Depression is a highly prevalent clinical condition which has been estimated to affect a growing part of the population in western countries. Alongside expenditure on diagnostics and treatment, there is a high economic impact due to lost productivity. Although a range of treatments are available, diagnoses are currently costly and require subjective assessment by a specialist. Moreover, treatment selection can be lengthy and can involve trial and error. To develop better diagnostics, stratification, and treatments for depression, we need a better understanding of the condition across different levels - from neural mechanisms to cognition and behaviour. Computational modelling is an emergent theory-driven approach which can aid linking data across different levels of analysis - from neural mechanisms and computations in the brain, to cognitive algorithms and observable behaviour. Some models integrate diverse findings and make predictions, while others enable inference of clinical measures which are not obvious in raw data. Modelling can lead to better understanding of depression, and in turn to better stratification and treatments. On the other hand, machine learning and classification methods can help detect clinically-relevant patterns in experimental data in a purely data-driven manner. This can lead to development of better screening and diagnostic methods. In the current work, we first review some of the most prominent neurocognitive theories of depression, as well as existing studies which used computational modelling methods. Based on our review, we argue that modelling can provide a rich set of tools for a better understanding of the condition. We then develop two novel computational modelling accounts of depression. In the first account, we propose an explicit mechanistic link between a robust behavioural negative bias effect and some of the widely reported or theorised neural aspects of depression - hyperactive amygdala and inhibited dopamine release. In the second account, we attempt to better explain depressive cognitive deficits and show how they can arise from depression-relevant etiological factors - altered valuation and controllability estimates. Finally, in the third part of this work we attempt to develop a novel system for detecting depressive symptoms based on a combination of face-tracking, eye-tracking and cognitive performance measures. We evaluate the system in a pilot experiment and show that a combination of measures can achieve better results than measures from each domain separately.

Memory deficits in Alzheimer’s disease (AD) and mild cognitive impairment (MCI) can be reflected in language-based tests, especially spontaneous speech tasks. Three spontaneous speech tests were developed in this study, including Thai Picture description (TPD), Thai Story Recall (TSR), and Semi-structured Interview for Thai (SIT) Ninety-eight Thai older adults underwent screening tests and three spontaneous speech tests. Then they were classified into three groups, including healthy control (HC), MCI, and AD. Their verbal responses were extracted into the content variables and acoustic features. Then the discriminant ability and accuracy in differentiating HC, MCI, and AD were examined with by Multivariate Discriminant Analysis (MDA) and analysis of the ROC curve and AUC. Two content variables showed significant differences among three groups of participants, i.e., correct information unit (CIU) of the TPD and delayed recall scores of the TSR. For acoustic features, ANOVAs revealed that three variables were significantly different among the three experimental groups, i.e., total utterance time in delayed recall, number of voice breaks in the TPD, and the SIT. The result of a stepwise estimation in MDA presented that the best combination of predictive model was CIU and backward digit span (BDS), in which provides 61.1% of correct classification. This discriminant function showed AUC of .81 in differentiating HC and MCI, AUC of .91 in distinguishing HC and AD, and AUC of .86 in detecting persons with cognitive impairments (MCI and AD) from HC. In conclusion, the combination of CIU of TPD and BDS is suitable for differentiating AD and persons with cognitive impairments from HC. However, there is no appropriate predictor in distinguishing MCI and AD.

