Modulation of Mediotemporal and Ventrostriatal Function in Humans by Delta 9-Tetrahydrocannabinol A Neural Basis for the Effects of Cannabis sativa on Learning and Psychosis

Context: Cannabis sativa use can impair verbal learning, provoke acute psychosis, and increase the risk of schizophrenia. It is unclear where C sativa acts in the human brain to modulate verbal learning and to induce psychotic symptoms. Objectives: To investigate the effects of 2 main psychoactive constituents of C sativa, Delta 9-tetrahydrocannabinol (Delta 9-THC) and cannabidiol, on regional brain function during verbal paired associate learning. Design: Subjects were studied on 3 separate occasions using a block design functional magnetic resonance imaging paradigm while performing a verbal paired associate learning task. Each imaging session was preceded by the ingestion of Delta 9-THC (10 mg), cannabidiol (600 mg), or placebo in a double-blind, randomized, placebo-controlled, repeated-measures, within-subject design. Setting: University research center. Participants: Fifteen healthy, native English-speaking, right-handed men of white race/ethnicity who had used C sativa 15 times or less and had minimal exposure to other illicit drugs in their lifetime. Main Outcome Measures: Regional brain activation ( blood oxygen level-dependent response), performance in a verbal learning task, and objective and subjective ratings of psychotic symptoms, anxiety, intoxication, and sedation. Results: Delta 9-Tetrahydrocannabinol increased psychotic symptoms and levels of anxiety, intoxication, and sedation, whereas no significant effect was noted on these parameters following administration of cannabidiol. Performance in the verbal learning task was not significantly modulated by either drug. Administration of Delta 9-THC augmented activation in the parahippocampal gyrus during blocks 2 and 3 such that the normal linear decrement in activation across repeated encoding blocks was no longer evident. Delta 9-Tetrahydrocannabinol also attenuated the normal time-dependent change in ventrostriatal activation during retrieval of word pairs, which was directly correlated with concurrently induced psychotic symptoms. In contrast, administration of cannabidiol had no such effect. Conclusion: The modulation of mediotemporal and ventrostriatal function by Delta 9-THC may underlie the effects of C sativa on verbal learning and psychotic symptoms, respectively.

Symbol/Meaning paired-associate recall: an "archetypal memory" advantage?

The theory of the archetypes and the hypothesis of the collective unconscious are two of the central characteristics of analytical psychology. These provoke, however, varying reactions among academic psychologists. Empirical studies which test these hypotheses are rare. Rosen, Smith, Huston and Gonzales proposed a cognitive psychological experimental paradigm to investigate the nature of archetypes and the collective unconscious as archetypal (evolutionary) memory. In this article we report the results of a cross-cultural replication of Rosen et al. conducted in the German-speaking part of Switzerland. In short, this experiment corroborated previous findings by Rosen et al., based on English speakers, and demonstrated a recall advantage for archetypal symbol meaning pairs vs. other symbol/meaning pairings. The fact that the same pattern of results was observed across two different cultures and languages makes it less likely that they are attributable to a specific cultural or linguistic context.

Cerebellar Pathology Does Not Impair Performance on Identification or Categorization Tasks

In comparison to the basal ganglia, prefrontal cortex, and medial temporal lobes, the cerebellum has been absent from recent research on the neural substrates of categorization and identification, two prominent tasks in the learning and memory literature. To investigate the contribution of the cerebellum to these tasks, we tested patients with cerebellar pathology (seven with bilateral degeneration, six with unilateral lesions, and two with midline damage) on rule-based and information-integration categorization tasks and an identification task. In rule-based tasks, it is assumed that participants learn the categories through an explicit reasoning process. In information-integration tasks, optimal performance requires the integration of information from multiple stimulus dimensions, and participants are typically unaware of the decision strategy. The identification task, in contrast, required participants to learn arbitrary, color-word associations. The cerebellar patients performed similar to matched controls on all three tasks and performance did not vary with the extent of cerebellar pathology. Although the interpretation of these null results requires caution, these data contribute to the current debate on cerebellar contributions to cognition by providing boundary conditions on understanding the neural substrates of categorization and identification, and help define the functional domain of the cerebellum in learning and memory.

