Esta tese consiste da elaboração, validação, aplicação e avaliação de uma Sequência Didática (SD) para licenciandos de Ciências Biológicas, baseada em Ensino por Investigação (EI) e Pesquisa Baseada em Design (DBR, sigla do termo em inglês, Design Based Research), que utiliza episódios da História da Biologia do século XVIII, com os objetivos gerais de promover conhecimentos históricos específicos (conteúdo histórico), revisitar conceitos dos tipos de reprodução animal (conteúdo científico) sob a perspectiva de sua aplicação didática e promover concepções informadas sobre a Natureza da Ciência (NdC). Os episódios históricos foram orientados nas investigações de reprodução animal realizados pelos naturalistas genebreses Charles Bonnet (1720-1793) e Abraham Trembley (1710-1784) que culminaram no reconhecimento de modos de reprodução assexual, alguns deles desconhecidos até então. Ao estudar espécimes de afídeos, popularmente conhecido como \"pulgões\", Bonnet identificou e descreveu a \"multiplicação sem acasalamento\" (partenogênese). Ao estudar os \"pólipos de água doce\" (hidra, do grupo dos cnidários), Trembley descreveu a reprodução por regeneração e brotamento. Com base nos métodos de pesquisa da História da Ciência, esses conteúdos históricos são apresentados em capítulos específicos a fim de oferecer o contexto mais amplo da pesquisa com seres vivos no século XVIII. O conteúdo histórico subsidiou a criação de materiais instrucionais que resultaram em produtos educacionais da presente tese. O primeiro deles são Narrativas Históricas, estruturadas segundo o Ensino por Investigação, em que o conteúdo é organizado a partir das próprias questões de pesquisa Trembley e Bonnet, utilizando linguagem coloquial e posicionando o leitor/aluno no contexto de pesquisa da época. O enredo é ainda entremeado de momentos para pensar (THINK), que provocam interrupções para a discussão de aspectos da natureza da ciência mais diretamente envolvidos. O segundo recurso instrucional desenvolvido se trata de protótipos de um Objeto Virtual de Aprendizagem sobre os estudos de Bonnet com reprodução em pulgões. O terceiro, um roteiro de condução de Replicação Física de Experimentos Históricos, com estudos de Abraham Trembley sobre os pólipos de água doce. Esses materiais instrucionais e as estratégias para sua aplicação junto a estudantes integram uma SD planejada, implementada e analisada segundo a Pesquisa Baseada em Design (DBR). A abordagem DBR se concretiza por aplicações sucessivas, chamadas \"iterações\", de versões da SD, chamadas \"protótipos\", de cujas análises são extraídos Princípios de Design que devem nortear não apenas o refinamento da SD ao longo das iterações em curso, como oferecer parâmetros, tanto teóricos quanto práticos, para a construção de novas SDs, em contextos semelhantes de ensino. A SD elaborada nesta pesquisa passou por duas validações e duas iterações. A primeira validação foi realizada por quatro professores da escola básica participantes do Laboratório de História da Biologia e Ensino do IB-USP, em 2015. A segunda validação foi realizada por especialistas da pesquisa de interface entre história e filosofia da ciência e ensino, da Universidade de Buenos Aires e Instituto, Buenos Aires, Argentina, em 2017. A primeira iteração da SD foi realizada com dez licenciandos matriculados na disciplina optativa livre Estratégias para o Ensino de Genética e Evolução no Ensino Médio, do curso de Ciências Biológicas do Instituto de Biociências da Universidade de São Paulo (IB-USP), no 2º semestre de 2015. A segunda, com 10 licenciandos da disciplina de Prática Pedagógica em Biologia I, do curso de Licenciatura em Ciências, habilitação em Ciências Biológicas, da Universidade Federal de São Paulo (Unifesp), campus de Diadema, no segundo semestre de 2016. Em ambos os casos, foi apresentado Termo de Consentimento Livre e Esclarecido (TCLE) aos participantes da pesquisa. Os instrumentos de coleta de dados compreenderam observação do pesquisador, gravação de áudio das atividades, produções dos alunos, questionários e entrevistas. Para a análise, preponderantemente qualitativa, foi realizada triangulação dos dados coletados e comparação cm rubricas previamente validadas e estabelecidas, com o objetivo de determinar as variáveis relevantes na promoção da aprendizagem dos conteúdos metacientíficos e científicos abordados na SD e no delineamento de indicadores para proposição de Princípios de Design. Os resultados deste trabalho, coletados por meio de ciclos iterativos de protótipos de uma SD fundamentados pelo DBR, permitem concluir que a associação