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

TY - JOUR

T1 - Tryptophan depletion reduces right inferior prefrontal activation during response inhibition in fast, event-related fMRI

AU - Rubia, Katya

AU - Lee, Francis

AU - Cleare, Anthony J

AU - Tunstall, Nigel

AU - Fu, Cynthia H Y

AU - Brammer, Michael

AU - McGuire, Phillip

PY - 2005/6

Y1 - 2005/6

N2 - RATIONALE AND 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.

AB - RATIONALE AND 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.

KW - Adult

KW - Affect/drug effects

KW - Aggression/drug effects

KW - Amino Acids/pharmacology

KW - Choice Behavior/drug effects

KW - Cross-Over Studies

KW - Double-Blind Method

KW - Female

KW - Functional Laterality/physiology

KW - Humans

KW - Image Processing, Computer-Assisted

KW - Impulsive Behavior/psychology

KW - Magnetic Resonance Imaging

KW - Male

KW - Prefrontal Cortex/physiology

KW - Psychomotor Performance/drug effects

KW - Reaction Time/drug effects

KW - Tryptophan/physiology

U2 - 10.1007/s00213-004-2116-z

DO - 10.1007/s00213-004-2116-z

M3 - Article

C2 - 15887056

SN - 0033-3158

VL - 179

SP - 791

EP - 803

JO - Psychopharmacology

JF - Psychopharmacology

IS - 4

ER -