Melbourne School of Psychological Sciences - Theses
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ItemUsing single subject manual independent component analysis on resting-state fMRI data( 2019)It is important to understand the influence of common artefacts when processing fMRI data, and how best to remove these in order to produce reliable outcomes. This information affects clinicians and researchers. Little is known about functional connectivity in people with genetic generalised epilepsy at present, making it an ideal cohort to examine while using a quality data processing pipeline. The present thesis discusses individual artefactual contribution, and how to deal with artefact using single subject manual independent component analysis (SSM-ICA). A systematic review of the literature (Chapter two) found people with genetic generalised epilepsy to have reduced functional connectivity in the default mode and attention networks relative to healthy controls. A methods study (Chapter three) investigated functional connectivity in juvenile absence epilepsy, a subtype of genetic generalised epilepsy. Results showed reduced connectivity strength relative to controls. Further, incremental removal of artefacts using single subject manual independent component analysis showed fewer correlations breaching the .05 threshold. These areas were more confined to default mode and attention networks, suggesting most correlations derived without the use of SSM-ICA are spurious. Signal-to-noise ratios were also significantly higher in both incremental cleaning conditions.
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ItemThe neuroprotective effects of music training in epilepsy( 2018)Music is central to modern life and ubiquitous in human culture. A unique functional neurobiological property of music is its greater bilateral representation in the brain, which is hypothesised to account for the proposed relative preservation of music functions in the face of neurological injury, particularly the paroxysmal ictal and inter-ictal network disruption associated with focal epilepsy. Furthermore, specialised training in music may enhance this ‘neuroresilience’ of music functions, in addition to potentially protecting the brain against the effects of future neurological disruption on non-music cognitive abilities. The neurobiological mechanisms underpinning music-related neuroresilience and neuroprotection, however, remain unclear. The current thesis therefore explored these two themes of cognitive resilience and the potential neuroprotective effects of music training, through the critical analysis of extant literature describing music and non-music cognitive abilities in non-musicians (Chapter 2) and musicians (Chapter 4) with neurological disorders, a case-control experimental group study investigating music-related resilience and neuroprotection using the neurological model of focal epilepsy (Chapter 3), and a case study describing the unique preservation of music (but not verbal) memory in a musician with bilateral temporal lobe epilepsy (Chapter 5). Chapter 2 comprehensively reviewed 65 studies examining a range of music functions in pre-surgical or post-surgical non-musicians with focal epilepsy. Overall, the findings of this review provided evidence that music cognitive deficits are relatively common in non-musicians with epilepsy, with many domains affected in at least half of the patient cohorts. Considerable variability in impairment was evident, however, with post-surgical epilepsy cohorts tending to exhibit more frequent deficits than pre-surgical patients. This was especially evident for music functions associated with broader, multi-domain networks (e.g., melodic and musical emotion processing) compared to lower-level musical processing (e.g., pitch discrimination). A rightward asymmetry was observed for many music deficits, particularly for the domains of melodic processing and singing. Although these results contradicted the idea of music’s resistance to disease and the benefits of bilateral functional organisation, a number of limitations were identified within this literature, which made the interpretation of the findings challenging. Critically, examination of music cognitive abilities in isolation from non-music functions such as language and verbal memory does not allow for the comparison of the relative neuroresilience of music versus non-music skills. Consequently, the case-control group study presented in Chapter 3 assessed music and non-music cognition in focal epilepsy patients with and without music training, and healthy control participants with and without music training. The results indicated a pervasive pattern of verbal cognitive impairments (e.g., verbal fluency, abstract reasoning, and memory) and select music cognitive difficulties (melodic discrimination and metre identification) in epilepsy non-musicians compared to controls (musicians and non-musicians combined). In contrast, epilepsy musicians displayed preserved verbal cognition on all measures except verbal fluency, and no significant deficits in music cognition. The results were interpreted as a neuroprotective effect of music training in the epilepsy musician group, which benefited cognitive abilities that likely share processing components and neural substrates with the skills required to learn to play an instrument. This includes training-related enhancement of brain regions in fronto-temporo-parietal networks and their underlying structural connections (e.g., superior longitudinal and arcuate fasciculi), which support core cognitive processes such as working memory and executive control. This interpretation was strengthened by the finding that musicians who began training earlier in life (<=7 years old) tended to