Human Brain Ages With Hierarchy-Selective Attenuation of Prediction Errors

This is a sel -a chi ed e sion o an o iginal a icle. This e sion may di e om he o iginal in pagina ion and ypog aphic de ails. Au ho (s): Ti le: Yea : Ve sion: Copy igh : Righ s: Righ s u l: Please ci e he o iginal e sion: CC BY-NC 4.0 h ps://c ea i ecommons.o g/licenses/by-nc/4.0/ Human B ain Ages Wi h Hie a chy-Selec i e A enua ion o P edic ion E o s © The Au ho (s) 2020. Published by Ox o d Uni e si y P ess. All igh s ese ed. Published e sion Hsu, Yi-Fang; Waszak, Flo ian; S ömme , Juho; Hämäläinen, Ja mo A. Hsu, Y.-F., Waszak, F., S ömme , J., & Hämäläinen, J. A. (2021). Human B ain Ages Wi h Hie a chy-Selec i e A enua ion o P edic ion E o s. Ce eb al Co ex, 31(4), 2156-2168. h ps://doi.o g/10.1093/ce co /bhaa352 2021 © The Au ho (s) 2020. Published by Ox o d Uni e si y P ess. All igh s ese ed. Fo pe missions, please e-mail: [email p o ec ed] This is an Open Access a icle dis ibu ed unde he e ms o he C ea i e Commons A ibu ion Non-Comme cial License (h p://c ea i ecommons.o g/ licenses/by-nc/4.0/), which pe mi s non-comme cial e-use, dis ibu ion, and ep oduc ion in any medium, p o ided he o iginal wo k is p ope ly ci ed. Fo comme cial e-use, please con ac [email p o ec ed] Ce eb al Co ex, 2020;00: 1–13 doi: 10.1093/ce co /bhaa352 O iginal A icle ORIGINAL ARTICLE Human B ain Ages Wi h Hie a chy-Selec i e A enua ion o P edic ion E o s Yi-Fang Hsu 1,2, Flo ian Waszak3,4, Juho S ömme 5and Ja mo A. Hämäläinen5 1Depa men o Educa ional Psychology and Counselling, Na ional Taiwan No mal Uni e si y, 106308 Taipei, Taiwan, 2Ins i u e o Resea ch Excellence in Lea ning Sciences, Na ional Taiwan No mal Uni e si y, 106308 Taipei, Taiwan, 3Cen e Na ional de la Reche che Scien i ique (CNRS), In eg a i e Neu oscience and Cogni ion Cen e (INCC), Uni é Mix e de Reche che 8002, 75006 Pa is, F ance, 4Uni e si é de Pa is, 75006 Pa is, F ance and 5Jy äskylä Cen e o In e disciplina y B ain Resea ch, Depa men o Psychology, Uni e si y o Jy äskylä, 40014 Jy äskylä, Finland Add ess co espondence o Yi-Fang Hsu, No.162, Sec. 1, Heping E. Rd, Da-an Dis ic , 106308 Taipei, Taiwan. Email: yi- ang.hsu@can ab.ne Abs ac F om he pe spec i e o p edic i e coding, ou b ain embodies a hie a chical gene a i e model o ealize pe cep ion, which p oac i ely p edic s he s a is ical s uc u e o senso y inpu s. How a e hese p edic i e p ocesses modi ied as we age? Recen esea ch sugges ed ha aging leads o dec eased weigh ing o senso y inpu s and inc eased eliance on p edic ions. He e we in es iga ed whe he his age- ela ed shi om senso ium o p edic ions occu s a all le els o hie a chical message passing. We eco ded he elec oencephalog aphy esponses wi h an audi o y local–global pa adigm in a coho o 108 heal hy pa icipan s om 3 g oups: senio s, adul s, and adolescen s. The de ec ion o local de iancy seems la gely p ese ed in olde indi iduals a ea lie la ency (including he misma ch nega i i y ollowed by he P3a bu no he eo ien ing nega i i y). In con as , he de ec ion o global de iancy is clea ly comp omised in olde indi iduals, as hey showed wo se ask pe o mance and a enua ed P3b. Ou indings demons a e ha olde b ains show li le decline in senso y (i.e., i s -o de ) p edic ion e o s bu signi ican diminu ion in con ex ual (i.e., second-o de ) p edic ion e o s. Age- ela ed de icien main enance o audi o y in o ma ion in wo king memo y migh a ec whe he and how lowe -le el p edic ion e o s p opaga e o he highe le el. Key wo ds: aging, audi o y pe cep ion, elec oencephalog aphy (EEG), p edic ion e o s, p edic i e coding In oduc ion P edic i e p ocessing is undamen al o audi ion.This is because he audi o y sys em essen ially deals wi h sequen ial inpu s, which con ains ele an in o ma ion in he imminen u u e. The p edic i e coding model o pe cep ion u he delinea es ha he pe cep ual sys em uses a hie a chical gene a i e model o p oac i ely ep esen he s a is ical s uc u e o senso y inpu s (F is on 2005,2009;Egne e al. 2010;Feldman and F is on 2010; o e iews see Cla k 2013;Heilb on and Chai 2018). Speci ically, pe cep ion in ol es he ma ching o a cascade o op-down p edic ions wi h senso y inpu s, which aims o minimize p edic ion e o s (o he inconsis ency