The overall objective of this dissertation was to increase scientific understanding of brain reserve. Chapter 1 describes how brain reserve has come to be viewed in two distinct ways: differential expression of brain injury on the basis of individual differences in gross brain properties (neurological), or on the basis of lifespan patterns of complex mental activity (behavioural). Evidence in the Alzheimer???s disease and ageing literature has been extensive, yet with conflicting reports. In order to better evaluate this evidence, a systematic review of cohort studies is the focus of Chapter 2. Complex mental activity was found to be associated with reduced incidence of dementia and slowed rate of cognitive decline. Neurological brain reserve evidence was limited. A major task of this dissertation was to develop a more standard and complete behavioural brain reserve instrument. Chapter 3 relates the development of the Lifetime of Experiences Questionnaire (LEQ) in a group of 86 healthy elderly. The LEQ had adequate levels of internal consistency and reliability. In a validation test, higher LEQ scores were also found to predict attenuated cognitive decline over 18 months independent of covariates including premorbid IQ. Chapter 4 describes how both LEQ (as a measure of behavioural brain reserve) and intracranial volume (as a measure of neurological brain reserve) significantly predicted cognitive decline over three years in a sample of 70 aged subjects. Total LEQ was furthermore significantly correlated with hippocampal volume independent of intracranial volume, and this association mediated the relationship with cognitive decline. Behavioural brain reserve may therefore work by protecting individuals from hippocampal atrophy. The fifth chapter explores therapeutic and neurobiological aspects of behavioural brain reserve in a preliminary fashion. A randomized-control mental activity trial was run with 20 healthy elderly who received repeat magnetic resonance spectroscopy. Mental activity subjects were found to have selective and sustained upregulation of phosphocreatine metabolism in the hippocampal region, a finding of potential neuroprotective significance. Experience-dependent neuroplasticity is proposed as a unifying framework in the final chapter, allowing synthesis of the present findings and reconciliation of the neurological and behavioural approaches to brain reserve.

The overall objective of this dissertation was to increase scientific understanding of brain reserve. Chapter 1 describes how brain reserve has come to be viewed in two distinct ways: differential expression of brain injury on the basis of individual differences in gross brain properties (neurological), or on the basis of lifespan patterns of complex mental activity (behavioural). Evidence in the Alzheimer???s disease and ageing literature has been extensive, yet with conflicting reports. In order to better evaluate this evidence, a systematic review of cohort studies is the focus of Chapter 2. Complex mental activity was found to be associated with reduced incidence of dementia and slowed rate of cognitive decline. Neurological brain reserve evidence was limited. A major task of this dissertation was to develop a more standard and complete behavioural brain reserve instrument. Chapter 3 relates the development of the Lifetime of Experiences Questionnaire (LEQ) in a group of 86 healthy elderly. The LEQ had adequate levels of internal consistency and reliability. In a validation test, higher LEQ scores were also found to predict attenuated cognitive decline over 18 months independent of covariates including premorbid IQ. Chapter 4 describes how both LEQ (as a measure of behavioural brain reserve) and intracranial volume (as a measure of neurological brain reserve) significantly predicted cognitive decline over three years in a sample of 70 aged subjects. Total LEQ was furthermore significantly correlated with hippocampal volume independent of intracranial volume, and this association mediated the relationship with cognitive decline. Behavioural brain reserve may therefore work by protecting individuals from hippocampal atrophy. The fifth chapter explores therapeutic and neurobiological aspects of behavioural brain reserve in a preliminary fashion. A randomized-control mental activity trial was run with 20 healthy elderly who received repeat magnetic resonance spectroscopy. Mental activity subjects were found to have selective and sustained upregulation of phosphocreatine metabolism in the hippocampal region, a finding of potential neuroprotective significance. Experience-dependent neuroplasticity is proposed as a unifying framework in the final chapter, allowing synthesis of the present findings and reconciliation of the neurological and behavioural approaches to brain reserve.

