Epidermal growth factor receptor (EGFR) is a key modulator of a number of cellular processes such as cell fate, proliferation, migration, and apoptosis. The EGFR gene is commonly amplified in a number of cancers and EGFR has been implicated in Alzheimer’s disease, but its role in this context is uncertain. An internal ribosome entry site (IRES) within the EGFR 5’untranslated region (UTR) has been previously discovered which maintains EGFR expression under hypoxic conditions and has a high requirement for the eukaryotic initiation factor (eIF) 4A helicase. Requirement for eIF4A suggests that the structure of the IRES is important in its regulation. Identifying the structure of the IRES and the conditions in which the IRES is active could lead to the development of therapeutics targeting the IRES. The IRES was investigated using bicistronic luciferase vectors. The IRES was found to be active in serum starvation stress but this activation appeared to be cell type specific, suggesting the IRES may depend upon tissue specific trans-acting factors for function. The EGFR IRES appears to not be modular, drawing similarities to the L-myc IRES. Structural data was used to improve prediction models for the IRES, which identified a structural switch that may be regulated by trans-acting factors. Targeting the IRES with anti-sense oligonucleotides proved moderately successful in inhibiting cap-independent translation. To study translational control in an environment closer to those found in Alzheimer’s disease, a 3-dimensional model was developed. Although the model was not spherical and could not be used as intended, it may be useful as a model for studying stress gradients. The effects that EGF stimulation has on translational regulation is poorly understood, yet may be a significant mediator in disease. RNA-seq allows for the quantification of the entire transcriptome for a given condition, whilst polysome profiling fractions mRNA based on ribosomal association. Through polysome profiling, RNA-seq and ontological clustering, it was revealed that EGF increased the translational efficiency of genes associated with Alzheimer’s disease aetiology. Some of these genes were found to be directly connected to the production and oligomerisation of the amyloid beta protein.

The increasing incidence of obesity around the world has become a major problem with health and economic implications for most countries, and one which currently available methods of weight management including diet, exercise and lifestyle advice all seem incapable of controlling. The premise of this project was that some instances of adult obesity could be due to adverse, unresolved childhood traumas and experiences the consequences of which were continuing to act subconsciously in those individuals to impede effective and maintained adult weight loss; and that hypnosis was an appropriate exploratory tool for identifying and resolving these problems to facilitate more effectual weight management. For this purpose a group of seven overweight female volunteers were invited to undertake a series of “state”, dissociative hypnosis sessions involving regression back through their childhood and early adulthood. The resulting recalled autobiography from each participant’s series of hypnosis sessions was recorded, transcribed and analysed to constitute a piece of narrative autoethnography of their childhood past. All seven participants in this project were able to utilise hypnosis effectively to enable them to recall barely remembered past events, feelings and connections which, they realised for the first time as adults, had had a major and long-lasting impact on how they felt about food, their body weight or their body image. Hypnotically recalled memories of guilt and anger were associated with dysfunctional family relationships and childhood eating experiences. For most of these participants the strength of the association between these past times and feelings, and their current long-term overweight problem came as a total surprise. Even in advance of any weight loss most participants were inspired by their discoveries and felt that the telling of this hidden story had had a transformative benefit for them in bringing about reconciliation with the past, understanding of the present and planning for their future. These narrative accounts and results suggest that hypnosis might have wider application for use as an ethnological modality in sociology and health studies more generally.