be ween an icipa ed and incoming signals) in he sys em. How a e hese p edic i e p ocesses modi ied as we age? No mal aging ypically deg ades p ecision o pe iphe al and cen al p ocessing, which leads o dec eased weigh ing o sen- so y inpu s and inc eased eliance on p edic ions (Wolpe e al. 2016;Chan e al. 2017). Recen neu ocompu a ional esea ch Downloaded om h ps://academic.oup.com/ce co /ad ance-a icle/doi/10.1093/ce co /bhaa352/6014977 by Jy askyla Uni e si y use on 08 Decembe 2020 2Ce eb al Co ex, 2020, Vol. 00, No. 00 quan i ying he synap ic coupling unde lying he misma ch nega i i y (MMN) also ound an age- ela ed a enua ion o lea ning-dependen inc ease in o wa d connec i i y om p ima y audi o y co ex speaking o a educed sensi i i y o ascending a e en s o p edic ion e o s (Mo an e al. 2014) as well as an age- ela ed inc ease o inhibi o y e ec a in e io on al gy us indica ing inc eased i ing a e o he inhibi o y neu ons (Coo ay e al. 2014) o e li espan. I seems ha olde b ains a e less p edisposed o upda ing he p io p obabili y es ima e, leading o a pe cep ion o he en i onmen inc easingly domina ed by op-down in o ma ion. In o he wo ds, age u ns ou b ain in o a s ubbo n p edic ion machine whe e he senso ium is weigh ed less o op imize p edic ions. This is consis en wi h epo s on age- ela ed shi s in neu onal ec ui men om senso y o on al egions (Da is e al. 2008). Howe e ,i is cu en ly unclea whe he his age- ela ed shi om senso ium o p edic ions occu s a all le els o hie a chical message passing, which includes senso y (i.e., i s -o de ) p edic ions and con ex ual (i.e., second-o de ) p edic ions. A well-es ablished audi o y local–global pa adigm (Bekinsch ein e al. 2009) p obing audi o y p edic ion a 2 hie a chical le els o de iancy ound ha he de ec ion o local/global de iancy in ol es dis inc neu onal sys ems (Wacongne e al. 2011; Chennu e al. 2013;El Ka oui e al. 2015). Local de iancy elici ed he MMN ( ega dless o pa icipan s’ ask), which e lec s a p ea en i e, au oma ic, and nonconscious esponse o a i s - o de iola ion o pa icipan s’ expec a ion cons uc ed on he basis o ecen senso y his o y. I o igina ed om a es ic ed ne wo k in ol ing bila e al Heschl’s gy us, supe io empo al gy us, and on al egion a a smalle ex en (Chennu e al. 2016; o e iews see Alho 1995) wi h a sligh delay (Rinne e al. 2000). Global de iancy, on he o he hand, elici ed he P3b (only when pa icipan s we e awa e o he iola ions o global egula i ies), which e lec s a second-o de iola ion o pa icipan s’ expec a ion o a gi en con ex ual ule. I is hough o index conscious access and upda ing in wo king memo y (Donchin and Coles 1988;Polich 2004,2007). I s pu a i e gene a o s in ol e a b ain-scale co ical ne wo k including p e on al, pa ie al, empo al, and cingula e egions (Ta kka e al. 1995;Polich 2004,2007;Pa el and Azzam 2005). Such dissocia ion o he consciousness-independen /-dependen capaci y o hie a chically p edic he local/global s uc u e o he audi o y en i onmen is sha ed by human (Fauge as e al. 2011,2012;King e al. 2013;S auss e al. 2015) and nonhuman p ima es (Uh ig e al. 2014,2016). An indisc imina e age- ela ed shi om senso ium o p e- dic ions should be associa ed wi h educed MMN and P3b, sig- naling educed p edic ion e o s due o dec eased weigh ing o senso y inpu s a bo h senso y and con ex ual le els. Ne e he- less, conclusions a e di icul o d aw om he li e a u e. P e- ious esea ch examining he age- ela ed changes in he MMN yielded equi ocal esul s. While some s udies ound no e idence o age-dependen a enua ion o he MMN (Pekkonen e al. 1993, 1996;Sch oede e al. 1995;Gun e e al. 1996;Kazme ski e al. 1997;Amenedo and Díaz 1998), o he s udies ound senio s o exhibi a smalle MMN (Czigle e al. 1992;Gae a e al. 1998,2001; Alain and Woods 1999;Coope e al. 2006;Schi e al. 2008). The lack o consensus was likely due o a ia ions in how pa ici- pan s’ a en ion was moni o ed, he leng h o he s imulus onse asynch ony (SOA), e c., making i di icul o judge whe he age a enua es he i s -o de p edic ion e o s. On he o he hand, while P3b was commonly epo ed o show age- ela ed changes in i s ampli ude, la ency, and opog aphy (Schi e al. 2008; an Din e en e al. 2018; o e iewsseeF iedman e al. 1997;F iedman 2003), i s