Melbourne School of Psychological Sciences - Theses

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    Psychological outcomes of those experiencing early pregnancy loss
    Bendavid, Jessie ( 2019)
    Early Pregnancy Loss (EPL), a loss occurring before 14 weeks gestation, is a relatively common event, occurring in about 20% of pregnancies. Although many women and their partners do not experience psychological difficulties associated with this loss, a significant minority experience intense and sustained grief, depression and anxiety symptoms. Reliable prevalence rates of serious psychological consequences for women are not well established, and those of partners are largely unknown. Furthermore, it is unclear what factors increase the risk for developing serious psychological symptoms. A range of potential risk factors have been identified, but remain under-researched and have not been rigorously studied. According to Cognitive Behavioural Theory, it is possible that cognitions surrounding the loss may be a particularly relevant risk factor. Yet this topic has rarely been examined and the studies that have are characterised by major methodological shortcomings. Importantly, partners are rarely included in these studies. This study aimed to determine prevalence rates for grief depression and anxiety over the first three and a half months after EPL. It also investigated cognitions after EPL through the Common-Sense Model of Illness Representation, and their link with grief, depression and anxiety symptoms. This study included 28 male partners and 68 women diagnosed with EPL who attended the Early Pregnancy Assessment Service at the Royal Women’s Hospital in Melbourne, Australia. Participants completed self-report measures two weeks (T1), and three months (T2) post-loss. These included the Perinatal Grief Scale, the Centre for Epidemiological Studies-Depression scale, the State Trait Anxiety Inventory, and the Illness Perception Questionnaire-Revised. Results showed that the prevalence of grief, depression and anxiety symptoms for women at T1 were 20.6%, 54.4%, and 52.9%, respectively. For partners, the prevalence rates were 0% for grief, 32.1% for depression, and 25% for anxiety. These rates decreased by T2. Illness perceptions were found to significantly predict grief, depression and anxiety. Unexpectedly, it was often better perceptions of the loss that predicted worse psychological outcomes. These findings provide new information about the experience of EPL and suggest that critical timing for assessment and treatment would be within the first 3 months after EPL. Treatment options, particularly in terms of grief theories presented in the introduction, are discussed. Considering the surprising results and that this is the first study to examine illness perceptions among this sample, replication of these results is needed.
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    The neuroprotective effects of music training in epilepsy
    Bird, Laura Jane ( 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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    Cognitive and psychosocial functioning in genetic generalised epilepsy
    LOUGHMAN, AMY ( 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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    Arbitrary associative memory: a candidate cognitive endophenotype for probable Alzheimer's disease
    Werden, Emile ( 2015)
    The genetic basis of sporadic, senile onset Alzheimer’s disease (AD) is not as well documented as familial, younger-onset AD. At present, there is no evidence to support monogenic inheritance in senile onset AD or “probable AD”. As far as genetic risk factors are concerned, the apolipoprotein E epsilon-4 allele is the only reliable genetic susceptibility factor for probable AD. The investigation of cognitive endophenotypes for probable AD, or cognitive markers of liability to the condition that are theoretically closer to its genetic mechanisms than its clinical phenotype, might assist in the identification of susceptibility genes for AD. This is especially the case if these cognitive differences reflect genetically predetermined differences in brain structure and function. The traditional view of probable AD is that cognitive dysfunction emerges many years, and possibly decades, after underlying brain neuropathological, metabolic, and structural changes have begun. According to this theory, while brain functional and structural changes might be present in middle age in people at risk of developing the disease, cognitive abnormalities emerge only when a “threshold” of neurodegeneration has been reached and unaffected brain regions can no longer compensate functionally for affected areas. An alternative viewpoint is that cognitive deficits are present in the earliest stages of probable AD, but that two issues have limited our ability to detect such changes: First, previous studies have utilised tests which are not sensitive to the earliest neurocognitive changes in the condition. Second, the heterogeneous clinical phenotype of probable AD has meant that the conventional approach of comparing mean scores on cognitive tests between low-risk and high-risk groups might be masking subsets of affected people within high-risk groups. The use of more sensitive tests, in conjunction with cognitive discrepancy analyses, which compare