RESEARCH REPORT
In eg a ion–seg ega ion dynamics in unc ional ne wo ks
o indi iduals diagnosed wi h schizoph enia
Se gio Iglesias-Pa o
1
| Juan Ruiz de Mi as
2
| Ma ia Felipa So iano
3
|
An onio J. Ib
añez-Molina
1
1
Depa men o Psychology, Uni e si y o
Jaén, Jaén, Spain
2
Depa men o So wa e Enginee ing,
Uni e si y o G anada, G anada, Spain
3
Men al Heal h Uni , San Agus ín
Hospi al de Lina es, Lina es, Spain
Co espondence
Se gio Iglesias-Pa o, Depa men o
Psychology, Uni e si y o Jaén, Jaén,
Spain.
Email: [email p o ec ed]
Funding in o ma ion
This esea ch was unded by Agencia
Es a al de In es igaci
on, AEI,
PID2019-105145RB-I00.
Edi ed by: John Foxe
Abs ac
Schizoph enia has been associa ed wi h dys unc ion in in o ma ion in eg a-
ion/seg ega ion dynamics. One o he neu al ne wo ks whose ole has been
mos in es iga ed in schizoph enia is he de aul mode ne wo k (DMN). In his
s udy, we ha e explo ed he possible al e a ion o in eg a ion and seg ega ion
dynamics in indi iduals diagnosed wi h schizoph enia wi h espec o heal hy
con ols, based on he s udy o he opological p ope ies o he g aphs de i ed
om he unc ional connec i i y be ween he nodes o he DMN in he es ing
s a e. Ou esul s indica e ha he pa ien s show a diminu ion o he modula -
i y o he DMN and a highe global e iciency, in spa se g aphs. Ou da a
emphasise he in e es in s udying empo al changes in ne wo k measu es and
a e compa ible wi h he hypo hesis o andomiza ion o unc ional ne wo ks
in schizoph enia.
KEYWORDS
EEG, heal hy con ol, in eg a ion, schizoph enia, seg ega ion
1|INTRODUCTION
Schizoph enia (SCZ) is a complex, ch onic men al
illness cha ac e ized by a se ies o symp oms, including
posi i e (e.g., hallucina ions and delusions), nega i e
(e.g., diminished emo ional exp ession and a oli ion) and
cogni i e symp oms (e.g., diso ganized speech, hough
and/o a en ion). E en oday, he causes o schizoph e-
nia emain subjec o deba e and esea ch. Ne e heless,
i has been p oposed ha he pa hophysiology o schizo-
ph enia may be associa ed wi h dys unc ional pa e ns o
in eg a ion/seg ega ion in dis ibu ed neu al ne wo ks,
a he han wi h he dis up ion o he unc ion wi hin
any speci ic s uc u e (F is on & F i h, 1995; Wang
e al., 2015; Zhou e al., 2007).
One o he neu al ne wo ks whose possible dys unc-
ion has been equen ly associa ed wi h diagnosis o
SCZ is he de aul mode ne wo k (DMN). The DMN is
a la ge-scale ne wo k ha in ol es associa ion co ex
and pa alimbic egions bu spa e senso y and mo o
co ex, loca ed along he midline o he p e on al
co ex, encompassing he os al an e io cingula e
co ex, pos e io cingula e co ex and p ecuneus
(Buckne e al., 2008). I has been p oposed ha his
ne wo k is esponsible o men al simula ions ha a e
used adap i ely in in e nally o ien ed asks
Abb e ia ion: BEM, bounda y elemen me hod; DMN, de aul mode
ne wo k; EEG, elec oencephalog am; HC, heal hy con ols; ICA,
independen componen analysis; SCZ, schizoph enia.
Recei ed: 10 No embe 2022 Re ised: 16 Ma ch 2023 Accep ed: 16 Ma ch 2023
DOI: 10.1111/ejn.15970
This is an open access a icle unde he e ms o he C ea i e Commons A ibu ion-NonComme cial-NoDe i s License, which pe mi s use and dis ibu ion in any
medium, p o ided he o iginal wo k is p ope ly ci ed, he use is non-comme cial and no modi ica ions o adap a ions a e made.
© 2023 The Au ho s. Eu opean Jou nal o Neu oscience published by Fede a ion o Eu opean Neu oscience Socie ies and John Wiley & Sons L d.
Eu J Neu osci. 2023;1–15. wileyonlinelib a y.com/jou nal/ejn 1
(Buckne , 2013; Sp eng e al., 2009). The ac i a ion o
he DMN is an i-co ela ed wi h he ac i i y o b ain
ne wo ks esponsible o ex e nal in o ma ion p oces-
sing (B essle & Menon, 2010). Thus, in passi e asks
whe e he expe imen e ’s equi emen s a e minimized,
he DMN is mo e ac i e, and he ac i i y in he a eas
o he co ex esponsible o senso y p ocessing is
educed (Uddin e al., 2009. Likewise, i has been
obse ed ha he DMN shows a lowe ac i a ion du ing
he pe o mance o cogni i e asks han in he es ing
s a e o in asks ha equi e in e nal concen a ion
( an Buu en e al., 2012).
