Investigações das evidências de validade dos testes devem ser contínuas, a fim de aprimorar aspectos teóricos e empíricos, abrangendo o significado dos escores do teste, as consequências e sua utilidade. A presente tese investigou evidências de validade Benton Visual Retention Test ou Teste de Retenção Visual de Benton (BVRT) para a avaliação da memória visual e habilidades visuoconstrutivas na amostra total de normatização do teste no Brasil. Mais especificamente, investigaram-se a Administração A (Memória) e Administração C (Cópia) do BVRT. O primeiro estudo aborda aspectos históricos e conceituais da avaliação neuropsicológica na interface com a Psicometria, as principais funções neuropsicológicas avaliadas pelo BVRT e suas bases neurais. Os três capítulos empíricos investigam fontes de evidência de validade do teste utilizando diferentes técnicas de análise de dados. No Capítulo II, por meio da Modelagem de Rasch, observou-se a necessidade de incluir itens nos dois extremos da escala logit para a Administração C (Cópia). A análise também forneceu uma proposta de avaliação considerando a dificuldade específica de cada item. O Capítulo III investigou a influência de outras variáveis no BVRT tendo se encontrado padrões em forma de U-invertido em função da idade, da infância até a terceira idade, principalmente na memória visual, avaliada pelo BVRT. Ainda, a Modelagem de Equações Estruturais permitiu identificar um efeito fixo da variável Quociente Intelectual (QI) na Administração A (Memória) do BVRT em diferentes grupos etários, sendo que nos grupos dos adultos e idosos observou-se uma relação positiva e significativa entre os anos de estudo e o desempenho no BVRT. No Capítulo IV, realizou-se a comparação de um grupo clínico de pacientes pós-Acidente Vascular Cerebral unilateral e um grupo controle, emparelhado por idade e anos de estudo, e encontrou-se um pior desempenho do grupo clínico no teste, principalmente na Administração C (Cópia). Em complemento, o método de série de casos, evidenciou dissociações fortes e clássicas entre as duas administrações do BVRT. As evidências de validade do BVRT investigadas na presente tese reforçam a necessidade de aprimoramento das características dos itens do teste e ressaltam a importância de se considerar variáveis sociodemográficas, como a idade e anos de estudo, e variáveis cognitivas como o QI na determinação do desempenho do BVRT. A tese contribui para as investigações de diferentes fontes de evidências de validade para o BVRT em amostras brasileiras. A utilidade do BVRT na avaliação clínica de pacientes pós-AVC foi evidenciada, uma vez que o teste permitiu a investigação de déficits de memória visual e habilidades visuoconstrutivas separadamente, o que pode implicar no melhor planejamento dos programas de reabilitação de pacientes. / Tests evidence validity investigations should be continuous to improve theoretical and empirical issues, including scores meaning, consequences and utility. This doctoral dissertation investigated Benton Visual Retention Test (BVRT) evidence validity in evaluating visual memory and visuo-constructive abilities in Brazilian total norming sample of the test. Specifically, were investigated de Adminstration A (Memory) and Administration C (Copy) from BVRT. Chapter I consisted of a review about historical and conceptual aspects in neuropsychology evaluation in relation to psychometrics, the main neuropsychological functions evaluated by BVRT and its neural basis. Three empirical studies were performed in relation to sources of validity evidence using diferent data analysis tecniques. In Chapter II we used Rasch analisys and observed the need of itens in both extremes of logit scale for the Administration C (Copy). In addition, a new strategie of interpretation considering the itens difficulty was presented. Chapter III investigated variables influences on the BVRT scores and showed an inverted-U shaped trend considering the age, in childhood to old age, mainly in visual memory evaluated with BVRT. Still, using Structural Equation Modelling in different age groups we identified a fix effect for IQ in Administration A (Memory) of BVRT and a positive and significative relation between years of shooling and the BVRT performance in adults and old age groups. Last, in Chapter IV, we did a comparative study between a clinical group of unilateral stroke patients and a control group paired by age and years of schooling, and we found a worst performance in the clinical group, mainly at Administration C (Copy). Also, the case series method showed strong and classic dissociations between both BVRT administrations. This doctoral dissertation investigated different sources of evidence validity in Brazilian samples. The results highlighted the utility of the test in clinical evaluation of stroke patients considering that BVRT allowed the evaluation of visual memory and visuoconsttructive abilities separately, what can imply a better planning of patient’s rehabilitation programs.