entre episódios da história da biologia, natureza da ciência e ensino por investigação é uma estratégia eficiente para a promoção de aspectos relacionados ao fazer científico em disciplinas da formação inicial docente. Para aumentar a robustez dos Princípios de Design construídos nesta tese, novos ciclos de iteração, com número crescente alunos e cenários, são recomendados / This dissertation comprises of the elaboration, validation, application and evaluation of a Teaching Learning Sequence (TLS) aimed at preservice teachers of Biological Sciences, structured on Inquiry learning (EI) and Design Based Research (DBR) and based on episodes from the History of Biology of the eighteenth century. The main objectives of this dissertation are to promote specific historical knowledge (historical content), to review concepts of animal reproduction (scientific content) from the perspective of its didactic application and to foster informed conceptions about Nature of Science (NOS). The historical episodes were based in the studies on animal reproduction carried out by the naturalists Charles Bonnet (1720-1793) and Abraham Trembley (1710-1784) who culminated in the understanding of modes of asexual reproduction, some of them unknown until then. When studying specimens of aphids, popularly known as \"aphids\", Bonnet was able to identify and to describe the phenomenon of \"multiplication without mating\" (parthenogenesis). Abraham Trembley, when collecting and isolating water insects, observed a kind of creature, later named \"freshwater polyps\" (hydra, from the group of cnidarians). Their studies on hydra culminated on \"discovery\" of reproduction by regeneration and budding. Besides, based on research methods of History of Science, the historical contents were developed and presented in specific chapters in order to offer the broader context of research on living beings in the eighteenth century. Also, the historical content might subside the creation of instructional resources - the educational products of this dissertation. The first one are Historical Narratives, textual resources structured according to Inquiry learning, whose content is organized using problems from the very studies of Trembley and Bonnet, using colloquial language and positioning the reader/student in the research context of the time. The plot is still interspersed with THINK questions, which are specific break moments in order to discuss explicitly aspects of NOS most directly involved. The second resource are prototypes of a Virtual Learning Object based on Bonnet studies about reproduction in aphids. The third one, is a script of Physical Replication of Historical Experiments, about Abraham Trembley\'s studies on freshwater polyps. These instructional resources and didactical strategies compose a TLS, implemented, validated and analyzed according to the Design-Based Research (DBR). The DBR approach is a methodological and theoretical framework implemented through successive applications, or \"iterations\" of TLS versions (prototypes), after cycles of data analysis are extracted Design Principles that should guide not only the refinement of TLS during the ongoing iterations, as helping to create parameters, both theoretical and practical, for the construction of new TLS, in similar teaching contexts. The TLS elaborated in this research underwent two validations and two iterations. The first on was carried out by four primary high school teachers\' members of the Laboratory of History of Biology and Teaching of Institute of Biosciences - USP in 2015. The second one was carried out by specialists on history and philosophy of science and teaching of the University Buenos Aires, Argentina, in 2017. The first iteration of the TLS was applied and evaluated with ten undergraduates enrolled in the elective course, Strategies for Teaching Genetics and Evolution in High School, of the Biological Sciences course of the Institute of Biosciences of the University of São Paulo (IB-USP), in 2015. The second one, applied on ten preservice teachers enrolled on the discipline of Pedagogical Practice in Biology I, with preservice teachers at Federal University of São Paulo (UNIFESP), Diadema, in 2016. In both cases, a Free and Informed Consent Form (TCLE) was administered and signed by the research participants. The instruments of data collection of the TLS prototypes included participative observation, audio recording of activities and strategies, student productions, questionnaires and interviews. Due the predominantly qualitative analysis, the collected data were triangulated and