DMN al e a ions ha e been associa ed wi h a ious
symp oms o schizoph enia, including posi i e (Ro a ska-
Jagiela e al., 2010), nega i e (Wang e al., 2015) and cog-
ni i e symp oms (Zhou e al., 2016). Indi iduals wi h an
SCZ diagnosis ha e a diminished capaci y o deac i a e
DMN du ing ask pe o mance ( an Buu en e al., 2012;
Whi ield-Gab ieli e al., 2009; Whi ield-Gab ieli &
Fo d, 2012) and ele a ed DMN es ing-s a e unc ional
connec i i y (Liu e al., 2012; Shim e al., 2010;
Skudla ski e al., 2010; Whi ield-Gab ieli e al., 2009).
Howe e , he esul s a e no uni ocal, and some s udies
epo dec eased low- equency es ing-s a e unc ional
connec i i y wi hin he DMN (Hilland e al., 2022)o
widesp ead dec eased connec i i y including he DMN
(Liang e al., 2006).
The idea o coo dina ion dynamics p oposes ha he
endency o b ain egions o exp ess hei specialized
unc ions (seg ega ion) coexis s wi h endencies o coo -
dina e globally o mul iple unc ions (in eg a ion) and
ha his in eg a ion/seg ega ion balance may ha e an
e olu iona y unc ion (Deco e al., 2015). In his sense,
some au ho s ha e p oposed ha an imbalance in in e-
g a ion/seg ega ion capaci y may be ela ed o schizo-
ph enia (F is on e al., 1995; Hu e al., 2017; Liang
e al., 2006). The p esen wo k aims o explo e he possi-
ble al e a ion o in eg a ion and seg ega ion dynamics in
indi iduals wi h an SCZ diagnosis wi h espec o heal hy
con ols (HC), based on he s udy o he opological p op-
e ies o g aphs de i ed om he unc ional connec i i y
be ween he nodes o he DMN in es ing s a e. We s a
om he assump ion ha he b ain can be unde s ood as
a complex ne wo k, and we use g aph heo y as a concep-
ual amewo k o s udying he opological ea u es o
hese ne wo ks.
P e ious g aph- heo e ical esea ch in SCZ and o he
psychia ic diso de s has demons a ed a dis up ed bal-
ance be ween seg ega ion and in eg a ion wi hin he
unc ional b ain ne wo ks. Thus, Rubino e al. (2009),
analyzing weigh ed g aphs, ound ha he g oup o indi-
iduals wi h an SCZ diagnosis displayed lowe clus e ing
(an indica o o seg ega ion) and sho e pa h leng hs
(an indica o o in eg a ion) in compa ison o he HC
g oup. Likewise, Vé es e al. (2012) ound ha
opological p ope ies o clus e ing and modula i y
(i.e., seg ega ion) we e somewha educed in childhood-
onse SCZ-diagnosed indi iduals. S udying he opologi-
cal p ope ies o unc ional b ain ne wo ks, (Lynall
e al., 2010; Rubino e al., 2009) ound ha hey we e
less hie a chical, less small-wo ld, less clus e ed and less
e icien ly wi ed in indi iduals wi h an SCZ diagnosis.
Compa ing HC and indi iduals wi h an SCZ diagnosis,
(Basse e al., 2008) ound educed hie a chy and
inc eased connec ion dis ance in SCZ, and (Liu
e al., 2008) ound ha indi iduals wi h an SCZ diagnosis
exhibi ed lowe clus e ing and lowe pa h leng h han
HC, bu no di e ences we e ound be ween g oups in
e iciency. Du ing a wo-back wo king memo y ask,
Micheloyannis e al. (2006) ound ha indi iduals wi h
an SCZ diagnosis did no show small-wo ld p ope ies o
alpha, be a and gamma elec oencephalog am (EEG) e-
quency bands.
All hese wo ks show he bene i s o g aph heo y
o cha ac e ize unc ionally complex ne wo ks.
Howe e , mos o hem a e ocused on he s udy o he
b ain sys em as a whole (e.g., Basse e al., 2008;
Rubino e al., 2009) o , a mos , on he cha ac e iza-
ion o in e egional unc ional ela ionships (e.g., Liu
e al., 2008). Ve y ew include, speci ically, he s udy o
unc ional connec i i y wi hin he DMN. On he o he
hand, al hough mos o he ci ed wo ks ake ad an age
o he high spa ial esolu ion p o ided by MRI, how-
e e , his high empo al esolu ion is a he cos o
lowe empo al esolu ion. Fu he mo e, MRI
measu es ac i a ion- ela ed hemodynamics a he han
neu onal ac i i y in i sel (Bullmo e & Spo ns, 2009).
