MIDDLE-LATENCY AUDITORY EVOKED POTENTIALS IN
CHILDREN AT HIGH RISK FOR ALCOHOLISM
Au ho s: Soco o Rod íguez Holguín, Mon se a Co al, Fe nando Cada ei a
This is he pee e iewed e sion o he ollowing a icle: Rod íguez Holguín, S., Co al,
M. & Cada ei a, F. (2001). Middle-la ency audi o y e oked po en ials in child en a high
isk o alcoholism. Neu ophysiologie Clinique, 31, 40-47. doi: 10.1016/S0987-
7053(00)00241-0
This a icle may be used o non-comme cial pu poses in acco dance wi h Else ie
Te ms and Condi ions o Use o Sel -A chi ed Ve sions
1
Middle-la ency audi o y e oked po en ials in child en a high
isk o alcoholism
Soco o Rod íguez Holguín*1, Mon se a Co al, Fe nando Cada ei a
Depa amen o de Psicoloxía Clínica e Psicobioloxía, Uni e sidade de San iago de
Compos ela, Galiza, Spain
Summa y
Pu pose. In he cou se o a high- isk s udy o alcoholism, he middle-la ency audi o y
e oked po en ials (MAEPs) o child en o alcoholics we e explo ed. Ma e ial and
Me hods. A se ies o audi o y clicks (0.1 ms, 60 dB SL, 1.1/s) we e used o eco d he
Pa and Pb peaks o he MAEPs in 15 child en o alcoholics wi h a mul igene a ional
amily his o y o alcoholism, and 17 con ol subjec s, anging om 10 o 14 yea s o age.
Resul s. The la ency o Pb was sho e in he high- isk han in he con ol g oup, and
he e was also a signi ican isk g oup by age in e ac ion on Pa la ency. The ampli ude
o Pa was smalle in he child en o alcoholics. Conclusions. The cha ac e is ics o he
MAEPs o he high- isk subjec s did no ma ch he pa e n o abno mali ies p e iously
obse ed in ch onic alcoholics, which a e supposed o be a consequence o he
neu o oxic e ec s o e hanol. None heless, he esul s showed signi ican di e ences in
MAEPs be ween child en o alcoholics and con ols, poin ing o an anomalous pa e n o
in o ma ion ansmission om halamus o co ex ha should be u he analyzed using
la ge samples in a b oade age ange.
Keywo ds: alcoholism / child en o alcoholics / e en - ela ed po en ials / high isk /
middle-audi o y e oked esponses
(MAEPs)
1 Co espondence au ho
Recei ed 21 Decembe 1999; accep ed in e ised o m 2 Augus 2000
Pos -p in ( inal d a pos - e e eeing)
2
Po en iels é oqués audi i s de la ence moyenne chez les en an s d’alcooliques.
Résumé
Objec i s. É udie le isque possible d’alcoolisme chez des en an s d’alcooliques pa
l’en egis emen des po en iels é oqués audi i s de la ence moyenne (PEALM). Ma é iel
e mé hodes. Dans le bu d’en egis e les composan es Pa e Pb, une sé ie de clicks
(0.1 ms, 60 dB S.L, 1.1/s) a é é déli ée à deux popula ions d’en an s âgés de 10 à 14
ans: 17 en an s- émoins e 15 en an s aisan pa ie d’une amille d’alcooliques.
Résul a s. La la ence du Pb é ai accou cie chez les en an s d’alcooliques. L’ampli ude
du Pa é ai plus pe i e e il y a ai une in e ac ion signi ica i e âge/g oupe su la la ence
de ce po en iel chez ces en an s. Conclusions. Les PEALM des suje s à hau isque ne
p ésen en pas les mêmes anomalies que celles obse ées p écédemmen chez des
alcooliques ch oniques, qui son une conséquence des e e s neu o oxiques de l’alcool.
Cependan , les ésul a s mon en des di é ences signi ica i es des PEALM en e les
en an s d’alcooliques e les en an s con ôles, suggé an une anomalie dans la
ansmission d’in o ma ions du halamus au co ex. Ce e analyse de a ê e app o ondie
g âce à des échan illons plus g ands e un panel d’âges plus impo an .
