Donald T Stuss

Brain Canada, Montréal, Quebec, Canada

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Publications (232)879.18 Total impact

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    ABSTRACT: We explored the effects of age and time of day (TOD) on verbal fluency ability with respect to performance level and intraindividual variability (IIV). Verbal fluency, which involves complex cognitive operations, was examined in 20 older (mean age = 72.8 years) and 20 younger (mean age = 24.2 years) adults with test start time alternating between morning and evening across four days. Older adults generated more words in the morning and younger adults more in the evening, corresponding with self-report peak TOD. Age by TOD interactions were also observed across fluency tasks on the number of switches among subcategory exemplars during word generation and on the IIV observed in switching behavior. Older adults exhibited greater variability in switching in the evening than in the morning, whereas younger adults showed the opposite pattern. These findings demonstrate that processes involving energization (initiating and sustaining) and attentional control may be particularly sensitive to age differences in TOD influences on cognition.
    Aging Neuropsychology and Cognition 04/2015; DOI:10.1080/13825585.2015.1028326 · 1.07 Impact Factor
  • Donald T Stuss
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    ABSTRACT: The Province of Ontario recognized the pressing need to improve the understanding, diagnosis, and treatment of brain disorders. It also recognized that maximizing the existing strengths through a province-wide integrated approach was a pivotal mechanism. To achieve this, the Province established the Ontario Brain Institute. The goal of this article is to introduce the elements of the Ontario Brain Institute to the neuroscience community: the motivation for establishing it, the philosophy behind its creation, the principles guiding its development, the rapid evolution of its functional structure, the tools available to achieve its vision, and the management structure to ensure success. The singular goal of the Province and the Ontario Brain Institute is a comprehensive system that assures that basic research is embedded in the clinical system and is facilitating product development to accelerate benefits to both health and the economy of health: science with impact.
    The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 11/2014; 41(6):683-93. DOI:10.1017/cjn.2014.36 · 1.60 Impact Factor
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    ABSTRACT: Despite widespread use of second-generation cholinesterase inhibitors for the symptomatic treatment of Alzheimer's disease (AD), little is known about the long term effects of cholinergic treatment on global cognitive function and potential specific effects in different cognitive domains. The objectives of this study were to determine the association between cholinergic treatment and global cognitive function over one and two years in a cohort of patients with mild or moderate AD and identify potential differences in domain-specific cognitive outcomes within this cohort. A cohort of patients meeting the revised National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for mild or moderate AD, including patients both on treatment with a cholinesterase inhibitor and untreated controls (treated = 65, untreated = 65), were recruited from the Cognitive Neurology Clinic at Sunnybrook Health Sciences Centre, as part of the Sunnybrook Dementia Study. Patients were followed for one to two years and underwent standardized neuropsychological assessments to evaluate global and domain-specific cognitive function. Associations between cholinesterase inhibitor use and global and domain-specific cognitive outcome measures at one and two years of follow-up were estimated using mixed model linear regression, adjusting for age, education, and baseline mini mental state examination (MMSE). At one year, treated patients showed significantly less decline in global cognitive function, and treatment and time effects across tests of executive and visuospatial function. At two years, there was a significant trend towards less decline in global cognition for treated patients. Moreover, treated patients showed significant treatment and time effects across tests of executive functioning, memory, and visuospatial function. The present study offers two important contributions to knowledge of the effectiveness of cholinesterase inhibitor treatment in patients with mild-moderate AD: 1) that second-generation cholinesterase inhibitors demonstrate long-term effectiveness for reducing global cognitive decline over one to two years of follow-up, and 2) that decline in function for cognitive domains, including executive function, memory, and visuospatial skill that are primarily mediated by frontal networks and by the cholinergic system, rather than memory, may be slowed by treatment targeting the cholinergic system.
