Dopaminergic modulation of the trade-off between probability and time in economic decision-making.

Studies on animals and humans have demonstrated the importance of dopamine in modulating decision-making processes. In this work, we have tested dopaminergic modulation of economic decision-making and its neural correlates by administering either placebo or metoclopramide, a dopamine D2-receptor antagonist, to healthy subjects, during a functional MRI study. The decision-making task combined probability and time delay with a fixed monetary reward. For individual behavioral characterization, we used the Probability Time Trade-off (PTT) economic model, which integrates the traditional trade-offs of reward magnitude-time and reward magnitude-probability into a single measurement, thereby quantifying the subjective value of a delayed and probabilistic outcome. A regression analysis between BOLD signal and the PTT model index permitted to identify the neural substrate encoding the subjective reward-value. Behaviorally, medication reduced the rate of temporal discounting over probability, reflected in medicated subjects being more prone to postpone the reward in order to increase the outcome probability. In addition, medicated subjects showed less activity during the task in the postcentral gyrus as well as frontomedian areas, whereas there were no differences in the ventromedial orbitofrontal cortex (VMOFC) between groups when coding the subjective value. The present study demonstrates by means of behavior and imaging that dopamine modulation alters the probability-time trade-off in human economic decision-making.

The neural substrate and functional integration of uncertainty in decision making: an information theory approach.

Decision making can be regarded as the outcome of cognitive processes leading to the selection of a course of action among several alternatives. Borrowing a central measurement from information theory, Shannon entropy, we quantified the uncertainties produced by decisions of participants within an economic decision task under different configurations of reward probability and time. These descriptors were used to obtain blood oxygen level-dependent (BOLD) signal correlates of uncertainty and two clusters codifying the Shannon entropy of task configurations were identified: a large cluster including parts of the right middle cingulate cortex (MCC) and left and right pre-supplementary motor areas (pre-SMA) and a small cluster at the left anterior thalamus. Subsequent functional connectivity analyses using the psycho-physiological interactions model identified areas involved in the functional integration of uncertainty. Results indicate that clusters mostly located at frontal and temporal cortices experienced an increased connectivity with the right MCC and left and right pre-SMA as the uncertainty was higher. Furthermore, pre-SMA was also functionally connected to a rich set of areas, most of them associative areas located at occipital and parietal lobes. This study provides a map of the human brain segregation and integration (i.e., neural substrate and functional connectivity respectively) of the uncertainty associated to an economic decision making paradigm.

Effects on resting cerebral blood flow and functional connectivity induced by metoclopramide: a perfusion MRI study in healthy volunteers.

BACKGROUND AND PURPOSE The substituted benzamide, metoclopramide, is a dopamine receptor antagonist and is widely prescribed in the symptomatic treatment of nausea and vomiting, although it can cause adverse motor and non-motor side effects. The effects of metoclopramide on brain metabolism have not been investigated to date. EXPERIMENTAL APPROACH To determine the effects of metoclopramide on brain function, cerebral perfusion changes after a single oral dose were assessed in healthy volunteers using magnetic resonance imaging (MRI) techniques. Arterial spin labelling (ASL) perfusion MRI was used to measure cerebral blood flow before and after metoclopramide. Blood haemodynamics in the vertebral and internal carotid arteries were evaluated using phase-contrast MRI. KEY RESULTS Metoclopramide altered haemodynamics in the carotid arteries and the cerebral perfusion. Perfusion increased bilaterally in the putamen, consistent with antagonism of dopamine D(2) receptors by metoclopramide and possibly related to its motor side effects. In contrast, reduced perfusion was observed in the insular cortices and anterior temporal lobes. In addition, functional connectivity between the insular cortex and the dorsolateral prefrontal cortex was decreased. These cortical changes affecting neural circuits between high-order association areas may underlie certain neuropsychiatric conditions occasionally reported after metoclopramide administration. CONCLUSIONS AND IMPLICATIONS The present results show the sensitivity of ASL to detect small changes in regional blood flow, closely related to brain function, after a single pharmacological challenge, highlighting the potential of this technique for human pharmacological studies.