PET Studies of Cerebral Levodopa Metabolism: A Review of Clinical Findings and Modeling Approaches

Kumakura, Yoshitaka; Cumming, Paul

doi:10.1177/1073858409338217

Cited by 120 publications

(146 citation statements)

References 82 publications

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“…A radiolabeled variant of L-DOPA, [ 18 F]DOPA, allows quantification of individual levels of presynaptic dopamine in vivo by using positron emission tomography (PET) (22). Schlagenhauf et al (23) used this methodology to show an inverse relationship between ventral striatal presynaptic dopamine levels and an fMRI signal that indexed ventral striatal model-free learning signals.…”

Section: Significancementioning

confidence: 99%

Ventral striatal dopamine reflects behavioral and neural signatures of model-based control during sequential decision making

Deserno

Huys

Boehme

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

220

212

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Dual system theories suggest that behavioral control is parsed between a deliberative "model-based" and a more reflexive "modelfree" system. A balance of control exerted by these systems is thought to be related to dopamine neurotransmission. However, in the absence of direct measures of human dopamine, it remains unknown whether this reflects a quantitative relation with dopamine either in the striatum or other brain areas. Using a sequential decision task performed during functional magnetic resonance imaging, combined with striatal measures of dopamine using [ 18 F]DOPA positron emission tomography, we show that higher presynaptic ventral striatal dopamine levels were associated with a behavioral bias toward more model-based control. Higher presynaptic dopamine in ventral striatum was associated with greater coding of model-based signatures in lateral prefrontal cortex and diminished coding of model-free prediction errors in ventral striatum. Thus, interindividual variability in ventral striatal presynaptic dopamine reflects a balance in the behavioral expression and the neural signatures of model-free and model-based control. Our data provide a novel perspective on how alterations in presynaptic dopamine levels might be accompanied by a disruption of behavioral control as observed in aging or neuropsychiatric diseases such as schizophrenia and addiction.dopamine | decision making | reinforcement learning | PET | fMRI H uman choice behavior is influenced by both habitual and goal-directed systems (1). For example, having enjoyed a delicious dinner makes another subsequent visit to the same restaurant more likely. Upon returning at a later point, another visit could happen reflexively when walking past the restaurant, or alternatively be planned and involve reflection, for instance, by checking recent customer reviews to bolster against possible changes. These two decision modes differ fundamentally in terms of their control over actions and associated outcome consequences. Reflexive habitual preferences are retrospective and arise from a slow accumulation of rewards via iterative updating of expectations (2), for example by repeating dinner at the same place after having previously enjoyed tasty food there. In contrast, goal-directed behavior requires a prospective consideration of future outcomes associated with a set of actions (3). For example, knowledge that the chef has changed and subsequent reviews have been less good should reduce one's expectations. Thus, in the face of such change, a goaldirected system can adapt quickly, whereas a habitual system needs to experience an actual outcome before it can alter behavior in an adaptive manner (4). This dual-system theory has been formalized within computational models of learning that update expectations based on past rewards ("model-free") or map possible actions to their potential outcomes ("model-based") (5). There is evidence that model-based learning signals during the acquisition of task structure are encoded within prefrontal-parietal cortices, where...

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Section: Significancementioning

confidence: 99%

Ventral striatal dopamine reflects behavioral and neural signatures of model-based control during sequential decision making

Deserno

Huys

Boehme

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

220

212

View full text Add to dashboard Cite

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“…The realigned frames were then summated, creating a movement-corrected dynamic image, which was used in the analysis. The cerebellar reference region (Kumakura and Cumming, 2009) was defined using a probabilistic atlas (Martinez et al, 2003), and as previously described, regions of interest (ROI) in the whole striatum and its functional sub-divisions were delineated to create an ROI map (Egerton et al, 2010). The functional subdivisions of the striatum reflect the topographical arrangement of corticostriatal projections.…”

