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Publié par | universitat_ulm |
Publié le | 01 janvier 2010 |
Nombre de lectures | 9 |
Langue | English |
Extrait
Universität Ulm
Klinik für Psychiatrie und Psychotherapie III
Ärztlicher Direktor: Prof. Dr. med. Dr. phil. Manfred Spitzer
_________________________________________________________________
Effects of theta-burst transcranial magnetic
stimulation over the human motor cortex: A
neuroimaging study
Dissertation
zur Erlangung des Doktorgrades der Humanbiologie
der Medizinischen Fakultät
der Universität Ulm
vorgelegt von
Lizbeth Karina Cárdenas-Morales
aus Morelia, Mexiko
2010
Amtierender Dekan: Prof. Dr. Thomas Wirth
1. Berichterstatter: PD. Dr. Thomas Kammer
2. Berichterstatter: Prof. Dr. Harald Traue
Tag der Promotion: 22 Oktober 2010
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CONTENTS
1. INTRODUCTION............................................................................................. 1
1.1 Transcranial magnetic stimulation (TMS) .................................................... 2
1.1.1 Single pulse TMS....................................................................................... 3
1.1.2 Repetitive TMS (rTMS) .............................................................................. 4
1.1.3 Theta-burst stimulation (TBS) pattern...................................................... 10
1.1.4 Factors influencing the individual response to TMS................................. 14
1.1.5 Safety aspects of TMS and clinical use of TBS ....................................... 18
1.2 Combining neuroimaging techniques and rTMS over the M1 .................. 20
1.3 Aims of the study ........................................................................................ 25
2. MATERIAL AND METHODS ........................................................................ 26
2.1 Subjects ........................................................................................................ 26
2.2 Equipment..................................................................................................... 27
2.2.1 Trancranial magnetic stimulation ............................................................ 27
2.2.2 Magnetic Resonance Imaging ................................................................. 28
2.2.2.1 Structural imaging................................................................................. 29
2.2.2.2 BOLD Imaging ...................................................................................... 29
2.2.3.3 Perfusion imaging 29
2.2.4 BDNF Genotyping.................................................................................... 30
2.3 Experimental design 30
2.3.1 Electrophysiological monitoring ............................................................... 30
2.3.2 MRI sessions ........................................................................................... 31
2.4 Data Analysis................................................................................................ 33
2.4.1 Behavioral responses and cMAPs amplitude........................................... 33
2.4.2 BOLD....................................................................................................... 34
2.4.3 CASL 35
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3. RESULTS ..................................................................................................... 37
3.1 Effects of iTBS on contralateral cMAPs amplitude ................................... 37
3.2 fMRI Measurements ..................................................................................... 40
3.2.1 Choice reaction time task during BOLD experiment ................................ 40
3.2.2 Effects of iTBS on BOLD signal ............................................................... 42
3.2.3 Effects of iTBS on CASL perfusion .......................................................... 47
4. DISCUSSION................................................................................................... 50
4.1 EMG monitoring and choice reaction time task ........................................ 50
4.1 EMG recordings and BDNF ......................................................................... 52
4.2 Effects on fMRI ............................................................................................. 54
4.2.1 BOLD signal 54
4.2.2 Direction of BOLD modulation and possible mechanisms ...................... 55
4.2.3 Functional imaging at rest........................................................................ 57
4.3 Limitations and future prospects................................................................ 58
4.4 Conclusion.................................................................................................... 60
5. SUMMARY....................................................................................................... 61
6. REFERENCES................................................................................................. 63
APPENDIX........................................................................................................... 78
ACKNOWLEDGEMENTS.................................................................................... 86
CURRICULUM VITAE ......................................................................................... 87
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LIST OF ABBREVIATIONS
A Adenine
AC- PC Anterior comissure-posterior comissure
ALS Amyotrophic lateral sclerosis
AMPA α-Amino-3-Hydroxy-5-Methyl-4-isoxazolePropionic Acid
AMT Active motor threshold
ANOVA Analysis of variance
APB Abductor pollicis brevis
ASL Arterial spin labelling
BA Brodmann area
Brain-derived neurotrophic factor BDNF
BOLD Blood oxygen level dependent
BW Bandwidth
C Carboxyl
+2Ca Calcium
CaM Calmodulin
CaMKII Calmodulin-dependent kinase II
CASL Continuous arterial spin labelling
cMAPs compound muscle action potentials
cTBS continuous theta-burst stimulation
Direct D
dHb Deoxygenated hemoglobin
e.g. Exempli gratia
EMG Electromyography
EEG Electroencephalography
EPI Echo-planar imaging
Epsilon (value) ε
Fisher (test) F
False-discovery rate FDR
Family-wise error FWE
Functional magnetic resonance imaging fMRI
Gram g
γ-amino butyric acid GABA
v
GAD Glutamic acid decarboxylase
GLM General linear model
Glu Glutamate
Glx Glutamate/glutamine
G Guanine
h Hour
Hb Oxygenated hemoglobin
Hz Hertz
I Indirect
i.e. id est
Immediately early genes IEGs
IH Intact hemisphere
iTBS intermittent theta-burst stimulation
LTD Long-term depression
LTP Long-term potentiation
M1 Primary motor cortex
MEP Motor evoked potential
Met Metionine
+2Mg Magnesium
min Minute
Milliliter ml
mm Millimetre
MNI Montreal neurological institute
MRI Magnetic resonance imaging
MS Multiple sclerosis
msec Millisecond
mV Millivolt
Microsecond μs
Microvolt μV
Sample size (number of subjects) n
Amino (terminal of a protein) N
N-methyl-D-aspartate NMDA
Positron emission tomography PET
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PK Protein kinase
PMA Pre-motor area
PP Phosphatase pathway
PV Parvalbumine
rCBF Regional cerebral blood flow
ROI Region of Interest
RMT Resting motor threshold
rTMS Repetitive transcranial magnetic stimulation
RTs Reaction times
s Second
Primary somatosensory cortex S1
S2 Secondary somatosensory cortex
SD Standard deviation
SEM Standard error of the mean
SH Stroke hemisphere
SICI Short intracortical inhibition
SICF Short intracortical facilitation
SMA Supplementary motor area
SNP Single nucleotide polymorphism
SPECT Single-photon emission computerized tomography
Statistical parametric mapping SPM
TMS Transcranial magnetic stimulation
TE Echo time
TR Repetition time
Val Valine
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Contents
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Chapter 1. Introduction
1. INTRODUCTION
Transcranial magnetic stimulation (TMS) is a non-invasive technique able to
modulate human cortical excitability not just at the site of stimulation, but also at
remote areas. Several studies over the last years explored the therapeutic
potential of repetitive pulses of TMS (rTMS) in the treatment of neurological and
psychiatric disorders, but results are contradictory and its mechanisms are not
completely understood (Fitzgerald et al. 2006). However, the effects of rTMS on
cortical excitability seem to depend mainly on frequency and stimulation intensity
(Chen et al. 1997; Maeda et al. 2000; Fitzgerald et al. 2002).
Recently, a new method of repetitive TMS called theta-burst stimulation (TBS) was
developed (Huang et al. 2005). It requires lower stimulation intensity and a short
stimulation time as compared to other rTMS protocols. The effects of TBS on
motor cortex excitability have been mostly characterized by electrophysiological
measurements of motor ou