兒童皮層誘發(fā)電位中P1N1的增齡性變化及臨床應(yīng)用*(2)

盧偉 魯倩 莫玲燕

1 鄭州大學(xué)第一附屬醫(yī)院耳科(鄭州 450052); 2 首都醫(yī)科大學(xué)附屬北京同仁醫(yī)院,北京市耳鼻咽喉科學(xué)研究所,耳鼻咽喉頭頸科學(xué)教育部重點(diǎn)實(shí)驗(yàn)室(首都醫(yī)科大學(xué))

3.4 大齡兒童P1N1 這個(gè)年齡段包括了4歲到青春期的兒童,目前對(duì)于此年齡段的兒童P1N1的研究已經(jīng)相當(dāng)成熟。成人的P1N1是穩(wěn)定而普遍存在的,而兒童的P1N1的特性尚不明確。P1波幅及潛伏期隨年齡增長(zhǎng)而逐漸減小,直到20歲左右達(dá)到成人水平[10]。在這個(gè)年齡段,N1波分為N1a、N1b(圖3),N1a波只在一部分受試者中觀察到,N1b波在所有受試者中都存在,隨著年齡的增長(zhǎng),N1a波出現(xiàn)的頻率也增長(zhǎng),6～7歲兒童中N1a波出現(xiàn)概率為61%,8～9歲為63%,10～12歲為 69%,13～15歲為100%[10]。N1波的潛伏期及波幅,不同的研究顯示結(jié)果不同[10]：關(guān)于潛伏期,有報(bào)道在16歲之前,N1波的潛伏期隨著年齡的增加而減小[22],也有報(bào)道是在20歲之前[23];關(guān)于波幅,有學(xué)者認(rèn)為在15歲之前N1波的波幅隨年齡的增長(zhǎng)而增加,也有學(xué)者認(rèn)為潛伏期和波幅與年齡幾乎沒(méi)有關(guān)系[24]。N1波由三種亞型組成,也有報(bào)道認(rèn)為N1波可能存有其他的成分[3]。目前對(duì)N1波研究的重點(diǎn)為N1a與N1b。N1a波最早在6歲的兒童中觀察到,并且其出現(xiàn)的頻率隨著年齡的增加而增加,這種趨勢(shì)一直持續(xù)到13歲,但N1a波并不是在所有的兒童中都出現(xiàn),而N1b波幾乎存在于所有兒童中[10]。有學(xué)者認(rèn)為N1a波是成人N1波的前體[10],目前 N1a、N1b與成人N1波之間的關(guān)系尚未確定,將來(lái)對(duì)于達(dá)到成人N1波水平前的N1a、N1b變化的研究有重要意義。盡管有報(bào)道指出不同的刺激聲產(chǎn)生不同的P1N1波,但在不同刺激下,P1N1各波潛伏期、幅值變化的總趨勢(shì)是一致的[10]。隨著年齡的增長(zhǎng),由于神經(jīng)髓鞘不斷發(fā)育以及突觸同步化逐漸完善,P1N1各個(gè)成分在不斷的成熟[25]。

圖3 6～12歲兒童的N1a波

4 P1N1的臨床應(yīng)用和展望

4.1 行為聽(tīng)閾的評(píng)估 P1-N1-P2的刺激聲相對(duì)于ABR的短純音而言持續(xù)時(shí)間長(zhǎng),且頻率特異性好,對(duì)于肢體輕微活動(dòng)產(chǎn)生的電生理噪聲耐受性強(qiáng),而且反映的聽(tīng)覺(jué)通路更長(zhǎng),與PTA閾值相關(guān)性強(qiáng),閾值評(píng)估效果較好,所以P1-N1-P2閾值能客觀地反映受試兒的實(shí)際聽(tīng)力水平。有研究報(bào)道P1-N1-P2閾值與行為聽(tīng)閾之差在10 dB之內(nèi)[26]。當(dāng)患兒不能配合主觀行為測(cè)聽(tīng)時(shí),慢皮層P1-N1-N2反應(yīng)也可以作為一種選擇。但P1-N1-P2易受受試兒精神狀態(tài)及注意力水平的影響,對(duì)于不能保持穩(wěn)定清醒狀態(tài)的受試兒,其應(yīng)用受到限制。

