The metabotropic glutamate receptor, mGluR5, is densely expressed in brain regions involved in incentive learning processes. There is considerable evidence to suggest that following exposure to addictive drugs such as cocaine, adaptations in these brain areas may underlie the development and maintenance of behavioural responses related to addictive processes. The present thesis examines the role of mGluR5 in both incentive learning processes and some behavioural and neurobiological effects of cocaine. First, using a novel mutant mouse line in which mGluR5 is selectively knocked down in cells that express dopamine D1 receptors (D1R), I argue that this mGluR5 population is critically important for specific incentive learning processes. By blocking mGluR5 in wild-type mice with a selective antagonist, I then propose mGluR5 as necessary for the acquisition, but not the expression of an incentive association. Next, I present data showing that mGluR5 on dopaminoceptive neurons are not necessary for the „conditioned rewarding‟ properties of cocaine, measured in the conditioned place preference model, but do contribute to the psychomotor activating effects of cocaine. Finally, I present an immunohistochemistry study that examines cocaine-induced activation of the extracellular-signal related kinase (ERK) pathway. In the mGluR5 knock-down mice, activation of the ERK pathway in the striatum is disrupted following an acute injection of cocaine. Given the importance of the ERK pathway in establishing and maintaining long term memories, I propose that disruption of this pathway could contribute, in part, to some findings reported in the present thesis. Taken together, this thesis will argue that signalling through mGluR5 on D1R expressing neurons is important for the formation of incentive associations, and may contribute to neural adaptations necessary for the development and maintenance of behavioural responses related to addictive processes.

Oscillatory neural activity is closely related to cognition and behaviour, with synchronisation mechanisms playing a key role in the integration and functional organization of different cortical areas. Nevertheless, its informational content and relationship with behaviour - and hence cognition - are still to be fully understood. This thesis is concerned with better understanding the role of neuronal oscillations and information dynamics towards the generation of embodied cognitive behaviours and with investigating the efficacy of such systems as practical robot controllers. To this end, we develop a novel model based on the Kuramoto model of coupled phase oscillators and perform three minimally cognitive evolutionary robotics experiments. The analyses focus both on a behavioural level description, investigating the robot's trajectories, and on a mechanism level description, exploring the variables' dynamics and the information transfer properties within and between the agent's body and the environment. The first experiment demonstrates that in an active categorical perception task under normal and inverted vision, networks with a definite, but not too strong, propensity for synchronisation are more able to reconfigure, to organise themselves functionally, and to adapt to different behavioural conditions. The second experiment relates assembly constitution and phase reorganisation dynamics to performance in supervised and unsupervised learning tasks. We demonstrate that assembly dynamics facilitate the evolutionary process, can account for varying degrees of stimuli modulation of the sensorimotor interactions, and can contribute to solving different tasks leaving aside other plasticity mechanisms. The third experiment explores an associative learning task considering a more realistic connectivity pattern between neurons. We demonstrate that networks with travelling waves as a default solution perform poorly compared to networks that are normally synchronised in the absence of stimuli. Overall, this thesis shows that neural synchronisation dynamics, when suitably flexible and reconfigurable, produce an asymmetric flow of information and can generate minimally cognitive embodied behaviours.

