• Meta-analysis of 29 fMRI studies (n=2,579) revealed brain alterations in insomnia. • Right inferior frontal gyrus hypoactivation persisted across rest and task states • Brain functional alterations in insomnia correlate with 1,036 genes. • Synaptic upregulation and metabolic downregulation characterize insomnia • Strong transcriptional similarity found between insomnia and schizophrenia Background: Insomnia disorder (ID) affects 10-15% of adults globally but remains poorly characterized at the neural level. This study integrated meta-analytic neuroimaging findings with transcriptomic data to elucidate neural-molecular signatures of ID. Methods: We conducted coordinate-based meta-analyses of 29 fMRI studies (2,579 participants: 1,305 ID, 1,274 controls) examining resting-state and taskbased functional alterations in ID. Altered brain activity patterns were correlated with Allen Human Brain Atlas (AHBA) gene expression data using partial least squares (PLS) regression to identify ID-related genes. Further enrichment analyses revealed biological pathways associated with ID-related brain dysfunction. Results: Metaanalysis revealed convergent functional abnormalities across rest and task states, including salience network alterations (bilateral insula hyperactivity, anterior cingulate hypoactivity), decreased default mode network activity (bilateral precuneus), and executive function circuit disruptions. Critically, conjunction analysis identified stateindependent hypoactivation of the right inferior frontal gyrus. Functional decoding revealed this region's involvement in executive functions including inhibitory control, working memory, and attention. At molecular level, transcriptomic analysis identified 1,036 genes related to neural functional alterations. Positive genetic components were enriched for synaptic functions, whereas negative components linked to carbohydrate metabolism and mitochondrial processes. Conclusions: These findings reveal convergent neural dysfunction and underlying molecular mechanisms in ID, highlighting right inferior frontal gyrus hypoactivation as a candidate biomarker, and the identified synaptic and metabolic pathways as therapeutic targets for insomnia treatment.
Wang et al. (Wed,) studied this question.