performances within high-risk groups on combinations of tasks (e.g., Test A versus Test B) that are related to the neuroanatomical changes in probable AD, might reveal cognitive markers of liability to the condition. The current research focused on middle-aged people with a parental history of probable AD. These people are at a greater risk of developing the condition themselves, than any other first-degree relative, and this risk might be independent of the apolipoprotein E epsilon-4 allele. People with a maternal history of probable AD might be particularly vulnerable to developing the condition themselves, with studies suggesting that this group is more likely than people with a paternal history to demonstrate patterns of brain structural and metabolic change in middle-age that are similar to those observed in probable AD. Thus, the identification of cognitive markers of liability to probable AD in offspring of probable AD patients, and in particular, those with a maternal history of the condition, has the potential to assist in the early identification of the disease and, if these markers turn out to be endophenotypic in probable AD, it might also lead to the identification of putative susceptibility genes for the condition. The research had two major aims. The first aim was to summarise the limited data on the cognitive functioning of people with and without a parental history of probable AD, and determine whether conventional between-group analyses could reveal differences in cognitive functioning between these two groups. To this end, the investigator conducted a meta-analysis of 17 relevant studies in literature, and examined the magnitude of cognitive impairment across several domains, with a particular focus on episodic memory (Study 1). As expected, effect sizes for all cognitive domains were small, and none were significantly different to zero. The largest difference between groups was found for visuospatial ability (d = 0.16), with offspring of probable AD patients outperforming controls. This was followed by verbal ability (d = -0.10) and episodic memory (d = -0.09), with offspring performing worse than controls. Effect sizes for all other cognitive domains, including global cognition (d = 0), executive function (d = 0), attention and concentration (d = 0), and perceptual speed (d = -0.04) were essentially zero. The results suggested that differences in cognitive function between high-and low-risk groups were present, but subtle, and raised the possibility that the use of more sensitive memory tasks and analytical techniques, could reveal more pronounced deficits in memory function in the offspring group. The second aim of the research was to determine whether differences in arbitrary associative memory function were detectable in middle-aged people with a parental history of probable AD, using conventional between-group analyses and novel cognitive discrepancy analyses. Arbitrary associative memory function was examined for four reasons: First, the arbitrary associative memory system is responsible for the rapid uptake of novel relationships. This function is considered crucial for all new learning and memory in humans. Second, arbitrary associative memory is heavily reliant on the medial temporal lobe – a region that is affected in the earliest stages of probable AD. Third, measures of arbitrary associative cued-recall are sensitive to the earliest changes in cognition in amnestic mild cognitive impairment and probable AD, but have not been utilised in parental AD. Finally, the arbitrary associative recognition literature suggests that the ability to recognise that two similar items belong together, or “within-domain arbitrary associative recognition”, is heavily dependent on the rhinal cortex. The rhinal cortex, in turn, is the site of the earliest neuropathological change in AD. The ability to recognise that two dissimilar items belong together, or “between-domain arbitrary associative recognition”, is more dependent on the hippocampus. The hippocampus is affected at a later stage in AD. The investigator reasoned that within-domain and between-domain arbitrary associative recognition function could be differentially affected in the parental AD group and conducted two studies to investigate this hypothesis. Based on the staging of neuropathological and structural change in probable AD, it was hypothesised that a subset of people with a parental history of the condition would perform more poorly on within-domain arbitrary associative recognition tasks, than on between-domain recognition tasks. In Study 2, 25 cognitively and neurologically normal people, aged between 45 and 55 years, completed four novel arbitrary associative recognition tasks, developed by the investigator in a series of pilot studies. They had no first-degree family history of any dementia. Two within-domain arbitrary associative recognition tasks (i.e., word-word, face-face), and two between-domain arbitrary associative recognition tasks (i.e., word-face, pattern-word) were developed. The purpose of the study was to examine the difficulty of the recognition tasks. The results demonstrated that the tasks did not suffer from floor or ceiling effects. Discrimination scores for the word-word (d’ = 1.81 ± 0.62) and pattern-word tasks (d’ = 1.58 ± 0.56) were not significantly different, but both were significantly higher than scores