Orientador: Rickson Coelho Mesquita / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Física Gleb Wataghin / Made available in DSpace on 2018-08-25T21:15:48Z (GMT). No. of bitstreams: 1 CanoRodriguez_Reember_M.pdf: 7820145 bytes, checksum: a3b06ecbe442d6ecf0266b22a280fb76 (MD5) Previous issue date: 2014 / Resumo: A capacidade de observar a fisiologia funcional do tecido humano tem crescido rapidamente nos últimos anos. Entre outras técnicas, destaca-se a espectroscopia óptica de difusão (DOS), uma técnica emergente que utiliza os princípios da difusão de fótons e permite o monitoramento do tecido biológico de forma continua e portátil. A partir da luz (~ 700 - 900 nm) espalhada pelo tecido é possível determinar variações relativas do seu coeficiente de absorção, que estão relacionadas com as concentrações de oxi-hemoglobina (HbO2) e deoxi-hemoglobina (HbR) presentes no sangue. Neste trabalho, utilizamos a técnica de DOS no domínio da frequência, e a informação da defasagem da onda espalhada (em relação _a onda incidida) para determinação das propriedades ópticas absolutas do tecido biológico e, consequentemente, da sua fisiologia. Em particular, comparamos diferentes modelos de propagação da luz no tecido (semi-infinito e duas camadas) e as propriedades ópticas derivadas destes modelos. Além disso, investigamos métodos de calibração do sinal óptico no tecido, do ponto de vista teórico e experimental, mostrando sua aplicabilidade em experimentos com humanos, no estado de repouso e em intervenções cirúrgicas / Abstract: The ability to observe the functional physiology of human tissue has grown rapidly in recent years. Among other techniques, we highlight diffuse optical spectroscopy (DOS), an emerging technique that utilizes the principles of diffusion of photons and allows monitoring of biological tissue continuously and portable way. From the light (~700 - 900 nm) scattered by tissue it is possible to determine the relative changes in the absorption coefficient, which are related to the concentrations of oxyhemoglobin (HbO2), and deoxyhemoglobin (HbR) in the blood. In this study, we used the technique DOS in the frequency domain, and the phase information of the scattered wave (related to incident wave) for determining the absolute optical properties of biological tissue and, consequently, the physiology. In particular, we compared different models of propagation of light (semi-infinite and two-layer) and the optical properties of tissue derived from these models. Furthermore, we investigated methods of calibration of the optical signal on the tissue from both the experimental and theoretical perspectives, demostrating its applicability in experiments with humans in the resting state and in surgical interventions / Mestrado / Física / Mestre em Física

La gélatine est un biopolymère naturel obtenu après dénaturation et hydrolyse partielle de fibres de collagène, une protéine fibrillaire présente dans les tissus conjonctifs de toutes les espèces du règne animal. Elle est utilisée dans différentes industries, parmi lesquelles l’industrie agroalimentaire, pharmaceutique, photographique et cosmétique. Ses propriétés fonctionnelles dépendent du procédé de fabrication, mais également de l’origine des matières collagéniques. L’objectif de ce travail de thèse est la caractérisation de la matière première (couennes de porc), mais également de la gélatine obtenue lors du processus, par une méthode rapide et non destructive. L’utilisation de la spectroscopie proche infrarouge couplée à des méthodes chimiométriques, a permis de travailler à l’échelle du laboratoire, mais également sur la chaîne de production industrielle. Le premier chapitre porte sur l’étude de l’hétérogénéité des couennes de porc au laboratoire, en termes de teneur en protéines, matières grasses, matières sèches et collagène. Plusieurs modèles ont pu être développés pour prédire ces teneurs, à partir de spectres proche infrarouge collectés sur des couennes en mouvement. Les meilleurs modèles présentent des performances compatibles avec une utilisation dans l’usine. Le second chapitre adapte cette méthode à l’échelle industrielle, c’est-à-dire à partir du rendement en gélatine fabriquée pour un lot de 75t de couennes. L’approche prédictive ne s’est pas avérée concluante, cependant des approches de classification ont montré leur intérêt. Les deux essais suivants ont porté sur la gélatine. Le troisième chapitre porte sur le développement de modèles de prédiction des propriétés physico-chimiques d’échantillons de gélatine à partir de spectres proche