L’atteinte de la fonction endothéliale représente une phase précoce de l’athérosclérose, un stade où les patients sont généralement asymptomatiques. Il existe donc un intérêt certain à détecter la dysfonction endothéliale. Nous avons développé une technique de mesure des variations de flot artériel au niveau des membres supérieurs, basée sur la spectroscopie proche infrarouge (NIRS). Cette approche permettrait d’étudier le niveau d’atteinte vasculaire et probablement de quantifier le degré de dysfonction endothéliale périphérique lors d’une hyperémie réactive. L'expérience a été exécutée sur deux cohortes de 13 et de 15 patients et a été comparée à la pléthysmographie par jauge de contrainte (SGP) qui est considérée comme une méthode de référence. Par la suite, nous avons caractérisé la réponse endothéliale par modélisation de la courbe hyperémique du flot artériel. Des études préliminaires avaient démontré que la réponse hyperémique adoptait majoritairement une forme bi-modale. Nous avons tenté de séparer les composantes endothéliales-dépendantes et endothéliales-indépendantes de l’hyperémie. La quantification des deux composantes de la réaction hyperémique permet de calculer un indice de la ‘santé’ du système endothélial local. Cet indice est nommé le ηfactor. Les résultats montrent une forte corrélation des mesures de flots entre la technique développée et la méthode de référence (r=0.91). Nous avons conclu que NIRS est une approche précise pour la mesure non-invasive du flot artériel. Nous avons obtenu une bonne répétabilité (ICC = 0.9313) pour le ηfactor indiquant sa robustesse. Cependant des études supplémentaires sont nécessaires pour valider la valeur de diagnostic du facteur défini. Mots clés: hyperémie réactive, réponse myogénique, oxyde nitrique, athérosclérose, spectroscopie proche infrarouge / Atherosclerotic diseases are mainly caused by coronary and peripheral blood vessel disorders. Endothelial dysfunction represents an early phase in these diseases, when patients are generally asymptomatic. We developed a technique, based on near infrared spectroscopy (NIRS), for measurement of arterial blood flow variations in limbs during reactive hyperemia. The technique allows the study of the level of vascular impairment and probably quantifying the level of endothelial dysfunction at peripheral arteries. The experiment was performed on two cohorts of 13 and 15 patients and was compared to strain gauge plethysmography (SGP) which is considered as gold standard. Afterward, we characterized endothelial reaction during reactive hyperemia through blood flow variations by modeling the hyperemic curve. Preliminary studies have shown that the hyperemic response generally adopts a bimodal form. The first peak was attributed to myogenic reaction that is endothelial independent and the second one to local endothelial cells reaction. The quantification of the two hyperemic response components makes it possible to calculate an index of ‘health’ for local endothelial cells, named ηfactor. The results showed a strong correlation (r = 0.91) of blood flow measurements between the developed method and the gold standard. We concluded that NIRS is a precise technique for non-invasive measurement of blood flow. Moreover, we found a high repeatability (ICC = 0.9313) of the ηfactor in repeated measurements indicating its robustness. Nonetheless, more studies are required to validate the diagnosis value of the defined factor. Key words: reactive hyperemia, myogenic response, endothelial dependent vasodilatation, nitric oxide, atherosclerosis, near infrared spectroscopy (NIRS)

Au cours du vieillissement, des modifications dans la compréhension du discours ont été rapportées, attribuées en partie aux changements cognitifs encourus lors du vieillissement. Néanmoins, diverses études suggèrent une réorganisation cérébrale lors du vieillissement. Cette étude a pour but d'évaluer l'influence de l'âge lors d'une tâche de compréhension du discours à l'aide de l'imagerie optique. Comme première hypothèse, il est attendu que les participants jeunes auront plus de bonnes réponses au niveau des micropropositions et des macropropositions et des performances équivalentes au niveau du modèle de situation. La deuxième hypothèse est que les réseaux neuronaux utilisés lors de la compréhension du discours subiront une réorganisation