Lexical and nonlexical processing in developmental dyslexia: a case for different resources and different impairments

In a group of adult dyslexics word reading and, especially, word spelling are predicted more by what we have called lexical learning (tapped by a paired-associate task with pictures and written nonwords) than by phonological skills. Nonword reading and spelling, instead, are not associated with this task but they are predicted by phonological tasks. Consistently, surface and phonological dyslexics show opposite profiles on lexical learning and phonological tasks. The phonological dyslexics are more impaired on the phonological tasks, while the surface dyslexics are equally or more impaired on the lexical learning tasks. Finally, orthographic lexical learning explains more variation in spelling than in reading, and subtyping based on spelling returns more interpretable results than that based on reading. These results suggest that the quality of lexical representations is crucial to adult literacy skills. This is best measured by spelling and best predicted by a task of lexical learning. We hypothesize that lexical learning taps a uniquely human capacity to form new representations by recombining the units of a restricted set.

Behavioural and neural correlates of operant conditioning in Lymnaea stagnalis : role of previous experience during development /

The freshwater mollusc Lymnaea stagnalis was utilized in this study to further the understanding of how network properties change as a result of associative learning, and to determine whether or not this plasticity is dependent on previous experience during development. The respiratory and neural correlates of operant conditioning were first determined in normally reared Lymnaea. The same procedure was then applied to differentially reared Lymnaea, that is, animals that had never experienced aerial respiration during their development. The aim was to determine whether these animals would demonstrate the same responses to the training paradigm. In normally reared animals, a behavioural reduction in aerial respiration was accompanied by numerous changes within the neural network. Specifically, I provide evidence of changes at the level of the respiratory central pattern generator and the motor output. In the differentially reared animals, there was little behavioural data to suggest learning and memory. There were, however, significant differences in the network parameters, similar to those observed in normally reared animals. This demonstrated an effect of operant conditioning on differentially reared animals. In this thesis, I have identified additional correlates of operant conditioning in normally reared animals and provide evidence of associative learning in differentially reared animals. I conclude plasticity is not dependent on previous experience, but is rather ontogenetically programmed within the neural network.

Aplicação do modelo all-or-none em condições de aquisição de associação aos pares

O presente estudo teve por objetivo submeter a nova verificação experimental o modelo "all-or-none" de aprendizagem de pares-associados, em que as associações estímulo resposta são formadas inteiramente em uma única tentativa. Justifica o presente trabalho a necessidade de estudos na área da teoria da aprendizagem, a fim de fornecer subsídios para uma tecnologia educacional. A hipótese testada foi a de que a probabilidade de uma associação se efetuar é constante para qualquer número de treinos anteriores. Foram testados 100 sujeitos de classe de alfabetização, divididos em 5 grupos, com 5 níveis de reforçamentos e 5 grupos de itens. Foi usado um esquema de quadrados latinos, combinando três fatores em cinco níveis cada um: 1 - número de reforçamentos, 2 - grupo de itens e 3 - grupo de sujeitos. A análise dos resultados levou à aceitação da hipótese de que a aprendizagem é, em essência, all-or-none.

Influência do exercício físico em memória e funções executivas de pessoas com doença de Parkinson

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Memória espacial e morfometria tridimensional da micróglia de CA1 e do giro denteado do Cebus apella

