神经信号的同步和跨频耦合-检测及应用

神经信号的同步和跨频耦合——检测及应用孙俊峰[e-mail]上海交通大学生物医学工程学院(NatureRev.Neurosci.,2:229,2001)EEG:~ms;~cmfMRI:1-4s;2-4mmEEG(M.F.Bearet.al.,NeuroscienceExploringtheBrain,3rded)•锥体细胞突触电流产生微小电场•大量锥体细胞同步活动产生EEG(NatureRev.Neurosci.,2:229,2001)SegregationIntegration(Watts&Strogatz,Nature,1998)LargeClust.Coeff.C(p);SmallChar.PathLen.L(p)Small-worldBrainNetworks相位同步ChristiaanHuygens(1629--1695)荷兰科学家惠更斯在1665年观察到钟摆同步现象…同步不同步：HilbertTransform:PS脑电波信号的瞬时相位及同步(JunfengSun,et.al.,“Inferringfunctionalconnectivitywithphasesynchronizationanalysis:Areviewofmethodology”,ComputationalandMathematicalMethodsinMedicine,2012,239210,invitedreview)()()()()()()()()hhhjtststjstAte解析信号：滤波器：该定义适用于一般形式的信号瞬时相位：(JunfengSunandMichaelSmall,PhysicalReviewE80(2009):046219)多种瞬时相位定义方法（如基于小波变换）所对应的复信号均可写成原实信号通过某带通滤波器的形式瞬时相位定义研究噪声对相同步检测的影响含噪信号纯净信号噪声解析信号相位误差相位估计值相位理想值可证明：在中低等噪声水平下(信噪比5dB)，相位误差服从正态分布：如相位误差折叠到则其满足折叠高斯分布：(JunfengSunandMichaelSmall,PhysicalReviewE80(2009):046219)噪声对相同步检测的影响采用平均相位相干性(meanphasecoherence,MPC)作为相同步指数其中是两耦合系统之间的瞬时相位差如假设混合正态分布可用某一正态分布近似，则可证明相同步指数与噪声水平之间满足以下关系：由纯净信号估计出的同步指数噪声导致的影响由含噪信号估计出的同步指数(JunfengSunandMichaelSmall,PhysicalReviewE80(2009):046219)替代数据法(SurrogateTest)OriginalintracranialneuronalpotentialSurrogatedataoforiginalsignal(Schreiber&Schmitz,Surrogatetimeseries,PhysicaD142(2000)346–382)用于相位同步分析的替代数据法Rank-shuffledsurrogate(RSS)Phase-shuffledsurrogate(PSS)RSSofinstantaneousfrequency(RSS-IF)PSSofinstantaneousfrequency(PSS-IF)相位同步分析EEG时用多长的数据合适?100ms(J.Neurosci.,26(31):8168–8175,2006)700ms(IEEETrans.NeuralSyst.Rehabil.Eng.,17(3):224–233,2009)1s(IEEETrans.Biomed.Eng.,53(12):2501–2506,2006)10s(IEEETrans.Syst.,Man,Cybern.B,40(5):1294–1304,2010)23.6s(PhysicaD,144(3-4):358–369,2000)onemicrostateofEEGsignalsisusually50to200ms(Nat.Rev.Neurosci.,2(4):229–239,2001;Biol.Cybern.,83:35–45,2000;PNAS,107(42):18179–18184,2010)(JunfengSun,et.al.,“Inferringfunctionalconnectivitywithphasesynchronizationanalysis:Areviewofmethodology”,ComputationalandMathematicalMethodsinMedicine,2012,239210,invitedreview)(JunfengSun,XiangfeiHong,andShanbaoTong,“PhaseSynchronizationAnalysisofEEGSignals:AnEvaluationBasedonSurrogateTests”,IEEETransactionsonBiomedicalEngineering,59(8):2254-2263,2012)(JunfengSun,XiangfeiHong,andShanbaoTong,“PhaseSynchronizationAnalysisofEEGSignals:AnEvaluationBasedonSurrogateTests”,IEEETransactionsonBiomedicalEngineering,59(8):2254-2263,2012)•AdurationofEEGwavescover5~12cyclesisrecommended•ThePSSsurrogatemethodisrecommendedtoprovidesignificancetestforPSanalysis.