    Alzheimer's Research and Therapy 08/2014; 6(4):48. DOI:10.1186/alzrt280 · 3.50 Impact Factor
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    ABSTRACT: Background: Subcortical hyperintensities within the cholinergic fiber projections (chSH) on MRI are believed to reflect cerebral small vessel disease (SVD) which may adversely impact cognition. Additionally, hippocampal atrophy represents a commonly used biomarker to support the diagnosis of Alzheimer's disease (AD). Objective: To examine potential differences in neuropsychological test performance between AD patients (n = 234) with high and low chSH volumes and whether these differences corresponded to hippocampal atrophy. Methods: A modified version of Lesion Explorer was used to volumetrically quantify chSH severity. The Sunnybrook Hippocampal Volumetry Tool was applied to obtain hippocampal volumes. Composite z-scores to assess executive, memory, and visuospatial functioning were generated from standardized neuropsychological test performance scores. Results: Inter-method technique validation demonstrated a high degree of correspondence with the Cholinergic Pathways Hyperintensities Scale (n = 40, ρ = 0.84, p < 0.001). After adjusting for brain atrophy, disease severity, global SH volumes, and demographic variables, multivariate analyses revealed a significant group difference, with the high chSH group demonstrating poorer memory function compared to the low chSH group (p = 0.03). A significant difference was found between low and high chSH groups in total (p < 0.05) and left (p < 0.01) hippocampal volume. Conclusion: These results suggest degradation of the cholinergic projections due to strategic SVD may independently contribute to memory dysfunction and hippocampal atrophy. Future studies examining subcortical vasculopathy in the cholinergic pathways may have implications on the development of therapeutic strategies for dementia and SVD.
    Journal of Alzheimer's disease: JAD 08/2014; DOI:10.3233/JAD-140588 · 3.61 Impact Factor
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    ABSTRACT: Subcortical hyperintensities (SHs) are radiological entities commonly observed on magnetic resonance imaging (MRI) of patients with Alzheimer's disease (AD) and normal elderly controls. Although the presence of SH is believed to indicate some form of subcortical vasculopathy, pathological heterogeneity, methodological differences, and the contribution of brain atrophy associated with AD pathology have yielded inconsistent results in the literature. Using the Lesion Explorer (LE) MRI processing pipeline for SH quantification and brain atrophy, this study examined SH volumes of interest and cognitive function in a sample of patients with AD (n = 265) and normal elderly controls (n = 100) from the Sunnybrook Dementia Study. Compared with healthy controls, patients with AD were found to have less gray matter, less white matter, and more sulcal and ventricular cerebrospinal fluid (all significant, P <0.0001). Additionally, patients with AD had greater volumes of whole-brain SH (P <0.01), periventricular SH (pvSH) (P <0.01), deep white SH (dwSH) (P <0.05), and lacunar lesions (P <0.0001). In patients with AD, regression analyses revealed a significant association between global atrophy and pvSH (P = 0.02) and ventricular atrophy with whole-brain SH (P <0.0001). Regional volumes of interest revealed significant correlations with medial middle frontal SH volume and executive function (P <0.001) in normal controls but not in patients with AD, global pvSH volume and mental processing speed (P <0.01) in patients with AD, and left temporal SH volume and memory (P <0.01) in patients with AD. These brain-behavior relationships and correlations with brain atrophy suggest that subtle, yet measurable, signs of small vessel disease may have potential clinical relevance as targets for treatment in Alzheimer's dementia.
    Alzheimer's Research and Therapy 08/2014; 6(4):49. DOI:10.1186/alzrt279 · 3.50 Impact Factor
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    ABSTRACT: We report a single-case study of a female patient (VL) who exhibited frequent episodes of erroneous recollections triggered by everyday events. Based on neuropsychological testing, VL was classified as suffering from mild to moderate dementia (MMSE=18) and was given a diagnosis of probable Alzheimer’s disease. Her memory functions were uniformly impaired but her verbal abilities were generally well preserved. A structural MRI scan showed extensive areas of gray matter atrophy particularly in frontal and medial-temporal (MTL) areas. Results of experimental recognition tests showed that VL had very high false alarm rates on tests using pictures, faces and auditory stimuli, but lower false alarm rates on verbal tests. We provide a speculative account of her erroneous recollections in terms of her MTL and frontal pathology. In outline, we suggest that owing to binding failures in MTL regions, VL’s recognition processes were forced to rely on earlier than normal stages of analysis. Environmental features on a given recognition trial may have combined with fragments persisting from previous trials resulting in erroneous feelings of familiarity and of recollection that were not discounted or edited out, due to her impaired frontal processes.