O presente trabalho tem o intuito de Investigar possíveis correlações entre a morfologia da micróglia do hipocampo e giro denteado e o desempenho cognitivo individual em teste de memória espacial no Cebus apella. Devido ao bom desempenho do Cebus apella em tarefas cognitivas hipocampo-dependentes, utilizou-se testes selecionados da Bateria Cambridge de Testes Neuropsicológicos (CANTAB) utilizada previamente com sucesso tanto em primatas do Velho Mundo quanto em humanos. Empregou-se o teste motor de adaptação a tela para checar a adaptação dos indivíduos à tela sensível ao toque e o teste de aprendizado pareado (TAP) para avaliar aprendizado e memória espacial. Para o estudo da correlação entre o desempenho individual no TAP da bateria CANTAB e a morfologia da micróglia, foi necessário reconstruir e analisar parâmetros morfométricos selecionados a partir de micróglias reconstruídas dos terços médio e externo da camada molecular do giro denteado e do lacunosum molecular de CA1, empregando microscopia tridimensional. A definição dos limites da formação hipocampal foi feita empregando-se critérios arquitetônicos previamente definidos. Para imunomarcação seletiva de micróglias foi utilizado o anticorpo policlonal (anti-Iba1) dirigido contra a proteína adaptadora ligante de cálcio ionizado Iba-1. A partir de procedimentos de estatística multivariada identificou-se a ocorrência de agrupamentos microgliais baseados em parâmetros morfométricos que permitiram a distinção de pelo menos dois grandes grupos microgliais em todos os indivíduos. Os resultados comportamentais expressos em taxa de aprendizado e alguns dos parâmetros morfométricos da micróglia dos terços externo e médio da camada molecular do giro denteado revelaram significativas correlações, lineares e não lineares. Em contraste, nenhuma correlação dessa natureza foi encontrada no lacunosum molecular de CA1. Nós sugerimos baseado no presente e em trabalhos anteriores que a correlação entre desempenho cognitivo e a complexidade estrutural da glia não é um atributo exclusivo dos astrócitos e que a morfologia da micróglia da camada molecular do giro denteado pode estar associada ainda que de forma indireta ao desempenho individual em testes de memória espacial.

Estudo exploratório comparativo do declínio cognitivo senil após estimulação multissensorial e cognitiva em idosos institucionalizados e não institucionalizados

O objetivo do presente trabalho foi investigar, empregando testes neuropsicológicos selecionados, a duração dos efeitos benéficos do programa de estimulação multissensorial e cognitiva realizado em idosos vivendo em instituições de longa permanência ou em comunidade. Os participantes do estudo foram idosos institucionalizados (n=20, 75,1 ± 6,8 anos de idade) e não institucionalizados (n=15, 74,1 ± 3,9 anos de idade), com 65 anos de idade ou mais, sem histórico de traumatismo crânio-encefálico, acidente vascular encefálico ou depressão primária, acuidade visual mínima 20/30 mensurada pelo Teste de Snellen e que participaram regularmente do Programa de Estimulação Multissensorial e Cognitiva. Foram realizadas reavaliações em cinco períodos (2, 4, 6, 8 e 12 meses) após a finalização da intervenção multissensorial e cognitiva. Para isso empregou-se o Mini Exame do Estado Mental (MEEM); nomeação de Boston; fluência verbal semântica (FVS) e fonológica (FVF), testes da Bateria Montreal de Avaliação da Comunicação (MAC), Teste de Narrativa “Roubo de Biscoitos” e testes neuropsicológicos selecionados da Bateria Cambridge (CANTAB) incluindo: Triagem Motora (Motor Screening – MOT); Processamento Rápido de Informação Visual (Rapid Visual Information Processing – RVP); Tempo de Reação (Reaction Time - RTI); Aprendizagem Pareada (Paired Associates Learning - PAL); Memória de Trabalho Espacial (Spatial Working Memory - SWM) e Pareamento com Atraso (Delayed matching to sample - DMS). Os resultados apontaram diferenças estatisticamente significativas entre os grupos revelando taxa de declínio cognitivo maior nos idosos institucionalizados. Esses resultados confirmam sugestão anterior de que o ambiente pobre de estímulos somato-motores e cognitivos das instituições de longa permanência aceleram o declínio cognitivo senil. Além disso, a análise das curvas ROC seguido dos cálculos de sensibilidade, especificidade e eficiência para cada teste revelou que os testes da bateria CANTAB para memória e aprendizado espacial pareado assim como para memória espacial de trabalho permitiram a distinção entre os grupos I e NI em todas janelas de reavaliação. Os resultados demonstraram que uma vez cessado o programa de estimulação, se observa em ambos os grupos declínio cognitivo progressivo, com perdas mais precoces e mais intensas nos idosos institucionalizados do que naqueles vivendo em comunidade com suas famílias. Além disso, observou-se que a duração dos efeitos benéficos sobre o desempenho nos testes neuropsicológicos de ambos os grupos é heterogêneo, e que os efeitos de proteção guardam relação estreita com a natureza das oficinas. Por conta disso os escores dos testes de linguagem declinaram mais lentamente. Os resultados reúnem evidências que permitem a recomendação de programas regulares de estimulação somatomotora e cognitiva para idosos institucionalizados com o intuito de promover a redução da taxa de progressão do declínio cognitivo senil.

