En i onmen al Resea ch 226 (2023) 115574
A ailable online 24 Feb ua y 2023
0013-9351/© 2023 The Au ho s. Published by Else ie Inc. This is an open access a icle unde he CC BY license (h p://c ea i ecommons.o g/licenses/by/4.0/).
The e ec s o exposu e o oad a ic noise a school on cen al audi o y
pa hway unc ional connec i i y
Ge a d Ma ínez-Vila ella
a
,
c
, Jesus Pujol
a
,
b
, Lau a Blanco-Hinojo
a
,
b
,
g
, Joan Deus
a
,
c
,
Ioa Ri as
d
,
e
,
, Cecilia Pe sa en o
d
,
e
,
, Jo di Sunye
d
,
e
,
,
g
, Ma ia Fo as e
d
,
e
,
,
h
,
*
a
MRI Resea ch Uni , Depa men o Radiology, Hospi al del Ma , Ba celona, Spain
b
CIBER de Salud Men al, Ins i u o de Salud Ca los III, Ba celona, Spain
c
Depa men o Clinical and Heal h Psychology, Au onomous Uni e si y o Ba celona, Ba celona, Spain
d
ISGlobal, Ba celona, Spain
e
Pompeu Fab a Uni e si y (UPF), Ba celona, Spain
CIBER Epidemiología y Salud Pública (CIBEREsp), Spain
g
IMIM (Hospi al del Ma Medical Resea ch Ins i u e), Ba celona, Spain
h
PHAGEX Resea ch G oup, Blanque na School o Heal h Science, Uni e si a Ramon Llull (URL), Ba celona, Spain
ARTICLE INFO
Handling Edi o : Jose L Domingo
Keywo ds:
Noise
T a ic
Child en
Audi ion
B ain
Neu oimaging
ABSTRACT
As he wo ld becomes mo e u banized, mo e people become exposed o a ic and he isks associa ed wi h a
highe exposu e o oad a ic noise inc ease. Excessi e exposu e o en i onmen al noise could po en ially
in e e e wi h unc ional ma u a ion o he audi o y b ain in de eloping indi iduals. The aim o he p esen s udy
was o assess he associa ion be ween exposu e o annual a e age oad a ic noise (LAeq) in schools and
unc ional connec i i y o key elemen s o he cen al audi o y pa hway in schoolchild en. A o al o 229 child en
om 34 ep esen a i e schools in he ci y o Ba celona wi h ages be ween 8 and 12 yea s (49.2% gi ls) we e
e alua ed. LAeq was ob ained as he mean o 2-consecu i e day measu emen s inside class ooms be o e lessons
s a ed ollowing s anda d p ocedu es o ob ain an indica o o long- e m oad a ic noise le els. A egion-o -
in e es unc ional connec i i y Magne ic Resonance Imaging (MRI) app oach was adop ed. Func ional con-
nec i i y maps we e gene a ed o he in e io colliculus, medial genicula e body o he halamus and p ima y
audi o y co ex as key le els o he cen al audi o y pa hway. Road a ic noise in schools was signi ican ly
associa ed wi h s onge connec i i y be ween he in e io colliculus and a bila e al halamic egion adjacen o
he medial genicula e body, and wi h s onge connec i i y be ween he medial genicula e body and a bila e al
b ains em egion adjacen o he in e io colliculus. Such a unc ional connec i i y s eng hening e ec did no
ex end o he ce eb al co ex. The ana omy o he associa ion implica ing subco ical elays sugges s ha p o-
longed oad a ic noise exposu e in de eloping indi iduals may accele a e ma u a ion in he basic elemen s o
he audi o y pa hway. Fu u e esea ch is wa an ed o es ablish whe he such a as e ma u a ion in ea ly
pa hway le els may ul ima ely educe he de eloping po en ial in he whole audi o y sys em.
1. In oduc ion
Wi hin ou u banized wo ld, exposu e o noise has become un-
a oidable, especially in highly u banized a eas and majo ci ies whe e
demand o anspo and oad a ic has su e ed a g ea g ow h du ing
he las yea s (Eu opean En i onmen al Agency, 2020). En i onmen al
noise has been associa ed wi h a ange o di e en audi o y and
non-audi o y ad e se heal h e ec s (Basne e al., 2014; Basne and
McGui e, 2018; Egge mon , 2017; Kempen e al., 2018; Wo ld Heal h
O ganiza ion, 2018) including annoyance (Guski e al., 2017; Oh s om
e al., 2006), sleep dis u bance (Basne and McGui e, 2018; Smi h e al.,
2022), ca dio ascula diseases (Kempen e al., 2018) and mo ali y
Abb e ia ions: CSF, ce eb ospinal luid; dB, decibels; EPI, echoplana imaging; ISO, In e na ional S anda ds O ganiza ion; LAeq, A-weigh ed equi alen sound
p essu e le els; MNI, Mon eal Neu ological Ins i u e; MRI, Magne ic Resonance Imaging; MRI, unc ional Magne ic Resonance Imaging; FEW, amily-wise e o ;
ROI, egions o in e es ; SPM, S a is ical Pa ame ic Mapping; WHO, Wo ld Heal h O ganiza ion.
* Co esponding au ho . ISGlobal, Ba celona, Spain. Biomedical Resea ch Pa k (PRBB). Doc o Aiguade , 88. 08003 Ba celona, Spain.
E-mail add ess: [email p o ec ed] (M. Fo as e ).
Con en s lis s a ailable a ScienceDi ec
En i onmen al Resea ch
jou nal homepage: www.else ie .com/loca e/en es
h ps://doi.o g/10.1016/j.en es.2023.115574
Recei ed 4 No embe 2022; Recei ed in e ised o m 21 Feb ua y 2023; Accep ed 23 Feb ua y 2023
En i onmen al Resea ch 226 (2023) 115574
2
(Cole-Hun e e al., 2022), among o he s (Cla k e al., 2020). Due o i s
public heal h ele ance, he Wo ld Heal h O ganiza ion (WHO) has been
de eloping ecommenda ions and guidelines wi h he aim o limi he
le els o en i onmen al noise exposu e and p o ec human heal h
(Wo ld Heal h O ganiza ion, 2018).
Focusing on he possible ha m ul e ec s p oduced in child en, oad
a ic noise in school en i onmen has been associa ed wi h poo e
men al heal h, al hough he e idence is s ill limi ed (Cla k and Pau-
no ic, 2018; Cla k e al., 2020), and wi h poo e cogni i e pe o mance
and de elopmen (Cla k e al., 2020; Cla k and Pauno ic, 2018; E ickson
and Newman, 2017; S ans eld e al., 2005; S ans eld and Cla k, 2015;
Ma heson e al., 2010; Fo as e e al., 2022). These s udies ha e mos ly
ocused on noise exposu e a school, whe e child en spend mos o he
weekdays and concen a ion occu s.
To ou knowledge, he e is only one unc ional imaging s udy
explo ing he possible impac o oad a ic noise on b ain in school-
child en (P´
e ez-C espo e al., 2022). In his unc ional connec i i y MRI
app oach, P´
e ez-C espo e al. ocused on home-ou doo exposu e o oad
a ic noise and comp ehensi ely assessed he whole co ex and majo
subco ical s uc u es and ound no signi ican esul s sugges i e o g oss
noise- ela ed unc ional epe cussions. Howe e , he subco ical ele-
men s o he cen al audi o y pa hway we e no speci ically e alua ed in
his s udy. The e o e, a de ailed, audi o y sys em-speci ic analysis may
be aluable o po en ially cap u e mo e p ecise e ec s o oad a ic
noise on unc ional connec i i y du ing b ain de elopmen .