Submitted by Carvalho Dias João Paulo (joao.dias@famerp.br) on 2018-04-12T17:42:05Z No. of bitstreams: 1 karinakellyborges_tese.pdf: 4166303 bytes, checksum: 6285f0b896e90ee79617143e2fd72af2 (MD5) / Made available in DSpace on 2018-04-12T17:42:05Z (GMT). No. of bitstreams: 1 karinakellyborges_tese.pdf: 4166303 bytes, checksum: 6285f0b896e90ee79617143e2fd72af2 (MD5) Previous issue date: 2016-11-24 / Introduction: Parkinson's disease (PD) is a chronic progressive disease that affects physical, cognitive and emotional aspects. Objective: The aim of this study was to evaluate the occurrence of changes in cognition and symptoms of mental disorders pre and post implant DBS (Deep Brain Stimulation) through a Neuropsychological Assessment (NA). Casuistics and Method: This is a descriptive study in which patients with PD, candidates and submitted to implantation of DBS have participated. NA was performed in these patients before and after implantation of DBS with the following instruments: Wechsler Adult Intelligence Scale; Trail Making Test - Form A and B; Stroop Test; Boston Naming Test; Hooper Visual Organization Test; Wechsler Memory Scale-Revised (WMS-R); Rey Complex Figure; Rey Auditory Verbal Learning Test (RAVLT); Wisconsin Card Sorting Test (WCST) and Beck´s Depression and Anxiety Inventory . Results: From the 29 patients evaluated; the mean age was 60.2 (± 9.35) years , mainly males (n = 19), married (n = 21), with complete primary education (n = 22) and retired ( n = 24). The average time of diagnosis was 11.37 years (± 5.47), the mean age of onset 48.63 (± 7.36). The stage of PD was light to moderate. Clinical evaluation showed significant differences pre and post DBS, with improvement in symptoms. The NA has identified improvement after DBS overall intelligence quotient (p = 0.0022), in activities related to processing speed, and symptoms of mental disorders: depression (p <0.0001), anxiety (p = 0.0038) and apathy (p <0.001). Worsening after DBS was Identified in executive function, memory and verbal fluency. Conclusions: After DBS implantation, there was improvement in symptoms of depression, anxiety and apathy. In general, there was no improvement in cognitive function. / Introdução: Doença de Parkinson (DP) é uma doença crônica progressiva, que compromete aspectos físicos, cognitivos e emocionais. Objetivo: O objetivo deste estudo foi avaliar a ocorrência de alterações na cognição e nos sintomas de transtornos mentais pré e pós implante de DBS (Deep Brain Stimulation) por meio de uma avaliação neuropsicológica (AN). Casuística e Método: Estudo descritivo, no qual participaram pacientes com DP, candidatos e submetidos ao implante de DBS. Foi realizada AN nos pacientes pré e pós implante de DBS com os seguintes instrumentos: Wechsler Adult Intelligence Scale; Trail Making Test - Forma A e B; Stroop Test; Boston Naming Test; Hooper Visual Organization Test; Wechsler Memory Scale- Revised (WMS-R); Figura Complexa de Rey; Rey Auditory Verbal Learning Test (RAVLT); Wisconsin Cards Sorting Test (WCST) e Escalas de Depressão e de Ansiedade de Beck. Resultados: Dos 29 pacientes avaliados, a média de idade foi 60,2 (± 9,35) anos, eram principalmente do sexo masculino (n=19), casados (n=21), com ensino fundamental completo (n=22) e aposentados (n=24). O tempo médio de diagnóstico da doença foi 11,37 anos (± 5,47), a média de idade de início 48,63 (± 7,36). O estágio da DP era leve a moderado. A avaliação clínica indicou diferença significante pré e pós DBS, com melhora dos sintomas. A AN identificou melhora pós DBS no quociente intelectual geral (p=0,0022), nas atividades relacionadas à velocidade de processamento, e nos sintomas de transtornos mentais: depressão (p<0,0001), ansiedade (p=0,0038) e apatia (p<0,001). Identificou piora pós DBS na função executiva, memória e fluência verbal. Conclusões: Após o implante de DBS houve melhora dos sintomas de depressão, ansiedade e apatia. Não houve melhora da função cognitiva em geral.

