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1.  Inverted-U shaped dopamine actions on human working memory and cognitive control 
Biological psychiatry  2011;69(12):e113-e125.
Brain dopamine has long been implicated in cognitive control processes, including working memory. However, the precise role of dopamine in cognition is not well understood, partly because there is large variability in the response to dopaminergic drugs both across different behaviors and across different individuals. We review evidence from a series of studies with experimental animals, healthy humans and patients with Parkinson’s disease, which highlight two important factors that contribute to this large variability. First, the existence of an optimum dopamine level for cognitive function implicates the need to take into account baseline levels of dopamine when isolating dopamine’s effects. Second, cognitive control is a multi-factorial phenomenon, requiring a dynamic balance between cognitive stability and cognitive flexibility. These distinct components might implicate the prefrontal cortex and the striatum respectively. Manipulating dopamine will thus have paradoxical consequences for distinct cognitive control processes depending on distinct basal or optimal levels of dopamine in different brain regions.
PMCID: PMC3111448  PMID: 21531388
Working memory; cognitive control; prefrontal cortex; striatum; dopamine; fMRI
2.  Enhanced frontal function in Parkinson’s disease 
Brain  2009;133(1):225-233.
We investigated the role of dopamine in working memory by examining effects of withdrawing dopaminergic medication in patients with Parkinson’s disease. Resistance to distraction during a delayed response task was abnormally enhanced in Parkinson’s disease patients OFF medication relative to controls. Conversely, performance on a backward digit span test was impaired in these same Parkinson’s disease patients OFF medication. Dopaminergic medication reinstated susceptibility to distraction and backward digit span performance, so that performance of Parkinson’s disease patients ON medication did not differ from that of controls. We hypothesize that the enhanced distractor resistance and impaired backward digit span in Parkinson’s disease reflects low dopamine levels in the striatum, and perhaps upregulated frontal dopamine levels. Dopaminergic medication may reinstate distractibility by normalizing the balance between striatal and prefrontal dopamine transmission.
PMCID: PMC2801327  PMID: 19995871
working memory; cognitive deficits; dopamine; Parkinson’s disease; basal ganglia
3.  Striatal dopamine predicts outcome-specific reversal learning and its sensitivity to dopaminergic drug administration 
Individual variability in reward-based learning has been ascribed to quantitative variation in baseline levels of striatal dopamine. However, direct evidence for this pervasive hypothesis has hitherto been unavailable. We demonstrate that individual differences in reward-based reversal learning reflect variation in baseline striatal dopamine synthesis capacity, as measured with neurochemical positron emission tomography. Subjects with high baseline dopamine synthesis in the striatum showed relatively better reversal learning from unexpected rewards than from unexpected punishments, whereas subjects with low baseline dopamine synthesis in the striatum showed the reverse pattern. In addition, baseline dopamine synthesis predicted the direction of dopaminergic drug effects. The D2 receptor agonist bromocriptine improved reward- relative to punishment-based reversal learning in subjects with low baseline dopamine synthesis capacity, while impairing it in subjects with high baseline dopamine synthesis capacity in the striatum. Finally, this pattern of drug effects was outcome-specific, and driven primarily by drug effects on punishment-, but not reward-based reversal learning. These data demonstrate that the effects of D2 receptor stimulation on reversal learning in humans depend on task demands and baseline striatal dopamine synthesis capacity.
PMCID: PMC2940719  PMID: 19193900
dopamine; reward; punishment; striatum; PET; Learning
4.  Biological changes associated with healthy versus pathological aging: A symposium review 
Ageing research reviews  2009;8(2):140-146.
The Douglas Mental Health University Institute, in collaboration with the McGill Centre for Studies in Aging, organized a two day symposium entitled “Biological Changes Associated with Healthy Versus Pathological Aging” that was held in December 13 and 14, 2007 on the Douglas campus. The symposium involved presentations on current trends in aging and dementia research across several sub-disciplines: genetics, neurochemistry, structural and functional neuroimaging and clinical treatment and rehabilitation. The goal of this symposium was to provide a forum for knowledge-transfer between scientists and clinicians with different specializations in order to promote cross-fertilization of research ideas that would lead to future collaborative neuroscience research in aging and dementia. In this review article we summarize the presentations made by the thirteen international scientists at the symposium and highlight: (i) past research, and future research trends in neuroscience of aging and dementia and (ii) links across levels of analysis that can lead to fruitful transdisciplinary research programs that will advance knowledge about the neurobiological changes associated with healthy aging and dementia.
PMCID: PMC2671241  PMID: 19274854
healthy aging; dementia; hippocampus; prefrontal cortex; amyloid deposition; MRI; volumetry; dopamine
5.  Bimanual simultaneous motor performance and impaired ability to shift attention in Parkinson's disease. 
The ability to share time and to shift attention between bimanual simultaneous motor tasks were studied in 18 patients with Parkinson's disease (PD) and 19 age- and intelligence-matched controls. The task consisted of drawing triangles with the dominant hand and squeezing a rubber bulb with the nondominant hand. Motor performance was measured using the variables: amplitude of squeezing, frequency of squeezing and velocity of drawing triangles. After eliminating variance due to baseline differences in single-handed performance, the bimanual simultaneous performance of PD and controls turned out to be similar to the frequency of squeezing and the velocity of drawing triangles. The amplitude of squeezing, however, differed between the two groups: it was significantly reduced in PD. Arguably the disturbance in the bimanual performance of PD patients was not due to a disorder of time sharing, but to a decreased ability to shift attention from the visually cued task to the non visually cued task. The results agree with current evidence that PD patients are more impaired when they have to rely upon internal control for the regulation of shifting attention than when external cues are available.
PMCID: PMC488173  PMID: 2213046
6.  Cognitive and motor shifting aptitude disorder in Parkinson's disease. 
Eighteen patients suffering from Parkinson's disease and nineteen control subjects, who were matched for age and intelligence, were compared in tests measuring "shifting aptitude" at cognitive and motor levels (word production, sorting blocks or animals, and finger pushing sequences). It was found that Parkinson patients produced fewer different names of animals and professions in one minute than control subjects, needed more trials for detecting a shift in a sorting criterion, and produced fewer finger responses in a change of pushing sequence than control subjects. These results are interpreted as reflecting a central programming deficit that manifests itself in verbal, figural and motor modalities, that is, a diminished "shifting aptitude" characteristic of patients with dysfunctioning basal ganglia. The results are discussed in relation to changes of behaviour organisations in animals with dysfunctioning basal ganglia.
PMCID: PMC1027818  PMID: 6736974

Results 1-6 (6)