Finally, mos o hese pape s o e a s a iona y iew o
he unc ional ela ionships be ween ne wo k commu-
ni ies, as hey end o calcula e unc ional ela ionships
om measu es based on a e ages o he eco dings.
Fo hese easons, in he p esen wo k, we will use
EEG es ing s a e eco dings o compa e he dynamical
opological p ope ies o he DMN in pa ien s wi h SCZ
and HC.
Speci ically, we wan o compa e he dynamics o
in eg a ion (global e iciency) and seg ega ion
(modula i y) o he DMN in SC pa ien s and HC. To his
end (see Figu e 1, o a de ailed wo k low), we p oceeded
o eco d he EEG o indi iduals wi h an SCZ diagnosis
and HC du ing 161 s o es ing s a e. We hen pe o med
he econs uc ion o he co ical sou ces, which we
subsequen ly pa celed in o he 14 DMN egions using he
Desikan–Killiany a las (Desikan e al., 2006). Fo each o
hese egions and o each subjec , using a sliding win-
dow sys em, we ob ained 798 co ela ion ma ices,
2IGLESIAS-PARRO ET AL.
14609568, 0, Downloaded om h ps://onlinelib a y.wiley.com/doi/10.1111/ejn.15970 by Uni e sidad De G anada, Wiley Online Lib a y on [09/05/2023]. See he Te ms and Condi ions (h ps://onlinelib a y.wiley.com/ e ms-and-condi ions) on Wiley Online Lib a y o ules o use; OA a icles a e go e ned by he applicable C ea i e Commons License
co esponding o each one o he 798 sliding windows,
ha we bina ized using a ious h esholds ( om 0.1 o
0.6). F om each o hese unc ional ne wo ks o e ime,
we ob ained modula i y and o e all e iciency. Fo each
ime se ies o hese wo measu es (global e iciency and
modula i y) ha epo edly map in eg a ion and seg ega-
ion, espec i ely, we calcula ed he coe icien o a ia-
ion and he mean and hen p oceeded o compa e hem
be ween g oups.
2|METHODS
2.1 |Pa icipan s
The sample o his s udy consis ed o a g oup o indi id-
uals wi h an SCZ diagnosis and a g oup o heal hy con-
ols. The g oup o indi iduals wi h an SCZ diagnosis
(he eina e e e ed o as he SCZ g oup) consis ed o
11 pa icipan s who we e ec ui ed a he Hospi al Uni-
e si a io San Agus ín (Lina es, Jaén). The inclusion c i-
e ia o pa icipa ion we e an ICD-10 diagnosis o
schizoph enia (F20), psycho ic diso de (F23) o schizo-
ph enic diso de (F25). The pa icipan ’s diagnosis was
made by he uni psychologis . The mean age o his
g oup was 36.27 yea s (SD =10.28 yea s; min =23,
max =53). Ou o all he pa icipan s, wo (18.18%) we e
women. All pa icipan s we e dex e ous. Rega ding he
educa ional le el o he pa icipan s, wo had p ima y
educa ion, eigh had seconda y educa ion and one had
highe educa ion. Rega ding he medica ion,
all pa icipan s we e ecei ing an ipsycho ic medica ion
(all a ypical). In addi ion o an ipsycho ics, one o he
pa icipan s was ecei ing an idep essan s. Due o di e -
ences in ac i e p inciples, doses and adminis a ion
me hods, we con e ed he doses o all an ipsycho ics
in o chlo p omazine equi alen s (M=818.18 mg,
SD =407.75 mg).
Twen y pa icipan s in he con ol g oup (he eina -
e e e ed o as he HC g oup) we e ec ui ed om
he s uden s o he Uni e si y o Jaén, he s a o he
Uni e si y S . Agus in Hospi al o Lina es (Jaén) and an
Adul School o Lina es (Jaén). The a e age age o his
g oup was 40.72 yea s (SD =11.96 yea s; min =23,
max =57). Ou o all pa icipan s, se en (35%) we e
women. Only wo pa icipan s we e le -handed.