measu emen was usually based on he classi ica ion o he audi o y de ian /s anda d s imuli ha i s elici ed he MMN. The e o e, i emains unde e mined o wha ex en he P3b uncon oundedly e lec s he second-o de p edic ion e o s. To es whe he he age- ela ed shi om senso ium o p edic ions is hie a chy selec i e, he e we eco ded he elec oencephalog aphy (EEG) esponses wi h an audi o y local– global pa adigm, which o hogonally manipula ed local (i.e., i s -o de ) and global (i.e., second-o de ) egula i ies (Fig. 1). In a coho o 108 heal hy pa icipan s om 3 g oups: senio s (≥55 yea s old), adul s (19–54 yea s old), and adolescen s (≤18 yea s old), we ound ha olde b ains show li le decline in he MMN signaling senso y (i.e., i s -o de ) p edic ion e o s bu signi ican diminu ion in he P3b signaling con ex ual (i.e., second-o de ) p edic ion e o s, which is ela ed o de icien main enance o audi o y in o ma ion in wo king memo y. Ma e ials and Me hods Pa icipan s A o al o 108 heal hy olun ee s including 36 senio s (age be ween 55 and 82 yea s, mean = 65.31, s anda d de ia ion [SD] = 7.03), 36 adul s (age be ween 19 and 27 yea s, mean= 21.17, SD = 2.01), and 36 adolescen s (age be ween 15 and 18 yea s, mean = 16.97, SD = 0.81) pa icipa ed in he expe imen wi h no his o y o neu ological, neu opsychia ic, o isual/hea ing impai men s as indica ed by sel - epo . Pa icipan s p o ided us wi h in o ma ion abou hei gende , handedness, le el o educa ion, and ma i al s a us. Pa icipan s ga e w i en in o med consen and we e paid o pa icipa ion. The s udy was conduc ed in acco dance wi h he Decla a ion o Helsinki and app o ed by he Resea ch E hics Commi ee a Na ional Taiwan No mal Uni e si y. A powe analysis was conduc ed in G∗Powe 3.1.9.7 (Faul e al. 2007,2009) using a model o 1- way analysis o a iance (ANOVA) wi h 3 g oups, each wi h a sample size o 36. Wi h alpha se a 0.05, he powe o de ec a medium-sized e ec ( = 0.25) was 0.63 and he powe o de ec a la ge-sized e ec ( = 0.40) was 0.96. Pa icipan s unde wen a neu opsychological e alua ion o cogni i e unc ions. Thei wo king memo y was measu ed wi h 3 sub es s in Wechsle Adul In elligence Scale-Fou h Edi ion, including Digi Span, Le e -Numbe Sequencing, and A i hme ic. Thei dep essi e symp oms we e measu ed wi h he Cen e o Epidemiological S udies-Dep ession (CES-D) scale (Radlo 1977;Chien and Cheng 1985). I is a 20-i em sel - epo scale ha asks one o a e how o en o e he pas week he/she expe ienced symp oms associa ed wi h dep ession. Response op ions ange om1 o4 o eachi em(1 a elyo noneo he ime [<1 day], 2 some o li le o he ime [1–2 days], 3 occasionally o a mode a e amoun o ime [3–4 days], 4 mos o all o he ime [5–7 days]). Thei le el o pe cei ed s ess was measu ed wi h he Pe cei ed S ess Scale (PSS) (Cohen e al. 1983;Chu 2005). I is a 14-i em sel - epo scale ha asks abou one’s eelings and hough s du ing he las mon h. Response op ions ange om 0 o 4 o each i em (0 ne e , 1 almos ne e , 2 some imes, 3 ai ly o en, 4 e y o en). All es s we e adminis e ed and sco ed by a licensed counseling psychologis acco ding o s anda d p ocedu es. Demog aphic cha ac e is ics and cogni i e unc ions o he pa icipan s a e summa ized in Table 1. Downloaded om h ps://academic.oup.com/ce co /ad ance-a icle/doi/10.1093/ce co /bhaa352/6014977 by Jy askyla Uni e si y use on 08 Decembe 2020 Age-Rela ed A enua ion o P edic ion E o s Hsu e al. 3 Figu e 1. Schema ic illus a ion o he audi o y local–global pa adigm. (A). On each ial, 5 sinusoidal ones o 50-ms du a ion we e p esen ed wi h a 200 ms SOA. Each ial was ollowed by a ji e ed ITI o 700–1000 ms. (B). In each block, 2 di e en ypes o one quin e s we e p esen ed, he i s using he 5- ime epe i ion o he same one (i.e., XXXXX) and he second wi h a change in he las one (i.e., XXXXY). Hal o he blocks con ained equen epe i ion and in equen change in he las one (uppe : 80% XXXXX and 20% XXXXY) and hal con ained in equen epe i ion and equen change in he las one (lowe : 20% XXXXX and 80% XXXXY). The las one in each one quin e (i.e., p obe) is ma ked in g ay as i is he one o in e es . Each block s a ed wi h a leas 20 equen one quin e s o es ablish he global egula i y be o e he i s in equen one quin e appea ed. Pa icipan s we e ins uc ed o 