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Psychopharmacology (Berl). 2007 Feb;190(3):383-9. Epub 2006 Dec 19.

Effects of elevated plasma tryptophan on brain activation associated with the Stroop task.

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Cellular Nutrition Research Group, Nuffield Department of Anaesthetics, University of Oxford, Radcliffe Infirmary, Oxford, OX2 6HE, UK.



Central fatigue, such as that found in chronic fatigue syndrome, is a state in which cognition and action require increasing effort and performance is impaired without evidence for reduced peripheral motor responsiveness. Previous studies identified functional changes in subcortical regions in patients who experience central fatigue but did not address neural correlates of the subjective experience of fatigue.


This study investigated responses to acute tryptophan feeding (after administration of 30 mg/kg body mass) using functional magnetic resonance imaging to investigate neural correlates of central fatigue during a cognitively demanding exercise, the counting Stroop task.


In a double-blind, cross-over study, eight subjects ingested L: -tryptophan (Trp) or placebo (Plac) on two separate test days. Neutral (N) and interference (I) Stroop tasks were carried out.


Plasma-free tryptophan (p[FT]) increased tenfold after L: -Trp administration (P < 0.01). Although reaction times were longer after Trp (mean+/-SD, Plac-Neut 669 +/- 163 ms, I 715 +/- 174 ms, P < 0.01; Trp-Neut 712 +/- 193 ms, I 761 +/- 198 ms, P < 0.05), the Stroop effect was not significantly different between Plac and Trp. L: -Trp administration was associated with relatively decreased activation in regions, including the left postcentral, angular, inferior frontal, and the lateral orbital gyri and the inferior frontal sulcus relative to Plac. Relatively increased activation was found after Trp in the left precuneus and in the posterior cingulate gyrus.


Thus, Trp administration before the Stroop task caused distributed functional changes in primary sensory and in multimodal neocortex, including changes in a brain region, the activity of which has been shown previously to vary with conscious awareness (precuneus). Previous reports suggest that primary mechanisms of central fatigue may be predominantly subcortical. The present results demonstrate that neocortical activity changes are also found. Whether this activity contributes to the primary mechanisms underlying central fatigue or not, the neocortical activity changes may provide an index of the conscious experience.

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