display greater benefits for verbal cognitive abilities. Furthermore, the overall more pervasive pattern of non-music cognitive deficits in patient non-musicians supported the notion of music’s greater relative resilience to the cognitive consequences of epilepsy. The critical literature review in Chapter 4 extended the findings of Chapter 3, by synthesising the evidence from 87 studies (comprising 99 unique cases) of musicians with either epilepsy, stroke, dementia, herpes simplex virus encephalitis, and patients undergoing surgical resection of brain tumours. The collated findings across populations indicated that impairment was generally more commonly reported for non-music compared to music cognitive functions, and that the frequency of music and non-music impairments varied as a function of disease aetiology. A comparison between epilepsy, stroke, and dementia cases revealed the greatest levels of music and non-music functional preservation in epilepsy musicians. Moreover, epilepsy musicians demonstrated fewer overall deficits in music versus non-music domains, with only select impairments in language, verbal/visual memory, attention, and music reading. These findings reinforced the results from Chapter 3, highlighting the relative neuroresilience of music functions, and the protective effects of music training in epilepsy. Given the more widespread patterns of impairment observed in stroke and dementia cases, however, music training does not appear to provide neuroprotection for untrained abilities (i.e., ‘far’ transfer) in patients with sudden acute neurological insult (stroke) or diffuse and progressive cerebral atrophy (dementia). Finally, Chapter 5 described the case of a particularly interesting musician with bilateral temporal lobe epilepsy and hippocampal sclerosis, who had taken part in the group study from Chapter 3. This musician (BK) exhibited a profound discrepancy between his intact melodic learning and memory skills and severely impaired verbal and visual memory, illustrating the possible upper limits to the potential for music training to compensate for bilateral temporal lobe disruption. BK’s preserved music memory was intriguing, and it was hypothsised that he was engaging the dorsal fronto-temporal circuit implicated in working memory and articulatory rehearsal, to facilitate the encoding, storage, and retrieval of musical information. To investigate this further, BK was assessed on a task of melodic learning with articulatory suppression, involving trials of digit span forward serial recall after the presentation of each of eight short, novel melodic sequences that he was to remember. Comparison with his performance on the same task without phonological interference revealed a disruptive effect of the extraneous auditory information for remembering atonal melodic sequences. This suggested that articulatory rehearsal was an effective encoding strategy for processing and remembering these stimuli, implicating at least partial mediation of BK’s music memory via training-enhanced working memory circuits. These intriguing findings provided further evidence for the beneficial effects of music training-related neuroplasticity for multiple music and non-music cognitive systems, in addition to emphasising the relative resilience of music functions, against the effects of even severe bilateral network disruption. As suggested by Chapter 4, these benefits appear to be unique and specific to epilepsy, and do not provide the same level of cognitive sparing in musicians with non-epileptic bilateral neurological damage. This thesis discusses the above findings in the context of methodological limitations in the music neuroscience literature, including a dearth of group studies comparing musicians and non-musicians with neurological disorders. These findings have critical implications for music education, emphasising the importance of access to music within schools, in light of the evidence that engaging in music learning early in life may be associated with neuroplastic changes that benefit the brain and cognition later in life. In addition, examination of the possible therapeutic effects of music training in individuals with epilepsy may shed further light on the neurobiological mechanisms underpinning music-related neuroplasticity, and how time-sensitive these processes are in relation to the development of seizures.
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ItemCharacterising changes in brain structure and neuropsychological function in the psychoses of epilepsy( 2018)Psychosis of epilepsy (POE) is a poorly understood condition which can have a devastating impact on people with epilepsy. Despite over a century of investigation into the relationship between epilepsy and psychosis, the structural neurobiological basis and neuropsychological deficits of POE remain unclear. Research in schizophrenia, the paradigmatic psychotic disorder, strongly suggests that psychosis is underpinned by abnormal neurodevelopmental processes which lead to altered brain structure and psychotic symptoms in later life. Moreover, both epilepsy and psychosis are increasingly understood as disorders of large-scale brain networks such as the default mode network (DMN) and the cognitive control network (CCN). The neurodevelopmental model of psychosis on the one hand, and the contemporary understanding of epilepsy and psychosis as network disorders on the other, underpin the primary aim of this thesis, which was to investigate changes in brain structure and neuropsychological function in POE. Understanding the structural neurobiological and neuropsychological deficits of POE is critical as it may provide insights into its neurobiological and developmental mechanisms. Following the introductory chapters (1-3), a