Visual Speech Segmentation: Using Facial Cues to Locate Word Boundaries in Continuous Speech

Speech is typically a multimodal phenomenon, yet few studies have focused on the exclusive contributions of visual cues to language acquisition. To address this gap, we investigated whether visual prosodic information can facilitate speech segmentation. Previous research has demonstrated that language learners can use lexical stress and pitch cues to segment speech and that learners can extract this information from talking faces. Thus, we created an artificial speech stream that contained minimal segmentation cues and paired it with two synchronous facial displays in which visual prosody was either informative or uninformative for identifying word boundaries. Across three familiarisation conditions (audio stream alone, facial streams alone, and paired audiovisual), learning occurred only when the facial displays were informative to word boundaries, suggesting that facial cues can help learners solve the early challenges of language acquisition.

Activity of primate inferotemporal neurons related to a sought target in pair-association task.

Visual long-term memory in primates has been assessed by using the pair-association (PA) task, in which a subject retrieves and chooses the paired associate of a cue picture. Our previous studies on single neurons in the anterior inferotemporal (AIT) cortex suggested their roles in representing paired associates in the mind. To test the possibility that the delay activity of AIT neurons is related to a particular picture as a sought target, we devised the PA with color switch (PACS) task. In the PACS task, the necessity for memory retrieval and its initiation time were controlled by a color switch in the middle of the delay period. A control task, in which there is no color switch, corresponds to the conventional delayed matching-to-sample (DMS) task where the monkey chooses the same picture as a cue. We found that AIT neurons started to respond just after the color switch in the PACS task, when the cue-optimal picture's associate was presented as a cue. In contrast, they showed no response change in the DMS task. We confirmed that this effect is not due to the visual response to colors. Furthermore, when the cue-optimal picture was presented as a cue, these neurons showed suppression after the color switch in the PACS task. These results suggest that the activity of AIT neurons mediates gating mechanisms that preferentially pass information about a sought target, even when the sought target is retrieved from long-term memory.

Functional activation of the human ventrolateral frontal cortex during mnemonic retrieval of verbal information.

Regional cerebral blood flow was measured with positron emission tomography during the performance of a verbal free recall task, a verbal paired associate task, and tasks that required the production of verbal responses either by speaking or writing. Examination of the differences in regional cerebral blood flow between these conditions demonstrated that the left ventrolateral frontal cortical area 45 is involved in the recall of verbal information from long-term memory, in addition to its contribution to speech. The act of writing activated a network of areas involving posterior parietal cortex and sensorimotor areas but not ventrolateral frontal cortex.

The role of learning and growth hormone-releasing factor in the control of protein intake in rats /

