Influence of binge drinking on the resting state functional connectivity of university Students: A follow-up study

In luence o binge d inking on he es ing s a e unc ional connec i i y o uni e si y S uden s: A ollow-up s udy Samuel Su´ a ez-Su´ a ez a , Fe nando Cada ei a b,c , Al onso Ba ´ os-Losce ales d , Jos´ e Manuel P´ e ez-Ga cía e , Soco o Rod íguez Holguín b,c , Ja ie Blanco-Ramos e, , Sonia Doallo b,c,* a Depa men o Heal h Sciences, Uni e si y o Bu gos 09001 Bu gos, Spain b Depa amen o de Psicoloxía Clínica e Psicobioloxía, Facul ade de Psicoloxía, Uni e sidade de San iago de Compos ela, San iago de Compos ela, Spain c Ins i u o de Psicoloxía (IPsiUS), Uni e sidade de San iago de Compos ela, Spain d Depa amen o de Psicología B´ asica, ClínicaSpain y Psicobiología, Uni e si a Jaume I, Cas ell´ o de la Plana, Spain e Depa men o Educa ional Psychology and Psychobiology, Facul y o Educa ion, Uni e sidad In e nacional de La Rioja, Log o˜ no, Spain Fundaci´ on Pública Andaluza pa a la In es igaci´ on Biosani a ia en Andalucía O ien al, FIBAO, Spain ARTICLE INFO Keywo ds: Binge d inking Res ing-s a e Func ional magne ic esonance imaging Func ional connec i i y Adolescence ABSTRACT Binge D inking (BD) is cha ac e ized by consuming la ge amoun s o alcohol on one occasion, posing isks o b ain unc ion. None heless, i emains he mos p e alen consump ion pa e n among s uden s. C oss-sec ional s udies ha e explo ed he ela ionship be ween BD and anomalies in es ing-s a e unc ional connec i i y (RS- FC), bu he medium/long- e m consequences o BD on RS-FC du ing de elopmen al pe iods emain ela i ely unexplo ed. In his wo-yea ollow-up s udy, he impac o sus ained BD on RS-FC was in es iga ed in 44 college s uden s (16 binge-d inke s) ia wo MRI sessions a ages 18–19 and 20–21. Using a seed- o- oxel app oach, RS- FC di e ences we e examined in nodes o he main b ain unc ional ne wo ks ulne able o alcohol misuse, acco ding o p e ious s udies. G oup di e ences in RS-FC we e obse ed in ou o he explo ed b ain egions. Binge d inke s, compa ed o he con ol g oup, exhibi ed, a he second assessmen , dec eased connec i i y be ween he igh SFG (execu i e con ol ne wo k) and igh p ecen al gy us, he ACC (salience ne wo k) and igh pos cen al gy us, and he le amygdala (emo ional ne wo k) and medial on al gy us/do sal ACC. Con e sely, binge d inke s showed inc eased connec i i y be ween he igh Nacc ( ewa d ne wo k) and ou clus e s comp ising bila e al middle on al gy us (MFG), igh middle cingula e co ex, and igh MFG ex ending o SFG. Main aining a BD pa e n du ing c i ical neu ode elopmen al yea s impac s RS-FC, indica ing mid- o- long- e m al e a ions in unc ional b ain o ganiza ion. This s udy p o ides new insigh s in o he neu o oxic e - ec s o adolescen alcohol misuse, emphasizing he need o longi udinal s udies add essing he las ing conse- quences on b ain unc ional connec i i y. 1. In oduc ion Alcohol consump ion is a signi ican social and heal h issue among you h and adolescen s in mos Wes e n coun ies, associa ed wi h nume ous ad e se ou comes such as inc eased isk o iolence, inju ies, acciden s, and men al heal h issues (Rehm & Shield, 2013; Welsh e al., 2017; Wo ld Heal h O ganiza ion, 2018). Among he di e en haza dous consump ion pa e ns p esen in you h, binge d inking (BD) is he mos p e alen , wi h a ound 35 % o s uden s be ween 15 and 25 yea s o age p ac icing BD in Eu ope (ESPAD, 2020) and 30 % o pa icipan s be ween 18 and 25 in he USA (SAMHSA, 2023) in he p e ious 30 days. This consump ion pa e n cha ac e ized by he in ake o g ea amoun s o alcohol on a single occasion, ollowed by wi hd awal pe iods, is usually de ined as he consump ion o 70 g (male) o 50 g ( emale) o alcohol wi hin an app oxima ely 2-h pe iod (NIAAA, 2004). P e ious esea ch sugges s * Co esponding au ho a : Dp o. de Psicoloxía Clínica e Psicobioloxía, Facul ade de Psicoloxía, Uni e sidade de San iago de Compos ela. E-mail add esses: [email p o ec ed] (S. Su´ a ez-Su´ a ez), [email p o ec ed] (F. Cada ei a), [email p o ec ed] (A. Ba ´ os-Losce ales), josemanuel. [email p o ec ed] (J.M. P´ e ez-Ga cía), [email p o ec ed] (S.R. Holguín), [email p o ec ed] (J. Blanco-Ramos), [email p o ec ed] (S. Doallo). Con en s lis s a ailable a ScienceDi ec Addic i e Beha io s Repo s jou nal homepage: www.else ie .com/loca e/ab ep h ps://doi.o g/10.1016/j.ab ep.2025.100585 Recei ed 3 May 2024; Recei ed in e ised o m 20 Decembe 2024; Accep ed 8 