Noradrenergic and Dopaminergic modulation of meta-cognition and meta-control

Humans and animals use multiple control systems for decision-making. This involvement is subject to meta-cognitive regulation - as a form of control over control or meta-control. However, the nature of this meta-control is unclear. For instance, Model-based (MB) control may be boosted when decision-makers generally lack confidence as it is more statistically efficient; or it may be suppressed, since the MB controller can correctly assess its own unreliability. Since control and metacontrol are themselves subject to the influence of neuromodulators, we examined the effects of perturbing the noradrenergic (NE) and dopaminergic (DA) systems with propranolol and L-DOPA, respectively. We first administered a simple perceptual task to examine the effects of the manipulations on meta-cognitive ability. Using Bayesian analyses, we found that 81% of group M-ratio samples were lower under propranolol relative to placebo, suggesting a decrease of meta-cognitive ability; and 60% of group M-ratio samples were higher under L-DOPA relative to placebo, considered as no effect of L-DOPA on meta-cognitive ability . We then asked subjects to provide choices and confidence ratings in a two-outcome decision-making task that has been used to dissociate Model-free (MF) and MB control. MB behavior was enhanced by propranolol, while MF behavior was not significantly affected by either drug. The interaction between confidence and MF/MB behavior was highly variable under propranolol, but under L-DOPA, the interaction was significantly lower/higher relative to placebo. Our results suggest a decrease in metacognitive ability under the influence of propranolol and an enhancement of MB behavior and meta-control under the influence of propranolol and L-DOPA, respectively. These findings shed light on the role of NE and DA in different aspects of control and meta-control and suggest potential avenues for mitigating dysfunction.