Background: Multiple sclerosis is a chronic neurodegenerative condition that can significantly impair length and quality of life. Comorbidity (the presence of additional chronic conditions) has been reported as common in multiple sclerosis and is associated with diagnostic delays, increased disability, and higher mortality rates in people with multiple sclerosis. Multiple sclerosis is a stressful condition, with a highly unpredictable disease course, often necessitating complex and unpleasant treatment regimens. Stress in multiple sclerosis raises the risk of significant mental illness, impacts negatively on quality of life, and may be associated with an increased risk of disease relapse (although the evidence supporting this latter link is limited). Current stress management strategies in multiple sclerosis are limited, with a recent systematic review identifying only one high quality study supporting the use of cognitive behavioural therapy. Mindfulness-based interventions have been demonstrated to help with stress management in other long-term conditions, such as anxiety and recurrent depression. Very little is known about the use and effectiveness of mindfulness-based interventions in people with multiple sclerosis. Methods: This thesis followed the United Kingdom Medical Research Council guidance (2008) on developing and evaluating complex interventions. The research commenced with an epidemiological study of comorbidity in multiple sclerosis using a nationally representative cross-sectional primary care database from Scotland (n=1,268,859, of whom 3,826 had multiple sclerosis). The analysis focused on 39 other long-term conditions, comparing prevalence rates for people with multiple sclerosis aged 25 or over versus matched controls, controlling for age, sex, and socio-economic status. Results are presented as odds ratios (ORs) with 95% confidence intervals (95%CI), and p values. Secondly, a systematic review was conducted to evaluate the evidence for the effectiveness of mindfulness-based interventions in people with multiple sclerosis in terms of reducing perceived stress and other relevant secondary outcomes, including mental health, physical health, and quality of life. Study quality was determined using the Cochrane Collaboration quality assessment tool. Following this, a phase-2 randomised controlled trial was undertaken, testing the feasibility of delivering a Mindfulness-Based Stress Reduction course to a group of (n=25) people with multiple sclerosis versus wait-list control (n=25). Primary patient report outcome measures were perceived stress (Perceived Stress Scale-10) and health-related quality of life (EQ-5D-5L). Secondary patient report outcomes included the Multiple Sclerosis Quality of Life Inventory, mindfulness (the Mindful Attention Awareness Scale), self-compassion (the Self-Compassion Scale-short form), and emotional lability (the Emotional Lability Questionnaire). Results are reported in ‘p’ values and effect sizes (ES - Cohen’s ‘d’) with 95%CIs. A linked qualitative process evaluation nested within the randomised controlled trial assessed Mindfulness-Based Stress Reduction instructor and participant experience through semi-structured interviews with 17 participants and the two instructors. In order to organise and summarise the data, the Framework Approach to thematic analysis was employed. The emergent themes from the thematic analysis were then scrutinised under the theoretical ‘lens’ of Normalisation Process Theory, as a means of conceptualising the data and assessing potential implementation issues. Results: Epidemiology People with multiple sclerosis in Scotland aged 25 years or over were more than twice as likely to have comorbidity of one or more long-term conditions than matched controls (OR 2.44; 95%CI 2.26-2.64). Mental health comorbidity was particularly prevalent in people with multiple sclerosis, being almost three times as common compared with controls (OR 2.94; 95% CI 2.75-3.14). Depression (OR 3.30; 95%CI 3.10 – 3.57) and anxiety (OR 3.18; 95%CI 2.89 – 3.50) were particularly common. As the number of physical health conditions rose in people with multiple sclerosis, so too did the prevalence of mental health comorbidity. Certain neurological conditions (epilepsy, pain, migraine, visual impairment) and gastrointestinal conditions (constipation, irritable bowel syndrome) were also more common in people with multiple sclerosis. Systematic review Three published controlled outcome studies using mindfulness-based interventions in people with multiple sclerosis were identified. Only one study was of high methodological quality. The findings suggested that mindfulness-based interventions may improve quality of life, mental health (anxiety and depression), and some physical outcome measures (fatigue, pain, standing balance), with effects lasting for up to six months post-treatment. Meta-analysis was not possible due to heterogeneity amongst studies. Since the systematic review was conducted, three further studies of mindfulness-based interventions in people with multiple sclerosis have been published. These studies were generally of low methodological quality, but they did add some further evidence that such interventions can improve scores for anxiety, depression, stress, pain, fatigue, co-ordination, balance, and quality of life. However, the overall weight of evidence supporting the use of mindfulness-based interventions in people with multiple sclerosis remains limited. Randomised controlled trial The recruitment target of 50 participants was met within the pre-defined three-month window. Outcome measure completion rates were good immediately post-intervention (90%) and at study end-point, three months post-intervention (88%). However, participant attendance at the weekly 2.5 hours mindfulness sessions was only 60%, and average home practice times were less than the suggested amount of 45 minutes, six days per week. In adjusted models (controlling for age, sex, deprivation, previous yoga/meditation experience) for primary patient-report outcomes immediately post-intervention, perceived stress scores improved with a large overall effect size (ES 0.93; p<0.01), and large effects were also evident on subscales of negative stress appraisal (ES 0.82; p<0.05), and on stress resilience items (ES 0.92; p<0.05). Quality of life scores showed only very small improvements overall (ES 0.17; p=0.48), with only the anxiety/depression subscale showing a small effect size immediately post-intervention (ES 0.41; p=0.16). Secondary patient report outcomes showed improvements with large effect sizes immediately post-intervention in scores for depression (ES 1.35; p<0.05), positive affect (ES 0.87; p=0.13), anxiety (ES 0.85; p=0.05), and self-compassion (ES 0.80; p<0.01). At study endpoint three-months post-intervention, adjusted models revealed that the beneficial effects on perceived stress and improvements in stress resilience had diminished to small effect sizes (ES 0.26; p=0.39, and ES 0.46; p=0.05 respectively). Quality of life scores showed negligible improvement overall (ES 0.08; p=0.71), but a small beneficial effect persisted on the anxiety/depression subscale (ES 0.26; p=0.42). For secondary patient-report outcomes at study endpoint, the large effect sizes found immediately post-intervention for depression were no longer apparent (ES 0.01; p=1.00), but remained evident for positive affect (ES 0.90; p=0.54), anxiety (ES 0.82; p=0.15), and self-compassion (ES 0.83; p<0.05), with large effect size improvements also noted for mindfulness (ES 1.13; p < 0.001) and prospective memory (ES 0.81; p<0.05). Qualitative evaluation: People who came on the Mindfulness-Based Stress Reduction course generally reported benefits, namely reduced stress, less pain, and improved relationships. / Four main themes were identified in the thematic analysis: 1) ‘Coming together for the course’ 2) ‘Doing the work’ 3) ‘Getting it, or not’, and 4) ‘Moving forward and improving the course’. Using the ‘lens’ of Normalisation Process Theory, these themes were further scrutinised, and potential barriers and facilitators to taking part were identified. Recommendations derived from this process included: a) inclusion of a pre-course orientation session in future courses to address participant expectations; b) making the course environment more disability-friendly; c) making the course materials more multiple sclerosis- and ability-appropriate; and d) embedding routine monitoring into future courses. Conclusions: The work of this thesis has demonstrated that among multiple sclerosis patients in Scotland, both physical and mental health comorbidities are common. There is limited published evidence supporting the use of mindfulness-based interventions in people with multiple sclerosis, but some indication that these interventions may improve anxiety, depression, stress, pain, fatigue, balance, co-ordination, and quality of life. Findings from the exploratory phase-2 randomised controlled trial suggest that delivering Mindfulness-Based Stress Reduction to people with multiple sclerosis under trial conditions is feasible with some evidence of likely effectiveness. Mindfulness-Based Stress Reduction generally appears to be acceptable, accessible, and implementable for people with multiple sclerosis, but an orientation session should be provided pre-course, and course materials may need to be carefully tailored to meet the complex needs of more disabled individuals with multiple sclerosis.

The last few years have seen an increase in brain-computer interface (BCI) research for the able-bodied population. One of these new branches involves collaborative BCIs (cBCIs), in which information from several users is combined to improve the performance of a BCI system. This thesis is focused on cBCIs with the aim of increasing understanding of how they can be used to improve performance of single-user BCIs based on event-related potentials (ERPs). The objectives are: (1) to study and compare different methods of creating groups using exclusively electroencephalography (EEG) signals, (2) to develop a theoretical model to establish where the highest gains may be expected from creating groups, and (3) to analyse the information that can be extracted by merging signals from multiple users. For this, two scenarios involving real-world stimuli (images presented at high rates and movies) were studied. The first scenario consisted of a visual search task in which images were presented at high frequencies. Three modes of combining EEG recordings from different users were tested to improve the detection of different ERPs, namely the P300 (associated with the presence of events of interest) and the N2pc (associated with shifts of attention). We showed that the detection and localisation of targets can improve significantly when information from multiple viewers is combined. In the second scenario, feature movies were introduced to study variations in ERPs in response to cuts through cBCI techniques. A distinct, previously unreported, ERP appears in relation to such cuts, the amplitude of which is not modulated by visual effects such as the low-level properties of the frames surrounding the discontinuity. However, significant variations that depended on the movie were found. We hypothesise that these techniques can be used to build on the attentional theory of cinematic continuity by providing an extra source of information: the brain.

