Marburg, Universiẗat, Diss., 2000.

Les résultats de la Stimulation Magnétique Transcrânienne répétée (rTMS) dans le traitement des troubles dépressifs résistants, bien que positifs, sont modestes. Ces résultats modérés pourraient s’expliquer par une mauvaise définition de la cible thérapeutique. En effet, la cible thérapeutique dans cette indication est le cortex dorsolatéral préfrontal, c’est-à-dire une large région corticale constituée de plusieurs sub-régions cyto-architecturalement différentes, dont les aires 9 et 46 de Brodmann (BA 9 et BA 46). A partir de l’hypothèse que seule l’une de ces 2 sub-régions pourrait représenter une cible thérapeutique efficace en rTMS, une étude est réalisée afin de comparer la réponse thérapeutique observée par stimulations appliquées sur l’aire 9 et sur l’aire 46 de Brodmann.Quinze patients souffrant de troubles dépressifs (âge moyen : 55 ans) sont randomisés dans une étude en cross-over. Les patients reçoivent 10 séances de rTMS sur chacune des 2 aires (wash-out de 4 semaines entre les 2 séries de stimulation). La rTMS est administrée à 1 Hz sur le cortex droit (120 % du seuil moteur, 360 stimuli par séance). Un neuronavigateur est utilisé pour cibler la BA 9 et BA 46. Les effets thérapeutiques sont mesurés en aveugle avec des échelles standardisées (échelles de dépression de Hamilton et de Montgomery).Les résultats montrent que la rTMS peut être efficace aussi bien sur l’aire 9 que sur l’aire 46 de Brodmann. Toutefois, parmi les répondants, seulement deux d’entre eux ont présenté une réponse thérapeutique sur les 2 aires cérébrales. La plupart des participants n’ont répondu qu’à une seule des deux cibles corticales.Ce résultat suggère que l’identification systématique de la meilleure cible corticale pourrait augmenter les résultats thérapeutiques de la rTMS dans le traitement des troubles dépressifs. Par ailleurs, d’autres paramètres (anatomiques, génétiques, endocriniens) pourraient être déterminants dans l’efficacité des stimulations cérébrales / No abstract

Title: Measuring electrical brain activity during stimulation of trigger zones from concept of Vojta principle Objectives: The aim of this study is to clarify whether there is a change in the electrical brain activity evaluated by the sLORETA program during the stimulation of trigger zones according to the Vojta concept. The source activity during stimulation of trigger zones was scanned from the scalp EEG and compared with the sLORETA program with the source activity measured at rest, before and after the stimulation of the trigger zones. Methods: The research was conducted on 11 healthy adult subjects. The entire research group is consisted of women aged in range 19-32. The data was obtained from the scalp EEG before, during and after stimulation of trigger zones according to Vojta concept. For each proband the measurement of resting EEG with both open and closed eyes (2 x 10 minutes) was first performed, then the measurements were taken during the stimulation of trigger zones with open and closed eyes (2 x 15 minutes). Finally, a resting EEG was measured, alternating open and closed eyes after five minutes (4 x 5 minutes). There was a pause of at least 15 minutes between each stimulation of trigger zones. The order of open and closed eyes during resting EEG and during stimulation of trigger...

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Title: Prolonged apnea: monitoring brain activity in freedivers Objectives: The aim of this study is to monitor the brain electrical activity during the prolonged apnea in freedivers. Prolonged apnea in the water and prolonged dry apnea were compared to each other and also to a resting state before the apnea, all states with the eyes closed. Brain activity was obtained from the scalp EEG and evaluated using the sLORETA program. Methods: The research was conducted in 11 healthy men at the age of 23 - 51. The data was obtained from the scalp EEG. The record was first taken at a resting state before the apneas with eyes closed, then at maximum prolonged dry apnea with eyes closed and finally at maximum prolonged apnea in the water with eyes closed. The lenghts of the prolonged apneas ranged from 2:15 minutes to 5:30 minutes in idividual probands. There were pauses of at least three minutes between each apnea as by the proband's needs. The compared pair groups were following: prolonged apnea in the water against prolonged dry apnea, prolonged apnea in the water against resting state before the apnea and finally prolonged dry apnea against resting state before the apnea, all with the eyes closed. Selected sections of EEG record without artefacts were processed by sLORETA program. In the statistical...

Title: Cerebral projection of haptic contact via sLORETA imaging Objectives: The aim of this work is to evaluate changes in intracerebral source activity via sLORETA imaging during haptic stimulation of hands, while this contact is modified by a mirror illusion in comparison to calm state with open eyes. The work seeks to specify localization of such activity. Methods: Ten healthy volunteers aged 23-42 participated in the experiment. The electrical brain activity was detected with scalp EEG. The experiment was divided in 5 phases. First we measured the brain activity during calm state with open and with closed eyes, each for 5 minutes. Afterwards the subjects were seated at a table with a mirror occluding their right hand and reflecting their left hand. The brain activity was than recorded during 4 modifications of the experiment in duration of 2 minutes each. The first modification contained symmetrical haptic contact on both hands, modification 2 involved stimulation on the left hand only, during modification 3 the stimulus was applied on the right hand only and modification 4 had no tactile stimulus on neither side. The order of modifications for each individual was randomized. The EEG data were converted into sLORETA program, which allows to localize the source of the recorded brain activity...