While excessi e noise le els can di ec ly lead o hea ing impai men ,
noise may also lead o a neu opa hy o he inne ea wi hou impac ing
he hea ing h eshold, bu al e ing hea ing pe cep ion, which could
a ec lea ning (Plack e al., 2014). Mo eo e , a p e ious MRI s udy
obse ed ha mode a e exposu e o noise in a s (65 dB, 2 mon hs, i.e.
sub-ch onic exposu e) was able o c ea e changes in he genicula e body
and audi o y co ex (Lau e al., 2015a). Such e ec may be e en mo e
ele an du ing childhood o e en la e in adolescence, when elemen s
o he cen al audi o y pa hway a e s ill de eloping, as obse ed in he
b ains em unc ion and ma u a ion o obliga o y co ical audi o y
e oked po en ial componen s (Skoe e al., 2015; Wunde lich e al.,
2006). The unde s anding o how en i onmen al noise could a ec he
b ain de elopmen o he speci ic s uc u es in ol ed in hea ing is also
impo an gi en ha i has been demons a ed in mammalians s udies
ha he audi o y pa hway is a highly dis ibu ed ne wo k, which ex-
hibi s ex ensi e de elopmen al neu oplas ici y, as well as no able
adap a ion o ad e se condi ions and disease (Bandyopadhyay e al.,
2010; Sch eine and Polley, 2014; Lau e al., 2015a). A he same ime,
li le is ye known abou how his neu oplas ici y could impac lea ning
(Sch eine and Polley, 2014). Besides, childhood is a c ucial pe iod o
o e all b ain ma u a ion (S ans eld and Cla k, 2015; Pujol e al., 2016)
and child en ha e been desc ibed as a pa icula ly ulne able popula-
ion o he e ec s o en i onmen al noise, pa icula ly o anspo a ion
noise a school in ela ion o cogni i e de elopmen (Cla k and Pau-
no ic, 2018; Cla k e al., 2020; E ickson and Newman, 2017; Fo as e
e al., 2022; an Kamp and Da ies, 2013). We hus pos ula e ha p o-
longed exposu e o oad a ic noise a school du ing b ain de elopmen
would a ec ine neu onal coupling a he basic le els o audi o y signal
p ocessing. So, on one hand, pe sis en audi o y inpu could hypo he -
ically accele a e he ma u a ion o p ima y neu al connec ions in he
audi o y pa hway. On he o he , en i onmen al noise migh in e e e
wi h o he ele an sounds ha need p ocessing, c ea ing a low quali y
audi o y s imuli which could ul ima ely hampe he ma u a ion o
high-o de connec ions a he co ex.
The cen al audi o y pa hway begins when he cochlea ne e en e s
he b ains em. The neu al ac i i y is i s ly p ocessed in se e al nuclei (e.
g., cochlea nuclea complex, supe io oli e and medial nucleus o
apezoid body) and is hen con e gen ly ansmi ed o he in e io
colliculus ha is a hub ecei ing bo h he audi o y inpu (Ress and
Chand aseka an, 2013) and descending p ojec ions om he audi o y
co ex (Wine , 2005; S ebbings e al., 2014) and p ima ily p ocessing
he basic aspec s o he audi o y signal (De Ma ino e al., 2013; Moe el
e al., 2015; Ress and Chand aseka an, 2013). The in e io colliculus
p ojec s ipsila e ally and con ala e ally o he medial genicula e body,
which is he halamic elay o he pa hway ha u he con ibu es o
encoding he equency and localiza ion o sound (Mihai e al., 2019).
F om he halamus, he audi o y signal is ansmi ed o he p ima y
audi o y co ex.
The aim o he p esen s udy was o assess he associa ion be ween
school-indoo exposu e o annual a e age oad a ic noise and unc-
ional connec i i y o key elemen s o he cen al audi o y pa hway in
schoolchild en. The in e io colliculus, medial genicula e body and
p ima y audi o y co ex we e hus speci ically a ge ed o gene a e
unc ional connec i i y MRI maps using a egion-o -in e es app oach.
2. Me hods
2.1. Pa icipan s
This s udy was de eloped in he con ex o a la ge-scale p ojec
designed o assess he e ec s o en i onmen al ac o s on b ain de el-
opmen in child en (BREATHE p ojec ). S udy design and pa icipan
selec ion ha e been desc ibed in ull de ail elsewhe e (Sunye e al.,
2015; Pujol e al., 2016). In sho , he BREATHE p ojec ec ui ed 2897
child en o o m a ep esen a i e sample o schoolchild en in Ba celona
(Sunye e al., 2015). A ep esen a i e subsample o 278 child en om
34 schools was ec ui ed om he la ge coho o pa icipa e in neu-
oimaging. The MRI p ocedu e was explained in de ail o he pa en s o
legal gua dians by phone, p io o p o iding he in o med consen o
pa icipa e in he s udy. All he MRI p ocedu e was explained again by a
ained in es iga o and any cla i ica ion was also p o ided o bo h
child en and pa en s be o e s a ing he scan acquisi ion. The e we e 3
child en ha did no wan o pe o m he MRI be o e i s a ed, and 10
child en ha wan ed o in e up he acquisi ion once i had s a ed. In
he cu en s udy, we included 229 child en (49.2% gi ls) wi h comple e
noise exposu e assessmen and alid MRI da a. The mean age a MRI
was 9.7 yea s, SD 0.8 yea s and ange 8.0–12.1 yea s.
2.2. Noise exposu e assessmen and con ex ual cha ac e is ics
We measu ed oad a ic noise in wo campaigns, he i s s a ing in
Janua y 2012 (cold season) and he second 6 mon hs la e (wa m sea-
son). In each campaign, noise was assessed in he class oom a each
school o 2 days. We ollowed he p o ocol o ISO 1996–2 (2007) which
allows o ob ain long- e m noise le els pe o ming sho - e m noise
measu emen s. We assessed LAeq in decibels (dB), i.e. A-weigh ed
equi alen sound p essu e le els, which ep esen s a e age noise le els.
Measu emen s we e pe o med h ough h ee consecu i e10-min e-
co dings in di e en posi ions in one class oom wi h a calib a ed CESVA
SC160 de ice. Measu emen s we e ob ained wi h closed windows and
be o e lessons s a ed o ob ain backg ound oad a ic noise le els. This
was epea ed again he day a e . Measu emen s we e supe ised o
iden i y i ele an sounds and hese we e la e emo ed o p ocu e a
speci ic measu e o oad a ic noise. Due o incomple e da a du ing he
i s campaign, he exposu e used in he p esen s udy was he 2-day
a e age o he second campaign measu emen s.
The in aclass co ela ions (ICC) o he means o each campaign we e
e y high (i.e. ICC =0.89 (be ween he 2-day mean o each campaign)
and ICC =0.94 (mean o he 2 campaigns). This suppo s he use o he
2-day a e age o he second campaign as a ma ke o long- e m school-
indoo exposu e o oad a ic noise.
Addi ional cha ac e is ics we e collec ed, as p e iously desc ibed
(Sunye e al., 2015), including age and sex o he child, ma e nal ed-
uca ion, home and school ulne abili y index a census ac le el,
beha io al p oblems (S eng hs and Di icul ies Ques ionnai e)
answe ed by pa en s, and annual a e age le els o a ic- ela ed ai
pollu ion (i.e. ni ogen dioxide and elemen al ca bon) measu ed in he
G. Ma ínez-Vila ella e al.
En i onmen al Resea ch 226 (2023) 115574
3
class oom du ing he campaigns o yea 2012.