Mo s-clé: alcoolisme / en an s d’alcooliques / po en iels é oqués audi i s de la ence
moyenne (PEALM) / isque
Pos -p in ( inal d a pos - e e eeing)
3
In oduc ion
Resea ch in o alcoholism has ex ensi ely employed psychophsysiological and
neu ophysiological measu es wi h he aim o de e mining he e ec s o ch onic alcohol
abuse on he unc ion o he ne ous sys em and iden i ying ulne abili y ma ke s ha
could di e en ia e hose subjec s liable o de elop alcoholism.
The spon aneous EEG ac i i y as well as senso y e oked po en ials and cogni i e
e en - ela ed po en ials ha e been used o assess alcoholic pa ien s. In subjec s a
amilial isk o alcoholism, bo h spon aneous EEG and e en - ela ed po en ials (mos ly
P300) ha e been s udied as gene ic ulne abili y ma ke s, so long as abno mali ies
obse ed in abs inen alcoholics a e also p esen in child en o alcoholics ( o e iew see
[5]). Ea ly e oked po en ials (EPs) ha e been less employed once i was epo ed ha
abno mali ies a ec ing audi o y b ains em e oked esponses in alcoholics we e no
obse able in child en o an alcoholic a he [6]. The ac ha some o he anomalous
elec ophysiological cha ac e is ics i s ound in ch onic alcoholics ha e been iden i ied
in hei alcohol-nai e ela i es [7, 8, 20, 32, 36] indica es ha hey a e no only a esul
o he neu o oxic e ec s o subs ance abuse, and migh be assessed as pu a i e o
elec ophysiological ma ke s o he de elopmen o alcoholism.
Al hough he EPs’ abno mali ies ha e been epo ed in alcoholics o ea ly [9, 13,
14] and la e [13, 15, 31] componen s in he audi o y modali y, ew s udies ha e assessed
he middle-la ency audi o y e oked po en ials (MAEPs) in ela ion o alcoholism. In a
p e ious s udy a ou labo a o y, he Na and Pa componen s o he MAEPs we e
assessed in a g oup o abs inen alcoholics and ma ched con ols [16]. Alcoholics
p esen ed sho e la encies o Na and Pa han con ols, which we e in e p e ed as he
esul o a disinhibi o y e ec o dec eased GABAe gic ac i i y a he halamic le el,
induced by he ch onic exposu e o alcohol. These esul s we e subsequen ly con i med
in a s udy in animals wi h a long pe iod o ch onic e hanol in ake [18].
Al hough he MAEPs’ abno mali ies we e ini ially a ibu ed o he neu o oxic
consequences o alcohol, bo h de ici s in inhibi ion and GABAe gic unc ion anomalies
ha e been ela ed o gene ic ulne abili y o alcoholism: de ici s in elec ophysiological
inhibi ion ha e been p oposed as he cause o abno mali ies in o he componen s o
e en - ela ed po en ials, such as P3b and P3a ampli ude educ ions, bo h in alcoholics
and hei child en [30, 33]. Au onomic psychophysiological s udies also poin o p oblems
wi h inhibi ion o he in o ma ion inpu , indica ed by he ca diac hype eac i i y o s ess ul
and no el s imuli [29]. Fu he mo e, gene ic di e ences in GABAA ecep o unc ion ha e
been p oposed as media ing di e ences in he esponsi eness o he seda i e and
anes hesic e ec s o alcohol be ween selec i e b eeding oden s [1, 37]. Then, i was
Pos -p in ( inal d a pos - e e eeing)
4
conside ed o in e es o explo e hese middle-la ency esponses in child en o alcoholic
pa en s when esea ch in o high isk o alcoholism was ini ia ed in ou g oup.
To assess he possibili y ha MAEPs we e anomalous in high- isk subjec s, he
p esen s udy assessed a sample o young child en o alcoholics wi h a mul igene a ional
amily his o y o alcoholism and con ols.