Janua y 2025 Addic i e Beha io s Repo s 21 (2025) 100585 A ailable online 10 Janua y 2025 2352-8532/© 2025 Published by Else ie L d. This is an open access a icle unde he CC BY-NC-ND license ( h p://c ea i ecommons.o g/licenses/by-nc-nd/4.0/ ). ha main aining a pa e n o acu e and in e mi en alcohol use du ing adolescence and eme ging adul hood has pa icula ly dele e ious e ec s on he b ain (Hille -S u mh¨ o el & Spea , 2018; Jacobus & Tape , 2013). As such, BD has been ela ed o s uc u al and unc ional abno mali ies (Almeida-An unes e al., 2021; Ca bia e al., 2018; Lees e al., 2019; P´ e ez-Ga cía e al., 2022), and i is conside ed a isk ac o o de el- oping alcohol use diso de s (AUD) (Addolo a o e al., 2018; Bonomo e al., 2004). Mo eo e , he highes a es o BD occu be ween he ages o 18 and 25 (SAMSHA, 2019), when di e en b ain s uc u es and hei connec i i y a e s ill unde ma u a ion (Cao e al., 2014; Luna e al., 2015), leading o a heigh ened ulne abili y o he neu o oxic e ec s o alcohol (Ba a & Tape , 2010; Squeglia & G ay, 2016). Amid he ple ho a o changes ha ake place du ing b ain de elop- men , he eo ganiza ion and inc easing e iciency o la ge-scale in insic unc ional ne wo ks (IFNs) suppo s he age- ela ed imp o e- men obse ed in di e en cogni i e abili ies and sel - egula ion p o- cesses (S e ens, 2016). Whole-b ain unc ional magne ic esonance imaging in es ing-s a e ( s- MRI) is a ele an echnique o assess unc ional connec i i y (FC) (i.e., he s a is ical ela ionship among wo o mo e neu ophysiological e en s, (F is on, 2011) be ween egions comp ised in hese IFNs. This kind o analysis, based on he ime se ies o spon aneous luc ua ions in he blood-oxygen-le el-dependen (BOLD) ac i i y, has consis en ly iden i ied se e al IFNs (Biswal e al., 1995; Raichle, 2011; Thomas Yeo e al., 2011) and has allowed o ela e he p esence o impai men s in FC wi h mul iple pa hological condi ions including AUD (Dupuy & Chan aud, 2016; Su he land e al., 2012). Howe e , he po en ial abno mali ies in s- MRI FC associa ed wi h BD a e s ill no ye well cha ac e ized, wi h only a hand ul o a icles explo ing his ela ionship (A ienzo e al., 2019; C ane e al., 2018; He man e al., 2018; Mo is e al., 2016; Sousa e al., 2019; Tong e al., 2021). Fu he mo e, he possibili y o s udying longi udinal e ec s o BD beha io s opens he doo o unde s and he dys egula ion o neu- o unc ional ne wo ks by epea ed cycles o in oxica ion and wi hd awal ha a e sugges ed o con ibu e o he de elopmen o AUD in neu o- biological models o addic ion (e.g., Koob & Volkow, 2016). Pa icu- la ly, p elimina y e idence indica es ha his p og ession om ec ea ional o pa hological consump ion pa e ns may esul om he dys egula ion o on al, s ia al and limbic ci cui y (E e i & Robbins, 2016; Zil e s and e al., 2018). Fo ins ance, p io s udies wi h clinical popula ions ac oss AUD se e i y le els ha e epo ed abno mal FC be- ween and wi hin nodes o he execu i e con ol (ECN) and a en ional (ATN) ne wo ks (Galand a e al., 2019; Mülle -Oeh ing e al., 2015; Y. Wang e al., 2018; Weiland e al., 2014; Zhu e al., 2015), he de aul mode ne wo k (DMN) (Chan aud e al., 2011; Mülle -Oeh ing e al., 2015; Zhu e al., 2015, 2017), he salience ne wo k (SAN) (Galand a e al., 2019; Mülle -Oeh ing e al., 2015; Zhu e al., 2015, 2017), he ewa d ne wo k (RWN) (Camchong e al., 2013; Mülle -Oeh ing e al., 2015; J. Wang e al., 2016) and he emo ion ne wo k (EMN) (Zhu e al., 2017). Al hough s ill eme ging, s udies wi h BD samples epo ed anomalies wi hin mos o he explo ed IFNs wi hou a clea pa e n in he di ec ion o he BD e ec on he FC. Bo h inc eased (Sousa e al., 2019) and dec eased (A ienzo e al., 2019; Mo is e al., 2016) FC has been obse ed in b ain a eas ela ed o he ECN (i.e., middle and in e io on al gy us) and he con ol o mo o esponses (e.g., sub halamic nucleus). Also, compa ed o con ols, young binge d inke s (BDs) showed an inc eased FC in on al and subco ical a eas closely ela ed o salience de ec ion (an e io cingula e co ex [ACC]) and ewa d p ocessing (cauda e, nucleus accumbens [Nacc] and o bi o on al co ex [OFC]) (A ienzo e al., 2019). On he o he hand, dec eased in a- ne wo k FC o he ATN has been obse ed be ween he igh sup a- ma ginal gy us, on al egions and insula co ex (He man e al., 2018). In his same di ec ion, C ane and colleagues (C ane e al., 2018) e- po ed dec eased FC be ween he amygdala, an essen ial componen o he EMN, and OFC in young BDs. Finally, he only longi