Michael Valenzuela

University of Sydney, Sydney, New South Wales, Australia

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Publications (119)612.32 Total impact

  • Amit Lampit · Shantel L Duffy · Michael Valenzuela
    Physical Exercise Interventions for Mental Health, Edited by Linda Lam, Michelle Riba, 01/2016: chapter 10; Cambridge University Press., ISBN: 9781107097094
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    ABSTRACT: During evolution a unique anterior-posterior flexure posited the canine dentate gyrus in two distinct dorsal and ventral positions. We therefore sought to explore neurogenesis and neurogenic cell-related difference along the canine hippocampal dorsal-ventral axis. Post mortem histological analysis revealed 49.1% greater doublecortin (DCX)-positive cells and a 158.5% greater percentage of double labeled DCX-positive/neuronal nuclei (NeuN) positive cells in the dorsal subgranular zone compared to the ventral. We then show neural precursor cells isolated from fresh hippocampal tissue are capable of proliferating long term, and after differentiation, express neuronal and glial markers. Dorsal hippocampal isolates produced a 120.0% higher frequency of sphere-forming neural precursor cells compared to ventral hippocampal tissue. Histological DCX and neurosphere assay results were highly correlated. Overall, we provide the first evidence that the dorsal canine hippocampus has a markedly higher rate of adult neurogenesis than the ventral hippocampus, possibly related to a greater frequency of contributory neural precursor cells. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Neuroscience Letters 03/2015; 593. DOI:10.1016/j.neulet.2015.03.017 · 2.06 Impact Factor
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    Amit Lampit · Harry Hallock · Chao Suo · Sharon L Naismith · Michael Valenzuela
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    ABSTRACT: Computerized cognitive training (CCT) is a safe and inexpensive intervention to enhance cognitive performance in the elderly. However, the neural underpinning of CCT-induced effects and the timecourse by which such neural changes occur are unknown. Here, we report on results from a pilot study of healthy older adults who underwent three 1-h weekly sessions of either multidomain CCT program (n = 7) or an active control intervention (n = 5) over 12 weeks. Multimodal magnetic resonance imaging (MRI) scans and cognitive assessments were performed at baseline and after 9 and 36 h of training. Voxel-based structural analysis revealed a significant Group × Time interaction in the right post-central gyrus indicating increased gray matter density in the CCT group compared to active control at both follow-ups. Across the entire sample, there were significant positive correlations between changes in the post-central gyrus and change in global cognition after 36 h of training. A post-hoc vertex-based analysis found a significant between-group difference in rate of thickness change between baseline and post-training in the left fusiform gyrus, as well as a large cluster in the right parietal lobe covering the supramarginal and post-central gyri. Resting-state functional connectivity between the posterior cingulate and the superior frontal gyrus, and between the right hippocampus and the superior temporal gyrus significantly differed between the two groups after 9 h of training and correlated with cognitive change post-training. No significant interactions were found for any of the spectroscopy and diffusion tensor imaging data. Though preliminary, our results suggest that functional change may precede structural and cognitive change, and that about one-half of the structural change occurs within the first 9 h of training. Future studies are required to determine the role of these brain changes in the mechanisms underlying CCT-induced cognitive effects.
    Frontiers in Aging Neuroscience 03/2015; 7(14). DOI:10.3389/fnagi.2015.00014 · 2.84 Impact Factor
  • Brain Stimulation 03/2015; 8(2):424-425. DOI:10.1016/j.brs.2015.01.354 · 5.43 Impact Factor
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    ABSTRACT: Functional compensation in late life is poorly understood but may be vital to understanding long-term cognitive trajectories. To study this we first established an empirically-derived threshold to distinguish hippocampal atrophy in those with Mild Cognitive Impairment (MCI n=34) from those with proficient cognition (PRO n=22), using data from a population-based cohort. Next, to identify compensatory networks we compared cortical activity patterns during a graded spatial working memory (SWM) task in only cognitively proficient individuals, either with (PROATR ) or without hippocampal atrophy (PRONIL ). Multivariate Partial Least Squares analyses revealed that these groups engaged spatially distinct SWM-related networks. In those with hippocampal atrophy and under conditions of basic-SWM demand, expression of a posterior compensatory network (PCN) comprised of calcarine and posterior parietal cortex strongly correlated with superior SWM performance (r=-0.96). In these individuals, basic level SWM response times were faster and no less accurate than in those with no hippocampal atrophy. Cognitively proficient older individuals with hippocampal atrophy may therefore uniquely engage posterior brain areas when performing simple spatial working memory tasks. This article is protected by copyright. All rights reserved. © 2014 Wiley Periodicals, Inc.