Me hods and ma e ials
Subjec s
The subjec s we e 32 child en anging om 10 o 14 yea s o age. The high isk (HR)
g oup (N = 15, eigh emales, mean = 12.2 ± 1.5 yea s) consis ed o child en o an
alcoholic a he wi h a high-densi y amily his o y o alcoholism. The subjec s in he HR
g oup we e selec ed om communi y ea men cen es, whe e hei a he s had been
diagnosed and ea ed. All he alcoholic a he s me DSM-III-R [4] c i e ia o alcohol
dependence (diagnosis made by he s a o he cen es was co obo a ed du ing he
selec ion in e iew). Those wi h a his o y o psychopa hological p oblems o he han
seconda y o alcoholism (acco ding o he clinical his o y om he cen es and he
in o ma ion collec ed du ing he selec ion in e iew) we e excluded.
The amily his o y o alcoholism was asce ained om a he s and mo he s using
he amily his o y in e iew me hod. Only child en o alcoholic a he s who had a leas
wo o he i s o second-deg ee alcoholic ela i es we e included. The con ol (CN) g oup
(N = 17, en emales, mean = 11.8 ± 1.4 yea s) consis ed o child en o non-alcoholic
a he s wi hou a amily his o y o alcoholism. To gua an ee homogenei y wi h ega d o
socio-demog aphic a iables, con ol subjec s we e ec ui ed om olun a y amilies
om schools in he egion wi hin he same age ange and socioeconomic s a us as hose
in he HR g oup. Con ol amilies who epo ed any p oblems wi h alcohol in i s o
seconddeg ee ela i es we e excluded.
O he exclusion c i e ia we e simila o he wo g oups, and included
consump ion o alcohol o o he d ugs, a his o y o psychopa hological diso de s,
p ena al exposu e o alcohol, de elopmen al o school e a da ion, a posi i e
neu ological his o y, majo medical p oblems, cu en medica ion, non-co ec ed senso y
de ici s, a amily his o y o majo men al diseases and p oblems o alcoholism in he
mo he . In o ma ion abou inclusion and exclusion c i e ia was ob ained h ough de ailed
semi-s uc u ed in e iews wi h bo h he child en and hei a he s and mo he s. The
in e iews we e a ansla ed and adap ed e sion o he Semi-S uc u ed Assessmen
Pos -p in ( inal d a pos - e e eeing)

5
o he Gene ics o Alcoholism (SSAGA), e sions o adul s, child en, adolescen s and
pa en s, as well as he Family His o y Assessmen Module, designed by he
Collabo a i e S udy on he Gene ics o Alcoholism (COGA) [10]. Ques ions abou
indi idual and amilial psychopa hological p oblems we e based on DSM-III-R c i e ia
and a leas one o he diagnos ic classi ica ion sys em. In o ma ion was also ob ained
du ing he in e iews abou demog aphic da a, amily ela ions, school achie emen and
social ac i i ies.
The inal sample was well ma ched on age, socioeconomic s a us and educa ion (all
subjec s we e en olled in compulso y schooling and ollowed he g ade acco ding o age)
be ween he g oups ( able I).
Table I. Demog aphic cha ac e is ics o con ol and high- isk g oups.
Con ols
High-Risk
P
(N = 17)
(N = 15)
Gende ( /m)
10/7
8/7
Age ( ange)
10–14
10–14
Mean (SD)
11.8 (1.4)
12.2 (1.5)
0.412
Educa ion (yea s)
6.1 (1.3)
7.0 (1.3)
0.059
/m: emale/male.
P ocedu e
Families who me equi emen s o he s udy we e asked o pa icipa e; hose who
ag eed signed a consen o m, and hen ecei ed an appoin men o he assessmen .
When child en a i ed a he labo a o y (ea ly in he mo ning o in he a e noon), he
membe s o s a showed hem he labo a o y and explained he con en s and p ocedu e
o he assessmen .
The subjec s sa in a com o able a mchai , in an elec ically-isola ed, soundand
ligh -a enua ed labo a o y. They ecei ed ins uc ions o a oid mo ing du ing he es s
and o di ec hei gaze o a poin 1 m in on o hei eyes whe e he s imuli we e
p esen ed.
