Brain aging is a heterogeneous phenomenon, and this thesis illustrates how the course of aging can vary within individuals over time and between individuals as a function of age, sex, and genetic variability. We used two contrasts from magnetic resonance imaging (MRI), namely spin-lattice T1-weighted imaging, and quantitative susceptibility mapping (QSM) from gradient-echo images, to picture the aging brain, by means of morphometric measures and brain-iron concentrations. Within each study, the same rigorous imaging acquisitioning protocols were used over large samples sizes of 167-183 individuals, which contribute to the uniqueness of the studies. Most of the current knowledge about the aging brain rests on the foundation of cross-sectional age-related differences, and studies I and III contribute to current knowledge with longitudinal designs to investigate individual rates of change. The importance of genetic variation in relation to regional brain changes was addressed with a specific emphasis on functional polymorphisms involved in pro-inflammatory responses. These studies further shed light on the importance of bi-directional relations between structural integrity and maintained cognitive abilities over time. Study II is the largest study to date to have quantitative susceptibility estimates examined in healthy adults, and the first in-vivo report to show a lowering in overall subcortical brain iron estimates in women from midlife to old age. Studies I and III are unique by examining longitudinal differences in anatomical brain regions using high resolution images from a 4 Tesla scanner. Peripheral vascular risk factors were not strong determinants of either brain- or cognitive changes in the studied samples. The results are discussed in the context of cognitive reserve, the brain maintenance hypothesis, and potential influences of hormones, inflammation and oxidative stress.

L’objectif de ce travail était d’appréhender le déficit associatif en mémoire épisodique des adultes âgés en termes de déclin des processus stratégiques. Comme composantes du déficit lié à l’âge des processus stratégiques, nous avons étudié les stratégies de mémoire en tant qu’opérations contrôlées, puis dans le cadre de la métamémoire en tant que processus de régulation, et finalement selon une approche neuropsychologique nous avons considéré le fonctionnement exécutivo-frontal comme élément essentiel de la mise en œuvre de stratégies mnésiques. L’ensemble des résultats suggère que le déficit associatif des adultes âgés est en partie dû à leur diminution des capacités d’initiation, d’exécution et d’adaptation de stratégies lors de l’encodage et de la récupération. En outre, le dysfonctionnement exécutif des adultes âgés limiterait leur capacité d’exploiter efficacement une stratégie mise en œuvre à l’apprentissage et à la récupération. Toutefois, l’augmentation de la quantité de support cognitif et l’amélioration de la qualité de ce dernier a permis de compenser leur déficit associatif en mémoire épisodique. Globalement, ce travail suggère que les adultes âgés bénéficieraient d’une réserve cognitive qui leur permettrait, à condition de support et d’entraînement cognitif, de compenser en partie leur déficit associatif en mémoire épisodique. / The main goal of this thesis was to evaluate the age-related associative memory deficit in terms of encoding and retrieval strategies impairment. We studied memory strategies in terms of control processes, then within metamemory framework in terms of regulation process, and finally according to a neuropsychological approach we considered the executive control as a critical factor in the implementation of memory strategies. Results suggest that the age-related associative deficit is partly due to their reduction of the abilities of initiation, implementation and adaptation of strategies during encoding and retrieval. Moreover, the age-related executive dysfunction would restrict their ability to exploit efficiently a strategy implemented during encoding and/or retrieval. Nevertheless, the increase of the quantity of cognitive support and the improvement of its quality allowed compensating their associative deficit in episodic memory. Finally, this thesis suggests that older adults benefit from cognitive plasticity which would allow them, on the condition of support and on cognitive training, partly compensating their associative memory deficit.

Previous research has shown that individuals who are inconsistently handed (IH) outperform consistently handed (IH) individuals on episodic and spatial memory tasks as well as many others. This current study examines whether handedness is related to a person’s ability to recall autobiographical memories (AM) - episodic memories about oneself. Participants were first asked to recall seven memories that will be cued by seven cue words: earth, friend, dream, power, love, trouble, and opinion. They later expanded on those memories to include more detail, then self-rated how well they were able to remember them on five aspects of AM (spatial layout, content, reliving, vividness, and belief) using a modified version of the Autobiographical Memory Questionnaire (AMQ). Ninety-seven participants (44.3% female, Age: 19 to 69 years) were included in the data analysis. All ninety-seven were recruited through Amazon’s Mechanical Turk system and were financially compensated for their time. Results showed no main effect of handedness on AM in regards to all five AM aspects tested, meaning IH’s did not outperform CH’s in regards to autobiographical memory recall.

