Stroke is a major public health problem and stroke patients suffer much mortality and morbidity due to chest infections, especially in the acute period. Chest infections are associated with respiratory muscle weakness and poor cough. We studied ischaemic hemispheric stroke patients within two weeks of their first-ever stroke to investigate their respiratory physiology, volitional and non-volitional respiratory muscle strength and voluntary and reflex cough function. -- Patients were weak on voluntary but not involuntary tests of expiratory muscle function. They were also impaired on tests of both voluntary and reflex cough. The data we collected suggests that impairment may be due in part to ineffective coordination of the complex cough manoeuvre, following cerebral ischaemia. -- To further investigate the underlying reasons for impaired cough flow we studied functional residual capacity (FRC) in a group of stroke patients with mild impairments. In the semi-recumbent position patients’ FRC was significantly lowered, compared with healthy controls even in these acute patients little residual disability. The low FRC was strongly associated with low cough inspired volume and low cough inspired volume was associated with poor cough flow. -- Transcranial magnetic stimulation was used to investigate the corticomotor projection to the abdominal muscles. We also designed a cough training protocol to be tried initially in the lab, to see if there is an effect of cough training on corticomotor excitability. This was a feasibility study in two patients; we make recommendations to increase the training duration to ten minutes and suggest how TMS could be used to assess the effect of training on corticomotor excitability. If an effect is shown in the lab across a number of patients, the training regimen could then be tried over longer periods in a clinical trial.

Background: In cognitive models of psychosis, reasoning and reasoning biases are central to the development and maintenance of delusions. In particular, individuals with psychosis tend to gather less data before making a decision, hence ‘jumping to conclusions’ (JTC), compared to the general population. This data-gathering bias makes individuals more likely to reach an inaccurate decision and may thus act as both a vulnerability factor for the development of delusions, and a maintaining factor. However, while evidence for the presence of the bias is robust, understanding of the associated mechanisms is limited, particularly in the early course of psychosis. Understanding what factors may influence the bias in First Episode Psychosis (FEP) will inform the development of early psychological interventions, which may reduce the distress and disability associated with psychosis. The thesis: The four studies in this thesis examined the neuropsychological and symptom correlates of the JTC data-gathering bias in FEP employing a case-control design. Method: 140 clinical participants and 132 non-clinical controls completed two versions of a probabilistic reasoning task, the Beads Task. Clinical participants completed measures of psychotic symptoms, and non-clinical participants completed a measure of subclinical psychotic symptoms. All participants completed a comprehensive neuropsychological assessment. Demographic data were collected for all participants. Results: The JTC data-gathering bias was significantly more prevalent in the clinical group with FEP than in the non-clinical control group, in both versions of the probabilistic task. A clear, very strong association was found between neuropsychological performances and the presence of the JTC bias across the groups. A weak, but significant association was found between the presence of current delusions and the JTC bias in the clinical group. Contrary to expectations, no associations were found between the JTC bias and subclinical psychotic symptoms in the non-clinical control group. Conclusions: This study is the first to find a link between neuropsychological functioning and the JTC bias in the largest FEP group and non-clinical control group yet reported. The findings of this study elucidate ambiguities in the literature and help clarify the direction of cognitive intervention in psychosis.

Background: There is a high frequency of the risk-conferring APOE e4 allele in African populations, but in some studies, the risk of dementia is less than in Caucasians in Europe and North America. In an admixed population of older Cubans I estimate the prevalence, incidence, correlates and impact of dementia among older Cubans; I assess the effects of reported ethnicity, admixture and apolipoprotein E genotype on dementia prevalence and estimate the association between cardiovascular risk factors and dementia incidence. -- Methods: I undertook a one phase survey (baseline) of all over 65 year old residents of seven catchment areas in Cuba (n=2944) during 2003 to 2007. Dementia diagnosis was established according to DSM-IV and 10/66 criteria. APOE genotype was determined in 2520 participants, and genetic admixture in 235 dementia cases and 349 controls. Baseline data was used to estimate prevalence, impact, and the effect of ethinicity, and apolipoprotein E genotype on dementia prevalence. The case control study was used to test the hypothesis that the effect of APOE genotype on dementia is modified by ethnic group. An incidence wave was conducted 4.5 years after cohort inception in order to estimate incidence and cardiovascular risk factors associations -- Results: The prevalence of DSM-IV dementia was 6.4% and 10.8% according to the 10/66. Both dementia outcomes were associated with older age, less education, a family history of dementia, shorter leg length and smaller skull circumference. Dementia, rather than physical health problems or depression, was the main contributor to needs for care and caregiver cutting back on work. The incidence rate of 10/66 dementia was 20.5 per 1000/pyear (95% Cl, 17.6-23.5). African admixture was linearly related to number of APOE e4 alleles, but was not associated with the prevalence of dementia.