cérébrale lors du vieillissement. Trente-deux participants ont pris part à cette étude : 16 jeunes adultes et 16 adultes âgés. Alors que les participants étaient sous enregistrement en imagerie optique au niveau du cortex préfrontal (CPF), ils ont lu des courtes histoires chacune suivie d’une phrase et devaient décider si elle était en accord ou non avec la précédente histoire. Les résultats ne montrent aucune différence entre les groupes au niveau de l’exactitude des réponses, contrairement à la littérature. Le CPF a été davantage activé par les adultes âgés comparativement aux jeunes adultes témoignant d’une réorganisation cérébrale. / During aging, changes in discourse comprehension have been reported, attributed in part by cognitive changes that occur during aging. Moreover, various studies suggest a cerebral reorganization with aging. This study aims to evaluate the influence of aging on cerebral reorganization during discourse comprehension using near infrared spectroscopy (NIRS). The first hypothesis is that younger adults will have better accuracy on micropropositions and macropropositions, but will have equivalent performance for the situation model. The second hypothesis is that the neural networks used for discourse comprehension will be reorganized during aging. Thirty-two participants took part in this study: 16 young adults and 16 older adults. While undergoing NIRS recording on the prefrontal cortex (PFC), the participants read short stories each followed by a sentence deciding if it was in agreement or not with the previous story. Results didn’t show any differences for accuracy between the group, in opposition with the literature. The PFC was more activated by the older adults compared to the younger adults showing a cerebral reorganization.

Le vieillissement normal est associé à une réorganisation cérébrale qui peut être influencée par plusieurs facteurs. Des théories comme la réserve cognitive de Stern (2002) tentent d’expliquer les effets de ces différents facteurs. Certains, le niveau de scolarité par exemple, sont encore mal connus. Pourtant, le niveau de scolarité est connu pour avoir un impact sur les performances cognitives tout au long de la vie. Le but de ce mémoire est d’étudier les effets du niveau de scolarité sur l’oxygénation cérébrale de personnes âgées en santé lors d’une tâche d’évocation lexicale orthographique et sémantique. Chaque tâche est divisée selon un critère « plus productive » et « moins productive ». Les âgés faiblement scolarisés produisent moins de mots que les âgés fortement scolarisés. De plus, la différence de mots produits entre le critère plus productif et moins productif est plus grande pour la tâche sémantique que pour la tâche orthographique. Du point de vue hémodynamique, les deux groupes ont des activations semblables, contredisant le phénomène HAROLD. De plus, les participants peu scolarisés tendent à activer de façon plus importante l’hémisphère gauche, peu importe la tâche ou la condition. Par contre, les activations varient selon la tâche et la condition dans le cas du groupe fortement scolarisé. / Normal aging is associated with cerebral reorganisation which can be influenced by many factors. For example, the theory cognitive reserve (Stern, 2002) is trying to explain how those factors can have an impact on the reorganization. However, some factors, such as educational level, are known to have an impact on cognitive performance. The aim of this dissertation is to study the effect of educational level in cerebral oxygenation of healthy older adults during both phonologic and semantic verbal fluency tasks. Each task is divided into two criteria: more productive and less productive. Behavioural data showed that less educated elderly generate fewer words than more educated ones for both tasks. Moreover, the differences between the number of words for the more productive criterion and the less productive one are higher for the semantic than for the phonologic task. NIRS data showed that both groups activated prefrontal cortex, without difference between them. In addition, less educated participants tend to have bigger activations in the left hemisphere regardless of the task and the criterion. On the other hand, higher educated participants’ activations vary according to the task and the criterion unlike the HAROLD model’s predictions.

