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P U E F
Dissertations in Health Sciences
Florinda Ines Maria Ferreri
TMS and TMS-EEG Studies
on the Excitability, Connectivity and
Plasticity of the Human Motor Cortex
FLORINDA INES MARIA FERRERI
TMSandTMS‐EEGstudiesonthe
excitability,connectivityandplasticityof
thehumanmotorcortex
TobepresentedbypermissionoftheFacultyofHealthSciences,UniversityofEasternFinlandfor
publicexaminationinML3,MedistudiaBuilding,onFriday,September9
th
,2011,at14:00
PublicationsoftheUniversityofEasternFinland
DissertationsinHealthSciences
Number69
DepartmentofClinicalNeurophysiology,InstituteofClinicalMedicine,SchoolofMedicine,Faculty
ofHealthSciences
UniversityofEasternFinland
Kuopio
2011
Kopijyvä
Kuopio,2011
SeriesEditors:
ProfessorVeli‐MattiKosma,M.D.,Ph.D.
InstituteofClinicalMedicine,Pathology
FacultyofHealthSciences
ProfessorHanneleTurunen,Ph.D.
DepartmentofNursingScience
FacultyofHealthSciences
ProfessorOlliGröhn,Ph.D.
A.I.VirtanenInstituteforMolecularSciences
FacultyofHealthSciences
Distributo
r:
UniversityofEasternFinland
KuopioCampusLibrary
P.O.Box1627
FI‐70211Kuopio,Finland
http://www.uef.fi/kirjasto
ISBN(print):978‐952‐61‐0505‐5
ISBN(pdf):978‐952‐61‐0506‐2
ISSN(print):1798‐5706
ISSN(pdf):1798‐5714
ISSN‐L:1798‐5706
III
Author’saddress: DepartmentofClinicalNeurophysiology,InstituteofClinicalMedicine
SchoolofMedicine,FacultyofHealthSciences
UniversityofEasternFinland
KUOPIO
FINLAND
DepartmentofNeurology
SchoolofMedicine
UniversityCampusBiomedicoofRome
ROME
ITALY
Supervisors: ProfessorEsaMervaala,MD,PhD
DepartmentofClinicalNeurophysiology,InstituteofClinicalMedicine
SchoolofMedi
cine,FacultyofHealthSciences
UniversityofEasternFinlandFaculty
KUOPIO
FINLAND
ProfessorPaoloMariaRossini,MD,PhD
DepartmentofNeurology
CatholicUniversityofRome
ROME
ITALY
DoctorSaraMäättä,MD,PhD
DepartmentofClinicalNeurophysiology,InstituteofClinicalMedicine
SchoolofMedicine,FacultyofHealthSciences
UniversityofEasternFin
landFaculty
KUOPIO
FINLAND
Reviewers: ProfessorMarkHallett,MD,PhD
HumanMotorControlSection
MedicalNeurologyBranch,NINDS
NationalInstituteofHealth
BETHESDA,MD
USA
ProfessorUlfZiemann,MD,PhD
DepartmentofNeurology
Goethe‐University
FRANKFURT
GERMANY
Opponent: ProfessorJohnRothwell,MD,PhD
DepartmentofNeurology
InstituteofNeurology,QueenSqua
re
LONDON
ENGLAND
IV
V
FerreriFlorindaInesMaria
TMSandEEG‐TMSstudiesonhumancorticalexcitability,connectivityandplasticity,86p.
UniversityofEasternFinland,FacultyofHealthSciences,2011
PublicationsoftheUniversityofEasternFinland.DissertationsinHealthSciencesNumber69.2011.86p.
ISBN(print):978‐952‐61‐0505‐5
ISBN(pdf
):978‐952‐61‐0506‐2
ISSN(print):1798‐5706
ISSN(pdf):1798‐5714
ISSN‐L:1798‐5706
ABSTRACT
Thisthesis,consistingoffiveoriginalpublications(I‐V)andasummary,exploresthe
feasibility of combining transcranial magnetic stimulation (TMS) and
electroencephalography (EEG) for the examination of the cortical excitability and
connectivity of the human cerebral cortex, both in healthy and pathological condition. It
addressessomeissuescrucialforabetterelucidationofthemechanismsunderlyinghuman
brainneuroplasticity.TheseriesofstudiesclearlydemonstratedthatTMS‐withorwithout
EEG‐ is asensitive and objectivemeasure of the effect ofdifferent kinds ofnon‐invasive
manipulation of the brain’s activity. Moreover TMS and TMS‐EEG co‐registration are
valuablemethodstostudycorticalexcitability,connectivityandfunctionalorganizationin
healthysubjects andneurologicalpatients such asAlzheimer’sdisease patients. Theyare
along with clinical, neuropsychological, andneuroimaging datainexpensive measures of
diseaseprogression,supplementingtraditionalmethodstoassesstheeffectsoftherapies.
Takentogether,thefindingspresentedinthisthesisareimportantfortheadoptionof
the TMS and TMS‐EEG co‐registration techniques as a tool for basic neurophysiological
researchand,inthefuture,evenforclinicaldiagnosticspurposes.
NationalLibraryofMedicalClassification:WL141.5.T7,WL150,WL307,WL335,WT155
Medical Subject Headings (MeSH): Transcranial Magnetic Stimulation; Electroencephalography;
Electromagnetic Fields; Electric Stimulation/methods; Motor Cortex; Evoked Potentials, Motor; Brain
Mapping;Brain/physiology;Brain/radiationeffects;CellularPhone;AlzheimerDisease
VI
VII
FerreriFlorindaInesMaria
TMSandEEG‐TMSstudiesonhumancorticalexcitability,connectivityandplasticity,86p.