2.3. MRI acquisi ion
MRI was acqui ed wi h a 1.5 T Signa Exci e sys em (Gene al Elec ic,
Milwaukee, WI, USA), which was equipped wi h an eigh -channel
phased-a ay head coil and used a single-sho echoplana imaging
(EPI) so wa e. The comple e s udy p o ocol included a high- esolu ion
3D ana omical sequence, di usion enso imaging (DTI) o 25 di ec ions,
p o on (1 H) magne ic esonance spec oscopy based on he P o on
B ain Exam-Single Voxel (PROBE-SV) so wa e and wo unc ional MRI
sequences ( ask-ac i a ion and es ing-s a e unc ional imaging). The
acquisi ion de ails o each sequence a e p o ided elsewhe e (Pujol e al.,
2016). The cu en s udy was based on he speci ic analysis o he
unc ional MRI es ing-s a e sequence ha consis ed o g adien ecalled
acquisi ion in he s eady s a e wi h epe i ion ime o 2000 ms, echo ime
o 50 ms; ield o iew o 24 cm, 64 ×64-pixel ma ix, pulse angle o 90◦,
slice hickness o 4 mm (in e -slice gap, 1.5 mm). A o al o 22 in e -
lea ed slices pa allel o he an e io -pos e io commissu e line co e ing
he b ain we e p esc ibed. The sequence was aken in es ing s a e and
las ed 6 min in o al. 180 whole-b ain EPI olumes we e ob ained om
he scan. To allow magne iza ion o each equilib ium, he i s ou
(addi ional) images in each un we e disca ded. Child en we e ins uc-
ed o elax, keep hei eyes closed, and lie s ill du ing he scan.
2.4. Image p ep ocessing
S anda d p ocedu es p e iously used by ou g oup we e conside ed
o he p esen unc ional MRI analysis (Pujol e al., 2016). The s eps o
image p ep ocessing consis ed o mo ion co ec ion, spa ial no maliza-
ion and smoo hing ca ied ou wi h a Gaussian il e ( ull-wid h
hal -maximum, 8 mm). The da a was di ec ly no malized o he s anda d
S a is ical Pa ame ic Mapping (SPM) EPI empla e and e-sliced o 2
mm iso opic esolu ion in Mon eal Neu ological Ins i u e (MNI) space.
Low- equency d i s below 0.008 Hz we e emo ed using a Disc e e
cosine T ans o m (DCT) il e . Fu he mo e, we ob ained es ima es o
ce eb ospinal luid (CSF), whi e ma e , and global b ain signal luc u-
a ions (using s anda d masks in MNI space om SPM), which we e
included as nuisance (con ounding) a iables in he eg ession analyses.
To con ol o po en ial head mo ion e ec s, he nex s eps we e
adop ed: a) Con en ional alignmen o SPM ime-se ies o he i s image
olume in each subjec ; b) Exclusion o 22 pa icipan s ( om an o iginal
g oup o 251 child en wi h comple e es ing-s a e MRI) due o la ge
head mo ion (boxplo -de ined ou lie s) (Pujol e al., 2014), leading o a
inal sample o 229 child en; c) Inclusion o mo ion- ela ed eg esso s
and es ima es o global b ain signal luc ua ions as con ounding a i-
ables in i s -le el (single-subjec ) analyses; d) To disca d
mo ion-a ec ed olumes wi hin subjec , censo ing-based MRI signal
a i ac emo al (sc ubbing) (Powe e al., 2014) was used. Fo each
indi idual, in e - ame mo ion measu emen s (Pujol e al., 2014) we e
used as an indica o o da a quali y o lag olumes o ques ionable
quali y ac oss he un. Fo poin s wi h in e - ame mo ion >0.2 mm, he
co esponding olume as well as he immedia ely p e ious and subse-
quen wo olumes we e emo ed. This led o he exclusion o a mean o
10.8 (6.0%) ±13.4 ol ou o 180 MRI es ing-s a e sequence olumes;
e) Fu he exclusion o po en ial mo ion e ec s applying a summa y
measu emen o each subjec (mean in e - ame mo ion ac oss he MRI
un) as a eg esso in he second-le el (g oup) analyses in SPM (Pujol
e al., 2014).
2.5. De ini ion o connec i i y maps
The objec i e o his s udy was o selec i ely analyze unc ional
connec i i y o key nodes o he cen al audi o y pa hway up o he
p ima y audi o y co ex (Be lo e al., 2020; Moe el e al., 2015; Sche-
linski e al., 2022). Thus, we a ge ed he in e io colliculus, he medial
genicula e body o he halamus and he p ima y audi o y co ex.
Based on p e ious s udies (Díaz e al., 2012; Fi zhugh e al., 2019;
Si ek e al., 2019; Schelinski e al., 2022), he egions o in e es (ROI)
(o ‘seeds’) we e cen e ed a MNI coo dina es (in mm): (i) in e io col-
liculus [x =5, y = − 35, z = − 10]; (ii) medial genicula e body [x =16, y
= − 24, z = − 6]; and (iii) p ima y audi o y co ex (Heschl’s gy us) [x =
45, y = − 19, z =7]. Each seed egion was de ined as a 3.5-mm adial
sphe e using he Ma sBa ROI oolbox in MNI s e eo axic space (B e
e al., 2003). Nex , he mean ROI alue a each ime poin o e he
ime-se ies was compu ed o ex ac he signals o in e es o each seed
egion. To gene a e he connec i i y maps, he signal ime cou se o a
selec ed seed egion was applied as a eg esso o be co ela ed wi h he
signal ime cou se o e e y oxel in he b ain o p oduce i s -le el
(single-subjec ) oxel-wise s a is ical pa ame ic maps.
3. S a is ical analysis
3.1. Associa ion be ween noise and connec i i y maps: oxel-wise
co ela ion analysis
A e indi idual p ep ocessing o each unc ional image sequence,
sepa a e second-le el analysis we e pe o med using SPM o map oxel-
wise ac oss-subjec co ela ion be ween school-indoo noise (exposu e)
and he selec ed unc ional connec i i y maps (ou come) o he cen al
audi o y pa hway. A mo ion summa y measu e (mean in e ame mo-
ion [Pujol e al., 2014]) o each pa icipan was included as a nuisance
a iable.
The esul s we e conside ed signi ican a a heigh h eshold o p <
0.005, sa is ying he amily-wise e o (FWE) a e co ec ion PFWE
<0.05 using SPM. Conside ing s udy aims and he small size o he
ana omical s uc u es examined (Moe el e al., 2015; Ress and Chan-
d aseka an, 2013; Si ek e al., 2019), a small olume co ec ion
app oach was adop ed o es o signi ican esul s wi hin he assessed
le els o he audi o y pa hway. Resul s ana omically ela ed o he
in e io colliculus le el we e co ec ed o he es ima ed olume o he
b ains em (WFU Picka lass), hose ela ed o he medial genicula e body
we e co ec ed o he olume o he halamus (WFU Picka lass; Kelle
e al., 2012), and he co ical le el o he olume o he p ima y audi-
o y co ex (WFU Picka lass). A whole-b ain co ec ion h esholding was
conside ed o es o signi ican esul s be ween each audi o y pa hway
egion-o -in e es and he es o he b ain.
3.2. Sensi i i y analyses
The e ec o po en ial con ounde s on he associa ion be ween noise
and unc ional connec i i y was es ed (one-by-one and combined) o
each signi ican inding including age, sex, pa en al educa ion, home
and school ulne abili y index, beha io al p oblems, o annual a e age
le els o a ic- ela ed ai pollu ion using mul i a ia e linea eg ession
models. Simila ly, gi en ha he oxel-wise co ela ion analysis did no
allow o mul ile el analysis, we es ed he e ec o school using a linea
mixed-e ec model be ween noise and unc ional connec i i y,
including all he con ounde s abo e plus a andom e ec by school.
4. Resul s
Table 1 summa izes he cha ac e is ics o he s udy sample. The
annual a e age school-indoo noise le els showed a mean o 37.4 dB (SD
4.7 and ange 28.8–48.0 dB) and median (in e qua ile ange, IQR) o
39.9 (8.4) dB, which exceeded he maximum backg ound noise le el
(35 dB) ecommended in school class ooms (Be glund e al., 1999).