for the face-face (d’ = 0.64 ± 0.39) and word-face (d’ = 0.82 ± 0.41) tasks. Discrimination scores for the latter two tasks were also not significantly different. The results of Study 2 meant that discrepancies in within-domain and between-domain arbitrary associative recognition could be examined at “easy” and “hard” difficulty levels in people with a parental history of probable AD in Study 3. The word-word and pattern-word tasks comprised the “easy” cognitive discrepancy, while the face-face and word-face tasks comprised the “hard” cognitive discrepancy. Twenty three people with only a parental history of probable AD, and 30 people without a first-degree family history of any dementia, completed a range of clinical memory tests (e.g., California Verbal Learning Test-II), as well as arbitrary associative cued-recall (e.g., Paired Associate Learning Test of the Cambridge Neuropsychological Test Automated Battery) and arbitrary associative recognition tasks (e.g., novel word-word face-face, word-face, and pattern-word tasks). As predicted, mean scores on the clinical memory tasks were compared between groups, and no significant differences were found; however, contrary to predictions, offspring did not perform worse than controls on measures of arbitrary associative cued-recall and recognition. The hypothesis that group membership (offspring, control) and apolipoprotein epsilon 4 status (positive, negative) would not interact to affect memory test scores was partially supported, with significant interactions found only for average discrimination scores on the Face-Face and Word-Face tasks. No between-group differences were found on memory test scores when the parental AD group was broken down into maternal AD and paternal AD subgroups. Cognitive discrepancy analyses were conducted on z-scores for the arbitrary associative recognition tasks. It was hypothesised that, when z-scores on each within-domain and between-domain task were compared within groups (e.g., word-word minus pattern-word; face-face minus word-face), greater-than-expected percentages of offspring would perform more poorly on the within-domain tasks, than on the between-domain tasks – i.e., display negative cognitive discrepancy scores or negative cognitive profiles. Controls were expected to perform similarly on the within-domain and between-domain arbitrary associative recognition tasks – i.e., display neutral discrepancy scores. The hypotheses were partially supported: while associations between group (offspring and control) and profile type were not statistically significant, the percentages of offspring who displayed negative cognitive profiles were greater than expected by chance alone. This pattern was found for most indices of within-domain and between-domain arbitrary associative recognition function. Moreover, as predicted, the results were largely driven by the maternal AD group, with greater-than-expected percentages of these people displaying negative discrepancy scores. When task difficulty was ignored and z-scores for composite within-domain (e.g., word-word, face-face) and between-domain (e.g., pattern-word, word-face) variables were compared, the association between parental history type (maternal AD, paternal AD, control) and profile type (negative, positive) was statistically significant. By contrast, controls were consistently more likely to display neutral or positive discrepancy scores. The current research challenges the notion that differences in cognitive function are not detectable in middle-aged people at risk of probable AD and raises the possibility that deficits in arbitrary associative memory are endophenotypic in the condition. It is hoped that the knowledge gained from the present research will add to the growing body of literature attempting to assist in the early detection of probable AD and will encourage other researchers to search for cognitive endophenotypes for the condition, as it might provide some clues about its underlying neurobiological and genetic mechanisms.
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    The effect of vascular risk factors in dementia of the Alzheimer's type
    Restrepo, Carolina ( 2016)
    The influence of vascular risk factors on Alzheimer’s disease and its clinical presentation is an area of intense scientific debate. There is now growing evidence to suggest that the presence of vascular risk factors in early-stage Alzheimer’s disease might accelerate its clinical presentation. Previous studies have also demonstrated that clinically healthy individuals with vascular risk factors perform below expectations on cognitive assessment. Further, the burden of vascular risk factors might be a predictor of future cognitive decline. However, the relationship between vascular risk factors and cognitive deterioration in healthy older adults has not been clearly established. The aim of this study was to investigate the relationship between vascular risk factors and cognitive function in a large cohort of 768 cognitively healthy older individuals drawn from the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Ageing. This thesis addresses four main questions: (1) is there a difference in cognitive performance between individuals with and without vascular risk factors?, (2) does the presence of vascular risk factors affect the rate of cognitive change? (3) does the number of vascular