Individuals With Amnesia are not Stuck in Time: Evidence From Risky Decision-Making, Intertemporal Choice, and Scaffolded Narratives

This dissertation investigates the supposition that individuals with amnesia are cognitively stuck in time. In Experiment 1, I used a Galton-Crovitz cueing paradigm to test etiologically diverse amnesic cases on their ability to richly recollect autobiographical episodic memories and imagine future experiences. In Experiment 2, I use two behavioural economics tasks (a risky decision-making task and an intertemporal choice task) to examine whether amnesic cases judgment and decision-making reflects proneness to risky choices or steep disregard for the future. In Experiment 3, I examine the flexibility of amnesics intertemporal choice by testing whether cueing them with personal future events increases their value of future rewards as it does in healthy controls. In Experiment 4, I attempt to decrease the severity of amnesic cases episodic memory and prospection impairment by using structured and personally meaningful cues rather than the single cue words featured in the Galton-Crovitz paradigm. I replicated existing research showing that those with MTL damage have impaired ability to (re)construct rich and detailed narratives of past and future experiences, and I extended this finding for the first time to a lateral dorsal thalamic stroke case (Experiment 1). Despite this impairment in mental time travel, the same amnesic cases made financial decisions that a) systematically considered and valued the future and b) showed normal sensitivity to risk (Experiment 2). The normalcy of intertemporal choice in amnesia extends beyond basic rates of future reward discounting in intertemporal choice. In controls, cues to imagine future experiences can modulate decision-making by increasing the value one places on future rewards. Here, most amnesic cases also retain this modulatory effect, despite having impaired ability to generate detailed representations of future experiences (Experiment 3). Finally, I found that the severity of episodic prospection impairment in MTL amnesia is cue-dependent and likely overestimated in current research: specific, personally meaningful cues lead to an appreciable reduction of episodic prospection impairment over single cue words for those with mild-moderate amnesia (Experiment 4). Collectively, results challenge assumptions that amnesic populations are cognitively confined to the present and call for refinement to simple accounts of limited temporality in individuals with amnesia

Audit of Antenatal Testing of Sexually Transmissible Infections and Blood Borne Viruses at Western Australian Hospitals

In August 2007, the Western Australian Department of Health (DOH) released updated recommendations for testing of sexually transmissible infections (STI) and blood-borne viruses (BBV) in antenates. Prior to this, the Royal Australian & New Zealand College of Obstetricians & Gynaecologists (RANZCOG) antenatal testing recommendations had been accepted practice in most antenatal settings. The RANZCOG recommends that testing for HIV, syphilis, hepatitis B and C be offered at the first antenatal visit. The DOH recommends that in addition, chlamydia testing be offered. We conducted a baseline audit of antenatal STI/BBV testing in women who delivered at selected public hospitals before the DOH recommendations. We examined the medical records of 200 women who had delivered before 1st July 2007 from each of the sevenWAhospitals included in the audit. STI and BBV testing information and demographic data were collected. Of the 1,409 women included, 1,205 (86%) were non-Aboriginal and 200 (14%) were Aboriginal. High proportions of women had been tested for HIV (76%), syphilis (86%), hepatitis C (87%) and hepatitis B (88%). Overall, 72% of women had undergone STI/BBV testing in accordance with RANZCOG recommendations. However, chlamydia testing was evident in only 18% of records. STI/BBV prevalence ranged from 3.9% (CI 1.5– 6.3%) for chlamydia, to 1.7% (CI 1–2.4%) for hepatitis C, 0.7% (CI 0.3–1.2) for hepatitis B and 0.6% (CI 0.2–1) for syphilis. Prior to the DOH recommendations, nearly three-quarters of antenates had undergone STI/BBV testing in accordance with RANZCOG recommendations, but less than one fifth had been tested for chlamydia. The DOH recommendations will be further promoted with the assistance of hospitals and other stakeholders. A future audit will be conducted to determine the proportion of women tested according to the DOH recommendations. The hand book from this conference is available for download Published in 2008 by the Australasian Society for HIV Medicine Inc © Australasian Society for HIV Medicine Inc 2008 ISBN: 978-1-920773-59-

A low-cost solution for documenting distribution and abundance of endangered marine fauna and impacts from fisheries