infrarouge, mettant en évidence de hautes capacités de prédiction de ces paramètres (r²>0,9). Enfin, ce chapitre propose de relier les caractéristiques moléculaires de la gélatine à ses propriétés physico-chimiques, par la technique de Asymmetrical Flow Field-Flow Fractionation couplée à un détecteur de diffusion de la lumière Multiangulaire (MALS). Les paramètres de caractérisation de l’AFlFFF-MALS permettent de discriminer partiellement des échantillons de gélatine dont les paramètres de bloom et de viscosité sont différents. / Gelatin is a natural biopolymer obtained after denaturation and partial hydrolysis of collagen fibers, a fibrillar protein present in the connective tissues of all species of the animal kingdom. It is used in various industries, including the agri-food, pharmaceutical, photographic and cosmetic industries. Its functional properties depend on the manufacturing process, but also on the origin of the collagenous materials. The objective of this thesis is to characterize the raw material (pig rind), but also the gelatin obtained during the process, by a fast and non-destructive tool. The use of near-infrared spectroscopy coupled with chemometric methods allowed us to work on the scale of the laboratory but also on the industrial chain. The first study examines the heterogeneity of pig rinds, under laboratory conditions, in terms of protein, fat, moisture and collagen contents. Several models have been developed to predict these levels, from near infrared spectra collected on moving rinds. The best models have good performances. In the second industrial scale trial, an approach to gelatin yield from 75 tons batches was proposed. The predictive approach has not been conclusive; however, classification approaches have shown interesting results. The next two tests were on gelatin. The third test allowed the development of models for predicting the physicochemical properties of gelatin samples from near-infrared spectra, demonstrating very good predictive capabilities of these parameters (r²> 0.9). Finally, a final test allowed to link the molecular characteristics of the gelatin to its physicochemical properties, by the technique of Asymmetrical Field-Flow Fractionation coupled with a Multiangular Light Scattering Detector (MALS). The characterization parameters of AFlFFF-MALS make it possible to partially discriminate gelatin samples with different bloom and viscosity parameters.

Master of Science / Department of Kinesiology / Thomas J. Barstow / Limb blood flow increases linearly with exercise intensity; however, invasive measurements of microvascular muscle blood flow during incremental exercise have demonstrated submaximal plateaus. Diffuse correlation spectroscopy (DCS) noninvasively quantifies relative changes in microvascular blood flow at rest via a blood flow index (BFI). The purpose of this study was to quantify relative changes in tissue blood flow during exercise using DCS, compare the BFI of the flexor digitorum superficialis (BFI[subscript]FDS) muscle to brachial artery blood flow (Q̇[subscript]BA) measured via Doppler ultrasound, and employ near infrared spectroscopy (NIRS) alongside DCS to simultaneously measure perfusive and diffusive oxygen transport within a single volume of exercising skeletal muscle tissue. We hypothesized Q̇[subscript]BA would increase with increasing exercise intensity until task failure, BFI[subscript]FDS would plateau at a submaximal work rate, and muscle oxygenation characteristics (total-[heme], deoxy-[heme], and % saturation) measured with NIRS would demonstrate a plateau at a similar work rate as BFI[subscript]FDS. Sixteen subjects (23.3 ± 3.9 yrs; 170.8 ± 1.9 cm; 72.8 ± 3.4 kg) participated in this study. Peak power (P[subscript]peak) was determined for each subject (6.2 ± 1.4W) via an incremental handgrip exercise test to task failure. Measurements of Q̇[subscript]BA, BFI[subscript]FDS, total-[heme], deoxy-[heme], and % saturation were made during each stage of the incremental exercise test. Q̇[subscript]BA increased with exercise intensity until the final work rate transition (p < 0.05). No increases in BFI[subscript]FDS or muscle oxygenation characteristics were observed at exercise intensities greater than 51.5 ± 22.9% of P[subscript]peak and were measured simultaneously in a single volume of exercising skeletal muscle tissue. Differences in muscle recruitment amongst muscles of the whole limb may explain the discrepancies observed in Q̇[subscript]BA and BFI[subscript]FDS responses during incremental exercise and should be further investigated.

