Refraining from reacting does not only involve reactive inhibitory mechanisms. It was recently found that inhibitory control also relies strongly on proactive mechanisms. However, since most available studies have focused on reactive stopping, little is known about how proactive inhibition of response is implemented. Two behavioral experiments were conducted to identify the temporal dynamics of this executive function. They manipulated respectively the time during which inhibitory control must be sustained until a stimulus occurs, and the time limit allowed to set up inhibition before a stimulus occurs. The results show that inhibitory control is not set up after but before instruction, and is not transient and sporadic but sustained across time. Consistent with our previous neuroimaging findings, these results suggest that proactive inhibition of response is the default mode of executive control. This implies that top-down control of sensorimotor reactivity would consist of a temporary release (up to several seconds), when appropriate (when the environment becomes predictable), of the default locking state. This conclusion is discussed with regard to current anatomo-functional models of inhibitory control, and to methodological features of studies of attention and sensorimotor control.

The neurobehavioral underpinnings of pathological gambling are not well understood. Insight might be gained by understanding pharmacological effects on the reward system in patients with Parkinson’s disease (PD). Treatment with dopamine agonists (DAs) has been associated with pathological gambling in PD patients. However, how DAs are involved in the development of this form of addiction is unknown. We tested the hypothesis that tonic stimulation of dopamine receptors specifically desensitizes the dopaminergic reward system by preventing decreases in dopaminergic transmission that occurs with negative feedback. Using functional magnetic resonance imaging, we studied PD patients during three sessions of a probabilistic reward task in random order: off medication, after levodopa (LD) treatment, and after an equivalent dose of DA (pramipexole). For each trial, a reward prediction error value was computed using outcome, stake, and probability. Pramipexole specifically changed activity of the orbitofrontal cortex (OFC) in two ways that were both associated with increased risk taking in an out-of-magnet task. Outcome-induced activations were generally higher with pramipexole compared with LD or off medication. In addition, only pramipexole greatly diminished trial-by-trial correlation with reward prediction error values. Further analysis yielded that this resulted mainly from impaired deactivation in trials with negative errors in reward prediction. We propose that DAs prevent pauses in dopamine transmission and thereby impair the negative reinforcing effect of losing. Our findings raise the question of whether pathological gambling may in part stem from an impaired capacity of the OFC to guide behavior when facing negative consequences.