Static and dynamic balance are essential in daily and sports life. Many factors have been identified as influencing static balance control, two of which are carrying additional weight and localized muscle fatigue but their influence on dynamic balance in sport activities has not been fully established. Therefore, the aim of this thesis was to investigate the characteristics of dynamic balance in sport related activities, with specific reference to the influence of body mass changes and muscular fatigue. Study one: The objectives of study one (methodological study, n = 5) were to apply the extrapolated Centre of Mass (XCoM) method and other relevant variables (centre of pressure, CoP; Centre of Mass, CoM; shear forces, Fh; kinetic energy, KE; momentum, P; and angular impulse, AI) to investigate sport related activities such as hopping and jumping. Many studies have represented the CoP data without mentioning its accuracy so several experiments were done to establish the agreement between the CoP and the projected CoM in a static condition. It was found that there was an inaccuracy with the average difference about 4mm. This meant that the angular impulse could not be reliably calculated. Its horizontal component, representing the Friction Torque (Q), could be reliably computed for dynamic balance. The implementation of the XCoM method was found to be practical for evaluating both static and dynamic balance. The general findings were that the CoP, the CoM, the XCoM, Fh, and Qwere more informative than the other variables (e.g. KE, P, and AI) during static and dynamic balance. The XCoM method was found to be applicable to dynamic balance as well as static balance. Study 2: The objectives of study two (baseline study, n =20) were to implement Matlab procedures for quantifying selected static and dynamic balance variables, establish baseline data of selected variables which characterize static and dynamic balance activities in a population of healthy young adult males, and to examine any trial effects on these variables. The results indicated that the implementation of Matlab procedures for quantifying selected static and dynamic balance variables was practical and enabled baseline data to be established for selected variables. There was no significant trial effect. Recommendations were made for suitable tests to be used in later studies. Specifically it was found that one foot-tiptoes tests either in static or dynamic balance are too challenging for most participants in normal circumstances. A one foot-flat eyes open test was considered to be representative and challenging for static balance, while adding further vertical jump and landing tests (two feet flat and one foot flat vertical jump) to the horizontal jumping and hopping for dynamic balance was considered to be more representative of sports situations. The main differences between horizontal and vertical jumping were in anterior-posterior direction. Study 3: The objectives of study three (differentiation study, n =20) were to establish the influence of physical (external added weight) and neurophysiological (fatigue) factors on static and dynamic balance in sport related activities. This was typified statically by the Romberg test (one foot flat, eyes open) and dynamically by jumping and hopping in both horizontal and vertical directions. Statically, added weight increased body's inertia and therefore decreased body sway in anterior-posterior direction though not significantly. Dynamically, added weight significantly increased body sway in both mideo-lateral and anterior-posterior directions, indicating instability, and the use of the counter rotating segments mechanism to maintain balance was demonstrated. Fatigue on the other hand significantly increased body sway during static balance as a neurophysiological adaptation primarily to the inverted pendulum mechanism. Dynamically, fatigue significantly increased body sway in both mideo-lateral and anterior-posterior directions again indicating instability but with a greater use of counter rotating segments mechanism. Differential adaptations for each of the two balance mechanisms (inverted pendulum and counter rotating segments) were found between one foot flat and two feet flat dynamic conditions, as participants relied more heavily on the first in the one foot flat conditions and relied more on the second in the two feet flat conditions. Conclusion: Results from this thesis are expected to aid towards advancing the understanding of balance in sport related activities, and can provide a solid foundation for future work in this area. In particular, a method was established to assess static and dynamic balance, baseline data for these associations was provided, and differential adaptations to physical or neurophysiological constraints were found. Valuable associations between specific variables and the first two mechanisms of balance were demonstrated.

