Tryptophan depletion reduces right inferior prefrontal activation during response inhibition in fast, event-related fMRI

In animal and human studies, the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) has been implicated in mediating impulsiveness and aggression. To test the hypothesis that 5-HT modulates neuro-cognitive brain activation during inhibitory control, we examined the effect of acute tryptophan depletion (ATD), a dietary challenge, which has been shown to decrease 5-HT synthesis in the brain, on functional brain activation during a go/no-go task. Nine healthy, right-handed volunteers performed a rapid, event-related go/no-go task in two functional magnetic resonance imaging (fMRI) scanning sessions, 5 h after either a tryptophan-free or a balanced amino acid drink in a double-blind, sham depletion-controlled, counterbalanced, crossover design. The task required subjects to selectively execute or inhibit a motor response. Tryptophan depletion significantly lowered total plasma tryptophan concentration by 80%, but did not significantly alter inhibitory performance or mood ratings. ATD significantly reduced right orbito-inferior prefrontal activation during the no-go condition, and increased activation in superior and medial temporal cortices. These findings provide neuro-functional evidence of a serotonergic modulation of right inferior prefrontal during inhibitory motor control. The increased engagement of temporal brain regions may reflect compensatory mechanisms.