1) iden i y in equen ials and 2) coun he numbe o in equen ials in each block. S imuli A o al o 14 sinusoidal ones we e gene a ed using Sound Fo ge P o 10.0 (Sony C ea i e So wa e Inc.). The du a ion o each one was 50 ms (including 5 ms ise/ all imes). The equency o each one was wi hin he ange o 261.626–987.767 Hz, ma ching he absolu e equency o a se ies o 14 na u al keys on a mode n piano (i.e., C4 D4 E4 F4 G4 A4 B4 C5 D5 E5 F5 G5 A5 B5) (Table 2). Unlike p e ious esea ch using 2 ones in he audi o y local– global pa adigm (Bekinsch ein e al. 2009;Wacongne e al. 2011; Chennu e al. 2013;El Ka oui e al. 2015) (i.e., blocks o equen epe i ion and in equen change: 80% AAAAA +20% AAAAB o 80% BBBBB +20% BBBBA; blocks o in equen epe i ion and equen change: 20% AAAAA +80% AAAAB o 20% BBBBB +80% BBBBA), he e we in oduced a ia ion in pi ch using 14 ones. Speci ically, om he pool o 14 ones, 2 di e en ypes o one quin e s we e c ea ed, he i s using he 5- ime epe i ion o he same one (i.e., he XXXXX ype, which could be C4-C4-C4-C4- C4, D4-D4-D4-D4-D4, E4-E4-E4-E4-E4, e c.) and he second wi h a change in he las one (i.e., he XXXXY ype, which could be C4-C4-C4-C4-A5, D4-D4-D4-D4-B4, E4-E4-E4-E4-C5, e c.). The e- a e , o blocks o equen epe i ion and in equen change (Fig. 1Buppe ) 80% o he ials we e andomly sampled om he XXXXX ype and 20% om he XXXXY ype, whe eas o blocks o in equen epe i ion and equen change (i.e., Fig. 1B lowe ) 20% o he ials we e andomly sampled om he XXXXX ype and 80% om he XXXXY ype. Such a ia ion in pi ch no only dec eased s imulus-speci ic e ec s (ensu ing ha neu o- physiological esponses indeed e lec p edic ion e o s pe se) bu also inc eased ask di icul y (which helps e eal indi idual di e ences in ask pe o mance). P ocedu es A o al o 1000 one quin e s we e p esen ed in 8 blocks in andomized o de . Hal o he blocks con ained equen epe i- ion and in equen change in he las one (i.e., Fig. 1Buppe : 80% XXXXX and 20% XXXXY) and hal con ained in equen epe i ion and equen change in he las one (i.e.,Fig. 1Blowe : 20% XXXXX and 80% XXXXY). Bo h block ypes p esen ed a local egula i y whe e he i h one could be iden ical o di e en om p eceding ones (hence he local s anda d and he local de ian ) and a global egula i y whe e one one quin e could be mo e o less common han he o he (hence he global s anda d and he global de ian ) (Fig. 1B). In each block, he numbe o one quin e s a ied be ween 110 and 140, wi h he numbe o equen one quin e s a ied be ween 88 and 112 and he numbe o in equen one quin e s a ied be ween 22 and 28 o main ain he 80:20 equency a io. Each block s a ed wi h a leas 20 equen one quin e s o es ablish he global egula i y be o e he i s in equen one quin e appea ed. A g ay ixa ion c oss agains black backg ound emained on he sc een o he du a ion o each block ( iewed om a dis ance o 120 cm). In each ial, a one quin e was p esen ed wi h a 200 ms SOA and an in ensi y o maximum 82 dB (56– 82 dBA; 65–82 dBC). Each ial was ollowed by a ji e ed in e ial in e al (ITI) o 700–1000 ms. Pa icipan s we e ins uc ed o 1) iden i y in equen ials and 2) coun he numbe o in equen ials in each block. The whole expe imen ook a ound 29 min (i.e., 1000 ials ×1700 ms). E-p ime e sion 2.0 (Psychology So - wa e Tools) was used o s imulus p esen a ion. S imula ion was andomized indi idually o each pa icipan and deli e ed binau ally ia headphones (Sennheise PX200-II). Downloaded om h ps://academic.oup.com/ce co /ad ance-a icle/doi/10.1093/ce co /bhaa352/6014977 by Jy askyla Uni e si y use on 08 Decembe 2020 4Ce eb al Co ex, 2020, Vol. 00, No. 00 Table 1 Demog aphic cha ac e is ics and cogni i e unc ions o he pa icipan s Senio s Adul s Adolescen s Gende Male 10 13 20 Female 26 23 16 Handedness Righ 33 33 34 Le 1 2 2 Ambidex ous 2 1 0 Le el o educa ion P ima y 2 0 0 Seconda y192636 Te ia y 15 10 0 Ma i al s a us Single 3 35 36 Ma ied 27 1 0 Di o ced200 Widowed 4 0 0 Wo king memo y (Digi Span) Min 17 29 24 Max434647 Mean 30.39 36.56 36.64 SD 5.93 4.69 5.54 Wo king memo y (Le e -Numbe Sequencing) Min 13 16 17 Max263029 Mean 19.36 23.86 24.00 SD 3.02 3.36 2.81 Wo king memo y (A i hme ic) Min 9 11 12 Max232223 Mean 15.69 18.42 19.00 SD 4.03 2.64 2.56 Dep essi e symp oms (CES-D) Min 20 23 23 Max406858 Mean 