L’étude du cerveau humain est un domaine en plein essor et les techniques non-invasives de l’étudier sont très prometteuses. Afin de l’étudier de manière non-invasive, notre laboratoire utilise principalement l’imagerie par résonance magnétique fonctionnelle (IRMf) et l’imagerie optique diffuse (IOD) continue pour mesurer et localiser l’activité cérébrale induite par une tâche visuelle, cognitive ou motrice. Le signal de ces deux techniques repose, entre autres, sur les concentrations d’hémoglobine cérébrale à cause du couplage qui existe entre l’activité neuronale et le flux sanguin local dans le cerveau. Pour être en mesure de comparer les deux signaux (et éventuellement calibrer le signal d’IRMf par l’IOD), où chaque signal est relatif à son propre niveau de base physiologique inconnu, une nouvelle technique ayant la capacité de mesurer le niveau de base physiologique est nécessaire. Cette nouvelle technique est l’IOD résolue temporellement qui permet d’estimer les concentrations d’hémoglobine cérébrale. Ce nouveau système permet donc de quantifier le niveau de base physiologique en termes de concentrations d’hémoglobine cérébrale absolue. L’objectif général de ma maîtrise était de développer un tel système afin de l’utiliser dans une large étude portant sur la condition cardiovasculaire, le vieillissement, la neuroimagerie ainsi que les performances cognitives. Il a fallu tout d’abord construire le système, le caractériser puis valider les résultats avant de pouvoir l’utiliser sur les sujets de recherche. La validation s’est premièrement réalisée sur des fantômes homogènes ainsi qu’hétérogènes (deux couches) qui ont été développés. La validation des concentrations d’hémoglobine cérébrale a été réalisée via une tâche cognitive et appuyée par les tests sanguins des sujets de recherche. Finalement, on présente les résultats obtenus dans une large étude employant le système d’IOD résolue temporellement en se concentrant sur les différences reliées au vieillissement. / Our understanding of the functional organization of the human brain has been greatly influenced by the development of new medical imaging techniques. Pr. Hoge’s research has focused on the use of functional magnetic resonance imaging (fMRI) and continuous diffuse optical imaging (DOI) for non-invasive localization and quantification of brain activity associated with behavioral stimuli or tasks (e.g. cognitive, motor or visual). The respective signals of both techniques are based on cerebral haemoglobin concentrations because of the coupling that exists between neuronal activity and cerebral blood flow. Relating BOLD fMRI signals with those acquired using DOI has been complicated by the fact that fMRI yields fractional change values, while the majority of DOI methods have provided absolute changes from an unknown baseline. To address this, we adopted a newer technique known as time-resolved DOI, which allows absolute quantification of cerebral haemoglobin concentrations. Time-resolved DOI thus has the capacity to quantify the subject’s resting hemoglobin concentrations in absolute micromolar units. The main objective of my masters’ project was to implement and optimize a time-resolved DOI system for use in a large study exploring the links between cardiovascular fitness, aging, neuroimaging markers, and cognitive performance. In this thesis we describe the fabrication of the system, followed by its characterisation and validation using solid optical phantoms (homogeneous and heterogeneous) developed for this purpose. Haemoglobin concentrations obtained non-invasively with the system are validated against blood draws, while the sensitivity to variations in concentration are assessed during a cognitive task. Finally, we present the results of a large study in which the time-resolved DOI system was used to characterize age-related vascular changes in the brain.