Fisheries bycatch is a widespread and serious issue that leads to declines of many important and threatened marine species. However, documenting the distribution, abundance, population trends and threats to sparse populations of marine species is often beyond the capacity of developing countries because such work is complex, time consuming and often extremely expensive. We have developed a flexible tool to document spatial distribution and population trends for dugongs and other marine species in the form of an interview questionnaire supported by a structured data upload sheet and a comprehensive project manual. Recognising the effort invested in getting interviewers to remote locations, the questionnaire is comprehensive, but low cost. The questionnaire has already been deployed in 18 countries across the Indo-Pacific region. Project teams spent an average of USD 5,000 per country and obtained large data sets on dugong distribution, trends, catch and bycatch, and threat overlaps. Findings indicated that >50% of respondents had never seen dugongs and that 20% had seen a single dugong in their lifetimes despite living and fishing in areas of known or suspected dugong habitat, suggesting that dugongs occurred in low numbers. Only 3% of respondents had seen mother and calf pairs, indicative of low reproductive output. Dugong hunting was still common in several countries. Gillnets and hook and line were the most common fishing gears, with the greatest mortality caused by gillnets. The questionnaire has also been used to study manatees in the Caribbean, coastal cetaceans along the eastern Gulf of Thailand and western Peninsular Malaysia, and river dolphins in Peru. This questionnaire is a powerful tool for studying distribution and relative abundance for marine species and fishery pressures, and determining potential conservation hotspot areas. We provide the questionnaire and supporting documents for open-access use by the scientific and conservation communities

Reviews and perspectives Individuals with episodic amnesia are not stuck in time

a b s t r a c t The metaphor that individuals with episodic amnesia due to hippocampal damage are "stuck in time" persists in science, philosophy, and everyday life despite mounting evidence that episodic amnesia can spare many central aspects of temporal consciousness. Here we describe some of this evidence, focusing specifically on KC, one of the most thoroughly documented and severe cases of episodic amnesia on record. KC understands the concept of time, knows that it passes, and can orient himself with respect to his personal past and future. He expresses typical attitudes toward his past and future, and he is able to make future-regarding decisions. Theories claiming that the hippocampus plays an essential role in temporal consciousness need to be revised in light of these findings

R-PEP-27, a Potent Renin Inhibitor, Decreases Plasma Angiotensin II and Blood Pressure in Normal Volunteers

The hemodynamic and humoral effects of the specific human renin inhibitor R-PEP-27 were studied in six normal human subjects on low and high sodium intake diets. An intravenous infusion of R-PEP-27 (0.5 to 16 μg/min/kg body wt) reduced blood pressure in a dose-dependent fashion; the mean arterial blood pressure at the end of the infusion fell from 128 ± 4/83 ± 4 to 119 ± 3/71 ± 3 mm Hg (mean ± SEM) (P < .01) during the low sodium intake diet. R-PEP-27 had no effect on blood pressure during the high sodium intake diet. R-PEP-27 significantly reduced plasma angiotensin II and aldosterone concentrations. The temporal response to R-PEP-27 suggests that it is a shortlived although highly potent competitive inhibitor of renin; this peptide is a valuable and specific physiologic probe of the renin-angiotensin system. Am J Hypertens 1994;7:295-30

Comparing Generic and Condition-Specific Preference-Based Measures in Epilepsy: EQ-5D-3L and NEWQOL-6D

Background: There is debate about the psychometric characteristics of the three-level EuroQol five-dimensional questionnaire (EQ-5D-3L) for use in epilepsy. In response to the concerns, an epilepsy-specific preference-based measure (NEWQOL-6D) was developed. The psychometric characteristics of the NEWQOL-6D, however, have not been assessed. Objectives: To investigate the validity and responsiveness of the EQ-5D-3L and the Quality of Life in Newly Diagnosed Epilepsy Instrument-six dimensions (NEWQOL-6D) for use in the assessment of treatments for newly diagnosed focal epilepsy. Methods: The analysis used data from the Standard And New Antiepileptic Drugs trial including patients with focal epilepsy. We assessed convergent validity using correlations, and known-group validity across different epilepsy and general health severity indicators using analysis of variance and effect sizes. The responsiveness of the measures to change over time was assessed using standardized response means. We also assessed agreement between the measures. Results: There was some level of convergence and agreement between the measures in terms of utility score but divergence in the concepts measured by the descriptive systems. Both instruments displayed known-group validity, with significant differences between severity groups, and generally slightly larger effect sizes for the NEWQOL-6D across the epilepsy-specific indicators. Evidence for responsiveness was less clear, with small to moderate standardized response means demonstrating different levels of change across different indicators. Conclusions: There was an overall tendency for the NEWQOL-6D to better reflect differences across groups, but this does not translate into large absolute utility differences. Both the EQ-5D-3L and the NEWQOL-6D show some evidence of validity for providing utility values for economic evaluations in newly diagnosed focal epilepsy

Cortical Thickness Estimation in Individuals With Cerebral Small Vessel Disease, Focal Atrophy, and Chronic Stroke Lesions