There is considerable research to date in the field of stress, particularly with respect to questionnaire research. There is, however, a lack of recent research on stress in the British Army which addresses either traumatic or organisational stress. This study considers soldiers' experiences of both occupational and traumatic stress, in addition to identifying the contribution of an individual's expectations and evaluations of a deployment, on mental well-being. Furthermore, this research methodology incorporates standardised psychological questionnaires, free response items and interviews with personnel, which serve to provide a comprehensive approach with high face validity. This study aims to encompass the major aspects which influence the onset and course of stress, including stress experiences, individual differences and coping, in one model. Both studies incorporate traumatic and organisational stress, which is particularly relevant in the military profession, where there is risk of exposure to traumatic events. This study attempts to redress the paucity of research on stress in the British Army as a result of conflicts since WWII, in addition to countering the lack of research into occupational stress in the British Army, or information of a longitudinal nature. This study also provides a much needed 'baseline' of data across the British Army regarding stress experiences and reactions. The study also incorporates qualitative aspects, where the respondents are asked what they define as stressful experiences, as opposed to completing a list of pre-defined 'stressors', in addition to incorporating interviews to validate the responses. Finally, an individual's evaluation of a situation, or belief in their actions is taken into account in this research. It is argued that this is of particular importance in a military operational context, when soldiers are no longer deploying in defence of their country against an external threat. It was therefore considered important to establish if there were any effects on psychological well-being based on an individual's evaluation of the deployment situation. This research was conducted in two phases: Study 1 which is a cross-sectional study, proportionate to size across the British Army, and Study 2 which is a longitudinal survey, before and after a six month operational deployment to Northern Ireland. The questionnaire material incorporates both standardised questionnaires and a specific Army questionnaire designed for the study. Support was found for the proposed models of both general (Study 1) and operational stress (Study 2). Previous findings were supported concerning the interrelationships between neuroticism, anxiety, emotion focused coping and adverse life events, and were independent of mastery, self esteem, problem focused coping and well-being. Thirty three and thirty nine percent of respondents reported General Health Questionnaire (GHQ12) values above the cut off criteria for Study 1 and Study 2, respectively. Individual differences concerning reported mental health were noted, particularly with respect to age, marital status and the occurrence of a significant life event. Recommendations addressed the lack of clear evidence for adopting a 'screening out' procedure based upon personality characteristics for mainstream Army deployments. It was suggested that the traumatic aspects of the research could benefit from an alternative questionnaire to the Impact of Events Scale (IES), due to some of the difficulties found in using the questionnaire. It was also suggested that coping strategies should be investigated in greater detail, within a more context specific manner with tighter response definitions. Finally, it is believed that the impact of cumulative operational deployments on the mental health of soldiers needs to be thoroughly researched.

The purpose of this thesis was to examine the nature of executive function deficits in ecstasy users, and the contribution of these executive functions to performance on other cognitive tasks. Using recent theoretical models of executive functioning recreational ecstasy-polydrug users were tested in laboratory settings on measures of mental set switching, response inhibition, memory updating and access to semantic memory. It was found that ecstasy users performed significantly worse than nonusers on measures of updating and access, although cocaine also emerged as an important factor in deficits in access. The contribution of access and updating to performance on more complex executive function tasks was then assessedI.t was found that while associative learning is relatively independent of access and updating, the same was not true for everyday memory and syllogistic reasoning. Ecstasy group related deficits in syllogistic reasoning were slightly attenuated following control for access and substantially following control for updating. It emerged that everyday memory deficits were more related to the use of cannabis than the use of ecstasy. The results of this thesis have serious implications for those who use ecstasy and should be used in educating such individuals. Outside the area of Psychopharmacology this thesis provides further support for the nature of executive functions and their relationship with syllogistic reasoning and everyday memory. Future research should assess executive functions along the same paradigm and seek to recruit polydrug control groups.

