Primary brain tumours are recognised as the most common form of solid tumours in children, with pilocytic astrocytoma, medulloblastoma and ependymoma being found most frequently. Despite their high mortality rate, early detection can be facilitated through the use of Magnetic Resonance Imaging (MRI), which is the preferred scanning technique for paediatric patients. MRI offers a variety of imaging sequences through structural and functional imaging, as well as providing complementary tissue information. However visual examination of MR images provides limited ability to characterise distinct histological types of brain tumours. In order to improve diagnostic classification, we explore the use of a computer-aided system based on texture analysis (TA) methods. TA has been applied on conventional MRI but has been less commonly studied on diffusion MRI of brain-related pathology. Furthermore, the combination of textural features derived from both imaging approaches has not yet been widely studied. In this thesis, the aim of the research is to investigate TA based on multi-centre multimodal MRI, in order to provide more comprehensive information and develop an automated processing framework for the classification of childhood brain tumours.

The objective of this thesis was to develop a new methodology for the improvement of the interface properties of gold electrodes for neural implants. The goal was to increase the surface area without a change in geometrical footprint of the electrode with nano-fabrication tools. A process has been created that uses Nanosphere Lithography for masking layer deposition and anisotropic etching to fabricate nanostructures on the surface of the electrodes. Optimisation of the process parameters led to a control of structure shape, which allowed to produce a variety of shapes. The effect of the nano-structures on the interface was investigated by impedance spectroscopy and complementary electrochemical measurements. It showed that the interface impedance could be decreased significantly by up to a magnitude of scale with the surface modifications. In addition a porous columnar form of sputtered gold was found that also showed decreased interface impedance compared to standard gold films. A set of neural implants was designed and fabricated to test the effect of surface modification in vitro in neurological tissue. The surface modification process was successfully implemented in the device fabrication. The in-vitro assessment showed signs of improved interface performance compared to unmodified devices.

Objective: The National Policy and Strategy for the Provision of Neuro-Rehabilitation Services in Ireland (2011) Report recommend further development of a case management approach utilising a key worker role to identify intensive users of unplanned acute and secondary care services. In addressing this form of practice, this study examined how the role of the key worker could support primary carers for people with a Traumatic Brain Injury (TBI) within the community after leaving hospital. Methods: The study employed an action research approach in which the researcher worked with six primary carers of people with TBI. Through a participatory approach, the role of the key worker was introduced and developed as a pilot project over six months. Findings: Identified roles of the key worker ranged from providing TBI education, case management services, development of a support network, professional guidance, empowering the primary carer within the case management process to offering emotional support. Conclusion: The research supports the British Society of Rehabilitation Medicine National Clinical Guidelines (BSRM, 2003) model of TBI rehabilitation by suggesting the allocation of a key worker to form part of a multidisciplinary team of rehabilitative services within the community.

The use of memory strategies can promote independence in people who have an acquired brain injury but people often do not take readily to using such strategies. Certain demographic variables have been associated with the use of memory strategies these variables cannot be changed through therapeutic interventions. The aim of this thesis is to explore variables that may be modifiable through rehabilitation e.g. health beliefs and perceptions of aids, to see whether they help us understand factors influencing the uptake of memory strategies. The thesis consists of three studies. The first uses Interpretative Phenomenological Analysis to explore how people feel about using memory strategies. The second is a cross sectional questionnaire design exploring the predictive power of variables identified in the first study to predict the use of strategies together with demographic variables. The third is a single case study utilising findings from the first two studies to help an individual use a mobile phone and Google calendar as a memory aid. A key factor in the use of memory compensations is the need to ‘fit’ the aid to an individual’s lifestyle. Consequently, there is greater optimism for those who may otherwise be regarded as unlikely to use aids.

The overarching aim of this thesis was to better understand the behavioural, cognitive, and neural corollaries of blunted cardiovascular and/or cortisol reactions to acute psychological stress. As such, it was also concerned to further test the proposition that blunted cardiovascular and cortisol reactions to acute psychological stress are markers of an unconscious dysfunction in the motivational areas of the brain. These aims were achieved by using a mixed methods interdisciplinary approach encompassing both laboratory stress studies and secondary analyses of epidemiological datasets. Chapter 2 adduced evidence that blunted cardiovascular and cortisol reactivity was associated with a non-substance addiction, namely exercise dependence. Chapter 3 demonstrated that blunted cardiovascular and cortisol reactivity was related to disordered eating behaviour. Differences in stress reactivity between healthy controls and exercise dependent individuals or disordered eaters could not be explained by actual stress task performance, how engaged or how stressful participants found the stress task, cardio-respiratory fitness, and a number of other potential confounders. Chapters 4, 5, and 6 demonstrated that poor cognitive ability was associated with blunted stress reactivity retrospectively, cross-sectionally, and prospectively. Additionally, Chapter 6 demonstrated that blunted cardiac reactivity predicted cognitive decline over a 7 year period. Chapter 7 revealed brain activation differences between pre-determined exaggerated and blunted cardiac stress reactors during an acute stress exposure in a fMRI paradigm. Blunted cardiac reactors showed hypo-activation in the areas of the brain associated with motivation and emotion compared to exaggerated reactors. There were no reactivity group differences in subjective measures of the stressfulness and difficulty of and engagement with the stress task. Overall, the research reported in this thesis provides further evidence that blunted cardiovascular and cortisol reactions to stress are associated with a number of adverse health and behavioural outcomes and may be a peripheral marker of some form of disengagement in those areas of the brain that support motivated behaviour.

