Toxicokinetics of domoic acid in a nonhuman primate model (Macaca fascicularis)

Thesis (Master's)--University of Washington, 2016-06

Genetic influences on cognitive processes associated with distraction: An event-related potential study of the slow wave

The efficiency of inhibitory control processes has been proposed as a mechanism constraining working-memory capacity. In order to investigate genetic influences on processes that may reflect interference control, event-related potential (ER-P) activity recorded at frontal sites, during distracting and nondistracting conditions of a working-memory task, in a sample of 509 twin pairs was examined. The ERP component of interest was the slow wave (SW). Considerable overlap in source of genetic influence was found, with a common genetic factor accounting for 37 - 45% of SW variance irrespective of condition. However, 3 - 8 % of SW variance in the distracting condition was influenced by an independent genetic source. These results suggest that neural responses to irrelevant and distracting information, that may disrupt working-memory performance, differ in a fundamental way from perceptual and memory-based processing in a working-memory task. Furthermore, the results are consistent with the view that cognition is a complex genetic trait influenced by numerous genes of small influence.

Real-Time Gene-Expression Extraction with Fast Classification (FC) Networks

Fast Classification (FC) networks were inspired by a biologically plausible mechanism for short term memory where learning occurs instantaneously. Both weights and the topology for an FC network are mapped directly from the training samples by using a prescriptive training scheme. Only two presentations of the training data are required to train an FC network. Compared with iterative learning algorithms such as Back-propagation (which may require many hundreds of presentations of the training data), the training of FC networks is extremely fast and learning convergence is always guaranteed. Thus FC networks may be suitable for applications where real-time classification is needed. In this paper, the FC networks are applied for the real-time extraction of gene expressions for Chlamydia microarray data. Both the classification performance and learning time of the FC networks are compared with the Multi-Layer Proceptron (MLP) networks and support-vector-machines (SVM) in the same classification task. The FC networks are shown to have extremely fast learning time and comparable classification accuracy.

A MEMÓRIA DE CURTO PRAZO DO UNIVERSITÁRIO E A PRÁTICA DE JOGOS: UM ESTUDO EXPLORATÓRIO

Este estudo avalia inicialmente a memória de curto prazo de estudantes universitários; verifica a seguir as modalidades de jogos por esses universitários e a frequência com que os mesmos são praticados e, finalmente, relaciona o nível de memória de curto prazo verificado com a prática de jogos. Parte da hipótese de que a prática de jogos influencia na memória de curto prazo. Utiliza-se do Teste Pictórico de Memória TEPIC-M de Rueda, F. J. M. e Sisto, F. F., devidamente validado para nossa realidade e de escala auto-avaliativa de prática de jogos de lazer/esporte, a qual visa verificar o tipo de jogo praticado, de movimentação física, raciocínio lógico ou conhecimento e os jogos digitais. Desenvolve-se junto a 100 universitários, de ambos os sexos. Os resultados são analisados por meio do Statistical Package for Social Sciences for Windows, SPSS, versão 12.0. Os níveis de memória de curto prazo encontrados foram muito baixos: Inferior (66%), Médio Inferior (25%); Médio (2%); Médio Superior (6%) e Superior (1%). A prática de jogos em suas diversas modalidades também foi reduzida em Jogos de Movimento, JM, e em Jogos Digitais, JD (25%) e maior em Jogos de Raciocínio, JR (61%). A comparação entre os resultados do TEPIC-M e a frequência de participação em JM, revelou-se positiva, uma vez que os que não praticam nunca JM, 74%, não atingiram sequer o nível médio de memória; o mesmo sendo observado em relação à JD, com 70% dos participantes que não praticam esses jogos, sem atingir o nível médio de memória; e, em relação a JR, uma porcentagem menor (44%) dos que não praticam esses jogos, sem atingir o nível médio de memória, dados que indiretamente, comprovam a hipótese deste estudo.