Child en had a mean (SD) age o 9.7 (0.8) yea s, median (IQR) o 9.8
(1.3), 49.2% we e gi ls, 67.7% o mo he s and 57.8% o pa ne s had
uni e si y s udies. No di e ences we e obse ed be ween he included
MRI sample and he excluded MRI sample excep ha he included
sample was sligh ly olde (0.1 y) and had sligh ly less gi ls (1.9%)
G. Ma ínez-Vila ella e al.
En i onmen al Resea ch 226 (2023) 115574
4
compa ed o he o al ec ui ed MRI sample. The annual a e age
school-ou doo noise le els showed a mean o 62.4 (6.4) dB and a
Spea man’s co ela ion wi h school-indoo noise le els o 0.15 (p- alue
=0.023).
4.1. Func ional connec i i y maps
The unc ional connec i i y map gene a ed om a egion-o -in e es
(seed) placed a in e io colliculus iden i ied a ne wo k ha bila e ally
included he uppe b ains em, he ce ebellum, he halamus-pul ina ,
hypo halamus, he len i o m nuclei and se e al a eas o he ce eb al
co ex such as isual co ex, insula, an e io cingula e co ex and su-
pe io empo al gy us (Table 2).
The medial genicula e body unc ional connec i i y map included
he con ala e al halamus, and bila e ally he uppe b ains em wi h
bo h colliculi, he len i o m nuclei, he ce ebellum and co ical a eas
such as supplemen a y mo o co ex, senso y-mo o co ex, isual co -
ex, la e al empo o-occipi al, insula, on o-pa ie al ope culum and
supe io empo al gy us.
The p ima y audi o y co ex unc ional connec i i y map iden i ied a
ne wo k ha included he con ala e al audi o y co ex, and bila e al
insula, on o-pa ie al ope culum, senso y-mo o co ex, isual co ex,
an e io cingula e co ex, and subco ical a eas such as he midb ain,
hypo halamus, halamus and he colliculi in he uppe b ains em.
Finally, he unc ional connec i i y maps ob ained om ou selec ed
ROIs eliably cap u ed he ele an b ain s uc u es p ocessing audi o y
s imuli (Boyen e al., 2014; Smi h e al., 2009; Heckne e al., 2021). Fo
example, ou ex ensi e p ima y co ex seed map included 63.8% o he
ne wo k iden i ied in he me a-analysis by Heckne e al. (2021) based
on 122 ask-ac i a ion audi o y expe imen s. Fig. 1 compa a i ely il-
lus a es he unc ional ana omy o bo h ou es ing-s a e p ima y
audi o y co ex seed map and he se o egions o signi ican con e -
gence ac oss asks du ing audi o y s imuli p ocessing.
4.2. Associa ions be ween exposu e o oad a ic noise and unc ional
connec i i y
Signi ican and ana omically speci ic associa ions be ween school-
indoo oad a ic noise and unc ional connec i i y measu es we e
obse ed in he in e io colliculus and medial genicula e body maps.
Wi hin he in e io colliculus unc ional connec i i y map, measu ed
noise was associa ed wi h highe connec i i y be ween he in e io
colliculus seed egion and a bila e al halamic egion adjacen o he
medial genicula e body in ol ing pa o he pul ina nucleus (Fig. 2
and Table 3). Recip ocally, in he medial genicula e body map, noise
was associa ed wi h highe connec i i y be ween he medial genicula e
body seed and a bila e al egion adjacen o he in e io colliculus
(Fig. 3). The e o e, school-indoo exposu e o oad a ic noise in
child en was associa ed wi h s onge connec i i y no ably wi hin he
subco ical audi o y pa hway (Table 3). No signi ican indings we e
obse ed in ol ing mo e dis an s uc u es a he whole-b ain h eshold.
As o he p ima y audi o y co ex (Heschl’s gy us) unc ional con-
nec i i y map, no signi ican esul s we e obse ed bo h a whole-b ain
and audi o y-pa hway h esholding. Howe e , i is o in e es o men ion
Table 1
Main s udy sample cha ac e is ics and compa ison be ween he included (n =
229) and excluded MRI pa icipan s (n =49).
Va iables Included
a,b
(n
=229)
Excluded
a,c
(n =49)
To al
a,b
(n
=278)
p-
alue
d
Indoo oad a ic
noise le els (LAeq, in
dB)
36.9 (8.4) 35.5 (7.6) 36.9 (8.4) 0.581
Age a MRI (y) 9.8 (1.3) 9.3 (1.5) 9.7 (1.3) 0.036
Home socioeconomic
ulne abili y index
(n)
0.4 (0.3) 0.4 (0.4) 0.4 (0.3) 0.699
School socioeconomic
ulne abili y index
(n)
0.4 (0.5) 0.5 (0.5) 0.4 (0.5) 0.137
Beha io al p oblems
(poin s)
8 (7) 8 (8) 8 (7) 0.419
Annual a e age NO
2
le els (
μ
g/m
3
)
29.6 (14.7) 29.8 (16.1) 29.6
(14.7)
0.446
Annual a e age
elemen al ca bon
le els (
μ
g/m
3
)
1.2 (0.9) 1.2 (0.7) 1.2 (0.9) 0.853
0.4 (0.5) 0.5 (0.5) 0.4 (0.5) 0.137
Sex
Gi ls 48.9 65.3 51.8 0.037
Boys 51.1 34.7 48.2
Ma e nal educa ion
Illi e a e 0.9 2.1 1.1 0.114
No s udies 2.2 0 1.8
P ima y 5.8 14.6 7.3
Seconda y 23.5 29.2 24.5
Uni e si y 67.7 54.2 65.3
Pa e nal educa ion
Ili e a e 0.9 0 0.8 0.200
No s udies 0.9 2.2 1.1
P ima y 7.3 17.8 9.1
Seconda y 33 31.1 32.7
Uni e si y 57.8 48.9 56.3
a
Da a a e median (in e qua ile ange) o pe cen age (%).
b
Va iables ha e no missing o less han 10% missing obse a ions.
c
Va iables ha e no missing o less han 10% missing obse a ions, excep
LAeq wi h 55.1% o missing obse a ions and age a MRI wi h 30.6% o missing
obse a ions.
d
K uskal–Wallis es o Chi-squa e es o s a a o included and excluded
pa icipan s wi h con inuous o ca ego ical a iables, espec i ely.
Table 2
Func ional connec i i y maps.