Cytomegalovirus (CMV) is ubiquitous and the incidence of human infection increases with age. CMV exacerbates immunosenescence and is associated with increased mortality and morbidity in older adults. Cognitive decline in older generations causes great personal and financial burden. Here, examination of the Lothian Birth Cohort (1936) establishes an association between higher CMV IgG tires and a decline in general cognitive ability. This work also further defines the influence of CMV and Epstein-Barr virus (EBV) infection upon immune repertoire. Analysis of the 1000 Elders cohort in Birmingham demonstrates that CMV-and EBV-specific T cell responses remain stable over a period of ten years. However, CMV seronegative older adults display higher EBV viral loads compared to CMV seropositive individuals despite a similar frequency of EBV-specific T cell responses in both groups. In addition, CMV serostatus does not appear to influence the phenotype of EBV-specific T cell responses. Collectively, this study defines an association between high CMV IgG titres and decreased cognitive ability in older adults and demonstrates differential control of EBV by CMV seropositive and negative adults. High EBV viral loads may impact negatively upon the health of older adults; this should be studied further in future work.

There has been renewed interest into affective symptoms and psychological approaches to schizophrenia and other psychosis, yet no in-depth investigation as to the course, consequences or indeed psychological causes of depression in a phase specific manner in the important first episode. Our understanding of risk and aetiological processes in psychotic illness will only advance once we accurately identify the “end phenotype” of psychotic illness. This series of studies investigates the course of depression in first episode psychosis, its significance in terms of suicidal thinking, and relation to both diagnosis and other symptom domains. Depression in the acute and post psychotic phases is explored, through the importance of the awareness and appraisal of positive symptoms, and diagnosis itself. Significant findings include a pervasive nature of depression throughout the course of first episode psychosis, the predictive nature of prodromal depression and the high prevalence of suicidal acts. Appeasement and engagement with voices, subordination to persecutors and the (ineffective) use of safety behaviours drive a position of entrapment, demoralization and a lack of control. In addition negative illness appraisals are stable and may vary between cultural groups. Implications are explored, in terms of clinical practice, aetiological pathways, potential treatments and intervention strategies

Volume 1: Research component There are three papers contained in this volume, all concerned with maternal mental health problems in the perinatal period. The first is a review that examines the existing literature on eating disorders in the perinatal period. It examines prevalence, symptomatology levels across the perinatal period and factors associated with development and remission from eating disorders in the perinatal period. The second paper is a report of research, carried out by the author, investigating obsessive compulsive disorder, bonding and meta-cognitions in new mothers. It specifically examines whether bonding is impaired in new mothers with OCD when compared with mothers who have no symptoms of OCD, a subject that has not been investigated in previous research. Both papers have been prepared for submission to Archives of Women‟s Mental Health. The final paper is a public domain paper describing the literature review and empirical papers and has been used to disseminate the findings of the research amongst participants, mother and baby organisations and mental health professionals. The appendices contain information regarding ethical approval, measures used and instructions to authors from the Archives of Women‟s Mental Health. Volume 2: Clinical component This volume contains five clinical practice reports (CPR) submitted during the doctorate course. These reports reflect the training of the course and the work completed over the three years of the course. CPR 1 and 2 were conducted during a child and adolescent placement. CPR 1 describes a doctor phobia in a five year old girl, formulated from a behavioural and a systemic perspective. CPR 2 reports a single case experimental design study on a narrative intervention for sleep difficulties in a nine year old boy. CPR 3 describes a qualitative service evaluation of a waiting list initiative and changes to the referral system to a Psychological Therapies Service within an adult mental health service. CPR 4 is a case study of a CBT intervention for a client with OCD in a specialist adult service. The abstract of CPR 5, a presentation on a CBT and narrative intervention for anger in a woman with a learning disability in an inpatient setting. The names and identifying details have been changed or removed from these reports to protect anonymity.

The other-race effect refers to the impoverished individuation and recognition of other-race faces relative to own-race faces. The aim of this thesis was to investigate non-racial ingroup/outgroup categorisation, inter-/intra-racial context, and encoding conditions as signalling cues that affect own- and other-race face processing. Across eight experiments using both behavioural and neuroimaging methods, I demonstrated (1) that the context in which own- and other-race faces are encountered can determine the salience of racial category membership, with implications for how (and how much) non-racial ingroup/outgroup status influences own- and other-race face perception, (2) that task demands can lead perceivers toward more or less configural processing regardless of target ingroup/outgroup status, with implications for the influence of non-racial ingroup/outgroup status, and (3) that both racial and non-racial ingroup/outgroup status have the potential to influence the early stages of face perception. These findings both support and extend the Categorisation–Individuation Model, yielding a more comprehensive insight into the other-race effect.

This thesis presents the design and the fabrication process of a three-dimensional (3D) neural interface consisting of a bundle of parallel micro-channels with (100μmx100μm) cross-sectional area and embedded micro-electrodes. This is a regenerative implant that is able to stimulate and record extracellular neural signals in the peripheral nervous system as demonstrated by the \(in-vivo\) experiments conducted in collaboration as part of this project. These implants have the potential to be developed into long-term neural interfaces capable of extracting neural signals from stumps of severed peripheral nerves to use as control inputs for muscles simulators or artificial limbs for amputees. The skeleton of the device is entirely made of flexible polyimide films. Gold micro-electrodes and micro-channels of photosensitive polyimide are patterned directly on polyimide substrates. After fabrication, the 2D electrode micro-channel array is rolled into a 3D structure forming concentric rolls of closed micro-channel arrays with a Swiss-roll like arrangement. Microflex Interconnection technique (MFI) was incorporated successfully into the implant. The performance of the implant microelectrodes was characterised \(in-vitro\) through impedance spectroscopy and \(in-vivo\) via implantation in animals for three months. The ability of the electrodes to stimulate and capture action potentials from regenerated tissue was also assessed.