This thesis explores care staff and nurses’ experiences of aggression and violence whilst working in dementia and adult acute psychiatric facilities. Chapter one presents a systematic literature review of studies based on the perceptions and impact of aggression from patients with dementia, adopting a care staff perspective. The findings highlighted the subjective experiences of aggression, care staff perceptions of its causes and the physical and psychological impact which aggression had on care staff. A key finding was that care staff perceptions of aggression and its impact influenced patient care and the reporting of aggression. The chapter discusses key implications for practice and policy and identifies recommendations for future research. Chapter two consists of an empirical study exploring nurses’ lived experiences of violence from patients whilst working on adult acute psychiatric facilities. Eight nurses were recruited from two hospital sites and completed semi-structured interviews. Analysis of the data revealed the personal perceptions of violence and its causes and the psychological, physical, occupational and relational impact that violence had on the nurses. All nurses employed individual and group survival strategies to help manage their experiences of violence and its impact. Implications for clinical practice and policy and recommendations for future research are discussed. Chapter three presents a reflective account of my research journey throughout training to be a Clinical Psychologist. I use a reflexive stance to explore the development of my research interest, the meaning of violence and to discuss my own responses to the nurses’ experiences. The paper also explores how I managed different roles during the research process and how I have developed as a clinician and researcher.

This thesis examines auditory selective attention as a possible cause of Auditory Processing Disorder (APD). APD is a diagnosis based on the clinical needs of the 5% of children who present with listening difficulties but demonstrate normal hearing. This thesis will focus on developmental APD, which affects children with no known infection, trauma or primary cause inducing their listening difficulties. It will seek to address the current lack of understanding of the root causes of APD, which leads to significant variation in clinical referral routes, resulting in inconsistent methods of diagnosis and treatment. APD has historically been approached via a bottom-up route of assessing auditory processing skills, such as temporal-spatial abilities. The inconsistent results of bottom-up studies has led to debate regarding the diagnosis and treatment of APD, resulting in extensive batteries of tests being conducted on children. However, recent evidence suggests that studies on the causality of APD should be refocused on top-down processes such as auditory attention and memory – hence the focus of this thesis on auditory selective attention. The thesis begins by assessing a new test of auditory selective attention, the Test of Attention in Listening (TAiL), to ensure that it measures auditory rather than supramodal attention. Having established the modality-specificity of TAiL, the thesis examines the development of auditory selective attention to both spatial and non-spatial auditory stimulus features, across tasks of varying levels of perceptual demand. Finally, the thesis assesses the selective attention ability of children with listening difficulties. Specifically, listeners’ selective attention is assessed in both the auditory and visual domains, using both spatially- and non-spatially-based tasks. If auditory selective attention deficits are found in those with listening difficulties, this will provide a basis for the diagnosis and treatment of APD to be constructed and managed from a psychological viewpoint rather than an audiological one.

Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation method that involves the application of weak electric currents to the scalp. tACS has the potential to be an inexpensive, easily administrable, and well-tolerated multi-purpose tool for cognitive and clinical neuroscience as it could be applied to establish the functional role of rhythmic brain activity, and to treat neural disorders, in particular those where these rhythms have gone awry. However, the mechanisms by which tACS produces both "online" and "offline" effects (that is, those that manifest during stimulation and those that last beyond stimulation offset) are to date still poorly understood. If the potential of tACS is to be harnessed effectively to alter brain activity in a controlled manner, it is fundamental to have a good understanding of how tACS interacts with neuronal dynamics, and of the conditions that promote its effect. This thesis describes three experiments that were conducted to elucidate the mechanisms by which tACS interacts with underlying neural network activity. Experiments 1 and 2 investigated the mechanism by which tACS at alpha frequencies (8 12 Hz, α-tACS) over occipital cortex induces the lasting aftereffects on posterior α power that were previously described in the literature. Two mechanisms have been suggested to underlie alpha power enhancement after α tACS: entrainment of endogenous brain oscillations and/or changes in oscillatory neural networks through spike timing-dependent plasticity (STDP). In Experiment 1, we tested to what extent plasticity can account for tACS-aftereffects when controlling for entrainment characteristics. To this end, we used a novel, intermittent α-tACS protocol and investigated the strength of the aftereffect as a function of phase continuity between successive tACS episodes, as well as the match between stimulation frequency and individual alpha frequency (IAF). Alpha aftereffects were successfully replicated with enhanced α power after intermittent stimulation compared to sham. These aftereffects did not exhibit any of the expected characteristics of prolonged entrainment in that they were independent of tACS phase-continuity and did not show stable phase alignment or synchronisation to the stimulation frequency. These results indicate that prolonged entrainment is insufficient to explain the aftereffects and suggest that the latter emerge through some form of network plasticity. To clarify the nature of these plasticity mechanisms, we then aimed to assess whether STDP could explain the α power increase. We developed a conceptual STDP model that predicted bi-directional changes in α power depending on the relative mismatch between the tACS frequency and IAF. After observing in Experiment 1 that tACS at frequencies slightly lower than the IAF produced α enhancement, Experiment 2 used a similar intermittent protocol that manipulated tACS frequency to be either slightly lower or higher than IAF to respectively enhance or suppress α activity. In addition, a control condition with continuous stimulation aimed to replicate previous results from other groups. However, we did not observe a systematic α power change in any of the active conditions. The lack of consistency between the two experiments raises concerns regarding the reproducibility and effect size of tACS aftereffects. The third experiment investigated the mechanism of online effects and tested predictions that were based on the assumption that entrainment is the underlying process mediating behavioural changes during tACS. We capitalised on two well-described phenomena: firstly, the association between α power lateralisation and visuospatial attention, and secondly, the fluctuation of perceptual performance with α phase. Specifically, the experiment tested whether event-related α-tACS applied over right parieto-occipital cortex can induce a visuospatial bias in a peripheral dot detection task that would reflect α power lateralisation, and whether detection performance depends on the phase of the tACS waveform. In control trials either no tACS or 40 Hz-tACS (gamma) was applied to make use of the putative opposing roles of alpha and gamma oscillations in visual processing. As expected from lateralised enhancement of alpha oscillations, visual detection accuracy was weakly impaired for targets presented in the left visual field, contralateral to tACS. However, this effect was neither frequency specific nor waveform phase-dependent. Therefore, it is unlikely that the negative effect of tACS on visuospatial performance reflects entrainment. Overall, the results of these experiments only partially met our hypotheses. Experiment 1 produced the α enhancement that was expected based on the literature while the follow-up experiment failed to reproduce these results under similar conditions. This outcome demonstrates at best that tACS aftereffects on α activity are not robust, may vary widely across individuals, and might be extremely sensitive to small changes in experimental parameters and state variables. The results of the third experiment call into question the assumption of online entrainment as basis for the observed behavioural effect. These findings point to the need for improved methodology, for more systematic and exhaustive exploration of the relative effects of tACS across different parameter settings, tasks, and individuals; and for the replication of promising but thus far often anecdotal results. They also inspire guidelines for more informative experimental designs.

The purpose of this thesis was to assess the integrity of the serotonin system, by measuring the neurophysiological response to tasks that measure executive functions, and neuroendocrine function in ecstasy users and non-users. Each of the proposed executive functions outlined in Miyake et al.’s (2000) conceptual framework (inhibition, switching and updating) as well as the addition of access to semantic/long term memory made by Fisk and Sharp (2004), was assessed using behavioural tasks in combination with EEG and fNIRS. Behavioural performance between ecstasy users and various controls (polydrug and drug naive) was equivalent throughout the thesis. However ERP analysis revealed ecstasy-related atypicalities in cognitive processing during inhibitory control, switching and access. Ecstasy users displayed increases in P2 and N2 components during these tasks that reflect recruitment of additional resources. A diminished P3 response during the switching task was evident for ecstasy users and polydrug users relative to controls. Regression analyses suggest that lifetime cannabis use may be an important factor for this function. Results from fNIRS suggest that ecstasy users show an increased haemodynamic response during all four executive functions relative to non-users, which suggests that ecstasy users are engaged in more effortful cognition than controls. Increases in neuronal activation whilst performing at a similar level behaviourally are understood as recruitment of additional resources. Again during switching cannabis use may have been an important factor. Another aim of this thesis was to assess neuroendocrine function. Ecstasy users displayed elevated basal cortisol levels relative to polydrug controls and drug naive controls. The results suggest that ecstasy is detrimental to the integrity of the HPA-axis. This thesis provides support for ecstasy-related damage to the serotonergic system and should be used in educating prospective ecstasy users of relative harms.