systematic review of the neuroimaging literature in POE was undertaken. The results of this review informed the 3 structural neuroimaging studies and 1 neuropsychological study that followed. Study 1 comprised the first examination of volumetric changes in hippocampal subregions in POE, undertaken in the largest POE sample to date (n = 50). It addresses the methodological limitations of past studies of the hippocampus in POE, which were identified via the systematic review. The results of Study 1 showed hippocampal volume loss on a postero-anterior gradient, with severe decreases in the tail, and moderate volume decreases in the body, but no difference in the hippocampal head in POE relative to matched epilepsy controls (EC). These findings suggest that posterior hippocampal atrophy may be a structural biomarker of POE. The hippocampus can be further subdivided into distinct subfields which, along with the hippocampal fissure, were not captured by the assessment of hippocampal subregions undertaken in Study 1. Specific subfields, and the hippocampal fissure, have been shown to be affected in other non-epilepsy related psychotic disorders, and have not previously been examined in POE. Therefore, Study 2 comprised the first assessment of hippocampal subfields and the hippocampal fissure in POE. The results revealed an enlarged right hippocampal fissure in POE, with no difference in subfield volumes relative to EC. Moreover, because the volume of the right hippocampal fissure was not related to duration of epilepsy or age of habitual seizure onset, hippocampal fissure enlargement is likely underpinned by abnormal neurodevelopment. Together, Studies 1 and 2 provide strong evidence for structural hippocampal abnormalities in POE. Study 3 examined changes in cortical thickness, area, and volume in POE relative to EC, comparing patients with postictal psychosis (PIP) and interictal psychosis (IP) - the two main POE subtypes. This study was also motivated by the findings of the systematic review, which highlighted that only two studies have examined cortical changes in POE, one showing cortical thickening in PIP and the other showing cortical thinning in IP. Study 3 directly investigated this distinction, revealing cortical thickening in nodes of the CCN and DMN in POE overall, with more extensive thickening in visual processing regions in IP. Study 4 comprised an examination of the neuropsychological performance of POE patients and was informed by the structural changes identified in Studies 1-3. The results revealed that patients with POE displayed significantly poorer performance on tasks supported by nodes of the DMN (verbal memory and visual memory) relative to EC and healthy controls (HC), and on tasks supported by the CCN (working memory and verbal fluency), relative to HC. Considered together, the results of this thesis advance our knowledge of the structural neurobiological basis and neuropsychological deficits of POE. Specifically, they suggest that hippocampal abnormalities and cortical thickening in nodes of key brain networks are involved in its neuropathogenesis, and underpin altered neuropsychological function. The findings of this thesis also provide initial evidence that these structural changes may reflect the impact of epilepsy on neurodevelopmental processes, and provide some new insights into the neurobiological mechanisms underpinning POE. A neurodevelopmental model of POE is proposed, wherein altered hippocampal development and interruption of normal synaptic pruning leads to cortical thickening within specific large-scale brain networks. These structural changes may underpin the cognitive deficits and psychiatric symptoms of POE.
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ItemCognitive and psychosocial functioning in genetic generalised epilepsy( 2017)Genetic generalised epilepsies (GGE) are a common, but under-studied cluster of epileptic syndromes of predominantly child and adolescent onset. The primary syndromes of GGE are childhood absence epilepsy (CAE), juvenile absence epilepsy(JAE), juvenile myoclonic epilepsy (JME), and genetic generalised epilepsy with generalised tonic-clonic seizures only (GTSCO). Important questions remain regarding: the degree of cognitive and psychopathological comorbidity, particularly in adults and in syndromes other than JME; effects of the disease on cognitive function; and psychopathology and psychosocial wellbeing in these patient groups. This thesis aimed to provide a detailed and quantitative description of cognitive function and psychopathology in GGE, assess the impact of contributing factors including subclinical epileptiform discharges on cognitive and psychopathology outcomes, and to evaluate the relationship between psychopathology and cognition. Methods employed include narrative systematic review, quantitative meta-analysis, and prospective assessment of cognitive and psychosocial functioning of a relatively large sample of people with GGE. Results indicated mild to moderately large reductions across most cognitive factors relative to that of healthy control participants and age-based normative data, with a relative weakness in long-term retrieval and memory function. Short-term memory function was not reduced relative to age-based normative data. Overall cognitive ability and memory function was negatively associated with total duration of epileptiform discharges during a 24-hour period. Approximately 50% of the sample reported elevated symptoms on a measure of psychopathology spanning six symptom types, with depression and anxiety the most common amongst these. Collectively, these findings highlight the need for increased awareness, screening and the provision of services for psychological comorbidities for people with GGE.