Rega ding he educa ional le el o he pa icipan s, one
had p ima y educa ion, 12 had seconda y educa ion
and se en had highe educa ion. The e was no
signi ican associa ion be ween sex and g oup
(χ
2
[1, N =31] =0.97, p=0.32) o be ween g oup and
educa ion le el (χ
2
[2, N =31] =3.29, p=0.19). The
FIGURE 1 P incipal s eps in he wo k low. (a) EEG measu emen in HC and SCZ. (b) Sou ce modeling. (c) Pa cella ion o he de aul
mode ne wo k. (d) We calcula e wi h co ela ion coe icien he unc ional connec i i y in ime (798 ma ices). (e) Bina ize he ma ices wi h
h esholds om 0.1 o 0.6. ( ) We cons uc he unc ional ne wo ks (in ime, one o each ma ix and a each h eshold). (g) We ob ain o
each ma ix and a each h eshold, ne wo k measu emen s: modula i y and global e iciency. (h) Cha ac e ize he dynamics o he se ies as
well as s a iona y measu es. (i) Be ween-g oup compa isons. EEG, elec oencephalog am; HC, heal hy con ols; SCZ, schizoph enia; ROI,
egion o in e es .
IGLESIAS-PARRO ET AL.3
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g oups did no di e signi ican ly wi h espec o age
( [29] =1.03, p=0.30).
Fo bo h g oups, he exclusion c i e ia we e ei he a
concu en diagnosis o neu ological diso de , a concu -
en diagnosis o subs ance abuse diso de , a his o y o
de elopmen al disabili y, an inabili y o sign in o med
consen , ision diso de s ( ision diso de s ha , al hough
co ec ed wi h su ge y, glasses o con ac lenses, esul in
a loss o isual acui y, e.g., ca a ac s) o hea ing diso de s
(unless co ec ed wi h hea ing aids o su ge y). In addi-
ion, an exclusion c i e ion o he con ol g oup was he
diagnosis o a men al diso de (as epo ed e bally by
he pa icipan s). All pa icipan s ga e w i en in o med
consen in acco dance wi h he Decla a ion o Helsinki,
and he Jaén Resea ch E hics Commi ee app o ed he
s udy.
The Spanish e sion (Pe al a & Cues a, 1994) o he
Posi i e and Nega i e Synd ome Scale (PANSS, Kay
e al., 1989) was used o assess psychopa hology. PANSS
consis s o 30 i ems ha e alua e schizoph enic syn-
d ome, and each i em is sco ed acco ding o a scale o
7 deg ees o in ensi y o se e i y, whe e 1 is equi alen o
he absence o he symp om and 7 o he p esence wi h
se e i y. PANSS can be di ided in o h ee subscales: he
posi i e subscale o 7 i ems (M=13.95, SD =4.5), he
nega i e subscale o 7 i ems (M=19.27, SD =8.18), and
he gene al psychopa hology subscale o 16 i ems ha
e alua es he p esence o o he symp oms in he pa ien
(dep ession, anxie y and diso ien a ion, among o he s)
(M=29.36, SD =7.06).
2.2 |EEG acquisi ion
EEG da a we e acqui ed while he pa icipan s we e
ins uc ed o es wi h hei eyes open and look a a s a-
iona y c oss on a moni o . An ac i e elec ode cap
(ac iCAP™) was used o acqui e da a om he in e na-
ional 10–20 sys em o 32 scalp si es. All elec odes we e
e e enced o bo h mas oids. Elec ode impedance was
kep lowe han 5 kΩ. The EEG da a we e collec ed o
161 s a a a e o 500 Hz h ough a B ainAmps™ampli-
ie . Da a p ocessing was pe o med wi h he B ain
Vision Analyze so wa e EEGLAB (Delo me &
Makeig, 2004) and MATLAB cus om sc ip s. We applied
a bandpass il e wi h cu -o equencies o 0.5 and
30 Hz. Blinks and o he a e ac s we e ex ac ed using
in omax independen componen analysis (ICA) (Bell &
Sejnowski, 1995). ICA componen s wi h a e ac s we e
selec ed ia isual inspec ion o he scalp opog aphy,
powe spec a and aw ac i i y om all componen s.
Once all noisy componen s we e selec ed, hey we e elim-
ina ed om he o iginal signals.
2.3 |Sou ce econs uc ion
A sou ce model consis ing o 15,002 cu en dipoles was
used o calcula e Ke nel in e sion ma ices o each
subjec wi h sLORETA implemen ed in B ains o m
(Pascual-Ma qui, 2002). As an MRI empla e, we used he
ICBM152 b ain, dis ibu ed wi h he B ains o m package.
Dipole o ien a ions we e cons ained no mal o he
co ex. Using he bounda y elemen me hod (BEM) as
implemen ed in he OpenMEEG model (Co si
e al., 2020; Kybic e al., 2005), he o wa d EEG model
was compu ed o each subjec . We used he iden i y
ma ix as he noise co a iance ma ix.