    Hippocampus 02/2015; 25(5). DOI:10.1002/hipo.22395 · 4.30 Impact Factor
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    Amit Lampit · Harry Hallock · Michael Valenzuela
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    ABSTRACT: New effective interventions to attenuate age-related cognitive decline are a global priority. Computerized cognitive training (CCT) is believed to be safe and can be inexpensive, but neither its efficacy in enhancing cognitive performance in healthy older adults nor the impact of design factors on such efficacy has been systematically analyzed. Our aim therefore was to quantitatively assess whether CCT programs can enhance cognition in healthy older adults, discriminate responsive from nonresponsive cognitive domains, and identify the most salient design factors. We systematically searched Medline, Embase, and PsycINFO for relevant studies from the databases' inception to 9 July 2014. Eligible studies were randomized controlled trials investigating the effects of ≥4 h of CCT on performance in neuropsychological tests in older adults without dementia or other cognitive impairment. Fifty-two studies encompassing 4,885 participants were eligible. Intervention designs varied considerably, but after removal of one outlier, heterogeneity across studies was small (I2 = 29.92%). There was no systematic evidence of publication bias. The overall effect size (Hedges' g, random effects model) for CCT versus control was small and statistically significant, g = 0.22 (95% CI 0.15 to 0.29). Small to moderate effect sizes were found for nonverbal memory, g = 0.24 (95% CI 0.09 to 0.38); verbal memory, g = 0.08 (95% CI 0.01 to 0.15); working memory (WM), g = 0.22 (95% CI 0.09 to 0.35); processing speed, g = 0.31 (95% CI 0.11 to 0.50); and visuospatial skills, g = 0.30 (95% CI 0.07 to 0.54). No significant effects were found for executive functions and attention. Moderator analyses revealed that home-based administration was ineffective compared to group-based training, and that more than three training sessions per week was ineffective versus three or fewer. There was no evidence for the effectiveness of WM training, and only weak evidence for sessions less than 30 min. These results are limited to healthy older adults, and do not address the durability of training effects. CCT is modestly effective at improving cognitive performance in healthy older adults, but efficacy varies across cognitive domains and is largely determined by design choices. Unsupervised at-home training and training more than three times per week are specifically ineffective. Further research is required to enhance efficacy of the intervention. Please see later in the article for the Editors' Summary.
    PLoS Medicine 11/2014; 11(11):e1001756. DOI:10.1371/journal.pmed.1001756 · 14.00 Impact Factor
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    ABSTRACT: Background Mild cognitive impairment (MCI) increases dementia risk with no pharmacologic treatment available. Methods The Study of Mental and Resistance Training was a randomized, double-blind, double-sham controlled trial of adults with MCI. Participants were randomized to 2 supervised interventions: active or sham physical training (high intensity progressive resistance training vs seated calisthenics) plus active or sham cognitive training (computerized, multidomain cognitive training vs watching videos/quizzes), 2–3 days/week for 6 months with 18-month follow-up. Primary outcomes were global cognitive function (Alzheimer's Disease Assessment Scale-cognitive subscale; ADAS-Cog) and functional independence (Bayer Activities of Daily Living). Secondary outcomes included executive function, memory, and speed/attention tests, and cognitive domain scores. Results One hundred adults with MCI [70.1 (6.7) years; 68% women] were enrolled and analyzed. Resistance training significantly improved the primary outcome ADAS-Cog; [relative effect size (95% confidence interval) −0.33 (−0.73, 0.06); P < .05] at 6 months and executive function (Wechsler Adult Intelligence Scale Matrices; P = .016) across 18 months. Normal ADAS-Cog scores occurred in 48% (24/49) after resistance training vs 27% (14/51) without resistance training [P < .03; odds ratio (95% confidence interval) 3.50 (1.18, 10.48)]. Cognitive training only attenuated decline in Memory Domain at 6 months (P < .02). Resistance training 18-month benefit was 74% higher (P = .02) for Executive Domain compared with combined training [z-score change = 0.42 (0.22, 0.63) resistance training vs 0.11 (−0.60, 0.28) combined] and 48% higher (P < .04) for Global Domain [z-score change = .0.45 (0.29, 0.61) resistance training vs 0.23 (0.10, 0.36) combined]. Conclusions Resistance training significantly improved global cognitive function, with maintenance of executive and global benefits over 18 months.