Introdução: o aumento da população idosa traz uma demanda significativa sobre as ciências da saúde para lidar com os problemas característicos do envelhecimento. Neste contexto, as demências são as desordens neuropsiquiátricas de maior impacto atualmente. Poucas pesquisas acerca do CCL foram dedicadas a analisar a função neuropsicológica da tomada de decisão. Esta é definida como o processo de escolher uma ação específica, dentro de um rol de alternativas possíveis, que produza o resultado mais vantajoso para o sujeito. Logo, ela possui papel clínico fundamental, pois subsidia importante espectro da funcionalidade. Objetivo: avaliar se idosos com CCL amnéstico de múltiplos domínios ou de único domínio apresentam prejuízos na tomada de decisão sob risco, quando comparados a idosos saudáveis. Métodos: foram analisados os desempenhos de 20 sujeitos (9 CCL e 11 controles) no teste de tomada de decisão Cambridge Gambling Task (CGT). Utilizou-se modelo linear geral acompanhado de análise de covariância para idade, anos de escolaridade e escore do Mini Exame do Estado Mental. Resultados: Foi verificado efeito de grupo e da idade sobre a aversão ao atraso, proporção global de aposta e assunção de risco. Conclusão: pacientes com CCL demonstraram maior impulsividade nas escolhas das apostas, além de terem apostado menos ao longo de todo o CGT. O déficit no controle da impulsividade pode ser um indicador de maior risco para conversão para demência, hipótese esta que necessita ser mais investigada. Apostas menores podem constituir estratégia compensatória em reação à impulsividade ou, ainda, ser resultado da menor confiança do paciente com CCL em suas capacidades para lidar com o teste / Introduction: The increase in elderly population brings a significant demand upon the health sciences to deal with aging-specific issues. In this context, dementia is currently the group of neuropsychiatric disorders with the greatest impact. Research on cerebral reserve shows the importance of early treatment in these syndromes, highlighting the need for comprehension about Mild Cognitive Impairment (MCI), classically defined by literature as a prodromic stage for dementia. Few existing studies on MCI aimed at investigating the neuropsychological function of decision-making, which is defined as the process of choosing a specific action among several options in order to achieve the most advantageous outcome. Therefore, this function has a fundamental clinical role, since it grants the basis for the individual functionality. Objective: investigate possible deficits in the decision-making of a sample of elderly patients diagnosed with amnestic MCI of multiple or single domain by comparing their performance with that of healthy ones. Methods: the performances of a sample 20 subjects (9 MCI and 11 controls) in the Cambridge Gambling Task (CGT) were analysed. General linear model with covariance analysis for age, years of schooling and the Mini Mental State Examination scores was used for the statistical analyses. Results: it was found that group and age effect on delay aversion, overall proportion bet, and risk taking. Conclusion: MCI patients showed higher impulsivity on bet choices and made smaller bets throughout the CGT run. The impulsivity control deficit can be an indicator of the conversion risk from MCI to dementia, hypothesis that needs further investigation. Smaller bets may be a compensatory strategy for the increased impulsivity or the result of MCI patients less confidence in their own cognitive ability to deal with the test

A síndrome de Noonan é uma doença autossômica dominante geneticamente heterogênea caracterizada por aspectos faciais distintos, atraso no desenvolvimento, dificuldades de aprendizado, baixa estatura, defeitos cardíacos congênitos, pectus excavatum e pescoço alado. Mutações que alteram genes que codificam proteínas com atuação na via RAS-MAPK causam a síndrome de Noonan e têm sido bastante estudadas. No entanto, há poucas informações sobre o perfil cognitivo da síndrome de Noonan. Neste estudo, diferentes aspectos da cognição foram avaliados (inteligência, funções executivas e habilidade viso-construtiva) em um grupo de 28 pacientes com a síndrome de Noonan, incluindo crianças e adultos, por meio das Escalas Wechsler de Inteligência, pelo Teste Wisconsin de Classificação de Cartas e pelo Teste Figuras Complexas de Rey. Houve uma variação de QI entre 59 e 119, além de melhores resultados em pacientes com mutação no gene PTPN11. No domínio das funções executivas, pacientes tiveram pior desempenho em categorização e flexibilidade cognitiva, embora sem prejuízos em sustentação atencional. Os pacientes demonstraram importantes falhas no planejamento do ato motor no teste de viso-construção e melhores resultados no grupo de pacientes com mutação no gene SOS1. Apesar da eficiência intelectual relativamente intacta, pacientes com a síndrome de Noonan mostraram prejuízos significativos em outros domínios cognitivos, indicando que a avaliação neuropsicológica é importante no manejo clínico da síndrome e um valioso recurso em seu planejamento terapêutico / Noonan syndrome is an autosomal dominant genetically heterogeneous disorder characterized by distinctive