risk factors influence cognition? and (4) does the presence of vascular risk factors increase the likelihood of developing Mild Cognitive Impairment? Participants were aged between 60–95 years, (M= 69.9 ± 6.9). All participants underwent a comprehensive baseline assessment and three additional serial assessments were repeated at 18-month intervals over a 54-month period. By the end of the study period, 172 individuals had withdrawn from the cohort. Of the remaining 596 participants, 43 had attracted a classification of Mild Cognitive Impairment. The sample was divided into subgroups of those with and without vascular risk factors. Participants in the vascular risk factors sub-group had at least one of the following risk factors: (1) hypertension, (2) diabetes, (3) dyslipidaemia, (4) Body Mass Index > 30 kg/m², (5) chronic kidney disease, (6) smoking history of more than 20 cigarettes per day for more than one year, and (7) elevated homocysteine levels (males>16.2 μmol/L; females>13.6 μmol/L). This thesis comprises a series of analyses. For the first analysis, demographic characteristics of individuals with and without vascular risk factors was compared. The data suggested that vascular risk factors were associated with older age (F (1, 712) = 8.1, p = 0.005), lower level of education (χ2 (1, n =711) = 7.8, p = 0.005) and apolipoprotein E ε4 carriage (χ2 (1, n = 714) =6.9, p = 0.009). In the second analysis, a statistically significant difference in cognitive performance between individuals with and without vascular risk factors was identified (F (4, 669) = 4.28, p = 0.002; partial eta square = 0.03). The results revealed that participants with vascular risk factors demonstrated poorer performance on variables that assessed visual cognition and executive functions than participants without vascular risk factors. In the third analysis, from a longitudinal perspective, five specific neuropsychological tests were subjected to a linear mixed model adjusted for age and apolipoprotein E ε4 carriage. The presence of vascular risk factors was associated with increased rates of cognitive decline on measures of verbal fluency (F (2, 1096.8) = 3.03, p < 0.05) and visuospatial skills (F (1204.6, 1) = 1.055; p < 0.05). The relationship between vascular risk factors and cognitive decline became more evident in the fourth analysis when the neuropsychological test battery was reduced into cognitive composite measures. Participants with vascular risk factors showed significantly greater decline on measures of verbal (F (624.016, 1) = 7.2; p = 0.01) and visual (F (1775.533, 1) = 6.89; p = 0.01) memory, as well as on visuospatial skills (F (1204.6, 1) = 1.055; p = 0.03) and executive functions (F (1821.035, 1) = 4.48; p = 0.03). No difference was found in the language composite measure. In the fifth analysis, higher vascular risk factor burden was associated with increased rates of cognitive decline, suggesting the presence of a dose-response relationship. In individuals with three or more vascular risk factors, a higher magnitude of decline on tasks that measure executive functions (Cohen's d = 0.35), visuospatial skills (Cohen's d = 0.35) and visual memory (Cohen's d = 0.47) was identified. No dose-response relationship was found in either the language or verbal memory cognitive domains. The sixth analysis focused on the group of participants who attracted a diagnosis of MCI over the 54 months. The data showed that there was a significant difference in the vascular risk factor burden distribution between individuals who remain cognitively stable and those who transition to Mild Cognitive Impairment (X² (2) = 44.88, p < 0.001), with greater risk factor burden observed in the latter. The interaction effect between clinical classification and presence/absence of vascular risk factors on the cognitive composite factors was further investigated. The only cognitive variable that showed a statistically significant difference was the visuospatial skill composite (1, 513) = 5.52; p = 0.019; partial eta square = 0.011). Finally, the analysis showed that vascular risk factors increased the likelihood of developing Mild Cognitive Impairment by 39%. In conclusion, the data suggest that vascular risk factors confer a degree of cognitive vulnerability on cognitively healthy older adults. This effect appears to be selective, impacting executive functions and visuospatial cognition but not language and verbal memory. Executive functions and visuospatial cognition are complex cognitive domains and share extensive distributed networks, which may increase their susceptibility to vascular risk factors over time. Based on the overall findings of this research, we propose that vascular risk factors – in combination with genetic and demographic factors – contribute to a reduction of brain reserve, precipitating an earlier onset of cognitive decline in the transition to Mild Cognitive Impairment. This implies that individuals who suffer from several risk factors may have less brain reserve and may therefore be more susceptible to developing dementia. Vascular risk factors are preventable for at least 95% of people with relatively simple changes in diet and lifestyle. The findings from this thesis contribute to a developing literature suggesting that decreases in vascular risk may reduce susceptibility for dementia and cognitive decline in later life.