Length, lexicality, and articulatory suppression in immediate recall:evidence against the articulatory loop

Influential models of short-term memory have attributed the fact that short words are recalled better than longer words in serial recall (the length effect) to articulatory rehearsal. Crucial for this link is the finding that the length effect disappears under articulatory suppression. We show, instead, that, under suppression, the length effect is abolished or reversed for real words but remains robust for nonwords. The latter finding is demonstrated in a variety of conditions: with lists of three and four nonwords, with nonwords drawn from closed and open sets, with spoken and written presentation, and with written and spoken output. Our interpretation is that the standard length effect derives from the number of phonological units to be retained. The length effect is abolished or reversed under suppression because this condition encourages reliance on lexical-semantic representations. Using these representations, longer words can more easily be reconstructed from degraded phonology than shorter words. © 2005 Elsevier Inc. All rights reserved.

School mathematics and dyslexia: aspects of the interrelationship

This investigation sought to explore the nature and extent of school mathematical difficulties among the dyslexic population. Anecdotal reports have suggested that many dyslexics may have difficulties in arithmetic, but few systematic studies have previously been undertaken. The literature pertaining to dyslexia and school mathematics respectively is reviewed. Clues are sought in studies of dyscalculia. These seem inadequate in accounting for dyslexics' reported mathematical difficulties. Similarities between aspects of language and mathematics are examined for underlying commonalities that may partially account for concomitant problems in mathematics, in individuals with a written language dysfunction. The performance of children taught using different mathematics work-schemes is assessed to ascertain if these are associated with differential levels of achievement that may be reflected in the dyslexic population few are found. Findings from studies designed to assess the relationship between written language failure and achievement in mathematics are reported. Study 1 reveals large correlational differences between subtest scores (Wechsler Intelligence Scale for Children, Wechsler, 1976) and three mathematics tests, for young dyslexics and children without literacy difficulties. However, few differences are found between levels of attainment, at this age (6 ½ - 9 years). Further studies indicate that, for dyslexics, achievement in school mathematics, may be independent of measured intelligence, as is the case with their literacy skills. Studies 3 and 4 reveal that dyslexics' performances on a range of school mathematical topics gets relatively worse compared with that of Controls (age range 8 - 17 years), as they get older. Extensive item analyses reveal many errors relating strongly to known deficits in the dyslexics' learning style - poor short-term memory, sequencing skills and verbal labelling strategies. Subgroups of dyslexics are identified on the basis of mathematical performance. Tentative explanations, involving alternative neuropsychological approaches, are offered for the measured differences in attainment between these groups.

Impaired sustained attention and executive dysfunction:bipolar disorder versus depression-specific markers of affective disorders

Objective - To identify neurocognitive measures that could be used as objective markers of bipolar disorder. Methods - We examined executive function, sustained attention and short-term memory as neurocognitive domains in 18 participants with bipolar disorder in euthymic state (Beuth), 14 in depressed state (Bdep), 20 with unipolar depression (Udep) and 28 healthy control participants (HC). We conducted four-group comparisons followed by relevant post hoc analyses. Results - Udep and Bdep, but not Beuth showed impaired executive function (p = 0.045 and p = 0.046, respectively). Both Bdep and Beuth, but not Udep, showed impaired sustained attention (p = 0.001 and p = 0.045, respectively). The four groups did not differ significantly on short-term memory. Impaired sustained attention and executive dysfunction were not associated with depression severity, duration of illness and age of illness onset. Only a small number of abnormal neurocognitive measures were associated with medication in Bdep and Beuth. Conclusion - Impaired sustained attention appears specific to bipolar disorder and present in both Beuth and Bdep; it may represent an objective marker of bipolar disorder. Executive dysfunction by contrast, appears to be present in Udep and Bdep and likely represents a marker of depression.

Morphological-compound dysgraphia in an aphasic patient:"A wild write through the lexicon"

We describe the case of a dysgraphic aphasic individual-S.G.W.-who, in writing to dictation, produced high rates of formally related errors consisting of both lexical substitutions and what we call morphological-compound errors involving legal or illegal combinations of morphemes. These errors were produced in the context of a minimal number of semantic errors. We could exclude problems with phonological discrimination and phonological short-term memory. We also excluded rapid decay of lexical information and/or weak activation of word forms and letter representations since S.G.W.'s spelling showed no effect of delay and no consistent length effects, but, instead, paradoxical complexity effects with segmental, lexical, and morphological errors that were more complex than the target. The case of S.G.W. strongly resembles that of another dysgraphic individual reported in the literature-D.W.-suggesting that this pattern of errors can be replicated across patients. In particular, both patients show unusual errors resulting in the production of neologistic compounds (e.g., "bed button" in response to "bed"). These patterns can be explained if we accept two claims: (a) Brain damage can produce both a reduction and an increase in lexical activation; and (b) there are direct connections between phonological and orthographic lexical representations (a third spelling route). We suggest that both patients are suffering from a difficulty of lexical selection resulting from excessive activation of formally related lexical representations. This hypothesis is strongly supported by S.G.W.'s worse performance in spelling to dictation than in written naming, which shows that a phonological input, activating a cohort of formally related lexical representations, increases selection difficulties. © 2014 Taylor & Francis.

