Working Memory Capacity Predicts Dopamine Synthesis Capacity in the Human Striatum

Cools, Roshan; Gibbs, Sasha E. B.; Miyakawa, Asako; Jagust, William J.; D’Esposito, Mark

doi:10.1523/jneurosci.4475-07.2008

Cited by 275 publications

(288 citation statements)

References 51 publications

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“…Using PET, we now demonstrate that interindividual differences in ventral striatal presynaptic dopamine levels are related to this bias toward model-based control. This accords with other studies that report enhanced cognitive capacities in subjects with higher levels of striatal F-DOPA uptake (17,18). Cognitive capacity, particularly as it relates to working memory function, is also linked to the extent to which individuals exploit model-based control (19).…”

Section: Discussionsupporting

confidence: 89%

“…16). On the other hand, individual variation of striatal presynaptic dopamine, quantified using neurochemical imaging, is known to positively relate to variability in "prefrontal" cognitive capacities (17,18), which might also limit the capacity for model-based learning (19). Indeed, depletion of presynaptic dopamine precursors and Parkinson's disease both compromised goal-directed behavior in a devaluation experiment and a slips-of-action test, whereas habitual learning remained intact (20,21).…”

Section: Significancementioning

confidence: 99%

See 1 more Smart Citation

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: Discussionsupporting

confidence: 89%

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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“…Remarkably, the same lateralization pattern was found in a previous study comparing performance subgroups of patients and controls (Tan et al, 2006) and is additionally supported by a meta-analysis indicating a strong performance-activation relationship in right dlPFC (Van Snellenberg et al, 2006). Previous studies indicate that this relationship is mediated by dopamine: while WM capacity correlated positively with dopamine synthesis in healthy subjects (Cools et al, 2008), the latter predicted dlPFC activation during WM in prodromal subjects (Fusar-Poli et al, 2010).…”

Section: Prefrontal Activation and Cognitive Performancesupporting

confidence: 83%

Reduced Prefrontal-Parietal Effective Connectivity and Working Memory Deficits in Schizophrenia

et al. 2012

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The neural mechanisms behind cognitive deficits in schizophrenia still remain unclear. Functional neuroimaging studies on working memory (WM) yielded inconsistent results, suggesting task performance as a moderating variable of prefrontal activation. Beyond regional specific activation, disordered integration of brain regions was supposed as a critical pathophysiological mechanism of cognitive deficits in schizophrenia. Here, we first hypothesized that prefrontal activation implicated in WM depends primarily on task performance and therefore stratified participants into performance subgroups. Second, in line with the dysconnectivity hypothesis, we asked whether connectivity in the prefrontal-parietal network underlying WM is altered in all patients. We used functional magnetic resonance imaging in human subjects (41 schizophrenia patients, 42 healthy controls) and dynamic causal modeling to examine effective connectivity during a WM task. In line with our first hypothesis, we found that prefrontal activation was differentially modulated by task performance: there was a significant task by group by performance interaction revealing an increase of activation with performance in patients and a decrease with performance in controls. Beyond that, we show for the first time that WM-dependent effective connectivity from prefrontal to parietal cortex is reduced in all schizophrenia patients. This finding was independent of performance. In conclusion, our results are in line with the highly influential hypothesis that the relationship between WM performance and prefrontal activation follows an inverted U-shaped function. Moreover, this study in a large sample of patients reveals a mechanism underlying prefrontal inefficiency and cognitive deficits in schizophrenia, thereby providing direct experimental evidence for the dysconnectivity hypothesis.

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“…It has been reported that the working memory and learning functions were correlated with the baseline dopamine synthesis capacity (Cools et al, 2008(Cools et al, , 2009. Further studies to investigate the effects of antipsychotics on such higher brain functions in relation with changes in dopamine synthesis capacity should be considered (Vernaleken et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Effects of the Antipsychotic Risperidone on Dopamine Synthesis in Human Brain Measured by Positron Emission Tomography with l-[β-¹¹C]DOPA: A Stabilizing Effect for Dopaminergic Neurotransmission?

Ito¹,

Takano²,

Takahashi³

et al. 2009

J. Neurosci.

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receptors corresponding dose of risperidone was observed, the changes in dopamine synthesis capacity by the administration of risperidone were not significant, nor was the relation between the occupancy of dopamine D 2 receptors and these changes. A significant negative correlation was observed between the baseline dopamine synthesis capacity and the changes in dopamine synthesis capacity by risperidone, indicating that this antipsychotic can be assumed to stabilize the dopamine synthesis capacity. The therapeutic effects of risperidone in schizophrenia might be related to such stabilizing effects on dopaminergic neurotransmission responsivity.

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Working Memory Capacity Predicts Dopamine Synthesis Capacity in the Human Striatum

Cited by 275 publications

References 51 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

Reduced Prefrontal-Parietal Effective Connectivity and Working Memory Deficits in Schizophrenia

Effects of the Antipsychotic Risperidone on Dopamine Synthesis in Human Brain Measured by Positron Emission Tomography with l-[β-¹¹C]DOPA: A Stabilizing Effect for Dopaminergic Neurotransmission?

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Working Memory Capacity Predicts Dopamine Synthesis Capacity in the Human Striatum

Cited by 275 publications

References 51 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

Reduced Prefrontal-Parietal Effective Connectivity and Working Memory Deficits in Schizophrenia

Effects of the Antipsychotic Risperidone on Dopamine Synthesis in Human Brain Measured by Positron Emission Tomography with l-[β-11C]DOPA: A Stabilizing Effect for Dopaminergic Neurotransmission?

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Effects of the Antipsychotic Risperidone on Dopamine Synthesis in Human Brain Measured by Positron Emission Tomography with l-[β-¹¹C]DOPA: A Stabilizing Effect for Dopaminergic Neurotransmission?