facial features, developmental delay, learning difficulties, short stature, congenital heart defects, pectus excavatum and webbed neck. Mutations that alter genes encoding proteins with roles in the RAS-MAPK pathway cause Noonan syndrome and have been well studied. However, there are few information about the cognitive profile of the Noonan syndrome. In this study, different aspects of cognition were assessed (intelligence, executive functions and visuo-construction ability) in a group of 28 patients with Noonan syndrome, including children and adults, by using Wechsler Intelligence Scales, Wisconsin Card Sorting Test and Rey Complex Figure Test. There was a variation of IQ between 59 and 119, besides better results in patients with mutation in PTPN11 gene. On the domain executive functions patients performed worse in categories achieved and cognitive flexibility, although no impairments in sustained attention. Patients showed important faults in planning of motor act in visuo-construction test and better results in the group of patients with mutation in SOS1 gene. Despite the relatively intact intelligence level, patients with Noonan syndrome showed significant impairments in other cognitive domains, indicating that neuropsychological assessment is important in clinical management of the syndrome and valiable resource of treatment planning

It is increasingly recognised that the broadly defined behavioural phenotype of attention deficit – hyperactivity disorder (ADHD) is a heterogeneous condition and that this heterogeneity is seen across all levels of analysis from the genetic and environmental causes to the associated neuropsychological deficits, the clinical presentation and response to treatment. This work investigated whether the more restrictive and clinically homogeneous hyperkinetic disorder (HKD) phenotype is associated with reduced neuropsychological heterogeneity compared with the broader ADHD phenotype. Using a well known, broad based battery of neuropsychological tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB) and a computerised Go/NoGo task in a large well described group of boys with rigorously diagnosed HKD who were stimulant medication naïve at baseline, it was demonstrated that the neuropsychological heterogeneity in the HKD boys was very similar to that seen previously in children with ADHD. Interestingly, and contrary to popular opinion, the strongest associations were with more simple recognition memory tasks with a low executive demand. Although there were significant associations between HKD and deficits on a range of tasks with high executive demands these were less strong. Could this neuropsychological heterogeneity be a function of different developmental issues or comorbidity? With respect to development there was evidence that boys with HKD lagged behind the healthy boys with respect to the development of their neuropsychological performance. However the pattern of development was similar with the performance of the HKD boys paralleling that of the healthy boys, suggesting that the neuropsychological heterogeneity seen in HKD is not accounted for by developmental issues. With respect to the relationship between neuropsychological functioning and comorbidity, the impact of comorbid oppositional defiant disorder (ODD) and conductdisorder (CD), it was found that all three clinical groups (pure HKD, HKD + ODD and HKD + CD) demonstrated deficits on several tasks compared with the healthy boys. Compared with healthy boys each of the three clinical groups was associated with at least one unique neuropsychological deficit. This suggests that comorbidity between HKD and both ODD and CD may contribute to the neuropsychological heterogeneity in the HKD boys. Is there an association between clinical and neuropsychological responses to the treatment of HKD with the stimulant drug methylphenidate (MPH)? Detailed analyses were conducted to investigate heterogeneity of clinical and neuropsychological response in these boys to MPH. As predicted in previous studies there is evidence for clinical heterogeneity in response with between 68 and 78% of boys with HKD responding to MPH treatment at either one or both of the doses. The precise proportion responding was dependent on the scale and definition of response used. Clinical response was not predicted by age but was predicted to a degree by severity of symptoms at baseline and it was generally true that better response was predicted by lower (better) scores at baseline. Baseline performance on a component reflecting recognition memory performance at baseline predicted clinical response to the lower (0.3 mg/kg/dose), but not the higher (0.6, mg/kg/dose) dose of MPH with poorer baseline neuropsychological performance predicting a better clinical response. Whilst there was improvement on some neuropsychological measures following administration of MPH there was little association between clinical and neuropsychological responses to medication. Clinical response was only associated with neuropsychological response on a single measure from a single task (Go/NoGo Block 2 Errors to Distractors), a task that did not itself discriminate between the HKD boys and healthy Controls at baseline.