Patterns and effects of notetaking by learning -disabled and nondisabled adolescents: A comparative study

This study analyzes the qualitative and quantitative patterns of notetaking by learning disabled (LD) and nondisabled (ND) adolescents and the effectiveness of notetaking and review as measured by the subjects' ability to recall information presented during a lecture. The study also examines relationships between certain learner characteristics and notetaking. The following notetaking variables were investigated: note completeness, number of critical ideas recorded, levels of processing information, organizational strategies, fluency of notes, and legibility of notes. The learner characteristics examined pertained to measures on achievement, short-term memory, listening comprehension, and verbal ability.^ Students from the 11th and 12th grades were randomly selected from four senior high schools in Dade County, Florida. Seventy learning disabled and 79 nondisabled subjects were shown a video tape lecture and required to take notes. The lecture conditions controlled for presentation rate, prior knowledge, information density, and difficulty level. After 8 weeks, their notes were returned to the subjects for a review period, and a posttest was administered.^ Results of this study suggest significant differences (p $\le$.01) in the patterns of notetaking between LD and ND groups not due to differences in the learner characteristics listed above. In addition, certain notetaking variables such as process levels, number of critical ideas, and note completeness were found to be significantly correlated to learning outcome. Further, deficiencies in the spontaneous use of organizational strategies and abbreviations adversely affected the notetaking effectiveness of learning disabled students.^ Both LD and ND subjects recalled more information recorded in their notes than not recorded. This difference was significant only for the ND group. By contrast, LD subjects compensated for their poor notetaking skills and recalled significantly more information not recorded on their notes than did ND subjects. The major implications of these findings suggest that LD and ND subjects exhibit very different entry behaviors when asked to perform a notetaking task; hence, teaching approaches to notetaking must differ as well. ^

Riconoscimento real-time di gesture tramite tecniche di machine learning

Il riconoscimento delle gesture è un tema di ricerca che sta acquisendo sempre più popolarità, specialmente negli ultimi anni, grazie ai progressi tecnologici dei dispositivi embedded e dei sensori. Lo scopo di questa tesi è quello di utilizzare alcune tecniche di machine learning per realizzare un sistema in grado di riconoscere e classificare in tempo reale i gesti delle mani, a partire dai segnali mioelettrici (EMG) prodotti dai muscoli. Inoltre, per consentire il riconoscimento di movimenti spaziali complessi, verranno elaborati anche segnali di tipo inerziale, provenienti da una Inertial Measurement Unit (IMU) provvista di accelerometro, giroscopio e magnetometro. La prima parte della tesi, oltre ad offrire una panoramica sui dispositivi wearable e sui sensori, si occuperà di analizzare alcune tecniche per la classificazione di sequenze temporali, evidenziandone vantaggi e svantaggi. In particolare, verranno considerati approcci basati su Dynamic Time Warping (DTW), Hidden Markov Models (HMM), e reti neurali ricorrenti (RNN) di tipo Long Short-Term Memory (LSTM), che rappresentano una delle ultime evoluzioni nel campo del deep learning. La seconda parte, invece, riguarderà il progetto vero e proprio. Verrà impiegato il dispositivo wearable Myo di Thalmic Labs come caso di studio, e saranno applicate nel dettaglio le tecniche basate su DTW e HMM per progettare e realizzare un framework in grado di eseguire il riconoscimento real-time di gesture. Il capitolo finale mostrerà i risultati ottenuti (fornendo anche un confronto tra le tecniche analizzate), sia per la classificazione di gesture isolate che per il riconoscimento in tempo reale.

