Aberrant local and global neural activation patterns in pediatric Prader-Willi syndrome

Front Neurosci. 2026 Apr 15:20:1696114. doi: 10.3389/fnins.2026.1696114. eCollection 2026.

Abstract

Purpose: Although cognitive disorders in children with Prader-Willi syndrome (PWS) are linked to abnormalities in spontaneous neural activation and functional connectivity (FC), the specific neural activation patterns remain uncertain, especially in young children with PWS.

Methods: The current study set out to explore specific local and global neural activation in pediatric PWS using the amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo), and seed-based whole brain FC. Information was gathered from 35 pediatric PWS patients and 33 healthy controls (HC). Both groups' ALFF and ReHo values were computed, and FC were constructed on the basis of altered ALFF and ReHo regions. The relationships between altered ALFF, ReHo, and FC and the Griffiths Developmental Scales (GDS) of the PWS group were analyzed using partial correlation analysis.

Results: Both ALFF and ReHo exhibited decreases in occipital lobe, temporal lobe, and cingulate gyrus, and altered ReHo was present in parietal lobe, frontal lobe, and basal ganglia areas. Moreover, ALFF and ReHo also exhibited increases in occipital and temporal lobes. Decreased FC was detected in the visual network (VN), sensorimotor network (SMN), salience network (SAN), and default mode network (DMN). The SMN-, cingulate-, and occipital lobe-related neural activation patterns were significantly positively correlated with the GDS score.

Conclusion: The PWS group was characterized mainly by decreased neuronal physiological function and the ReHo was similar to ALFF but more extensive. The decreased local and global brain neural activation patterns may serve as early physiological indicators of cognitive abnormalities.

Keywords: Prader–Willi syndrome; functional connectivity; low-frequency fluctuations; magnetic resonance imaging; regional homogeneity.