Multiple sclerosis (MS) is a prevalent and progressive autoimmune inflammatory disease affecting both white and gray matter and resulting in lesions and atrophy within the central nervous system (CNS) (Bermel & Bakshi, 2006; Confavreux & Vukusic, 2006; Cree, 2012; Friese, Schattling, & Fugger, 2014). Fine motor impairment, including manual motor speed and fine motor dexterity deficits, is common in MS patients (e.g., Benedict et al., 2011; Chipchase, Lincoln, & Radford, 2003). However, impairment does not progress uniformly across patients (Confavreux, Vukusic, Moreau, & Adeleine, 2000; Filippi & Rocca, 2011; Scalfari, Neuhaus, Daumer, DeLuca, & Muraro, 2013) and the association between disease burden and physical disability is moderate at best (Bermel & Bakshi, 2006; Filippi et al., 2013). Though the brain reserve hypothesis has helped to explain the clinico-pathologic dissociation between cognitive functioning and disease burden in MS patients (Sumowski et al., 2013; Sumowski et al., 2014a), there is no published literature on brain reserve and motor functioning in MS. Instead, only preliminary data have been presented on brain reserve and general physical disability (Sumowski et al., 2014b). As such, the purpose of this dissertation was to examine the protective effect of brain reserve, estimated via intracranial volume (ICV), on fine motor functioning in relapse-onset MS patients. A sample of 178 relapse-onset, right-handed MS patients underwent neuropsychological testing along with neurological examination, including magnetic resonance imaging (MRI). As part of the evaluation, patients were administered the Nine Hole Peg Test (NHPT; a measure of fine motor speed and dexterity) and the Finger Tapping Test (FTT; a measure of manual motor speed), which served as this study’s outcomes (i.e., dependent variables). Predictors (i.e., independent variables) included demographic variables (age, sex), disease variables (disease duration and disease phenotype, including relapsing-remitting MS (RRMS) or secondary-progressive MS (SPMS)), MRI estimates of disease burden (T2 lesion volume [T2LV], normalized brain volumes as measures of cerebral atrophy), and MRI-derived measures of ICV as an estimate of brain reserve. Results revealed that phenotype (r = .56, p < .001) significantly predicted performance on the NHPT, such that patients with SPMS did worse than patients with RRMS. Regarding disease burden, T2LV (r = .24, p = .001) and normalized gray matter volume (r = -.18, p = .019) predicted NHPT, with less disease burden associated with better performance. Greater ICV (r = -.21, p =.006) was also significantly associated with better performance on the NHPT. Next, phenotype (r = -.45, p < .001) predicted FTT with SPMS patients again performing worse than RRMS patients. Sex (r = .40, p < .001) was a significant predictor of FTT with men outperforming women, on average. For FTT, normalized gray matter volume (r = .36, p < .001) was the only measure of disease burden that predicted performance, with greater volume (i.e., less atrophy) associated with better performance. Similarly, greater ICV (r = .31, p < .001) significantly predicted better performance on the FTT. For both NHPT and FTT, interactions between measures of disease burden and ICV were not significant. As such, some evidence from this study was not consistent with the reserve hypothesis; however, this finding may be due to differences in the way brain reserve impacts motor outcomes (relative to cognitive outcomes). Nonetheless, as ICV was associated with better performance for both outcome measures, these findings provide partial support for the brain reserve hypothesis in fine motor functioning in MS. Therefore, findings from this study have real-life applications with regard to improved understanding of fine motor disability in MS and identification of patients at risk for upper extremity dysfunction, leading to the possibility of early intervention. Findings also have implications for informing clinical research in MS. Future research should examine the protective effect of brain reserve on fine motor functioning within larger cross-sectional samples (i.e., RRMS vs. SPMS), within primary-progressive MS (PPMS) patients, and when using additional measures of upper extremity disability (e.g., Grip Strength Test). Longitudinal research would also help to determine whether there is a moderating effect of brain reserve on fine motor disability progression as well as allow patients to serve as their own baseline, which would control for individual differences in motor functioning. Next, examining reserve in patients experiencing lesions and atrophy in specific brain regions underlying motor function (e.g., cerebellum and precentral gyrus) may help explain why interactions between disease burden and ICV were not significant within the present study. Finally, by testing the brain reserve hypothesis as it relates to fine motor functioning in non-clinical, healthy controls, it would be possible to determine whether the protective effect of reserve is present premorbidly.