27.92 35.58 34.14 SD 4.87 9.84 8.23 Le el o pe cei ed s ess (PSS) Min 0 17 14 Max354131 Mean 25.72 25.58 25.33 SD 6.21 5.18 4.60 Table 2 F equency (Hz) o each one C4 D4 E4 F4 G4 A4 B4 F equency 261.63 293.67 329.63 349.23 392.00 440.00 493.88 C5 D5 E5 F5 G5 A5 B5 F equency 523.25 587.33 659.26 698.46 783.99 880.00 987.77 Da a Reco ding and Analysis EEG Reco ding and P ep ocessing EEG was eco ded om 62 sin e ed Ag/AgCl elec odes on a Neu oscan quik-cap acco ding o he ex ended 10–20 sys em. The g ound elec ode was placed a AFz and he e e ence elec ode was placed be ween Cz and CPz. Eye mo emen s we e moni o ed by addi ional 4 elec odes placed abo e and below he le eye and a he ou e can hi o bo h eyes, which we e bipo- la ized online o yield e ical and ho izon al elec ooculog am, espec i ely.All signals we e ampli ied and online il e ed a 0.1– 100 Hz wi h he Neu oscan Synamps 2 ampli ie (Compumedics Neu oscan) and sampled a 500 Hz. Epochs ex ended om −900 o 498 ms ela i e o p obe onse , using a −100 o 0 ms p es imulus baseline. Ocula a i ac co - ec ion was conduc ed wi h independen componen analysis in EEGlab (Delo me and Makeig 2004). The da a we e ecom- pu ed o a e age e e ence, high-pass il e ed a 0.5 Hz and low-pass il e ed a 20 Hz. Epochs con aining ol age de ia ions exceeding ±100 μV ela i e o baseline a any o he elec odes we e ejec ed. The ial numbe s a e a i ac ejec ion in each condi ion a e lis ed in Table 3. S a is ical Analysis o E en -Rela ed Po en ial (ERP) Ampli ude Local e ec was de ined as he di e ence be ween all local de ian s and local s anda ds (a e aged ac oss global manip- ula ion). Global e ec was de ined as he di e ence be ween all global de ian s and global s anda ds (a e aged ac oss local manipula ion). G oup di e ence in local and global e ec s was de ined as local as well as global di e ence ERPs (i.e., de ian −s anda d) be ween senio s, adul s, and adolescen s. Clus e -based pe mu a ion s a is ics we e pe o med in BESA S a is ics 2.0 (B ain Elec ic Sou ce Analysis, Ge many) on he ERPs om 0 o 498 ms ela i e o p obe onse . Clus e -based pe mu a ion s a is ics ha e 2 essen ial s eps (Ma is and Oos en- eld 2007). Fi s , he desi ed es (local and global e ec s: pai ed- sample - es be ween de ian and s anda d; g oup e ec : 1-way Downloaded om h ps://academic.oup.com/ce co /ad ance-a icle/doi/10.1093/ce co /bhaa352/6014977 by Jy askyla Uni e si y use on 08 Decembe 2020 Age-Rela ed A enua ion o P edic ion E o s Hsu e al. 5 Table 3 Range, mean, and SD o ial numbe s a e a i ac ejec ion in each condi ion Senio s Adul s Adolescen s Local s anda d Global s anda d Min 190 299 259 Max 420 414 424 Mean 361.56 367.36 375.64 SD 50.95 29.28 30.81 Local de ian Global de ian Min 42 71 63 Max 105 103 106 Mean 91.33 93.00 93.94 SD 12.82 7.98 8.05 Local s anda d Global de ian Min 59 70 64 Max 102 104 104 Mean 92.17 93.72 93.67 SD 9.92 7.55 8.46 Local de ian Global s anda d Min 211 298 235 Max 406 407 412 Mean 363.17 370.39 374.36 SD 42.61 30.14 33.37 ANOVA be ween senio s, adul s, and adolescen s) is un o e all ime poin s and elec odes. Values below a ce ain h eshold (clus e alpha 0.05) a e clus e ed based on empo al adjacency (consecu i e ime poin s) and spa ial adjacency (elec ode dis- ance 4 cm). All - alues/F- alues o he clus e s a e summed o o m he clus e es s a is ic. Second, a pe mu a ion dis i- bu ion o es ima e he clus e es s a is ic is gene a ed wi h he boo s apping me hod,which andomly eassigns he condi- ion/g oup labels and pe o ms he a o emen ioned es ing and clus e ing p ocedu e again (numbe o pe mu a ions 3000).I he obse ed clus e es s a is ic in con as o pe mu a ion dis i- bu ion is <0.05/6 (local and global e ec s in 3 g oups)= 0.008, he obse ed clus e is conside ed o be s a is ically signi ican . S a is ical Analysis o Beha io al Measu es One-way ANOVA (pe o med in SPSS 23) be ween senio s, adul s, and adolescen s was conduc ed o examine g oup di e ence on cogni i e unc ions (including wo king memo y, dep essi e symp oms, and le el o pe cei ed s ess) as well as ask pe o - mance (including iden i ica ion accu acy and coun ing e o s). To u he explo e he ela ion be ween cogni i e unc ions and EEG, we conduc ed a pa ial co ela ion be ween wo king memo y