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No. of bitstreams: 2 Dissertação Victor de Melo Caixeta - 2015.pdf: 2750656 bytes, checksum: c7c2c97e0c6537b3d17aa54409152ad3 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2015-10-15 / Background: Corticobasal Degeneration (CBD) is an rare and heterogeneous disease in its presentations, representing an great diagnostic challenge. There aren´t, in Brasil, large CBD case series, and there aren´t many in the world as well. Its cognitive and behavioural aspects have received little (despite growing) attention. Objectives: To describe sociodemographic, clinic, neuropsychiatric, neuropathological, and neuroradiologic aspects in a large brazilian DCB case series. To perform a literature review on CBD, with special focus on cognitive and behavioural aspects. Methods: 70 patients data was collected, with CBD diagnosis according to the Cambridge criteria modified by Bak and Hodges (2011). The patients underwent clinical, neuropsychiatric, neuroradiologic (structural and functional) and pathologic (in six cases) retrospective analysis. There were studied clinical, sociodemographic, neuropsychiatric, neuroanatomic variables and family history. Results and Discussion: The mean age at onset was 62.8 years (sd=9,5), and both sexes were equally affected (52,9% male). Hemispheric asymmetry was present in 97% of cases, and the left brain hemisphere was the most affected (68,2% of cases). The most frequent initial presentation was “psychiatric” (with changes in behaviour and/or mood), present in 68,1% of cases, followed by motor-extrapyramidal presentation (54.3%). In the course of the disease, the predominant clinical form (phenotype) was the extrapyramidal-motor with 61.4% of cases, followed by "psychiatric" with 51.4%. There were five cases with presentation of Posterior Cortical Atrophy (PCA) In 37.7% there were not found classic CBD syndromes (e.g., alien hand syndrome). We found 18.7% of cases with family DCB, with four families presenting a phenotype not yet described, of CBD with NPH (Normal Pressure Hydrocephalus). We also observed cognitive and functional impairments in the evaluated scales (MMSE, Pfeffer and CDR), and frequent medical and psychiatric comorbidities, especially diabetes mellitus (23.5%), hypothyroidism (22.1%) and Bipolar Spectrum Disorders (46, 4%), the last two significantly more frequent in the sample. There were six cases of rapidly progressive DCB and six confirmed by autopsy CBD cases in the sample. Conclusion: We observed, in agreement with the literature, a wide variety of CBD presentations, including new and little described phenotypes (NPH and PCA). In the characterization of the sample, we observed a great prevalence and importance of cognitive, affective and behavioural presentations. / Introdução: A Degeneração Corticobasal (DCB), é uma doença rara e heterogênea em suas apresentações, representando um grande desafio diagnóstico. Não há descrições de grandes amostras de DCB no Brasil, e poucas no mundo. Seus aspectos cognitivos e comportamentais têm recebido pouca (apesar de crescente) atenção. Objetivos: Descrever aspectos sociodemográficos, clínicos, neuropsiquiátricos, neuropatológicos e de neuroimagem em uma grande série de casos brasileiros com DCB. Realizar uma revisão da literatura sobre a DCB, com especial enfoque em aspectos cognitivos e comportamentais. Metodologia: Foram colhidos dados de 70 pacientes com DCB de acordo com critérios de Cambridge modificados por Bak e Hodges (2011). Os pacientes foram submetidos à avaliação retrospectiva clínica e neuropsiquiátrica, de neuroimagem estrutural e funcional e seis pacientes ao exame neuropatológico. Foram estudadas variáveis sociodemográficas, clínicas, neuropsiquiátricas, neuroanatômicas, e antecedentes familiares. Resultados e Discussão: A idade média de início dos sintomas foi de 62,8 anos (dp=9,5), sendo os dois sexos igualmente afetados (52,9% masculino). Assimetria hemisférica esteve presente em 97% dos casos e o hemisfério esquerdo foi o mais acometido (68,2% dos casos). A apresentação inicial mais freqüente foi a “psiquiátrica” (com alterações do comportamento e/ou humor), presente em 68,1% dos casos, seguida da apresentação motora-extrapiramidal (54,3%). No decorrer da doença, a forma clínica (fenótipo) predominante foi a motora-extrapiramidal, com 61,4% dos casos, seguida da “psiquiátrica”, com 51,4%. Houve cinco casos com apresentação de Atrofia Cortical Posterior (ACP). Em 37,7% não ocorreram achados clássicos da DCB (por exemplo, síndrome da mão estrangeira). Encontramos 18,7% de casos com DCB familiar, com quatro famílias apresentando um fenótipo ainda não descrito, de DCB com HPN (Hidrocefalia de Pressão Normal). Observamos também prejuízos cognitivos e funcionais nas escalas avaliadas (MEEM, Pfeffer e CDR), e comorbidades clínicas e psiquiátricas frequentes, em especial Diabetes Mellitus (23,5%), hipotireoidismo (22,1%) e Transtornos do Espectro Bipolar (46,4%), os dois últimos com frequência na amostra significativamente maior que na população. Houve seis casos de DCB rapidamente progressiva e seis casos confirmados por necropsia na amostra. Conclusão: Observamos, em consenso com a literatura, uma grande variedade de apresentações da DCB, inclusive com formas novas e pouco descritas (HPN e ACP). Na caracterização da amostra, percebemos grande frequência e importância das apresentações comportamentais, afetivas e cognitivas.