2.4 |Pa cella ion
The sou ce model was hen ana omically pa cella ed
using he Desikan–Killiany a las (Desikan e al., 2006)
a ailable in B ains o m, as no indi idual ana omies o
he pa icipan s we e a ailable. Au oma ed pa cella ion
by his me hod has been shown o be compa able o
manual labelling (Fischl e al., 2004). Acco ding o his
pa celing scheme, he DMN was de ined as he ollowing
14 egions o in e es (ROIs): Is hmus cingula e L, Is h-
mus cingula e R, La e al o bi o on al L, La e al o bi o
on al R, Medial o bi o on al L, Medial o bi o
on al R, Pa ahippocampal L, Pa ahippocampal R, Pos-
e io cingula e L, Pos e io cingula e R, P ecuneus L,
P ecuneus R, Ros al an e io cingula e L and
Ros al an e io cingula e R (whe e L s ands o le and
R o igh ).
2.5 |Func ional connec i i y
We calcula ed he Spea man co ela ion coe icien
be ween he 14 nodes o he DMN ha we ob ained a e
pa cella ion. To ake ad an age o he empo al esolu-
ion o he EEG eco dings and hus be able o explo e
he empo al dynamics o in eg a ion and seg ega ion in
he DMN, we used a sliding window o 2000 ms wi h a
90% o o e lap on each s ep and ob ained a o al o
798 unc ional connec i i y ma ices o each pa icipan .
The du a ion o he ime se ies o which we applied he
sliding window was 161 s.
The opological p ope ies o he ne wo ks ob ained
a e bina izing he ma ix o in e egional co ela ions
will depend on he choice o he h eshold alue. In his
sense, i he h eshold is high and he esul ing numbe
o edges is low, he ne wo k will be poo ly connec ed and
some egional nodes may be disconnec ed. On he o he
hand, i he h eshold is low, and he numbe o edges is
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14609568, 0, Downloaded om h ps://onlinelib a y.wiley.com/doi/10.1111/ejn.15970 by Uni e sidad De G anada, Wiley Online Lib a y on [09/05/2023]. See he Te ms and Condi ions (h ps://onlinelib a y.wiley.com/ e ms-and-condi ions) on Wiley Online Lib a y o ules o use; OA a icles a e go e ned by he applicable C ea i e Commons License
high, he ne wo k will be mo e densely connec ed bu
will also ha e a andom opology (Basse e al., 2008).
Following he ecommenda ion o Rubino and Spo ns
(2010) ha ne wo ks should ideally be cha ac e ized
ac oss a b oad ange o h esholds, in his pape , we used
h esholds om 0.1 o 0.6 in s eps o 0.1. Th esholds o
0.1–0.6 p oduce ne wo ks limi ed o 90–40% o he
120 possible edges in a ully connec ed ne wo k o
14 nodes. Following Su e al. (2015), we ha e selec ed his
ange o cos s because hey co e he spec um o
meaning ul ne wo ks o es ing s a e da a. Thus, we
ob ained a o al o 798 bina y ma ices (unweigh ed and
undi ec ed) o each o he six h esholds explo ed. In his
s udy, we emo ed nega i e connec ions om he
ne wo k o a oid in e e ence (Mu phy & Fox, 2017;
Rubino & Spo ns, 2010).
2.6 |G aph measu es
Fo each bina y g aph, a each h eshold le el, we calcu-
la e he global e iciency and he ne wo k modula i y.
The g aph measu es we e calcula ed wi h he B ain Con-
nec i i y Toolbox, a MATLAB oolbox de eloped by
(Rubino & Spo ns, 2010). These da a, anonymized, a e
s o ed in Figsha e (DOI: 10.6084/m9. igsha e.21975899)
and also he sc ip s (DOI: 10.6084/m9. igsha e.21990005).
Bo h will be a ailable upon easoned eques .
Acco ding o Rubino and Spo ns (2010), he
unc ional seg ega ion me ics cap u e he abili y o a
ne wo k o pe o m specialized p ocessing. The p esence
o clus e s in unc ional ne wo ks is in e p e ed as an
indica ion o seg ega ed neu al p ocessing. In his pape ,
we will measu e ne wo k seg ega ion using modula i y.
Modules in ne wo ks co espond o clus e s o nodes ha
a e in e nally s ongly coupled bu ex e nally only weakly
coupled (Spo ns & Be zel, 2016). Acco ding o Simon
(1962), modula i y is a dis inc i e cha ac e is ic o com-
plex sys ems, and he impo ance o modula b ain ne -
wo ks in shaping b ain dynamics has been iden i ied as a
powe ul incen i e o empi ically s udy changes in b ain
modula i y in men al diso de s (Fo ni o e al., 2015).
