The role of 5-HT in response inhibition and re-engagement

In animal and human research, the neurotransmitter serotonin (5-HT) has been implicated in inhibitory control. Using functional magnetic resonance imaging (fMRI), the present study investigated the acute effects of pharmacological modulation of the serotonergic system on brain activation during response inhibition and re-engagement in healthy human volunteers. In a randomized double-blind placebo-controlled cross-over design 14 men received either a single oral dose of the selective serotonin reuptake inhibitor (SSRI) escitalopram (10 mg) or a placebo. At the time of the expected plasma peak concentration, participants performed a stop–change task during fMRI. Escitalopram did not affect behavioural performance, since the main effect did not reveal significant differences between reaction times of go-, stop- or change-trials. During successful response inhibition, escitalopram, however, was associated with enhanced brain activation in right prefrontal cortex, right supplementary/pre-motor and bilateral cingulate cortex, and subcortical regions. During inhibition failures, escitalopram also modulated a broad network of brain regions, including anterior cingulate, right parietal cortex, right orbitofrontal cortex, and areas in right temporal cortex and subcortical regions. During response re-engagement escitalopram increased brain activation in right inferior frontal gyrus and precuneus as well as in left middle temporal gyrus. The results implicate the involvement of 5-HT in neural regulation of response inhibition and re-engagement. This study also provides evidence that 5-HT affects both action restraint and action cancellation through modulation of activation of brain areas. The results support the view for a fronto-striatal circuitry for response inhibition in conjunction with serotonin.