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Background: Post-stroke depression (PSD) is a common phenomenon and has a negative impact on rehabilitation, recovery and quality of life. About one third of stroke patients suffer communication problems, including aphasia, which is a condition that mainly affects their ability in understanding and/or producing language. The frequency of depressive symptoms in post-stroke aphasia has been difficult to determine as most studies have excluded stroke patients with aphasia due to methodological limitations. As a result, depression remains often under-diagnosed and untreated in these patients. Objectives: The purpose of this thesis was 1) to develop and validate a revised version of the Visual Analogue Mood Scales (YAMS), and 2) to identify factors which may be associated with low mood in stroke patients with aphasia. Method: The items Happy and Energetic of the VAMS were reversed for a more consistent format. All participants completed a questionnaire including the revised version of the VAMS (VAMS-R), the Hospital & Anxiety Depression Scale (BADS), but also four key items of the VAMS-R which were repeated with and without verbal descriptors to assess their content and test-rest reliability. Aphasic stroke patients were recruited both from hospital and community settings and completed assessments at recruitment and at six months follow up. Participants were assessed on measures of communication, cognition, mood, activities of daily living, and disability associated with living with aphasia. Carers also completed assessments of caregiving strain and satisfaction with care at six months follow up. Results: The VAMS-R showed good evidence of validity and reliability in a community sample of 50 older adults and in 71 stroke patients with aphasia. In the main study, 132 aphasic stroke patients were invited to take part, 71 consented and completed baseline assessments and 63 were followed up at six months. Most participants (n=47) were recruited in the community, 38 were men, mean age was 70 years old and the mean time post-stroke was 15 months. Almost half of the aphasic stroke patients recruited had low mood at baseline (55%) and at follow up (44%) based either on their self-report or the observer-rated mood scores. Physical impairment, demographic and medical information, ADL and leisure activities were not shown to be significant predictors of depression. Communication impairment was significantly related to low mood, but was not predictive of self report mood outcomes at both end points. Disability and emotional consequences living with aphasia were predictive of low mood and accounted for 37% of the variance in self-report mood scores at recruitment and for 48% of the variance at follow up. Baseline language battery scores and follow up Carer Strain Index scores were predictive of the observer-rated mood scores at follow up. Conclusions: The VAMS-R, VASES and SADQ-21 could be used to screen for symptoms of low mood in aphasic stroke patients who cannot complete conventional mood assessments that rely on verbal communication. The main factors found to predict low mood in stroke patients with aphasia were disability associated with living with aphasia, carer strain and communication impairment. The factors identified are amenable to psychological intervention and future research should address interventions for the management of post-stroke depression in aphasia. The need to include people with aphasia in future post-stroke depression research is also highlighted.

The aim of this thesis is to explore the social and ethical issues surrounding the use of neurotechnologies to control sleep and enhance cognition in British society. Empirically, the project is based on a case study of the wake-promoting drug modafinil. Data analysis involved the study of a corpus of 77 UK news articles and 40 semi-structured interviews with three stakeholder groups: scientists and clinicians, shift workers and students. The analytical framework used was informed by previous work in both medical sociology and bioethics and developed using key concepts drawn from Science and Technology Studies. Conceptualising modafinil as a sociotechnical object, different discourses surrounding sleep, cognitive enhancement and pharmaceutical use were explored to assess how sociotechnical spaces for ‘therapy’ and ‘enhancement’ are being constructed and negotiated in different domains of social life. The analysis of the ways in which modafinil use was positioned and of how various uses were negotiated in both media and stakeholder discourse shows how different groups can conceptualise the same technology in very different ways depending on who is doing the defining, how the users are imagined and the specific context of use. It was apparent that drugs contain not only technological scripts for how and by whom they are to be used, but also strong cultural scripts relating to legitimacy and acceptability of when, where, for what purpose they should be used. Importantly, it demonstrates that although norms may overlap to some degree, there is no universal set of norms defining and delimiting how modafinil should be used in contemporary society. The adoption of an STS perspective, which takes a critical stance towards both technology and users, has shown how the adoption of a therapy-enhancement distinction devoid of context oversimplifies the debate around the use of drugs such as modafinil and does not capture the reality of stakeholder perspectives.