    Journal of the American Medical Directors Association 10/2014; 15(12). DOI:10.1016/j.jamda.2014.09.010 · 4.78 Impact Factor
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    ABSTRACT: Domestic dogs have become a model organism for studying the extent and consequences of morphological diversity, especially in the skull. It has been demonstrated that Cephalic Index (CI, skull width/skull length) correlates with central concentration of ganglion cells in the retina and with ventral rotation of the cerebral hemispheres. These changes may be reflected in the behaviour of breeds with different skulls shapes. This study explored skull variation in the breed groups (n=7) described by the Australian National Kennel Club (ANKC) to determine if CI differed significantly among the breed groups; groups were expected to differ not least in behaviour. The CI of 12 representative dogs (females, n=6; males, n=6) of the most popular breeds (n=80; total n=960 dogs) were measured. Multivariate analysis of variance was performed to determine CI variance among the breed groups and between previously reported clusters of breeds with similar DNA, which identifies common ancestry. While CI differed significantly among some breed groups, neither the breed groupings nor the DNA clusters satisfactorily explained all the variance in CI. The results show that breed groupings and genetic clusters only partially explain CI differences. They also suggest that CI is on a continuum and that the definition of three categories of canine skull as dolichocephalic, mesocephalic and brachycephalic may be overly arbitrary.
    Journal of Veterinary Behavior Clinical Applications and Research 09/2014; 9(5). DOI:10.1016/j.jveb.2014.04.007 · 1.22 Impact Factor
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    Amit Lampit · Claus Ebster · Michael Valenzuela
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    ABSTRACT: Cognitive skills are important predictors of job performance, but the extent to which computerized cognitive training (CCT) can improve job performance in healthy adults is unclear. We report, for the first time, that a CCT program aimed at attention, memory, reasoning and visuo-spatial abilities can enhance productivity in healthy younger adults on bookkeeping tasks with high relevance to real-world job performance. 44 business students (77.3% female, mean age 21.4 ± 2.6 years) were assigned to either (a) 20 h of CCT, or (b) 20 h of computerized arithmetic training (active control) by a matched sampling procedure. Both interventions were conducted over a period of 6 weeks, 3-4 1-h sessions per week. Transfer of skills to performance on a 60-min paper-based bookkeeping task was measured at three time points-baseline, after 10 h and after 20 h of training. Repeated measures ANOVA found a significant Group X Time effect on productivity (F = 7.033, df = 1.745; 73.273, p = 0.003) with a significant interaction at both the 10-h (Relative Cohen's effect size = 0.38, p = 0.014) and 20-h time points (Relative Cohen's effect size = 0.40, p = 0.003). No significant effects were found on accuracy or on Conners' Continuous Performance Test, a measure of sustained attention. The results are discussed in reference to previous findings on the relationship between brain plasticity and job performance. Generalization of results requires further study.
