This thesis explores what a range of people know and understand about cognitive impairment. The research presented here also explores the language and terminology that people use when discussing cognitive impairment. In order to do so, a mixed methods design was employed, involving three related studies; a systematic review of the literature about knowledge and understanding of mild cognitive impairment (MCI), a questionnaire study exploring respondents’ knowledge and understanding of cognitive impairment, and an interview study building on the results of the questionnaire and exploring perceptions of cognitive impairment in-depth. The systematic review included 30 studies; 20 qualitative articles and 10 survey studies. The questionnaire study received 417 responses predominantly from England, but including some international responses. Questionnaire respondents were drawn from six population groups: people living with cognitive impairment, care partners, younger adults, older adults, healthcare professionals, and dementia specialists. Twenty-one semi-structured interviews were conducted with representatives from each of these six participant groups. The findings from these studies suggest that most participants were able to offer a definition of cognitive impairment, highlighting similar symptoms (focusing on memory problems) and causes (such as brain damage and ageing). Participants discussed cognitive impairment in the context of dementia and were uncertain as to whether the two were synonymous or different. Where participants felt that cognitive impairment and dementia were different, they were unable to articulate these differences suggesting that the boundaries between cognitive impairment and dementia are not clear to the wider population. Participants offered causation accounts and narratives which suggested both controllable and uncontrollable factors may play a role in cognitive health, but participants generally claimed that cognitive impairment was beyond an individual’s personal sphere of control. Participants identified that professionals and the lay population used different language and labels when discussing cognitive impairment and most felt that MCI was not an acceptable or appropriate label. The use of the word memory in diagnostic services for cognitive impairment and dementia (such as memory clinic, memory assessment service) is challenged as this may contribute to the perception that cognitive impairment and dementia are conditions which are solely or primarily characterised by a memory impairment. The results of the studies inform the development of an illness representation model of cognitive impairment, providing a framework on which to base future information resources, media messages and public health and awareness campaigns. This thesis has begun to address a key gap in the literature, considering the views of a range of populations about cognitive impairment. However, future research is needed to explore factors which influence perspectives about cognitive impairment and to consider whether these perspectives change over time and can be influenced by educational campaigns and information.

Functional magnetic resonance imaging (fMRI) is an important tool for understanding neural mechanisms underlying human brain function. Understanding how the human brain responds to stimuli and how different cortical regions represent the information, and if these representational spaces are shared across brains and critical for our understanding of how the brain works. Recently, multivariate pattern analysis (MVPA) has a growing importance to predict mental states from fMRI data and to detect the coarse and fine scale neural responses. However, a major limitation of MVPA is the difficulty of aligning features across brains due to high variability in subjects’ responses and hence MVPA has been generally used as a subject specific analysis. Hyperalignment, solved this problem of feature alignment across brains by mapping neural responses into a common model to facilitate between subject classifications. Another technique of growing importance in understanding brain function is real-time fMRI Neurofeedback, which can be used to enable individuals to alter their brain activity. It facilitates people’s ability to learn control of their cognitive processes like motor control and pain by learning to modulate their brain activation in targeted regions. The aim of this PhD research is to decode and to align the motor representations of multi-joint arm actions based on different modalities of motor simulation, for instance Motor Imagery (MI) and Action Observation (AO) using functional Magnetic Resonance Imaging (fMRI) and to explore the feasibility of using a real-time fMRI neurofeedback to alter these action representations. The first experimental study of this thesis was performed on able-bodied participants to align the neural representation of multi-joint arm actions (lift, knock and throw) during MI tasks in the motor cortex using hyperalignment. Results showed that hyperalignment affords a statistically higher between-subject classification (BSC) performance compared to anatomical alignment. Also, hyperalignment is sensitive to the order in which subjects entered the hyperalignment algorithm to create the common model space. These results demonstrate the effectiveness of hyperalignment to align neural responses in motor cortex across subjects to enable BSC of motor imagery. The second study extended the use of hyperalignment to align fronto-parietal motor regions by addressing the problems of localization and cortical parcellation using cortex based alignment. Also, representational similarity analysis (RSA) was applied to investigate the shared neural code between AO+MI and MI of different actions. Results of MVPA revealed that these actions as well as their modalities can be decoded using the subject’s native or the hyperaligned neural responses. Furthermore, the RSA showed that AO+MI and MI representations formed separate clusters but that the representational organization of action types within these clusters was identical. These findings suggest that the neural representations of AO+MI and MI are neither the same nor totally distinct but exhibit a similar structural geometry with respect to different types of action. Results also showed that MI dominates in the AO+MI condition. The third study was performed on phantom limb pain (PLP) patients to explore the feasibility of using real-time fMRI neurofeedback to down-regulate the activity of premotor (PM) and anterior cingulate (ACC) cortices and whether the successful modulation will reduce the pain intensity. Results demonstrated that PLP patients were able to gain control and decrease the ACC and PM activation. Those patients reported decrease in the ongoing level of pain after training, but it was not statistically significant. The fourth study was conducted on healthy participants to study the effectiveness of fMRI neurofeedback on improving motor function by targeting Supplementary Motor Cortex (SMA). Results showed that participants learnt to up-regulate their SMA activation using MI of complex body actions as a mental strategy. In addition, behavioural changes, i.e. shortening of motor reaction time was found in those participants. These results suggest that fMRI neurofeedback can assist participants to develop greater control over motor regions involved in motor-skill learning and it can be translated into an improvement in motor function. In summary, this PhD thesis extends and validates the usefulness of hyperalignment to align the fronto-parietal motor regions and explores its ability to generalise across different levels of motor representation. Furthermore, it sheds light on the dominant role of MI in the AO+MI condition by examining the neural representational similarity of AO+MI and MI tasks. In addition, the fMRI neurofeedback studies in this thesis provide proof-of-principle of using this technology to reduce pain in clinical applications and to enhance motor functions in a healthy population, with the potential for translation into the clinical environment.