Background: Sensorimotor Psychotherapy is an approach for working with people who have experienced trauma (e.g. post-traumatic stress disorder [PTSD]) that is based on contemporary philosophies of embodiment and the expanse of neurobiological evidence for the effect of psychological trauma on the physical body. Thus, Sensorimotor Psychotherapy places central importance on working with the body in therapy. Method: This study explored the experiences of 10 therapists and 2 clients who have had Sensorimotor Psychotherapy, and in particular, what it was like to use the body in therapy. Semi-structured interviews were used in order to gain detailed information regarding how the using the body in therapy is experienced. Results: An inductive thematic analysis of interview transcripts identified four main themes: 1) accessing the truth through the body, 2) dilemmas of mind and body, 3) the elusiveness of words, and 4) change occurs through and within the body. 'Accessing the truth through the body' had three further subthemes: 'access', 'truth', and 'depth'. In this theme, participants described Sensorimotor Psychotherapy as being able to access the core of a problem through its use of working with the body ('access'), and that in doing so it reaches the truth of a problem or previous traumatic experience ('truth'). In order to reach and access the truth, participants described the work as having great 'depth'. 'Dilemmas of mind and body' had two further subthemes: 'the interfering mind' and ' the telling body'. In this theme, participants described the mind and body in very different ways, suggesting a dualism of mind and body. Participants described how 'the interfering mind' can distract from dealing with the real and genuine issue (accessed through the body), and that 'the telling body' was a source of genuine and important knowledge regarding a traumatic experience. The 'elusiveness of words' referred to how the participants found it difficult to describe their experiences in words, alluding to the elusiveness of words to describe the process of Sensorimotor Psychotherapy. Participants considered and discussed progress and change in Sensorimotor Psychotherapy as occurring through and within the body ('change occurs through and within the body'). Discussion: In conclusion, the participants in this study felt that by working primarily with the body, Sensorimotor Psychotherapy is able to deeply access the direct core of traumatic experience, and that parts of this process are difficult to describe in words. Furthermore, a dualism of mind and body was implicated by the participants, and change was considered to occur through and within the body. Other therapies for PTSD could consider including more focus on the body, and also consider acknowledging perceived dilemmas between the mind and body. The limitations of this study include possible sampling bias, and the verbal interview technique being unable to explore the nuanced bodily experience of the therapy. Future research should expand the sample to include those who had neutral or negative experiences of Sensorimotor Psychotherapy, and explore methods that can capture the bodily experience of the therapy considering the difficulty of the 'elusiveness of words'.

Intrapersonal Externalities are outcomes from a decision which affect the payoffs from future decisions. Positive intrapersonal externalities represent self-investment in one's future self, such as learning a musical instrument or exercising. Negative intrapersonal externalities represent a disinvestment in one's future self, such as eating sugary food or smoking a cigarette. An individual who succumbs to the lure of an immediate payoff in lieu of future potential earnings is considered to be choosing myopically, and it is hypothesised that addictions are one such situation. This failure of the decision-making system to optimise its choices contrasts with delay discounting, in which an individual is assumed to choose rationally but to discount the future, and impulsive disinhibition, in which an individual is assumed to be unable to control their actions even while they state a preference for an action they do not take. This thesis starts by measuring the relationship between delay discounting and impulsive disinhibition with a range of addictive behaviours in a large online study, and finds that while they are consistent predictors there is further variance to explain. It then examines the validity of the intrapersonal externalities model, and finds that it adds independent variance beyond delay discounting and impulsivity in predicting smoking behaviour; there is no evidence that performance in intrapersonal externalities tasks is related to trait impulsivity. It also uses intrapersonal externalities in the laboratory to study advice seeking and taking in an impulsive decision-making context, which would be incompatible with delay discounting or impulsive disinhibition theory. This thesis concludes that the intrapersonal externalities model has been shown to be a viable third model to understand addictive decisions, and suggests that it could be extended to study social addictions.