Some of the psychological problems associated with epilepsy have their origins in the ability of people with epilepsy (PWE) to engage in meaningful and appropriate social interactions. PWE often report difficulties in social settings, yet there is a paucity of research investigating the socio-cognitive skills of this group. This thesis aimed to investigate these skills and relate them to the patient's perceived impact of epilepsy on their social competence. An additional objective was to see whether studying social cognition in focal epilepsy might provide some insight into the organic basis of social cognitive abilities in the normal population. The thesis consists of four separate studies which aimed to investigate social cognition and social functioning in patients with focal epilepsy. With this in mind, a test battery assessing a range of skills linked to social cognition was administered to a cross section of experimental groups (N=95). These included patients with seizure foci in the right frontal lobe (RF), left frontal lobe (LF), right temporal lobe (RT), left temporal lobe (LT) and a group with idiopathic generalised epilepsy (IGE). A normal control group (NC) and a frontal head injured (FHI) group with no epilepsy were also recruited for the study. In Studies 1 and 2 theory of mind (ToM) deficits were apparent in people with RF and LT epilepsy. These groups demonstrated impairment in the appreciation of false belief and deception at first and second order levels of intentionality. They also exhibited deficits in the appreciation of pragmatic language when attempting to infer the meaning underlying hints given by story characters. These impairments were in part attributable to deficits in narrative memory in the LT group. In Study 3 embedding problems within a social context significantly facilitated conditional reasoning in the NC, LT and RF groups but not in the other experimental groups. This finding was unexpected and suggests a double dissociation between ToM and social conditional reasoning. Study 4 investigated the extent to which socio-cognitive impairment was associated with the perceived impact of epilepsy on everyday social functioning. No statistically significant relationship between these variables was found, although a significant negative correlation between education level and impact of epilepsy was observed. Taken together the findings suggest that impairment in ToM may be a particular feature of right frontal lobe pathology and that social conditional reasoning and ToM may be functionally dissociated. PWE do not appear to have insight into their social functioning difficulties, which may well reflect underlying pathology. In light of this, future research should obtain objective measures of social competence from `significant others'. This is the only series of studies to date to assess social cognition in people with frontal lobe epilepsy (FLE) and temporal lobe epilepsy (TLE) within the same design. It is also the first time that social conditional reasoning in epilepsy has been systematically assessed and represents one of the largest lesion studies within the field of social cognition. It is hoped that some of the test material used in the thesis, may prove to be a useful and inexpensive clinical resource to help identify PWE who are at risk of reduced social competence, and in localising the site of seizure foci in patients during clinical audit, particularly where anterior foci are suspected.

No description available.