Objetivo: Avaliar quais fatores são relevantes no desenvolvimento neuropsicológico e de linguagem em pacientes portadores da Síndrome de Crouzon. Modelo: Estudo transversal em pacientes com Síndrome de Crouzon com diagnóstico estabelecido por genética clinica, submetidos a protocolo de avaliação multidisciplinar (avaliação clínica, social, neuropsicológica, fonoaudiológica e neurorradiológica). Local: Hospital de Reabilitação de Anomalias Craniofaciais, Universidade de São Paulo (HRAC-USP), Bauru. Pacientes: Foram selecionados 10 pacientes que preencheram todos os critérios de inclusão. Todos os pacientes eram acompanhados no Ambulatório de Cirurgia Craniofacial do HRAC-USP, e foram submetidos a avaliação clínica, perfil sócio-econômico, avaliação neuropsicológica, avaliação fonoaudiológica, questionário de qualidade de vida familiar e ressonância magnética encefálica. Resultados: Houve correlação estatisticamente significante entre o desenvolvimento neuropsicológico e o diagnóstico fonoaudiológico (p=0,003). Entretanto, fatores como a realização de cirurgia craniana, alterações encontradas em neuroimagem, aspectos sócio-econômicos e qualidade de vida familiar não influenciaram no desenvolvimento neuropsicológico e de linguagem. Em relação à qualidade de vida, houve predomínio do fator 2 (pessimismo) do questionário de recursos e estresse simplificado. Conclusões: Na amostra estudada, existiu correlação entre o desenvolvimento neuropsicológico e de linguagem. / Objective: To evaluate relevant factors to the neuropsychological development and language acquisition in patients with Crouzon syndrome. Model: Transversal study of patients with Crouzon syndrome diagnosed by clinical genetics examination, who underwent a multidisciplinary team assessment (craniofacial, socioeconomic, neuroradiological, neuropsychological and language evaluations). Setting: Hospital de Reabilitação de Anomalias Craniofaciais, Universidade de São Paulo (HRAC-USP), Bauru. Participants: Ten patients with Crouzon syndrome accompanied by the craniofacial surgery team of the HRAC-USP, who fulfilled all the inclusion criteria, and underwent clinical, socioeconomic, neuropsychological, language, quality of life and neuroradiological (brain magnetic resonance imaging) assessments. Results: Neuropsychological development and language performance had a statistically significant correlation (p=0,003). However, variables as craniofacial surgery, neuroimaging abnormalities, socioeconomic and quality of life findings did not show any relationship with either neuropsychological or language development. Regarding to quality of life, there was a higher prevalence of pessimism (factor II of the short form of the questionnaire on resources and stress). Conclusions: In the present study, we found a correlation between neuropsychological development and language acquisition.

