Chemistry of the Adaptive Mind: Lessons from Dopamine.

The brain faces various computational tradeoffs, such as the stability-flexibility dilemma. The major ascending neuromodulatory systems are well suited to dynamically regulate these tradeoffs depending on changing task demands. This follows from various general principles of chemical neuromodulation, which are illustrated with evidence from pharmacological neuroimaging studies on striatal dopamine's role in output gating and cost-benefit choice of cognitive tasks. The work raises open questions, including those regarding the top-down cortical control of the midbrain dopamine system, and begins to elucidate the mechanisms underlying the variability in catecholaminergic drug effects. Such drug effects depend on the baseline state of distinct target brain regions, reflecting, in part, the systems' self-regulatory capacity to maintain equilibrium. It is hypothesized that the basal tone of different dopaminergic projection systems reflects the perceived statistics of the environment computed in frontal cortex. By normalizing dopamine levels, dopaminergic drugs might counteract the bias elicited by the perceived environment.