The overall objective of this dissertation was to increase scientific understanding of brain reserve. Chapter 1 describes how brain reserve has come to be viewed in two distinct ways: differential expression of brain injury on the basis of individual differences in gross brain properties (neurological), or on the basis of lifespan patterns of complex mental activity (behavioural). Evidence in the Alzheimer???s disease and ageing literature has been extensive, yet with conflicting reports. In order to better evaluate this evidence, a systematic review of cohort studies is the focus of Chapter 2. Complex mental activity was found to be associated with reduced incidence of dementia and slowed rate of cognitive decline. Neurological brain reserve evidence was limited. A major task of this dissertation was to develop a more standard and complete behavioural brain reserve instrument. Chapter 3 relates the development of the Lifetime of Experiences Questionnaire (LEQ) in a group of 86 healthy elderly. The LEQ had adequate levels of internal consistency and reliability. In a validation test, higher LEQ scores were also found to predict attenuated cognitive decline over 18 months independent of covariates including premorbid IQ. Chapter 4 describes how both LEQ (as a measure of behavioural brain reserve) and intracranial volume (as a measure of neurological brain reserve) significantly predicted cognitive decline over three years in a sample of 70 aged subjects. Total LEQ was furthermore significantly correlated with hippocampal volume independent of intracranial volume, and this association mediated the relationship with cognitive decline. Behavioural brain reserve may therefore work by protecting individuals from hippocampal atrophy. The fifth chapter explores therapeutic and neurobiological aspects of behavioural brain reserve in a preliminary fashion. A randomized-control mental activity trial was run with 20 healthy elderly who received repeat magnetic resonance spectroscopy. Mental activity subjects were found to have selective and sustained upregulation of phosphocreatine metabolism in the hippocampal region, a finding of potential neuroprotective significance. Experience-dependent neuroplasticity is proposed as a unifying framework in the final chapter, allowing synthesis of the present findings and reconciliation of the neurological and behavioural approaches to brain reserve.

No description available.

In the present study, using both implicit and explicit measures, we addressed the issue of whether strongly developed relationships towards brands could be modified through the use of evaluative conditioning. Using an online survey, individual participant brand lists were created, and formed the basis of this experiment. Participants were then exposed to conditioning during a longitudinal study. Throughout the experiment, a combination of explicit and implicit measures was used to assess changes in attitude. Specifically, participants were asked to rate the brand names on a Likert-type scale. Simultaneously, changes in the brains electrical activity in response to the brands were recorded via electroencephalography (EEG). Upon completion of this task, participants underwent two Implicit Association Tests (IAT; one for liked brands and one for disliked brands). There were two main findings of this study. Firstly, no significant changes in attitude were observed via the use of explicit measures, and those that were found relating to the IAT were regarded as questionable. Secondly, EEG presented consistent results which showed that conditioning elicited changes in cortical activity towards both liked and disliked brands, which suggest it may be a useful tool in measuring the impact of evaluative conditioning that is not reflected in verbal responses.

University of Macau / Faculty of Health Sciences

Autism is a life-long neurodevelopmental condition. Autistic individuals have difficulties in communicative and social ability, and repetitive and stereotypic behavior. It has proposed that these symptoms are caused by underconnectivity in the autistic brain. Functional imaging studies have reported functional underconnectivity in autism. In this thesis, the structural connectivity of the autistic brain was studied. White matter contains axon fibers, which connect different cortical and subcortical brain regions. To measure the structural connectivity, Diffusion tensor imaging (DTI) was applied. Since water diffusion in axons inside the white matter is directional, by measuring the magnitude and direction of water diffusion in white matter, the structural integrity of white matter fibers could be estimated. In this thesis, the background of autism as a genetic, neurological and behavioral condition is outlined. The methods needed to acquire and analyze DTI data are illustrated. A meta-analysis on abnormalities found in autistic brain using DTI was conducted and the most consistently reported regions with DTI differences in autism compared to typically developing controls are described. The results of the metaanalysis were localized to white matter tracts likely to be involved, and the possible associations between anatomy and autistic behavioral features are discussed. Finally, a DTI tractography study was conducted in a sample but clinically representative sample of patients with ASD and eighteen major white matter tracts were explored. Underconnectivity in several tracts was identified. It is hoped that the findings reported here will enhance our understanding of widespread underconnectivity in autism. / published_or_final_version / Psychiatry / Master / Master of Philosophy

