Amplification and Suppression of Distinct Brainwide Activity Patterns by Catecholamines.

The widely projecting catecholaminergic (norepinephrine and dopamine) neurotransmitter systems profoundly shape the state of neuronal networks in the forebrain. Current models posit that the effects of catecholaminergic modulation on network dynamics are homogeneous across the brain. However, the brain is equipped with a variety of catecholamine receptors with distinct functional effects and heterogeneous density across brain regions. Consequently, catecholaminergic effects on brainwide network dynamics might be more spatially specific than assumed. We tested this idea through the analysis of fMRI measurements performed in humans (19 females, 5 males) at "rest" under pharmacological (atomoxetine-induced) elevation of catecholamine levels.Weused a linear decomposition technique to identify spatial patterns of correlated fMRI signal fluctuations that were either increased or decreased by atomoxetine. This yielded two distinct spatial patterns,eachexpressingreliableandspecificdrugeffects.Thespatial structure ofbothfluctuation patternsresembledthespatial distribution of the expression of catecholamine receptor genes: α1 norepinephrine receptors (for the fluctuation pattern: placebo > atomoxetine), D2-like dopamine receptors (pattern: atomoxetine > placebo), and β norepinephrine receptors (for both patterns, with correlations of opposite sign). We conclude that catecholaminergic effectsonthe forebrain are spatiallymorestructured than traditionallyassumedandat least in part explained by the heterogeneous distribution of various catecholamine receptors. Our findings link catecholaminergic effects on largescale brain networks to low-level characteristics of the underlying neurotransmitter systems. They also provide key constraints for the development of realistic models of neuromodulatory effects on large-scale brain network dynamics. [ABSTRACT FROM AUTHOR]