Policy to involve patients and the public in health service development and medical research has been widely promoted in the United Kingdom on the grounds that this will improve the quality of services and research. This thesis investigates how stroke survivors were involved in two enterprises: the Transforming Stroke Services Project (TSSP) hosted in the NHS; and an established Stroke Research Programme (SRP) located in a medical school. Data were collected in an ethnographic study conducted over a three-year period in south London. Drawing on Lukes’ three-dimensional view of power and embodied health movement theory, the thesis considers the implicit claims of user involvement policy that involving the public in the work of professionals will lead to patient empowerment, creation of new forms of knowledge, and a transformation of unequal relations between patients and professionals. In the TSSP, stroke survivors were positioned as ‘partners’ in the project to modernise stroke services, yet the parameters of the partnership were determined from the outset by professionals. Transformation of patient and professional roles was not a goal that stroke survivors engaged in the TSSP particularly shared, deferring to professionals as ‘the experts’. In the SRP, user involvement activities were similarly determined by professionals, and were adopted to demonstrate policy compliance; user involvement was given salience by being transformed into an object of investigation. Patients’ experiential knowledge was ascribed value of a different order to expert knowledge, which was incompatible with any transformation of traditional patient and professional roles. User involvement policy is shown to borrow from embodied health movements in terms of discourse and concern with diverse forms of knowledge and action. Yet whilst user involvement policy opens up space for citizen engagement, seeking the resources of service users, it inhibits their capacity for protest; the policy prevents an Embodied Health Movement from forming, but creates a new bureaucratised form of biosociality.

This thesis is divided into three sections. Section one, the literature review, considers the experiences of general hospital staff caring for patients with dementia. 14 papers were included in the meta-synthesis. Five key themes were constructed from the analysis: the unknown and undesirable; constraints of the environmental and organisational context; emphasising the physical health of patients; recognising the benefits of person-centred care; and identifying the need for training. The synthesis identified how a lack of knowledge of dementia, particularly regarding behaviours that are considered challenging, can contribute to low staff confidence and negativity towards these patients. This, along with organisational constraints, can impact on ability to provide person-centred care. The benefits of dementia training have been recognised. Clinical and research implications of the findings are discussed. Section two, the empirical paper, considered the experiences of staff within general hospitals regarding the use of truth and deception when caring for patients with dementia. In particular, it explored their decision making processes when choosing whether to tell the truth or to deceive. A grounded theory methodology was used to construct a theoretical model of this process. The analysis identified how ‘triggers’ set in motion the need for a response. Various ‘mediating factors’ (including a lack of communication, the individual’s interpretation of their role and responsibility, and their ethical framework) influenced how staff chose to ‘respond’ to those triggers. Again, clinical and research implications have been recognised. Section three, the critical appraisal, offers a reflective account of the research journey. These reflections are organised into six categories that consider the researcher’s own decision-making processes when carrying out the empirical paper.

The phenomenology of impulsive compulsive behaviours in patients with Parkinson’s disease (PD) treated with dopaminergic therapy has been reviewed. Neuropsychological studies have been conducted to explore the behavioural mechanisms responsible for these socially devastating disorders, which affect a substantial proportion of treated patients. Results demonstrated that poor information sampling and impaired working memory capacity, especially when mental manipulation of information was required, distinguish PD patients with impulsive compulsive behaviours from those without. A direct comparison to non PD-patients with addictions revealed that impulsive PD patients closely resembled illicit drug abusers, whereas non-impulsive PD patients treated with a dopamine agonist performed similarly to pathological gamblers. PD patients who were not taking dopamine agonists performed as well as healthy volunteers, even when treated with deep brain stimulation. Therefore, dopamine agonists are the single most important risk factor for impulsive choice in PD. Conversely, response inhibition and feedback learning were intact in medicated PD patients with impulsive compulsive behaviours. Furthermore, all PD patients became more risk prone after dopaminergic medication, but greater salivary cortisol release only correlated with risk taking behaviour in the PD group with behavioural addictions. Cortisol plays also a prominent role in stress regulation. Therefore, the literature was reviewed to explore links between emotional stress and PD.

