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The field of cognitive neuroscience has benefited greatly from multimodal investigations of the human brain, which integrate various tools and neuroimaging data to understand brain functions and guide treatments for brain disorders. In this dissertation, we present a series of studies that illustrate the use of multimodal approaches to investigate brain structure and function, brain connectivity, and neuromodulation effects. Firstly, we propose a novel landmark-guided region-based spatial normalization technique to accurately quantify brain morphology, which can improve the sensitivity and specificity of functional imaging studies. Subsequently, we shift the investigation to the characteristics of functional brain activity due to visual stimulations. Our findings reveal that the task-evoked positive blood-oxygen-level dependent (BOLD) response is accompanied by sustained negative BOLD responses in the visual cortex. These negative BOLD responses are likely generated through subcortical neuromodulatory systems with distributed ascending projections to the cortex. To further explore the cortico-subcortical relationship, we conduct a multimodal investigation that involves simultaneous data acquisition of pupillometry, electroencephalography (EEG), and functional magnetic resonance imaging (fMRI). This investigation aims to examine the connectivity of brain circuits involved in the cognitive processes of salient stimuli. Using pupillary response as a surrogate measure of activity in the locus coeruleus-norepinephrine system, we find that the pupillary response is associated with the reorganization of functional brain networks during salience processing. In addition, we propose a cortico-subcortical integrated network reorganization model with potential implications for understanding attentional processing and network switching. Lastly, we employ a multimodal investigation that involves concurrent transcranial magnetic stimulation (TMS), EEG, and fMRI to explore network perturbations and measurements of the propagation effects. In a preliminary exploration on brain-state dependency of TMS-induced effects, we find that the propagation of left dorsolateral prefrontal cortex TMS to regions in the lateral frontoparietal network might depend on the brain-state, as indexed by the EEG prefrontal alpha phase. Overall, the studies in this dissertation contribute to the understanding of the structural and functional characteristics of brain network systems, and may inform future investigations that use multimodal methodological approaches, such as pupillometry, brain connectivity, and neuromodulation tools. The work presented in this dissertation has potential implications for the development of efficient and personalized treatments for major depressive disorder, attention deficit hyperactivity disorder, and Alzheimer's disease.

Past research found performance differences between monolingual and bilingual children in the domain of executive functions (EF). Furthermore, recent studies have reported advantages in processing efficiency or mental effort in bilingual adults and children. These studies mostly focused on the investigation of “cold” EF tasks. Studies including measures of “hot” EF, i.e., tasks operating in an emotionally significant setting, are limited and hence results are inconclusive. In the present study, we extend previous research by investigating performance in a task of the “hot” EF domain by both behavioral data and mental effort via pupillary changes during task performance. Seventy-three monolingual and bilingual school children (mean age = 107.23 months, SD = 10.26) solved the Iowa Gambling Task in two different conditions. In the standard task, characterized by constant gains and occasional losses, children did not learn to improve their decision-making behavior. In a reversed task version, characterized by constant losses and occasional gains, both monolinguals and bilinguals learned to improve their decision-making behavior over the course of the task. In both versions of the task, children switched choices more often after losses than after gains. Bilinguals switched their choices less often than monolinguals in the reversed task, indicating a slightly more mature decision-making strategy. Mental effort did not differ between monolinguals and bilinguals. Conclusions of these findings for the bilingual advantage assumption will be discussed.

No description available.