Le procédé d'agglomération humide trouve des applications dans des secteurs industriels d'importance (e.g. agroalimentaire, pharmaceutique, génie civil, etc.) et s'appuie encore fortement sur le savoir-faire des opérateurs. Ce travail porte sur l'étude des contributions des apports hydriques et mécaniques à l'agglomération humide d'une poudre réactive (transformation de la semoule de blé en grains de couscous). Une approche découplée des apports d'eau et d'énergie mécanique est proposée. L'apport d'eau est étudié par la modélisation de l'influence des paramètres formulation et procédé de l'atomisation liquide sur la taille des gouttes pulvérisées. Les apports d'énergie mécanique sont étudiés à l'aide d'un équipement modèle de malaxage. La répartition des contraintes verticales dans le milieu granulaire à l'état statique est identifiée via une "cartographie 2D des isocontraintes". Le comportement de la poudre au malaxage est étudié au cours du déplacement de la pale dans le malaxeur modèle, par l'analyse des champs de vitesses des particules (obtenus par vélocimétrie par images de particules), et par la mesure des contraintes verticales au niveau de la pale. Une étude de la sthénique et de la cinématique des écoulements granulaires permet d'identifier des longueurs caractéristiques impliquées dans le comportement du milieu granulaire à l'état statique et sous sollicitation mécanique. L'étude couplée des apports hydriques et mécaniques est réalisée par suivi des dynamiques d'agglomération humide dans un malaxeur à pale. Elles sont décrites par des mesures en continu de la consommation énergétique et des mesures in situ des spectres d'absorption proche infra-rouge. / The wet agglomeration process presents large applications in different industrial fields (e.g. food, pharmaceutics, civil engineering, etc.) and is still mainly based on technical know-how and empiricism of operators. This thesis work investigates the contributions of water and mechanical energy inputs to the wet agglomeration of a reactive powder, in the particular case of the transformation of durum wheat semolina in couscous grains. A uncoupled approach of both water and mechanical energy inputs is carried out. The water addition is studied through a modelisation of the influence of operating and formulation parameters of the liquid atomization process on the droplet size. Mechanical energy inputs are studied using a model experimental mixing equipment. Vertical stress distribution in the granular bed in static conditions is identified thanks to the establishment of a "2D iso-stress cartography". The granular medium behaviour under mechanical solicitation is studied during the blade motion in the model mixing equipment thanks to the analysis of granular flows and velocity fields (obtained by particle image velocimetry) and to vertical stress measurements directly on the blade. A sthenic and kinematic study of granular flows allows to identify characteristic lengths involved in the granular medium behaviour under mechanical solicitation. The coupled study of water and mechanical inputs is conducted by following in-line the wet agglomeration dynamics in a pilot mixing device using energetical consumption measurements as well as in situ acquiring of near infrared absorption spectra.

Chernozem became the crucial soil for the beginnings of soil science through the work of Dokuchaev from 1883. Since then the genesis of chernozems in Central Europe has raised many questions among soil scientists, botanists and paleo-environmentalists. While in Eastern Europe chernozems have been described as zonal soils, that are typical for continental steppe and forest-steppe areas, there are areas in Central Europe which are predisposed by their climatic characteristics to the presence of woodlands. The goal of this dissertation is to enrich the discussion about the genesis of chernozems by restoring the environmental conditions that were prevalent during the formation of chernozem soils in Central Europe. Chernozems are usually developed on loess with a very thick and dark organic surface which passes directly to a calcareous horizon. The organic matter underwent a polymerization in dependence on climate contrasts. However, in Central Europe, the climatic characteristics of the areas of chernozems are a bit different. These chernozems are supposed to have been formed under the climatic conditions that dominated Central Europe during the Late Glacial and the Early Holocene. The climatic nuances may contribute to the explanation of the differences in distribution of chernozems ("drier") and...

