Serotonergic modulation of intrinsic functional connectivity

Serotonin functions as an essential neuromodulator that serves a multitude of roles, most prominently balancing mood [1]. Serotonergic challenge has been observed to reduce intrinsic functional connectivity in brain regions implicated in mood regulation [2-4]. However, the full scope of serotonergic action on functional connectivity in the human brain has not been explored. Here, we show evidence that a single dose of a serotonin reuptake inhibitor dramatically alters functional connectivity throughout the whole brain in healthy subjects (n = 22). Our network-centrality analysis reveals a widespread decrease in connectivity in most cortical and subcortical areas. In the cerebellum and thalamus, however, we find localized increases. These rapid and brain-encompassing connectivity changes linked to acute serotonin transporter blockade suggest a key role for the serotonin transporter in the modulation of the functional macroscale connectome