Background: Self-injury is reported to be common in autism spectrum disorder (ASD). However, there are limited robust data detailing the prevalence, persistence, associated person characteristics and operant function of self-injury in ASD. Method: Three large scale survey studies were employed to establish the prevalence, persistence and risk markers for self-injury in ASD compared to contrast groups. Experimental functional analyses were conducted, including a fine grained temporal analysis of behaviours associated with self-injury. Results: Self-injury was displayed by 50% of the ASD sample and was persistent over three years in 77.8% of the group. Self-injury was associated with higher levels of autistic behaviour in individuals without idiopathic autism. Self-injury was associated with higher levels of impulsivity, hyperactivity, painful health conditions, repetitive behaviours and lower levels of adaptive behaviour. ‘ASD weighted’ operant functions for self-injury were identified for the majority of children with ASD. Conclusions: Self-injury is prevalent and persistent in ASD. The presence of ASD phenomenology is a risk marker for self-injury. There is a role for repetitive behaviours, pain and impaired behavioural inhibition in the development and persistence of self-injury. Self-injury is likely to be maintained by operant reinforcement in many individuals with ASD, through ‘ASD weighted’ reinforcement contingencies.

This thesis has evaluated the roles of dorsal and ventral processing streams in recognition and use of objects. Four main empirical studies are presented. First, to investigate how the cortical brain processes semantic and action knowledge in different object-related tasks, I examined structural data from stroke patients (Chapter 2) and functional data from healthy individuals (Chapter 3) using a voxel-wise statistical analysis method. Using data of different modalities (structural CT, fMRI) from different sources (patients’ lesions; healthy subjects’ functional activity) handled with a systematic analysis approach, I attempted to find convergent evidence to support the dissociation of semantic and action processing. Second, I also looked into the potential differentiation within the mechanisms underlying object-related action (Chapter 4) and object naming (Chapter 5) separately. Overall, comparable findings were provided from the voxel-based morphometric analysis of patients’ lesion data and the fMRI study with healthy participants: an association was observed between ventral brain structures and the retrieval of semantic knowledge/object recognition while a dorsal fronto-parietal-occipital network was found to support the processing of action knowledge/object-oriented action. Specific dissociations were also observed within the representations for object-oriented actions as well as the mechanisms underlying naming of objects.

The Drosophila Toll receptor is crucial for dorsoventral patterning in embryos, and for innate immunity. Toll also functions during central nervous system development, promoting neuronal survival and targeting. There are nine Toll paralogues in Drosophila, and it is unknown whether any of these also function in the CNS. Toll’s ligand, Spz, has an NGF domain. NGF is a vertebrate neurotrophin - a growth factor that regulates the development and function of the nervous system. Drosophila Neurotrophin 1 (DNT1), identified by homology to the vertebrate neurotrophin BDNF, and DNT2 are paralogues of spz. The three DNTs – DNT1, DNT2 and spz – are structural and functional homologues of vertebrate neurotrophins, and they promote neuronal survival, targeting and synaptogenesis in Drosophila. However, the receptors for DNT1 and DNT2 are unknown. Here, using a combination of in situ hybridisations and reporters that drive GFP expression, I investigate the expression of Toll paralogues in the Drosophila nervous system. By generating null mutant flies and gain-of-function transgenic flies, I examine genetic interactions between Tolls and DNTs. I also investigate the rolls of these receptors in adult locomotion, axon targeting and cell survival. Finally, in cell culture, I test whether DNTs can signal through Tolls to activate NFκB.