    Neuropsychologia 04/2014; 56. DOI:10.1016/j.neuropsychologia.2014.02.007 · 3.45 Impact Factor
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    ABSTRACT: Functional contributions of cognitive impairment may vary by domain and severity. (1) To characterize frequency of cognitive impairment by domain after stroke by severity (mild: -1.5 ≤ z-score < -2; severe: Z ≤ -2) and time (sub-acute: < 90d; chronic: 90d-2yrs); and (2) To assess the association of cognitive impairment with function in chronic stroke. Cognitive function was characterized among 215 people with sub-acute or chronic stroke (66.8 years, 43.3% female). Z-scores by cognitive domain were determined from normative data. Function was defined as the number of IADLs minimally independent. 76.3% of sub-acute and 67.3% of chronic stroke participants had cognitive impairment in ≥ 1 domain (p-for-difference = 0.09). Severe impairment was most common in psychomotor speed (sub-acute: 53.5%; chronic: 33.7%). Impairment in executive function was common (sub-acute: 39.5%; chronic: 30.7%) but was usually mild. Severe impairment in psychomotor speed, visuospatial function, and language and any impairment in executive function and memory was associated with IADL impairment (p < 0.03). Mild cognitive impairment is common after stroke but is not associated with functional disability. Impairment in psychomotor speed, executive function, and visuospatial function is common and associated with functional impairment so should be a focus of screening and rehabilitation post-stroke.
    Neurorehabilitation 01/2014; 34(2). DOI:10.3233/NRE-131030 · 1.74 Impact Factor
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    ABSTRACT: To compare the validity of the Montreal Cognitive Assessment (MoCA) with the criterion standard of standardized neuropsychological testing and to compare the convergent validity of the MoCA with that of existing screening tools and global measures of cognition. Cross-sectional observational study. Tertiary care hospital-based cognitive neurology subspecialty clinic. A convenience sample of 107 individuals with mild Alzheimer's disease (AD, n = 75) or mild cognitive impairment (MCI, n = 32) from the Sunnybrook Dementia Study. In addition to the MoCA, all participants completed the Mini-Mental State Examination (MMSE), the Mattis Dementia Rating Scale (DRS), and detailed neuropsychological testing. Convergent validity was supported, with MoCA scores correlating well with the MMSE (correlation coefficient (r) = 0.66, P < .001) and the DRS (r = 0.77, P < .001) and the MoCA better associated with the DRS than did the MMSE. Criterion validity was supported, with MoCA subscores according to cognitive domain correlating well with analogous neuropsychological tests and, in the case of memory (area under the receiver operating characteristic curve (AUC) = 0.86), executive (AUC = 0.79), and visuospatial function (AUC = 0.79), being reasonably sensitive to impairment in those domains. The MoCA is a valid assessment of cognition that shows good agreement with existing screening tools and global measures (convergent validity) and was superior to the MMSE in this regard. The MoCA domain-specific subscores align with performance on more-detailed neuropsychological tests, suggesting not only good criterion validity for the MoCA, but also that it may be useful in guiding further neuropsychological testing.
    Journal of the American Geriatrics Society 12/2013; 61(12). DOI:10.1111/jgs.12541 · 4.22 Impact Factor
  • David P Salmon, Donald T Stuss
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    ABSTRACT: Frontotemporal degeneration is the overarching label used to describe a spectrum of neurodegenerative disorders characterized by relatively circumscribed frontal and temporal lobar atrophy that leads to profound changes in personality, behavior, or language. The dementia syndrome associated with frontotemporal degeneration is usually divided into 2 broad categories: a language-based variant referred to as primary progressive aphasia(1) and a behavioral variant frontotemporal dementia (bvFTD) in which changes in social cognition, behavior, and personality are the earliest and most prominent features.(2) Although not as common as Alzheimer disease (AD), FTD is not rare and accounts for about 9% of all cases of dementia, and is particularly prevalent when the age at onset of dementia is younger than 65 years.(3.)