It is increasingly recognised that chronic exposure to opioids has been associated with neuropsychological impairment during both active use and following a period of abstinence. The overall objective of this thesis was to review the relevant prior literature in a systematic manner and subsequently to describe the effects of chronic exposure to prescribed and illicit opioids using an ambispective cohort study design. A systematic literature review was conducted to identify if chronic (defined as a period for more than 3 months) exposure to opioids (prescribed and/or illicit) was associated with measurable neuropsychological deficits. This review was conducted accordingly to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines. The results were subsequently described within three cognitive domains of intelligence, executive function and memory and learning. Out of a total of 905 articles extracted between 1964 and 2009, 49 articles were considered appropriate for selection and review. Studies of current and abstinent chronic opioid users (illicit heroin users, patients prescribed methadone for illicit opioid dependence and patients taking opioids as part of the management of chronic pain) have identified performance deficits in measures of executive functioning and memory. These have included impairments within the domains of cognitive and motor impulsivity, strategic planning, cognitive flexibility, attention and memory. However other studies found no clear deficits when comparing the performance of healthy controls. The literature suggested that these neuropsychological deficits may be subject to at least partial recovery following initiation of methadone or total withdrawal from any opioids.This review also highlighted several methodological issues that affect the reliability, validity and clinical relevance of the results obtained. Subsequently a two year ambispective cohort design study was conducted which tested representative opioid exposed participants and healthy controls. Cohorts of participants with validated histories of illicit heroin use (HEROIN, n=24), stabilised methadone maintenance (METHADONE, n=29), chronic opioid prescriptions for pain (CHRONIC PAIN, n=28) and controls (HEALTHY CONTROL, n=28) were recruited. The study was designed to test neuropsychological performance in the HEALTHY CONTROL and CHRONIC PAIN groups on one occasion; and for the HEROIN and METHADONE groups on three and two occasions respectively. The intention was to describe neuropsychological performance in the HEROIN group under conditions of stable illicit heroin use, in controlled opioid withdrawal and when subsequently stabilised on methadone. For the METHADONE group, participants were tested twice, six months apart, to test for changes induced by chronic exposure to methadone. Eligible, screened and consented individuals were tested on nine tests from the CANTAB test battery. Data were analysed using univariate or repeated measures ANCOVA with a between subjects factor of GROUP. Further a priori subgroup analyses were conducted using (1) a two-group factor reflecting DEPENDENCE status and (2) a two-group factor reflecting INJECTING status separately as between subject factors. The homogeneity of variance across groups in repeated-measures design ANCOVAs was assessed by the Mauchly Sphericity Test. NART, age in years, SIMD, total Fagerström score, years in education and past alcohol use in years were used as covariates. A significance level of p<0.01 was applied due to multiple testing, in addition to the post-hoc Bonferroni correction procedure. On the Cambridge Gambling Task (CGT), HEROIN users placed higher bets earlier and risked more. They also showed increased motor impulsivity, impaired strategic planning and visuospatial memory on the Affective Go-NoGo (AGN), Stockings of Cambridge (SOC), and Delayed Matching to Sample(DMS) respectively. METHADONE users deliberated longer and placed higher bets earlier on the CGT, but did not show a tendency to risk more. METHADONE users were also more inattentive and demonstrated poor strategic planning and visuospatial memory on the Spatial Span (SSP) task. The CHRONIC PAIN participants did not exhibit significant impairment in neuropsychological performance on all the CANTAB tasks. Participants from the HEROIN, METHADONE and CHRONIC PAIN groups did not present with impaired cognitive flexibility. Chronic opioid dependence is associated with neuropsychological impairment reflected in altered performance on measures of risk taking and strategic planning. These data support the hypothesis that these neuropsychological impairments reflect an underlying trait vulnerability to drug taking and/or dependence rather than an effect of chronic exposure to opioids. Notably, motor impulsivity and visuo-spatial memory in HEROIN users improved after three weeks stability with methadone. Methadone use seems to confer improvement in some aspects of neuropsychological performance following cessation of heroin and sustains other deficits during long term stable methadone treatment. Dependence and injecting status do not contribute to the causation or deterioration of the identified neuropsychological impairments. Further long term longitudinal studies to help elucidate cognitive endophenotypes responsible for the components in the initiation, continuation and deterioration of neuropsychological deficits present in an opioid dependent population is necessary.