Heu is ically, modula i y compa es he numbe o edges
inside a clus e wi h he expec ed numbe o edges ha
one would ind in he clus e i he ne wo k we e a an-
dom ne wo k (wi h he same numbe o nodes, bu an-
domly a ached). Acco ding o Newman and Gi an
(2003), modula i y can be quan i ied by he ollowing
exp ession:
Q¼1
2EX
ij
Aij eij

δmi,mj

:
whe e A
ij
is he ij elemen o he adjacency ma ix o he
g aph G ( he connec ion s a us be ween iand j:A
i
=1
when link ij exis s; A
ij
=0, o he wise), e
ij
is he ac ion
o edges in he ne wo k ha connec e ices in he same
communi y and δ(m
i
,m
j
) is he K onecke del a unc ion
and equals 1 i nodes iand jbelong o he same module
(i.e., m
i
=m
j
) and 0 o he wise.
On he o he hand, he in eg a ion me ics cap u e
he abili y o apidly combine specialized in o ma ion
om dis ibu ed b ain egions. In his wo k, we selec ed
global e iciency as he measu e o ne wo k in eg a ion.
A la ge global e iciency alue o he b ain ne wo k ep-
esen s a highe in o ma ion ansmission e iciency and
a highe in eg a ion deg ee o he b ain ne wo k. In unc-
ional b ain ne wo ks, global e iciency is in e sely
ela ed o he opological dis ance be ween nodes
( he pa h leng h) and p o ides a measu e o he o e all
capaci y o pa allel in o ma ion ans e and in eg a ed
p ocessing among dis ibu ed componen s o he sys em
wi h he ad an age o e he a e age pa h leng h ha i
can be calcula ed in disconnec ed ne wo ks (Bullmo e &
Spo ns, 2012; La o a & Ma chio i, 2001). The ne wo k
can be ep esen ed as a g aph G(N,M) wi h Nnodes and
Medges. The global e iciency is de ined as ollows:
Eglob ¼1
NN1ðÞ
X
j≠iG
1
lij
whe e l
ij
is he mean o he sho es pa h leng h ( he a e -
age numbe o s eps along he sho es pa hs o all possi-
ble pai s o ne wo k nodes) be ween nodes iand j. Fo an
undi ec ed g aph o Nnodes, he mean o he sho es
pa h leng h is as ollows:
lij ¼1
NN1ðÞ
X
j≠iG
dij
whe e dij is he leng h o he sho es pa h be ween nodes
iand j.
Fo a mo e echnical desc ip ion o g aph-based me -
ics equen ly used in b ain ne wo ks, see Bullmo e and
Spo ns (2009) and Rubino and Spo ns (2010). A g aphic
ep esen a ion o hese concep s can be ound in
Figu e 2.
3|DATA ANALYSIS AND
RESULTS
F om he bina y g aphs, we ob ained he dependen
a iables (e iciency and modula i y) bo h s a ic and
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dynamic. These da a we e analyzed using mixed-e ec s
analysis o a iance wi h, g oup, h eshold and hei
in e ac ion as ixed ac o s and pa icipan s as andom
ac o s. Analyses we e pe o med in R using he lme ()
unc ion o he lme4 package (Ba es e al., 2015). Pos hoc
compa isons and in e ac ion analyses we e made using
emmeans package (Len h, 2021). To con ol he e o
ype I due o he numbe o compa isons we used he d
p ocedu e (Benjamini & Yeku ieli, 2001).
3.1 |Dynamic measu es
In o de o s udy he empo al dynamics o modula i y
and e iciency, o bo h me ics we calcula ed he a ia-
ion coe icien (VC), and hese da a we e summi ed o a
mixed model wi h in e cep as a andom ac o and g oup
and h eshold as ixed ac o s. The VC allows o compa e
he a iabili y o he se ies independen ly o he means o
each g oup.
The esul s o he coe icien o a ia ion o
modula i y (see Figu e 3) showed a signi ican e ec o
g oup (F[1,31] =5.25; p=0.02), a signi ican e ec o
h eshold (F[5155] =9.64; p< 0.01) and a signi ican
e ec o he in e ac ion (F[5155] =2.29; p=0.04).
Pai wise compa isons o e he in e ac ion e ealed
ha o h eshold alues o 0.6, he a iabili y in modu-
la i y was signi ican ly highe ( [199] =3.80; p< 0.01)
o HC (M=98.6, SD =111.0) han o SCZ
(M=36.5, SD =36.3).
The esul s o he coe icien o a ia ion o e iciency
(see Figu e 4) showed a signi ican e ec o h eshold
(F[5155] =3.85; p< 0.01). No signi ican e ec o g oup
(F[1,31] < 1) nei he o he in e ac ion (F[5155] =1.03,
p=0.39) was ound. Pos hoc compa isons showed he
ollowing signi ican di e ences in VC depending on
h eshold: T1 < T3 ( [145] =3.39, p< 0.01), T1 < T4
( [145] =2.95, p< 0.01), T2 < T3 ( [145] =2.32,
p=0.02) and T6 < T4 ( [145] =2.41, p=0.01). Signi i-
can con as s a e shown in Table 1.