The evaluation of visual art involves sensory, emotional and cognitive processes that lead to an aesthetic judgement or an aesthetic emotion (e.g. beauty). Aesthetic experiences are multisensory processes that undergo a variety of stages. Early processes occur in the visual and sensory cortices, and are central to object identification that may be no different from visual experiences of everyday objects. Later processing stages are related to complex human thought consisting of emotion and cognition that involve areas such as the orbitofrontal cortex, hippocampus and prefrontal cortex (PFC). The later stages are concerned with the comprehension and meaningful analysis of the artwork that contribute to the formation of an aesthetic judgement or emotion. This thesis aims to investigate affective evaluations and their interactions with cognitive processes during the later processing stages of the aesthetic experience in the rostral prefrontal cortex (rPFC). The role of the rPFC will be explored using functional near-infrared spectroscopy (fNIRS) with reference to existing frameworks. Specifically: hemispheric asymmetry in the processing of emotional stimuli, the Gateway Hypothesis and the Default Mode Network will be explored. Experimental WorkA database of sixty images was created in an online survey (chapter 3) at the beginning of the experimental programme. Images were rated online (N = 1028) for complexity, comprehension, novelty, activation, attraction and valence providing stimuli that could be systematically manipulated according to their psychological properties in the experimental studies. The first hypothesis (is the rPFC involved in early perceptual processes such as complexity during aesthetic experience?) was addressed in a pilot study (chapter 4) and repeated in the first experimental study (chapter 5). Both cognitive (high/low complexity) and emotional (positive/negative valence) aspects of the images were manipulated. Images were shown for sixty second and analysed in three time periods (early, middle and late) each consisting of twenty seconds. The results showed an interaction between valence and time with positive images yielding greater activation in the early period and negative images in the late period. This highlighted the importance of long exposure times to capture the aesthetic experience. The second hypothesis (is the rPFC involved in implicit memory formation such as the comprehension of an image during aesthetic experience) was investigated in chapter 6 where the levels of comprehension (high/low) and postive/negative valence associated with the viewed image were manipulated. An interaction between comprehension and valence was found with respect to rPFC activity. Positive easy to comprehend images and negative difficult to comprehend images yielded greater rPFC oxygenation. These findings indicated that the experience of pleasure in positive artworks and increased cognitive effort during the resolution of uncertainty or threat in negative artworks is related to rPFC activation. The third hypothesis (is the rPFC involved in prospective memory during aesthetic experience?) was investigated in chapter 7 where positive and negative artworks were shown under two conditions. Condition one asked participants to introspect about their emotions and condition two to direct their attention to features in the image through a spot-the-difference task. A main effect of emotion was found, but no interaction or effect for condition. Greater rPFC activation was found during the contemplation of positive images. This may be attributed to pleasantness experienced in relation to these images. The last question (is the rPFC involved in self-referential processing and is this important to aesthetic experience?) was investigated in chapter 8 where participants viewed negative and positive images under two viewing conditions. Condition one asked participants to introspect about their own emotions (Self) and condition two about the artist’s emotions at the time of painting (Other). The other-condition resulted in overall greater rPFC activation indicating that participants found it more challenging to think of another’s emotions. An interaction showed greater rPFC activation for positive images in the self -condition and greater activation for negative images in the other-condition. This may have been the result of a positive bias and the detection of self-relevance in positive images and the analysis of threat or uncertainty in negative images. Conclusions: This thesis used a cognitive model of the aesthetic experience as a framework to understand the interaction between emotional and cognitive processes in the formation of an aesthetic judgement or emotion. No evidence for asymmetrical processing of emotional stimuli, or the Gateway Hypothesis was found. The research reported here indicates that the rPFC has an important role during the later processing stages of the aesthetic experience. Viewing negative visual art activated rPFC when the images were difficult to comprehend and when participants thought about the artist’s feelings. Positive emotions, on the other hand, activated rPFC when the images were easy to comprehend and when participants thought about their own feelings. The contemplation of visual art was continuously associated with medial rPFC activation, indicating that the rPFC has a key role in self-relevant processing of visual art. The rPFC may aid personal value judgements of visual art (e.g. this artwork means xyz to me) because this area of the brain mediates the interaction between self-relevance, autobiographical memories and continuously changing emotional states.

Thesis (Masters Diploma (Technology)--Cape Technikon, Cape Town, 1986 / Child psychiatrists have become increasingly aware of the existence. of affective disorders in prepubertal and pubertal patients. This has led to the investigation of possible biological factors contributing to the disorders. Due to the lack of availability of human brain material, different parameters have been investigated in the periphery in order to obtain information regarding the aetiology of major depressive disorder. The neurotransmitters, NA, 5-HT and DA have been implicated in depression. Levels of the metabolites of these transmitters have been measured in plasma, urine and CSF of adult depressed patients. Two other peripheral "tools" used in the study of major depressive disorder are blood platelets and lymphocytes. The former contain cr 2 -adrenoceptors and imipramine binding sites (indicative of 5-HT uptake into the platelet) and the latter S-adrenoceptors. Platelets have been widely used as a model for indirectly evaluating changes in central cr2-adrenoceptor and imipramine binding whereas lymphocytes have been used to measure changes in S-adrenoceptor binding and activity in adults with major depressive disorder.