As Boas Práticas de Fabricação de Medicamentos (BPFM) enfatizam que a indústria farmacêutica deve dirigir seus esforços no sentido de compreender a variação do processo, incluindo as fontes, o grau de variação e o impacto dessa variação nas características de qualidade do produto. O processo de fabricação de medicamentos tem apresentado significativas mudanças, em especial no que se refere à introdução de tecnologias analíticas que permitem o controle do processo em tempo real. A abordagem baseada na análise de risco e no novo Sistema de Qualidade Farmacêutica constitui ponto central das BPFM para o século XXI. Os órgãos regulatórios têm exigido da indústria farmacêutica sua adesão na melhoria contínua relativa ao desempenho de seus processos e, por consequência, na qualidade do produto. O objetivo do presente trabalho foi o desenvolvimento e validação de método analítico empregando espectroscopia no infravermelho próximo, assim como a avaliação do processo de fabricação de comprimidos de Captopril 25 mg, empregando abordagem racional-científica. Com referência à avaliação do processo, foram adotadas as seguintes ferramentas: análise de modos e efeitos de falhas (FMEA); gráficos de controle; índices de capacidade e análise de variância (ANOVA). A espectroscopia por infravermelho próximo (NIR) foi selecionada por apresentar maior rapidez na obtenção dos resultados, maior simplicidade na preparação das amostras, multiplicidade das análises a partir de uma única leitura e por apresentar característica não invasiva. Os resultados comprovaram a adequação dessa tecnologia na avaliação quantitativa do Captopril nas etapas de mistura de pós e de compressão. Os desvios padrão relativos na determinação da uniformidade de Captopril na mistura de pós e nos comprimidos empregando método no NIR foram, respectivamente 3,15 e 0,18%. No que se refere à avaliação da estabilidade e da capacidade do processo, as ferramentas adotadas permitiram a compreensão das fontes de variabilidade, assim como a determinação de seu grau, nas diferentes etapas do processo. Os índices de capacidade (CpK) relativos à uniformidade de Captopril (% p/v) na mistura de pós, ao peso médio do comprimido, à uniformidade de conteúdo e à % (p/v) dissolvida de Captopril, no ensaio de dissolução, foram 0,70, 1,94, 1,80 e 2,19, respectivamente. / The Good Manufacturing Practices (GMP) for Medicinal Products point out that the pharmaceutical industry must direct efforts to understand the variation of the processes, including the sources, the level of variation and the variation impact on the process in characteristics of the product. The manufacturing process has shown meaningful changes, especially in the introduction of new analytical technologies that allow the process control in real time. The approach based on risk analyses and on the new Pharmaceutical Quality System is a central key for the GMP for the XXI century. The Regulatory Agencies have demanded the pharmaceutical industry to adhere the continuous improvement related to the performance of its processes and, consequently, the product quality. Thus, the present paper aimed the development and validation of the analytical method employing NIR spectroscopy as the assessment of manufacturing process of Captopril 25 mg tablets, using rational scientific approach. Regarding the process assessment, the following tools were adopted: analysis of failure modes and effects analysis (FMEA), control charts, capability indexes, as well as analysis of variance (ANOVA). The near-infrared spectroscopy was selected due to its greater speed in getting the results, simplicity in sample preparation, and multiplicity of analysis from a single reading and provide non-invasive feature. The results confirmed the suitability of this technology in quantitative assessment of Captopril on the steps of mixing powders and compression. The relative standard deviations for the determination of Captopril uniformity in the post mixtures and in the tablets employing NIR were 3,15 e 0,18%, respectively. In reference to the stability assessment and process capacity, the tools adopted permitted the understanding of the sources of variability, as well as the determination of their level in different phases of the process. The capacity indexes relating to Captopril uniformity (% p/v) in the powder mixture, the average weight of the tablet, the content uniformity and the % (p/v) dissolved Captopril, in the dissolution assay were 0,70, 1,94, 1,80 and 2,19, respectively.