The s imuli we e 400 a e ac ion clicks (0.1 ms du a ion) gene a ed by he S im
module o a Neu oscan sys em and p esen ed binau ally a a a e o 1.1/s h ough
ea phones, wi h an in ensi y 60 dB SL (60 dB abo e indi idual pe cep ual h eshold,
es ima ed using he me hod o ascending and descending limi s wi h a ia ion in e als
o 0.75 dB SPL). The expe imen al pa adigm (bo h s imuli cha ac e is ics and eco ding
pa ame e s) was selec ed o op imize he eco dabili y o bo h Pa and Pb. Tones a e
Pos -p in ( inal d a pos - e e eeing)
6
equen ly used o ob ain he Pb peak, and i has been epo ed ha low equency (500
Hz), long-du a ion (60 ms) one bu s s a e op imal o e oke Pb [26]; howe e , hese
pa ame e s a e no he bes o ob aining Pa, due o he long du a ion o he s imuli, which
o e lap wi h he ea lie MAEP componen s. Clicks a e he mos common s imuli used o
eco d Pa [35]. The in e -s imulus in e al was also he esul o a ade-o ; a highe a e
would be adequa e o ob ain Pa, and i would pe mi us o use a la ge numbe o s imuli
pe un; none heless, he eco dabili y o Pb would be se iously impai ed, due o
ampli ude dec ease wi h epe i ion a es highe han 1/s.
Elec oencephalog aphic (EEG) ac i i y was eco ded a Cz and Fz (S anda d
Elec ode Posi ion Nomencla u e [3, 21]) using in elec odes, e e ed o linked ea lobes,
and wi h a o ehead g ound. Addi ional elec odes we e used o moni o eye mo emen s
(sup ao bi al and he ou e can hus o he le eye, e e ed o an in ao bi al elec ode).
EEG ac i i y was il e ed (1-300 Hz) and ampli ied 50 K (G ass Neu oda a Acquisi ion
Sys em, mod. 12, connec ed o a Neu o Scan, Inc. sys em o he analog- o-digi al
con e sion and s o age). Impedance alues we e kep a 5 KΩ o below.
EEG was con inuously sampled a a a e o 1500 Hz. The signal was p ocessed
o -line: EEG was epoched om 10 ms p e-s imulus o 100 ms pos -s imulus, digi ally
il e ed a 10–300 Hz, linea ends we e elimina ed and he signal was adjus ed o 0 mV
p es imulus baseline and a e aged (400 epochs). Mo eo e , o assess he ep oducibili y
o he wa e o ms, he i s 200 segmen s we e a e aged sepa a ely om he las 200
segmen s, and he in a-class co ela ion be ween he wo aces we e pe o med.
Da a analysis
Peak la encies (ms) and ampli udes (µV) o Pa and Pb a each elec ode we e measu ed
wi h a semi-au oma ic peak de ec ion p og am. Fi s , a compu e algo i hm was used o
sea ch o he maximum nega i e peak ampli ude o each elec ode wi hin he
p ede ined la ency window: 25-40 and 50-80 ms o Pa and Pb espec i ely. Peaks we e
hen e i ied and adjus ed by isual inspec ion, and hose which we e doub ul we e
e ised by a second expe ienced membe o he labo a o y, blind o he isk s a us o he
subjec and he ini ial peak. Ampli ude and la ency alues we e au oma ically expo ed
o an ASCII ile o subsequen analyses.
P elimina y isk g oup (con ol, HR) by gende (male, emale), and isk g oup
(con ol, HR) by age ( i e le els, 10-14 yea s old) ANOVAs we e made o de e mining
he inclusion o gende and age a iables in he design. As gende mani es ed no main
e ec s o in e ac ions in hese analyses, bo h gende s we e conside ed join ly. Age
showed an in e ac ion wi h he isk g oup ac o o he Pa la ency, hen i was conside ed
Pos -p in ( inal d a pos - e e eeing)
7
in he inal analysis; his demog aphic ac o had no e ec s on he o he dependen
a iables, whe e i was excluded om subsequen analyses.