    Frontiers in Psychology 07/2014; 5:794. DOI:10.3389/fpsyg.2014.00794 · 2.80 Impact Factor
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    ABSTRACT: The purpose of this descriptive correlational study was to explore potential gender differences in the relationship of dementia severity, age, APOE status, cognitive reserve and co-morbidity, (two potentially modifiable factors), to delirium severity in older adults. Baseline data from an ongoing clinical trial and a Poisson regression procedure were used in the analyses. Participants were 148 elderly individuals with dementia and delirium admitted to post-acute care. In women, delirium severity was related to dementia severity (p = 0.002) and co-morbidity moderated that effect (p = 0.03). In men, education was marginally associated with delirium severity (p = 0.06). Implications for research are discussed.
    Archives of Psychiatric Nursing 06/2014; 28(3). DOI:10.1016/j.apnu.2014.01.004 · 1.03 Impact Factor
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    ABSTRACT: Background: Home-based computerised cognitive training (CCT) is ineffective at enhancing global cognition, a key marker of cognitive ageing. Objectives: To test the effectiveness of supervised, group-based, multidomain CCT on global cognition in older adults and to characterise the dose-response relationship during and after training. Design: A randomised, double-blind, longitudinal, active-controlled trial. Setting: Community-based training centre in Sydney, Australia Participants: Eighty nondemented community-dwelling older adults (mean age = 72.1, 68.8% females) with multiple dementia risk factors but no major neuropsychiatric or sensory disorder. Of the 80 participants admitted to the study, 65 completed post-training assessment and 55 were followed up one year after training cessation. Interventions: Thirty-six group-based sessions over three months of either CCT targeting memory, speed, attention, language and reasoning tasks, or active control training comprising audiovisual educational exercises. Measurements: Primary outcome was change from baseline in global cognition as defined by a composite score of memory, speed and executive function. Secondary outcome was 15-month change in Bayer Activities of Daily Living from baseline to one year post-training. Results: Intention-to-treat analyses revealed significant effects on global cognition in the cognitive training group compared to active control after three weeks of training (ES = 0.33, P=.039) that increased after 3 months of training (ES = 0.49, P=.003) and persisted three months after training cessation (ES = 0.30, P=0.023). Significant and durable improvements were also noted in memory and processing speed. Dose-response characteristics differed among cognitive domains. Training effects waned gradually but residual gains were noted twelve months post-training. No significant effects on activities of daily living were noted and there were no adverse effects. Conclusions: In older adults with multiple dementia risk factors, group-based CCT is a safe and effective intervention for enhancing overall cognition, memory and processing speed. Dose-response relationships vary for each cognitive domain, vital information for clinical and community implementation and further trial design.
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    ABSTRACT: Objectives Cognitive impairments associated with aging and dementia are major sources of burden, deterioration in life quality, and reduced psychological well-being (PWB). Preventative measures to both reduce incident disease and improve PWB in those afflicted are increasingly targeting individuals with mild cognitive impairment (MCI) at early disease stage. However, there is very limited information regarding the relationships between early cognitive changes and memory concern, and life quality and PWB in adults with MCI; furthermore, PWB outcomes are too commonly overlooked in intervention trials. The purpose of this study was therefore to empirically test a theoretical model of PWB in MCI in order to inform clinical intervention. Methods Baseline data from a convenience sample of 100 community-dwelling adults diagnosed with MCI enrolled in the Study of Mental Activity and Regular Training (SMART) trial were collected. A series of regression analyses were performed to develop a reduced model, then hierarchical regression with the Baron Kenny test of mediation derived the final three-tiered model of PWB. Results Significant predictors of PWB were subjective memory concern, cognitive function, evaluations of quality of life, and negative affect, with a final model explaining 61% of the variance of PWB in MCI. Discussion Our empirical findings support a theoretical tiered model of PWB in MCI and contribute to an understanding of the way in which early subtle cognitive deficits impact upon PWB. Multiple targets and entry points for clinical intervention were identified. These include improving the cognitive difficulties associated with MCI. Additionally, these highlight the importance of reducing memory concern, addressing low mood, and suggest that improving a person’s quality of life may attenuate the negative effects of depression and anxiety on PWB in this cohort.
