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Tackling frontal lobe–related functions in PKU through functional brain imaging: a Stroop task in adult patients

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Profound mental retardation in phenylketonuria (PKU) can be prevented by a low phenylalanine (Phe) diet. However, even patients treated early have inconsistently shown deficits in several frontal lobe–related neuropsychological tasks such as the widely accepted Stroop task. The goal of this study was to investigate whether adult patients exhibit altered brain activation in Stroop-related locations in comparison to healthy controls and if an acute increase in blood Phe levels in patients has an effect on activation patterns.


Seventeen male, early-treated patients with classic PKU (mean ± SD age: 31.0 ± 5.2 years) and 15 male healthy controls (32.1 ± 6.4 years) were compared using a color-word matching Stroop task in a functional magnetic resonance imaging (fMRI) study at 3T. Participants were scanned twice, and an oral Phe load (100 mg/kg body weight) was administered to patients prior to one of the fMRI sessions (placebo-controlled). Activity in brain regions that are known to be involved in Stroop tasks was assessed.


PKU patients exhibited poorer accuracy in incongruent trials. Reaction times were not significantly different. There were no consistent differences in BOLD activations in Stroop-associated brain regions. The oral Phe administration had no significant effect on brain activity.


Neither a generally slower task performance nor distinctively altered functioning of brain networks involved in a task representing a subset of dopamine-dependent executive functions could be proven. Decreased accuracy and inconsistent findings in posterior areas necessitate further study of frontal-lobe functioning in PKU patients in larger study samples.

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We thank all patients and healthy control subjects for participating in this study. We thank Stefan Zysset for kindly providing the Stroop paradigm, Prof. Thorsten Marquardt, University Hospital Muenster, Department of Pediatrics, Head of Metabolic Unit, for amino acid quantification, and Jana Hansmeier and Silvia Knaup for their assistance with the scanning procedure. We appreciate the generous support of SHS Company, Heilbronn, Germany.

Details of funding

The study was financially supported by the SHS Company, Heilbronn, Germany and by the Institute of Clinical Radiology and the Department of Pediatrics, University Hospital Muenster. The authors confirm independence from the sponsors. The content of the article has not been influenced by the sponsors.

Author information

Correspondence to Bettina Pfleiderer.

Additional information

Competing interest: None declared.

Benedikt Sundermann and Bettina Pfleiderer contributed equally to the paper.

Communicated by: Sedel Frederic

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Table 1

Number of PKU patients with different WM lesion scores ranging from 0 to 12. Subgroup 1 = receiving Phe at the first and placebo at the second session, subgroup 2 = vice versa (DOC 27 kb)

Supplementary Table 2

Peak coordinates of group × session interactions, contrast incongruent > neutral, P < 0.005 (uncorrected), spatial extent threshold: 10 voxels (DOC 36 kb)

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Sundermann, B., Pfleiderer, B., Möller, H.E. et al. Tackling frontal lobe–related functions in PKU through functional brain imaging: a Stroop task in adult patients. J Inherit Metab Dis 34, 711 (2011). https://doi.org/10.1007/s10545-011-9318-4

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  • Stroop Task
  • Incongruent Trial
  • Incongruent Condition
  • Structural Magnetic Resonance Imaging
  • fMRI Session