Self-harm thoughts and behaviour have been found to be associated with a wide variety of distal and proximal factors; however, few studies have examined how these factors work together to increase the risk of self-harm. A key distal factor is a history of child and family adversity, which attachment theory views as a precursor of attachment insecurities that may increase the risk of later self-harm. A key proximal factor is the desire to escape from overwhelming distress, and Williams (2001) cry of pain model describes a process that could help better understand the reasons behind seeking escape via self-harm. This research investigated whether insecurely attached individuals tend to feel trapped and whether entrapment leads to self-harm thoughts (suicide ideation [Chapter 2] and thoughts about non-suicidal self-injury [Chapter 3]). This research also investigated whether feelings of entrapment among insecurely attached individuals varied as a function of problem-solving (as assessed with the Means-Ends Problem-Solving [MEPS] procedure [Chapter 4] and a diary study [Chapter 5]). The effect of stressful events on subsequent feelings of defeat and entrapment, and the role of attachment, was also examined using an experimental design (Chapter 6). Self-harm thoughts were common among insecurely attached individuals and among those who felt trapped. Entrapment was reported by insecurely attached individuals, but this feeling did not explain their self-harm thoughts nor did it vary as a function of problem-solving. In response to a laboratory stressor, attachment insecurities seem to exacerbate negative emotions. The findings suggest that assessment of attachment styles could help to identify individuals at risk of self-harm. Moreover, interventions aimed at reducing feelings of entrapment could decrease the risk of self-harm. Still, studies are needed to clarify the direction of the relationships between attachment, entrapment and self-harm, and the psychological mechanisms that might underlie these relationships.

This thesis investigates autism as it has been understood in the cognitive and social (neuro)sciences, within the United Kingdom, since 1985. Of specific interest is how these sciences discover, construct, and experiment upon individuals who are understood as socially abnormal. Theoretically, the thesis is positioned between Foucauldian History and Philosophy of Science, Medical Sociology, and Science and Technology Studies. Empirically, two key sources of information are relied upon. Firstly, there is an extensive critical reading of the published literature from 1985 to the present. Secondly, twenty qualitative research interviews were conducted with academic researchers, based within the UK, and with core interests in psychology in general and autism in particular. It is firstly argued that the cognitive sciences rely upon a particular, historically novel, construction of the social in order to articulate autism as social disorder. It is then argued that, although autism is frequently reported as heterogeneous and illusory within the laboratory, social disorder appears self-evident when the autistic individual is required to interact with both the researcher and broader society. Following these findings it is argued that the researcher does not observe autism but, rather, that they achieve it. Finally it is argued that the language of autism is itself capable of ushering in novel conceptualisations of social conduct that may apply to all individuals and not just those diagnosed with the condition. Following these empirical findings it is argued that autism is best understood as the consequence of particular socio-historical conditions. It is asked if these socio-historical conditions may include a novel knowledge-power nexus arising in the mid-twentieth century, named here a socio-emotive politics, of which autism is just one consequence.