Righ hemisphe e Le hemisphe e
x y z x y z
In e io colliculus
F on o-pa ie al ope culum 36 20 8 4.3 -32 18 10 4.4
Insula 40 -24 2 4.6 -42 -22 2 4.1
Supe io empo al gy us 48 0 -12 12.5 -48 -4 -12 10.4
An e io cingula e co ex 12 32 28 4.1 -12 22 30 4.1
Visual co ex 10 -78 10 4.7 -10 -82 10 5.6
Len i o m nuclei 16 -6 -2 8.2 -16 -8 -4 7.9
Ce ebellum 8 -66 -16 8.7 -8 -66 -16 10.0
Thalamus-pul ina 12 -30 4 7.7 -12 -28 4 6.8
Hypo halamus 4 -4 -10 8.4 -4 -4 -10 8.9
Uppe b ains em 4 -34 -26 7.6 -6 -34 -26 6.2
Medial genicula e body
Soma osenso y-mo o co ex 24 -32 60 4.7 -40 -30 62 3.9
12 -8 68 8.7 -12 -12 68 6.7
Supplemen a y mo o a ea 10 -8 58 8.8 -8 -10 58 7.3
Supe io empo al gy us 50 -10 -8 5.2 -54 -2 -6 5.3
La e al empo o-occipi al co ex 46 -62 -2 6.4 -50 -66 2 6.6
Visual co ex 8 -86 2 6.7 -4 -96 8 7.5
Insula 40 12 -14 9.6 -40 10 -14 9.2
Ce ebellum 16 -62 -24 7.7 -12 -64 20 8.5
Con ala e al halamus -14 -24 -2 34.7
Midb ain culliculi 4 -34 -8 9.7 -4 -34 -6 9.0
Uppe b ains em 4 -26 -32 12.2 -6 -26 -30 9.9
P ima y audi o y co ex
Con ala e al audi o y co ex -40 -16 8 37.0
Soma osenso y-mo o co ex 44 -24 66 7.3 -36 -26 68 4.4
Supplemen a y mo o a ea 10 -10 62 4.1
An e io cingula e co ex 6 42 8 10.3 -4 40 10 12.1
F on o-pa ie al ope culum 36 26 6 18.4 -42 22 2 17.2
Insula 40 14 2 24.3 -38 10 2 22.2
Visual co ex 18 10.7 -12 -74 16 14.8
Midb ain colliculi 4 -32 -4 7.3 -2 -32 -4 7.1
Hypo halamus 4 -4 -10 7.0 -4 -4 -10 8.2
x y z a e coo dina es gi en in Mon eal Neu ological Ins i u e (MNI) space.
S a is ics co espond o a co ec ed h eshold P
FWE
<0.05 es ima ed using SPM.
T deno es s a is ic ans o med o Pea son’s .
G. Ma ínez-Vila ella e al.
En i onmen al Resea ch 226 (2023) 115574
5
ha noise showed a nega i e co ela ion wi h he s eng h o
connec i i y be ween he p ima y audi o y co ex seed egion and
bila e al in e io colliculus in a highly speci ic manne (Fig. 4). The e-
o e, he di ec ion o po en ial noise e ec s (s eng hen e sus weaken
unc ional connec i i y) was dis inc o bo h co ical and subco ical
le els o he audi o y pa hway.
No con ounding e ec was obse ed when including age, sex,
pa en al educa ion, home and school ulne abili y index, beha io al
p oblems, annual a e age le els o a ic- ela ed ai pollu ion, o school
as andom e ec . In speci ic, dec eases in β coe icien s a e he inclu-
sion o single con ounde s o hei combina ion we e ma ginal (mean ±
SD, 0.9% ±1.5%) wi h no a iables a ec ing he p ima y esul s wi h β
educ ions g ea e han 5%.
5. Discussion
To ou knowledge, his is he i s s udy o in es iga e he po en ial
epe cussions o oad a ic noise in schools on unc ional connec i i y
Fig. 1. Rende display o he p ima y audi o y co ex es ing-s a e seed map
gene a ed in ou s udy (A), ask-based audi o y ne wo k iden i ied by Heckne
e al. (2021), me a-analysis (B) and hei o e lap (C). All he maps a e
h esholded a clus e -le el p <0.05, amily-wise e o -co ec ed (FWE) o
mul iple compa isons, wi h a clus e - o ming h eshold a p <0.001. The map
o he Heckne e al. (2021) me a-analysis was publicly a ailable ia he ANIMA
da abase (h ps://anima.inm7.de).
Fig. 2. Resul s om he unc ional connec i i y MRI analysis. Rep esen a i e iews o he unc ional connec i i y map gene a ed om a egion-o -in e es placed a
he in e io colliculus a e shown in he op images. Bo om images illus a e he egions showing a signi ican posi i e associa ion be ween school-indoo exposu e o
oad a ic noise (LAeq, in dB) and unc ional connec i i y. T deno es s a is ic ans o med o Pea son’s .
Table 3
Co ela ions be ween unc ional connec i i y and school-indoo oad a ic
noise.
Clus e -le el Peak-le el
Voxels P
FWE-
co
x y z p
In e io Colliculus Seed Map
Righ Thalamus 145 0.017 14 -32 8 3.3 5e-4
Le Thalamus 113 0.026 -14 -28 6 3.2 9e-4
Medial Genicula e Body Seed Map
Righ In e io Midb ain Tec um 149 0.031 8 -38 -22 4.0 5e-5
Le In e io Midb ain Tec um “ “ -6 -38 -20 3.8 8e-5
P ima y audi o y co ex Seed Map
a
In e io Colliculus 63 0.65 2 -34 -8 2.7 0.004
x y z, coo dina es gi en in Mon eal Neu ological Ins i u e (MNI) space. S a is-
ics a co ec ed h eshold P
FWE
<0.05 using SPM Small olume co ec ion.
a
High h eshold o p <0.05 no sa is ying he SPM small olume co ec ion.
G. Ma ínez-Vila ella e al.
En i onmen al Resea ch 226 (2023) 115574
6
in he cen al audi o y pa hway in p ima y school child en. School-
indoo noise was signi ican ly associa ed wi h s onge connec i i y
be ween he in e io colliculus and a bila e al halamic egion adjacen
o he medial genicula e body, and wi h s onge connec i i y be ween
he medial genicula e body and a bila e al b ains em egion adjacen o
he in e io colliculus. Such a connec i i y s eng hening e ec did no
ex end o he co ical le el o he audi o y pa hway (Heschl’s gy us).
Ra he , i a all, he di ec ion o such associa ion showed an opposi e
(weakening) endency.
Despi e he di e en noise exposu e assessmen , which p e en s ull
compa ison, he absence o signi ican indings in dis an b ain a eas
would be in line wi h he epo ed lack o any e ec o esiden ial
exposu e o oad a ic noise on co ical unc ional connec i i y in he
comp ehensi e imaging assessmen by P´
e ez-C espo e al. (2022) also in
a schoolchild en coho . The e o e, he da a could po en ially indica e
ha he epe cussions o exposu e o oad a ic noise migh be sub le
Fig. 3. Rep esen a i e iews o he unc ional connec i i y map gene a ed om a egion-o -in e es placed a he medial genicula e body o he halamus a e shown
in he op images. Bo om images illus a e he egions showing a signi ican posi i e associa ion be ween school-indoo exposu e o oad a ic noise (LAeq, in dB)
and unc ional connec i i y. T deno es s a is ic ans o med o Pea son’s .
Fig. 4. Rep esen a i e iews o he unc ional connec i i y map gene a ed om a egion-o -in e es placed a he p ima y audi o y co ex ( op), and he egion
showing a nega i e, albei no signi ican , associa ion be ween school-indoo exposu e o oad a ic noise (LAeq, in dB) and unc ional connec i i y (bo om). T
deno es s a is ic ans o med o Pea son’s .
G. Ma ínez-Vila ella e al.
En i onmen al Resea ch 226 (2023) 115574
7
and sys em-speci ic, wi h signi ican associa ions limi ed wi hin he
subco ical po ion o he cen al audi o y pa hway. Rema kably, al-
e a ions in he subco ical s uc u es o he audi o y pa hway due o
ch onic noise exposu e ha e also been epo ed in oden s (Chang and
Me zenich, 2003; Lau e al., 2015a, 2015b).
We obse ed a posi i e associa ion be ween exposu e o noise and
he s eng h o unc ional connec i i y. In he con ex o de elopmen ,
such a di ec ion o indings can be in e p e ed as exp essing highe
wi hin-ne wo k in eg a ion (Cao e al., 2017; Oldham and Fo ni o,
2019; Pujol e al., 2016). Excessi e noise exposu e is belie ed o place
ex a senso y demands on child en (Simon e al., 2022), and p e ious
s udies ha e demons a ed ha backg ound noise in school en i on-
men s may indeed inc ease, o ins ance, lis ening e o (Peelle, 2018;
P odi and Visen in, 2015). Conside ing ha he ma u a ion o he
audi o y pa hway is no ye comple e in school-age child en, and he
ele a ed plas ici y po en ial o his pa hway (Lau e al., 2015a), a highe
senso y demand may plausibly in luence he de elopmen al shaping o
he pa hway (Simon e al., 2022). Ou hypo hesis is ha highe noise
exposu e, as a o m o so bu sus ained biological s ess, would accel-
e a e he ma u a ion o he cen al audi o y pa hway in he o m o
ea lie unc ional coupling be ween i s basic le els.