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    Assessment of the effects of transcranial direct current stimulation (tDCS) on neurophysiologic, cognitive, and behavioral outcome measures
    Horvath, Jared ( 2016)
    Transcranial Direct Current Stimulation (tDCS) is a form of non-invasive brain stimulation that serves to modulate brain activity via the passing of a weak, electrical current through the head. Despite public and clinical excitement, the effects of tDCS reported in the literature have been inconsistent. Accordingly, the reliability of this device remains unclear. The purpose of this PhD was to explore the consistency and reliability of inter- and intra-subject tDCS effects. First, I conducted research exploring the effects of four tDCS parameters (polarity, current density, electrode location, and stimulation-to-task relationship) on simple visual motor reaction time (smRT). 150 individuals were assigned to one of 5 experimental groups (2 mA anodal, 2 mA cathodal, 1 mA anodal, 1 mA cathodal, or sham) across 3 different conditions (M1 target with the reference over an orbitofrontal, bilateral, or extracephalic location). Participants received 20min stimulation while undertaking an smRT task 5min preceeding, during, and 5min following stimulation. Results revealed tDCS demonstrated no significant effect on any smRT parameter. In my next study, 30 participants underwent 7min of anodal, cathodal, or sham stimulation using a bilateral M1 electrode montage. Participants undertook an smRT task for 5min preceeding, during, and 20min following stimulation: however, the cueing stimulus utilized was auditory rather than visual. As before, this experiment produced null results. Next, 2 participants undertook 8 separate sessions of 1min cathodal tDCS utilizing a bilateral M1 montage. Participants undertook an smRT task for 1min preceding, during, and following stimulation. Again, this experiment produced null-results. To determine a cognitive measure reliably amenable to stimulation, I next conducted a quantitative review of every inter-lab replicated cognitive task in the tDCS literature. Of the 59 analyses exploring 52 outcome measures across three-tiers of inclusion stringency (gleaned from 138 studies), none demonstrated a significantly reliable response to tDCS. To determine a physiologic outcome measure amenable to stimulation, I conducted a second quantitative review of every inter-lab replicated physiologic outcome measure in the tDCS literature. Of the 31 measures (gleaned from 145 studies), only 1 reached statistical significance: motor evoked potential (MEP) amplitude modulation. At the time of the analysis, no data had been generated exploring intra-subject reliability of this outcome. In my final study, I explored the effect of multiple identical tDCS sessions on MEP amplitude modulation within individuals. 14 participants each underwent 9 sessions of 10min tDCS (3 anodal, 3 cathodal, 3 sham). MEP amplitudes were measured prior to and for 30min following stimulation. Results demonstrated tDCS effects on MEP amplituted are highly variable within individuals across sessions. Group-wide analysis demonstrated no significant effect of tDCS on MEP amplitude compared to sham. Regression analysis demonstrated modulation of MEP amplitude may be explainable by regression-to-the-mean and non-experimental variables. Based on the experimental investigations conducted and the comprehensive reviews of the existing literature, there is currently insufficient evidence that tDCS produces a reliable effect. In the conclusion, I explore potential explanations for the current state of the tDCS literature and suggest future directions for this tool.
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    Cognitively relevant networks in Alzheimer's disease: the preferential contribution of amyloid-β and hyperphosphorylated tau
    Malpas, Charles Benjamin ( 2015)
    Alzheimer's disease (AD) is characterised by two cardinal pathologies, namely the extracellular accumulation amyloid-related aggregates, and the intracellular formation of tau-related neurofibrillary tangles. Both of these pathologies disrupt normal neuronal function, but develop according to different anatomical trajectories. While cerebral tau-pathology first forms in mesial temporal structures, amyloid-pathology first accumulates in neocortex. The eventual distribution of these pathologies reflects their origins. The mesial temporal structures are the most heavily affected by tau-pathology while amyloid-pathology is most prominently deposited in neocortical regions. This raises the possibility that the cardinal pathologies preferentially disrupt different brain networks, resulting in differential contributions to the cognitive expression of AD. The present inquiry aimed to clarify the relationship between the cardinal pathologies and the disruption of cognitively relevant networks. It was predicted that tau-pathology would preferentially disrupt mesial temporal networks associated with fundamental memory function. In contrast, it was expected that amyloid-pathology would be preferentially associated with neocortical, particularly anterior, networks associated with the executive functions. The first study investigated the preferential association hypothesis in 191 patients with mild cognitive impairment. As expected, CSF biomarkers of tau-pathology were most strongly associated with measures of memory function. The relationship between amyloid-pathology and memory was indirect, that is, mediated by tau-pathology. Amyloid-pathology had a separate, tau-independent, relationship with