Section: Image Analysismentioning

confidence: 99%

“…Dopamine synthesis capacity can be indexed in humans using a radiolabeled dopamine precursor, L-3,4-dihydroxyphenylalanine (L-DOPA) with positron emission tomography (PET; Kumakura and Cumming, 2009). Our primary hypothesis was, therefore, that cigarette smokers would have increased dopamine synthesis capacity compared with non-smoker controls.…”

Section: Introductionmentioning

confidence: 99%

Dopamine Function in Cigarette Smokers: An [18F]-DOPA PET Study

Bloomfield

Pepper

Egerton

et al. 2014

Neuropsychopharmacol

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Tobacco addiction is a global public health problem. Addiction to tobacco is thought to involve the effects of nicotine on the dopaminergic system. Only one study has previously investigated dopamine synthesis capacity in cigarette smokers. This study, exclusively in male volunteers, reported increased dopamine synthesis capacity in heavy smokers compared with non-smokers. We sought to determine whether dopamine synthesis capacity was elevated in a larger sample of cigarette smokers that included females. Dopamine synthesis capacity was measured in 15 daily moderate smokers with 15 sex-and age-matched control subjects who had never smoked tobacco. Dopamine synthesis capacity (indexed as the influx rate constant K i cer ) was measured with positron emission tomography and 3,4-dihydroxy-6-[ 18 F]-fluoro-l-phenylalanine. There was no significant group difference in dopamine synthesis capacity between smokers and non-smoker controls in the whole striatum (t 28 ¼ 0.64, p ¼ 0.53) or any of its functional subdivisions. In smokers, there were no significant relationships between the number of cigarettes smoked per day and dopamine synthesis capacity in the whole striatum (r ¼ À 0.23, p ¼ 0.41) or any striatal subdivision. These findings indicate that moderate smoking is not associated with altered striatal dopamine synthesis capacity.

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“…These realigned frames were then summated, creating a movement-corrected dynamic image to be used in the analysis. Standardized regions in Montreal Neurologic Institute space were defined in the cerebellum (as it contains few, if any, dopaminergic terminals, it is used to provide data on nonspecific uptake 24 ) using a probabilistic atlas 25 and in the whole striatum delineated as previously described to create a Region of Interest (ROI) map. 26 SPM5 (http://www.fil.ion.ucl.ac.uk/spm) was then used to normalize the ROI map together with the tracer specific ([ 18 F]-DOPA) template (the template aids normalization) to each individual PET summation image.…”

Section: Image Analysismentioning

confidence: 99%

Dopaminergic Function in the Psychosis Spectrum: An [18F]-DOPA Imaging Study in Healthy Individuals With Auditory Hallucinations

Howes

Shotbolt

Bloomfield

et al. 2012

Schizophrenia Bulletin

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Background:The psychosis phenotype appears to exist in the population as a continuum, but it is not clear if subclinical psychotic symptoms and psychotic disorders share the same neurobiology. We investigated whether the dopaminergic dysfunction seen in psychotic disorders is also present in healthy, well-functioning people with hallucinations. Methods: We compared dopamine synthesis capacity (us-positron emission tomography imaging) in 16 healthy individuals with frequent persistent auditory verbal hallucinations (hallucinating group) with that in 16 matched controls. Results: There was no significant difference in dopamine synthesis capacity in the striatum, or its functional subdivisions, between groups and no relationship between subclinical psychotic symptom severity or schizotypal traits and dopamine synthesis capacity in the hallucinating group. Conclusions: Altered dopamine synthesis capacity is unlikely to underlie subclinical hallucinations, suggesting that although there may be a phenomenological psychosis continuum, there are distinctions at the neurobiological level.

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PET Studies of Cerebral Levodopa Metabolism: A Review of Clinical Findings and Modeling Approaches

Cited by 120 publications

References 82 publications

Ventral striatal dopamine reflects behavioral and neural signatures of model-based control during sequential decision making

Ventral striatal dopamine reflects behavioral and neural signatures of model-based control during sequential decision making

Dopamine Function in Cigarette Smokers: An [18F]-DOPA PET Study

Dopaminergic Function in the Psychosis Spectrum: An [18F]-DOPA Imaging Study in Healthy Individuals With Auditory Hallucinations

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