 Background and Objectives: ‘Neurodevelopmental disorders’ is often synonymously used with childhood developmental disorders such as autism spectrum disorder (ASD), however, increasingly new lines of evidence from genetics and epidemiology suggests having schizophrenia and bipolar disorder to be included as well. For example, there is a strong tendency for schizophrenia and bipolar disorder to occur in people with ASD and shared aetiological factors such as prenatal infection and maternal vitamin D deficiency during pregnancy have all been linked with increased risks in all three conditions. To investigate into this, I have turned to brain imaging, a technique which has opened up a new horizon for neurobiologists. Typically, neuroimaging studies focus on one disorder, matching patients with healthy volunteers and compare their brain structures volumetric differences. On the other hand, such studies are limited by various factors including small ample size, low power, no psychiatric control group, and sample or design heterogeneity. Methods: To summarize all the data into a more meaningful biological representation, Anatomical Likelihood Estimation (ALE), a cutting edge meta-analytic approach was applied. The rationale behind ALE is that it identifies brain differences most consistently reported across studies, while filtering away differences that are least documented. In this thesis, a novel application of ALE known as “dual disorder ALE” is introduced, which serves to estimate the extent of brain regional differences implicated in either disorder – in other words, a method to quantify which areas of the brain are more likely to be affected by ASD, schizophrenia or bipolar disorder. Findings: The analysis is separated into two parts. First, dual disorder ALE technique was applied to investigate the relationship between ASD and first-episode schizophrenia. Data from 25 MRI studies was extracted comprising 660 participants (308 ASD, 352 schizophrenia) and 801 healthy controls. In ASD and FE schizophrenia, there were similar brain differences near the limbic-striato-thalamic circuitry, and distinctive brain differences including amygdala, caudate, frontal and medial gyrus for schizophrenia and putamen for ASD. In the second part comparing bipolar disorder and schizophrenia, data from 651 schizophrenic patients, 540 bipolar patients, and 1438 healthy controls was used, and matched one-to-one by pairing up bipolar disorder studies with corresponding schizophrenia studies to minimize confounders. The ALE result indicated that there are substantial overlaps across the two disorders, with schizophrenia having more extensive brain differences than bipolar disorder. Conclusions: Both parts of the analysis suggest that there are similar aetiological pressures affecting neurodevelopmental disorders including ASD, schizophrenia and bipolar disorder. / published_or_final_version / Psychiatry / Master / Master of Philosophy

Volumetric analysis (VA) in magnetic resonance imaging (MRI) has provided great comprehension of the neuroanatomical changes associated to normal cognition and progression from mild cognitive impairment (MCI) to Alzheimer’s disease (AD), the most common form of dementia. However, the use of VA has primarily focused in gray matter changes; the emergence of diffusion tensor imaging (DTI) has allowed a better understanding of the microstructural changes in both white and gray matters in MCI and AD patients, with numerous studies showing DTI to be more sensitive than VA in discriminating between MCI to AD. Diffusion kurtosis imaging (DKI), an extension of DTI, is speculated to be more sensitive in detecting changes due to differences in mathematical modeling, as it accounts for non-Gaussian diffusion in the brain. Studies using DKI suggested kurtosis parameters—axial, radial, and mean kurtoses—are able to provide further microstructural details in additional information to tensor and diffusion parameters, namely axial, radial, and mean diffusivities, and fractional anisotropy. In this study, DKI is compared to DTI and VA in an attempt to evaluate the sensitivities of each technique. DKI of all four cerebral lobes and VA of the hippocampus were performed in 30 patients, 18 diagnosed with AD and 12 with MCI. Mann-Whitney U test was performed to determine differences between MCI and AD, and correlations between diffusion parameters and hippocampal volume to mini-mental state examination (MMSE) scores as a biomarker of cognitive function were tested using Pearson’s R correlation test. MMSE scores were statistically different between sexes (p = 0.025) and between MCI and AD groups (p = 0.048), as well as positively correlated with age (p = 0.004). A marginal trend was observed in the hippocampal volume between MCI and AD (p = 0.077), and did not significantly correlate with MMSE. Several diffusivity and kurtosis parameters were significantly different between MCI and AD groups in the white and gray matters of the parietal and occipital lobes. Only tensor parameters had significant negative correlations with MMSE scores in within-group analyses of the two lobes. Correlational tests of white and gray matters of all four lobes to MMSE scores revealed more significant correlations between tensor parameters than kurtosis parameters. Findings from the present study provide further evidence that diffusion MRI is a more sensitive technique than VA in the discrimination between MCI and AD. Results from this study also corroborate with another DKI study exploring diffusivity in neuroanatomical regions predominately composed of white matter in AD progression. While DKI provides additional information on the microstructural changes of white matter and gray matter during disease progression in the brain, whether DKI is superior to DTI requires further research. Diffusion MRI appears to be more advantageous when comparing cognitive function on a continuum like MMSE scores than segregated groups. / published_or_final_version / Diagnostic Radiology / Master / Master of Medical Sciences

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