information processing speed. In the second study, the hypothesis was investigated in 39 patients with dementia of the Alzheimer's type using CSF biomarkers and functional connectivity analyses obtained from resting state functional magnetic resonance imaging. Tau-pathology was preferentially associated with functional connectivity in the mesial temporal regions. Amyloid-pathology was preferentially associated with functional connectivity in the dorsal anterior cingulate cortex, a region intimately connected to anterior neocortical structures. In the third study, the hypothesis was investigated in the same cohort using CSF biomarkers, structural magnetic resonance imaging, and fluorodeoxyglucose positron emission tomography (18F-FDG-PET). Amyloid-related pathology was preferentially related to the posterior cingulate and lateral temporal cortices, while no preferential relationships were found for tau-pathology. Taken together, these findings provide early support for the preferential effects of the cardinal pathologies. The results support the link between tau-pathology, mesial temporal structures, and fundamental memory impairment in AD. Less support was found for the association between amyloid-pathology, neocortical networks, and executive function. While amyloid-pathology was preferentially associated with structurofunctional changes in a number of neocortical regions, the predicted relationship with executive function was not strongly supported. The emerging view is that abnormal tau is a destructive, intracellular pathology with a proximal relationship to cognitive impairment in AD. In contrast, abnormal amyloid is a pan-cerebral, extracellular pathology that subtly disrupts diffusely represented networks. The present findings have implications for disease-modifying therapeutic trials in AD, arguing for the need to match neurocognitive and neuroimaging endpoints with the cardinal pathology being targeted by the treatment. Overall, this thesis opens up a new, and more complex, view of the cardinal pathologies and their relationship to cognitively relevant brain networks.
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    Assessing the relationship between executive function, coping, stress, depression, anxiety and quality of life in multiple sclerosis
    GRECH, LISA ( 2014)
    Background: Compared to healthy controls, people with multiple sclerosis (PwMS) use fewer adaptive and more maladaptive coping strategies when managing stressors and they experience higher rates of depression, anxiety and adjustment disorders. In addition, PwMS experience a high prevalence of cognitive impairment, including executive dysfunction, which has been linked to depression and anxiety. Aims: The current study examined the relationship between executive function, coping strategy use and psychosocial adjustment outcomes including stress, depression, anxiety and quality of life (QoL) in PwMS. The research assessed i) the ability of coping strategies and executive function to predict maladaptive and adaptive adjustment outcomes, and ii) the relationship between executive function and coping and whether there is a moderating and mediating relationship of different coping strategies between executive function and psychosocial adjustment in PwMS. Methods: Participants (N=107) with relapsing remitting or secondary progressive multiple sclerosis were administered tasks of executive function and completed self-report measures of stress, depression, anxiety, QoL and coping. Results: Consistent with expectations, stress, depression, anxiety and QoL were predicted by adaptive and maladaptive coping styles. Similarly, coping strategies, total coping and an adaptive coping index were predicted by tasks of executive function. Lower scores on tasks of executive function best predicted higher use of maladaptive strategies, but also adaptive strategies, while higher scores were limited in their ability to predict adaptive coping strategies. Tasks of executive function that most often predicted coping strategies included tasks of working memory, cognitive flexibility, information processing and attention. However, contrary to expectations, there was limited support for a relationship between tasks of executive function and psychosocial adjustment outcomes. An indirect relationship was found between executive function performance and adjustment through individual maladaptive coping strategies and adaptive coping strategies, as well as for an index of adaptive coping. Higher executive function performance was related to better adjustment via lower venting and behavioral disengagement, as well as higher scores on the adaptive coping index, whereas lower executive function performance was related to better adjustment via higher growth and acceptance. In general, better executive function and psychosocial adjustment was associated with minimal use of adaptive coping strategies, or greater use of maladaptive coping strategies. Conclusion: Executive function and psychosocial adjustment is mediated and moderated by coping strategies used by PwMS. Well-preserved executive function provides relative protection from poorer adjustment in the presence of high maladaptive or low adaptive coping. PwMS who perform poorly on tasks of executive function benefit from using less cognitively demanding coping strategies to enhance adjustment outcomes and this area that would benefit from further research to underpin effective intervention strategies. Findings from this study will assist with development of patient resources and patient management aimed at enhancing adaptive psychosocial adjustment in PwMS.