    Neurology 05/2013; DOI:10.1212/WNL.0b013e318296ea38 · 8.30 Impact Factor
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    ABSTRACT: Schizophrenia (SCZ)-related verbal memory impairment is hypothesized to be mediated, in part, by frontal lobe (FTL) dysfunction. However, little research has contrasted the performance of SCZ patients with that of patients exhibiting circumscribed frontal lesions. The current study compared verbal episodic memory in patients with SCZ and focal FTL lesions (left frontal, LF; right frontal, RF; and bi-frontal, BF) on a four-trial list learning task consisting of three lists of varying semantic organizational structure. Each dependent variable was examined at two levels: scores collapsed across all four trials and learning scores (i.e., trial 4-trial 1). Performance deficits were observed in each patient group across most dependent measures at both levels. Regarding patient group differences, SCZ patients outperformed LF/BF patients (i.e., either learning scores or scores collapsed across trial) on free recall, primacy, primary memory, secondary memory, and subjective organization, whereas they only outperformed RF patients on the semantically blocked list on recency and primary memory. Collectively, these results indicate that the pattern of memory performance is largely similar between patients with SCZ and those with RF lesions. These data support tentative arguments that verbal episodic memory deficits in SCZ may be mediated by frontal dysfunction in the right hemisphere.
    The Clinical Neuropsychologist 05/2013; 27(4). DOI:10.1080/13854046.2013.780640 · 1.58 Impact Factor
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    ABSTRACT: We studied behavioral variant frontotemporal dementia (bvFTD) using object alternation (OA) as a novel probe of cognition. This task was adopted from animal models and is sensitive to ventrolateral-orbitofrontal and medial frontal function in humans. OA was administered to bvFTD patients, normal controls, and a dementia control group with Alzheimer disease (AD). Two other frontal lobe measures adopted from animal models were administered: delayed response (DR) and delayed alternation (DA). Brain volumes were measured using the semiautomatic brain region extraction method. Compared with the normal controls, bvFTD patients were significantly impaired on OA and DR. For OA and DR, sensitivities and specificities were 100% and 51.5% (cutoff=22.5 errors) and 9.5% and 98% (cutoff=1.5 errors), respectively. Negative predictive value (NPV) for OA was 100% at all prevalence rates. Comparing AD with bvFTD, there were no significant differences on OA, DR, or DA. Nevertheless, positive predictive value (PPV) and NPV were good at all prevalence rates for OA (cutoff=36.5 errors) and DA (cutoff=6 errors); PPV was good for DR (cutoff=9 errors). Error scores above cutoffs favored diagnosis of AD. Performance on OA was significantly related to medial frontal gray matter atrophy. OA, together with DR and DA, may facilitate assessment of bvFTD as a novel probe of medial frontal function.
    Alzheimer disease and associated disorders 04/2013; 27(4). DOI:10.1097/WAD.0b013e318293b546 · 2.69 Impact Factor
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    ABSTRACT: Difficulties remembering one's own experiences via episodic memory may affect the ability to imagine other people's experiences during theory of mind (ToM). Previous work shows that the same set of brain regions recruited during tests of episodic memory and future imagining are also engaged during standard laboratory tests ofToM. However, hippocampal amnesic patients who show deficits in past and future thinking, show intact performance on ToM tests, which involve unknown people or fictional characters. Here we present data from a developmental amnesic person (H.C.) and a group of demographically matched con-trols, who were tested on a naturalistic test of ToM that involved describing other people's experiences in response to photos of personally familiar others ("pToM" condition) and unfamiliar others ("ToM" condition). We also included a condition that involved recollect-ing past experiences in response to personal photos ("EM" condition). Narratives were scored using an adapted Autobiographical Interview scoring procedure. Due to the visually rich stimuli, internal details were further classified as either descriptive (i.e., details that describe the visual content of the photo) or elaborative (i.e., details that go beyond what is visually depicted in the photo). Relative to controls, H.C. generated significantly fewer elaborative details in response to the pToM and EM photos and an equivalent number of elaborative details in response to the ToM photos. These data converge with previous neu-roimaging results showing that the brain regions underlying pToM and episodic memory overlap to a greater extent than those supporting ToM. Taken together, these results sug-gest that detailed episodic representations supported by the hippocampus may be pivotal for imagining the experiences of personally familiar, but not unfamiliar, others.