UniversityofEasternFinland,FacultyofHealthSciences,2011
PublicationsoftheUniversityofEasternFinland.DissertationsinHealthSciencesNumber69.2011.86p.
ISBN(print):978‐952‐61‐0505‐5
ISBN(pdf
):978‐952‐61‐0506‐2
ISSN(print):1798‐5706
ISSN(pdf):1798‐5714
ISSN‐L:1798‐5706
TIIVISTELMÄ
Tässäväitöskirjatyössä,jokakoostuuviidestäosajulkaisustajaniidenyhteenvedosta,
tutkittiin transkraniaalisen magneettistimulaation (TMS) ja siihen yhdistetyn
aivosähkökäyrän (EEG) soveltuvuutta aivokuoren ärtyvyyden ja eri aivokuorialuiden
välisten toiminnallisten yhteyksien tutkimisessa. Tutkimus toi uutta tietoa aivokuoren
muovautuvuudesta. Tulokset osoittavat, että TMS – joko yhdistettynä EEG:hen tai ilman
sitä‐mittaa hyvin aivokuoren toiminnallisia muutoksia. Lisäksi tulokset osoittivat, että
TMS ja TMS‐EEG kuvaavat hyvin aivokuoren ärtyvyyttä, toiminnallisia yhteyksiä ja
toiminna
n muutoksia niin terveillä koehenkilöillä kuin neurologisilla potilaillakin (tässä
tutkimuksessa Alzheimerin tautia sairastavat potilaat). Menetelmää voi käyttää yhdessä
neuropsykologisten ja kuvantamistutkimusten kanssa, kun arvioidaan sairauden
etenemistä. Lisäksi TMS: n avulla voi arvioida lääkevastetta. Väitöskirjatyön tulokset
lisäävät TMS: n ja TMS‐EEG: n käytettävyyttä neuropsykologisessa tutkimustyössä ja
tulevaisuudessamyöskliinisessädiagnostiikassa.
Yleinensuomalainenasiasanasto(YSA):aivokuori,EEG,transkraniaalinenmagneettistimulaatio,
aivotutkimus,matkapuhelimet,säteily,Alzheimerintauti
VIII
IX
Acknowledgements
Thisworkrepresentstoacertainextentthesynthesisofmyjourneyintheintriguing
field of the neuroscience which began in 1999 when, as a young and inexpert medical
student, I decided to get some experience in the Department of Neurosurgery at the
ChildrenʹsHospital,HarvardMedicalSchool,Boston.
When,in2006,Iwas aresidentinNeurology,attendingtheLabofProfessorGiulio
TononiintheCenterforSleepandConsciousnessoftheUniversityofWisconsin,Madison,
andImet Dr. SaraMäättä,Ineverimaginedthat Iwouldhaveachanceto do myPhDin
Finland. The ideacamein a funnycontest in Chicago,and I’m sincerelyand profoundly
indebted to Sara for that. She helped and amiably supported me on this experience. We
haveastrongandtruefriendshipandacommonloveforscience,provedovertheseyears
onseveraloccasionsallovertheworldfromMiamitoRovaniemiviaIstanbul,PortoCervo,
SantaMariadiLeuca,TaorminaandRavello.I’malsoindebtedtoProfessorEsaMervaala,
who warmly welcomedme to hisDepartment in Kuopio,accepting with enthusiasmthe
challengeoftraininganItalianstudent.
Completing this dissertation tooka relatively long time, as most of the work was
performedduringtheweekends,thevacationsandthelimitedtimeIcouldsparefromthe
demandingscheduleofmydaily activity. Thisthesiscollectsallmyscientificeffortssince
2000, when I started my internship in the Department of Neurology at the University
Campus Biomedico of Rome under the guidance of my ‘Magister’ Professor Paolo Maria
Rossini, who supervised my studiesand research from the very beginning. I thank him
with all myheart: my wholecareer would nothave been possiblewithout his guidance,
continuous support, and contributions that go far beyond scientific borders. He has
incessantly inspired me withhis creative scientificthi
nkingand thoroughness andunder
hisguidanceIwasabletocrystallizemymethodologicalapproachforstudyingthehuman
brain and integrate the results into a framework of known neurological and
neurophysiological data. Most importantly, with his unique approach to life, medical
science in general and neurological science in particular, Professor Rossini provided me
with qualities that will forever remain part of my own style. Iʹm deeply thankful to
ProfessorRossiniforadding a scientificessencetomythoughtsandforbeingthe‘spiritus
movens’ofmywork.
IamalsogratefultoP
rofessorMarkHallettandProfessorUlfZiemannforreviewing
thisthesis,andparticularlytoProfessorJohnRothwellforacceptingtobetheopponentin
the academic defense of my work. I’m deeply honored by the contributions of these
scientists.
I thank Professor Vincenzo Denaro, Professor Flavio Keller, Professor Giordano
DicuonzoandProfessorPaolaBinettiwhotrustedmefromthebeginning.
Thisworkrepresentsnotonlytheefforts madebymeovertheselastyearsbutalso
thesum of thecontributionof many people whohelpedme in reaching thisgoal.I have
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