compared to validated and established rubrics, in order to determining the relevant variables in the promotion of the learning of the meta-scientific and scientific content addressed in the TLS and the delineation of indicators for proposition Principles of Design. The results of this work, collected through iterative cycles of TLS prototypes, allow to conclude that the association between episodes of the history of biology, nature of science and Inquiry learning is an efficient strategy for the promotion of NOS aspects related to make scientific in disciplines of initial teacher training. Nevertheless, in order to increase the robustness of the Design Principles proposed in this dissertation, new iteration cycles, if possible increasing the amount of participants and similar educational scenarios, are recommended

Esta tese consiste da elaboração, validação, aplicação e avaliação de uma Sequência Didática (SD) para licenciandos de Ciências Biológicas, baseada em Ensino por Investigação (EI) e Pesquisa Baseada em Design (DBR, sigla do termo em inglês, Design Based Research), que utiliza episódios da História da Biologia do século XVIII, com os objetivos gerais de promover conhecimentos históricos específicos (conteúdo histórico), revisitar conceitos dos tipos de reprodução animal (conteúdo científico) sob a perspectiva de sua aplicação didática e promover concepções informadas sobre a Natureza da Ciência (NdC). Os episódios históricos foram orientados nas investigações de reprodução animal realizados pelos naturalistas genebreses Charles Bonnet (1720-1793) e Abraham Trembley (1710-1784) que culminaram no reconhecimento de modos de reprodução assexual, alguns deles desconhecidos até então. Ao estudar espécimes de afídeos, popularmente conhecido como \"pulgões\", Bonnet identificou e descreveu a \"multiplicação sem acasalamento\" (partenogênese). Ao estudar os \"pólipos de água doce\" (hidra, do grupo dos cnidários), Trembley descreveu a reprodução por regeneração e brotamento. Com base nos métodos de pesquisa da História da Ciência, esses conteúdos históricos são apresentados em capítulos específicos a fim de oferecer o contexto mais amplo da pesquisa com seres vivos no século XVIII. O conteúdo histórico subsidiou a criação de materiais instrucionais que resultaram em produtos educacionais da presente tese. O primeiro deles são Narrativas Históricas, estruturadas segundo o Ensino por Investigação, em que o conteúdo é organizado a partir das próprias questões de pesquisa Trembley e Bonnet, utilizando linguagem coloquial e posicionando o leitor/aluno no contexto de pesquisa da época. O enredo é ainda entremeado de momentos para pensar (THINK), que provocam interrupções para a discussão de aspectos da natureza da ciência mais diretamente envolvidos. O segundo recurso instrucional desenvolvido se trata de protótipos de um Objeto Virtual de Aprendizagem sobre os estudos de Bonnet com reprodução em pulgões. O terceiro, um roteiro de condução de Replicação Física de Experimentos Históricos, com estudos de Abraham Trembley sobre os pólipos de água doce. Esses materiais instrucionais e as estratégias para sua aplicação junto a estudantes integram uma SD planejada, implementada e analisada segundo a Pesquisa Baseada em Design (DBR). A abordagem DBR se concretiza por aplicações sucessivas, chamadas \"iterações\", de versões da SD, chamadas \"protótipos\", de cujas análises são extraídos Princípios de Design que devem nortear não apenas o refinamento da SD ao longo das iterações em curso, como oferecer parâmetros, tanto teóricos quanto práticos, para a construção de novas SDs, em contextos semelhantes de ensino. A SD elaborada nesta pesquisa passou por duas validações e duas iterações. A primeira validação foi realizada por quatro professores da escola básica participantes do Laboratório de História da Biologia e Ensino do IB-USP, em 2015. A segunda validação foi realizada por especialistas da pesquisa de interface entre história e filosofia da ciência e ensino, da Universidade de Buenos Aires e Instituto, Buenos Aires, Argentina, em 2017. A primeira iteração da SD foi realizada com dez licenciandos matriculados na disciplina optativa livre Estratégias para o Ensino de Genética e Evolução no Ensino Médio, do curso de Ciências Biológicas do Instituto de Biociências da Universidade de São Paulo (IB-USP), no 2º semestre de 2015. A segunda, com 10 licenciandos da disciplina de Prática Pedagógica em Biologia I, do curso de Licenciatura em Ciências, habilitação em Ciências Biológicas, da Universidade Federal de São Paulo (Unifesp), campus de Diadema, no