Melanopsin (Opn4) is the opsin photopigment of intrinsically photosensitive retinal ganglion cells (ipRGCs). It has a conserved opsin structure and activation mechanism, yet demonstrates unusual functional properties that suggest it will possess unique structure-function relationships. The aim of this thesis was to characterise key OPN4 residues by examining the impact of non-synonymous mutations on melanopsin function. A genotype-driven screen of a chemically-mutagenized mouse archive led to the identification of a novel Opn4 mutant, S310A, located at a known opsin spectral tuning site. Action spectra from ipRGC and pupil light responses (PLR) of Opn4^S310A mice revealed no change in wavelength of peak sensitivity. However, Opn4^S310A PLR was significantly less sensitive at longer wavelengths, consistent with a short-wavelength shift in spectral sensitivity. This suggests S310A acts as a spectral tuning site in melanopsin. Next, the impact of naturally-occurring missense variants in human melanopsin (hOPN4) was examined in vitro. Fluorescent calcium imaging of 16 hOPN4 variants expressed in HEK293 cells revealed four hOPN4 variants abolished or attenuated responses to light (Y146C, R168C, G208S and S308F). These variants were located in conserved opsin motifs for chromophore binding or hydrogen-bond networks, functional roles apparently shared by melanopsin. Finally, two hOPN4 single nucleotide polymorphisms (SNPs) P10L and T394I, associated with abnormal non-image forming behaviour in humans, were explored in vivo. Using targeted viral-delivery of hOPN4 SNPs to mouse ipRGCs, a range of OPN4-driven behaviours, such as circadian photoentrainment and pupil light responses, were found to be comparable with hOPN4 WT control. Multi-electrode array recordings of ipRGCs transduced with hOPN4 T394I virus had significantly attenuated sensitivity and faster response offset, indicating this site may be functionally important for melanopsin activity but compensatory rod and cone input limits changes to non-image forming behaviour.

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2018-11-14T12:45:33Z No. of bitstreams: 2 Dissertação - Cleyton Rafael Gomes Silva - 2018.pdf: 3259568 bytes, checksum: 21f7d8194e8929ef29e8df95ef8f6a0a (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2018-11-14T13:02:15Z (GMT) No. of bitstreams: 2 Dissertação - Cleyton Rafael Gomes Silva - 2018.pdf: 3259568 bytes, checksum: 21f7d8194e8929ef29e8df95ef8f6a0a (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2018-11-14T13:02:15Z (GMT). No. of bitstreams: 2 Dissertação - Cleyton Rafael Gomes Silva - 2018.pdf: 3259568 bytes, checksum: 21f7d8194e8929ef29e8df95ef8f6a0a (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2018-09-28 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Examining human pupillary behavior is a non-invasive, low-cost method for assessing neurological activity. Changes in this behavior are correlated to various health conditions, such as: Parkinson’s, Alzheimer’s, autism and diabetes. In order to obtain information about the pupillary behavior, it is necessary to measure the pupil diameter in procedures that induce pupillary reflexes, known as Pupilometry. Pupillary measurement is made by filming the procedures when applying computer vision techniques for pupil recognition. The objective of this research was to develop an Automated Pupilometry System (SAP) to support the investigation of patients with type II diabetes mellitus. SAP was able to record, induce, and extract 96 pupil features. In the experiment with 15 healthy patients and 16 diabetics, a 94% accuracy in the identification of diabetics type II was obtained, demonstrating the efficiency of SAP for the performance of examinations, and evidencing the potential of pupil use in the investigation of diabetes mellitus type II. / Examinar o comportamento pupilar humano é um método não-invasivo e de baixo-custo para avaliar atividade neurológica. Alterações neste comportamento são correlacionadas a várias condições de saúde, como: Parkinson, Alzheimer, autismo e diabetes. Para se obter informações do comportamento pupilar é necessário medir o diâmetro da pupila em procedimentos que induzem os reflexos pupilares, conhecidos como Pupilometria. A medição pupilar é feita por meio da filmagem dos procedimentos ao aplicar-se técnicas de visão computacional para reconhecimento da pupila. O objetivo desta pesquisa foi desenvolver um Sistema Automatizado de Pupilometria (SAP) para apoiar a investigação de pacientes com diabetes mellitus tipo II. O SAP foi capaz de gravar, induzir, e extrair 96 característicaspupilares. No experimento com 15 pacientes saudáveis e 16 diabéticos foi obtida uma acurácia de 94% na identificação de diabéticos tipo II, demonstrando a eficiência do SAP para a performance de exames, e evidenciando o potencial do uso da pupila na investigação de diabetes mellitus tipo II.