22q11.2 Deletion Syndrome is a genetic syndrome that occurs in incidence of 1:4000 and is associated with variable phenotypic expression. It is caused by a deletion at chromosome 22q11.2. Individuals with 22q11.2DS have a greatly increased risk of developing neuropsychiatric disorders, in particular schizophrenia in adulthood, and ADHD and ASD in childhood. This thesis sought to investigate the possible molecular mechanisms that underlie the psychiatric variability in 22q11.2DS by studying a well-characterized cohort of 76 children with 22q11.2DS. Four mechanisms were investigated: (a) dosage sensitivity of genes within 22q11.2 region, (b) a disruption of the expression of genes flanking the deletion i.e. positional effect and genome-wide, (c) the presence of additional genetic risk variants within the 22q11.2 region, and (d) the presence of additional CNVs outside of the 22q11.2 deleted region. While this work revealed significant evidence for differential expression of 39 of the genes spanned by the deletion, there was no significant evidence for a positional effect at other genes on chromosome 22. The genome-wide differential gene expression analysis revealed four significantly enriched biological networks (FDR < 0.05) that are involved in: 1) translation, protein synthesis machinery, and post-translation modifications; 2) apoptosis; 3) regulation of the immune system; and 4) intramembrane organelles. The association analyses of genetic variants present on the non-deleted 22q11.2 chromosome did not identify any that were significantly associated with psychiatric phenotypes in 22q11.2DS. The genome-wide screen for additional CNVs identified a non-significant trend that large, rare CNVs were enriched in 22q11.2DS patients with psychiatric phenotypes, however there was no evidence that these additional CNVs were enriched for CNVs that had been previously implicated in developmental delay and neuropsychiatric disease. In addition, in this thesis also investigated the role of deletions at 22q11.2 in a large cohort of individuals with idiopathic Parkinson’s disease. This provided significant evidence that deletions at 22q11.2 increase the risk of Parkinson’s disease, particularly the early-onset form. Taken together,the data presented in this PhD suggested that the mechanism by which haploinsufficiency at 22q11.2 increases risk to psychiatric illness is likely to be complex. To follow up this work, future studies should utilise larger numbers of samples, use neurologically relevant tissue and apply more sophisticated approaches to screen for changes in gene expression and additional genetic variants.

Huntington’s disease (HD) is a primary example of a basal ganglia disorder, from which, medium spiny neurons in the striatum degenerate. As this causes a breakdown in basal ganglia cortico-thalamic circuitry, this leads to a range of symptoms including motor, cognitive and behavioural deficits. One therapeutic option is to replace medium spiny neurons with precursor striatal cells and reconnect the lost circuitry. However, the lack of performance based functional outcome measures for people with HD have made it difficult to assess how the graft affects standards of daily living. Although neuroimaging techniques can be used to quantify the morphological and molecular effects that the intervention has on that brain region, and associated circuitry, an important question still remains, namely whether there has been any effect on functional ability. Using assessments that have high ecological validity, such as dual tasks could be a valuable measure, especially as previous studies suggest that the striatum is required for optimal performance in such tasks. Therefore the focus of this thesis was to design, develop and assess performance based functional tasks that involve the neurocircuity affected in HD; namely the basal ganglia. The aim of the study in Chapter 2 was to select, develop and evaluate motor-cognitive dual task paradigms for use in people with HD. The findings revealed that the Step and Stroop which targeted lower limb function, best distinguished disease stage in HD compared to the other lower limb assessments tested. During this experiment, it became apparent that upper limb assessments for people with HD were particularly limited. Therefore, in Part 2, a new upper limb dual task assessment was developed and called the Clinch token transfer test (C3t). The findings revealed that this was sensitive to disease stage and could provide a useful outcome measure for people with HD in the future. To take the findings from Chapter 2 further, a new, standardised C3t was developed. This version was evaluated, optimised, and then validated in a large group of people gene positive for HD, and in heathy controls. The findings revealed that the C3t significantly correlated with all the Unified Huntington Disease Rating Scale measures, successfully distinguished between all disease stages, and revealed that the performance in this task was also sensitive to the subtle disease symptoms in the early stages of HD. As the Stroop task is commonly used in people with HD, the aim of Chapter 3 was to use immediate early gene expression to identify if the striatum was activated during a rodent analogue of the Stroop task. The findings revealed what could be the first in a series of experiments in that, striatal activation significantly correlated with performance in the congruent and the incongruent versions of this test when compared to cage controls. The findings presented in this thesis support that dual task assessments could have an important role in assessing function in HD, which could translate to performance in tasks that affect the standards of daily living. Importantly, as different dual tasks can result in different levels of dual task interference, this suggests that practice effects could affect how sensitive some dual task paradigms are over others. In addition, selecting outcome measures that are specific to the regions affected in HD, in both clinic and in pre-clinical models, will permit sensitive tracking of neurodegeneration, and could also be used to assess the outcomes of therapies that target this specific neural region.