3.2 |S a iona y measu es
We also calcula ed he means ac oss all ime windows o
modula i y and e iciency and hese da a we e summi ed
o a mixed model wi h in e cep as a andom ac o and
g oup and h eshold as ixed ac o s.
The esul s o he mean o modula i y (see Figu e 5)
showed a signi ican e ec o g oup (F[1,31] =7.43;
p=0.01) and a signi ican e ec o h eshold (F[5155]
=27.69; p< 0.01), bu no signi ican e ec was ound o
he in e ac ion (F[5155] =2.25; p=0.051). Pos hoc
compa isons showed he mean o modula i y was
signi ican ly ( [33.1] =2.63; p=0.01) highe o he HC
g oup (M=0.99, SD =0.02) han o he SCZ g oup
FIGURE 2 Ne wo k opologies and
g aph measu es. (a) Ne wo k opology
examples: Random ne wo ks, wi h
andomly de e mined connec ions, ha e
high global e iciency, as shown by he
many connec ions c ossing he cen e o
he g aph, and low modula i y, as
shown by he ela i ely ew connec ions
be ween nea by nodes. La ice ne wo ks
show he e e se pa e n. (b) A
simula ed ne wo k is used o illus a e
common e ms in ne wo k analysis.
Nodes a e ep esen ed as ci cles, and
edges a e ep esen ed as lines.
6IGLESIAS-PARRO ET AL.
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(M=0.89, SD =0.03). Signi ican pos hoc compa isons
o h eshold a e shown in Table 2.
The esul s o he mean o e iciency (see Figu e 6)
showed a signi ican e ec o h eshold (F[5155]
=342.83; p< 0.01) and a signi ican e ec o in e ac ion
(F[5155] =2.41; p=0.03). No signi ican e ec o g oup
(F[1,31] < 1) was ound. Pai wise compa isons o e he
in e ac ion e ealed ha o a h eshold alue o 0.5, he
mean in e iciency was signi ican ly lowe ( [89.5] =2.00;
p=0.04) o HC (M=0.16, SD =0.01) han o indi id-
uals wi h an SCZ diagnosis (M=0.19, SD =0.01).
3.3 |Rela ionship wi h symp om
se e i y
To s udy he possible ela ionship be ween schizoph enia
symp om se e i y and g aph measu es, we calcula ed
FIGURE 4 Main e ec o he
coe icien o a ia ion o e iciency
depending on h eshold. VC, a ia ion
coe icien .
FIGURE 3 Main e ec s and
in e ac ion o he coe icien o
a ia ion o modula i y depending on
g oup and h eshold. (a) In e ac ion
g oup by h eshold. (b) Main e ec o
g oup. (c) Main e ec o h eshold. SCZ,
schizoph enia; VC, a ia ion coe icien .
IGLESIAS-PARRO ET AL.7
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Spea man’s co ela ion coe icien be ween PANSS sub-
scales and he measu es o in eg a ion and seg ega ion.
In addi ion, we included he chlo p omazine equi alen
dose and he age o he pa ien s. The esul s a e p esen ed
in Table 3.
As can be seen in he able abo e, no signi ican ela-
ionships we e ound be ween ne wo k measu es and
symp oma ology. These esul s a e in line wi h hose
ob ained by o he au ho s (Lynall e al., 2010; Shon
e al., 2018), who also ound no signi ican ela ionship
be ween symp om se e i y and modula i y o e iciency.
4|DISCUSSION
The heal hy human b ain ope a es in a pe manen
dynamic o seg ega ion and in eg a ion o in o ma ion
om in e nal and ex e nal sou ces. This capaci y o
dynamic in eg a ion–seg ega ion can be conside ed an
e olu iona y success, necessa y o su i al in an e e -
changing en i onmen (Deco e al., 2015). The cou se o
ce ain men al illnesses, howe e , could a ec his
dynamic. In his sense, i has been p oposed ha SCZ
could be ela ed o an imbalance in he in o ma ion
in eg a ion–seg ega ion dynamics (F is on & F i h, 1995).
Speci ically, DMN unc ioning has been ound o be
abno mal in schizoph enia (Hu e al., 2017).
On he o he hand, esea ch on b ain o ganiza ion
based on he es ing s a e has la gely igno ed he po en-
ial o empo al a iabili y, implici ly assuming ha he
ela ionships be ween and wi hin he di e en b ain ne -
wo ks a e s a iona y ac oss he du a ion o he eco dings
(Allen e al., 2014). Howe e , some esea ch ha has
FIGURE 5 Signi ican Main e ec s
o he mean o modula i y depending
on g oup and h eshold. (a) Main e ec
o g oup. (b) Main e ec o h eshold.