udinal s- MRI FC s udy on BD published o da e, o ou knowledge, epo ed dec eased connec i i y be ween DMN and en al a en ion ne wo k ac oss a 2- yea ollow-up h ough ne wo k-le el analysis (Tong e al., 2021). I is impo an o no e ha he a ailable e idence sugges s ha some impai men s associa ed wi h BD du ing you h would only a ise a e main aining his consump ion pa e n in he mid o long- e m. Fo ins ance, impai men s in he FC o he DMN ha e only been desc ibed by s udies wi h a longi udinal app oach (Co eas e al., 2016; Tong e al., 2021). Thus, conside ing he sca ci y o longi udinal s udies, we deemed i c ucial o explo e changes in s- MRI FC ela ed wi h main aining a BD pa e n du ing eme ging adul hood. He e, we in es iga e he FC o young BDs du ing a 2-yea pe iod using a seed- o- oxel FC me hod by examining a se o c i ical nodes o ele an IFNs — ollowing he app oach p oposed by Mulle -Oeh ing e al. (2018, 2015) — in which alcohol misuse- ela ed anomalies ha e been desc ibed (i.e. DMN, ECN, SAN, ATN, EMN and RWN). Like p e- ious longi udinal s udies in he ield (Co eas e al., 2016; Tong e al., 2021) we expec o see di e ences eme ge be ween g oups a he end o he 2-yea ollow-up pe iod. Mo e speci ically, we hypo hesized ha he pa e ns o FC in BDs and con ols would di e du ing he ollow-up pe iod in a seed-dependen way, e ealing dis inc i e neu obiological alcohol- ela ed changes in each seed. Based on p e ious e idence, we expec ed ha BDs, compa ed o con ols, would show in he 2nd s 1s assessmen : i) dec eased FC in he supe io pa ie al lobule (SPL; (He man e al., 2018) as a node o he ATN and he amygdala (C ane e al., 2018) as pa o he EMN; ii) inc eased FC in he Nacc and he ACC (A ienzo e al., 2019) as nodes o he RWN and he SAN, espec i ely; and iii) we will explo e abno mali ies in he FC o he supe io on al gy us (SFG) and pos e io cingula e co ex (PCC) associa ed espec i ely wi h he ECN and DMN. 2. Ma e ials and me hods 2.1. Pa icipan s A sample o uni e si y s uden s was assessed a wo di e en ime- poin s when hey we e a hei i s (18–19 yea s old) and hi d (20–21 yea s old) academic yea s. Wi hin he amewo k o a b oade esea ch p ojec 85 olun ee s we e ini ially selec ed o unde wen MRI assessmen om a pool o 2998 i s -yea s uden s om he Uni e si y o San iago de Compos ela (USC, Spain). Pa icipan s we e selec ed based on hei willingness o pa ici- pa e and he esponses o a class oom ques ionnai e ha assessed alcohol and subs ance consump ion, including he adap ed e sions o di e en s anda dized ques ionnai es such as he Alcohol Use Diso de s Iden i ica ion Tes (AUDIT) (Saunde s e al., 1993; Va ela e al., 2005), among o he s. Pa icipan s hen comple ed a semi-s uc u ed in e iew and se e al s anda dized ques ionnai es (see supp. ma e ial o mo e de ails ega ding sample selec ion p ocedu e and e e ences o p e ious esul s) o ensu e hey me selec ion c i e ia (see Table 1). This s udy was app o ed by he Bioe hics Commi ee o he USC. Acco ding o he NIAAA’s de ini ion o BD (NIAAA, 2004), we clas- si ied as BDs hose pa icipan s who d ank 3 70 g (male) o 3 50 g ( e- male) o alcohol in one d inking occasion (i.e., BD episode) a leas six imes o he las six mon hs. Pa icipan s who did no each his alcohol consump ion h eshold we e classi ied as con ols (CN). All pa icipan s ul illed he g oup classi ica ion c i e ia a bo h e alua ions. Ou o 85 subjec s, 55 pa icipa ed in bo h neu oimaging assessmen s and 44 (16 BDs) main ained a s able consump ion pa e n o he du a ion o he s udy. A e he exclusion om he analysis o wo pa - icipan s due o echnical p oblems du ing image acquisi ion and se en pa icipan s due o excessi e head mo emen , he inal sample included 35 igh -handed pa icipan s, wi h 14 BDs (7 emales) and 21 CN (10 emales) (see Table 2). S. Su´ a ez-Su´ a ez e al. Addic i e Beha io s Repo s 21 (2025) 100585 2 2.2. Imaging da a acquisi ion MRI scans we e collec ed wi h a 3 T Achie a Philips body scanne (Philips Medical Sys ems, Bes , NL) equipped wi h a 32-channel SENSE head coil (loca ed a he Uni e si y Hospi al Complex o San iago de Compos ela) using a T2*-weigh ed echo-plana imaging sequence wi h he ollowing acquisi ion pa ame e s: TR/TE =3000/30 ms, lip angle =87◦, FOV =230 ×230 mm, oxel size =3 mm 3 , 45 axial slices and 200 olumes (10 min), p eceded by 4 “dummy” unc ional olumes o allow o signal-equilib a ion e ec s. Pa icipan s we e ins uc ed o lie quie ly wi h hei eyes ixed on a cen al ixa ion c oss and no o hink abou any hing. High- esolu ion ana omical T1-weigh ed images we e acqui ed using a 3D u bo ield-echo sequence wi h he ollowing pa- ame e s: TR/TE =7.7/3.4 ms, lip angle =8◦, FOV =240 mm, oxel size =0.8 mm 3 , 200 ans e se slices (7 min). 