It is commonly observed that people with autism spectrum disorder (ASD) make fewer attempts to have social contact. A recent theory suggests that reduced motivation to have social interactions might be the root for social difficulties in ASD (Chevallier, Kohls, Troiani, Brodkin, & Schultz, 2012). There are currently few simple behavioural ways to test these claims. The aim of this research was 1) to develop a measure of social seeking component of social motivation that is simple enough to be used with a large population of people with ASD; and 2) to test if there is evidence of reduced social seeking in people with ASD. As the first part of this research, I developed and tested a simple behavioural paradigm “Choose-A-Movie” (CAM) that evaluates the effort participants make to view social vs non-social stimuli hence estimating the reward value of the stimuli. It was found that typical adults prefer to watch social stimuli more but they trade-off their stimuli preference for effort. In experiment 2 I used the same paradigm with adults with and without ASD and found that unlike typical adults people with ASD prefer non-social stimuli but they too trade-off their stimuli preference for effort. Having established the efficacy of the CAM paradigm in adults with and without ASD, in experiment 3 I explored CAM’s efficacy for younger participants. A comparison between adolescents with and without ASD on CAM showed that both groups prefer choice requiring less effort, and participants with ASD prefer non-social stimuli to social. However unlike typical adults, typical adolescents did not show a preference for social stimuli. Though these experiments supported the reduced social motivation theory of ASD, they raised questions about the development of social seeking in typical people. Therefore, in experiment 4 I tested participants between ages 4-20 years on CAM. The results showed that typical individuals undergo a decline in their social seeking tendencies during pre-adolescence. This highlights the need for developmental evaluation of social seeking in both ASD and non-ASD populations. Finally, in experiment 5 the CAM paradigm was compared with an Approach-avoidance (AA) task, a frequently used measure of social seeking (Aharon et al., 2001). The findings suggested that social preference could be elicited more strongly in typical adults using CAM paradigm. Furthermore the autistic traits of participants were a reliable predictor of social seeking on CAM but not on AA task. These results raise the question of whether different tools claiming to measure social seeking target the same behaviour. Overall, this research shows that social motivation can be quantified using a simple behavioural paradigm – CAM that targets social seeking component of it, and also that social motivation is reduced in people with ASD. At the same time this research raises important questions about 1) developmental changes in social seeking in typical people, and 2) if different tools of social seeking, measure the same underlying construct. It is important to explore these questions to have a better understanding of social seeking in people with ASD.

The Stroke Drivers Screening Assessment (SDSA) is a collection of three cognitive tests found predictive of driving in stroke patients. Whilst two of the test (Square Matrices and Road Sign Recognition) were good predictors of on-road performance, it remained unknown whether the SDSA could predict fitness to drive for people with other acquired neurological disabilities. The on-road test, considered the 'gold standard' of driving ability, was the criterion against which SDSA performance was compared. Since the SDSA's validity depends on the reliability of the driving instructor's decision, it seemed important to check that this was consistent with instructors elsewhere. Therefore this study had three aims:- i)To examine the content and concurrent validity of the SDSA sub test. ii)To determine whether the SDSA, either alone or in conjunction with other cognitive tests, could predict fitness to drive for patients with acquired neurological disabilities other than stroke. iii) to check the inter-rater reliability of the gold standard of driving ability (used in studies to validate the SDSA).