Objetivo: Avaliar as alterações cranianas e encefálicas de pacientes com encefalocele anterior e analisar fatores relevantes ao seu desenvolvimento neuropsicológico, de linguagem e na qualidade de vida. Modelo: Estudo transversal em pacientes com encefalocele anterior submetidos à avaliação multidisciplinar (craniofacial, socioeconômica, neurorradiológica, neuropsicológica e fonoaudiológica). Local: Hospital de Reabilitação de Anomalias Craniofaciais, Universidade de São Paulo (HRAC-USP), Bauru. Participantes: Dez pacientes com encefalocele anterior em acompanhamento com equipe de cirurgia craniofacial do HRAC-USP, submetidos à avaliação neurorradiológica (tomografia de crânio e ressonância magnética encefálica), socioeconômica, neuropsicológica, de linguagem e de qualidade de vida familiar. Resultados: Houve predomínio das encefaloceles fronto-etmoidais (70% dos pacientes), sendo malformação de corpo caloso a alteração encefálica mais encontrada (60%). Observou-se deficiência intelectual em 30%, distúrbio de linguagem em 40% e de aprendizagem em 30%. Houve correlação estatisticamente significante (p=0,045) entre diagnóstico neuropsicológico e o de linguagem. Variáveis como classe socioeconômica, nível educacional dos pais, malformações encefálicas e qualidade de vida familiar não se correlacionaram com os achados neuropsicológicos ou de linguagem. O fator II (pessimismo) do questionário de recursos e estresse simplificado predominou em 60% dos casos. Conclusões: Alterações cranianas, encefálicas, neuropsicológicas e de linguagem de pacientes com encefalocele anterior foram analisadas, havendo correlação entre o diagnóstico neuropsicológico e o de linguagem. / Objective: To evaluate cranial and brain abnormalities in patients with anterior encephalocele and to analyze relevant aspects to their neuropsychological development, language and quality of live. Model: Transversal study in patients with anterior encephalocele, who underwent a multidisciplinary team assessment (craniofacial, socioeconomic, neuroradiological, neuropsychological and language evaluations). Setting: Hospital de Reabilitação de Anomalias Craniofaciais, Universidade de São Paulo (HRAC-USP), Bauru. Participants: Ten patients with anterior encephalocele accompanied by the craniofacial surgery team of the HRAC-USP, who underwent neuroradiological (skull computed tomography and brain magnetic resonance), socioeconomic, neuropsychological, language and quality of life evaluations. Results: There was predominance of frontoethmoidal encephaloceles (70% of patients), and corpus callosum malformation was the most frequent brain abnormality (60%). Intellectual disability was observed in 30%, language disorder in 40% and learning disorder in 30%. Significant statistical correlation (p=0,045) was found between neuropsychological and language diagnoses. Variables such as socioeconomic status, parents educational level, brain abnormalities and quality of life did not correlate either to neuropsychological or language findings. Factor II (pessimism) of the short form of the questionnaire on resources and stress was predominant in 60% of the cases. Conclusions: Cranial, brain, neuropsychological and language disorders of patients with anterior encephalocele were analyzed, showing presence of correlation between the neuropsychological diagnosis and the language one.

INTRODUÇÃO: Portadores de esquizofrenia podem apresentar déficits cognitivos proeminentes, especialmente nos campos da atenção, memória e funções executivas. Este trabalho teve a finalidade de propor e investigar um programa de treino cognitivo da atenção e memória de baixo custo, realizado em grupos, para pacientes brasileiros com esquizofrenia. MÉTODOS: Cinqüenta e sete pacientes ambulatoriais de duas instituições de saúde mental, de ambos os sexos, com idades entre 18 e 50 anos, que preencheram os critérios do DSM-IV-R para esquizofrenia foram convidados a participar do estudo. Os pacientes foram triados quanto ao tipo de medicação utilizada, histórico de doenças neurológicas, abuso ou dependência atual de substâncias psicoativas, ter participado de programa de treino cognitivo nos últimos 6 meses, e avaliados quanto aos sintomas, quoeficiente de inteligência (Q.I.), atenção, memória e qualidade de vida. Dezessete pacientes compuseram a amostra final e foram aleatorizados em dois grupos, treino cognitivo ou treino placebo. As intervenções tiveram duração total de 20 sessões, ao longo de cinco meses. Os profissionais responsáveis pelas avaliações foram cegos a qual condição os pacientes foram alocados, bem como os