Sprachverstehen erfordert ein Zusammenspiel verschiedener mentaler Prozesse. Zuerst muss der kontinuierliche akustische Sprachstrom in einzelne Einheiten (z.B. Wörter) unterteilt werden. Segmentale und suprasegmentale linguistische Information unterstützt den Segmentierungsprozess. Wissen über die neuronalen Mechanismen dieser Prozesse ist wesentlich um Sprachverarbeitungs- und Sprachentwicklungsprozesse zu verstehen. Ziel der Dissertation ist die Charakterisierung neuronale Korrelate der Verarbeitung sprachrelevanter akustischer Information bei Erwachsenen und Säuglingen mittels kombinierter Nahinfrarot-Spektroskopie- und Elektroenzephalographie-Messungen. Studie I untersucht zeitliche und topographische Aspekte der phonotaktischen Verarbeitung bei Erwachsenen. Die Ergebnisse zeigen, dass phonotaktische Information links-hemisphärisch verarbeitet wird. Ob diese Lateralisierung auf die linguistischen oder akustischen Eigenschaften der Reize zurückzuführen ist bleibt unklar. Erwachsenen-Studien zeigen, dass die lateralisierte Verarbeitung von Sprache aus der Spezialisierung des auditorischen Kortex für bestimmte zeitliche akustische Variationen im Sprachsignal resultiert. Studie II und III untersuchen, ob diese Asymmetrie bereits bei Säuglingen vorliegt. Dafür werden zeitlich variierte nicht-sprachliche akustische Reize präsentiert. Die zeitlichen Variationen entsprechen kritischen Modulationen im Sprachsignal. Studie II zeigt, dass bei Neugeborenen die zeitlichen Modulationen zu differenzierten und lateralisierten Verarbeitungsmustern führen, die über die ersten Lebensmonate konstant bleiben (Studie III). Die Ergebnisse unterstützen die Annahme, dass die lateralisierte Verarbeitung von Sprache mit einer Spezialisierung des auditorischen Kortex für bestimmte zeitliche Frequenzen zusammenhängt. Das Gehirn ist von Geburt auf die Wahrnehmung zeitlicher akustischen Variationen spezialisiert, die für die Entschlüsselung des Sprachsignals relevant sind. / The comprehension of spoken language requires the segmentation of the continuous acoustic speech stream into smaller units (e.g., words). Segmental and suprasegmental linguistic information guide the segmentation process. Investigating the underlying neuronal mechanisms is crucial for understanding the general nature of language perception, and language acquisition in infancy. This dissertation aimed to determine neuronal mechanisms underlying the perception of basic auditory cues relevant for the segmentation of speech in adults and infants using concurrent recordings of near-infrared spectroscopy and electroencephalography. Study I assessed temporal and topographic characteristics of phonotactic processing in adults, thus forming the basis for future studies in infants. The results show that phonotactic processing recruits a left hemispheric network. Whether these asymmetries are a function of linguistic attributes or of basic temporal signal properties is under debate. Studies in adults link hemispheric specialization for speech perception to an asymmetry in cortical tuning and reveal that the auditory cortices are differentially sensitive to temporal features of speech. Whether this asymmetry is already established in infancy is addressed by study II and III. These studies used acoustic non-linguistic sounds that vary in their temporal structure, thus sharing critical temporal features with language. Study II reveals that newborns process temporally varying stimuli in a differential and lateralized fashion. Study III indicates that this lateralization pattern remains constant over the first months of life. The findings support the notion that the lateralization of language functions might result from a specialization for different acoustic properties. The data provide further evidence that language acquisition is linked to basic capacities in auditory processing, and reveal that from birth the brain is tuned to critical temporal properties of linguistic signals.