Doctor of Philosophy / Department of Anatomy and Physiology / Thomas J. Barstow / The interaction between dynamic muscle contractions and the associated muscle blood flow is very intriguing leading to questions regarding the net effect of these contractions on oxygen delivery and utilization by the working muscle. Study 1 examined the impact of contractions on muscle blood flow at the level of the femoral artery. We demonstrated that muscle contractions had either a facilitory, neutral, or net impedance effect during upright knee extension exercise as intensity increased from very light to ~70% peak work rate. This led to the question of what impact a change in contraction frequency might have on the coupling of blood flow to metabolic rate during cycling exercise. The blood flow/VO2 relationship has been shown to be linear and robust at both the central (i.e., cardiac output/pulmonary VO2) and peripheral (leg blood flow/leg VO2) levels. However, an increase in contraction frequency has been reported to either decrease, have no effect, or increase the blood flow response during exercise. Study 2 determined if the steady state coupling between muscle blood flow and metabolic rate (centrally and/or peripherally) would be altered by varying contraction frequency. Our results indicate that both central and peripheral blood flow/VO2 relationships are robust and remain tightly coupled regardless of changes in contraction frequency. Study 3 examined muscle microvascular hemoglobin concentration and oxygenation within the contraction/relaxation cycle to determine if microvascular RBC volume was preserved and if oxygen extraction occurred during contractions. We concluded that microvascular RBC volume was preserved during muscle contractions (i.e., RBCs remained in the capillaries), which could facilitate continued oxygen delivery. Further, there was a cyclic pattern of deoxygenation/oxygenation that corresponded with the contraction/relaxation phases of the contraction cycle, with deoxyhemoglobin increasing significantly during the contractile phase. These data suggest that oxygen extraction continues to occur during muscle contractions. Significant insight has been gained on the impact of muscle contractions on oxygen delivery to and exchange in active skeletal muscle. This series of studies forms a base of knowledge that furthers our understanding of the mechanisms which govern the control of skeletal muscle blood flow and its coupling to muscle metabolic rate.

Orientador: Jarbas José Rodrigues Rohwedder / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-27T15:32:58Z (GMT). No. of bitstreams: 1 Santos_LiviaMartinsdos_D.pdf: 6212654 bytes, checksum: f20eb97ce2aae510654340b401468dd2 (MD5) Previous issue date: 2015 / Resumo: A contaminação de solos oriundos de derrames de compostos derivados do petróleo é um problema que representa riscos ao meio ambiente e a população. Dentre os constituintes do petróleo, os BTEX são os mais tóxicos. O uso da espectroscopia no infravermelho próximo (NIR) foi empregado como uma ferramenta analítica visando a determinação de BTEX em amostras de solo. À um espectrofotômetro construído no laboratório foi adaptado uma célula de medida, uma célula de amostra e uma válvula esfera responsável pela conexão entre essas duas células. Uma bomba de vácuo foi adaptada ao instrumento visando facilitar o enriquecimento da fase vapor dos hidrocarbonetos voláteis na célula de medida, a qual operou com uma pressão de 29,0 inHg abaixo da pressão do laboratório (APL). Os espectros obtidos da fase vapor contendo os hidrocarbonetos aromáticos apresentaram sobreposição de bandas de absorção. Desta forma, foi necessária a construção de modelos de calibração multivariados empregando Regressão por Mínimos Quadrados Parciais (PLS). Os resultados do melhor modelo de regressão obtidos a melhores condições experimentais mostraram que os valores de RMSECV foram de 12,4 mg kg-1, 47,3 mg kg-1, 72,4 mg kg-1 e 58,6 mg kg-1, respectivamente, para benzeno, tolueno, etilbenzeno e xilenos. Esses valores estão de acordo com os valores orientadores para solo da CETESB de 2005, com exceção para o benzeno que encontra-se acima do valor permitido. Para cada tipo de solo é necessário a construção de modelos de calibração, pois a composição do solo influencia na determinação dos hidrocarbonetos / Abstract: The contamination