Such accele a ion o ma u a ion o s em elemen s in he audi o y
pa hway, howe e , could in e e e wi h he de elopmen al p og ess o
mo e dis al le els ha ma u e la e , leading o a as e , bu ul ima ely
less comple e, audi o y sys em de elopmen (Tooley e al., 2021). In his
ega d, i is impo an o indica e ha p e ious mammalian s udies ha e
demons a ed ha en i onmen al noise may delay he o ganiza ional
ma u a ion o he audi o y co ex (Chang and Me zenich, 2003). In ac ,
in ou s udy, we ound no e idence o a s eng hening e ec o en i-
onmen al noise on he connec i i y o he p ima y audi o y co ex.
Mo eo e , as emphasized abo e, he co ela ion o noise speci ically
wi h he connec i i y be ween he p ima y audi o y co ex and he
in e io colliculus showed he opposi e di ec ion, which could po en-
ially indica e a lowe ma u a ion, al hough his associa ion was no
signi ican . In e es ingly, he descending co ical p ojec ion o he
audi o y pa hway bypasses he medial genicula e body on i s way o he
in e io colliculus (Ja ad e al., 2014; Palme and Rees, 2010). Fu he
esea ch is wa an ed o es ablish whe he p olonged noise exposu e
could ul ima ely in e e e wi h he ma u a ion o he highes -o de
p ocesses in he audi o y sys em and whe he his could a ec a en-
ion o lea ning, as obse ed in epidemiological s udies (Cla k e al.,
2020; Fo as e e al., 2022).
As o he speci ici y o he ana omical esul s o he colliculus, noise
was associa ed wi h highe connec i i y be ween he egion o in e es
(in e io colliculus) and a egion adjacen o he medial genicula e body
o he halamus. Bo h he in e io colliculus and he medial genicula e
body a e key audi o y pa hway nodes. Howe e , i was pe haps some-
wha su p ising ha he implica ed egion included a pa o he pul-
ina , which is he pos e io nuclea complex in he halamus mos
equen ly associa ed wi h p ocessing o isual in o ma ion (Ku zawski
e al., 2022; Pu usho haman e al., 2012; Zhou e al., 2016). None he-
less, p e ious s udies in humans and p ima es ha e demons a ed ha
he pul ina has a key ole in he p ocessing, egula ion and in eg a ion
o mul isenso y in o ma ion, including audi o y signals (F oesel e al.,
2021; Chou e al., 2020). The ole o he pul ina may be pa icula ly
ele an in ambiguous (e.g., noisy) en i onmen s, whe e senso y
pe cep ion elies on he combina ion o senso y in o ma ion om
a ious sou ces (F oesel e al., 2021).
One o he common limi a ions when using MRI in child en and
especially in unc ional MRI, is he po en ial impac o head mo emen s
on he quali y o he image. We conside ed his issue ca e ully and
adop ed se e al means o igo ously con ol he e ec s o mo ion, as
indica ed in he me hods. Also, a highe MRI signal may be ob ained
using a highe magne ic ield (i.e., 3-T magne s o e en ul a-high ields
a 7 T). Ano he limi a ion is he use o a 1.5-T magne ins ead o 3 T
op ion. The 3 T op ion was a ailable, howe e , he FP7-ERC E hics
Re iew Commi ee sugges ed o limi magne ic ield s eng h in chil-
d en. Rela ed o he la e , ano he limi a ion o he s udy is he a he
low spa ial esolu ion o he MRI images and he smoo hing applied in
he p ep ocessing analysis (8 mm FWHM), specially o iden i ying small
s uc u es as, o example, he medial genicula e body. A g ea e eso-
lu ion could ha e imp o ed he p ecision and s eng h o he esul s.
Finally, some exposu e misclassi ica ion in noise le els may be p esen
due o he shi o class ooms be ween he 2 academic yea s co e ed by
his s udy o he posi ion o some class ooms owa ds he s ee . As his
e o may ac in bo h di ec ions, we canno exclude non-di e en ial
misclassi ica ion, which could ha e biased ou esul s owa ds he
null. The main s eng hs o he s udy include he la ge sample size o a
neu oimage s udy and he de ailed exposu e assessmen o oad a ic
noise, ca ied ou in he class oom, whe e child en spen mos o he
ime and concen a ion occu s. Mo eo e , he exposu e assessmen was
ep esen a i e o long- e m exposu e du ing he s udy pe iod, as
obse ed by he high in aclass co ela ion be ween he 2-day mea-
su emen campaigns as epo ed in he me hods. We also expec mea-
su emen s aken be o e lessons s a ed o be ep esen a i e o he daily
exposu e o oad a ic noise, gi en ha he oad a ic noise le els
measu ed ou side he school be o e lessons s a ed we e highly co e-
la ed wi h he annual a e age noise le els o he day ime (Spea man’s
ank =0.86) es ima ed a he same posi ion om Ba celona’s S a egic
Noise Map o yea 2012 (Eu opean Commission Di ec i e, 2002).
In conclusion, ou esul s ha e e ealed ha long- e m exposu e o
oad a ic noise inside schools was associa ed wi h s onge unc ional
connec i i y in he subco ical elays o he audi o y pa hway in p ima y
school child en. This inding may sugges ha p olonged noise exposu e
o oad a ic noise in de eloping indi iduals may accele a e ma u a-
ion o basic elemen s o he cen al audi o y sys em, which could ul i-
ma ely in e e e wi h he de eloping po en ial in he whole audi o y
sys em.
Au ho s indi idual con ibu ion
Ge a d Ma ínez-Vila ella: da a cu a ion, o mal analysis, me hod-
ology, w i ing – o iginal d a . Jesus Pujol: concep ualiza ion, o mal
analysis, me hodology, supe ision, w i ing – e iew & edi ing. Lau a
Blanco-Hinojo: o mal analysis, me hodology, w i ing – e iew & edi -
ing. Joan Deus: supe ision, w i ing – e iew & edi ing. Ioa Ri as:
me hodology, w i ing – e iew & edi ing. Cecilia Pe sa en o: me hod-
ology, w i ing – e iew & edi ing. Jo di Sunye : concep ualiza ion,
me hodology, unding acquisi ion, supe ision, w i ing – e iew &
edi ing. Ma ia Fo as e : concep ualiza ion, me hodology, da a cu a ion,
unding acquisi ion, supe ision, w i ing – e iew & edi ing.
Funding
This esea ch ecei ed unding om he ollowing sou ces: Eu opean
Resea ch Council (ERC) G an Ag eemen No 268479 - BREATHE p oj-
ec (JS). The Eu opean Union’s Ho izon 2020 esea ch and inno a ion
p og am unde g an ag eemen No 874724 -Equal-li e (MF). Equal-li e
is pa o he Eu opean Human Exposome Ne wo k. The Bea iu de Pin´
os
P og amme and he Minis y o Resea ch and Uni e si ies o he Go -
e nmen o Ca alonia (2017 BP 00173, MF). The Eu opean Union’s
Ho izon 2020 esea ch and inno a ion p og amme unde he Ma ie
Sklodowska-Cu ie g an ag eemen No 886121 (IR). Eu opean Resea ch
Council G an ag eemen numbe 785994 (H2020) – Ai NB (JS). We also
acknowledge suppo om he Spanish Minis y o Science and Inno-
a ion and S a e Resea ch Agency h ough he “Cen o de Excelencia
Se e o Ochoa 2019–2023” P og am (CEX2018-000806-S, h ps://www.
ciencia.gob.es/si e-web/en/O ganismos-y-Cen os/Cen os-y-Uni
dades-de-Excelencia.h ml, and he Gene ali a de Ca alunya h ough he
CERCA P og am (h ps://ce ca.ca /).