Die Arbeit stellt die optische Methode der Nahinfraotspektroskopie (NIRS) in der Anwendung zur Messung von Oxygenierungsänderungen am Kopf des Erwachsenen dar. Dabei werden zunächst methodische Aspekte behandelt. Dies schließt (i) die Frage ein ob Änderungen des Redox-Status der Cytochromoxidase mit der NIRS bestimmt werden können; (ii) diskutiert die Ergebnisse zur Darstellbarkeit schneller optischer Signale, wie sie in invasiven Studien als Korrelat der elektrophysiologisch messbaren neuronalen Prozesse bekannt sind und (iii) richtet sich auf die bessere Definition des Messvolumens, sowohl im Sinne einer zweidimensionalen Bildgebung der Oxygenierungs-änderungen an der Hirnoberfläche als auch die Möglichkeiten zu einer Tiefenauflösung. Bezüglich der grundlegenden physiologischen Fragestellungen thematisiert die Arbeit im zweiten Teil Fragestellungen der neuro-vaskulären Kopplung. Dies ist die Frage, wie sich die neuronale, elektrophysiologisch meßbare Aktivität von Neuronen in eine hämodynamische Antwort übersetzt. Hier sind die Einordnung der NIRS-Befunde in ein Modell der vaskulären Antwort aber auch gleichzeitige Messungen mit elektrophysiologischen Methoden und weiteren vaskulär-basierten Methoden, insbesondere der funktionellen Kernspintomographie, Fokus. Schließlich stellt die Arbeit die klinischen Perspektiven in der Neurologie dar, wie sie sich besonders für die vaskulären Erkrankungen des Gehirns aber auch für Fragestellungen bei Epilepsie und Migräne ergeben. / We here present a optical method, near-infrared spectroscopy (NIRS), and its application for non-invasive measurement of oxygenation changes in the adult head. The first part deals with methodological aspects of NIRS. This includes (i) the question whether changes of cytochrome-oxidase redox state can be monitored by NIRS; (ii) the discussion of study results investigating the non-invasive detectability of fast optical signals , known to reflect electrophysiological changes in invasive animal preparations; (iii) and finally the issue how the sampling volume can be better defined, and with respect to a two-dimensional imaging approach of cortical oxygenation changes and the methodological options to achieve a depth resolution. In a second chapter we then focus on the underlying physiological issues mainly raising questions concerning neuro-vascular coupling. Neuro-vascular coupling means the translation of neuronal activity, as can be measured by electrophysiological methods, into the haemodynamic response. Here the focus is on how the results of functional NIRS studies can be interpreted in the light of a model of the vascular response. Also the simultaneous assessment of electrophysiological parameters or the parameters of other methods based on the vascular response, especially fMRI, are dealt with in this chapter. Finally the here presented work gives perspectives of potential clinical applications of the method. This primarily means the application in stroke and other vascularly diseases in neurology, but also includes questions in the clinical fields of epilepsy and migraine.

In this thesis the optical method of Near-Infrared-Spectroscopy (NIRS) is evaluated with regards to its capability of non-invasive detection of Leão´s cortical spreading depression (CSD) and spontaneous peri-infarct-depolarizations (PID). With the NIR-spectrometer NIRO 500 (Hamamatsu, Japan) regional cerebral oxy-genation (rCBO) changes were measured during CSD in 9, and during PID in 10 barbiturate anesthatized rats. The method if NIRS that relies on oxygen-dependent absorption changes of hemo-globin and cytochrome oxydase as well as the high penetrability of biologic tissues for light in the range between 700 and 1000 nm proved suitable to detect and to distinguish both CSD and PID experimentally. This distinction relies on the robust decrease of deoxy- and increase of oxyhemo-globin concentrations (i.e. a relative hyperoxemia) during CSD while PID is cha-racterized by an initial increase of deoxy- and decrease of oxyhemoglobin (relative hypooxemia). Despite the profound anatomical differences between gyrencephalic humans and lyssencephalic rats, the observed patterns of rCBO changes may guide the inter-pretation of future NIRS measurements in patients with migraines with aura (CSD) or stroke (PID). However, for concentration changes of oxydized cytochrome aa3 with its low con-centration compared to the hemoglobins, the pathophysiological interpretation of the data obtained with NIRO 500 is confounded by the limits of attenuation mea-surements at only four wavelengths. A validation of the cytochrome oxydase signal and an improved quantification of all concentration changes is highly desirable and may be achieved by employment of a continuous-wavelength device measuring the full spectral range of the near infrared. It would also allow to measure the mean optical pathlength in the highly scattering tissue and to correct for its physiologically occuring changes e.g. by measurements at the water absorption peak. Similar improvements would enhance the value of the method for further physiolo-gical and pathophysiological studies because NIRS provides the unique opportu-nity to obtain simultaneous data on blood oxygenation as well as the redox state of the mitochondrial cytochrome oxydase.