A neuropsicologia infantil e uma area distinta dentro da neuropsicologia clinica e o seu surgimento e uma consequencia do reconhecimento de que as relacoes cerebrocomportamento na crianca diferem significativamente dessas relacoes no adulto. Diversos testes neuropsicologicos tem sido desenvolvidos especialmente para administracao em computador, incluindo a bateria CANTAB que tem sido amplamente utilizada em pesquisas com diferentes grupos de idade e patologias. Em relacao ao desenvolvimento, alguns aspectos da atencao estao presentes no inicio da infancia enquanto outros continuam a se desenvolver ao longo da infancia e adolescencia. A memoria sofre inumeras alteracoes ao longo da vida, especialmente na idade pre-escolar. E as funcoes executivas demoram mais tempo para se desenvolver por completo e estudos apontam que alguns componentes ja estao presentes de forma imatura em criancas entre os 6 e 12 anos de idade, mas a completa maturacao acontece com a idade. O objetivo dessa pesquisa foi investigar o desenvolvimento da atencao, memoria e funcoes executivas em criancas e adolescentes dos 6 aos 12 anos de idade com o CANTAB, buscando padroes especificos de desenvolvimento para os componente dessas funcoes. Foram avaliados 85 criancas e adolescentes (43 masculino) entre 6 e 12 anos de idade, sem historico de disturbios neurologicos e/ou psiquiatricos, exposicao cronica a agentes toxicos, lesao ou cirurgia cerebral e problemas de desenvolvimento. Foram utilizados o teste Matrizes Progressiva Coloridas de Raven e os seguintes subtestes do CANTAB: Choice Reaction Time, Rapid Visual Information Processing, Pattern Recognition Memory, Delayed Matching to Sample, Spatial Recognition Memory, Spatial Span, Stockings of Cambridge, Intra-Extra Dimensional Set Shift, Stop Signal Task e Information Sampling Task. Os resultados indicaram que a atencao, a memoria e as funcoes executivas apresentam melhora no desenvolvimento nas idades avaliadas. A atencao visual simples, percepcao visual e capacidade de conceituacao ja estao desenvolvidas aos 6 anos. A amplitude atencional, memoria visual, memoria espacial, flexibilidade mental e controle mental estao em desenvolvimento nas idades avaliadas e apresentam um bom desempenho aos 12 anos. O planejamento e atencao sustentada apresentaram melhoras, mas ainda nao alcancaram o pleno desenvolvimento. A, tomada de decisao e controle inibitorio nao apresentaram aprimoramentos significativos e sua maturacao deve ocorrer apos os 12 anos. A bateria CANTAB se mostrou eficaz na avaliacao de criancas e adolescentes brasileiros de 6 a 12 anos de idade com alta aplicabilidade nessa amostra e resultados compativeis com a literatura. A comparacao entre os nossos resultados e aqueles encontrados nos estudos internacionais com o CANTAB indica compatibilidade entre boa parte dos grupos etarios avaliados, independentemente das diferencas culturais existentes / Child neuropsychology is a distinct area in the clinical neuropsychology and its emergence is a consequence of the acknowledgment that the brain-behavior relationships in child differ significantly from those in adult. Several neuropsychology tests have been developed to be administered in computers, including the CANTAB that has been widely used by researchers concerning different ages and pathologies groups. In regard to the development, some aspects of attention are present in the beginning of childhood while others continue to develop along the childhood and youth. Memory processes undergo many changes throughout life, especially in preschool age. Executive functions take longer to fully develop and researches indicate that some components are present in immature form on child between 6 to 12 years old, but the complete ripening occurs with age increase. The aim of this work was to investigate the development of attention, memory and executive functions in children and teenagers from 6 to 12 years old using the CANTAB, and verify if there are specific patterns of development for the components of these functions. There were evaluated 85 children and teenagers (43 male) between 6 to 12 years old with no history of neurological and/or psychiatric disorders, chronic exposures to toxic agents, injury or brain surgery and development disorders. They were submitted to the Ravens progressive matrices and the following CANTABs subtests: Choice Reaction Time, Rapid Visual Information Processing, Pattern Recognition Memory, Delayed Matching to Sample, Spatial Recognition Memory, Spatial Span, Stockings of Cambridge, Intra-Extra Dimensional Set Shift, Stop Signal Task e Information Sampling Task. The results indicated improvements in attention, memory and executive functions in the development in the age groups evaluated. Simple visual attention, visual perception and conceptualization capacity seem to be developed at 6 years old. Attentional span, visual memory, spatial memory, mental flexibility and mental control are in ongoing development in the age groups evaluated, and a good performance is reached at 12 years old. Planning ability and sustained attention showed improvements in age groups evaluated but they have not reached fully development. Decision making and inhibitory control do not showed significant improvement and their ripening should occur after the 12 years old. The CANTAB battery was effective to evaluate Brazilians children and teenagers from 6 to 12 years old with high applicability in this sample and results consistent with the literature. The comparison between our results and those found in the international studies with CANTAB indicates compatibility in almost all age evaluated, regardless cultural differences