    Frontiers in Psychology 01/2013; 3. DOI:10.3389/fpsyg.2012.00588 · 2.80 Impact Factor
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    ABSTRACT: With increasing knowledge of clinical in vivo biomarkers and the pathological intricacies of Alzheimer's disease (AD), nosology is evolving. Harmonized consensus criteria that emphasize prototypic illness continue to develop to achieve diagnostic clarity for treatment decisions and clinical trials. However, it is clear that AD is clinically heterogeneous in presentation and progression, demonstrating variable topographic distributions of atrophy and hypometabolism/hypoperfusion. AD furthermore often keeps company with other conditions that may further nuance clinical expression, such as synucleinopathy exacerbating executive and visuospatial dysfunction and vascular pathologies (particularly small vessel disease that is increasingly ubiquitous with human aging) accentuating frontal-dysexecutive symptomatology. That some of these atypical clinical patterns recur may imply the existence of distinct AD variants. For example, focal temporal lobe dysfunction is associated with a pure amnestic syndrome, very slow decline, with atrophy and neurofibrillary tangles limited largely to the medial temporal region including the entorhinal cortex. Left parietal atrophy and/or hypometabolism/hypoperfusion are associated with language symptoms, younger age of onset, and faster rate of decline - a potential 'language variant' of AD. Conversely, the same pattern but predominantly affecting the right parietal lobe is associated with a similar syndrome but with visuospatial symptoms replacing impaired language function. Finally, the extremely rare frontal variant is associated with executive dysfunction out of keeping with degree of memory decline and may have prominent behavioural symptoms. Genotypic differences may underlie some of these subtypes; for example, absence of apolipoprotein E e4 is often associated with atypicality in younger onset AD. Understanding the mechanisms behind this variability merits further investigation, informed by recent advances in imaging techniques, biomarker assays, and quantitative pathological methods, in conjunction with standardized clinical, functional, neuropsychological and neurobehavioral evaluations. Such an understanding is needed to facilitate 'personalized AD medicine', and eventually allow for clinical trials targeting specific AD subtypes. Although the focus legitimately remains on prototypic illness, continuing efforts to develop disease-modifying therapies should not exclude the rarer AD subtypes and common comorbid presentations, as is currently often the case. Only by treating them as well can we address the full burden of this devastating dementia syndrome.
    Alzheimer's Research and Therapy 01/2013; 5(1):1. DOI:10.1186/alzrt155 · 3.50 Impact Factor
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    ABSTRACT: Coping has been suggested as the final common pathway related to outcome after traumatic brain injury (TBI). Different types of coping have been related to either positive or negative psychosocial outcomes. As a result, a small set of studies have attempted to remediate coping through intervention, but the effectiveness of these studies has been modest. We propose that three primary factors are limiting our ability to effectively remediate coping following TBI through intervention TBI: 1) limited understanding of inter-patient variability following TBI; 2) limited understanding of the mechanisms underlying coping following TBI; and 3) reliance on self-report measures of coping. We discuss these obstacles in the context of a model of frontal lobe function, and in light of recent behavioural work on coping.
    Neurorehabilitation 01/2013; 32(4):721-8. DOI:10.3233/NRE-130897 · 1.74 Impact Factor
  • Donald T Stuss
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    ABSTRACT: Receiving the National Academy of Neuropsychology's Lifetime Contributions to Neuropsychology Award promoted reflection on values and decisions. Selecting the topic of the presentation associated with the award also led to rumination. The term "lifetime" was the deciding factor: how does one choose and start a career path, what advice might one give to individuals embarking on their own career, and what goals does one set up early in one's career? What are the "drivers" in one's life? This was the topic of my presentation, and the theme of this manuscript. There were two drivers that can be traced to two important early career choices. These two drivers also ended up forming the two primary research themes on the functions of the frontal lobes. After a brief review of the reasons for the roads chosen in my career path, a summary of the two themes of research is presented.