segundo semestre de 2016. Em ambos os casos, foi apresentado Termo de Consentimento Livre e Esclarecido (TCLE) aos participantes da pesquisa. Os instrumentos de coleta de dados compreenderam observação do pesquisador, gravação de áudio das atividades, produções dos alunos, questionários e entrevistas. Para a análise, preponderantemente qualitativa, foi realizada triangulação dos dados coletados e comparação cm rubricas previamente validadas e estabelecidas, com o objetivo de determinar as variáveis relevantes na promoção da aprendizagem dos conteúdos metacientíficos e científicos abordados na SD e no delineamento de indicadores para proposição de Princípios de Design. Os resultados deste trabalho, coletados por meio de ciclos iterativos de protótipos de uma SD fundamentados pelo DBR, permitem concluir que a associação entre episódios da história da biologia, natureza da ciência e ensino por investigação é uma estratégia eficiente para a promoção de aspectos relacionados ao fazer científico em disciplinas da formação inicial docente. Para aumentar a robustez dos Princípios de Design construídos nesta tese, novos ciclos de iteração, com número crescente alunos e cenários, são recomendados / This dissertation comprises of the elaboration, validation, application and evaluation of a Teaching Learning Sequence (TLS) aimed at preservice teachers of Biological Sciences, structured on Inquiry learning (EI) and Design Based Research (DBR) and based on episodes from the History of Biology of the eighteenth century. The main objectives of this dissertation are to promote specific historical knowledge (historical content), to review concepts of animal reproduction (scientific content) from the perspective of its didactic application and to foster informed conceptions about Nature of Science (NOS). The historical episodes were based in the studies on animal reproduction carried out by the naturalists Charles Bonnet (1720-1793) and Abraham Trembley (1710-1784) who culminated in the understanding of modes of asexual reproduction, some of them unknown until then. When studying specimens of aphids, popularly known as \"aphids\", Bonnet was able to identify and to describe the phenomenon of \"multiplication without mating\" (parthenogenesis). Abraham Trembley, when collecting and isolating water insects, observed a kind of creature, later named \"freshwater polyps\" (hydra, from the group of cnidarians). Their studies on hydra culminated on \"discovery\" of reproduction by regeneration and budding. Besides, based on research methods of History of Science, the historical contents were developed and presented in specific chapters in order to offer the broader context of research on living beings in the eighteenth century. Also, the historical content might subside the creation of instructional resources - the educational products of this dissertation. The first one are Historical Narratives, textual resources structured according to Inquiry learning, whose content is organized using problems from the very studies of Trembley and Bonnet, using colloquial language and positioning the reader/student in the research context of the time. The plot is still interspersed with THINK questions, which are specific break moments in order to discuss explicitly aspects of NOS most directly involved. The second resource are prototypes of a Virtual Learning Object based on Bonnet studies about reproduction in aphids. The third one, is a script of Physical Replication of Historical Experiments, about Abraham Trembley\'s studies on freshwater polyps. These instructional resources and didactical strategies compose a TLS, implemented, validated and analyzed according to the Design-Based Research (DBR). The DBR approach is a methodological and theoretical framework implemented through successive applications, or \"iterations\" of TLS versions (prototypes), after cycles of data analysis are extracted Design Principles that should guide not only the refinement of TLS during the ongoing iterations, as helping to create parameters, both theoretical and practical, for the construction of new TLS, in similar teaching contexts. The TLS elaborated in this research underwent two validations and two iterations. The first on was carried out by four primary high school teachers\' members of the Laboratory of History of Biology and Teaching of Institute of Biosciences - USP in 2015. The second one was carried out by specialists on history and philosophy of science and teaching of the University Buenos Aires, Argentina, in 2017. The first iteration of the TLS was applied and evaluated with