Table Of ContentSpringer Theses
Recognizing Outstanding Ph.D. Research
Javier Gomez-Pilar
Characterization
of Neural Activity
Using Complex
Network Theory
An Application to the Study
of Schizophrenia
Springer Theses
Recognizing Outstanding Ph.D. Research
Aims and Scope
The series “Springer Theses” brings together a selection of the very best Ph.D.
theses from around the world and across the physical sciences. Nominated and
endorsed by two recognized specialists, each published volume has been selected
foritsscientificexcellenceandthehighimpactofitscontentsforthepertinentfield
of research. For greater accessibility to non-specialists, the published versions
includeanextendedintroduction,aswellasaforewordbythestudent’ssupervisor
explainingthespecialrelevanceoftheworkforthefield.Asawhole,theserieswill
provide a valuable resource both for newcomers to the research fields described,
and for other scientists seeking detailed background information on special
questions. Finally, it provides an accredited documentation of the valuable
contributions made by today’s younger generation of scientists.
Theses are accepted into the series by invited nomination only
and must fulfill all of the following criteria
(cid:129) They must be written in good English.
(cid:129) ThetopicshouldfallwithintheconfinesofChemistry,Physics,EarthSciences,
Engineeringandrelatedinterdisciplinary fields such asMaterials,Nanoscience,
Chemical Engineering, Complex Systems and Biophysics.
(cid:129) The work reported in the thesis must represent a significant scientific advance.
(cid:129) Ifthethesisincludespreviouslypublishedmaterial,permissiontoreproducethis
must be gained from the respective copyright holder.
(cid:129) They must have been examined and passed during the 12 months prior to
nomination.
(cid:129) Each thesis should include a foreword by the supervisor outlining the signifi-
cance of its content.
(cid:129) The theses should have a clearly defined structure including an introduction
accessible to scientists not expert in that particular field.
More information about this series at http://www.springer.com/series/8790
Javier Gomez-Pilar
Characterization of Neural
Activity Using Complex
Network Theory
An Application to the Study of Schizophrenia
Doctoral Thesis accepted by
University of Valladolid, Spain
123
Author Supervisors
Dr. Javier Gomez-Pilar Dr. RobertoHornero Sánchez
Biomedical Engineering Group Biomedical Engineering Group
University of Valladolid University of Valladolid
Valladolid, Spain Valladolid, Spain
CentrodeInvestigaciónBiomédica
Dr. Jesús PozaCrespo
enReddeBioingeniería
Biomedical Engineering Group
Biomateriales y Nanomedicina
University of Valladolid
(CIBER-BBN)
Valladolid, Spain
Valladolid, Spain
ISSN 2190-5053 ISSN 2190-5061 (electronic)
SpringerTheses
ISBN978-3-030-49899-3 ISBN978-3-030-49900-6 (eBook)
https://doi.org/10.1007/978-3-030-49900-6
©TheEditor(s)(ifapplicable)andTheAuthor(s),underexclusivelicensetoSpringerNature
SwitzerlandAG2021
Thisworkissubjecttocopyright.AllrightsaresolelyandexclusivelylicensedbythePublisher,whether
thewholeorpartofthematerialisconcerned,specificallytherightsoftranslation,reprinting,reuseof
illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and
transmissionorinformationstorageandretrieval,electronicadaptation,computersoftware,orbysimilar
ordissimilarmethodologynowknownorhereafterdeveloped.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this
publicationdoesnotimply,evenintheabsenceofaspecificstatement,thatsuchnamesareexemptfrom
therelevantprotectivelawsandregulationsandthereforefreeforgeneraluse.
The publisher, the authors and the editors are safe to assume that the advice and information in this
book are believed to be true and accurate at the date of publication. Neither the publisher nor the
authorsortheeditorsgiveawarranty,expressorimplied,withrespecttothematerialcontainedhereinor
for any errors or omissions that may have been made. The publisher remains neutral with regard to
jurisdictionalclaimsinpublishedmapsandinstitutionalaffiliations.
ThisSpringerimprintispublishedbytheregisteredcompanySpringerNatureSwitzerlandAG
Theregisteredcompanyaddressis:Gewerbestrasse11,6330Cham,Switzerland
To Vero,
thanks for your infinite patience,
your constant smile,
your uninterrupted support.
’
Supervisors Foreword
ItismyhonortointroducetheThesisworkofDr.JavierGomez-Pilar,acceptedfor
publication within Springer Theses and awarded for the outstanding original work
carriedout.ThepaththatleadstotheThesisbeganin2012,whenDr.Gomez-Pilar
started his collaboration with our research group (Biomedical Engineering Group)
at the University of Valladolid, Spain. His first contact with biomedical signal
processing were the studies that Dr. Gomez-Pilar carried out during his Final
Degree Project in Telecommunications Engineering (“Spectral and nonlinear
analysis of the heart rate variability to aid in the diagnosis of apnea-hypopnea
syndrome”, 2012) and his Master Thesis in Information and Communications
Technologies(“Extractionandclassificationoffeaturesfromtheelectrocardiogram
andheartratevariability.Applicationtotheapnea-hypopneasyndrome”,2013);in
bothofthem,heobtainedthehighestqualifications.Sincethen,hewasendeavoring
to gain deeper knowledge of advanced signal processing methods and new
methodological approaches based on complex network theory. As a natural con-
sequence, he embarked on his career as a Ph.D. student in the Information and
Telecommunications Technologies Doctoral Program. In the period 2013–2018,
Dr. Gomez-Pilar collaborated in several R&D projects, mainly focused on neural
signal processing in psychiatric and neurological disorders. He defended his doc-
toralThesisattheUniversityofValladolidinDecember2018(“Characterizationof
Neural Activity using Complex Network Theory. Application to the Identification
of the Altered Neural Substrates in Schizophrenia”), in which he obtained the
highest quantification (Summa Cum Laude).