pacientes, que não sabiam a qual grupo pertenciam. Para as análises estatísticas, na comparação dos grupos na linha de base foram utilizados o teste Mann-Whitney para as variáveis contínuas e o teste qui-quadrado para as variáveis categóricas. Para as comparações entre os grupos em diferentes momentos (antes e após as intervenções) foi utilizada ANOVA não paramétrica de dados ordinais com medidas repetidas. RESULTADOS: Não houve diferença entre os grupos com respeito à instituição à qual os pacientes pertenciam, sexo, idade, estado civil, escolaridade, tipo de medicação utilizada, tempo de doença, número de internações e quoeficiente de inteligência (Q.I.) Os grupos também foram comparáveis na linha de base quanto à sintomatologia, medidas atencionais e medidas de memória, com exceção da memória visual de longo prazo, sendo que o grupo experimental apresentou desempenho superior. Algumas diferenças também foram encontradas na qualidade de vida na linha de base, sendo que o grupo experimental apresentou visão da saúde em geral e da saúde psicológica mais positiva do que o experimental. As analises finais indicaram melhora do grupo experimental em relação ao placebo em controle inibitório e melhora do grupo experimental em atenção alternada ao longo do tempo. Ambos os grupos apresentaram melhoras em processamento de informação, atenção seletiva, funções executivas e memória visual de longo prazo. O grupo placebo apresentou melhoras em comparação ao controle em velocidade de processamento, concentração e memória verbal de longo prazo. Não foram encontradas diferenças em funcionalidade da memória ou qualidade de vida. Quanto à sintomatologia, ambos os grupos apresentaram melhoras nas sub-escalas sintomas positivos e psicopatologia geral da Escala das Síndromes Positivas e Negativas em Esquizofrenia PANSS ao longo do tempo. CONCLUSÕES: O treino cognitivo de baixo custo aqui proposto pode proporcionar algumas melhoras cognitivas, especialmente sobre o sub-domínio atencional de controle inibitório e se mostra valido para o tratamento de pacientes com esquizofrenia / INTRODUCTION: Patients with schizophrenia can have prominent cognitive deficits, especially in attention, memory and executive functions. Therefore, this research aimed to propose and assess a low cost attention and memory cognitive training program, to be delivered in small groups, for Brazilian patients with schizophrenia. METHOD: Fifty-seven outpatients from two mental health units, from both genders, with ages between 18 and 50 years and who fulfilled DSM-IV-R criteria for schizophrenia were invited to participate in this trial. Subjects were screened based on the type of medication, history of neurological conditions, abuse or dependency of psychoactive substances, participation in a cognitive training program in the last six months, and were assessed for symptoms, intelligence quoeficiente (I.Q.), attention, memory and quality of life. Seventeen subjects comprised the final sample and were randomized in two groups: cognitive training or placebo training. Each intervention was composed of a total of 20 sessions, which took place along five months. Raters were blind to patients condition, as well as the patients, who did not know to each group they were allocated. In order to compare groups on baseline, Mann-Whitney test was used to the continuous variables and qui-squared test was used to the categorical variables. A nonparametric repeated measures ANOVA was used for comparisons between groups in different moments (pre and post intervention). RESULTS: There were no significant differences between groups in relation to mental health unit to which they had been treated, gender, age, marital status, schooling, medication, disease duration, number of hospitalization and I.Q. Groups were also matched at baseline for symptoms, attention and memory measures, except for long term visual memory, which was superior in the experimental group. Some differences were also observed in quality of life, as the experimental group showed a more positive view of general health and psychological health. Final comparisons indicated an improvement in the experimental group in relation to the placebo group in inhibitory control and improvement of the experimental group along time in alternate attention. Both groups improved in information processing, selective attention, executive functions and long term visual memory. Placebo group showed improvements in relation to the experimental group in measures of processing speed, concentration and long term verbal memory. No differences were found in or quality of life. Both groups improved along time in positive symptoms and general psychopathology as measured by the Positive and negative Syndrome Scale in Schizophrenia (PANSS). CONCLUSIONS: The low-cost cognitive training which was proposed enabled some improvements in cognition, especially in inhibitory control and presents itself as a valid treatment for people with schizophrenia

