Abstract
Patients with classic galactosemia, a genetic metabolic disorder, encounter cognitive impairments, including motor (speech), language, and memory deficits. We used functional magnetic resonance imaging to evaluate spontaneous functional connectivity during rest to investigate potential abnormalities in neural networks. We characterized networks using seed-based correlation analysis in 13 adolescent patients and 13 matched controls. Results point towards alterations in several networks, including well-known resting-state networks (e.g. default mode, salience, visual network). Particularly, patients showed alterations in networks encompassing medial prefrontal cortex, parietal lobule and (pre)cuneus, involved in spatial orientation and attention. Furthermore, altered connectivity of networks including the insula and superior frontal gyrus -important for sensory-motor integration and motor (speech) planning- was demonstrated. Lastly, abnormalities were found in networks involving occipital regions, linked to visuospatial capacities and working memory. Importantly, across several seeds, altered functional connectivity to the superior frontal cortex, anterior insula, parietal lobule and the (pre)cuneus was observed in patients, suggesting special importance of these brain regions. Moreover, these alterations correlated with neurocognitive test results, supporting a relation with the clinical phenotype. Our findings contribute to improved characterization of brain impairments in classic galactosemia and provide directions for further investigations.
Highlights
The brain represents one of the target organs of damage in classic galactosemia, an inborn error of galactose metabolism, resulting in chronic impairments with significant impact on quality of life and general performance[1,2,3]
More extensive regions of the frontal lobe, right precuneus, posterior cingulate cortex (PCC), right middle temporal gyrus (MTG) and anterior cingulate cortex (ACC) were correlated with the right medial frontal seed, and in addition the right parietal region was correlated
Decreased connectivity in patients was demonstrated in right superior parietal lobe (SPL), left temporal pole and left middle temporal gyrus (MTG)
Summary
The brain represents one of the target organs of damage in classic galactosemia, an inborn error of galactose metabolism, resulting in chronic impairments with significant impact on quality of life and general performance[1,2,3]. Several studies demonstrated cerebral or cerebellar atrophy and decreased tissue density of grey matter[17, 19, 20, 22, 23, 25, 26, 29]. This neuronal loss has been speculated to result from direct toxicity of galactose and its metabolites or aberrant glycosylation[26]. Increased grey matter density in the inferior frontal and medial prefrontal cortex, which could reflect compensation for problematic motor and cognitive functions (memory, language) or abnormal maturation[29]. The left inferior frontal gyrus (IFG), the right insula and the left pre-supplementary motor area (pre-SMA) were subsequently selected as seeds for a seed-based functional connectivity analysis, which revealed variations in functional connectivity in comparison to controls
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