Understanding the mnemonic functions of the brain has been extensively facilitated by the development of functional neuroimaging techniques such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). The present thesis aims at investigating the neural mechanisms underlying memory for personally experienced events (episodic memory), using PET. In paper I, similarities between encoding and retrieval of enacted (motor) information were explored. We observed increased retrieval activation in right premotor areas in the brain when sentences encoded by motor enactment and sentences encoded by maintenance rehearsal were contrasted. In paper II, overlap between encoding and retrieval was explicitly tested for three types of event information: spatial, item, and temporal. Using conjunction analyses, we found that encoding and retrieval of spatial information was associated with increased brain activity in bilateral inferior parietal regions. Encoding and retrieval of item information were related to increased activation in right inferior temporal cortex, and encoding and retrieval of temporal information were associated with increased activation in left inferior temporal and left inferior frontal cortex. In paper III, brain activity associated with retrieval success was examined. Conditions included three levels of retrieval success (high, medium, and low level), for two types of information (pictures and sentences). The results showed a pattern of activation that distinguished between brain regions involved in processing of sentences vs. processing of pictures. A second pattern that distinguished between brain regions involved in encoding vs. retrieval processes, irrespectively of material (sentences and pictures) and retrieval success, was also found. The manipulation of retrieval success was associated with systematic changes in the correlation between material specific regions and other areas of the brain. In study IV, changes in activation related to successful retrieval of pictures were investigated. More specifically, we expected to find decreases in infero-temporal (IT) regions of the brain that were associated with successful recognition memory. As expected, we found a region in left IT cortex that showed decreased activation related to memory for event information. This decrease in activation could be dissociated from responses related to novelty detection, and perceptual priming. The results from study I and II are discussed in relation to findings and theories regarding similarities between encoding and retrieval processes, and reactivation of modality-specific brain areas important for memory storage. The results from studies III and IV are discussed in relation to differences between encoding and retrieval processes, e.g. asymmetric frontal activation and sub-processes of episodic memory, such as retrieval mode, retrieval success, and novelty detection. Taken together, the studies show that different episodic memory processes are correlated with distinct brain areas, hence supporting the view that remembering is based on multiple component processes. / digitalisering@umu.se

The Diploma thesis is concerned with the human episodic-like memory and its changes during the course of healthy ageing. Episodic memory represents a memory of specific events and their spatiotemporal relations, involving conscious retrieval and mental time travel. As a testable analogy in animals, a concept of episodic-like memory has been suggested and defined as a memory of spatiotemporal location of a certain event in the past ("what-where-when"). Firstly, we focused on a methodological comparison of standard psychological tests of episodic memory and a novel non-verbal computer-based Episodic-Like Memory Test (EMT) with several variants of varying difficulty, capable of discerning the memory for pictures, their sequence and position (Vlček et al., 2009). The second goal of our study was to demonstrate the applicability of the concept of episodic-like memory ("what- where-when") as a model in the testing of human episodic memory. Compared with other tests of episodic memory, EMT test does not depend on the verbalization of content. Contrasting the results obtained from EMT and other standard tests was, therefore, of interest. The results from the EMT test were compared across three age cohorts (N = 58; young, middle-aged, aged) of healthy volunteers. In the spatial domain of episodic-like...

Episodic memory is a key feature in learning. One must remember past events to act upon a present situation. Episodic memory has been reported to be impaired in individuals with schizophrenia. In order to have an intact episodic memory the contextual features (context) must be bound to the content of the event; this mechanism is referred to as contextual binding. It is proposed that binding errors during the encoding process are responsible for episodic memory impairments in schizophrenia. Since the hippocampal formation is considered to be the central element for contextual binding, it is hypothesized that the synaptic disorganization described in this condition results in such a deficit. Moreover, the hippocampus mediates and influences other cognitive processes such as learning and executive functioning. Hence, a contextual binding deficit can have important consequences on cognition, behaviour and emotions. The object of this dissertation was to investigate the neurofunctioning, neuroanatomy and neurofunctional connectivity of the hippocampus while performing a task that utilized contextual binding mechanisms. Since spatial relational processing is part of contextual binding and is rooted in the hippocampal regions, visuospatial navigation, more precisely a wayfinding task, was used as a probe to activate the hippocampus and its associated regions in a group of patients with schizophrenia and matched healthy controls. The following dissertation presents three original research papers contributing to our understanding of the contextual binding and hippocampal deficits in schizophrenia. The first paper investigates the neurofunctioning of the hippocampus with a wayfinding task. The second paper investigates the hippocampal structural abnormality in schizophrenia and how it relates to performance during the wayfinding task. The third paper explores effective connectivity of the hippocampus with other brain regions involved in navigation in schizophrenia with a particular interest in the prefrontal cortex. These three studies demonstrate significant neurofunctional, neuroanatomical, and neurofunctional connectivity deficits in the hippocampus of the patients with schizophrenia compared to a healthy control population. Results of all three papers are further discussed in terms of research and clinical implications.