ten undergraduates enrolled in the elective course, Strategies for Teaching Genetics and Evolution in High School, of the Biological Sciences course of the Institute of Biosciences of the University of São Paulo (IB-USP), in 2015. The second one, applied on ten preservice teachers enrolled on the discipline of Pedagogical Practice in Biology I, with preservice teachers at Federal University of São Paulo (UNIFESP), Diadema, in 2016. In both cases, a Free and Informed Consent Form (TCLE) was administered and signed by the research participants. The instruments of data collection of the TLS prototypes included participative observation, audio recording of activities and strategies, student productions, questionnaires and interviews. Due the predominantly qualitative analysis, the collected data were triangulated and compared to validated and established rubrics, in order to determining the relevant variables in the promotion of the learning of the meta-scientific and scientific content addressed in the TLS and the delineation of indicators for proposition Principles of Design. The results of this work, collected through iterative cycles of TLS prototypes, allow to conclude that the association between episodes of the history of biology, nature of science and Inquiry learning is an efficient strategy for the promotion of NOS aspects related to make scientific in disciplines of initial teacher training. Nevertheless, in order to increase the robustness of the Design Principles proposed in this dissertation, new iteration cycles, if possible increasing the amount of participants and similar educational scenarios, are recommended

The mammalian neocortex is integral to all aspects of cognition, in particular perception across all sensory modalities. Whether computational principles can be identified that would explain why the cortex is so versatile and capable of adapting to various inputs is not clear. One well-known hypothesis is that the cortex implements a generative model, actively synthesising internal explanations of the sensory input. This ‘analysis by synthesis’ could be instantiated in the top-down connections in the hierarchy of cortical regions, and allow the cortex to evaluate its internal model and thus learn good representations of sensory input over time. Few computational models however exist that implement these principles. In this thesis, we investigate the deep Boltzmann machine (DBM) as a model of analysis by synthesis in the cortex, and demonstrate how three distinct perceptual phenomena can be interpreted in this light: visual hallucinations, bistable perception, and object-based attention. A common thread is that in all cases, the internally synthesised explanations go beyond, or deviate from, what is in the visual input. The DBM was recently introduced in machine learning, but combines several properties of interest for biological application. It constitutes a hierarchical generative model and carries both the semantics of a connectionist neural network and a probabilistic model. Thus, we can consider neuronal mechanisms but also (approximate) probabilistic inference, which has been proposed to underlie cortical processing, and contribute to the ongoing discussion concerning probabilistic or Bayesian models of cognition. Concretely, making use of the model’s capability to synthesise internal representations of sensory input, we model complex visual hallucinations resulting from loss of vision in Charles Bonnet syndrome.We demonstrate that homeostatic regulation of neuronal firing could be the underlying cause, reproduce various aspects of the syndrome, and examine a role for the neuromodulator acetylcholine. Next, we relate bistable perception to approximate, sampling-based probabilistic inference, and show how neuronal adaptation can be incorporated by providing a biological interpretation for a recently developed sampling algorithm. Finally, we explore how analysis by synthesis could be related to attentional feedback processing, employing the generative aspect of the DBM to implement a form of object-based attention. We thus present a model that uniquely combines several computational principles (sampling, neural processing, unsupervised learning) and is general enough to uniquely address a range of distinct perceptual phenomena. The connection to machine learning ensures theoretical grounding and practical evaluation of the underlying principles. Our results lend further credence to the hypothesis of a generative model in the brain, and promise fruitful interaction between neuroscience and Deep Learning approaches.