The Role of TET Proteins in the Epigenetic Regulation of Neural Gene Expression and Behavior

Understanding how genes affect behavior is critical to develop precise therapies for human behavioral disorders. The ability to investigate the relationship between genes and behavior has been greatly advanced over the last few decades due to progress in gene-targeting technology. Recently, the Tet gene family was discovered and implicated in epigenetic modification of DNA methylation by converting 5-methylcytosine to 5-hydroxymethylcytosine (5hmC). 5hmC and its catalysts, the TET proteins, are highly abundant in the postnatal brain but with unclear functions. To investigate their neural functions, we generated new lines of Tet1 and Tet3 mutant mice using a gene targeting approach. We designed both mutations to cause a frameshift by deleting the largest coding exon of Tet1 (Tet1Δe4) and the catalytic domain of Tet3 (Tet3Δe7-9). As Tet1 is also highly expressed in embryonic stem cells (ESCs), we generated Tet1 homozygous deleted ESCs through sequential targeting to compare the function of Tet1 in the brain to its role in ESCs. To test our hypothesis that TET proteins epigenetically regulate transcription of key neural genes important for normal brain function, we examined transcriptional and epigenetic differences in the Tet1Δe4 mouse brain. The oxytocin receptor (OXTR), a neural gene implicated in social behaviors, is suggested to be epigenetically regulated by an unknown mechanism. Interestingly, several human studies have found associations between OXTR DNA hypermethylation and a wide spectrum of behavioral traits and neuropsychiatric disorders including autism spectrum disorders. Here we report the first evidence for an epigenetic mechanism of Oxtr transcription as expression of Oxtr is reduced in the brains of Tet1Δe4-/- mice. Likewise, the CpG island overlapping the promoter of Oxtr is hypermethylated during early embryonic development and persists into adulthood. We also discovered altered histone modifications at the hypermethylated regions, indicating the loss of TET1 has broad effects on the chromatin structure at Oxtr. Unexpectedly, we discovered an array of novel mRNA isoforms of Oxtr that are selectively reduced in Tet1Δe4-/- mice. Additionally, Tet1Δe4-/- mice display increased agonistic behaviors and impaired maternal care and short-term memory. Our findings support a novel role for TET1 in regulating Oxtr expression by preventing DNA hypermethylation and implicate TET1 in social behaviors, offering novel insight into Oxtr epigenetic regulation and its role in neuropsychiatric disorders.

Investigating relative clauses in children with specific language impairment

Background: It is well documented that children with Specific Language Impairment (SLI) experience significant grammatical deficits. While much of the focus in the past has been on their morphosyntactic difficulties, less is known about their acquisition of complex syntactic structures such as relative clauses. The role of memory in language performance has also become increasingly prominent in the literature. Aims: This study aims to investigate the control of an important complex syntactic structure, the relative clause, by school age children with SLI in Ireland, using a newly devised sentence recall task. It also aims to explore the role of verbal and short-termworking memory in the performance of children with SLI on the sentence recall task, using a standardized battery of tests based on Baddeley’s model of working memory. Methods and Procedures: Thirty two children with SLI, thirty two age matched typically developing children (AM-TD) between the ages of 6 and 7,11 years and twenty younger typically developing (YTD) children between 4,7 and 5 years, completed the task. The sentence recall (SR) task included 52 complex sentences and 17 fillers. It included relative clauses that are used in natural discourse and that reflect a developmental hierarchy. The relative clauses were also controlled for length and varied in syntactic complexity, representing the full range of syntactic roles. There were seven different relative clause types attached to either the predicate nominal of a copular clause (Pn), or to the direct object of a transitive clause (Do). Responses were recorded, transcribed and entered into a database for analysis. TheWorkingMemory Test Battery for children (WMTB-C—Pickering & Gathercole, 2001) was administered in order to explore the role of short-term memory and working memory on the children’s performance on the SR task. Outcomes and Results: The children with SLI showed significantly greater difficulty than the AM-TD group and the YTD group. With the exception of the genitive subject clauses, the children with SLI scored significantly higher on all sentences containing a Pn main clause than those containing a transitive main clause. Analysis of error types revealed the frequent production of a different type of relative clause than that presented in the task—with a strong word order preference in the NVN direction indicated for the children with SLI. The SR performance for the children with SLI was most highly correlated with expressive language skills and digit recall. Conclusions and Implications: Children with SLI have significantly greater difficulty with relative clauses than YTD children who are on average two years younger—relative clauses are a delay within a delay. Unlike the YTD children they show a tendency to simplify relative clauses in the noun verb noun (NVN) direction. They show a developmental hierarchy in their production of relative clause constructions and are highly influenced by the frequency distribution of the relative clauses in the ambient language.