4.2 言語(yǔ)感知的評(píng)估 CAEP的發(fā)育受聽(tīng)覺(jué)經(jīng)驗(yàn)的影響,早期聽(tīng)覺(jué)經(jīng)驗(yàn)有助于皮層CAEP的發(fā)育。聽(tīng)覺(jué)傳導(dǎo)通路疾病患兒與正常兒童的P1-N1-P2有顯著的差異,尤其是言語(yǔ)功能障礙的兒童其N1波潛伏期明顯延長(zhǎng)[27]。在純音或言語(yǔ)聲刺激下,聽(tīng)神經(jīng)瘤(AN)患兒的 P1、N1波的潛伏期隨聽(tīng)力損失程度的增加而逐漸延長(zhǎng)[28]。AN患兒CAEP各波與他們的言語(yǔ)感知能力有著密切的關(guān)聯(lián)：在助聽(tīng)情況下,CAEP與同齡正常聽(tīng)力兒童相似的AN患兒,其言語(yǔ)感知能力得分較高;而CAEP潛伏期較同齡正常兒童延長(zhǎng)的AN患兒,其言語(yǔ)感知能力很差;CAEP各波缺失的AN患兒,其言語(yǔ)感知能力非常差[28]。由于CAEP與言語(yǔ)感知顯著相關(guān),而言語(yǔ)感知與神經(jīng)元同步化又有著密切聯(lián)系,因此CAEP檢測(cè)方法有助于預(yù)估神經(jīng)元失同步化的嚴(yán)重性。當(dāng)CAEP存在時(shí),表明有足夠的殘余神經(jīng)元同步化存在,能為編碼言語(yǔ)感知提供所需要的信息,因此CAEP可作為評(píng)估言語(yǔ)感知能力的檢測(cè)方法[28]。

4.3 聽(tīng)力障礙兒童助聽(tīng)后聽(tīng)力言語(yǔ)的評(píng)估 使用助聽(tīng)器后通常會(huì)導(dǎo)致皮層 ERP各成分波形潛伏期縮短,波幅增大[29]。感音神經(jīng)性聾兒助聽(tīng)后CAEP的改變表明,大部分5～24月齡的極重度聾患兒助聽(tīng)后對(duì)短聲誘發(fā)的CAEP閾值比未助聽(tīng)時(shí)低20 dB[30]。Kurtzberg等[31,32]以4個(gè)年齡從7月齡到27月齡、聽(tīng)力損失從中度到重度的嬰幼兒為受試對(duì)象,以言語(yǔ)聲為刺激聲進(jìn)行測(cè)試,發(fā)現(xiàn)助聽(tīng)后3名患兒有明顯的P1波及其后的寬大負(fù)波,并且這些外源性反應(yīng)只在助聽(tīng)下才會(huì)出現(xiàn),說(shuō)明助聽(tīng)后言語(yǔ)識(shí)別能力提高。因此,CAEP可以作為助聽(tīng)效果評(píng)估的客觀指標(biāo)。

4.4 電刺激誘發(fā)的CAEP 關(guān)于人工耳蝸植入兒童電刺激誘發(fā)的CAEP的研究在逐步開(kāi)展,其用于推斷聽(tīng)覺(jué)傳導(dǎo)通路的發(fā)育情況,評(píng)估人工耳蝸術(shù)后效果。植入人工耳蝸的兒童CAEP只有P1、N2波,而未記錄到N1波,N1波缺失可作為人工耳蝸植入兒童CAEP的明顯標(biāo)志[33,34]。電刺激誘發(fā)的CAEP有一寬大的正波及其前的負(fù)波[35],Sharma等[36]認(rèn)為這一正波為P1波,其潛伏期隨著年齡的增長(zhǎng)和人工耳蝸使用年限的增加而減小(圖4),P1潛伏期延長(zhǎng)與否表明了聽(tīng)覺(jué)傳導(dǎo)系統(tǒng)的發(fā)育程度,同時(shí),短潛伏期負(fù)波的出現(xiàn)(此負(fù)波可能波幅較小或波幅寬大),表明皮層神經(jīng)沖動(dòng)發(fā)放異常。不規(guī)則的皮層反應(yīng)可能由在聽(tīng)力損失期間皮層的異常變化所引起,也可能是由于使用人工耳蝸期間皮層的異常變化所造成,這些變化可能反映了除簡(jiǎn)單察覺(jué)反應(yīng)之外的其他皮層活動(dòng),而這些皮層活動(dòng)是獲得言語(yǔ)感知的必需成分[35]。Sharma等[36]通過(guò)對(duì)不同年齡階段的植入人工耳蝸的兒童與同齡正常兒童P1潛伏期的比較,發(fā)現(xiàn)3.5歲前植入人工耳蝸者,其P1潛伏期值與同齡正常兒童的P1潛伏期值類似;3.6歲到6.5歲植入人工耳蝸者,大部分患兒P1潛伏期與同齡正常兒童不同;7歲之后植入耳蝸者,與同齡兒童相比,P1潛伏期值顯著增加。因此推斷先天性聾患兒的聽(tīng)覺(jué)傳導(dǎo)通路并沒(méi)有完全退化或者說(shuō)仍具有很大的可塑性[36],3.5歲前是先天性聾患兒進(jìn)行耳蝸植入的最佳時(shí)期[37,38]。