Background: Regional changes to cortical thickness in individuals with neurodegenerative and cerebrovascular diseases (CVD) can be estimated using specialized neuroimaging software. However, the presence of cerebral small vessel disease, focal atrophy, and cortico-subcortical stroke lesions, pose significant challenges that increase the likelihood of misclassification errors and segmentation failures. Purpose: The main goal of this study was to examine a correction procedure developed for enhancing FreeSurfer’s (FS’s) cortical thickness estimation tool, particularly when applied to the most challenging MRI obtained from participants with chronic stroke and CVD, with varying degrees of neurovascular lesions and brain atrophy. Methods: In 155 CVD participants enrolled in the Ontario Neurodegenerative Disease Research Initiative (ONDRI), FS outputs were compared between a fully automated, unmodified procedure and a corrected procedure that accounted for potential sources of error due to atrophy and neurovascular lesions. Quality control (QC) measures were obtained from both procedures. Association between cortical thickness and global cognitive status as assessed by the Montreal Cognitive Assessment (MoCA) score was also investigated from both procedures. Results: Corrected procedures increased “Acceptable” QC ratings from 18 to 76% for the cortical ribbon and from 38 to 92% for tissue segmentation. Corrected procedures reduced “Fail” ratings from 11 to 0% for the cortical ribbon and 62 to 8% for tissue segmentation. FS-based segmentation of T1-weighted white matter hypointensities were significantly greater in the corrected procedure (5.8 mL vs. 15.9 mL, p \u3c 0.001). The unmodified procedure yielded no significant associations with global cognitive status, whereas the corrected procedure yielded positive associations between MoCA total score and clusters of cortical thickness in the left superior parietal (p = 0.018) and left insula (p = 0.04) regions. Further analyses with the corrected cortical thickness results and MoCA subscores showed a positive association between left superior parietal cortical thickness and Attention (p \u3c 0.001). Conclusion: These findings suggest that correction procedures which account for brain atrophy and neurovascular lesions can significantly improve FS’s segmentation results and reduce failure rates, thus maximizing power by preventing the loss of our important study participants. Future work will examine relationships between cortical thickness, cerebral small vessel disease, and cognitive dysfunction due to neurodegenerative disease in the ONDRI study

Improved Segmentation of the Intracranial and Ventricular Volumes in Populations with Cerebrovascular Lesions and Atrophy Using 3D CNNs

Successful segmentation of the total intracranial vault (ICV) and ventricles is of critical importance when studying neurodegeneration through neuroimaging. We present iCVMapper and VentMapper, robust algorithms that use a convolutional neural network (CNN) to segment the ICV and ventricles from both single and multi-contrast MRI data. Our models were trained on a large dataset from two multi-site studies (N = 528 subjects for ICV, N = 501 for ventricular segmentation) consisting of older adults with varying degrees of cerebrovascular lesions and atrophy, which pose significant challenges for most segmentation approaches. The models were tested on 238 participants, including subjects with vascular cognitive impairment and high white matter hyperintensity burden. Two of the three test sets came from studies not used in the training dataset. We assessed our algorithms relative to four state-of-the-art ICV extraction methods (MONSTR, BET, Deep Extraction, FreeSurfer, DeepMedic), as well as two ventricular segmentation tools (FreeSurfer, DeepMedic). Our multi-contrast models outperformed other methods across many of the evaluation metrics, with average Dice coefficients of 0.98 and 0.96 for ICV and ventricular segmentation respectively. Both models were also the most time efficient, segmenting the structures in orders of magnitude faster than some of the other available methods. Our networks showed an increased accuracy with the use of a conditional random field (CRF) as a post-processing step. We further validated both segmentation models, highlighting their robustness to images with lower resolution and signal-to-noise ratio, compared to tested techniques. The pipeline and models are available at: https://icvmapp3r.readthedocs.io and https://ventmapp3r.readthedocs.io to enable further investigation of the roles of ICV and ventricles in relation to normal aging and neurodegeneration in large multi-site studies

Investigating the contribution of white matter hyperintensities and cortical thickness to empathy in neurodegenerative and cerebrovascular diseases

Change in empathy is an increasingly recognised symptom of neurodegenerative diseases and contributes to caregiver burden and patient distress. Empathy impairment has been associated with brain atrophy but its relationship to white matter hyperintensities (WMH) is unknown. We aimed to investigate the relationships amongst WMH, brain atrophy, and empathy deficits in neurodegenerative and cerebrovascular diseases. Five hundred thirteen participants with Alzheimer’s disease/mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia (FTD), Parkinson’s disease, or cerebrovascular disease (CVD) were included. Empathy was assessed using the Interpersonal Reactivity Index. WMH were measured using a semi-automatic segmentation and FreeSurfer was used to measure cortical thickness. A heterogeneous pattern of cortical thinning was found between groups, with FTD showing thinning in frontotemporal regions and CVD in left superior parietal, left insula, and left postcentral. Results from both univariate and multivariate analyses revealed that several variables were associated with empathy, particularly cortical thickness in the fronto-insulo-temporal and cingulate regions, sex (female), global cognition, and right parietal and occipital WMH. Our results suggest that cortical atrophy and WMH may be associated with empathy deficits in neurodegenerative and cerebrovascular diseases. Future work should consider investigating the longitudinal effects of WMH and atrophy on empathy deficits in neurodegenerative and cerebrovascular diseases

Comparison of Pandemic (H1N1) 2009 and Seasonal Influenza, Western Australia, 2009

TOC summary: Infections were similar in terms of symptoms, risk factors, and proportion of patients hospitalized