Introdução: a descrição tradicional da Esclerose Múltipla (EM) enfatiza ser esta uma doença desmielinizante inflamatória acometendo a substância branca (SB) do sistema nervoso central. Porém, nas últimas décadas vêm sendo acumuladas evidências de acometimento da substância cinzenta (SC), tanto em estudos anátomo-patológicos como de imagem quantitativa de ressonância magnética (IRM-q). Este comprometimento da SC é mais evidente na fase crônica progressiva da doença, onde a atrofia predomina, sendo as alterações cognitivas entendidas como algo restrito a esta fase. No entanto, como foi provada a existência de dano axonal precoce na EM, nós hipotetizamos que existe comprometimento de funções superiores detectáveis por exames neuropsicológicos mesmo em pacientes com déficit mínimo. Objetivo: testar a hipótese de que existem alterações cognitivas precoces na EM mesmo com disabilidade mínima e dano tecidual discreto. Método: foram avaliados com bateria neuropsicológica extensiva e exames de IRM-q pormenorizados 17 indivíduos (6 homens e 11 mulheres) com EM recorrente remitente (RR), com diagnóstico clinicamente definido e comprovado por imagem de acordo com os critérios de McDonald. O tempo de doença foi igual ou inferior a cinco anos, contados a partir do diagnóstico e com disabilidade mínima (EDSS menor que 3). Um grupo controle de 17 voluntários normais pareados foi avaliado para comparação. Resultados: os pacientes apresentaram disfunção de funções superiores estatisticamente significantes que incluíram dificuldades de atenção, memória, velocidade de processamento de informação, habilidades visuoespaciais, planejamento, abstração verbal, raciocínio numérico, flexibilidade mental, controle inibitório, compreensão verbal e escores de QI (tanto de QI geral, quanto de QI de execução e verbal). Apresentaram-se preservados com relação aos controles: a capacidade de nomeação, a velocidade de processamento motor e o raciocínio lógico. Na IRM-q houve alterações significativas discretas, compatíveis com a fase inicial da doença. Conclusão: nossos achados sugerem que existe déficit cognitivo precoce na EMRR, mesmo quando a debilidade é incipiente ou ausente. / Introduction: the traditional description of Multiple Sclerosis (MS) emphasizes that this is an inflammatory demyelinating disease affecting the white matter (WM) of the central nervous system. However, in recent decades has been accumulated evidence of involvement of gray matter (GM), both in anatomical and pathological studies as a quantitative magnetic resonance imaging (MRI-q). This impairment of the GM is more evident in chronic progressive disease, where atrophy predominates, and cognitive changes seen as something restricted to this phase. However, as has proven the existence of early axonal damage in MS, we hypothesized that there is impairment of higher functions detectable by neuropsychological tests, even in patients with minimal deficit. Objective: to test the hypothesis that there are early cognitive changes in MS even with disabled with minimal tissue damage and discreet. Methods: we evaluated extensive neuropsychological and MRI scans q-detailed 17 subjects (6 men and 11 women) with relapsing remitting (RR), defined clinically diagnosed and confirmed by the image according to the McDonald criteria. Disease duration was equal to or less than five years, starting from the diagnosis and disabled with minimal (EDSS less than 3). A control group of 17 matched normal volunteers were evaluated for comparison. Results: patients showed impairment of higher functions were statistically significant, which included attention deficit, memory, speed of information processing, visuospatial abilities, planning, verbal abstraction, numerical reasoning, mental flexibility, inhibitory control, verbal comprehension and IQ scores (both IQ general, the implementation of IQ and verbal). Presented are preserved with respect to controls: the ability of appointment, the speed of motor processing and logical reasoning. In MRI-q discrete significant changes consistent with early disease was finding. Conclusion: our findings suggest that cognitive deficits exist in early RR-MS, even when the disability is weak or absent.