Orientador: Elenice Aparecida de Moraes Ferrari / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-24T09:45:43Z (GMT). No. of bitstreams: 1 Mendes_RubiaAparecidaPereiradeCarvalho_M.pdf: 3863370 bytes, checksum: 488ca978a38a7cb5f131a008fc5ceac4 (MD5) Previous issue date: 2013 / Resumo: Este estudo investigou a distribuição do cronotipo (matutino, intermediário e vespertino), a sonolência diurna, o desempenho em testes de memória e de compreensão de leitura em estudantes do turno da manhã e da tarde (12 a 17 anos). Na Fase 1, foram utilizados o Questionário de Cronotipo (HO) e o formulário para identificação de queixas de sono (n = 435). Na Fase 2 (n = 81) utilizou-se a Escala de Sonolência de Karolinska (KSS) aplicada imediatamente antes da sessão de testes, que ocorreram em dois horários (7h00 e 16h45), as Escalas de Leitura (EL) e de Desempenho Escolar em Língua Portuguesa (ED), o Teste de Extensão de Dígitos direto e inverso (SPANdir; SPANinv), o Teste dos Blocos de Corsi direto e inverso (CORSIdir; CORSIinv), o Teste de Memória Episódica imediato e tardio (MEI; MET) e o Teste de compreensão da leitura (CLOZE). Os resultados mostraram uma distribuição normal para os diferentes cronotipos, com aumento na vespertinidade em adolescentes mais velhos. As queixas mais freqüentes (Teste qui-quadrado) foram insônia e muita necessidade de sono predominantes em vespertinos, independentemente do turno de estudo. Os adolescentes de cronotipo matutinos estavam menos sonolentos em relação aos vespertinos, em ambos os horários testados, sendo que os testados no horário da tarde estavam menos sonolentos que os da manhã (ANOVA; p < 0,05). A pontuação média na EL e ED classificou os adolescentes em alto nível acadêmico (ANA), média = ou > que 5 (n = 50) e baixo nível acadêmico (BNA), média < que 5 (n = 31). A análise do conjunto de dados de todos os 81 sujeitos (ANA e BNA) mostrou melhor desempenho no teste CORSIinv realizado no horário da tarde (R = -0,5) em adolescentes vespertinos e no teste MET no horário da manhã (R = -0,4) em adolescentes menos sonolentos (Teste de Spearman; p < 0,05). Quando se analisou apenas os sujeitos ANA observou-se melhor desempenho dos adolescentes matutinos nos testes SPANinv realizados no horário da manhã (R = 0,3) e no teste MEI no horário da tarde (R = 0,4). Também foi verificado melhor desempenho em adolescentes menos sonolentos nos testes CORSIinv (R = -0,6) e CLOZE (R = -0,5) realizados no horário da manhã (Teste de Spearman; p < 0,05). Em conjunto, essas análises demonstraram que o cronotipo, a sonolência diurna, o nível de leitura e o desempenho escolar exercem influência no desempenho em testes de memória. Mais ainda, mostram a importância de se avaliar o nível acadêmico do indivíduo para precisar a relação que cronotipo e a sonolência exercem sobre a memória / Abstract: This study investigated the distribution of different chronotypes (morning, indifferent and evening), the diurnal sleepiness, the performance in tests of memory and reading comprehension in students (12-17 years old) of both morning and afternoon school periods. In the Phase 1, we used the Chronotype Questionnaire (HO) and Sleep Complaints form (n = 435). In Phase 2 (n = 81) there has been used the Karolinska Sleepiness Scale (KSS) immediately before the morning (7am) and afternoon (4:45pm) testing sessions, the Reading (SR) and School Performance in Portuguese Language (SP) Scales, the Digit Span (direct, SPANdir and inverse, SPANinv), Corsi Block (direct, CORSIdir and inverse, CORSIinv), Episodic Memory (immediate, IEM and late, LEM) and the reading comprehension test (Cloze). The results showed a normal distribution of the different chronotypes, with increased eveningness in older adolescents. The most frequent sleep complaints ( x -square test) were the need for longer sleep duration and the insomnia. Those complaints were more frequent in the evening type adolescents, regardless of the school period. The morning type adolescents were less sleepier than the evening type adolescents in both testing times, but during afternoon sessions they were less sleepier than during the morning sessions (ANOVA; p < 0,05). The adolescents were classified in high (HAL, score > 5, n = 50), or low academic level (LAL, score < 5, n = 31), accordingly to their SR and SP average score. The analysis considering all the 81 adolescents (ANA e BNA) indicated that evening type had better performance than the morning type adolescents in the CORSIinv test conducted at the afternoon time (R = -0.5), whereas less sleepy adolescents showed better performance than more sleepy adolescents (R = -0.4) in the MET test during the morning session (Spearman test; p < 0.05). Data analysis of the HAL students only showed that morning type adolescents performed better than evening type adolescents in the SPANinv test conducted in the morning (R = 0.3) and MEI test conducted in the afternoon (R= 0.4). Also the performance in CORSIinv (R = -0.6) and CLOZE tests (R = -0.5) was better in less sleepy than in more sleepy adolescents during the morning sessions (Spearman test; p < 0.05). Together, these results demonstrate that the performance of adolescents in memory tests can be influencied by their chronotype, sleepiness and level of academic performance. Furthermore, this study demonstrates that assessment of the academic level helps to clarify the role that chronotype and sleepiness have on memory / Mestrado / Fisiologia / Mestra em Biologia Funcional e Molecular