圖4 P1潛伏期隨人工耳蝸使用時(shí)間的變化情況[36]

4.5 展望 P1N1的波幅和潛伏期能夠反映聽(tīng)覺(jué)通路的發(fā)育程度。CAEP技術(shù)在行為閾值及聽(tīng)覺(jué)認(rèn)知功能的評(píng)估方面有重要的應(yīng)用價(jià)值,在不久的將來(lái),它將會(huì)廣泛運(yùn)用到臨床聽(tīng)力學(xué)中。

1 Davis PA.Effects of acoustic stimuli on the waking hu.Davis PA.Effects of acoustic stimuli on the waking human brain[J].J Neurophysiol,1939,2：494.

2 Reite M,Adams M,Simon J,et al.Audito ry M100 component 1：relationship to Heschl＇s gyri[J].Cognit Brain Research,1994,2：13.

3 N??t? nen R,Picton T.T he N1 wave of the human electric and magnetic response to sound：A review and an analysis of the component structure[J].Psychophysiology,1987,24：375.

4 Vaughan HG,Ritter W.T he source of auditory evoked responses reco rded from the human scalp[J].Electroencephalog r Clin Neurophysiol,1970,28：360.

5 Wolpaw JR,Penry JK.A temporal component of the auditory evoked response[J].Electroencephalog r Clin Neurophysiol,1975,39：609.

6 Mccallum WC,Curry SH.The form and distribution of auditory evoked potentials and CNVs when stimuli and responses are lateralized[J].Progress Brain Research,1980,54：767.

7 Picton TW,Woods DL,Baribeau-Braun J,et al.Evoked potential audiometry[J].Otolaryngol,1997,6：90.

8 Onishi S,Davis H.Effects of duration and rise time of tone bursts on evoked V potentials[J].Acoustical Society of America,1968,44：582.

9 Wunderlich JL,Cone-Wesson BK,Shepherd R.Maturation of the cortical auditory evoked potential in infants and young children[J].Hearing Research,2006,212：185.

10 Sharma A,Kraus N,McGee T,et al.Developmental changes in P1 and N1 central auditory responses elicited by consonant vowel sy llables[J].Electroencephalogr and Clinical Neurophysiology,1997,104：540.

11 Sakabe N,A rayama T,Suzuki T,et al.Human fetal evoked response to acoustic stimulation[J].Acta Oto-laryng ologica,1969,252：29.

12 Schleussner E,Schneider U.Developmental changes of auditoryevoked fields in fetuses[J].Experimental Neurology,2004,190：S59.

13 Starr A,Amlie RN,M artin WH,et al.Development of auditory function in newborn infants revealed by auditory brainstem potentials[J].Pediatrics,1977,60：831.

14 Lengle JM,Chen M,Wakai RT,et al.Improved neuromagnetic detection of fetal and neonatal auditory evoked responses[J].Clinical Neurophysiology,2001,112：785.

15 Little VM,Thomas DG,Letterman MR.Single-trial analyses of developmental trends in infant auditory event-related potentials[J].Neuropsychol,1999,16：455.

16 Barnet AB,Ohlrich ES,Weiss IP,et al.Auditory evoked potentials during sleep in normal children from 10 days to 3 years of age[J].Electroencephalog raphy and Clinical Neurophysiology,1975,39：29.