Introdução: independentemente do grau de incapacidade física, o declínio cognitivo tem sido considerado motivo de maior impacto em importantes aspectos da vida diária dos pacientes com Esclerose Múltipla (EM) como o gerenciamento de tarefas domésticas, participação na sociedade e manutenção do emprego. Alterações de Memória Episódica (ME) em pacientes com EM são comumente descritas na literatura, sendo observadas em 40% a 65% dos casos. Seu impacto já é observado em pacientes com Esclerose Múltipla Remitente-Recorrente (EMRR) incipiente e pode ser um indicador de pior prognóstico para evolução da doença. Adicionalmente, déficits na memória verbal bem como na velocidade de processamento de informação e função executiva predizem condição ocupacional dos portadores da doença. Há vários trabalhos transversais na literatura científica que visam investigar sobre alterações cognitivas encontradas nestes pacientes. Entretanto, os estudos longitudinais são escassos e estes têm revelado resultados inconclusivos e divergentes. Além disso, tanto nos estudos transversais quanto nos estudos longitudinais, não há preocupação em caracterizar de forma aprofundada o declínio da Memória Episódica Verbal (MEV) especificamente. Objetivo: neste estudo, investigamos a MEV de pacientes com EMRR e sua evolução através de avaliação longitudinal. Métodos: vinte e nove pacientes com EMRR foram submetidos a duas avaliações neuropsicológicas realizadas entre um intervalo de tempo médio de 4,5 anos. Vinte e seis controles saudáveis foram submetidos à uma única e idêntica avaliação neuropsicológica. Considerou-se nível de significância p < 0,05 para delinear diferenças estatísticas entre os grupos nas análises Mann Withney e Wilcoxon pareado. Resultados: não houve diferença estatística nos resultados dos testes de MEV entre a primeira e a segunda avaliação neuropsicológica realizada pelos pacientes. Houve discrepância estatística nos resultados dos testes de MEV entre o grupo de controles e grupo de pacientes no momento da avaliação inicial. Em contrapartida, no momento da segunda avaliação o grupo de pacientes não se diferenciou estatisticamente do grupo dos controles. Conclusões: a estabilização ou discreta melhora do desempenho dos pacientes com EMRR entre a avaliação inicial e o follow-up em testes de MEV, pode estar relacionada ao fato de que neste estudo foram incluídos predominantemente jovens adultos na amostra, com a forma clínica mais branda da doença. Possível processo de neuroplasticidade cerebral, ou mesmo inclusão de casos benignos da EM precisam ser considerados. Atrelado a isso, deve-se considerar que o breve período de follow-up pode não ter sido o suficiente para detectar possíveis déficits a longo prazo / Introduction: Regardless of the degree of physical disability, cognitive decline has been considered as having the greatest impact on important aspects of the daily life of Multiple Sclerosis (MS) patients, such as managing household tasks, participation in society and maintaining employment. Changes in Episodic Memory (EM) in MS patients are commonly described in the literature and are observed in 40% to 65% of cases. Its impact is already observed in patients with incipient Relapsing-Remitting Multiple Sclerosis (RRMS) and may be an indicator of a worse prognosis for disease progression. In addition, deficits in verbal memory as well as in the speed of information processing and executive function predict the occupational condition of the patients with the disease. There are several transversal works in the scientific literature that aim to investigate cognitive alterations found in these patients. However, longitudinal studies are scarce and these have revealed inconclusive and divergent results. Moreover, in both crosssectional studies and longitudinal studies, there is no concern to characterize in depth the decline of Verbal Episodic Memory (VEM) specifically. Objective: In this study, we investigated the VEM of patients with RRMS and its evolution through longitudinal evaluation. Methods: Twenty-nine patients with RRMS were submitted to two neuropsychological evaluations performed between a mean time interval of 4.5 years. Twenty-six healthy controls were submitted to a single and identical neuropsychological evaluation. A significance level of p < 0.05 was used to delineate statistical differences between the groups in the Mann Withney and Wilcoxon paired analyzes. Results: There was no statistical difference in the VEM results between the first and second neuropsychological