Neural correlates of working memory and its association with metabolic parameters in early-treated adults with phenylketonuria

Stephanie Abgottspon; Raphaela Muri; Shawn E. Christ; Michel Hochuli; Piotr Radojewski; Roman Trepp; Regula Everts

NeuroImage: Clinical (Jan 2022)

Neural correlates of working memory and its association with metabolic parameters in early-treated adults with phenylketonuria

Stephanie Abgottspon,
Raphaela Muri,
Shawn E. Christ,
Michel Hochuli,
Piotr Radojewski,
Roman Trepp,
Regula Everts

Affiliations

Stephanie Abgottspon: Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital and University of Bern, Switzerland; Graduate School for Health Sciences, University of Bern, Switzerland; Translational Imaging Center (TIC), Swiss Institute for Translational and Entrepreneurial Medicine, Bern, Switzerland
Raphaela Muri: Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital and University of Bern, Switzerland; Graduate School for Health Sciences, University of Bern, Switzerland; Support Center for Advanced Neuroimaging (SCAN), Institute of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital and University of Bern, Switzerland; Translational Imaging Center (TIC), Swiss Institute for Translational and Entrepreneurial Medicine, Bern, Switzerland
Shawn E. Christ: Department of Psychological Sciences, University of Missouri, Columbia, MO, USA
Michel Hochuli: Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital and University of Bern, Switzerland
Piotr Radojewski: Support Center for Advanced Neuroimaging (SCAN), Institute of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital and University of Bern, Switzerland; Translational Imaging Center (TIC), Swiss Institute for Translational and Entrepreneurial Medicine, Bern, Switzerland
Roman Trepp: Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital and University of Bern, Switzerland; Translational Imaging Center (TIC), Swiss Institute for Translational and Entrepreneurial Medicine, Bern, Switzerland
Regula Everts: Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital and University of Bern, Switzerland; Division of Neuropaediatrics, Development and Rehabilitation, Inselspital Bern, Children’s University Hospital, Bern, Switzerland; Translational Imaging Center (TIC), Swiss Institute for Translational and Entrepreneurial Medicine, Bern, Switzerland; Corresponding author at: Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital and University of Bern, 3010 Bern, Switzerland.

Journal volume & issue: Vol. 34
p. 102974

Abstract

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Background: Phenylketonuria (PKU) is an inborn error of metabolism affecting the conversion of phenylalanine (Phe) into tyrosine. Previous research has found cognitive and functional brain alterations in individuals with PKU even if treated early. However, little is known about working memory processing and its association with task performance and metabolic parameters. The aim of the present study was to examine neural correlates of working memory and its association with metabolic parameters in early-treated adults with PKU. Methods: This cross-sectional study included 20 early-treated adults with PKU (mean age: 31.4 years ± 9.0) and 40 healthy controls with comparable age, sex, and education (mean age: 29.8 years ± 8.2). All participants underwent functional magnetic resonance imaging (fMRI) of working memory to evaluate the fronto-parietal working memory network. Fasting blood samples were collected from the individuals with PKU to acquire a concurrent plasma amino acid profile, and retrospective Phe concentrations were obtained to estimate an index of dietary control. Results: On a cognitive level, early-treated adults with PKU displayed significantly lower accuracy but comparable reaction time in the working memory task compared to the control group. Whole-brain analyses did not reveal differences in working memory-related neural activation between the groups. Exploratory region-of-interest (ROI) analyses indicated reduced neural activation in the left and right middle frontal gyri and the right superior frontal gyrus in the PKU group compared to the control group. However, none of the ROI analyses survived correction for multiple comparisons. Neural activation was related to concurrent Phe, tyrosine, and tryptophan concentrations but not to retrospective Phe concentrations. Conclusion: In early-treated adults with PKU, cognitive performance and neural activation are slightly altered, a result that is partly related to metabolic parameters. This study offers a rare insight into the complex interplay between metabolic parameters, neural activation, and cognitive performance in a sample of individuals with PKU.

Published in NeuroImage: Clinical

ISSN: 2213-1582 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General): Computer applications to medicine. Medical informatics; Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry: Neurology. Diseases of the nervous system
Website: http://www.journals.elsevier.com/neuroimage-clinical/

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