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

Journal: Psychopharmacology (Berl). 2006 Dec 19; [E-publication ahead of print]

Authors and affiliation: Morgan RM, Parry AM, Arida RM, Matthews PM, Davies B, Castell LM. Cellular Nutrition Research Group, Nuffield Department of Anaesthetics, University of Oxford, Radcliffe Infirmary, Oxford, UK. [E-mail: lindy.castell@nda.ox.ac.uk ]

PMID: 17180619

Rationale: 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 [or conscious] experience of fatigue.

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

Materials and methods: In a double-blind, cross-over study, eight subjects ingested L: -tryptophan or Placebo on two separate test days.

Neutral and interference Stroop tasks were carried out. [Note: The Stroop task is a psychological test of our mental vitality and flexibility. The task takes advantage of our ability to read words more quickly and automatically than we can name colors. If a word is printed or displayed in a color different from the color it actually names – for example, if the word "green" is written in blue ink, we will say the word "green" more readily than we can name the color in which it is displayed, which in this case is "blue." The cognitive mechanism involved in this task is called inhibition. You have to inhibit or stop one response and say or do something else.]

Results: Plasma-free tryptophan (p[FT]) increased tenfold after L: -tryptophan administration (P < 0.01). Although reaction times were longer after L: -tryptophan (mean+/-SD, Placebo-Neutral 669 +/- 163 ms, I 715 +/- 174 ms, P < 0.01; L: -tryptophan Neutral 712 +/- 193 ms, I 761 +/- 198 ms, P < 0.05), the Stroop effect was not significantly different between Placebo and L: -tryptophan.

L: -tryptophan 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 Placebo. Relatively increased activation was found after L: -tryptophan in the left precuneus and in the posterior cingulate gyrus.

Conclusions: Thus, L: -tryptophan 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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