<div>Ketogenic diets (KDs) are high-fat low-carbohydrate diets that can exert positive effects on physical and neurological health. The more established therapeutic effects of KD are for treating epilepsy and diabetes. However, KD protective effects may apply to other inflammation related disorders associated with Hypothalamic-Pituitary-Adrenal (HPA) axis dysregulation, such as mood disorders. Chronic stress has been shown to elevate cytokine levels, disrupt neuroendocrine homeostasis, and cause anxiety and depressive-like behavior in animal models. In vitro experiments have shown that ketone bodies, a metabolite produced while on KD, can prevent the production of cytokines elevated in response to chronic stress and other pre-clinical experiments have suggested that ketone bodies can prevent anxiety-like behavior. Although this suggests that KDs have anti-inflammatory and mood stabilizing potential, these effects have yet to be explored. In this experiment, we assessed the behavioral and neuroendocrine effects of KD using male and female Long-Evans rats. Animals underwent three weeks of Chronic Mild Stress (CMS) while on KD or control Chow (CH). Body weight and food intake data were recorded daily, and depressive-like behaviors were assayed after the three weeks. Plasma Beta-Hydroxybutyrate (HB), Corticosterone (CORT) and Interleukin-1 beta (IL-1) were measured after behavior testing, along with hypothalamic Corticotropin-Releasing Hormone (CRH) and Neuropeptide Y (NPY) mRNA expression. CMS induced weight loss and reduced food intake in the control-diet groups, however the KD-fed male and female rats were resistant to CMS-induced weight loss and reduced food take. Female rats fed KD were protected from CMS-induced reductions in plasma CORT and hypothalamic NPY expression. Collectively, these data suggest anti-depressant potential of KDs against chronic stress, particularly in females. </div>

<p>Deficits in impulse control and decision-making have been implicated in the development and maintenance of alcohol use disorders (AUDs). Individuals with AUD often make disadvantageous choices under conditions of probabilistic risk. The Iowa Gambling Task (IGT) is often used to measure risky decision-making, in which impaired individuals tend to favor large, infrequent rewards even when punished for these choices, rather than smaller, safer, and more advantageous rewards. It remains poorly understood if these deficits are behaviors under genetic control and if ethanol intoxication may alter decision-making. High and Low Alcohol Preferring (HAP3 and LAP3, respectively) mice were trained on a novel gambling task to investigate these possible influences. In Experiment 1, HAP3s and LAP3s responded for a 0.1% saccharin solution, choosing between a risky and a safe option. Importantly, choosing the risky option was meant to be ultimately disadvantageous. In Experiment 2, these same HAP3 mice responded for saccharin or saccharin plus 10% ethanol. Contrary to hypothesis, LAP3s preferred the risky option more than HAP3s. Alcohol increased preference for the risky lever, but only in male mice. HAP3 preference for the safe lever may be explained by higher motivation to obtain sweet rewards, or higher overall avidity for responding. Ethanol-induced changes in male risk behavior may be explained by higher androgen levels, but further investigation is required. Similarly, continued research is necessary to optimize a risky decision-making task for both lines, and thus investigate possible genetic differences in risk acceptance that correlate with differences in alcohol intake. </p>

O transtorno bipolar (TB) é um transtorno grave, crônico e recorrente, e com um alto grau de prejuízo social e ocupacional. Pacientes com TB apresentam déficits em funções cognitivas como atenção, memória de trabalho verbal, funcionamento executivo. Estudos recentes têm sugerido que algumas dessas funções cognitivas podem ser candidatas a endofenótipos para o TB. Pacientes com TB também apresentam déficits na função cognitiva de reconhecimento de emoções faciais, mas o papel dessa função cognitiva como candidata a endofenótipo para o TB tem sido pouco estudado. O objetivo deste estudo foi avaliar a existência de déficits no reconhecimento de emoções em pacientes com TB e em seus parentes de primeiro grau quando comparados a um grupo de controles saudáveis. Foram estudados 23 pacientes com TB tipo I, 22 parentes de primeiro grau desses pacientes, e 27 controles saudáveis. Os instrumentos utilizados nas avaliações neuropsicológicas foram: Bateria de Reconhecimento de Emoções da Pennsylvannia (PENNCNP), e os subtestes de Vocabulário e Raciocínio Matricial da Escala Wechsler de Inteligência Abreviada (WASI). A partir dos dados obtidos, realizaram-se análise de variância (ANOVA) para variáveis que seguiam distribuição normal ou teste de Kruskal-Wallis para as demais. Os resultados mostraram que houve diferença estatisticamente significativa no número de respostas corretas para o reconhecimento de emoção tipo medo (p = 0,01) entre os três grupos. Pacientes com TB apresentaram menor número de respostas corretas para a emoção medo quando comparados a seus parentes e a