G. Ma ínez-Vila ella e al.
En i onmen al Resea ch 226 (2023) 115574
8
E hics
All pa en s o u o s signed he in o med consen o m app o ed by
he Resea ch E hical Commi ee (No. 2010/41221/I) o he IMIM-Pa c
de Salu MAR, Ba celona, Spain and he FP7-ERC-2010-AdG E hics Re-
iew Commi ee (268479–22022011).
Decla a ion o compe ing in e es
The au ho s decla e ha hey ha e no known compe ing inancial
in e es s o pe sonal ela ionships ha could ha e appea ed o in luence
he wo k epo ed in his pape .
Da a a ailabili y
The au ho s do no ha e pe mission o sha e da a.
Acknowledgemen s
This s udy would no ha e been possible wi hou he pa icipa ion o
he schools, amilies and child en o he BREATHE p ojec . This esea ch
has ecei ed unding om he ollowing sou ces: Eu opean Resea ch
Council (ERC) G an Ag eemen No 268479 - BREATHE p ojec (JS). The
Eu opean Union’s Ho izon 2020 esea ch and inno a ion p og am
unde g an ag eemen No 874724 -Equal-li e (MF). Equal-li e is pa o
he Eu opean Human Exposome Ne wo k. The Bea iu de Pin´
os P o-
g amme and he Minis y o Resea ch and Uni e si ies o he Go e n-
men o Ca alonia (2017 BP 00173, MF). The Eu opean Union’s Ho izon
2020 esea ch and inno a ion p og amme unde he Ma ie Sklodowska-
Cu ie g an ag eemen No 886121 (IR). Eu opean Resea ch Council
G an ag eemen numbe 785994 (H2020) – Ai NB (JS). We also
acknowledge suppo om he Spanish Minis y o Science and Inno-
a ion and S a e Resea ch Agency h ough he “Cen o de Excelencia
Se e o Ochoa 2019–2023” P og am (CEX2018-000806-S, h ps://www.
ciencia.gob.es/si e-web/en/O ganismos-y-Cen os/Cen os-y-Uni
dades-de-Excelencia.h ml, and he Gene ali a de Ca alunya h ough he
CERCA P og am (h ps://ce ca.ca /).
Re e ences
Bandyopadhyay, e al., 2010. Dicho omy o unc ional o ganiza ion in he mouse
audi o y co ex. Na . Neu osci. 13, 361–368.
Basne , M., McGui e, S., 2018. WHO en i onmen al noise guidelines o he Eu opean
egion: a sys ema ic e iew on en i onmen al noise and e ec s on sleep. In . J.
En i on. Res. Publ. Heal h 15 (3), 519.
Basne , M., e al., 2014. Audi o y and non-audi o y e ec s o noise on heal h. Lance 383
(9925), 1325–1332.
Be glund, B., Lind all, T., Schwela, D.H., Wo ld Heal h O ganiza ion, 1999.
Occupa ional and En i onmen al Heal h Team. Guidelines o Communi y Noise.
Wo ld Heal h O ganiza ion.
Be lo , E., e al., 2020. A 7 Tesla MRI in es iga ion o human inni us pe cep in co ical
and subco ical audi o y a eas. Neu oimage Clin 25, 102166.
Boyen, K., de Kleine, E., an Dijk, P., Lange s, D.R., 2014. Tinni us- ela ed dissocia ion
be ween co ical and subco ical neu al ac i i y in humans wi h mild o mode a e
senso ineu al hea ing loss. Hea . Res. 312, 48–59. h ps://doi.o g/10.1016/j.
hea es.2014.03.001. Epub 2014 Ma 12. PMID: 24631963.
B e , M., e al., 2003. Region o in e es analysis using an SPM oolbox. Neu oimage 16
(Supp l):abs ac 497.
Cao, M., e al., 2017. De elopmen al connec omics om in ancy h ough ea ly
childhood. T ends Neu osci. 40 (8), 494–506.
Chang, E.F., Me zenich, M.M., 2003. En i onmen al noise e a ds audi o y co ical
de elopmen . Science 300 (5618), 498–502.
Chou, X.L., e al., 2020. Con ex ual and c oss-modali y modula ion o audi o y co ical
p ocessing h ough pul ina media ed supp ession. Eli e 9, e54157.
Cla k, C., Pauno ic, K., 2018. WHO en i onmen al noise guidelines o he Eu opean
egion: a sys ema ic e iew on en i onmen al noise and quali y o li e, wellbeing and
men al heal h. In . J. En i on. Res. Publ. Heal h 15 (11), 2400.
Cla k, C., e al., 2020. E idence o en i onmen al noise e ec s on heal h o he Uni ed
Kingdom policy con ex : a sys ema ic e iew o he e ec s o en i onmen al noise on
men al heal h, wellbeing, quali y o li e, cance , demen ia, bi h, ep oduc i e
ou comes, and cogni ion. In . J. En i on. Res. Publ. Heal h 17 (2), 393.
Cole-Hun e , T., e al., 2022. Long- e m exposu e o oad a ic noise and all-cause and
cause-speci ic mo ali y: a Danish Nu se Coho s udy. Sci. To al En i on. 820,
153057 h ps://doi.o g/10.1016/j.sci o en .2022.153057.
De Ma ino, F., e al., 2013. Spa ial o ganiza ion o equency p e e ence and selec i i y
in he human in e io colliculus. Na . Commun. 4, 1386.
Díaz, B., e al., 2012. Dys unc ion o he audi o y halamus in de elopmen al dyslexia.
P oc. Na l. Acad. Sci. U. S. A. 109 (34), 13841–13846.
Egge mon , J.J., 2017. E ec s o long- e m non- auma ic noise exposu e on he adul
cen al audi o y sys em. Hea ing p oblems wi hou hea ing loss. Hea . Res. 352,
12–22.
E ickson, L.C., Newman, R.S., 2017. In luences o backg ound noise on in an s and
child en. Cu . Di . Psychol. Sci. 26 (5), 451–457.
Eu opean En i onmen al Agency, 2020. En i onmen al Noise in Eu ope – 2020.
Luxembo g.
Fi zhugh, M.C., e al., 2019. Func ional connec i i y o heschl’s gy us associa ed wi h
age- ela ed hea ing loss: a es ing-s a e MRI s udy. F on . Psychol. 10, 2485.
Fo as e , M., e al., 2022. Exposu e o oad a ic noise and cogni i e de elopmen in
schoolchild en in Ba celona, Spain: a popula ion-based. coho s udy. PLoS Med. 19
(6), e1004001.
F oesel, M., e al., 2021. A mul isenso y pe spec i e on o p ima e pul ina unc ions.
Neu osci. Biobeha . Re . 125, 231–243.
Guski, R., e al., 2017. WHO en i onmen al noise guidelines o he Eu opean egion: a
sys ema ic e iew on en i onmen al noise and annoyance. In . J. En i on. Res. Publ.
Heal h 14 (12), 1539.
Heckne , M.K., Cieslik, E.C., Küppe s, V., Fox, P.T., Eickho , S.B., Langne , R., 2021.
Delinea ing isual, audi o y and mo o egions in he human b ain wi h unc ional
neu oimaging: a B ainMap-based me a-analy ic syn hesis. PMID: 33976234; PMCID:
PMC8113600 Sci. Rep. 11 (1), 9942. h ps://doi.o g/10.1038/s41598-021-88773-9.
