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

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 experience of fatigue. OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Potentially adaptive functional changes in cognitive processing for patients with multiple sclerosis and their acute modulation by rivastigmine.

One explanation for the weak relationship between neuropsychological deficits and conventional measures of disease burden in multiple sclerosis is that brain 'plasticity' allows adaptive reorganization of cognitive functions to limit impairment, despite injury. We have tested this hypothesis. Ten patients with multiple sclerosis and 11 healthy controls were studied using a functional MRI (fMRI) counting Stroop task. The two subject groups had comparable performances, but a predominantly left medial prefrontal region [Brodmann area (BA) 8/9/10] was more active during the task in patients than in controls (corrected P < 0.001), while a right frontal region (including BA 45 and the basal ganglia) was more active in controls than in patients (corrected P = 0.004). The magnitude of the differences correlated with the normalized brain parenchymal volume, a measure of disease burden (r = -0.72, P = 0.02). We then tested the effects of acute administration of rivastigmine, a central cholinesterase inhibitor, on patterns of brain activation. In five out of five multiple sclerosis patients there was a relative normalization of the abnormal Stroop-associated brain activation, although no change in the patterns of brain activation was found in any of four healthy controls given the drug and tested in the same way. We suggest that recruitment of medial prefrontal cortex is a form of adaptive brain plasticity that compensates, in part, for relative deficits in processing related to the reduced right prefrontal cortex activity with multiple sclerosis. This functional plasticity is modulated by cholinergic agonism and must arise from potentially highly dynamic mechanisms such as the 'unmasking' of latent pathways.