Idiopathic intracranial hypertension (IIH) is common in obese women and can lead to significant visual impairment. The cause of IIH is unknown and management controversial, due to the lack of prospective trials. This thesis provides a comprehensive review of the aetiology and management of IIH. The hypothesis that IIH is associated with a pro-inflammatory cytokine profile, suggested by its established association with female gender and obesity, was tested. Laboratory studies demonstrated the novel finding of elevated leptin in the cerebrospinal fluid from women with IIH, suggesting a role in the pathogenesis of IIH. The first randomised controlled trial in IIH is then reported. Treatment with acetazolamide was examined prospectively in 50 patients, providing seminal information to guide the design of future large-scale trials and data on the natural history of the condition. The observation that management of IIH is guided by a variety of clinical parameters was translated into a simple composite scoring system which was prospectively tested. Visual fields and optic disc appearance are shown to have the greatest influence on clinical outcome. Finally, a systematic study of the evaluation of papilloedema in IIH highlights the major limitations of the widely adopted Frisen staging scheme in the condition.

Individuals with acquired brain injury-related memory impairment learned routes around a complex virtual reality town under various conditions. Errorless learning, a technique used with considerable success in verbal learning tasks after brain injury (e.g. Baddeley & Wilson, 1994), resulted in significantly fewer route errors than trial-and-error (or 'errorful') learning, demonstrating the technique's potential for training practical daily living skills. The combining of explicit, naturalistic route learning strategies of cognitive map creation and landmark memorization with errorless learning did not, within the sample as a whole, further improve its efficacy. However, closer analysis of performance by participants with impaired verbal ability or deficits in executive function indicates that people with such cognitive profiles may derive particular benefit from these additional strategies. Applications and suggestions for further research are discussed.

Background: This study validates the Neuropsychological Assessment Battery Screening Tool (NAB-S) against a battery of established neuropsychological tests, used as a convergent validity test battery (CVTB). Method: Forty-four participants with traumatic brain injury (TBI) were recruited from an outpatient clinic at a UK trauma centre and residential rehabilitation centre. The NAB-S and CVTB were administered to the sample. Results: Strong positive correlations were observed between NAB-S indices and NAB-S TBI index in comparison with indices for distinct cognitive domains from the CVTB, and the convergent validity test battery mean (CVTBM). There was a high collinearity between NAB-S subtest indices, and poor internal consistency for some indices. Semi-partial correlations revealed the unique variance between NAB-S and CVTB indices, which were highly significant for the NAB-S attention and memory indices. An area under the receiver operator characteristic curve (AUROC) revealed that the NAB-S and NAB-S TBI indices are highly predictive of impairment measured by the CVTB. Conclusions: The NAB-S has good predictive validity of overall impairment as measured by the CVTB and is an adequate screen of cognitive impairment following TBI. Some indices had poor internal consistency and high collinearity, suggesting that further assessment with more sophisticated tests would be warranted.

The principal aim of this thesis is to examine how emotion regulation and mindfulness are related to cardiovascular activity and the implications of these relationships for the understanding of aggression. Studies one and two aimed to detail the relationship of mindfulness to psychopathic traits and emotion regulation. Results of these studies collectively imply that mindfulness shares certain features with primary psychopathic traits, including reduced physiological responding to aversive stimuli. Study three aimed to investigate whether slow-paced breathing, associated with an increase in vagal output and thus decrease in heart rate, may exert effects on emotion regulation. Participation in a paced breathing course improved emotion regulation and increased trait mindfulness in a sample of male offenders. Study four aimed to explore how cardiovascular activity and psychopathic traits relate to female perpetrated intimate partner violence. Increased vagal activity, was found to be positively linked to proactive aggression and partner violence. Study five aimed to extend the results of Study four to a sample of male offenders. The results showed that high vagal activity is related to low empathy and good performance on the Stroop task. Collectively, these findings have implications for the use of mindfulness based treatments and the understanding of aggression.

Volume 1 contains a literature review, an empirical paper, and a public dissemination document. The literature review explores how people with Autistic Spectrum Disorder (ASD) experience their relationships with others. The results showed that compared with the general population, children and adolescents perceive their friendship quality to be lower and adults with ASD perceive their marital and parent-child relationships to be the same. A number of strategies are used by people with ASD to facilitate the development of relationships and other people also use strategies for this reason. Furthermore, people with ASD report a number of personal qualities that serve to either facilitate or inhibit the development of relationships. The empirical paper explores how much people with Asperger's syndrome understand about positive attachment behaviours between parents and young babies and whether this knowledge can be increased through the use of a DVD. Trait emotional intelligence, IQ and level of autistic symptomatology are explored as predicting factors. A significant increase in knowledge of positive attachment behaviours was observed at post intervention. This was maintained at follow-up. This significant increase in knowledge occurred for the total knowledge score as well as for four out of the seven attachment questions. Trait emotional intelligence, IQ and autistic symptomatology did not predict pre-intervention knowledge or increase in knowledge. The results of both papers are discussed within the context of previous research and clinical implications are considered. Volume 2 contains five clinical practice reports; Psychological Models, Service Evaluation, Single Case Experimental Design and two Case Studies.