Belohnungen sind im Leben des Menschen von enormer Bedeutung. Es wurde vermutet, dass die zentralen sozialen Schwierigkeiten bei Autismus-Spektrum-Störungen (ASS) auf eine verminderte Reaktionsfähigkeit auf spezifische soziale Belohnungen zurückzuführen sein könnten. Die Literatur zu diesem Thema ist jedoch nicht schlüssig. Diese Dissertation umfasst vier Studien, die die Reaktionsfähigkeit auf soziale und nicht-soziale Belohnungen unter besonderer Berücksichtigung von ASS und autistischen Merkmalen untersuchen. In den Studien 1 und 2 wurden neuronale (ereigniskorrelierte Potenziale), autonome (Pupillengröße) und verhaltensbezogene (Selbstberichte und Reaktionszeiten) Indizes der Reaktion auf soziale und nicht-soziale Belohnungen bei Personen mit ASC sowie mit ausgeprägten und geringen autistischen Merkmalen untersucht. Wir stellten fest, dass ein höheres Maß an autistischen Merkmalen bei klinischen ASS und in der Allgemeinbevölkerung mit einer verstärkten neuronalen und autonomen Verarbeitung, typischen Leistungen und einer geringeren selbstberichteten Belohnungssensitivität verbunden war. Studie 3 untersuchte die Auswirkungen von sozialer Vertrautheit und Belohnungskontext auf die Pupillenreaktionen. Die Ergebnisse deuten darauf hin, dass der Belohnungswert eines positiven Reizes bei vertrauten Gesichtern höher ist und von der Assoziation zwischen Handlung und Ergebnis abhängt. Studie 4 ist eine theoretische Perspektive zum Verständnis der Multidimensionalität von Belohnungen und zum Umgang damit. In allen Studien konnte ich nachweisen, dass das Belohnungsverhalten von ASS vielfältig und atypisch, aber nicht defizitär ist. Außerdem schlage ich eine Definition von Belohnung vor, die sie von einem rein positiven Stimulus unterscheidet. Schließlich erörtere ich diese Arbeit im breiteren Rahmen der sozialneuropsychologischen Forschung und zeige Möglichkeiten auf, wie sie in künftigen Studien weiter verbessert werden kann. / Rewards are immensely important in human lives. It has been suggested that the core social difficulties in autism spectrum conditions (ASC) may stem from lowered responsiveness to specifically social rewards. However, the literature on this topic is inconclusive. This dissertation includes four studies investigating reward responsiveness to social and non-social rewards with particular focus on ASC and autistic traits. Studies 1 and 2 investigated neuronal (event-related potentials), autonomic (pupil sizes) and behavioural (self-reports and reaction times) indexes of responsiveness to social and non-social rewards in individuals with ASC, and with high and low autistic traits. We observed that higher levels of autistic traits in clinical ASC and in the general population were linked to enhanced neuronal and autonomic processing, typical performance, and decreased self-reported reward sensitivity. Study 3 investigated the effects of social familiarity and rewarding context on pupillary responses. The results indicated that the reward value of a positive stimulus is higher for more familiar faces and depends on action-outcome associations. Study 4 is a theoretical perspective on understanding and working with multidimensionality of rewards. Across all studies, I provide evidence for multifaceted and atypical, but not deficient, reward responsiveness in ASC. Further, I propose a definition of reward which differentiates it from a merely positive stimulus. Finally, I discuss this work in the broader framework of social neuropsychology research and identify the ways in which it can be further improved in future studies.

This MA thesis is a descriptive theoretical study dealing with the work of the conference interpreter, teacher and researcher Kilian Seeber. The thesis explores individual fields of interest of Kilian Seeber and the results of his research. It describes mainly the cognitive load in simultaneous interpreting, prosody and intonation, but also ethical decisions in simultaneous interpreting and issues connected with training of trainers. Furthermore, the thesis presents Seeber's teaching and interpreting projects and, last but not least, the reaction to his work and its reception in the international interpreting community. Key words: Kilian Seeber, cognitive load, eye tracking experiment, pupillometry, prosody, intonation, ethical decisions, simultaneous interpreting, blended learning.