Regional cerebral blood flow correlates with transcriptional and cellular signatures in tinnitus.

PURPOSE: We aimed to examine alterations of brain regional cerebral blood flow (CBF) in tinnitus patients using arterial spin labeling (ASL), and applied an integrative imaging-transcriptomics approach to explore the potential transcriptional and cellular correlates of these changes.

METHODS

Participants included tinnitus patients (n = 56) and healthy controls (HCs) (n = 57). CBF images were acquired using an ASL sequence and analyzed. We used partial least square (PLS) regression to examine the spatial association between human brain gene expression (from the Allen Human Brain Atlas) and regional CBF changes in tinnitus. Bioinformatics and brain cell-type enrichment analyses were conducted using the genes that contributed significantly to the first PLS component.

RESULTS

Compared with HCs, tinnitus patients exhibited increased CBF, primarily in the transverse temporal and superior temporal gyrus (pFDR < 0.05). These CBF increases were positively correlated with perceived tinnitus loudness (VAS score, r = 0.34, p = 0.0009), but not with tinnitus handicap (THI score). The first PLS component explained 30.87% of CBF changes (pboot = 0.001), showing a strong spatial correlation between the weighted gene expression map and the case-control CBF t-map (r = 0.56, pspin < 0.05). Gene Ontology (GO) analyses revealed that the most significant gene sets were enriched for biological pathways related to protein phosphorylation. These negatively weighted genes were also significantly associated with GABAergic neurons.

CONCLUSION

Our findings identify spatial associations between genes, biological pathways, cell classes, and in vivo imaging correlates of tinnitus, particularly processes involving protein phosphorylation.