To fully understand how the brain works, it is necessary to relate the brain’s function to its anatomy. Cortical anatomy is subject-specific. It is character- ized by the thickness and number of intracortical layers, which differ from one cortical area to the next. Each cortical area fulfills a certain function. With magnetic res- onance imaging (MRI) it is possible to study structure and function in-vivo within the same subject. The resolution of ultra-high field MRI at 7T allows to resolve intracortical anatomy. This opens the possibility to relate cortical function of a sub- ject to its corresponding individual structural area, which is one of the main goals of neuroimaging. To parcellate the cortex based on its intracortical structure in-vivo, firstly, im- ages have to be quantitative and homogeneous so that they can be processed fully- automatically. Moreover, the resolution has to be high enough to resolve intracortical layers. Therefore, the in-vivo MR images acquired for this work are quantitative T1 maps at 0.5 mm isotropic resolution. Secondly, computational tools are needed to analyze the cortex observer-independ- ently. The most recent tools designed for this task are presented in this thesis. They comprise the segmentation of the cortex, and the construction of a novel equi-volume coordinate system of cortical depth. The equi-volume model is not restricted to in- vivo data, but is used on ultra-high resolution post-mortem data from MRI as well. It could also be used on 3D volumes reconstructed from 2D histological stains. An equi-volume coordinate system yields firstly intracortical surfaces that follow anatomical layers all along the cortex, even within areas that are severely folded where previous models fail. MR intensities can be mapped onto these equi-volume surfaces to identify the location and size of some structural areas. Surfaces com- puted with previous coordinate systems are shown to cross into different anatomical layers, and therefore also show artefactual patterns. Secondly, with the coordinate system one can compute cortical traverses perpendicularly to the intracortical sur- faces. Sampling intensities along equi-volume traverses results in cortical profiles that reflect an anatomical layer pattern, which is specific to every structural area. It is shown that profiles constructed with previous coordinate systems of cortical depth disguise the anatomical layer pattern or even show a wrong pattern. In contrast to equi-volume profiles these profiles from previous models are not suited to analyze the cortex observer-independently, and hence can not be used for automatic delineations of cortical areas. Equi-volume profiles from four different structural areas are presented. These pro- files show area-specific shapes that are to a certain degree preserved across subjects. Finally, the profiles are used to classify primary areas observer-independently.