Ja ad, F., e al., 2014. Audi o y ac s iden i ied wi h combined MRI and di usion
ac og aphy. Neu oimage 84, 562–574.
Kelle , S.S., e al., 2012. Volume es ima ion o he halamus using eesu e and
s e eology: consis ency be ween me hods. Neu oin o ma ics 10 (4), 341–350.
Kempen, E.V., e al., 2018. WHO en i onmen al noise guidelines o he Eu opean
egion: a sys ema ic e iew on en i onmen al noise and ca dio ascula and
me abolic e ec s: a summa y. PMID: 29470452; PMCID: PMC5858448 In . J.
En i on. Res. Publ. Heal h 15 (2), 379. h ps://doi.o g/10.3390/ije ph15020379.
Ku zawski, J.W., e al., 2022. Sho - e m plas ici y in he human isual halamus. Eli e
11, e74565.
Lau, C., e al., 2015a. Long- e m, passi e exposu e o non- auma ic acous ic noise
induces neu al adap a ion in he adul a medial genicula e body and audi o y
co ex. Neu oimage 107, 1–9.
Lau, C., e al., 2015b. Ch onic exposu e o b oadband noise a mode a e sound p essu e
le els spa ially shi s one-e oked esponses in he a audi o y midb ain.
Neu oimage 122, 44–51.
Ma heson, M., e al., 2010. The e ec s o oad a ic and ai c a noise exposu e on
child en’s episodic memo y: he RANCH p ojec . Noise Heal h 12 (49), 244–254.
Mihai, P.G., e al., 2019. Modula ion o ono opic en al medial genicula e body is
beha io ally ele an o speech ecogni ion. Eli e 8, e44837.
Moe el, M., e al., 2015. P ocessing o equency and loca ion in human subco ical
audi o y s uc u es. Sci. Rep. 5, 17048.
Oh s om, E., e al., 2006. E ec s o oad a ic noise and he bene i o access o
quie ness. J. Sound Vib. 295, 40–59.
Oldham, S., Fo ni o, A., 2019. The de elopmen o b ain ne wo k hubs. De Cogn
Neu osci 36, 100607.
Palme , A., Rees, A., 2010. The Ox o d Handbook o Audi o y Science: he Audi o y
B ain. s uc u al and unc ional o ganiza ion o he audi o y b ain. Ox o d
Uni e si y P ess, Sec ion I, pp. 9–64.
Peelle, J.E., 2018. Lis ening e o : how he cogni i e consequences o acous ic challenge
a e e lec ed in b ain and beha io . Ea Hea . 39 (2), 204–214.
P´
e ez-C espo, L., e al., 2022. Exposu e o a ic- ela ed ai pollu ion and noise du ing
p egnancy and childhood, and unc ional b ain connec i i y in p eadolescen s.
En i on. In . 164, 107275.
Plack, C.J., e al., 2014. Pe cep ual consequences o “hidden” hea ing loss. T ends in
Hea ing 18, 2331216514550621. h ps://doi.o g/10.1177/2331216514550621.
Powe , J.D., e al., 2014. Me hods o de ec , cha ac e ize, and emo e mo ion a i ac in
es ing s a e MRI. Neu oimage 84, 320–341.
P odi, N., Visen in, C., 2015. Lis ening e iciency du ing lessons unde a ious ypes o
noise. J. Acous . Soc. Am. 138 (4), 2438–2448.
Pujol, J., e al., 2014. Does mo ion- ela ed b ain unc ional connec i i y e lec bo h
a i ac s and genuine neu al ac i i y? Neu oimage 101, 87–95.
Pujol, J., e al., 2016. T a ic pollu ion exposu e is associa ed wi h al e ed b ain
connec i i y in school child en. Neu oimage 129, 175–184.
Pu usho haman, G., e al., 2012. Ga ing and con ol o p ima y isual co ex by pul ina .
Na . Neu osci. 15, 905–912.
Ress, D., Chand aseka an, B., 2013. Tono opic o ganiza ion in he dep h o human
in e io colliculus. F on . Hum. Neu osci. 7, 586.
Schelinski, S., e al., 2022. Al e ed p ocessing o communica ion signals in he
subco ical audi o y senso y pa hway in au ism. Hum. B ain Mapp. 43 (6),
1955–1972.
Sch eine , C.E., Polley, D.B., 2014. Audi o y map plas ici y: di e si y in causes and
consequences. Cu . Opin. Neu obiol. 24 (1), 143–156.
Simon, K.R., e al., 2022. En i onmen al noise, b ain s uc u e, and language
de elopmen in child en. B ain Lang. 229, 105112.
Si ek, K.R., e al., 2019. Mapping he human subco ical audi o y sys em using his ology,
pos mo em MRI and in i o MRI a 7T. Eli e 8, e48932.
Skoe, E., e al., 2015. S abili y and plas ici y o audi o y b ains em unc ion ac oss he
li espan. Ce eb . Co ex 25 (6), 1415–1426. h ps://doi.o g/10.1093/ce co /
bh 311.
G. Ma ínez-Vila ella e al.
En i onmen al Resea ch 226 (2023) 115574
9
Smi h, S.M., Fox, P.T., Mille , K.L., Glahn, D.C., Fox, P.M., Mackay, C.E., Filippini, N.,
Wa kins, K.E., To o, R., Lai d, A.R., Beckmann, C.F., 2009. Co espondence o he
b ain’s unc ional a chi ec u e du ing ac i a ion and es . P oc. Na l. Acad. Sci. U. S.
A. 106 (31), 13040–13045. h ps://doi.o g/10.1073/pnas.0905267106. Epub 2009
Jul 20. PMID: 19620724; PMCID: PMC2722273.
Smi h, M.G., e al., 2022. En i onmen al noise and e ec s on sleep: an upda e o he
WHO sys ema ic e iew and me a-analysis. En i on. Heal h Pe spec . 130 (7),
076001.
S ans eld, S., Cla k, C., 2015. Heal h e ec s o noise exposu e in child en. Cu En i on
Heal h Rep 2 (2), 171–178.
S ans eld, S.A., e al., 2005. RANCH s udy eam. Ai c a and oad a ic noise and
child en’s cogni ion and heal h: a c oss-na ional s udy. Lance 365 (9475),
1942–1949.
S ebbings, K.A., e al., 2014. The audi o y co icocollicula sys em: molecula and
ci cui -le el conside a ions. Hea . Res. 314, 51–59.
Sunye , J., e al., 2015. Associa ion be ween a ic- ela ed ai pollu ion in schools and
cogni i e de elopmen in p ima y school child en: a p ospec i e coho s udy. PLoS
Med. 12 (3), e1001792.
Tooley, U.A., e al., 2021. En i onmen al in luences on he pace o b ain de elopmen .
Na . Re . Neu osci. 22 (6), 372–384.
an Kamp, I., Da ies, H., 2013. Noise and heal h in ulne able g oups: a e iew. Noise
Heal h 15 (64), 153–159.
Wine , J.A., 2005. Decoding he audi o y co ico ugal sys ems. Hea . Res. 207 (1–2), 1–9.
Wo ld Heal h O ganiza ion, 2018. En i onmen al Noise Guidelines o he Eu opean
Region (Copenhagen).
Wunde lich, J.L., e al., 2006. Ma u a ion o CAEP in in an s and child en: a e iew.
Hea . Res. 212 (1–2), 212–223. h ps://doi.o g/10.1016/j.hea es.2005.11.008.
Zhou, H., e al., 2016. Pul ina -co ex in e ac ions in ision and a en ion. Neu on 89,
209–220.
G. Ma ínez-Vila ella e al.
