Cognitive and neural mechanisms of sense of self in neurodegenerative disorders

The ability to maintain a coherent and continuous ‘sense of self’ is a fundamental component of being human, enabling us to interact and function successfully in everyday life. While a sense of self is commonly accepted to involve both ‘extended’ (i.e., memories) and ‘interpersonal’ (i.e., social) elements, the precise cognitive and neural mechanisms underlying these aspects of the self remain poorly understood. This thesis draws upon theory and methods from contemporary cognitive neuroscience to examine the neurocognitive underpinnings of the extended and interpersonal self in Alzheimer’s disease (AD), semantic dementia (SD), and the behavioural variant of frontotemporal dementia (bvFTD): neurodegenerative disorders involving progressive cognitive and behavioural change as the result of degeneration to distinct brain networks. Employing a novel experimental method (the ‘NExt’ taxonomy), Part 1 of the thesis (Chapters 3 and 4) reveals how a full spectrum of episodic and semantic memory representations may be drawn upon to support one’s past and future life stories, giving rise to a sense of continuity of the extended self. Part 2 (Chapters 5 and 6) illustrates how the complex social interactions that comprise the interpersonal self may be deconstructed into several distinct, yet interacting, psychological components. Furthermore, neuroimaging analyses uncover widespread neural regions to be associated with both the extended and interpersonal aspects of the self, incorporating brain networks beyond those typically implicated in self-related processing. The improved neurocognitive characterisation of the self provided by this thesis highlights the complex, multifaceted nature of this construct. Moreover, from a clinical perspective, distinct profiles of the self unveiled across AD, SD, and bvFTD reveal how ultimately, ‘all is not lost’ in neurodegeneration

Student and teacher perceptions of a season of sport education in a regional primary school

An interpretive case study approach was employed to examine student and teacher perceptions of the implementation of a sport education in physical education program (SEPEP) in a Western Australian regional primary school. Choi’s (1992) curriculum dimensions were used as a framework. Three year seven teachers implemented SEPEP using a team teaching approach. The focus teacher, Ms Jenson, a highly regarded classroom teacher, described herself as non-sporty and lacking confidence and expertise in PE teaching. Students in her SEPEP volleyball class were considered less popular and less athletic when compared with those in the other two SEPEP classes. A focus volleyball team comprising five girls and a boy of varying sporting interests and abilities were targeted to determine student perceptions of the program. Both the students and the teachers were positive in their overall thoughts and feelings about SEPEP. Greater enjoyment of PE classes, improved range and level of learning outcomes and liking of the student-centred structure of the program were reported

Perceptions and needs of rural young people in the south-west of Western Australia : Implications for pedagogy

The original purpose of this study was to investigate youth needs, specifically in the south western region (the \u27South West\u27) of Western Australia, and then to explore how these needs might be addressed in terms of current curriculum and teaching practices. The following research questions guided our investigation: - What are the educational and occupational aspirations of young people from the South West of Western Australia? - What do young people identify as influences on their educational and occupational aspirations and attainment? As the data collection progressed, it was evident to all those involved that, whilst there were expressed needs, many of the young people we interviewed were quite happy with their lives and their lifestyle, despite having varied views of their school experiences (curriculum and teachers), some positive and some negative. The students were able to offer some very thoughtful and clear descriptions of what sorts of things work for them at school, what does not work, and what needs to happen to make school meaningful and relevant to their lives and needs. The title of this report reflects this finding -describing the perceptions as well as the needs of this age group

Neurocognitive mechanisms of theory of mind impairment in neurodegeneration: a transdiagnostic approach