Then, he da a we e analyzed using 2 x 2 mixed-model ANOVAs, wi h elec ode
si e (Fz, Cz) as a wi hin-subjec ac o and isk g oup (con ol, HR) as be ween-subjec s
ac o o he ampli udes o Pa and Pb, and he la ency o Pb, and using an Elec ode
(Fz, Cz) by isk g oup (con ol, HR) by age ( i e le els, 10-14-yea s old) design o he
la ency o Pa.
Resul s
Rep oducibili y o he eco dings and peak de ec abili y
The in a-class co ela ions be ween he wo wa e o ms ob ained om each subjec we e
high bo h o he con ol (Cz mean = .80 ± .17, Fz mean = .87 ± .12) and he high isk
g oup (Cz mean = .82 ± .17, Fz mean = .85 ± .18), and simila o he wo g oups ( = –
0.28, NS a Cz, and = 0.42, NS a Fz), indica ing an adequa e simila i y be ween he
wo segmen s o he un, and hen an adequa e ep oducibili y o he whole wa e o m.
The a e o de ec abili y o he wo main posi i e MAEP peaks we e accep able
in he ligh o p e ious epo s. Pa was obse able in 20 subjec s (62.5%, 11 con ols
and nine HR) and Pb was measu able in 26 subjec s (81.2%, 12 con ols and 14 HR).
Bo h Pa and Pb join ly we e obse ed in 18 o he 32 subjec s (nine con ols and nine
HR). Fou subjec s ( h ee con ols and one HR) showed a wa e o m consis ing o a
b oad posi i e de lec ion, peaking in he middle be ween he Pa and he Pb la ency
windows, and we e excluded om he s udy; his mo phology has been desc ibed
p e iously [27, 34]. The wa e o ms eco ded om ou ep esen a i e subjec s a e
p esen ed in igu e 1.
Risk g oup e ec s
Figu e 2 illus a es he g and a e aged EP wa e o ms o he con ol and HR subjec s
whe e bo h Pa and Pb we e measu able, and he desc ip i e da a a e summa ized in
able II. Signi ican e ec s a ec ing he isk g oup ac o we e obse ed o he ampli ude
o Pa (F [1, 18] = 9.925, P = 0.006) and he la ency o Pb (F [1,24] = 4.340, P = 0.048).
The ampli ude o Pa was smalle and he la ency o Pb was sho e in he HR g oup han
in he con ol g oup. Risk g oup and age ac o s mani es ed a signi ican in e ac ion on
he la ency o Pa (F [4, 10] = 31.124, P = 0.025), whe e he age ac o also had a
signi ican main e ec (F [4,10] = 3.652, P = 0.044). This in e ac ion e ec is illus a ed
Pos -p in ( inal d a pos - e e eeing)
8
in igu e 3, whe e i can be obse ed ha he la ency o Pa ends o diminish wi h age,
and his e ec was mo e p ominen in he HR g oup han in he con ol g oup. I mus be
no ed ha he eg ession unc ions a e non-signi ican , and hey a e only p esen ed o
illus a e he in e ac ion e ec . No isk g oup e ec s we e obse ed on Pb ampli ude. The
wi hin-subjec ac o elec ode si e was signi ican o he ampli ude o Pb (F [1, 24] =
23.571, P = 0.000), and he la ency o Pa (F [1, 10] = 9.915, P = 0.010) and Pb (F [1, 24]
= 4.870, P = 0.037).
Figu e 1. Indi idual wa e o ms om ou ep esen a i e subjec s, wo om he con ol g oup ( op)
and wo om he high- isk g oup (bo om). The le wa e o ms a e ep esen a i e o hose cases
whe e only Pb was iden i ied; he igh wa e o ms ep esen hose cases whe e bo h Pa and Pb
we e iden i ied.
Figu e 2. G and mean wa e o ms o he MAEPs o he con ol and he high- isk g oups, including
he o al sample (le ), hose subjec s who en e ed he Pa ANOVA (cen e ) and hose who en e ed
he Pb ANOVA ( igh ).
Pos -p in ( inal d a pos - e e eeing)