基于inter-subjectEEGpairs的显著性检测(S.PalvaandJ.M.Palva,TrendsinCognitiveSciences,16:(4),2012)(d)(e)(PhaseSynchronyamongNeuronalOscillationsintheHumanCortex,TheJournalofNeuroscience,25(15):3962,2005)m:n相位同步示例(phase-lockingfactor,PLF)幅度相位跨频耦合检测流程——方法一(Assessingtransientcross-frequencycouplinginEEGdata,JournalofNeuroscienceMethods,168:494–499,2008)幅度相位跨频耦检测流程——方法二(MeasuringPhase-AmplitudeCouplingBetweenNeuronalOscillationsofDifferentFrequencies,JNeurophysiol,104:1195–1210,2010)()z()()()fpAjtfztAte定义复合变量：(MeasuringPhase-AmplitudeCouplingBetweenNeuronalOscillationsofDifferentFrequencies,JNeurophysiol,104:1195–1210,2010)幅度相位跨频耦检测流程——方法二幅度相位跨频耦检测流程——方法二A:theta–LGphase-amplitudeplotsoftheoriginal(left)andarepresentativetrial-shuffledtimeseries(right)derivedfromactualhippocampaldata.B:meanMIfor200trial-shuffledandtheoriginalphase-amplitudetimeseries.DashedlinerepresentsthesignificancethresholdEEG的容积导体问题AnEEGrecordingconsistsofactivityarisingfrommanybrainandextra-brainprocesses基于信号包络正交化后的相关系数(Morlet’swavelets)(Large-scalecorticalcorrelationstructureofspontaneousoscillatoryactivity,NatureNeuroscience,15(6):884-,2012)基于包络正交化后的相关系数的Seed-map分析(Large-scalecorticalcorrelationstructureofspontaneousoscillatoryactivity,NatureNeuroscience,15(6):884-,2012)因果关系分析BiologicalCybernetics,2001.PRL:96(20):208103,2006;99(20):204101,2007;100(1):018701,2008;100(8):084101,2008;100(14):144103,2008;100(23):234101,2008.affectsGrangerCausalityVs.DynamiccausalmodelingCorrelationbetweenthesynchronymeasuresAcomparativestudyofsynchronymeasuresfortheearlydiagnosisofAlzheimer'sdiseasebasedonEEG,NeuroImage,2010,49:668–693研究1：(WenqingWu,JunfengSun,et.al.,ClinicalNeurophysiology,2011,122:21–26)NIHSS:NationalInstituteofHealthStrokeScaleNIHSS_1:recordedwithinsevendaysafterstrokeonsetNIHSS_2:recordedtwomonthsafterstrokeNIHSS_1Vs.NIHSS_2byt-test:*p0.01,**p0.001功能性连接强度统计(WenqingWu,JunfengSun,et.al.,ClinicalNeurophysiology,2011,122:21–26)(a)(b)Dashedline:normalizedvalueforthecontrolsubjectsTheinter-hemisphericsynchronysignificantlyreducedThelevelofsynchronizationbetweenlesionandintactareasintheipsilateralhemispheresignificantlyreducedafterstrokeThesynchronizationamongintactareasincreasedcomparedwiththecontrolsubjects脑半球间的连接强度与NIHSS的关系NIHSS：nationalInstituteofHealthStrokeScale脑缺血后早期脑半球间的连接强度越大，患者后期能康复得越好(WenqingWu,JunfengSun,et.al.,ClinicalNeurophysiology,2011,122:21–26)(Baron,etal.,Stroke,40:1315-1324,2009)Cortexactivationofstrokepatient•患者的对患侧手的实际运动和运动想象所激活的运动