Both learning and basic biological mechanisms have been shown to play a role in the control of protein int^e. It has previously been shown that rats can adapt their dietary selection patterns successfully in the face of changing macronutrient requirements and availability. In particular, it has been demonstrated that when access to dietary protein is restricted for a period of time, rats selectively increase their consumption of a proteincontaining diet when it becomes available. Furthermore, it has been shown that animals are able to associate various orosensory cues with a food's nutrient content. In addition to the role that learning plays in food intake, there are also various biological mechanisms that have been shown to be involved in the control of feeding behaviour. Numerous studies have documented that various hormones and neurotransmitter substances mediate food intake. One such hormone is growth hormone-releasing factor (GRF), a peptide that induces the release of growth hormone (GH) from the anterior pituitary gland. Recent research by Vaccarino and Dickson ( 1 994) suggests that GRF may stimulate food intake by acting as a neurotransmitter in the suprachiasmatic nucleus (SCN) and the adjacent medial preoptic area (MPOA). In particular, when GRF is injected directly into the SCN/MPOA, it has been shown to selectively enhance the intake of protein in both fooddeprived and sated rats. Thus, GRF may play a role in activating protein consumption generally, and when animals have a need for protein, GRF may serve to trigger proteinseeking behaviour. Although researchers have separately examined the role of learning and the central mechanisms involved in the control of protein selection, no one has yet attempted to bring together these two lines of study. Thus, the purpose of this study is to join these two parallel lines of research in order to further our understanding of mechanisms controlling protein selection. In order to ascertain the combined effects that GRF and learning have on protein intake several hypothesis were examined. One major hypothesis was that rats would successfully alter their dietary selection patterns in response to protein restriction. It was speculated that rats kept on a nutritionally complete maintenance diet (NCMD) would consume equal amount of the intermittently presented high protein conditioning diet (HPCD) and protein-free conditioning diet (PFCD). However, it was hypothesized that rats kept on a protein-free maintenance diet (PFMD) would selectively increase their intake of the HPCD. Another hypothesis was that rats would learn to associate a distinct marker flavour with the nutritional content of the diets. If an animal is able to make the association between a marker flavour and the nutrient content of the food, then it is hypothesized that they will consume more of a mixed diet (equal portion HPCD and PFCD) with the marker flavour that was previously paired with the HPCD (Mixednp-f) when kept on the PFMD. In addition, it was hypothesized that intracranial injection of GRF into the SCN/MPOA would result in a selective increase in HPCD as well as Mixednp-t consumption. Results demonstrated that rats did in fact selectively increase their consumption of the flavoured HPCD and Mixednp-f when kept on the NCMD. These findings indicate that the rats successfully learned about the nutrient content of the conditioning diets and were able to associate a distinct marker flavour with the nutrient content of the diets. However, the results failed to support previous findings that GRF increases protein intake. In contrast, the administration of GRF significantly reduced consumption of HPCD during the first hour of testing as compared to the no injection condition. In addition, no differences in the intake of the HPCD were found between the GRF and vehicle condition. Because GRF did not selectively increase HPCD consumption, it was not surprising that GRF also did not increase MixedHP-rintake. What was interesting was that administration of GRF and vehicle did not reduc^Mixednp-f consumption as it had decreased HPCD consumption.

E-Learning Used in a Training Course on Atraumatic Restorative Treatment (ART) for Brazilian Dentists

The purpose of this study was to assess the benefits of using e-learning resources in a dental training course on Atraumatic Restorative Treatment (ART). This e-course was given in a DVD format, which presented the ART technique and philosophy. The participants were twenty-four dentists from the Brazilian public health system. Prior to receiving the DVD, the dentists answered a questionnaire regarding their personal data, previous knowledge about ART, and general interest in training courses. The dentists also participated in an assessment process consisting of a test applied before and after the course. A single researcher corrected the tests, and intraexaminer reproducibility was calculated (kappa=0.89). Paired t-tests were carried out to compare the means between the assessments, showing a significant improvement in the performance of the subjects on the test taken after the course (p<0.05). A linear regression model was used with the difference between the means as the outcome. A greater improvement on the test results was observed among female dentists (p=0.034), dentists working for a shorter period of time in the public health system (p=0.042), and dentists who used the ART technique only for urgent and/or temporary treatment (p=0.010). In conclusion, e-learning has the potential of improving the knowledge that dentists working in the public health system have about ART, especially those with less clinical experience and less knowledge about the subject.

Extinction of affective learning: No evidence for dual process accounts of human learning

The acquisition and extinction of affective valence to neutral geometrical shape conditional stimuli was investigated in three experiments. Experiment 1 employed a differential conditioning procedure with aversive shock USs. Differential electrodermal responding was evident during acquisition and lost during extinction. As indexed by verbal ratings, the CS1 acquired negative valence during acquisition,which was reduced after extinction. Affective priming, a reaction time based demand free measure of stimulus valence, failed to provide evidence for affective learning. Experiment 2 employed pictures of happy and angry faces as USs.Valence ratings after acquisitionweremore positive for theCS paired with happy faces (CS-H) and less positive for the CS paired with angry faces (CS-A) than during baseline. Extinction training reduced the extent of acquired valence significantly for both CSs, however, ratings of the CS-A remained different from baseline. Affective priming confirmed these results yielding differences between CS-A and CS-H after acquisition for pleasant and unpleasant targets, but for pleasant targets only after extinction. Experiment 3 replicated the design of Experiment 2, but presented the US pictures backwardly masked. Neither rating nor affective priming measures yielded any evidence for affective learning. The present results confirm across two different experimental procedures that, contrary to predictions from dual process accounts of human learning, affective learning is subject to extinction.