2.3. Image p ocessing and RS-FC analysis Imaging da a we e p ocessed using S a is ical Pa ame ic Mapping (SPM12; h ps://www. il.ion.ucl.ac.uk/spm/so wa e/spm12/) imple- men ed in Ma lab ( e sion 2018a, The Ma hwo ks, Inc., Na ick, MA). The i s 5 unc ional olumes we e disca ded o a oid b ain signal ela ed o he ins uc ion sc een p esen ed a he beginning o he eco ding. Func ional images we e hen co ec ed o slice iming and ealigned and unw apped. The ana omical T1 images we e co egis e ed o he ealigned mean unc ional image, and hen images we e ans- o med in o s anda d MNI space using ana omical segmen a ion-based no maliza ion pa ame e s. The esul ing unc ional images we e spa ially smoo hed using a 7-mm FWHM Gaussian ke nel. Addi ional p ep ocessing s eps o educe spu ious BOLD a iances and RS-FC analysis we e ca ied ou using he CONN Func ional Con- nec i i y Toolbox 20 (Whi ield-Gab ieli & Nie o-Cas anon, 2012). A P incipal Componen Analysis (PCA) was applied o whi e ma e and CSF masks o es ima e po en ial sou ces o spu ious a iance ollowing he ana omical componen -based noise co ec ion me hod (aCompCo ; Behzadi e al., 2007). The iden i ied PCAs in each mask we e hen eg essed om he BOLD ime se ies, in addi ion o he six-mo emen pa ame e s. Fi s -o de empo al de i a i es and quad a ic e ec s o he mo ion- ela ed pa ame e s we e also included in he eg ession (see Supp. Ma e ial o u he desc ip ion ega ding mo emen co ec ion me hods). Func ional connec i i y analysis was pe o med using a seed- o- oxel app oach in a se o ROIs p e iously de ined as co e nodes o some o he main unc ional ne wo ks (i.e., DMN, ECN, SAN, ATN, EMN and RWN), ollowing a simila app oach o Mülle -Oeh ing e al. (2015, 2018). Six Seed egions we e selec ed o i e ne wo ks om he au o- ma ed ana omical labelling (AAL; Tzou io-Mazoye e al., 2002) em- pla e as ollows: PCC o he DMN, SFG o he ECN, ACC o he SAN, SPL o he ATN and he amygdala o he EMN. Fo he RWN, bila e al ROIs we e c ea ed o he Nacc based on he ana omical coo dina es de ined by p e ious s udies (Ne o e al., 2008; see Mülle -Oeh ing e al., 2015, 2018) (see Supp. Ma e ial o u he desc ip ion o seed de ini ion). The mean BOLD ime cou ses we e compu ed ac oss all oxels o e each seed egion. Fo each pa icipan , seed- o- oxel analyses we e pe o med by calcula ing Pea son’s bi a ia e co ela ion coe icien s be ween he ime se ies o each ROI and ha o all o he oxels in he b ain. A e applying a Fishe Z ans o ma ion, i s -le el co ela ion maps we e c ea ed o all olun ee s. Then, indi idual seed- o- oxel maps we e en e ed in o a second-le el andom-e ec s analysis wi h sex as a co a ia e. 2.4. S a is ical analysis Demog aphic and consump ion a iables we e submi ed o pai wise compa isons in ei he o he assessmen s be ween he g oups (BDs s. Table 1 Selec ion c i e ia es ablished in he s udy. Inclusion C i e a Exclusion C i e ia Con ol g oup (CN): Alcohol consump ion <6 BD episodes 1 o e he las 6 mon hs and cannabis consump ion <12 uni s o e he las 3 mon hs Ch onic medical condi ions ha could a ec neu ocogni i e unc ioning (diabe es, hypo hy oidism, li e diseases, e c.) His o y o neu ological diso de s o b ain inju y Binge d inke s (BDs): Alcohol consump ion ≥6 BD episodes o e he las 6 mon hs and cannabis consump ion <12 uni s o e he las 3 mon hs Pe sonal his o y o DSM-IV-TR Axis I and/ o II diagnosed diso de s (including SUD), o a sco e abo e 90 h pe cen il in he Global Se e i y Index (GSI) o in wo o mo e symp oms dimensions o he SCL-90- R Family his o y o majo psychopa hological diso de s in i s - deg ee ela i es Family his o y o i s -deg ee alcoholism o o he SUD AUDIT sco e >20 a he s a o he s udy Use o psychoac i e medica ions and/o use o illegal d ugs (excep occasional consump ion o cannabis) in he las 6 mon hs Non-co ec ed senso y de ici s and MRI con aindica ions 1 BD episode: consump ion o ≥5 ( emale) o ≥7 (male) Spanish s anda d d inks (10 g o alcohol) on one occasion; AUDIT, Alcohol Use Diso de s Iden- i ica ion Tes ; SUD, subs ance use diso de ; SCL-90-R, Symp om Checklis -90- Re ised. Table 2 Demog aphic and subs ance use cha ac e is ics o he inal sample (mean ±SD). Fi s e alua ion Second e alua ion Con ols BDs Con ols BDs N ( emales) 21 (10) 14 (7) 21 (10) 14 (7) Age 18.59 ( ±0.31) 18.55 ( ±0.31) 20.56 ( ±0.32) 20.57 ( ±0.3) Caucasian (%) 100 100 100 100 Mean ime (mon hs) be ween i s and second e alua ion — — 24.3 ( ±2.86) 23.5 ( ±3.13) A e age amewise displacemen (mm) 0.13 ( ±0.05) 0.13 ( ±0.04) 0.13 ( ±0.05) 0.15 ( ±0.06) Tobacco consump ion (n > 2 ciga e es pe day) 0 1 0 2 Cannabis consump ion in he las 30 days (n >1 uni and <4 uni s) c 0 1 0 2 Age o onse on d inking 16.5 ( ±0.94) 15.5 ( ±0.85) ** — — A e age # d inks pe d inking occasion 1.73 ( ±1.40) 7.1 ( ±2.66) *** 1.86 ( ±1.28) 8.27 ( ±3.01) *** Numbe o BD episodes ª , pas 6 mon hs 0.57 ( ±1.40) 21.5 ( ±10.33) *** 0.62 ( ±1.32) 29 ( ±18.86) *** To al AUDIT sco e b 1.57 ( ±1.94) 9.46 ( ±3.82) *** 1.76 ( ±1.92) 9.71 ( ±4.44) *** Age o onse measu ed as he sel - epo ed age o he i s ull d ink. ** p <0.01. *** p <0.001. ª BD episode: consump ion o ≥5 ( emale) o ≥7 (male) Spanish s anda d d inks (10 g o alcohol) on one occasion. b Missing sco es o he second (pa icipan 1) and he six h and se en h i ems (pa icipan 2) o he AUDIT a baseline we e eplaced by he co esponden g oup mean in each speci ic i em. c Cannabis consump ion was an exclusion c i e ion when i exceeded he >1 uni /week h eshold (see supp. Ma e ial). S. Su´ a ez-Su´ a ez e al. Addic i e Beha io s Repo s 21 (2025) 100585 3 con ols) using S uden ’s - es s o chi-squa ed es s when app op ia e. Mo eo e , 2x2 mixed-model ANOVAs we e employed o es po en ial di e ences be ween g oups o each alcohol- ela ed measu e ac oss e alua ions. Values associa ed wi h each assessmen (sco e in ime 1 and ime 2) we e submi ed as he wi hin-subjec s ac o “ ime” and g oup (BDs, CN) was submi ed as he be ween-subjec s ac o . All analyses we e done wi h SPSS so wa e ( e sion 26). To es o g oup di e ences ac oss he wo assessmen s (ini ial and ollow-up) in RS-FC, be ween-g oup con as analyses o each ROI we e pe o med wi h ime (wi hin-subjec ) and g oup (be ween-subjec ) as ac o s o in e es . All analyses we e se wi h a combined peak-and- ex en h eshold wi h a oxelwise le el o p < 0.001 (unco ec ed) and a clus e ex en h eshold o p < 0.05, co ec ed o amily-wise e o (FWE). Addi ionally, alse disco e y a e (FDR) co ec ion o mul iple compa isons was applied o con ol o he numbe o ROIs (see Supp. Ma e ial o de ails). Finally, Spea man’s ho co ela ion analyses we e pe o med o he whole sample o assess he ela ionship be ween he pe cen o change in FC ( om baseline o ollow-up; o a desc ip ion o his measu e see Supp. Ma e ial) —in hose ROIs ha showed signi ican be ween-g oup di e ences in he FC longi udinal analysis— and he in ensi y o alcohol consump ion habi s a ollow-up. Addi ional explo a o y analyses examining he impac o BD as a unc ion o biological sex can be ound in he Supplemen a y Ma e ial. 3. Resul s 3.1. Sample cha ac e is ics The e we e no signi ican di e ences be ween g oups in sex, age, ime be ween e alua ions o he amoun o mo emen ( amewise displacemen ) (see Table 2). As expec ed, BDs epo ed a signi ican ly g ea e deg ee o alcohol use han CN (see Table 2). Mo e speci ically, BDs epo ed signi ican ly ea lie alcohol onse ( =2.94; p =0.007), and a signi ican main e ec o g oup was ound in bo h assessmen s o : i) numbe o d inks pe d inking occasion (F 1, 33 =85.05, p <0.001); ii) numbe o BD episodes in he pas 6 mon hs (F 1, 33 =113.45, p <0.001); and iii) o al AUDIT sco e (F 1, 33 =65.4, p <0.001). A main e ec o ime was ound o he numbe o d inks pe d inking occasion (F 1, 33 =4.28, p =0.046) as bo h g oups sligh ly inc eased he mean numbe o d inks pe d inking episode in he ollow-up compa ed wi h he baseline (see Table 2). 3.2. Func ional connec i i y Func ional connec i i y analysis o he whole sample e ealed, o bo h MRI assessmen s, he expec ed es ing-s a e ne wo ks closely esembling wha was ound in p e ious s udies (Mülle -Oeh ing e al., 2018, 2015; see supplemen a y Figs. 2 and 3). The main enance o he BD pa e n e ealed g oup-by- ime signi i- can di e ences a a oxelwise le el o p unc < 0.001 and FWE-co ec ed clus e -ex en h eshold o p < 0.05 in ou o he six explo ed ne wo ks (i.e., SAN, EMN, ECN, and RWN; see Table 3). BDs showed a pa e n o dec eased (ECN, SAN, EMN) and inc eased (RWN) b ain connec i i y compa ed wi h con ols in he longi udinal analysis (2nd assessmen compa ed o 1s one). Speci ically, dec eased connec i i y was obse ed be ween i) he igh SFG, as a node o he ECN, and he igh p ecen al gy us (BA 6); ii) he ACC, as he seed o he SAN, and he igh pos - cen al gy us (BA 3); and iii) he le amygdala, as a c i ical node o he EMN, and he medial on al gy us (mFG) ex ending o he do sal ACC (dACC; BA 32, 9; see Table 3, Fig. 1). On he o he hand, BDs demon- s a ed g ea e FC ela i e o con ols in he 2nd s 1s MRI assessmen be ween he igh Nacc (RWN) and ou independen clus e s, including he middle on al gy us (MFG) (BA 8, 9) bila e ally, he igh middle cingula e co ex (MCC) and he igh MFG ex ending o he SFG (BA 6) (see Table 3, Fig. 2). 