and he size o local and global e ec s, whe e pa ic- ipan s’ sco es on CES-D and PSS we e con olled o o emo e he po en ial in luences o psychological ac o s (i.e., dep essi e symp oms and le el o pe cei ed s ess) on cogni i e unc ions. We also conduc ed a s epwise mul iple linea eg ession o e alua e whe he all sco es on wo king memo y sub es s we e necessa y o p edic he size o local and global e ec s. Resul s Cogni i e Func ions Signi ican g oup di e ence was ound on all bu he las measu e (Digi Span: F2,105 = 15.81, P<0.001; Le e -Numbe Sequencing: F2,105 = 26.63, P<0.001; A i hme ic: F2,105 = 11.29, P<0.001; CES-D: F2,105 = 9.52, P<0.001; PSS: F2,105 = 0.05, P= 0.95). Pos hoc compa ison o he g oup di e ence using Tukey’s Hones Signi ican Di e ence (HSD) es indica ed ha , in wo king memo y sub es s and CES-D (bu no PSS), senio s sco ed signi ican ly lowe han he 2 younge g oups, whe eas he 2 younge g oups did no signi ican ly di e om each o he (Table 4 and Fig. 2). Task Pe o mance Pa icipan s We e Asked o Iden i y In equen T ials Pa icipan s could iden i y which one quin e s we e global de ian s wi h an a e age accu acy o 0.91 ±0.02 s anda d e o (SE) (senio s: 0.78±0.04 SE; adul s: 0.97 ±0.01 SE; ado- lescen s: 0.98 ±0.01 SE). The e was a signi ican g oup di - e ence (F2,105 = 22.93, P<0.001) whe e senio s showed lowe iden i ica ion accu acy han he 2 younge g oups, whe eas he 2 younge g oups did no signi ican ly di e om each o he (Tukey’s HSD es : senio s–adul s: −0.18 ±0.03, P<0.001; senio s–adolescen s: −0.20 ±0.03, P<0.001; adul s–adolescen s: −0.02 ±0.03, P= 0.85). Pa icipan s We e Asked o Coun he Numbe o In equen T ials Pa icipan s’ coun ing e o s we e quan i ied as he absolu e di e ence be ween he ac ual and epo ed numbe o global de ian s. The a e age disc epancy was 6.47 ±0.56 SE (senio s: 8.99 ±1.00 SE; adul s: 5.49 ±0.97 SE; adolescen s: 4.93 ±0.79 SE). The e was a signi ican g oup di e ence (F2,105 = 5.64, P<0.01) whe e senio s showed la ge coun ing e o s han he 2 younge g oups, whe eas he 2 younge g oups did no signi ican ly di e om each o he (Tukey’s HSD es : senio s–adul s: 3.51 ±1.31, P<0.05; senio s–adolescen s: 4.06 ±1.31, P<0.01; adul s–adolescen s: 0.55 ±1.31, P= 0.91). EEG Figu e 3 shows he opog aphical dis ibu ions o local and global e ec s (i.e., de ian −s anda d) in each g oup. O e all, he pa e n was simila ac oss g oups, wi h senio s di e ging mo e om he 2 younge g oups. Local e ec mainly mani es ed as a on ocen al nega i i y a a ound 100–150 ms (i.e., MMN), a on ocen al posi i i y a a ound 200–300 ms (i.e., P3a), and a on ocen al nega i i y a a ound 350–450 ms (i.e., eo ien ing nega i i y [RON]). Global e ec mainly mani es ed as a on ocen al nega i i y a a ound 200 ms and a pa ie al posi i i y a a ound 250–450 ms (i.e., P3b). Downloaded om h ps://academic.oup.com/ce co /ad ance-a icle/doi/10.1093/ce co /bhaa352/6014977 by Jy askyla Uni e si y use on 08 Decembe 2020 6Ce eb al Co ex, 2020, Vol. 00, No. 00 Table 4 Pos hoc compa ison o he g oup e ec using Tukey’s HSD es (mean di e ence ±SE) Senio s−adul s Senio s−adolescen s Adul s−adolescen s Digi Span −6.17 ±1.28, P<0.001 −6.25 ±1.28, P<0.001 −0.08 ±1.28, P=1.00 Le e -Numbe Sequencing −4.50 ±0.72, P<0.001 −4.64 ±0.72, P<0.001 −0.14 ±0.72, P=0.98 A i hme ic −2.72 ±0.74, P≤0.001 −3.31 ±0.74, P<0.001 −0.58 ±0.74, P=0.71 CES-D −7.67 ±1.87, P<0.001 −6.22 ±1.87, P<0.010 1.44 ±1.87, P=0.72 Figu e 2. Raincloud plo s (Allen e al. 2019) o cogni i e unc ions measu ed wi h wo king memo y sub es s, CES-D, and PSS. Signi ican g oup e ec s we e ound in all bu he las measu e (∗∗∗P<0.001). Figu e 4Ashows he g and a e aged ERPs o local and global e ec s on ep esen a i e elec odes (i.e., FCz and Pz) in each g oup. Figu e 4Bshows he 2-D ( ime-by-pa icipan ) iews o he ERPs o illus a e he pu a i e g oup di e ence in local and global e ec s. Fo local e ec (uppe ), he e was a lack o on o- cen al nega i i y a a ound 350–450 ms (i.e., RON) in senio s. Fo global e ec (lowe ), he e was a lack o on ocen al nega i i y a a ound 200 ms and a diminished pa ie al posi i i y a a ound 250–450 ms (i.e., P3b) in senio s. Local and Global E ec s Clus e -based pe mu a ion s a is ics sugges ed ha signi ican local and global e ec s appea ed