    Archives of Clinical Neuropsychology 12/2012; 28(1). DOI:10.1093/arclin/acs107 · 1.92 Impact Factor
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    ABSTRACT: As humans, we are consciously aware of unobservable mental states, including our own during episodic memory and other people's by having a "theory of mind" (ToM). Episodic memory and ToM are closely related: they share a neural substrate and emerge close in time in ontogenetic development. This relationship is central to prominent child development and cognitive neuroscience theories of ToM, but its causal nature has not been tested empirically. The current study examined whether normal episodic memory development is necessary for normal ToM development. To investigate this, we tested H.C., a young woman with impaired episodic memory development due to early hippocampal damage, on a wide range of ToM measures. H.C.'s performance was indistinguishable from that of controls on all tests of ToM suggesting that, contrary to theoretical claims in the literature, normal episodic memory development and hippocampal function is not essential for the development of ToM.
    Neuropsychologia 10/2012; 50(14). DOI:10.1016/j.neuropsychologia.2012.10.016 · 3.45 Impact Factor
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    ABSTRACT: Apathy is best characterized in behavioral terms as an absence of responsiveness to stimuli as demonstrated by a lack of self-initiated action. The main thesis of this chapter is that there are different kinds of apathy. Each is separable on the basis of both the anatomical regions and the psychological mechanisms involved. The chapter is organized into 4 main sections written with the aim of establishing support for this thesis. In the first section, definitions of apathy are reviewed, and the authors introduce their approach to defining apathy states. The second section describes common causes of apathy and outlines the neuroanatomical regions involved. In the third section, the authors present their proposed conceptualization of the different kinds of apathy. The fourth section contains a review of what is known about treatment interventions for apathy. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
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    ABSTRACT: Switching between rapid and accurate responses is an important aspect of decision-making. However, the brain mechanisms important to smoothly change the speed-accuracy strategy remain mostly unclear. This issue was addressed here by using functional magnetic resonance imaging (fMRI). On each trial, right-handed healthy participants had to stress speed or accuracy in performing a color discrimination task on a target stimulus according to the instructions given by an initial cue. Participants were capable of trading speed for accuracy and vice versa. Analyses of cue-related fMRI activations revealed a significant recruitment of left middle frontal gyrus and right cerebellum when switching from speed to accuracy. The left superior parietal lobule was activated in the same switching condition but only after the target onset. The anterior cingulate cortex was more recruited, also after target presentation, when speed had to be maintained from one trial to the next. These results are interpreted within a theoretical framework that attributes a role in criterion-setting to the left lateral prefrontal cortex, perceptual evidence accumulation to the superior parietal lobule, and action energization to the anterior cingulate cortex, extending previous findings to the domain of speed-accuracy tradeoff regulations.
    Human Brain Mapping 07/2012; 33(7):1677-88. DOI:10.1002/hbm.21312 · 6.92 Impact Factor

Publication Stats

16k Citations
879.18 Total Impact Points


  • 2013–2014
    • Brain Canada
      Montréal, Quebec, Canada
  • 1989–2014
    • University of Toronto
      • • Department of Psychology
      • • Division of Neurology
      • • Rotman Research Institute
      Toronto, Ontario, Canada
  • 1998–2013
    • Sunnybrook Health Sciences Centre
      Toronto, Ontario, Canada
  • 2001–2012
    • Baycrest
      Toronto, Ontario, Canada
  • 2010
    • Scuola Internazionale Superiore di Studi Avanzati di Trieste
      Trst, Friuli Venezia Giulia, Italy
    • CUNY Graduate Center
      New York, New York, United States
  • 2007–2009
    • York University
      • Department of Psychology
      Toronto, Ontario, Canada
  • 2008
    • Cambridge Eco
      Cambridge, England, United Kingdom
    • Beth Israel Deaconess Medical Center
      • Department of Neurology
      Boston, MA, United States
  • 2006
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2005
    • Boston University
      Boston, Massachusetts, United States
  • 2003
    • Temple University
      • Department of Psychology
      Philadelphia, PA, United States
  • 1980–1993
    • University of Ottawa
      • • Division of Medical Oncology
      • • Department of Medicine
      Ottawa, Ontario, Canada
  • 1990
    • Ottawa University
      Kansas, United States
  • 1986
    • The Ottawa Hospital
      Ottawa, Ontario, Canada