To fully understand how the brain works, it is necessary to relate the brain’s function to its anatomy. Cortical anatomy is subject-specific. It is character- ized by the thickness and number of intracortical layers, which differ from one cortical area to the next. Each cortical area fulfills a certain function. With magnetic res- onance imaging (MRI) it is possible to study structure and function in-vivo within the same subject. The resolution of ultra-high field MRI at 7T allows to resolve intracortical anatomy. This opens the possibility to relate cortical function of a sub- ject to its corresponding individual structural area, which is one of the main goals of neuroimaging. To parcellate the cortex based on its intracortical structure in-vivo, firstly, im- ages have to be quantitative and homogeneous so that they can be processed fully- automatically. Moreover, the resolution has to be high enough to resolve intracortical layers. Therefore, the in-vivo MR images acquired for this work are quantitative T1 maps at 0.5 mm isotropic resolution. Secondly, computational tools are needed to analyze the cortex observer-independ- ently. The most recent tools designed for this task are presented in this thesis. They comprise the segmentation of the cortex, and the construction of a novel equi-volume coordinate system of cortical depth. The equi-volume model is not restricted to in- vivo data, but is used on ultra-high resolution post-mortem data from MRI as well. It could also be used on 3D volumes reconstructed from 2D histological stains. An equi-volume coordinate system yields firstly intracortical surfaces that follow anatomical layers all along the cortex, even within areas that are severely folded where previous models fail. MR intensities can be mapped onto these equi-volume surfaces to identify the location and size of some structural areas. Surfaces com- puted with previous coordinate systems are shown to cross into different anatomical layers, and therefore also show artefactual patterns. Secondly, with the coordinate system one can compute cortical traverses perpendicularly to the intracortical sur- faces. Sampling intensities along equi-volume traverses results in cortical profiles that reflect an anatomical layer pattern, which is specific to every structural area. It is shown that profiles constructed with previous coordinate systems of cortical depth disguise the anatomical layer pattern or even show a wrong pattern. In contrast to equi-volume profiles these profiles from previous models are not suited to analyze the cortex observer-independently, and hence can not be used for automatic delineations of cortical areas. Equi-volume profiles from four different structural areas are presented. These pro- files show area-specific shapes that are to a certain degree preserved across subjects. Finally, the profiles are used to classify primary areas observer-independently.:1 Introduction p. 1 2 Theoretical Background p. 5 2.1 Neuroanatomy of the human cerebral cortex . . . .p. 5 2.1.1 Macroscopical structure . . . . . . . . . . . .p. 5 2.1.2 Neurons: cell bodies and fibers . . . . . . . .p. 5 2.1.3 Cortical layers in cyto- and myeloarchitecture . . .p. 7 2.1.4 Microscopical structure: cortical areas and maps . .p. 11 2.2 Nuclear Magnetic Resonance . . . . . . . . . . . . . .p. 13 2.2.1 Proton spins in a static magnetic field B0 . . . . .p. 13 2.2.2 Excitation with B1 . . . . . . . . . . . . . . . . .p. 15 2.2.3 Relaxation times T1, T2 and T∗ 2 . . . . . . . . . .p. 16 2.2.4 The Bloch equations . . . . . . . . . . . . . . . . p. 17 2.3 Magnetic Resonance Imaging . . . . . . . . . . . . . .p. 20 2.3.1 Encoding of spatial location and k-space . . . . . .p. 20 2.3.2 Sequences and contrasts . . . . . . . . . . . . . . p. 22 2.3.3 Ultra-high resolution MRI . . . . . . . . . . . . . p. 24 2.3.4 Intracortical MRI: different contrasts and their sources p. 25 3 Image analysis with computed cortical laminae p. 29 3.1 Segmentation challenges of ultra-high resolution images p. 30 3.2 Reconstruction of cortical surfaces with the level set method p. 31 3.3 Myeloarchitectonic patterns on inflated hemispheres . . . . p. 33 3.4 Profiles revealing myeloarchitectonic laminar patterns . . .p. 36 3.5 Standard computational cortical layering models . . . . . . p. 38 3.6 Curvature bias of computed laminae and profiles . . . . . . p. 39 4 Materials and methods p. 41 4.1 Histology . . . . . p. 41 4.2 MR scanning . . . . p. 44 4.2.1 Ultra-high resolution post-mortem data p. 44 4.2.2 The MP2RAGE sequence . . . . . . . . p. 45 4.2.3 High-resolution in-vivo T1 maps . . . .p. 46 4.2.4 High-resolution in-vivo T∗ 2-weighted images p. 47 4.3 Image preprocessing and experiments . . . . . .p. 48 4.3.1 Fully-automatic tissue segmentation . . . . p. 48 4.3.2 Curvature Estimation . . . . . . . . . . . . p. 49 4.3.3 Preprocessing of post-mortem data . . . . . .p. 50 4.3.4 Experiments with occipital pole post-mortem data .p. 51 4.3.5 Preprocessing of in-vivo data . . . . . . . . . . p. 52 4.3.6 Evaluation experiments on in-vivo data . . . . . .p. 56 4.3.7 Application experiments on in-vivo data . . . . . p. 56 4.3.8 Software . . . . . . . . . . . . . . . . . . . . .p. 58 5 Computational cortical layering models p. 59 5.1 Implementation of standard models . .p. 60 5.1.1 The Laplace model . . . . . . . . .p. 60 5.1.2 The level set method . . . . . . . p. 61 5.1.3 The equidistant model . . . . . . .p. 62 5.2 The novel anatomically motivated equi-volume model p. 63 5.2.1 Bok’s equi-volume principle . . . . . .p. 63 5.2.2 Computational equi-volume layering . . p. 66 6 Validation of the novel equi-volume model p. 73 6.1 The equi-volume model versus previous models on post-mortem samples p. 73 6.1.1 Comparing computed surfaces and anatomical layers . . . . . . . . p. 73 6.1.2 Cortical profiles reflecting an anatomical layer . . . . . . . . .p. 79 6.2 The equi-volume model versus previous models on in-vivo data . . . .p. 82 6.2.1 Comparing computed surfaces and anatomical layers . . . . . . . . p. 82 6.2.2 Cortical profiles reflecting an anatomical layer . . . . . . . . .p. 85 6.3 Dependence of computed surfaces on cortical curvature . . . . .p. 87 6.3.1 Within a structural area . . . . . . . . . . . . . . . . . . p. 87 6.3.2 Artifactual patterns on inflated surfaces . . . . . . . . . .p. 87 7 Applying the equi-volume model: Analyzing cortical architecture in-vivo in different structural areas p. 91 7.1 Impact of resolution on cortical profiles . . . . . . . . . . . . . p. 91 7.2 Intersubject variability of cortical profiles . . . . . . . . . . . p. 94 7.3 Myeloarchitectonic patterns on inflated hemispheres . . . . . . .p. 95 7.3.1 Comparison of patterns with inflated labels . . . . . . . . . .p. 97 7.3.2 Patterns at different cortical depths . . . . . . . . . . . . .p. 97 7.4 Fully-automatic primary-area classification using cortical profiles p. 99 8 Discussion p. 105 8.1 The novel equi-volume model . . . . . . . . . . . . . . . . . . . . .p. 105 8.2 Analyzing cortical myeloarchitecture in-vivo with T1 maps . . . . . .p. 109 9 Conclusion and outlook p. 113 Bibliography p. 117 List of Figures p. 127