of soils due to petroleum compounds spills is a problem that represents risks to environment and population. Among petroleum constituents, the volatile aromatic hydrocarbons known as BTEX are toxic. This study aims to evaluate the use of near infrared spectroscopy as an analytical tool for determination of volatile hydrocarbons in soil samples. Spectra were obtained in a spectrophotometer built in the laboratory. It is also part of the instrument, a measuring cell with 540 mm of optical path, a sample cell and a valve which allows connection between the two cells. A vacuum pump was adapted to the instrument in order to facilitate enrichment of the vapor phase of the volatile hydrocarbons in the measuring cell, which operated at a pressure of 29.0 inHg below of the laboratory pressure (BLP). Spectra of the vapor phase containing aromatic hydrocarbons exhibited overlapping of absorption bands. Thus, it was necessary to construct multivariate calibration models using Partial Least Squares Regression (PLS). The results obtained for the calibration model provided values of RMSECV of 12.4 mg Kg¬-1, 47.3 mg Kg¬-1, 72.4 mg Kg¬-1 and 58.6 mg Kg¬-1 for benzene, toluene, ethylbenzene and xylenes, respectively. These values are in agreement with the 2005 CETESB guiding values for soil, except for benzene that is above the allowed value. For each type of soil, it was needed to build calibration models because soil composition affects the determination of hydrocarbons. The developed method is promising and may be used as a screening method to determine the occurrence of contamination in soils by BTEX / Doutorado / Quimica Analitica / Doutora em Ciências

Orientador: Ivo Milton Raimundo Júnior / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-27T23:35:46Z (GMT). No. of bitstreams: 1 Fontes_LaianedeMoura_D.pdf: 2914385 bytes, checksum: 3a68971b696f9f31967f1132ab348427 (MD5) Previous issue date: 2015 / Resumo: Este trabalho descreve o desenvolvimento de diferentes fases extratoras para a determinação de hidrocarbonetos aromáticos e de íons metálicos em água. Para o desenvolvimento das fases extratoras de polidimetilsiloxano e nanotubos de carbono (PDMS-NTC), os nanotubos foram tratados com ácido nítrico, octadecilamina e hipoclorito de sódio. Este último produziu grupos carboxílicos na superfície do nanomaterial, aumentando sua afinidade por hidrocarbonetos aromáticos. A fase extratora foi preparada pela dispersão dos NTC no PDMS e, depois de pronta, inserida num frasco preenchido com as soluções aquosas dos analitos. Após 60 minutos sob agitação, a fase extratora foi removida da solução, seca e inserida em um sistema de medidas, empregando-se um espectrofotômetro FT-NIR. A fase extratora com NTC oxidados com NaOCl possibilitou um aumento da capacidade de extração de 40% e 20% para tolueno e benzeno, respectivamente. No segundo momento, foram desenvolvidas membranas poliméricas plastificadas utilizando os reagentes complexantes Br-PADAP e TAN para a determinação de cobre e chumbo em água por espectroscopia de emissão óptica com plasma induzido por laser (LIBS). As membranas de PVC não forneceram resultados satisfatórios como fase extratora, pois a homogeneidade e estabilidade da superfície das membranas não puderam ser estabelecidas de maneira satisfatória. Papel de filtro analítico foi utilizado como fase extratora para a pré-concentração de íons cobre e chumbo em meio aquoso de forma eficiente, superando as desvantagens das medidas diretas de líquidos por LIBS. A capacidade de adsorção do papel de filtro foi favorecida pela utilização de soluções básicas, principalmente, entre pH 8,0 e 9,0. O tempo de extração foi de 30 minutos para cobre e 60 minutos para chumbo. Os limites de detecção encontrados foram de 0,22 e 0,53 mg L-1 para cobre e chumbo, respectivamente. Não foi observada interferência dos íons Ni (II), Zn (II), Cd (II) e Fe(III), tampouco influência da força iônica. O método proposto foi utilizado para a determinação de cobre e chumbo em amostra de água de torneira enriquecida em três níveis de concentrações. Recuperações na faixa de 98,8% - 114,3% foram obtidas indicando que a determinação direta de íons cobre e chumbo em amostras aquosas pela técnica LIBS utilizando papel de filtro como fase extratora apresenta potencial para a análise de amostras reais / Abstract: This work describes the development