SCZ, schizoph enia.
TABLE 2 Signi ican pos hoc compa isons o he mean o
modula i y depending on h eshold.
Con as d a io p alue
0.1–0.4 166 2.71 0.01
0.1–0.5 166 5.72 <0.01
0.1–0.6 166 8.92 <0.01
0.2–0.4 166 2.75 <0.01
0.2–0.5 166 5.76 <0.01
0.2–0.6 166 8.96 <0.01
0.3–0.5 166 4.71 <0.01
0.3–0.6 166 7.91 <0.01
0.4–0.5 166 3.00 <0.01
0.4–0.6 166 6.20 <0.01
0.5–0.6 166 3.20 <0.01
TABLE 1 Signi ican pos hoc compa isons o he mean o
e iciency depending on h eshold.
Con as d a io p alue
0.1–0.3 166 3.39 <0.01
0.1–0.4 166 2.95 <0.01
0.2–0.3 166 2.32 0.02
0.3–0.6 166 2.84 <0.01
0.4–0.6 166 2.41 0.01
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explici ly s udied es ing-s a e unc ional connec i i y
dynamics o he DMN has clea ly shown he ime- a ying
na u e o connec i i y (Chang & Glo e , 2010), e en in
indi iduals wi h an SCZ diagnosis (Sako
glu e al., 2010).
In he p esen wo k, we aimed o explo e he dynam-
ics o in eg a ion–seg ega ion in he DMN o pa ien s and
heal hy con ols. Fo his pu pose, om EEG eco dings,
we ob ained unc ional ne wo ks o e ime om which
we calcula ed he global e iciency and modula i y using
di e en h esholds o bina ise he ma ices. To s udy
he empo al e olu ion o hese indica o s, we calcula ed
he coe icien o a ia ion and compa ed i depending on
he g oups o pa icipan s (SCZ and HC), he h esholds
(0.1 o 0.6), and he in e ac ion be ween hese ac o s.
The esul s we ob ained ega ding he a iabili y o
he modula i y, indica e a la ge epe oi e o s a es o
connec i i y in he HC g oup han in he g oup o indi-
iduals wi h an SCZ diagnosis, pa icula ly in he adja-
cency ma ices ob ained a highe h esholds. These
esul s could sugges al e ed dynamic pe o mance o
b ain g aphs in indi iduals wi h an SCZ diagnosis and
a e in line wi h p e ious wo k (Alexande -Bloch
e al., 2010; Ro schy e al., 2012; Yu e al., 2015) in which
also has been ound ha he connec i i y s a es o HCs
FIGURE 6 Signi ican main e ec s
and in e ac ion o he mean o
e iciency depending on g oup and
h eshold. (a) In e ac ion g oup by
h eshold. (b) Main e ec o h eshold.
SCZ, schizoph enia.
TABLE 3 Co ela ion coe icien s and p alues (be ween b acke s) o PANSS, dynamical and s a iona y measu es o modula i y and
e iciency, age o pa icipan s and medica ion (CPZ).
PANSS P PANSS N PANSS G
Modula i y
M
Modula i y
VC
E iciency
M
E iciency
VC CPZ
PANSS N 0.43 (0.18)
PANSS G 0.79* (< .01) 0.74* (0.01)
Modula i y M 0.27 (0.43) 0.25 (0.47) 0.01 (0.98)
Modula i y
VC
0.21 (0.52) 0.26 (0.43) 0.20 (0.55) 0.57 (0.07)
E iciency M 0.36 (0.26) 0.21 (0.53) 0.48 (0.14) 0.22 (0.52) 0.71* (0.02)
E iciency VC 0.33 (0.31) 0.05 (0.89) 0.48 (0.14) 0.17 (0.61) 0.62* (0.05) 0.90* (< .01)
CPZ 0.39 (0.23) 0.44 (0.18) 0.36 (0.28) 0.08 (0.82) 0.42 (0.21) 0.30 (0.37) 0.30 (0.38)
Age 0.28 (0.41) 0.31 (0.36) 0.17 (0.63) 0.16 (0.65) 0.36 (0.27) 0.70* (0.02) 0.72* (0.02) 0.51 (0.11)
Abb e ia ions: CPZ, chlo p omazine equi alen ; Modula i y and E iciency M, mean measu es o modula i y and e iciency; Modula i y and
E iciency VC: a ia ion coe icien measu es o modula i y and e iciency; PANSS, Posi i e and Nega i e Synd ome Scale; PANSS G: gene al
psychopa hology; PANSS N, nega i e symp oms; PANSS P, posi i e symp oms.
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