Influential theories postulate distinct roles of catecholamines and acetylcholine in cognition and behavior. However, previous physiological work reported similar effects of these neuromodulators on the response properties
(specifically, the gain) of individual cortical neurons. Here, we show a double dissociation between the effects
of catecholamines and acetylcholine at the level of large-scale interactions between cortical areas in humans.
A pharmacological boost of catecholamine levels increased ...
Influential theories postulate distinct roles of catecholamines and acetylcholine in cognition and behavior. However, previous physiological work reported similar effects of these neuromodulators on the response properties
(specifically, the gain) of individual cortical neurons. Here, we show a double dissociation between the effects
of catecholamines and acetylcholine at the level of large-scale interactions between cortical areas in humans.
A pharmacological boost of catecholamine levels increased cortex-wide interactions during a visual task, but not
rest. An acetylcholine boost decreased interactions 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 increased by catecholamines) and intracortical transmission (more strongly reduced by acetylcholine).
The inferred catecholaminergic mechanism also predicted noisier decision-making, which we confirmed for both
perceptual and value-based choice behavior. Our work highlights specific circuit mechanisms for shaping cortical
network interactions and behavioral variability by key neuromodulatory systems.
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