ABSTRACT
Perceptual decisions are often accompanied by a feeling of decision confidence. Where parietal cortex is known for its crucial role in shaping such perceptual decisions, metacognitive evaluations are thought to additionally rely on (pre-)frontal cortex. Because of this supposed neural differentiation between these processes, perceptual and metacognitive decisions may be divergently affected by changes in internal (e.g., attention, arousal) and external (e.g., task and environmental demands) factors. Although intriguing, causal evidence for this hypothesis remains scarce. Here, we investigated the causal effect of two neuromodulatory systems on behavioral and neural measures of perceptual and metacognitive decision-making. Specifically, we pharmacologically elevated levels of catecholamines (with atomoxetine) and acetylcholine (with donepezil) in healthy adult human participants performing a visual discrimination task in which we gauged decision confidence, while electro-encephalography (EEG) was measured. Where cholinergic effects were not robust, catecholaminergic enhancement improved perceptual sensitivity, while at the same time leaving metacognitive sensitivity unaffected. Neurally, catecholaminergic elevation did not affect sensory representations of task-relevant visual stimuli, but instead enhanced well-known decision signals measured over centroparietal cortex, reflecting the accumulation of sensory evidence over time. Crucially, catecholaminergic enhancement concurrently impoverished neural markers measured over frontal cortex linked to the formation of metacognitive evaluations. Enhanced catecholaminergic neuromodulation thus improves perceptual, but not metacognitive decision-making.Significance statement Perceptual decisions about sensory input and the metacognitive evaluation of the accuracy of such decisions may be inversely affected by neuromodulatory systems regulating organisms' arousal levels. We tested this hypothesis by pharmacologically manipulating two neuromodulator systems (catecholaminergic, cholinergic) in humans, while measuring EEG. Elevated levels of catecholamines, but not acetylcholine, increased the accuracy of perceptual decisions, but not the accuracy of metacognitive evaluations thereof. Further, catecholamines enhanced neural markers over parietal cortex associated with the accumulation of evidence used for perceptual decision-making, while perturbing markers of metacognitive decision-making over frontal cortex. These findings align with current theories of perceptual decision-making, metacognition and cortical functioning and improve our understanding of the important role of neuromodulation in shaping human behavior and cognition.