The remaining three manuscripts deal with issues directly related to the graft survival and the use of gene therapy and animal models of PD, looking at the dynamics of viral vector gene expression in the pathological brain, an investigation of the two-layer staining obtained on immunohistochemical stained sections, and a re-assessment of the amphetamine induced rotational response of dopamine grafted animals

Transgenic rat models were used to investigate aspects of the role and expression of the circadian clock-regulated genes, vasopressin (VP) and Period 1 (Per1), in the suprachiasmatic nucleus (SCN), and the early growth response gene-1 (egr-1), in the SCN and anterior pituitary gland. Initial studies of the JP-17 and JP-59 (rat VP promoter / human growth hormone (hGH) reporter gene) transgenic lines detected expression of the reporter gene in the supraoptic nucleus (SON), but not the SCN, as determined by in situ hybridisation (ISH). Therefore, no further analysis of circadian clock-regulated VP expression could be conducted in these lines. Four (mPer1) promoter / destabilised enhanced green fluorescent protein (d2EGFP)) (Y) transgenic lines were generated, but failed to express the EGFP reporter gene. Sequence analysis of the transgene failed to explain the absence of expression. Subsequent studies in the egr-1 d4EGFP (57C) transgenic line detected tissue-specific constitutive expression and inducible expression in the brain, as determined by ISH. Region-specific and physiologically-regulated expression in the pituitary gland was also detected, as determined by Northern blot and dual ISH / immunohistochemical (IHC) analyses. Nevertheless, direct GFP fluorescence remained undetectable in this line. Seven egr-1/d2EGFP (Z) transgenic lines were then generated using a novel construct lacking the egr-1 intron present in the 57C construct. These transgenic lines demonstrated tissue-specific constitutive expression and inducible expression in the brain, and region-specific expression in the pituitary gland, at all levels of detection: transcript, protein and direct fluorescence. These findings indicate that the egr-1 intron is not required for directing tissue-specific and inducible expression in the rat. Z line rats will provide insights into the cellular progression of clock- and light- regulated responses in the brain. Potential uses of the egr-1/d2EGFP transgenic model are discussed

The work presented in herein focuses on the optimisation and use of established animal models to study behavioural, pharmacological, histological and molecular correlates of the debilitating motor side effects of current and future treatments for Parkinson’s disease, namely L-DOPA induced dyskinesia (LID) and graft induced dyskinesia (GID). Chapter 3 optimises the 6-OHDA lesion model in mice, from surgical approaches to behavioural assessment of motor function. The neurotoxin was injected at three different regions along the nigrostriatal tract to produce unique patterns of dopaminergic cell death in the midbrain. The resulting cell loss was correlated to behavioural deficits identified through an extensive battery of motor hand tests. Fully lesioned mice from each of the three models were chosen for chronic L-DOPA treatment, described in Chapter 4, where doses were increased every 1-2 weeks. Behaviour was assessed and correlated to deficits on motor hand tests prior to L-DOPA treatment, cell loss within sub regions of the midbrain, serotonergic density levels and upregulations in ΔFosB and striatal TH cell populations. Chapter 5 uses knowledge gained in previous chapters to use the most appropriate 6-OHDA mouse model of LID for the examination of changes in the Regulators of G-protein Signalling (RGS) following an acute and chronic L-DOPA treatment. RGS2 was the only one to increase significantly following either treatment regime. In Chapter 6 a well established rat model of GID (the induction of dyskinesia in the transplanted 6-OHDA lesioned rat through the administration of amphetamine) was used to assess the use of pharmacological agents known to reduce LID. Changes in locomotor function and abnormal inhibitory movements (AIMs) could be assessed giving an insight into the mechanism and receptors involved. To further the understanding of GID, Chapter 7 examines dopamine receptor levels, RGS transcript expression, and the proportions of dopamine and serotonin cells in the transplanted, 6-OHDA lesioned rodent brain. The aim was to determine any correlation between these parameters and amphetamine induced dyskinesia. Only the number of dopaminergic and serotonin cells could be correlated to dyskinesia and not the proportion of serotonin cells. As no previous mouse model of GID has been established, Chapter 8 demonstrates that transplantation of E12 ventral mesencephalon (VM) grafts can be optimised in the lesioned mouse of C57/Bl6 and CD1 strains to give functional recovery, and amphetamine induced dyskinesia. Both strains were also used to demonstrate that transplants were also able to reduce LID.