of extraction phases for determination of aromatic hydrocarbons and metal ions in water. For development of the phase based on polydimethilsiloxane and carbon nanotubes (PDMS-NTC), carbon nanotubes were previously functionalized with nitric acid, octadecylamine and sodium hypochlorite. The latter oxidizing agent produced carboxyl groups on the surface of the nanomaterial, increasing its affinity for aromatic hydrocarbons. The extraction phase was prepared by dispersing the functionalized NTC in PDMS, which was polymerized to form cylindrical monoliths. Extractions were performed by immersing the monolith in a flask filled with the aqueous solutions of analytes, containing 2.0 mol L-1 NaCl. After an extraction time of 60 min under constant stirring, the monolith was removed from the flask, dried and inserted in the measuring cell of the FT-NIR spectrophotometer. The extraction phase containing NTC oxidized by sodium hypochlorite allow an increase of the sensitivity of 40% and 20% for toluene and benzene, respectively. In the second part, plasticized polymeric membranes containing Br-PADAP or TAN as complexing reagents were developed for determination of lead and copper in water by laser induced breakdown spectroscopy (LIBS). The PVC membranes did not provide satisfactory results, as the homogeneity and the stability of the membrane could not be attained. Analytical filter paper was then employed as an extraction phase to efficiently pre-concentrate lead and copper ions from aqueous solution, circumventing the disadvantages of direct measurements of liquid phase by LIBS. The sorption capacity of the filter paper was enhanced in basic solutions, mainly within pH 8.0 and 9.0. The ideal extraction time for Cu(II) was 30 minutes and 60 minutes for Pb(II). The detection limits were estimated as 0.22 and 0.53 mg L-1 for Cu(II) and Pb(II), respectively. Interference of Ni (II), Zn (II), Cd (II) and Fe(II) ions were not observed, as well as the influence of the ionic strength. The proposed method was employed for determination of cooper and lead in tap water fortified at three concentrations levels. Recoveries in the range from 98.8% to 114.3% were obtained, indicating that direct determination of these ions in aqueous samples by the LIBS using filter paper as an extraction phase has a potential for analysis of aqueous samples / Doutorado / Quimica Analitica / Doutora em Ciências

The postural control-cognition dual-task literature has demonstrated greater postural stability through the examination of multiple kinetic and kinematic measures. Recently, sample entropy (SampEn) and wavelet discrete transform have supported the claim of automaticity, as higher SampEn values and a shift toward higher contribution from automatic sensory systems have been demonstrated in dual-task settings. In order to understand the cortical component of postural control, functional near-infrared spectroscopy (fNIRS) has been used to identify cortical activation under postural control conditions. However, the neural correlates of automatic postural behaviour have yet to be fully investigated. Therefore, the purpose of this study is to confirm the presence of automatic postural control through static and dynamic measurements, and to investigate the prefrontal cortex activation (PFC) when concurrently performing quiet standing and auditory cognitive tasks. Eighteen healthy young adults (21,4 ± 3,96yo), 12 females and 6 males, with no balance deficits were recruited. Participants were instructed to either quietly stand on a force platform (SM), perform three cognitive tasks while seated (SC) and perform a combination of SM and SC concurrently (DT). Results revealed automatic postural control as evidenced by lower area and standard deviation of center-of-pressure in DT conditions. As for SampEn and the wavelet analysis, greater values and a shift from vision to the cerebellum contribution were demonstrated in DT conditions. For the DNS task, a trend toward significantly lower right hemisphere PFC activation compared to left hemisphere activation in DT was evidenced, which potentially reiterate the presence of automaticity. Therefore, as demonstrated by this experiment, the simultaneous performance of a difficult cognitive task and posture yields automatic postural behaviour, and provides insight into the neural correlates of automaticity.