in all 3 g oups. Viola ion o he local egula i y (Fig. 5Auppe ) modula ed 3 clus e s o ERPs in senio s (clus e 1: 56–498 ms [P<0.0001]; clus e 2: 96–380 ms [P<0.0001]; clus e 3: 374–498 ms [P<0.008]), adul s (clus e 1: 94–498 ms [P<0.0001]; clus e 2: 172–498 ms [P<0.0001]; clus e 3: 68–168 ms [P≤0.001]), and adolescen s (clus e 1: 98– 498 ms [P<0.0001]; clus e 2: 172–498 ms [P<0.0001]; clus e 3: 60–164 ms [P<0.001]). Viola ion o he global egula i y (Fig. 5Alowe ) modula ed 2 clus e s o ERPs in senio s (clus e 1: 150–498 ms [P<0.0001]; clus e 2: 134–498 ms [P<0.0001]), adul s (clus e 1: 102–498 ms [P<0.0001]; clus e 2: 124–498 ms [P<0.0001]), and adolescen s (clus e 1: 96–498 ms [P<0.0001]; clus e 2: 124–498 ms [P<0.0001]). G oup Di e ence in Local and Global E ec s Clus e -based pe mu a ion s a is ics e ealed signi ican g oup di e ence in bo h local and global e ec s. Local e ec s modu- la ed 2 clus e s o ERPs (clus e 1: 14–498 ms [P<0.0001]; clus e 2: 262–422 ms [P<0.008]) (Fig. 5Buppe ). Pos hoc compa isons showed signi ican di e ence be ween senio s and adul s (clus- e 1: 274–498 ms [P<0.001]; clus e 2: 274–412 ms [P<0.008]) as well as be ween senio s and adolescen s (clus e 1: 266–498 ms [P<0.0001]; clus e 2: 262–422 ms [P≤0.001]). The e was no di - e ence be ween he 2 younge g oups. Global e ec s modula ed 1 clus e o ERPs (130–498 ms [P<0.0001]) (Fig. 5Blowe ). Pos hoc compa isons showed signi ican di e ence be ween senio s and adul s (clus e 1: 166–498 ms [P<0.0001]; clus e 2: 176– 498 ms [P<0.001]) as well as be ween senio s and adolescen s (132–498 ms [P<0.0001]). The e was no di e ence be ween he 2 younge g oups. Co ela ion Be ween Cogni i e Func ions and EEG To explo e he ela ion be ween cogni i e unc ions and EEG, we conduc ed a pa ial co ela ion be ween wo king memo y and he size o local and global e ec s, while con olling o pa icipan s’ sco es on CES-D and PSS. Wo king memo y was quan i ied as he sco es on wo king memo y sub es s. The size o local and global e ec s was quan i ied as di e ence ERPs (i.e., de ian −s anda d) on elec odes and ime poin s showing Downloaded om h ps://academic.oup.com/ce co /ad ance-a icle/doi/10.1093/ce co /bhaa352/6014977 by Jy askyla Uni e si y use on 08 Decembe 2020 Age-Rela ed A enua ion o P edic ion E o s Hsu e al. 7 Figu e 3. Topog aphical dis ibu ions o local and global e ec s (i.e., de ian −s anda d) in each g oup. Scalp maps a e plo ed om 50 o 450 ms a e he onse o he p obe (i.e., one o in e es ). Table 5 Pa ial co ela ion able (∗P<0.05 a e Benjamini–Hochbe g p ocedu e) Local e ec F2 o e 358 ±10 ms Local e ec P8 o e 360 ±10 ms Global e ec CP1 o e 460 ±10 ms Digi Span (104) = −0.30∗ (104) = 0.28∗ (104) = 0.40∗ Le e -Numbe Sequencing (104) = −0.26∗ (104) = 0.31∗ (104) = 0.37∗ A i hme ic (104) = −0.20∗ (104) = 0.17 (104) = 0.35∗ he mos signi ican g oup di e ence in clus e -based pe mu- a ion s a is ics (local e ec s: F2 o e 358 ±10 ms and P8 o e 360 ±10 ms; global e ec : CP1 o e 460 ±10 ms). The esul s showed ha wo king memo y was signi ican ly ela ed o he size o local and global e ec s (Table 5 and Fig. 6). Wo se wo k- ing memo y was associa ed wi h smalle RON in local e ec (mani es ing as smalle on ocen al nega i i y and smalle pa ie al posi i i y) and smalle P3b in global e ec . No ably, no co ela ion emained signi ican when we also con olled o pa icipan s’ age in addi ion o hei sco es on CES-D and PSS. A s epwise mul iple linea eg ession was conduc ed o e al- ua e whe he all sco es on wo king memo y sub es s we e nec- essa y o p edic he size o local and global e ec s. Fo local e ec on F2 (i.e., on al nega i i y o he RON), Digi Span sco e en e ed in o he eg ession model a s ep 1 and a signi ican eg ession equa ion was ound (F1,106 = 12.81, P≤0.001, adjus ed R2= 0.10). The eg ession equa ion was: p edic ed size o local e ec = −0.07 ×Digi Span sco e +1.81. Fo local e ec on P8 (i.e., pa ie al posi i i y o he RON), Le e -Numbe Sequencing sco e en e ed in o he eg ession model a s ep 1 and a signi ican eg ession equa ion was ound (F1,106 = 12.03, P≤0.001, adjus ed R2= 0.09). The eg ession equa ion was: p edic ed size o local e ec = 0.09 ×Le e -Numbe Sequencing sco e−1.48. Fo global e ec on CP1 (i.e., P3b), Digi Span sco e en e