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


METHODS
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.


RESULTS
ATD significantly reduced right orbito-inferior prefrontal activation during the no-go condition, and increased activation in superior and medial temporal cortices.


CONCLUSIONS
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.
Rubia
Katya
K
Institute of Psychiatry, King's College London, De Crespigny Park, SE5 8AF, London, UK. k.rubia@iop.kcl.ac.uk
Lee
Francis
F
Cleare
Anthony J
AJ
Tunstall
Nigel
N
Fu
Cynthia H Y
CH
Brammer
Michael
M
McGuire
Phillip
P
D000328:Adult; D000339:Affect / Q000187:drug effects; D000374:Aggression / Q000187:drug effects; D000596:Amino Acids / Q000494:pharmacology; D002755:Choice Behavior / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007175:Impulsive Behavior / Q000523:psychology; D008279:Magnetic Resonance Imaging; D008297:Male; D017397:Prefrontal Cortex / Q000502:physiology*; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D011930:Reaction Time / Q000187:drug effects; D014364:Tryptophan / Q000502:physiology*
D000596:Amino Acids; D014364:Tryptophan