Patients with atrial fibrillation (AF) require modification of ectopic electrical activity to avoid potentially fatal health complications. Catheter ablation therapy is a minimally invasive procedure to create tissue necrosis, called lesion, in areas of abnormal electrical activity. However, significant proportion of patients require repeat treatment from AF recurrences in part by electrical reconnection from incomplete lesions and conduction recovery. Current therapeutic approaches are limited by reliable methods to assess AF structural substrates and validate lesion sufficiency during procedures. In recent years, development of near-infrared optical spectroscopy has provided a non-invasive method to evaluate biological tissue. Near infrared spectroscopy (NIRS) is an optical technique that enables direct characterization of pathological tissue based on the absorption of major chromophores and light scattering. In this thesis, we explore the use of near-infrared optical spectroscopy to identify AF substrates and quantify lesion formation to improve treatment efficacy. First, we developed a near-infrared multispectral imaging system and present a model to assess lesion adequacy by direct visualization of cardiac lesions through an endoscope-integrated probe. Then, a custom single fiber integrated radiofrequency (RF) ablation catheter was fabricated to track irrigated lesion progression real-time on ex vivo swine hearts. A machine learning model was introduced to predict lesion size and transmurality. Additionally, we assess the feasibility of near-infrared spectroscopy by fabricating a NIRS-integrated open-irrigation RF ablation catheter and an algorithm to assess lesion dimensions based on key features derived from NIRS measurements. Using this model, we demonstrate real-time tracking of irrigated lesion delivery in both ex vivo and in vivo swine model. Lastly, we show left atrial endocardial mapping with NIRS-integrated RF mapping catheter to assess AF structural substrates. We present a classification algorithm for important AF structural substrates, such as pulmonary vein sleeve, normal myocardium, ablated tissue, and fibrosis, and a regression model to validate lesion adequacy. A near-infrared spectroscopy-based techniques to localize structural complexities and validate lesion sufficiency at the catheter tip could enhance the understanding of underlying AF substrates and improve treatment efficacy.

Inner speech has been implicated in Vygotsky´s theory of cognitive development. Converging evidence suggests that language skills as well as self-directed speech, in particular inner speech, is important for cognitive functions. However, the role of self-directed speech (including inner speech) in the relation between language skills and cognition have remained unclear. Despite a growing body of studies on the neural substrate of inner and overt speech, evidences of the neural differences between inner and overt speech have remained diffuse. The present dissertation aimed at filling the gap by investigating inner speech and its process of internalization with behavioral and neuroscientific methods. One study addressed the role of self-directed speech in the interplay between language skills and cognition by using the Tower of London task in children. Two studies addressed the neural correlates of the differences between inner and overt speech in adults and children during a picture-naming task by simultaneously applying the electroencephalography and functional near-infrared spectroscopy. The results of the first study confirmed that the internalization of speech is related to children´s cognition although it cannot explain the relation between language skills and problem-solving. The second study showed that inner speech is not overt speech without articulation, even more it is