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Inspiteofarecentincreaseinneuroimagingresearchintochronicinsomnia,ithasyettoestablishaconsistent findingaboutitsneuropathology.Thefunctionalstudiesaretoofewanddiverseinmethodologytoyieldanygeneral conclusions,theresultsofstructuralstudiesareeithercontradictoryorrequirereplication.Previousstudieshavedemonstrated widesexdifferencesinregionalbrainactivityunderdifferentsleepconditions;however,insomniahasnotbeenstudied.The currentstudyistoexploretheregionalbrainactivitiesinpatientswithchronicprimaryinsomnia(PCPIs)andtheirsexdifferences. MethodsForty-twoPCPIs(27females,15males)and42goodsleepers(GSs;24females,18males)wererecruited.SixPCPIs(3 males,3females)werescannedtwicebyMRItoexaminethetest-retestreliability.Amplitudeoflowfrequencyfluctuation(ALFF) methodwasusedtoassessthelocalbrainfeatures.ThemeansignalvaluesofthedifferentALFFareaswereanalyzedwitha receiveroperatingcharacteristic(ROC)curve.Simplelinearregressionanalysiswasperformedtoinvestigatetherelationships betweenclinicalfeaturesanddifferentbrainareas. Results FullfactorialANOVAanalysisshowedsignificantdifferenceinthemaineffectofgender.BothfemaleandmalePCPIs showedhigherALFFinthetemporallobeandoccipitallobe,especiallyinfemalePCPIs.FemalePCPIshadlowerALFFinthe bilateralcerebellumposteriorlobe,leftdorsolateralprefrontalcortex,andbilaterallimbiclobe;however,malePCPIsshowed lowerALFFintheleftoccipitalgyrus.ThemeansignalvalueofthecerebelluminfemalePCPIsshowednegativecorrelationswith negativeemotions.ComparedwithmalePCPIs,femalePCPIsshowedhigherALFFinthebilateralmiddletemporalgyrusand lowerALFFintheleftlimbiclobe.Thedifferentareasshowedhightest-reteststability(Clustersofcontiguousvolumes≥1080 mm3withanintraclasscorrelationcoefficient≥0.80).TheROCanalysisrevealedthatthedifferentALFFareasofboththePCPI-Fs andthePCPI-MsshowedhighAUCvaluesandhighdegreeofsensitivitiesandspecificities. ConclusionsFemalePCPIsshowedmoreregionalbraindifferenceswithhigherandlowerALFFresponsesthanmalePCPIs. However,theysharedanalogousexcessivehyperarousalmechanismandwidevariationsinaberrantbrainareas.Thesefindings willhelpusinsightintoadeeperunderstandingofthepathophysiologicalmechanismofthechronicprimaryinsomnia. Furthermore,thesexfactorshouldbetakenintoconsiderationinfuturefunctionalMRIstudies.