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ItemNeurocognitive and psychiatric markers of network disease in epilepsy( 2015)People with epilepsy frequently experience debilitating memory and mood difficulties. Autobiographic memory impairments are a vulnerability factor for developing and maintaining unipolar depression in the psychiatric population, yet despite the wealth of research examining cognition and behaviour in epilepsy, the links between them remain unclear. This thesis aimed to profile the autobiographic memory and mood function of patients with focal epilepsy relative to healthy controls, and characterise how these functions may be interlinked. Three behavioural studies were conducted to achieve these objectives. Participants were prospectively recruited from the Comprehensive Epilepsy Programme at Austin Health, Melbourne, between 2010-2014. The cognitive and psychiatric functioning of 85 adults with chronic focal epilepsy was compared to that of 72 sociodemographically-matched controls largely recruited from the patients’ families (N=157). Gold-standard psychometric measures assessed depressive symptoms and cognitive function. Study One was an initial qualitative exploration of the relationships between cognitive impairment and depression in a form of focal epilepsy not typically linked to memory disorder, to assess the effects of seizures and pathology on those functions. A well-characterised case series of nine patients with frontal lobe epilepsy (FLE) was contrasted to 24 matched controls. Results suggested that FLE can selectively interrupt the integrity of the autobiographic memory/cognitive control networks versus the affective network. Study Two aimed to quantitatively delineate the effects of seizure chronicity on impaired autobiographic memory in a large cohort of patients (n=85) relative to healthy controls (n=72), and the potential links between poor autobiographic recall and mood. This revealed that chronic seizures beginning in childhood dysregulate cognition-related networks important for autobiographic recall, while autobiographic memory impairments in patients with a more recent disease onset are largely linked to depressive symptoms, perhaps reflecting maladaptive psychological adjustment to the onset of epilepsy as an adult. Together, the first two studies show that autobiographic memory difficulties are only related to depression in certain epilepsy syndromes. Finally, Study Three comprised a data-driven investigation into the existence of a cognitive phenotype of depression in epilepsy. Results showed that of the 21 (25%) patients currently meeting criteria for a formal depressive disorder, 15 (71%) had a ‘Cognitive’ phenotype of the disorder, while six (29%) presented with a ‘Somatic’ phenotype. These findings are congruent with phenotypes of depression found in other populations, and suggest that different presentations of depression in epilepsy may uniquely index dysregulation of selected brain networks. Moreover the lack of seizure-related correlates to the Cognitive phenotype discounts the widespread assumption that cognitive and affective network dysfunction in epilepsy is a side-effect of seizures. The results of this thesis suggest that epilepsy can selectively disrupt large-scale brain networks important to cognition and affect, and that behavioural disturbances in people with epilepsy may be primary manifestations of the network disease.
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ItemThe assessment and treatment of concerns and anxiety in patients undergoing pre-surgical monitoring for epilepsy( 2006)The aim of the present study was to investigate the efficacy of an information package on reducing pre-surgical anxiety and concerns in patients with intractable epilepsy. Adverse psychological and social effects of temporal lobe epilepsy (TLE) are instrumental in anxiety and distress in these patients. This is brought into the hospital setting and exacerbated by the monitoring process and concomitant possibility of surgery where many patients prematurely curtailed the process at cost to themselves and the hospital.
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ItemThe ‘burden of normality’ following relief of chronic medical illness: a comparison of narcolepsy and epilepsy( 2001)Medical and technical advances have played a major role in the relief of chronic, lifestyle limiting medical illnesses. Issues relating to patient wellbeing and the ability to cope following the successful treatment of chronic illness have been addressed in recent years. This research endeavour has resulted from an increased recognition of the importance of the psychosocial issues in maximising treatment outcome. Recent research (Bladin, 1992; Wilson et. al., in press) has addressed the clinical features of psychosocial adaptation and adjustment following surgical treatment of chronic epilepsy. These features have been characterised as a syndrome, the 'burden of normality', comprising psychological, behavioural, affective and sociological change as patients discard roles associated with chronic illness and learn to become "well". The present study addresses the applicability of the burden of normality to another chronically ill population in which there is a chance for a dramatic relief of symptoms, that of narcolepsy. There has been no previous research into psychosocial adjustment following successful treatment of this condition. Importantly, narcolepsy and temporal lobe epilepsy (TLE) share a number of similar features which provide the rationale for this comparison. Most notably, both conditions have similar precursory features for the burden of normality. It was hypothesised that the symptoms of the burden of normality would be present in patients treated with stimulant medication (ritalin) for the relief of narcolepsy and patients who have undergone ATL for the relief of intractable seizures. It was also hypothesised that any differences in manifestations of symptoms would be related to 'disease-specific' features of the two conditions. Thirty three narcolepsy and 31 temporal lobectomy patients were recruited through routine outpatient followup at the Austin and Repatriation Medical Centre, Melbourne. All patients underwent in depth psychosocial review using the Austin CEP Interview. This is a formally coded, semi-structured interview that covers a broad range of issues, including symptoms of the burden of normality. The Beck Depression Inventory - Second Edition (BDI-II), and the State Trait Anxiety Inventory (STAI S-Anxiety) were also administered to assess mood states. This study documented the occurrence of symptoms of the burden of normality in the successfully treated narcolepsy and epilepsy populations. Symptoms of the burden of normality were proposed to stem from the psychological transition involved in discarding roles associated with "illness" and learning to become "well". Differences in symptom manifestation were argued to reflect 'disease specific' factors, including the later diagnosis and treatment of narcolepsy patients and issues related to differences in the nature of the treatment of the two conditions. It was concluded that the burden of normality appears to arise out of a general process of adjustment following relief of chronic medical illness. This indicates a strong need for preoperative counselling and psychosocial followup as potentially crucial services for patients with chronic illness who are offered the life-altering relief of their condition.