that prior phonological processes are downregulated. Moreover, the study showed that the brain differentiates between inner and overt speech even when no linguistic and motoric process is necessary. The results of the third study showed less differences between inner and overt speech in children indicating that inner speech is not yet adult-like. Even more it seems that inner speech represents linguistically the same like overt speech in the children´s brain.:Table of Content Danksagung VIII Bibliographische Darstellung X Zusammenfassung XI Summary XVI Theoretical Part 1 1 Introduction and Overview 2 1.1 Introduction 2 1.2 Theoretical Background 4 1.3 Development of Inner Speech 15 1.4 Behavioral Significance of Inner Speech 17 1.4.1 The Link between Inner Speech and Cognition 18 1.4.2 The Link between Inner Speech and Language 22 1.4.3 The Link between Language Skills and Cognition 23 1.5 Psycholinguistic and Biological Significance of Inner Speech 25 1.5.1 Speech Production Model 27 1.5.2 Differences between Inner and Overt Speech in the Brain 32 1.6 Overview of the Goals and Research Questions 42 2 Study Designs and Methodologies 46 2.1 Behavioral Methods 46 2.1.1 Tower of London 46 2.2 Neuroscientific Methods 51 2.2.1 Electroencephalography 52 2.2.1.1 Physiological Principles of the EEG 52 2.2.1.2 Technical Principles of the EEG 55 2.2.1.3 EEG Frequency Bands 57 2.2.1.4 Event-related Brain Potentials (ERPs) 58 2.2.2 Functional Near-Infrared Spectroscopy 59 2.2.2.1 Physical Principles of the fNIRS 59 2.2.2.2 Physiological Principles of the fNIRS 65 2.2.2.3 Technical Principles of the fNIRS - Measurement Setup 66 Empirical Part 68 Preliminary Note 69 3 Study 1 - The role of self-directed speech in problem-solving 70 3.1 Introduction 70 3.1.1 The Association between Language Skills and Executive Functions 71 3.1.2 The association between language skills and use of self-directed speech 72 3.1.3 The role of self-directed speech in Executive Functions 73 3.1.3.1 Quantitative and qualitative analysis of self-directed speech 73 3.1.3.2 Dual-task method 74 3.1.3.3 Triggering self-directed speech 75 3.2 The present study 76 3.3 Material and Method 78 3.3.1 Participants 78 3.3.2 General procedure 79 3.3.3 Measures 79 3.3.3.1 Language Skills 79 3.3.3.2 Receptive and Expressive Vocabulary 79 3.3.3.3 Expressive Grammar 80 3.3.3.4 Receptive Grammar 80 3.3.3.5 Non-verbal intelligence (IQ) 81 3.3.3.6 Complex EF (problem-solving ability) 81 3.3.4 Coding speech 84 3.3.4.1 Quantity 85 3.3.4.2 Quality: Internalization 85 3.3.4.3 Quality: Spatial language 86 3.3.4.4 Quality: Planning function 86 3.3.4.5 Quality: Grammatical completeness 87 3.3.4.6 Interrater reliability 87 3.4 Results 88 3.4.1 Preliminary analyses 88 3.4.1.1 Factor analysis 88 3.4.1.2 Bivariate Correlations between all study measures 88 3.4.2 Main analyses 90 3.4.2.1 H1: Relation between language skills and problem-solving 90 3.4.2.2 RQ: Role of self-directed speech 91 3.4.2.2.1 RQ1: Mediation effect of self-directed speech 91 3.4.2.2.2 RQ2: Susceptibility to articulatory suppression 95 3.4.2.2.3 RQ3: Prompting self-directed speech 96 3.5 Discussion 99 3.5.1 Limitations and Next Steps 105 3.5.2 Conclusion 107 4 Study 2 - Differences between inner and overt speech in adults 108 4.1 Introduction 108 4.2 Material and Method 114 4.2.1 Participants 114 4.2.2 Material 114 4.2.3 Tasks and Procedure 115 4.3 NIRS/EEG Data Recordings 117 4.3.1 fNIRS Data Recording 117 4.3.2 EEG Data Recording 118 4.4 Data analyses 119 4.4.1 fNIRS Data Analyses 119 4.4.2 EEG Data Analyses 120 4.5 Results 121 4.5.1 fNIRS results 121 4.5.2 EEG results 122 4.6 Discussion 127 4.7 Conclusions 131 5 Study 3 - Differences between inner and overt speech in children 133 5.1 Introduction 133 5.2 Material and Method 138 5.2.1 Participants 138 5.2.2 Material 139 5.2.3 Tasks and Procedure 139 5.3 NIRS/EEG Data Recordings 141 5.3.1 fNIRS Data Recording 141 5.3.2 EEG Data Recording 143 5.4 Data analyses 143 5.4.1 fNIRS Data: Analyses 143 5.4.2 EEG Data Analyses 144 5.5 Results 145 5.5.1 fNIRS results 145 5.5.2 EEG results 146 5.6 Discussion 146 5.7 Conclusion 150 6 General Discussion 151 6.1 What role does self-directed and inner speech play in the relation between language and cognition in children? 