Psicólogo / Las alucinaciones visuales son síntomas comunes en cuadros clínicos de diversa etiología. Particularmente en el contexto oftalmológico, el Síndrome de Charles Bonnet (SCB) se ha definido por la presencia de alucinaciones visuales generalmente complejas en sujetos con déficit adquirido en su capacidad visual y psicológicamente normales, pudiendo distinguir la naturaleza irreal de las visiones que experimentan. La presente investigación tiene como objetivo describir alucinaciones visuales y nivel de funcionamiento cognitivo en un grupo de pacientes con agudeza visual deficiente y adquirida con el fin de aportar evidencia sobre las características de las alucinaciones visuales y su presentación con conservación o deterioro de las funciones corticales superiores. Los hallazgos indican que las alucinaciones visuales preponderantes son de tipo elemental y estereotipadas presentándose en asociación a emociones displacenteras. Se observó en el grupo evaluado un nivel intelectual global conservado, destacando disfunción de las capacidades atencionales, mnésicas y de funciones ejecutivas. Se discute si estos déficits cognitivos específicos influyen en la manifestación clínica de alucinaciones visuales

Charles Bonnet syndrome (CBS) is defined as complex persistent visual hallucinations in the absence of mental disorder. It is associated with advanced age and poor vision. It is common, with prevalence estimates of up to 63% among older people with significant visual impairment. CBS would not be diagnosed in the presence of dementia, but its relationship to milder cognitive impairment is unclear. The few studies that have examined this are underpowered and provide contradictory results. There are 16 case reports of dementia emerging in people with a diagnosis of CBS. These cases raise the possibility of an association between impaired insight at diagnosis of CBS and the subsequent development of dementia. This thesis reports the findings of a prospective cohort study which describes changes in cognitive functioning over one year in patients with CBS and age-matched controls. Participants were recruited from low vision and glaucoma assessment clinics. A clinical assessment was carried out by an old age psychiatrist, and participants had a detailed assessment of visual functioning. This thesis also describes the findings of the first study to use voxel-based morphometry (VBM) to investigate changes in volume of grey and white matter in CBS. Participants were recruited from the same clinics as the cohort study, and underwent MRI scanning on a 1.5T scanner, to a protocol designed to produce 1mm3 voxels. Twelve participants with CBS and ten controls were followed up. Two people in the CBS group developed dementia, while none did in the control group. The CBS group showed a mean change in the score on the Addenbrooke’s cognitive examination (ACE-R) of -3.7 points, compared to a change of +1.4 in the control group. This difference was not statistically significant. The CBS participants performed worse on the verbal fluency item of the ACE-R, a difference which was statistically significant. The VBM analysis was conducted on 11 CBS participants and 11 controls. The CBS group showed an increase in grey matter volume in the right cerebellar hemisphere. This difference retained significance after family-wise error correction, non-stationary correction, and ANCOVA to control for the effects of possible confounders. As far as the author is aware, these are the most methodologically robust studies to date to have investigated cognition and morphological brain changes in CBS. The findings of the cohort study were inconclusive. However, the two cases of dementia in CBS patients add weight to the suspicion that this is a clinically important outcome in the condition, and the finding of abnormalities in frontal lobe testing in participants with CBS fits with a theoretical model of visual hallucination generation. Moreover, this type of research appears to be acceptable to a frail and visually disabled population, and studies powered to investigate this issue more fully would be feasible. The VBM findings report the presence of underlying structural brain abnormalities in CBS, in a region not usually associated with visual hallucinations. Possible links with Lewy body dementia, and implications for theories of visual hallucinations, are discussed.