The main focus of this project is the impact of Deep Brain Stimulation (DBS) surgery on reward responsiveness in Parkinson's disease (PD). This project aims to investigate what the neuropsychological effects of this surgical treatment can teach us about the mechanism of stimulation and its effects on the underlying neural circuits that are damaged in this disease. The first part of this project aims to review the evidence on apathy in Parkinson's disease. Studies published to date are discussed and critically reviewed, with reference to the occurrence of apathy in Parkinson's disease and the effects of neurosurgical intervention on the occurrence of apathy in Parkinson's disease. The second part of this project aims to assess Parkinson's disease patients who have undergone Deep Brain Stimulation surgery for the treatment of the motor symptoms of the disease. Specifically, this study aims to assess the impact of Deep Brain Stimulation on reward responsiveness, as measured by patient's motor performances on a simple reaction time task and a card-sorting task. The final part of this project is a critical appraisal of the research, reflecting on the research process the strengths and weakness of the study, changes I would make to improve the study and how further research could build upon the results obtained here are discussed.

We describe a Bayesian scheme to analyze images, which uses spatial priors encoded by a diffusion kernel, based on a weighted graph Laplacian. This provides a general framework to formulate a spatial model, whose parameters can be optimised. The standard practice using the software statistical parametric mapping (SPM) is to smooth imaging data using a fixed Gaussian kernel as a pre-processing step before applying a mass-univariate statistical model (e.g., a general linear model) to provide images of parameter estimates (Friston et al., 2006). This entails the strong assumption that data are generated smoothly throughout the brain. An alternative is to include smoothness in a multivariate statistical model (Penny et al., 2005). The advantage of the latter is that each parameter field is smoothed automatically, according to a measure of uncertainty, given the data. Explicit spatial priors enable formal model comparison of different prior assumptions, e.g. that data are generated from a stationary (i.e. fixed throughout the brain) or non-stationary spatial process. We describe the motivation, background material and theory used to formulate diffusion-based spatial priors for fMRI data and apply it to three different datasets, which include standard and high-resolution data. We compare mass-univariate ordinary least squares estimates of smoothed data and three Bayesian models spatially independent, stationary and non-stationary spatial models of non-smoothed data. The latter of which can be used to preserve boundaries between functionally selective regional responses of the brain, thereby increasing the spatial detail of inferences about cortical responses to experimental input.

The aim of this thesis was to test predictive coding as a model of cortical organization and function using a specific brain response, the mismatch negativity (MMN), and a novel tool for connectivity analysis, dynamic causal modelling (DCM). Predictive coding models state that the brain perceives and makes inferences about the world by recursively updating predictions about sensory input. Thus, perception would result from comparing bottom-up input from the environment with top-down predictions. The generation of the MMN, an event- related response elicited by violations in the regularity of a structured auditory sequence, has been discussed extensively in the literature. This thesis discusses the generation of the MMN in the light of predictive coding, in other words, the MMN could reflect prediction error, occurring whenever the current input does not match a previously learnt rule. This interpretation is tested using DCM, a methodological approach which assumes the activity in one cortical area is caused by the activity in another cortical area. In brief, this thesis assesses the validity of DCM, shows the usefulness of DCM in explaining how cortical activity is expressed at the scalp level and exploits the potential of DCM for testing hierarchical models underlying the MMN. The first part of this thesis is concerned with technical issues and establishing the validity of DCM. The second part addresses hierarchical cortical organization in MMN generation, plausible network models or mechanisms underlying the MMN, and finally, the effect of repetition or learning on the connectivity parameters of the causal model.

Worldwide, radiology continues to evolve. Not only do imaging techniques advance and become more sophisticated, but factors affecting human health change with every decade. The continued advancement of medical images (their acquisition and interpretation) puts a strain on medical specialists, even before individual patient needs are considered. Factors that influence the ability of the reader to deliver patient needs depend on not only the image, but also the readers' level of experience and expertise. Medical image acquisition, accuracy and interpretation have a hugely important role to play in patient safety. In neurology, referred patients are most frequently sent for computed tomography (CT) and magnetic resonance (MR) imaging of the brain to shed light on the origin and impact of disease. Whilst most observer performance studies focus on screening and detection of a few abnormalities in a non-diseased population, the diseases of 'older-age' are often neglected and treated reactively i.e. when a multitude of signs and symptoms appear, not necessarily as a preventive measure. Owing to the difficulty of measuring performance and the nature of expert interpretation when the technology itself is changing; neuroradiology has not been considered extensively from an observer performance perspective and studies concerning visual search in this area are very thin on the ground. Stroke is the focus of inquiry here for many reasons, but predominantly because urgent imaging of patients with quick feedback of image findings can reduce disability and save lives. If a further 10% of acute stroke patients received thrombolytic therapy within 3 hours of onset, over 1,000 people would regain independence per annum rather than rapidly deteriorate (DoH, 2006). Once treatment is administered and followed up effectively, patients can benefit from a further 5-10 years of life (Indredavik, 1999; DoH, 2007). The benefits of further treatment within this population are known. What isn't known is whether experts make errors of judgement within this clinical area, even if access to healthcare is increased.