    Clinical Interventions in Aging 05/2014; 9:779-92. DOI:10.2147/CIA.S58866 · 1.82 Impact Factor
  • 69th Annual Scientific Convention and Meeting of the Society of Biological Psychiatry, New York, USA; 05/2014
  • 69th Annual Scientific Convention and Meeting of the Society of Biological Psychiatry, New York, USA; 05/2014
  • 69th Annual Scientific Convention and Meeting of the Society of Biological Psychiatry, New York, USA; 05/2014
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    ABSTRACT: Aims ANZMTG 01.07 WBRTMel is a phase 3 randomized trial to address the role of whole brain radiation therapy (WBRT) after local treatment of 1–3 melanoma brain metastases. Modern radiation therapy technologies can now conformally spare the hippocampus during WBRT and therefore potentially reduce the risk of neurocognitive deficit. The aims of this study were to report the prevalence of melanoma metastases within the hippocampal sparing region and to identify variables that correlate with the presence of metastases within the hippocampal sparing region. Methods The pre-local treatment MRI scans of 77 eligible WBRTMel patients were used to contour the individual metastasis and the hippocampus. The volume, location and closest distance of each metastasis to the hippocampus were recorded. Binary logistic regression was performed to assess the influence of factors on the location of a metastasis within 5 mm of the hippocampus. Results The median age was 61 and 66% were male. The distribution of the 115 metastases was frontal (50, 43.5%), parietal (23, 20.0%), temporal (13, 11.2%), occipital (18, 15.7%), cerebellum (10, 8.6%) and pineal gland (1, 1.0%). The median aggregate volume of the metastasis was 3516 mm3. None of the metastases were within the hippocampus. Four patients (5.2%) had metastases within 5 mm of the hippocampus. The median distance from metastasis to the nearest hippocampus was 37.2 mm. Only the total volume of metastases was a significant predictor for the risk of a metastasis within the hippocampal sparing region (OR 1.071, 95% CI: 1.003–1.144, p = 0.040). Conclusions This study confirmed a low incidence of melanoma metastasis in the hippocampal sparing region at diagnosis. Given the lack of randomized data on the safety and benefit of hippocampal sparing WBRT, the current WBRTMel trial provides the opportunity to explore the feasibility of this technique.
    Radiotherapy and Oncology 04/2014; 111(1). DOI:10.1016/j.radonc.2014.01.012 · 4.86 Impact Factor
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    Kimberley Stuart · Mathew James Summers · Michael J Valenzuela · James C Vickers
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    ABSTRACT: Cognitive decline is a major factor in lowering the quality of life in older populations, and contributes substantially to social, economic, and health costs. As humans age, cognitive function decreases differentially, and individual differences in cognitive ageing are likely attributed to a range of causes, including environmental and genetic influences. The current study included 360 participants (240 females and 120 males) aged between 50 and 79 years from the Tasmanian Healthy Brain Project. The brain-derived neurotrophic factor (BDNF) Val66Met and Catechol-O-Methyltransferase (COMT) Val158Met polymorphisms were examined for their association with visual and auditory episodic memory performance. The polymorphisms were also investigated for their association with reported life-long engagement in complex cognitive activity using a retrospective questionnaire. Relative to the demographic variables, the gene variations were found to have no association with episodic memory performance, with the exception of the COMT polymorphism on a single measure of auditory memory (RAVLT). Several other studies also demonstrated that these polymorphisms have no, small, or inconsistent effects on memory function. The BDNF Val66Met and COMT Val158Met polymorphisms were also found to be of little significance to active engagement in complex cognitive activity throughout most of the lifespan. An association was detected between BDNF Val66Met and engagement in cognitive activity in early life (p = .04, d = .23), however this did not reach significance when adjusted for multiple comparisons. The biological mechanisms that underlie engagement in cognitive activity are elusive, thus the potential relationship between BDNF Val66Met genotype and early life cognitive engagement warrants further investigation.