ed in o he eg es- sion model a s ep 1 and a signi ican eg ession equa ion was ound (F1,106 = 21.43, P<0.001, adjus ed R2= 0.16). The eg ession equa ion was: p edic ed size o global e ec = 0.09 ×Digi Span sco e−1.60. Discussion He e we used an audi o y local–global pa adigm o in es i- ga e whe he he age- ela ed shi om senso ium o p edic- ions occu s a all le els o hie a chical message passing. An indisc imina e age- ela ed change should be associa ed wi h Downloaded om h ps://academic.oup.com/ce co /ad ance-a icle/doi/10.1093/ce co /bhaa352/6014977 by Jy askyla Uni e si y use on 08 Decembe 2020 8Ce eb al Co ex, 2020, Vol. 00, No. 00 Figu e 4. (A). G and a e aged ERPs o local and global e ec s on ep esen a i e elec odes (i.e., FCz and Pz) in each g oup. Shaded a ea ep esen s he s anda d e o o he mean. Time 0 ms ma ks he onse o he p obe (i.e., one o in e es ). Do ed lines ma k he onse o he 4 p eceding ones. (B). The 2-D ( ime-by-pa icipan ) iews o he ERPs in which local and global e ec s (i.e., de ian −s anda d) a e so ed along pa icipan s’ age, smoo hed ac oss neighbo ing pa icipan s using a ec angula (boxca ) mo ing a e age (smoo hing wid h = 10), and colo coded. The ace below each ERP image shows he g and-a e aged ERPs ac oss all pa icipan s. The ed do s on scalp maps ma k he posi ion o ep esen a i e elec odes o ease o e e ence. educed MMN and P3b, signaling educed p edic ion e o s due o dec eased weigh ing o senso y inpu s a bo h senso y and con ex ual le els. Measu ing hallma ks o hie a chical p edic- ion e o s, we ound ha olde b ains show li le educ ion in he MMN signaling senso y (i.e., i s -o de ) p edic ion e o s bu signi ican a enua ion in he P3b signaling con ex ual (i.e., second-o de ) p edic ion e o s. The esul s sugges ha , in no - mal aging, ou b ain as a p edic i e machine does no unde go an indisc imina e decline bu a speci ic a enua ion o Bayesian upda ing. Age- ela ed changes in no el y de ec ion ha e been he sub- jec o nume ous s udies. Ou indings ex end p e ious empi - ical wo k by demons a ing he hie a chy-selec i e changes in p edic i e p ocessing as we age. The de ec ion o local de iancy seems la gely p ese ed in olde indi iduals a ea lie la ency (including he MMN ollowed by he P3a bu no he RON). The lack o age-dependen di e ence a ea lie la ency is in line wi h p e ious esea ch whe e pa icipan s’ a en ion was ocused on he audi o y de ian /s anda d s imuli o less con- s ained on he co e ask (MMN: Pekkonen e al. 1993,1996; Sch oede e al. 1995;Gun e e al. 1996;Kazme ski e al. 1997; Amenedo and Díaz 1998; P3a: Mage e al. 2005;Be i e al. 2013). These indings sugges ed ha audi o y disc imina ion abili y emains e ec i e h oughou he li espan (a leas wi h he help o a en ion). In e es ingly, he de ec ion o local de iancy did di e ge by age a la e la ency, wi h olde indi iduals missing he RON (Mage e al. 2005;Ge zmann e al. 2013). Mo eo e , pa icipan s’ wo king memo y was a signi ican p edic o o he size o local e ec s a he RON, whe e wo se wo king memo y was associa ed wi h smalle RON. Toge he , he MMN/P3a/RON complex was hough o p o ide a neu ophysiological index o he cascade o 3 main p ocesses in ol ed in in olun a y a en ion con ols o de ian s (i.e., au oma ic change de ec ion, o ien ing o a en ion, and eco e y om dis ac ion o eo ien - ing o a en ion as a wo king memo y p ocess) (Sch öge and Wol 1998;Sch öge e al. 2000;Be i and Sch öge 2003;Be i e al. 2004;Be i 2008;Ho á h e al. 2008). The no mal MMN and P3a bu he missing RON in olde indi iduals likely e lec s hei in ac capaci y o de ec and o ien o senso y (i.e., i s - o de ) p edic ion e o s; hei challenge lies in he mo e gene al a emp o eco e om such pe u bing dis ac ion (i.e., local de iancy) o e ocus on hei ask (i.e., o 1) iden i y in equen ials and 2) coun he numbe o in equen ials in each block) due o limi a ions in wo king memo y. In con as , he de ec ion o global de iancy is clea ly com- p omised in olde indi iduals, as hey showed lowe accu acy in he iden i ica ion o global de ian s, mo e e o s in coun - ing global de ian s, and a enua ed P3b. The a enua ed P3b Downloaded om h ps://academic.oup.com/ce co /ad ance-a icle/doi/10.1093/ce co /bhaa352/6014977 by Jy askyla Uni e si y use on 08 Decembe 2020