Much of human interaction is predicated upon our innate capacity to infer the thoughts, beliefs, emotions, and perspectives of others, in short, to possess a “theory of mind” (ToM). While the term has evolved considerably since its inception, ToM encompasses our unique ability to apprehend the mental states of others, enabling us to anticipate and predict subsequent behavior. From a developmental perspective, ToM has been a topic of keen research interest, with numerous studies seeking to explicate the origins of this fundamental capacity and its disruption in developmental disorders such as autism. The study of ToM at the opposite end of the lifespan, however, is paradoxically new born, emerging as a topic of interest in its own right comparatively recently. Here, we consider the unique insights afforded by studying ToM capacity in neurodegenerative disorders. Arguing from a novel, transdiagnostic perspective, we consider how ToM vulnerability reflects the progressive degradation of neural circuits special- ized for an array of higher-order cognitive processes. This mechanistic approach enables us to consider the common and unique neurocognitive mechanisms that underpin ToM dysfunction across neurodegenerative disorders and for the first time examine its relation to behavioral disturbances across social, intimate, legal, and criminal settings. As such, we aim to provide a comprehensive overview of ToM research in neurodegeneration, the resultant challenges for family members, clinicians, and the legal profession, and future directions worthy of exploration

Trait Mindfulness Is Associated With Less Amyloid, Tau, and Cognitive Decline in Individuals at Risk for Alzheimer's Disease

BACKGROUND: Mindfulness, defined as nonjudgmental awareness of the present moment, has been associated with an array of mental and physical health benefits. Mindfulness may also represent a protective factor for Alzheimer's disease (AD). Here, we tested the potential protective effect of trait mindfulness on cognitive decline and AD pathology in older adults at risk for AD dementia. METHODS: Measures of trait mindfulness, longitudinal cognitive assessments, and amyloid-β (Aβ) and tau positron emission tomography scans were collected in 261 nondemented older adults with a family history of AD dementia from the PREVENT-AD (Pre-symptomatic Evaluation of Experimental or Novel Treatments for AD) observational cohort study. Multivariate partial least squares analyses were used to examine relationships between combinations of different facets of trait mindfulness and 1) cognitive decline, 2) Aβ, and 3) tau. RESULTS: Higher levels of mindful nonjudgment, describing, and nonreactivity were associated with less cognitive decline in attention, global cognition, and immediate and delayed memory. Higher levels of mindful nonjudgment and nonreactivity were related to less Aβ positron emission tomography signal in bilateral medial and lateral temporoparietal and frontal regions. Higher levels of mindful acting with awareness, describing, nonjudgment, and nonreactivity were associated with less tau positron emission tomography signal in bilateral medial and lateral temporal regions. CONCLUSIONS: Trait mindfulness was associated with less cognitive decline and less Aβ and tau in the brain in older adults at risk for AD dementia. Longitudinal studies examining the temporal relationship between trait mindfulness and AD markers, along with mindfulness intervention studies, will be important for further clarifying the potential protective benefits of mindfulness on AD risk

An efficient method for the incompressible Navier-Stokes equations on irregular domains with no-slip boundary conditions, high order up to the boundary

Common efficient schemes for the incompressible Navier-Stokes equations, such as projection or fractional step methods, have limited temporal accuracy as a result of matrix splitting errors, or introduce errors near the domain boundaries (which destroy uniform convergence to the solution). In this paper we recast the incompressible (constant density) Navier-Stokes equations (with the velocity prescribed at the boundary) as an equivalent system, for the primary variables velocity and pressure. We do this in the usual way away from the boundaries, by replacing the incompressibility condition on the velocity by a Poisson equation for the pressure. The key difference from the usual approaches occurs at the boundaries, where we use boundary conditions that unequivocally allow the pressure to be recovered from knowledge of the velocity at any fixed time. This avoids the common difficulty of an, apparently, over-determined Poisson problem. Since in this alternative formulation the pressure can be accurately and efficiently recovered from the velocity, the recast equations are ideal for numerical marching methods. The new system can be discretized using a variety of methods, in principle to any desired order of accuracy. In this work we illustrate the approach with a 2-D second order finite difference scheme on a Cartesian grid, and devise an algorithm to solve the equations on domains with curved (non-conforming) boundaries, including a case with a non-trivial topology (a circular obstruction inside the domain). This algorithm achieves second order accuracy (in L-infinity), for both the velocity and the pressure. The scheme has a natural extension to 3-D.Comment: 50 pages, 14 figure