Made available in DSpace on 2015-05-14T13:16:23Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 3324327 bytes, checksum: b85304a7fe276b9b7697e2cdf5a23471 (MD5) Previous issue date: 2013-12-06 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / This study aimed at verifying exposure levels for gasoline and ethanol vapors and their psychophysical, neurocognitive, and physiological consequences in a sample of Brazilian pump attendants. Gas chromatography and microclimate sensing were used to passive and active monitoring of environmental levels of vapors. The psychophysical evaluation comprised the chromatic tests Lanthony D15-d and Cambridge Color Test 2.0, the Contrast Sensitivity Function using vertical sinusoidal gratings and Metropsis at the frequencies 0.2, 0.5, 1.0, 2.0, 5.0, 10.0, and 16.0 cpd, and eye-tracking at 250 Hz. Except by the D15-d test, all vision tests were performed with the dominant eye. The neurocognitive evaluation included the Trial Making Tests (A and B) and the Rey's Complex Figure Test. After applying exclusion criteria, the physiological evaluation was carried out in 16 attendants, who had a blood test to assess hepatic-biliary functions by the following markers: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Direct Bilirubin (DB), Total Bilirubin (TB), and Gamma-glutamyl transpeptidase (GAMMA GT). The screening phase also included a questionnaire of Psychological and Neurophysiological Symptoms (PNS), a sociodemographic questionnaire, the Ishihara and the Rasquin 'E' tests. Thirty-eight pump attendants (Exposed Group) were selected, all males, with mean age of 32.66 years (SD = 1.30) and average schooling of 9.68 years (SD = 0.34). Thirty-eight volunteers (Control Group) were selected, all males, with mean age of 30.0 years (SD = 1.54), average schooling of 9.84 years (SD = 0.34), without reporting exposure to solvents and considered healthy following the inclusion criteria. The groups did not differ in age (p = .224) or schooling (p = .52), and all participants had normal or corrected-to-normal visual acuity 20/20. The Mann-Whitney test showed significant differences between scores in the Index of Color Confusion of the D15-d (p < .01, with losses in the tritan axis 75%), the Area of ellipses (protan, deutran, and tritan, all at p < .05), the frequencies 5, 10, and 16 cpd (p < .01), the Trail Making A (p < .01) and B (p < .05), the copy and memory of the Rey's complex figure (both at p < .01), and the number of saccades and trajectory time in the visual labyrinth (both at p < .01) as measure by the eye-tracker. The physiological evaluation showed changes in the values of DB (100 % of the pump attendants) and TB (62,5 %). Two attendants had combined changes in hepatic enzymes and biliburin. The Spearman correlation showed a significant association between the time of service and the areas protan (ρ = .46, p < .01) and deutan (ρ = .64, p < .01), the spatial frequency 5 cpd (ρ = .36, p < .05), and the Trail Making A (ρ = .40, p < .05) and B (ρ = .37, p < .05). The weight showed a tendency to attenuate the visual deficits, having a negative correlation with the area deutan (ρ = - .45, p < .01) and a positive one with contrast sensitivity at 0.20 cpd (ρ = .37, p < .05). Correlations were also found between DB and the time to perform the eye-tracker task (ρ = .58, p < .05) and the GGT and complaints of psychoneurovegetative instability (ρ = .57, p < .05). The Kruskal Wallis, and Mann-Whitney as a post-hoc test with Bonferroni's correction, showed that from 8 years of exposure there are consequences to color vision (Protan and Deutan) and for neurocognitive processes related to attention (Trail Making). The questionnaire PNS showed that 52.6% of pump attendants had symptoms of neuropsychological aggressions. Furthermore, there was a convergence between memory and attention complaints, with lower scores in the memory for the Rey's complex figure (ρ = - .34, p < .05). This study brings additional and new evidences for the consequences on color vision and contrast sensitivity, shows a potential occupational etiology in hepatic-biliary changes, presents neurocognitive xviii deficits in Brazilian pump attendants, and concludes that such deficits are correlated with chronic exposure (significant from 8 years of service) with a level of exposure to gasoline and ethanol below the Brazilian tolerance limit, but within an intervention level to gasoline vapor (168 and 153,40 ppm > 150 ppm) according to the Brazilian Standards for Work Health and Safety. / O objetivo deste estudo foi