0.08Hz)infMRIarehighlysynchronousbetweentheleftandrightprimarymotorcortexandalsosignificantlycorrelatedwithotherbrainregionsassociatedwithmotorfunction.Subsequentresearchhassimilarfindingsinvisual,auditory,andlin-guisticsystems,aswellasinthedefaultmodenetwork.Functionalinteractioninrestingstateexistsnotonlyinhumansbutalsoinratsandmonkeys(Luetal.,2012).TheslowdriftofrestingfMRIsignalsclearlyhasassociatedneuralorigins,althoughtheunderlyingmechanismofhowtheyin-teractisstillunclear(Luetal.,2007;Mantinietal.,2007;Scholvincketal.,2010).SimilartoEEGoscillationthatiscomposedofseveralspectralcomponents,studieshavesug-gestedthatthelow-frequencyoscillationofrestingfMRIcanbefurthercategorizedintoslow-4(0.027–0.073Hz)andslow-5(0.01–0.027Hz)(Zuoetal.,2010).TherestingdynamicsofBOLDsignalsatslow-4andslow-5reportedlyhavedifferentamplitudesoflow-frequencyfluc-tuation(ALFFs)inbasalganglia(slow-4>slow-5)andmedialprefrontalcortex(slow-5>slow-4)(Yuetal.,2014;Zuoetal.,2010).ALFFistheL1normoflow-frequencyBOLDfluctu-ation,andthepreferentialALFFdistributionsofslow-4andslow-5suggestedspectrumspecificityincertainbrainregions.Personalitiessuchasextraversionandneuroticismarecorre-latedwithslow-4andslow-5ALFFinseveralcerebralstruc-turesrelatedtoemotionprocessing(Weietal.,2014).Further,abnormalintrinsicbrainactivityinschizophreniacanbereflectedinthalamicandprecuneusALFFatslow-4andslow-5(Yuetal.,2014).InadditiontoALFF,otherregionalneuralpropertiesarealsoinfluencedbyBOLDspectrum.Regionalhomogeneity(ReHo),anindexmeasuringconcor-danceoftemporaldynamics,differsbetweenslow-4andslow-5atbasalganglia,limbic/paralimbicsystem,andsomecorticalareas(Yuetal.,2013).SimilartoALFF,ReHoinschizophreniashowssignificantgroupbyfrequencyinterac-tion(i.e.,patientvs.controlandslow-4vs.slow-5)inseveralbrainregions,suchasinferioroccipitalgyrus(IOG)andcau-date(Yuetal.,2013).Inadditiontoregionaleffects,Liangandcolleagues(2012)recentlyassociatedslow-4andslow-5withdifferentnodalandglobaltopologiesatthebrainnetworklevel.Con-vergingevidenceseemstohaveindicatedtheexistenceoftwosubspectrumsinBOLDat0.01–0.08Hz,similartodif-ferentfrequencybandsinEEG.Althoughsomereportshavedemonstrateddifferencesinthefrequencyeffectsofslow-4andslow-5onneuralcharacteristics,thesediffer-enceshaveneverbeenadequatelyandsystemicallyassessed.Thisstudyaimedtoelucidatedifferentneuralmanifestationsofslow-4andslow-5fromlocaltoglobalscales,namely,re-gionalproperty,interregionalinteraction,andnetworkfea-tures.Specifically,weexploredfrequencyeffectsonlocalneuralactivitiesusingReHoandmeanALFF(mALFF;ALFFateachvoxelnormalizedbythemeanALFFofvoxels