Longitudinal blood biomarker trajectories in preclinical Alzheimer's disease

INTRODUCTION: Plasma biomarkers are altered years prior to Alzheimer's disease (AD) clinical onset. METHODS: We measured longitudinal changes in plasma amyloid-beta (Aβ)42/40 ratio, pTau181, pTau231, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) in a cohort of older adults at risk of AD (n = 373 total, n = 229 with Aβ and tau positron emission tomography [PET] scans) considering genetic and demographic factors as possible modifiers of these markers' progression. RESULTS: Aβ42/40 ratio concentrations decreased, while NfL and GFAP values increased over the 4-year follow-up. Apolipoprotein E (APOE) ε4 carriers showed faster increase in plasma pTau181 than non-carriers. Older individuals showed a faster increase in plasma NfL, and females showed a faster increase in plasma GFAP values. In the PET subsample, individuals both Aβ-PET and tau-PET positive showed faster plasma pTau181 and GFAP increase compared to PET-negative individuals. DISCUSSION: Plasma markers can track biological change over time, with plasma pTau181 and GFAP markers showing longitudinal change in individuals with preclinical AD. HIGHLIGHTS: Longitudinal increase of plasma pTau181 and glial fibrillary acidic protein (GFAP) can be measured in the preclinical phase of AD. Apolipoprotein E ε4 carriers experience faster increase in plasma pTau181 over time than non-carriers. Female sex showed accelerated increase in plasma GFAP over time compared to males. Aβ42/40 and pTau231 values are already abnormal at baseline in individuals with both amyloid and tau PET burden

The role of ETG modes in JET-ILW pedestals with varying levels of power and fuelling

We present the results of GENE gyrokinetic calculations based on a series of JET-ITER-like-wall (ILW) type I ELMy H-mode discharges operating with similar experimental inputs but at different levels of power and gas fuelling. We show that turbulence due to electron-temperature-gradient (ETGs) modes produces a significant amount of heat flux in four JET-ILW discharges, and, when combined with neoclassical simulations, is able to reproduce the experimental heat flux for the two low gas pulses. The simulations plausibly reproduce the high-gas heat fluxes as well, although power balance analysis is complicated by short ELM cycles. By independently varying the normalised temperature gradients (omega(T)(e)) and normalised density gradients (omega(ne )) around their experimental values, we demonstrate that it is the ratio of these two quantities eta(e) = omega(Te)/omega(ne) that determines the location of the peak in the ETG growth rate and heat flux spectra. The heat flux increases rapidly as eta(e) increases above the experimental point, suggesting that ETGs limit the temperature gradient in these pulses. When quantities are normalised using the minor radius, only increases in omega(Te) produce appreciable increases in the ETG growth rates, as well as the largest increases in turbulent heat flux which follow scalings similar to that of critical balance theory. However, when the heat flux is normalised to the electron gyro-Bohm heat flux using the temperature gradient scale length L-Te, it follows a linear trend in correspondence with previous work by different authors

Spectroscopic camera analysis of the roles of molecularly assisted reaction chains during detachment in JET L-mode plasmas

The roles of the molecularly assisted ionization (MAI), recombination (MAR) and dissociation (MAD) reaction chains with respect to the purely atomic ionization and recombination processes were studied experimentally during detachment in low-confinement mode (L-mode) plasmas in JET with the help of experimentally inferred divertor plasma and neutral conditions, extracted previously from filtered camera observations of deuterium Balmer emission, and the reaction coefficients provided by the ADAS, AMJUEL and H2VIBR atomic and molecular databases. The direct contribution of MAI and MAR in the outer divertor particle balance was found to be inferior to the electron-atom ionization (EAI) and electron-ion recombination (EIR). Near the outer strike point, a strong atom source due to the D+2-driven MAD was, however, observed to correlate with the onset of detachment at outer strike point temperatures of Te,osp = 0.9-2.0 eV via increased plasma-neutral interactions before the increasing dominance of EIR at Te,osp < 0.9 eV, followed by increasing degree of detachment. The analysis was supported by predictions from EDGE2D-EIRENE simulations which were in qualitative agreement with the experimental observations