Animal episodic-like memory tasks represent important component of episodic memory research. However, currently available episodic-like memory tasks are not based on episodic-like memory or encompass important caveats. In our laboratory, we recently devised a novel one-trial trace association task (OTTAT) to examine one-time associations of temporally discontinuous stimuli. This thesis deals with the improvement of OTTAT protocol by rat strain and compartment divider ('doors') selection which optimally promote the establishment of invariable behaviour of rats in OTTAT. Moreover, the accuracy of one-trial associations is also assessed by determining specificity of "rapid escape" response to conditioned stimulus of given sound characteristics. In Experiment 1, rats (Sprague-Dawley (SD), n = 36; Wistar (WI), n = 17; Long-Evans (LE), n = 8) were habituated 15 min daily for 3 days with standard doors (9 x 11 cm opening) to modified light and dark apparatus. The number of transfers between compartments and values of time spent in dark compartment obtained from 3rd habituation session were evaluated as indicators of invariable behaviour of rats. We found WI rats spend significantly more time in dark compartment than LE (p = 0.002) and SD rats (p = 0.001) and have significantly fewer transfers than LE rats...

Episodic memory enables us to remember and recall life events from the past. Episodic memory is a specific type of long-term declarative memory, which undergoes changes in ontogeny. To examinate of episodic memory, "episodic-like memory model", was developed. This model focuses on three basic components of episodic memory: "What happened", "Where did it happen" and "When did it happen". The aim of this diploma thesis is to develop and to validate of particular tests of episodic memory with consideration for their feasibility for preschool children. In order to study episodic memory we used an "episodic-like memory model" and experiments which focused on: children's verbal ability, differentiation of two perspectives during remembering of events and timing memories on an autobiographical axis. We aimed to inspect the effect of age on performance in these tests, possible links between performance in these experiments and the effect of level and the three components of episodic memory on number of errors made. In our dataset we found a significant effect of the age of children in Sentence repetition test and in test of Object collection in the virtual house, in the same test we found a effect of the level on number of errors. We also found a significant correlation between correct responses in verbal...

A new mathematical model of short-term synaptic plasticity (STP) at the Schaffer collateral is introduced. Like other models of STP, the new model relates short-term synaptic plasticity to an interaction between facilitative and depressive dynamic influences. Unlike previous models, the new model successfully simulates facilitative and depressive dynamics within the framework of the synaptic vesicle cycle. The novelty of the model lies in the description of a competitive interaction between calcium-sensitive proteins for binding sites on the vesicle release machinery. By attributing specific molecular causes to observable presynaptic effects, the new model of STP can predict the effects of specific alterations to the presynaptic neurotransmitter release mechanism. This understanding will guide further experiments into presynaptic functionality, and may contribute insights into the development of pharmaceuticals that target illnesses manifesting aberrant synaptic dynamics, such as Fragile-X syndrome and schizophrenia. The new model of STP will also add realism to brain circuit models that simulate cognitive processes such as attention and memory. The hippocampal processing loop is an example of a brain circuit involved in memory formation. The hippocampus filters and organizes large amounts of spatio-temporal data in real time according to contextual significance. The role of synaptic dynamics in the hippocampal system is speculated to help keep the system close to a region of instability that increases encoding capacity and discriminating capability. In particular, synaptic dynamics at the Schaffer collateral are proposed to coordinate the output of the highly dynamic CA3 region of the hippocampus with the phase-code in the CA1 that modulates communication between the hippocampus and the neocortex.