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    Neural correlates of attention in the context of prematurity
    McInnes, Andrea Louise ( 2014)
    This study aimed to examine attention outcomes in a high-risk very preterm (VPT; <30 weeks’ gestational age) and/or very low birth weight (VLBW; <1250 g) children at 7 years, and to assess whether brain abnormality measured by neonatal magnetic resonance imaging (MRI) can predict later adverse outcome within this domain. It also aimed to investigate whether the attention difficulties observed at 7 years were associated with abnormalities in the key white matter pathways associated with attention. A cohort of 198/224 VPT/VLBW children and 70/77 term controls were examined. Neonatal MRI scans performed at term-equivalent age were assessed for white matter, cortical grey matter, deep grey matter, and cerebellar abnormalities. Standardised neuropsychological tests of attention and MRI scans were conducted at 7 years. Diffusion tractography analyses were performed on the key white matter tracts associated with attention (the superior longitudinal fasciculi, the cingulum bundles, and the reticular activating system). At 7 years of age, the VPT/VLBW group performed significantly worse than term controls on all attention outcomes. Associations between higher neonatal brain abnormality scores and adverse attention performances at 7 years were found in the VPT group; in particular, white matter and deep grey matter abnormalities were reasonable predictors of long-term attention outcomes. Findings at 7 years also revealed altered microstructural organisation and reduced tract volume within the proposed attention tracts in the VPT children compared with the term controls and also that, such alterations were related to the adverse attention outcomes in VPT children. Attention is a significant area of concern in VPT/VLBW children. This is the first study to show that neonatal brain pathology may be used to predict, in conjunction with other known risk factors, which children may be at risk of later adverse attention outcomes. This study also highlights the importance of white matter tract integrity for the development of attention abilities in VPT children.
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    Memory functioning during the menopausal transition: subjective experience and objective performance
    UNKENSTEIN, ANNE ( 2013)
    Whilst many women complain of forgetfulness during the menopausal transition, few studies have provided a detailed examination of women’s beliefs about memory at this stage of their lives. Furthermore, prior studies have not included assessment of prospective or incidental memory, memory domains that may relate to the type of memory lapses that women describe. Therefore, this study aimed to examine women’s subjective perceptions of memory as well as their objective memory performance across the menopausal transition, including measures that have not been examined in previous studies. An additional aim was to explore relationships between subjective perceptions of memory and objective memory performance, menopausal symptoms and psychological factors during the perimenopausal stage. An improved understanding of the determinants of memory self-efficacy would allow for a more informed response to women’s concerns about memory, and potential enhancement of women’s well-being during this time of transition. One hundred and thirty women, aged 40 to 60, were recruited from outpatient menopause and gynaecological clinics at the Royal Women’s Hospital, Melbourne. Women were divided into pre- (n = 36), peri- (n = 54) and postmenopausal (n = 40) groups according to the STRAW+10 criteria based on menstrual patterns. All women completed self-report measures of physical menopause symptoms, symptoms of depression and anxiety, sleep quality and attitude towards menopause. Scales examining various aspects of memory were also administered, measuring reported frequency of common memory mistakes, sense of control over memory, use of memory strategies, memory contentment, knowledge and motivation to perform well on memory tasks. The women also completed a comprehensive neuropsychological evaluation of memory, assessing verbal learning and memory, attention and working memory, information processing speed, executive function, semantic, incidental and prospective memory. The results indicated that perimenopausal women felt less content with their memory and reported more frequent forgetfulness, despite performing at a similar level to their pre- and postmenopausal peers on a challenging and comprehensive neuropsychological assessment. This sense of dissatisfaction with memory was accompanied by a more negative attitude towards menopause, when compared to women who had experienced the transition to menopause, but the level of anxiety, depressive and sleep symptoms was similar across pre-, peri- and postmenopausal groups. Perimenopausal women who expressed a stronger sense of control over their memory function, and had lower expectations of their memory reported feeling more content with their memory. At the time of transition to menopause, perceptions of more frequent forgetting were associated with attentional capacity, and memory contentment was related to attitude towards menopause. Subjective memory in perimenopausal women was also associated with anxiety, depressive, vasomotor and sleep problems. The findings do not indicate a significant impact of the menopausal transition on memory function. Nevertheless, this does not diminish the potential adverse impact of perimenopausal women’s negative appraisals of memory on their quality of life. Modification of factors that have been shown to be related to perceived forgetfulness and memory contentment could improve memory self-efficacy at midlife and beyond.