Abstract
We tested the hypothesis that brain white matter integrity mediates the relationship between phenylalanine (Phe) control and executive abilities in children with phenylketonuria (PKU; N = 36). To do so, we examined mean diffusivity (MD) from diffusion tensor imaging (DTI) in two white matter brain regions (posterior parietal-occipital, PPO; centrum semiovale, CSO) and lifetime phenylalanine (Phe) exposure; the executive abilities examined included verbal strategic processing, nonverbal strategic processing, and working memory. Mediation modeling showed that MD in the PPO and CSO mediated the relationship between Phe exposure and nonverbal strategic processing, MD in the CSO mediated the relationship between Phe exposure and verbal strategic processing, and MD in the PPO mediated the relationship between Phe exposure and working memory. These exploratory findings demonstrate the importance of using sophisticated modeling procedures to understand the interplay among metabolic control, neural factors, and functional outcomes in individuals with PKU.
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