    Neurobiology of Learning and Memory 01/2014; 110:1-7. DOI:10.1016/j.nlm.2014.01.013 · 4.04 Impact Factor
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    ABSTRACT: Many studies report an association of cognitive and social experiential factors and related traits with dementia risk. Further, many clinical-pathologic studies find a poor correspondence between levels of neuropathology and the presence of dementia and level of cognitive impairment. The poor correspondence suggests that other factors contribute to the maintenance or loss of cognitive function, with factors associated with the maintenance of function referred to as neural or cognitive reserve. This has led investigators to examine the associations of cognitive and social experiential factors with neuropathology as a first step in disentangling the complex associations between these experiential risk factors, neuropathology, and cognitive impairment. Despite the consistent associations of a range of cognitive and social lifestyle factors with cognitive decline and dementia risk, the extant clinical-pathologic data find only a single factor from one cohort, linguistic ability, related to AD pathology. Other factors, including education, harm avoidance, and emotional neglect, are associated with cerebrovascular disease. Overall, the associations are weak. Some factors, such as education, social networks, and purpose in life, modify the relation of neuropathology to cognition. Finally, some factors such as cognitive activity appear to bypass known pathologies altogether suggesting a more direct association with biologic indices that promote person-specific differences in reserve and resilience. Future work will first need to replicate findings across more studies to ensure the veracity of the existing data. Second, effort is needed to identify the molecular substrates of neural reserve as potential mediators of the association of lifestyle factors with cognition.
    Acta Neuropathologica 12/2013; 127(1). DOI:10.1007/s00401-013-1226-2 · 10.76 Impact Factor
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    ABSTRACT: Dogs offer unique opportunities to study correlations between morphology and behavior because skull shapes and body shape are so diverse among breeds. Several studies have shown relationships between canine cephalic index (CI: the ratio of skull width to skull length) and neural architecture. Data on the CI of adult, show-quality dogs (six males and six females) were sourced in Australia along with existing data on the breeds' height, bodyweight and related to data on 36 behavioral traits of companion dogs (n = 8,301) of various common breeds (n = 49) collected internationally using the Canine Behavioral Assessment and Research Questionnaire (C-BARQ). Stepwise backward elimination regressions revealed that, across the breeds, 33 behavioral traits all but one of which are undesirable in companion animals correlated with either height alone (n = 14), bodyweight alone (n = 5), CI alone (n = 3), bodyweight-and-skull shape combined (n = 2), height-and-skull shape combined (n = 3) or height-and-bodyweight combined (n = 6). For example, breed average height showed strongly significant inverse relationships (p<0.001) with mounting persons or objects, touch sensitivity, urination when left alone, dog-directed fear, separation-related problems, non-social fear, defecation when left alone, owner-directed aggression, begging for food, urine marking and attachment/attention-seeking, while bodyweight showed strongly significant inverse relationships (p<0.001) with excitability and being reported as hyperactive. Apart from trainability, all regression coefficients with height were negative indicating that, across the breeds, behavior becomes more problematic as height decreases. Allogrooming increased strongly (p<0.001) with CI and inversely with height. CI alone showed a strong significant positive relationship with self-grooming (p<0.001) but a negative relationship with chasing (p = 0.020). The current study demonstrates how aspects of CI (and therefore brain shape), bodyweight and height co-vary with behavior. The biological basis for, and significance of, these associations remain to be determined.
    PLoS ONE 12/2013; 8(12):e80529. DOI:10.1371/journal.pone.0080529 · 3.23 Impact Factor

Publication Stats

2k Citations
612.32 Total Impact Points

Institutions

  • 2008–2015
    • University of Sydney
      • • School of Medical Sciences
      • • Brain and Mind Research Institute
      Sydney, New South Wales, Australia
    • Universität Heidelberg
      Heidelburg, Baden-Württemberg, Germany
  • 2008–2013
    • University of New South Wales
      • School of Psychiatry
      Kensington, New South Wales, Australia
  • 2001–2012
    • Prince of Wales Hospital and Community Health Services
      • Institute of Neurological Sciences
      Sydney, New South Wales, Australia
  • 2011
    • University of South Wales
      Понтиприте, Wales, United Kingdom
    • Indiana University-Purdue University Indianapolis
      Indianapolis, Indiana, United States
    • Pacific Neuropsychiatric Institute
      Seattle, Washington, United States