3.3. Co ela ion analysis Spea man’s ho co ela ions e ealed signi ican ela ionships be- ween he pe cen o change in FC ac oss assessmen s and di e en alcohol consump ion measu es epo ed a he ollow-up. Rega ding alcohol consump ion, he numbe o BD episodes co ela ed wi h he FC o he ACC ( ho =-0.409, p =0.015) and wi h he FC o he le amygdala ( ho =0.375, p =0.026). The a e age numbe o d inks pe d inking episode co ela ed wi h he FC o he ACC ( ho =-0.345, p = 0.043), he le amygdala ( ho =0.369, p =0.029) and wi h he FC be ween he igh Nacc and he MCC ( ho =-0.397, p =0.018). Finally, o al AUDIT sco es ollowed a simila pa e n, showing a signi ican co ela ion wi h he FC o he ACC ( ho =-0.390, p =0.021) and he le amygdala ( ho =0.373, p =0.027) (see Supp. Ma e ial igu es S3a and b). 4. Discussion Longi udinal esul s show he e ec o main aining a BD pa e n o a leas wo yea s on he FC in ou ou o six in es iga ed egions. The e we e dec eases in FC in BDs compa ed o con ols be ween he igh SFG and he p ecen al gy us (ECN), be ween he le amygdala and he medial on al gy us/dACC (EMN), and be ween he ACC and he pos - cen al gy us (SAN). On he o he hand, inc eases in FC we e obse ed be ween he Nacc and he PCC and middle on al gy us (RWN). Fi s , he dec eased FC obse ed in BD ( s con ols) be ween he SFG and he p ecen al gy us suppo s, pa ially, ou hypo hesis based on he indings o BD (A ienzo e al., 2019) and AUD s udies (Galand a e al., 2019; Mülle -Oeh ing e al., 2015; Weiland e al., 2014). This Table 3 Func ional connec i i y di e ences be ween g oups 2nd s 1s assessmen . Ne wo k/ROI Region Side P FWE k x y Z T SAN/ACC CN >BDs Pos cen al gy us (BA 3) R 0.0058 232 46 −24 64 5.66 EMN/Amygdala L CN >BDs Medial on al gy us/ dACC (BA 32, 9) R 319 10 34 36 4.86 0.0007 ECN/SFG R CN >BDs P ecen al gy us (BA 6) R 0.0060 232 44 −4 62 5.16 RWN/NAcc R BDs >CN MFG (BA 8, 9) R 0.0020 269 34 26 36 5.25 MCC (BA 31) R 0.0305 159 12 −36 38 4.82 MFG (BA 8, 9) L 0.0012 293 −36 28 48 4.77 MFG/SFG (BA 6) R 0.0122 194 28 −4 52 4.33 No e. BA: B odmann A ea; CN, con ol g oup; BDs, binge d inke s. L, le ; R, igh ; SAN, salience ne wo k; EMN, emo ion ne wo k; ECN, execu i e con ol ne wo k; RWN, ewa d ne wo k; dACC, do sal an e io cingula e co ex; MCC, middle cingula e co ex; MFG, middle on al gy us; Nacc, nucleus accumbens; SFG, supe io on al gy us. All esul s a e signi ican a oxelwise le el o p unc < 0.001 a FWE-co ec ed clus e -ex en h eshold o p < 0.05 and su i ed FDR co ec ion o mul iple compa isons (q =0.05) o con ol o he numbe o explo ed ROIs (see Supp. Ma e ial o u he de ail). S. Su´ a ez-Su´ a ez e al. Addic i e Beha io s Repo s 21 (2025) 100585 4 connec i i y pa e n seems o e lec educed FC among b ain a eas p e iously iden i ied as pa o he ECN, a ne wo k ha has been ecen ly highligh ed o i s nega i e associa ion be ween FC and pas mon h’s BD (Lesnewich e al., 2022). Ou esul s also align pa ially wi h some o he p e ious epo s om c oss-sec ional s udies in he BD popula ion (e.g., A ienzo e al., 2019; Mo is e al., 2016; He man e al., 2018) and may be ela ed o he execu i e dys unc ion associa ed wi h mid and long- e m alcohol misuse (Golds ein & Volkow, 2011; Zil e - s and e al., 2018). Mo eo e , he dec eased FC o he amygdala wi h he mFG/dACC is in line wi h epo ed FC anomalies o his egion wi h on al a eas in s udies ocused on BD (C ane e al., 2018), adolescen s wi h mode a e consump ion o alcohol (Pe e s e al., 2015), social d inke s (Hu e al., 2018) and AUD pa ien s (Mülle -Oeh ing e al., 2015; Wade e al., 2017; Zhu e al., 2017). The amygdala-p e on al connec i i y is conside ed key o implemen ing adequa e emo ion- egula ion esponses (Kim e al., 2011; Ochsne e al., 2012), and dis up ion o his on -limbic ci cui y has been linked o addic ion ulne abili y (Koob & Volkow, 2016). Thus, ou esul s highligh how he main enance o a BD pa e n can lead o a dys unc ion o his c i ical neu al ci cui y. Con e sely, he