PT  - JOURNAL ARTICLE
AU  - T. Pfeffer
AU  - A. Ponce-Alvarez
AU  - T. Meindertsma
AU  - C. Gahnström
AU  - R. L. van den Brink
AU  - G. Nolte
AU  - K. Tsetsos
AU  - A.K. Engel
AU  - G. Deco
AU  - T.H. Donner
TI  - Dissociation between catecholamines and acetylcholine in the human cerebral cortex
AID  - 10.1101/2020.06.25.171199
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.06.25.171199
4099  - http://biorxiv.org/content/early/2020/06/25/2020.06.25.171199.short
4100  - http://biorxiv.org/content/early/2020/06/25/2020.06.25.171199.full
AB  - The catecholamine and acetylcholine systems control global brain states. Influential theoretical accounts postulate distinct computational roles of these systems. But previous empirical work observed only subtle, quantitative differences between their effects on single-neuron responses in the cortex. Here, we report a double dissociation between catecholamine and acetylcholine effects on large-scale cortical dynamics in humans. A pharmacological boost of catecholamine levels increased the cortex-wide coupling between regional fluctuations of population activity during a visual task. In contrast, a pharmacological acetylcholine boost decreased coupling during rest. Circuit modeling explained these results by distinct changes in local cortical circuit properties (specifically, excitation/inhibition balance) and predicted that catecholamines would promote more exploratory choice behavior. Indeed, we observed increased exploration under catecholamine boost in two behavioral tasks. We conclude that distinct local circuit mechanisms cause dissociated context-dependent catecholamine and acetylcholine effects on large-scale cortical dynamics.Competing Interest StatementThe authors have declared no competing interest.