evaluation performed by the patients. There was a statistical discrepancy in the VEM results between the control group and the patient group at the time of the initial evaluation. In contrast, at the time of the second evaluation, the group of patients did not differ statistically from the control group. Conclusions: The stabilization or discrete improvement in the performance of RRMS patients between the initial evaluation and the follow-up in the VEM trials may be related to the fact that in this study, predominantly young adults were included in the sample, with the mildest clinical form of the disease. Possible process of cerebral neuroplasticity, or even inclusion of benign cases of MS need to be considered. Coupled with this, one should consider that the brief follow-up period may not have been enough to detect possible long-term deficits

Vários estudos em esquizofrenia têm encontrado uma associação positiva entre desempenho cognitivo e status de trabalho, e foi relatado que o bom desempenho cognitivo no início prevê o sucesso das intervenções profissionais. No entanto, pouco se tem feito para investigar a influência das intervenções vocacionais sobre o desempenho cognitivo. Tem se levantado a hipótese de que intervenções profissionais podem compensar deficiências nas funções cognitivas mais básicas, que por sua vez podem refletir em aprimoramentos em domínios cognitivos mais complexos. Para testar esta hipótese foi realizado um estudo aleatorizado, controlado por placebo, para investigar o efeito de um programa de reabilitação profissional de 6 meses no desempenho cognitivo de pacientes esquizofrênicos em remissão. Foram recrutados 112 pacientes com esquizofrenia clinicamente estáveis e em remissão que desejavam participar de um programa de reabilitação profissional. Destes, 57 iniciaram imediatamente um programa de reabilitação vocacional de 6 meses, e os 55 restantes foram alocados no grupo controle, que recebeu acompanhamento ambulatorial por 6 meses. Além de uma bateria completa de testes neuropsicológicos, foram avaliadas também mudanças no status psicopatológico por meio de uma escala de qualidade de vida (QLS) e da Escala de Avaliação da Síndrome Positiva e Negativa (PANSS). Encontrou-se que a reabilitação vocacional melhorou significativamente o desempenho de pacientes em medidas cognitivas que avaliam funções executivas (formação do conceito, flexibilidade mental, controle inibitório, análise de situações sociais e habilidades de julgamento e crítica). Além disso, após 6 meses o grupo que trabalhou melhorou significativamente os sintomas negativos e a qualidade de vida, quando comparados aos controles. E ainda, o modelo de regressão logística, apontou que o sucesso da reabilitação vocacional está relacionado a um valor maior de QI e a uma pontuação menor na PANSS total. Juntamente com os resultados provenientes da literatura, as nossas conclusões reforçam a noção de que a inclusão em intervenções vocacionais aumenta a eficácia das estratégias terapêuticas em pacientes com esquizofrenia. / Several studies in schizophrenia found a positive association between cognitive performance and work status, and it has been reported that good cognitive performance at the outset does predict the success of vocational interventions. However little has been done to investigate the influence of vocational interventions itself on cognitive performance. It has been hypothesized that vocational interventions may compensate for impairments in the most basic cognitive functions, which in turn may reflect in improvements in more complex cognitive domains. To test this hypothesis we performed a randomized, placebo-controlled trial to investigate in remitted schizophrenic patients the effect of a 6-months vocational rehabilitation program on cognitive performance. We recruited 112 remitted and clinically stable schizophrenic patients who aimed to enter a vocational rehabilitation program. From these, 57 immediately entered a 6-months vocational rehabilitation program, and the remaining 55 formed our control group, which received out-clinic follow-up treatment during these 6 months. Besides a thorough neuropsychological test battery, we also assessed changes in the psychopathological status by means of the Positive and Negative Symptoms Scale (PANSS), and a Quality of Life Scale (QLS). We found that vocational rehabilitation significantly improved patients\' performance in cognitive measures that assess executive functions (concept formation, shifiting ability, flexibility, inhibitory control, and judgment and critics abilities). Moreover, after 6 months the vocational group improved significantly in the negative symptoms and in quality of life, as compared to controls. The model of logistic regression, pointed that the success of the vocational rehabilitation is related to a greater value of QI and a worse score in the total PANSS. Together with results from the literature, our findings reinforce the notion that the inclusion of vocational interventions does enhance the effectiveness of therapeutic strategies for schizophrenia patients.