Abstract Influential accounts postulate distinct roles of the catecholamine and acetylcholine neuromodulatory systems in cognition and behavior. But previous work found similar effects of these modulators on the response properties of individual cortical neurons. Here, we report a double dissociation between catecholamine and acetylcholine effects at the level of cortex-wide network interactions in humans. A pharmacological boost of catecholamine levels increased cortex-wide interactions during a visual task, but not rest. Conversely, an acetylcholine-boost decreased correlations during rest, but not task. Cortical circuit modeling explained this dissociation by differential changes in two circuit properties: the local excitation-inhibition balance (more strongly altered by catecholamines) and intracortical transmission (more strongly reduced by acetylcholine). The inferred catecholaminergic mechanism also predicted increased behavioral exploration, which we confirmed in human behavior during both a perceptual and value-based choice task. In sum, we identified specific circuit mechanisms for shaping cortex-wide network interactions and behavior by key neuromodulatory systems.

Circuit mechanisms for chemical modulation of cortex-wide network interactions and exploration behavior