Imagerie Musicale Involontaire : caractéristiques phénoménologiques et mnésiques

L’imagerie musicale involontaire (IMIN) est un phénomène mental extrêmement commun. Il peut être défini en tant que type d’imagerie mentale musicale qui devient consciente sans effort ou intentionnalité et qui n’est pas pathologique. La forme la plus connue d’IMIN est le « ver d’oreille », qui se présente généralement comme un court extrait musical tournant en boucle en tête et dont on se débarrasse difficilement. L’objectif principal de la présente thèse est d’investiguer les mécanismes cognitifs sous-tendant le phénomène puisque, malgré l’intérêt répandu dans les médias populaires, son étude expérimentale est récente et un modèle intégré n’a pas encore été proposé. Dans la première étude, l’induction expérimentale a été tentée et les caractéristiques des images mentales d’épisodes d’IMIN ont été investiguées. Dans le laboratoire, des chansons accrocheuses (versus des proverbes) ont été présentées répétitivement aux participants qui devaient ensuite les chanter le plus fidèlement possible. Ils ont par après quitté le laboratoire, une enregistreuse numérique en mains, avec la consigne d’enregistrer une reproduction vocale la plus fidèle possible de ce qu’ils avaient en tête lors de tous leurs épisodes d’IMIN sur une période de quatre jours, ainsi que de décrire leur timbre. L’expérience a été répétée deux semaines plus tard. Douze des dix-huit participants du groupe expérimental ont rapporté des pièces induites comme épisodes d’IMIN, ce qui confirme l’efficacité de la procédure d’induction. La tonalité et le tempo des productions ont ensuite été analysés et comparés à ceux des pièces originales. Similairement pour les épisodes d’IMIN induits et les autres, les tempi produits et, dans une moindre mesure pour les non-musiciens, les tonalités étaient proches des originaux. Le timbre décrit était généralement une version simplifiée de l’original (un instrument et/ou une voix). Trois études se sont ensuite intéressées au lien entre le potentiel d’IMIN et la mémorabilité. Dans une étude préliminaire, 150 chansons du palmarès francophone radiophonique ont été évaluées en ligne par 164 participants, sur leur niveau de familiarité, d’appréciation et de potentiel d’IMIN. Les pièces ont ensuite été divisées en groupes de stimuli à faible et à fort potentiel d’IMIN, qui ont été utilisés dans une tâche typique de rappel libre/reconnaissance, premièrement avec des francophones (pour qui les pièces étaient familières) et ensuite avec des non-francophones (pour qui les pièces étaient non-familières). Globalement, les pièces à fort potentiel d’IMIN étaient mieux rappelées et reconnues que les pièces à faible potentiel. Une dernière étude a investigué l’impact de la variabilité inter-stimulus du timbre sur les résultats précédents, en demandant à une chanteuse d’enregistrer les lignes vocales des pièces et en répétant l’expérience avec ces nouveaux stimuli. La différence précédemment observée entre les stimuli à fort et à faible potentiel d’IMIN dans la tâche de reconnaissance a ainsi disparu, ce qui suggère que le timbre est une caractéristique importante pour le potentiel d’IMIN. En guise de conclusion, nous suggérons que les phénomènes mentaux et les mécanismes cognitifs jouant un rôle dans les autres types de souvenirs involontaires peuvent aussi s’appliquer à l’IMIN. Dépendamment du contexte, la récupération mnésique des pièces peut résulter de la répétition en mémoire à court terme, de l’amorçage à court et long terme ou de l’indiçage provenant de stimuli dans l’environnement ou les pensées. Une des plus importantes différences observables entre l’IMIN et les autres souvenirs involontaires est la répétition. Nous proposons que la nature même de la musique, qui est définie par la répétition à un niveau micro- et macro-structurel en est responsable.