152 6.1.1 Quantitative and qualitative analyses of self-directed speech 152 6.1.2 Articulatory suppression of self-directed speech 155 6.1.3 Triggering self-directed speech 158 6.1.4 Conclusion 159 6.2 What distinguishes inner speech from external (overt) speech in adults? 160 6.2.1 Preparation phase 161 6.2.2 Execution phase 162 6.2.3 Conclusion 164 6.3 What distinguishes inner speech from external (overt) speech in children? 164 6.3.1 Preparation phase 165 6.3.2 Execution phase 167 6.3.3 Conclusion 169 6.4 Limitations and Future Research 169 6.5 Conclusion 176 7 References 179 Appendices 212 Coding Manual of Self-Directed Speech 213 Coding scheme 213 Coding Speech 214 Quantity of Private Speech 214 Quality of Private Speech 216 Speech Structure 216 Content Functions 218 Syntactic Features 221 Publications and Conference Contributions 222 Selbstständigkeitserklärung 225

Breast cancer is fast becoming the leading cause of mortality in women worldwide. As of this year, there are more than 3.1 million women with a history of breast cancer in the U.S., and about 41,760 women are expected to die from this disease. Neoadjuvant chemotherapy (NAC) has become a well-established therapy in the treatment of patients with locally advanced or primarily inoperable breast cancer. It consists of 3-9 months of drug treatment to shrink the tumor size before surgical removal of any remaining mass. A pathological complete response (pCR) is defined as complete disappearance of the tumor before surgery and correlates with 5-year overall survival of the treated patient. However, only 15-40% of subjects who undergo NAC will achieve a pCR, while the remaining patients do not benefit from a therapy that has considerable side effects. In this Ph.D. thesis, I explore the potential of diffuse optical tomography (DOT) for breast cancer imaging and NAC monitoring. The overall objective is two-fold. First, I seek to identify breast cancer patients who will not respond to NAC shortly after the initiation of a 5-9 months therapy regimen. Identifying these patients early will allow a switch to a more promising therapy and avoiding months of ineffective therapy with a drug regimen that has considerable side effects. Second, I use the optical data simultaneously obtained from the contralateral, non-tumor bearing breast to better understand the factors that modulate breast density and the source of its contrast in DOT. This work analyzed DOT data from 105 patients with stage II-III breast cancer under NAC regimen. Data processing and image analysis protocols were developed to more effectively evaluate static tissue contrast and dynamic functional imaging of the breast. Notably, we observed that there are differences in the time evolution of DOT features between pCR and non-pCR tumors under NAC, and DOT features can contribute to the successful prediction of pCR status from pretreatment imaging. Lastly, our analysis demonstrated a positive correlation between DOT feature and mammographic density classification, which could lead to research on the potential use of DOT as a predictor of breast cancer as well as an assessment tool to longitudinally evaluate the efficacy of chemoprevention strategies. These findings represent important steps towards the translation of DOT into current clinical workflow to contribute to better-personalized breast cancer therapies and breast cancer risk management.