educed FC obse ed in he ACC is con a y o ou hypo hesis o an inc emen in he FC o his egion in BDs (A ienzo e al., 2019). Despi e he unexpec ed di ec ion o he anomalies, he ela ionship be ween haza dous alcohol consump ion pa e ns and lowe ACC FC wi h on o-pa ie al egions is well documen ed (Mülle - Oeh ing e al., 2015; Zakiniaeiz e al., 2017). Mo e speci ically, he pos - cen al gy us (BA 3) has been iden i ied as pa o he senso y-mo o ne wo k (Damoiseaux e al., 2006), and i s in e ac ion wi h he ACC −as a node o he salience ne wo k- could be c i ical o in eg a ing in e ocep i e in o ma ion and con ibu e o conscious awa eness o in- e nal s a es (Chen e al., 2021; C i chley e al., 2004; Khalsa e al., 2009). In he con ex o ou s udy, his could mean ha p olonged BD habi s make i ha de o manage in e ocep i e esponses o salien s imuli (i.e. alcohol- ela ed cues), simila o he heigh ened awa eness o c a ing in pa ien s wi h AUD (Volkow e al., 2019; Volkow & Mo ales, 2015). On he o he hand, he inc eased b ain connec i i y obse ed a he Nacc is in line wi h ou hypo hesis and wi h p io indings ha showed abno mali ies in ewa d- ela ed a eas bo h in BDs and AUD pa ien s (e. g., A ienzo e al., 2019; Mülle -Oeh ing e al., 2015). This inc eased FC in appe i i e-d i en egions wi h on al execu i e egions (i.e., MFG and SFG) may subse e he miss egula ion o expec ancies and appe i- i e esponses owa ds alcohol- ela ed s imuli, p e iously epo ed in BDs (Ames e al., 2014; B umback e al., 2015). In e es ingly, he opposi e pa e n ( educed FC) has been sugges ed o help he main e- nance o abs inence in AUD (Camchong e al., 2013). O he wise, Fig. 1. Seed- o- oxel FC maps o he longi udinal analysis. Binge d inke s (BDs) in compa ison wi h con ols (CN) showed dec eased FC be ween i) he le amygdala and he medial on al gy us/dACC (BA 32, 9); ii) he ig h supe io on al gy us (SFG) and he p ecen al gy us (BA 6); iii) he ACC and he pos cen al gy us (BA 3). Resul s a e shown co ec ed o mul iple compa isons wi h a combined peak and clus e h eshold (peak p <0.001 and clus e p FWE co ec ed <0.05). Colo ba ep esen s - alues. MNI coo dina es can be ound in Table 3. L, le ; R igh . S. Su´ a ez-Su´ a ez e al. Addic i e Beha io s Repo s 21 (2025) 100585 5 al hough ou analysis does no allow us o con i m his in e p e a ion o he esul s, he connec i i y wi h he MCC could a ou au obiog aph- ical memo y p ocesses (Boccia e al., 2019; Rolls, 2019) and be ela ed o ewa d choice in gain-loss con ex s (Zeng e al., 2023), poin ing o- wa ds an imbalanced ela ionship be ween he ewa d and he de aul mode ne wo k. The e o e, BD- ela ed enhanced FC o he Nacc wi h he p e on al co ex and MCC may be in e p e ed as an ini ial imbalance ha ul ima ely could lead o disp opo iona e guidance o d ug c a ing o e beha io al con ol (E e i & Robbins, 2016; Koob & Volkow, 2016). Ou esul s may also be in e p e ed in e ms o how ac o s such as BD in luence de elopmen al changes in he b ain’s unc ional o gani- za ion (Menon, 2013). P e ious s udies ha e sugges ed ha while mo i a ional sys ems ma u e ea lie , he spa ial s uc u e o FC changes du ing la e adolescence pa icula ly a ec s medial (e.g., ACC), la e al on al (e.g., SFG) and pa ie al egions as well as i s connec i i y wi h subco ical s uc u es such as he amygdala and hippocampus (Pujol e al., 2021; S e ens, 2016). This pa e n o changes is hypo hesized o explain he highe le els o impulsi i y and sensa ion-seeking obse ed in adolescen s (S e ens, 2016; an Duij en oo de e al., 2016), making hem mo e ulne able o isky-beha io s such as BD. By analyzing he di e ences be ween BDs and con ols in ou longi udinal s udy allowed us o map he changes in he FC o ma u ing b ain a eas. In his sense, any di e ences no ed be ween g oups in he longi udinal analysis could be in luenced by he e ec s o BD on neu ode elopmen al p ocesses. Fo ins ance, p e ious s udies ha e shown ha FC be ween he amygdala and mPFC is age-dependen , wi h eme ging adul s showing s onge FC han adolescen s (Gaba d-Du nam e al., 2014). Hence, he diminished FC pa e n obse ed in he BD g oup o he amygdala, ACC, and SFG may e lec he impac o alcohol on he ongoing de elopmen al changes in hese s uc u es beyond he sho - e m neu o oxic e ec s o alcohol on b ain o ganiza ion. Despi e i s s eng hs, ou esea ch has some limi a ions ha mus be no ed. Fi s , he s ic exclusion c i e ia and he high mobili y o uni- e si y s uden s in hei hi d academic yea (mobili y p