17 Vaughan HG,Kurtzberg D.Electrophy siologic indices of normal and aberrant cortical maturation[M].In：Kellaway P,Noebels JL,Editors.Problems and Concepts in Developmental Neurophysiology,1989.263～287.

18 Novak GP,Kurtzberg D,K reuzer JA,et al.Co rtical responses to speech sounds and their formants in normal infants：maturational sequence and spatiotemporal analy sis.Electroen Clin Neurophysiol[J].Electroencephalogr and Clinical Neurophysiology,1989,73：295.

19 Mills DL,Coffey-Corina S,Neville HJ.Language comprehension and cerebral specialization from 13 to 20 months[J].Development Neuropsychology,1997,13：397.

20 Ceponiene R,Aro H,Alku P,et al.Eventrelated potential indices of auditory vowel processing in 3-year-old children[J].Clinical Neurophysiology,2003,114：652.

21 M olfese DL,Molfese VJ.Right-hemisphere responses from preschool children to temporal cues to speech and nonspeech materials：Electrophysiological correlates[J].Brain and Language,1988,33：245.

22 Tonnquist-Uhlen I,Borg E,Spens KE.Topography of auditory evoked long-latency potentials in normal children,with particular referenceto the N1 component[J].Electroencephalog raphy and Clinical Neurophy siology,1995,95：34.

23 Johnson R.Developmental evidence for modality-dependent P300 generators：A normative study[J].Psychophysiology,1989,26：651.

24 M artin L,Barajas JJ,Fernandez R,et al.Auditory eventrelated potentials in well-characterized groups of children[J].Electroencephalography and Clinical Neurophy siology,1988,71：375.

25 Courchesne E.Chronology of postnatal human brain development：Eventrelated potential,positron emission tomography,my elinogenesis,and synaptogenesis studies[M].In：Rohrbaugh JW,Parasuraman R,Johnson R,Editors.Event-related Brain Potentials：Basic Issues and Applications,1990.210～241.

26 Hyde M.The N1 response and its applications[J].Audio Neurootot,1997,2：28l.

27 Ponton CW,Eggermont JJ,Kwong B,et al.Maturation of human central auditory system activity：Evidence from multi-channel evoked potentials[J].Clinical Neurophysiology,2000,111：220.

28 Rance G,Cone-Wesson B,Wunderlich J,et al.Speech perception and cortical event related potentials in children with auditory neuropathy[J].Ear and Hearing,2002,23：239.

29 Korczak PA,Kurtzberg D,Stapells DR.Effects of sensorineural hearing loss and personal hearing AIDS on cortical event-related potential and behavioral measures of speechsound processing[J].Ear and Hearing,2005,26：165.

30 Rapin I,Graziani LJ.Auditory-evoked responses in normal,brain-damaged and deaf infants[J].Neurology,1967,17：881.

31 Kurtzberg D.Cortical event-related potential assessment of auditory sy stem function[J].Seminars in Hearing,1989,10：252.

32 Stapells DR,Kurtzberg D.Evoked potential assessment of auditory system integ rity in infants[J].Clinics in Perinatology,1991,18：497.

33 Singh S,Liasis A,Rajput K.et al.Event-related potentials in pediatric cochlear implant patients[J].Ear and Hearing,2004,25：598.

34 Ponton CW,Eggermont JJ.Of kittens and kids：Altered cortical maturation following profound deafness and cochlear implant use[J].Audiology&Neurootology,2001,6：363.

35 Karen A,Gordon KA,Tanaka S.Atypical cortical responses underlie poor speech perception in children using cochlear implants[J].Neurorepo rt,2005,16：2 041.

36 Gilley PM,Sharma A,Do rman MF,et al.Cortical reorganization in children with cochlear implants[J].Brain Research,2008,1 239：56.

37 Sharma A,Michael F,Dorman AJ,et al.Rapid development of cortical auditory evoked potentials after early cochlear implantation[J].Neuroreport,2002,13：1 365.

38 Sharma A,Michael F,Andrej K,et al.The influence of a sensitive period on central auditory development in children with unilateral and bilateral cochlear implants[J].Hearing Research,2005,203：134.

(全文完)