controles saudáveis. Não houve diferença no reconhecimento de emoções faciais para tristeza, felicidade, raiva e neutra. Houve também uma diferença estatisticamente significativa entre os três grupos no tempo médio de resposta para a emoção do tipo felicidade (p = 0,00). Conclui-se assim que distúrbios no reconhecimento de emoções em faces podem não ser candidatos a endofenótipos para o TB tipo I / Bipolar disorder (BD) is a severe, chronic and recurrent disorder, and with a high degree of social and occupational impairment. TB patients have deficits in cognitive functions such as attention, verbal working memory, executive functioning. Recent studies have suggested that some of these cognitive functions may be candidate endophenotypes for TB. TB patients also have deficits in cognitive function of recognition of facial emotions, but the role that cognitive function as a candidate endophenotype for TB has been little studied. The aim of this study was to evaluate the existence of deficits in emotion recognition in patients with TB and their first-degree relatives when compared to a group of healthy controls. 23 patients with BD type I, 22 firstdegree relatives of these patients, and 27 healthy controls were studied. The instruments used in neuropsychological evaluations were: Battery Recognition of Emotions Pennsylvannia (PENNCNP), and subtests Vocabulary and Matrix Reasoning Scale of the Wechsler Abbreviated Intelligence (WAS ). From the data obtained, performed analysis of variance (ANOVA) for variables that followed a normal distribution or the Kruskal - Wallis test to the other. The results showed a statistically significant difference in the number of correct answers for the recognition of emotion fear (p = 0.01) between the three groups type. TB patients had a lower number of correct responses to the emotion fear when compared to their relatives and healthy controls. There was no difference in the recognition of facial emotions sadness, happiness, anger and neutral. There was also a statistically significant difference between groups in the average response time for the emotion of happiness type (p = 0.00). It follows therefore that disturbances in recognizing emotions in faces may not be Candidates for endophenotypes for BD type I

A current challenge in neuroscience and systems biology is to better understand properties that allow organisms to exhibit and sustain appropriate behaviours despite the effects of perturbations (behavioural robustness). There are still significant theoretical difficulties in this endeavour, mainly due to the context-dependent nature of the problem. Biological robustness, in general, is considered in the literature as a property that emerges from the internal structure of organisms, rather than being a dynamical phenomenon involving agent-internal controls, the organism body, and the environment. Our hypothesis is that the capacity for behavioural robustness is rooted in dynamical processes that are distributed between agent ‘brain', body, and environment, rather than warranted exclusively by organisms' internal mechanisms. Distribution is operationally defined here based on perturbation analyses. Evolutionary Robotics (ER) techniques are used here to construct four computational models to study behavioural robustness from a systemic perspective. Dynamical systems theory provides the conceptual framework for these investigations. The first model evolves situated agents in a goalseeking scenario in the presence of neural noise perturbations. Results suggest that evolution implicitly selects neural systems that are noise-resistant during coupling behaviour by concentrating search in regions of the fitness landscape that retain functionality for goal approaching. The second model evolves situated, dynamically limited agents exhibiting minimalcognitive behaviour (categorization task). Results indicate a small but significant tendency toward better performance under most types of perturbations by agents showing further cognitivebehavioural dependency on their environments. The third model evolves experience-dependent robust behaviour in embodied, one-legged walking agents. Evidence suggests that robustness is rooted in both internal and external dynamics, but robust motion emerges always from the systemin-coupling. The fourth model implements a historically dependent, mobile-object tracking task under sensorimotor perturbations. Results indicate two different modes of distribution, one in which inner controls necessarily depend on a set of specific environmental factors to exhibit behaviour, then these controls will be more vulnerable to perturbations on that set, and another for which these factors are equally sufficient for behaviours. Vulnerability to perturbations depends on the particular distribution. In contrast to most existing approaches to the study of robustness, this thesis argues that behavioural robustness is better understood in the context of agent-environment dynamical couplings, not in terms of internal mechanisms. Such couplings, however, are not always the full determinants of robustness. Challenges and limitations of our approach are also identified for future studies.