og ams be ween uni e si ies), added o he usual d opou o longi udinal de- signs, esul ed in limi ed sample size, o cing us o be cau ious abou in e p e ing he indings, and signaling ha ou s udy would need alida ion om u u e la ge longi udinal coho s udies. Second, he absence o p io - o-alcohol onse MRI measu es makes i di icul o dis inguish which di e ences a e due o an al e a ion o de elopmen al p ocesses and which a e linked o mo e di ec alcohol neu o oxic e ec s. Las ly, he explo a o y cha ac e o his s udy has le some po en ially ele an hypo heses un es ed ha should be add essed by u u e s udies, such as he e ec o sex on he long- e m in e ac ions be ween BD and FC. In conclusion, ou esul s p o ide new e idence abou he impac o main aining a BD pa e n du ing a key ime ame o b ain de elopmen (i.e., 18–21 yea s o age). While p e ious s udies ha e shown ha BD can be ela ed o a signi ican ly di e en FC in some IFNs, he longi u- dinal na u e o he p esen s udy allows us o suppo wo c i ical poin s: i) some di e ences would a ise a e mid- o-long- e m main enance o he consump ion pa e n, and ii) he neu o oxic e ec s o alcohol while he b ain is s ill de eloping could lead o a signi ican ly di e en unc- ional o ganiza ion o he b ain. Rega ding he i s poin , al hough i could seem like a logical conclusion, he sca ci y o longi udinal designs wi h neu oimaging measu es is s ill a p oblem in ully unde s anding he addi i e neu o oxic e ec s ha BD could ha e in he long- e m. Las ly, u u e s udies should explo e he imbalance p oduced by he alcohol consump ion pa e n in ma u ing b ain a eas o explain he p e iously epo ed inc eased ulne abili y o BDs o de elop an AUD. Also, i emains o be seen i hese changes could impac FC in such a way ha po en ially hinde s he ypical adul b ain o ganiza ion e en a e abandoning BD habi s. 5. E hics This s udy was app o ed by he Bioe hics Commi ee o he USC and all pa icipan s ga e w i en in o m consen a he beginning o each o he scanning sessions. Fig. 2. Seed- o- oxel FC maps o he longi udinal analysis. Binge d inke s (BDs) in compa ison wi h con ols (CN) showed inc eased FC be ween he nucleus accumbens (Nacc) and i) he middle-pos e io cingula e co ex (BA 31); ii) he igh middle on al gy us (MFG, BA 8, 9) and he igh middle-supe io on al gy us (BA 6); iii) he le MFG (BA 8, 9). Resul s a e shown co ec ed o mul iple compa isons wi h a combined peak and clus e h eshold (peak p <0.001 and clus e p FWE co ec ed <0.05). Colo ba ep esen s - alues. MNI coo dina es can be ound in Table 3. S. Su´ a ez-Su´ a ez e al. Addic i e Beha io s Repo s 21 (2025) 100585 6 6. Con ibu o s F.C., S.R.H., and S.D. designed he s udy. S.S.-S., J.M.P.-G. and J.B.- R. pa icipa ed in he da a collec ion. S.R.H. and S.D. we e esponsible o sample selec ion. S.S.-S., A.B.-L., and S.D. analyzed and in e p e ed he da a. S.S.-S. w o e he a icle. All au ho s e iewed he inal e sion o he manusc ip and app o ed i o publica ion. CRediT au ho ship con ibu ion s a emen Samuel Su´ a ez-Su´ a ez: W i ing – e iew & edi ing, W i ing – o iginal d a , Me hodology, In es iga ion, Fo mal analysis, Da a cu a- ion. Fe nando Cada ei a: W i ing – e iew & edi ing, Valida ion, Supe ision, P ojec adminis a ion, Funding acquisi ion, Concep uali- za ion. Al onso Ba ´ os-Losce ales: W i ing – e iew & edi ing, So - wa e, Me hodology, In es iga ion, Fo mal analysis. Jos´ e Manuel P´ e ez- Ga cía: In es iga ion, Da a cu a ion. Soco o Rod íguez Holguín: P ojec adminis a ion, Da a cu a ion, Concep ualiza ion. Ja ie Blanco-Ramos: In es iga ion, Da a cu a ion. Sonia Doallo: W i ing – e iew & edi ing, Supe ision, Me hodology, In es iga ion, Da a cu a- ion, Concep ualiza ion. Funding This wo k was suppo ed by g an s om he Spanish Minis e io de Sanidad, Se icios Sociales e Igualdad, Plan Nacional sob e D ogas (PNSD 2015/034) Minis e io de Economıa y Compe i i idad (PSI2015- 70525-P) co- unded o Eu opean Regional De elopmen Fund, G an PID2020-113487RB-I00 unded by MCIN/AEI/h ps://doi.o g/10.130 39/501100011033 and Xun a de Galicia (GRC ED431C 2021/08). SS- S was suppo ed by a pos doc o al ellowship om he Uni e sidade de San iago de Compos ela co- unded wi h Eu opean Funds (Ma ga i a Salas 2022–2024). 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 . Appendix A. Supplemen a y ma e ial Supplemen a y da a o his a icle can be ound online a h ps://doi. o g/10.1016/j.ab ep.2025.100585. 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