Predicting the word frequency effect in naturalistic Chinese reading: A multilevel analysis of brain function and...

The word frequency effect (WFE) refers to the phenomenon whereby high-frequency words are processed more efficiently than low-frequency words. This robust effect is consistently observed across different languages and task paradigms. Previous studies have examined its neural mechanisms using techniques such as functional MRI, which identified brain regions involved in frequency-based lexical processing. However, it remains unclear whether these regions can longitudinally predict the magnitude of the WFE at the individual level. In this study, we combined eye-tracking technique with imaging-transcriptomic approaches to identify potential neurobiological markers underlying the WFE. Our results revealed a distributed set of cortical and subcortical regions whose regional homogeneity (ReHo) patterns negatively predicted the magnitude of the WFE, as estimated by first fixation duration and single fixation duration, with particular emphasis on the basal ganglia-thalamo-cortical circuits, underscoring their critical role in lexical processing efficiency. In addition, neurotransmitter systems enriched in WFE-related ReHo patterns were identified, and functional enrichment analyses revealed distinct biological processes for genes upregulated and downregulated in these areas. Furthermore, we observed divergent developmental trajectories between the two gene sets, highlighting temporally and regionally specific gene expression patterns that may support different aspects of lexical processing. This study advances our understanding of the neural-biological basis of the word frequency effect (WFE) integrating eye-movement, imaging, and transcriptomic approaches, and offers valuable insights for the early identification and targeted intervention of reading difficulties in educational settings.