TheThesisofDr.Gomez-Pilarsummarizesanoriginalandoutstandingresearch
focusedonschizophrenia,aneuropsychiatricdisorderthatbadlyimpactsonhigher
cognitive functions. The original conferences and journal papers included in the
Thesispresentanovelframeworkbasedontwoconceptsofparamountimportance
in signal processing and information theory, respectively: time-frequency analysis
and entropy. Thanks to the collaboration with the University Clinical Hospital of
Valladolid, Dr. Gomez-Pilar explored the neural underpinnings associated to the
cognitive processes that govern attention and attribution of relevance (salience)
during an auditory oddball paradigm. The analyses carried out in the Thesis are
vii
viii Supervisors’Foreword
basedonEvent-RelatedPotentials(ERPs)usingasingle-trialapproachtobeableto
capture the phase-based information of neural activity. Initially, the Thesis
addresses the relationship between the fluctuations of the time-frequency content
and entropy to explain the disruption that schizophrenia elicits on ERPs during a
cognitivetask.Theobtainedresultsconstitutethefirstevidenceonanalteredability
ofschizophreniapatientstomodulatetheirneuralactivity,whichbadlyaffectstheir
cognitiveperformance.Functionalgraphsareusedtogainadeeperinsightintothe
underlying neural processes involved in the attribution of relevance during the
cognitive task. For this purpose, several ERP-based chronnectomic measures were
usedintheThesistostudyhowthefunctionalnetworkisreorganized.Furthermore,
novel measures are introduced to explore the irregularity and complexity of net-
work topology, as well as to unravel the relationships between functional and
structural brain networks. The obtained results lead to a thorough characterization
oftime-varyingfunctionalnetworksduringtheoddballtaskandprovidenewclues
on how the secondary neural pathways play an important role to appropriately
reorganize the neural network. Both analyses (i.e., time-frequency and chronnec-
tomics) rely on entropy as a crucial concept to quantify the alterations of a
non-linear and dynamical system such as the brain. Finally, the original combi-
nation of concepts leads to a new methodology to model network reorganization
duringthecognitivetaskusingin-silicosimulations.Theresultsconfirmthecrucial
importanceofsecondaryneuralpathwaysand,interestingly,suggestthatthealtered
neuralsubstrateinschizophreniareflectstheinherentheterogeneityofthedisorder.
These novel research outcomes motivate indeed new and promising research lines
that could lead to a redefinition of the diagnosis of schizophrenia based on a
biological substrate rather than on a symptomatologic identification.
Valladolid, Spain Dr. Jesús Poza
March 2020 Dr. Roberto Hornero
Foreword
Bioengineering research is focused on carrying out research activities that pursue
the generation of new knowledge and the development of technological solutions
aimed at understanding and controlling human biological systems and their rela-
tionship with the environment. As a result, the analysis and evaluation of bodily
functions and structures is contemplated, as well as the compensation of certain
deficits, dependencies and pathologies. This work includes the capture of signals
andtheirprocessing,thesubsequentanalysisofthedataderivedfromthem,aswell
as any other type of biological data present, and the modelling of biosystems. In
different phases of this process, knowledge from various sources can be integrated
to guide the analysis of the data more accurately or complement the knowledge
resulting from it. The end point of this process culminates with the creation of
autonomous physical devices with communication capabilities, which can respond
to changing conditions in their environment, and multimodal two-way communi-
cationstrategies.ThemonographwrittenbyJavierGómez-Pilarisacontributionin
theareaofbioengineering,whichhasbeenreceivingagrowingdealofattentionby
the research community in the latest few years.
Thecontentsarefocusedonthestudy,developmentandassessmentofaspecific
framework to investigate neural interactions from the perspective of Complex
NetworkTheory. Particularly,thenewmeasures andthenovel models providedin
this Thesis are aimed at improving our current knowledge of schizophrenia
disorder.
Remarkably, the monograph is based on the first author’s doctoral thesis,
awarded for best Ph.D. Thesis in Bioengineering during the third edition of the
award call organized by the Bioengineering group of the Comité Español de
Automática (CEA), the Spanish Committee of Automatic Control, in 2019.
ThisannualawardisaimedatrecognizingtheoutstandingPh.D.researchinthe
bioengineering field.Participationrequiresatleastoneofthethesis’supervisorsto
be a partner of CEA and a member of the Bioengineering group. The jury is
composed of three well-known doctors in the field: two of them are partners of
CEA, and the third one is a foreign professor.
ix
x Foreword
Atotalof5Ph.D.theses,examinedin2018,weresubmittedtothisthirdedition
in 2019. Notably, their authors show altogether a scientific production of about 30
publications in international indexed journals, with more than 20 works published
in the top-quartile journals of their categories.
Javier Gomez-Pilar’s Ph.D. thesis was selected by the Bioengineering group of
CEA as the best among other excellent candidates. His outstanding Ph.D. work
clearly deserves the label “the best of the best”, which is also the Springer Theses
motto. Through this publication, we hope that Javier’s work reaches a large
international audience and becomes a valuable source of information and inspira-
tion for other students working in the bioengineering field. On behalf of CEA, we
wish Javier to continue his outstanding career and to keep his genuine enthusiasm
for science.
New York, USA Dr. Eduardo Rocon
March 2020 Coordinator of the Bioengineering
Group of CEA best thesis award