determinar os níveis de exposição aos vapores da gasolina e do etanol e verificar as consequências psicofísicas, neurocognitivas e fisiológicas em uma amostra de frentistas brasileiros. Para avaliar o nível de exposição ambiental foram realizados monitoramentos passivos e ativos de vapor com cromatografia gasosa e sensoriamento microclimático. A avaliação psicofísica foi realizada com os testes cromáticos de Lanthony D15-d e o Cambridge Color Teste 2,0; com a Função de Sensibilidade ao Contraste utilizando grades senoidais verticais e o Metropsis nas frequências 0,2; 0,5; 1,0; 2,0; 5,0; 10,0 e 16,0 cpg e com o rastreamento ocular utilizando um eyetracker 250 Hz. Todos os testes de visão, exceto o D15-d, foram realizados monocularmente com o olho dominante. A avaliação neurocognitiva ocorreu com os testes Trail Making A, B e com a Figura Complexa de Rey. A avaliação fisiológica, após utilização de parâmetros de exclusão, foi realizada pela análise de sangue de 16 frentistas verificando funções hepatotóxicas pelos marcadores Alanina Aminotransferase (ALT), Aspartato Aminotransferase (AST), Bilirrubina Direta (BD), Bilirrubina Total (BT) e Gamaglutamiltraspeptidase (GGT). Utilizou-se ainda o questionário de sintomas Psicológicos e Neurofisiológicos (PNF) além de um questionário sóciodemográfico e os testes de Ishihara e o ―E‖ de Rasquin na triagem. Essa etapa selecionou 38 frentistas do sexo masculino (Grupo Exposto), com idade média de 32,66 anos (DP = 1,30), grau de escolaridade média igual a 9,68 anos de estudo (DP = 0,34) e 38 voluntários (Grupo Controle) também do sexo masculino, sem histórico de exposição a solventes, considerados saudáveis pelos parâmetros de exclusão, com idade média de 31,00 anos (DP = 1,54) e grau de escolaridade médio de 9,84 anos de estudo (DP = 0,34). Não existiu diferença significativa entre a idade (p = 0,224) e o grau de escolaridade (p = 0,52) dos grupos que apresentaram ainda acuidade visual de 20/20 ou corrigida. Pelo teste de Mann-Whitney foram encontradas diferenças significativas entre os escores para: o Índice de Confusão de Cores do teste D15-d (p < 0,01, prevalecendo perdas no eixo tritan 75%), as Áreas das elipses (protan, deutan e tritan, ambos p < 0,05), as frequências 5 cpg, 10 cpg e 16 cpg (ambos p < 0,01), o teste Trail Making A (p < 0,01) e B (p < 0,05), a cópia e a memória da Figura complexa de Rey (ambas p < 0,01) e o número de sacadas e tempo de percurso do labirinto no eyetracker (ambos p < 0,01). A avaliação biológica demonstrou principalmente alterações nos valores da BD (100 % dos frentistas) e BT (62,5 %). Dois frentistas tiveram alterações combinadas de enzimas hepáticas e bilirrubinas. A correlação de Spearman demonstrou a influência do tempo de serviço no acréscimo das áreas protan (ρ = 0,46; p < 0,01) e deutan (ρ = 0,64; p < 0,01), além de correlações com a frequência de 5 cpg (ρ = 0,36; p < 0,05) e com os testes Trail Making A (ρ = 0,40; p < 0,05) e B (ρ = 0,37; p < 0,05). O peso apresentou a tendência de atenuar os déficits nos testes de visão, correlacionando negativamente com a área deutan (ρ = - 0,45; p < 0,01) e positivamente com a sensibilidade ao contraste na frequência 0,20 cpg (ρ = 0,37; p < 0,05). Existiram ainda correlações entre a BD e o tempo para realizar a prova no eyetracker (ρ = 0,58; p < 0,05) e entre o GGT e as queixas de instabilidade psiconeurovegetativa (ρ = 0,57; p < 0,05). Os testes Kruskal Wallis, e Mann- Whitney como post hoc com correção Bonferroni, demonstraram que a partir de 8 anos de exposição existem consequências para a visão de cores (Protan e Deutan) e para processos neurocognitivos relacionados a atenção (Trail Making A). O questionário PNF apontou que 52,60 % dos frentistas possuem sintomas de agressões neuropsicológicas. Além disso, existiram convergências entre as queixas de falta de memória e concentração, com menores pontuações da memória na Figura Complexa de Rey (ρ = - 0,34; p < 0,05). Este estudo confirma e avança nas descobertas de consequências na visão de cores e sensibilidade ao contraste, aponta uma possível etiologia ocupacional nas alterações hepatotóxicas, apresenta as deficiências neurocognitivas nos frentistas brasileiros e conclui que essas deficiências e as da visão de cores estão correlacionadas a uma exposição crônica (significativa aos 8 anos de serviço) com um nível de exposição a gasolina e ao álcool etílico abaixo do Limite de Tolerância brasileiro, mas a um nível de intervenção para o vapor de gasolina (168,00 e 153,40 ppm > 150 ppm) conforme as Normas de Saúde e Segurança do Trabalho brasileiras.