Sex-specific alterations of cerebral blood flow in subjective tinnitus patients: an arterial spin labeling study

Objective: To explore the cerebral blood flow (CBF) alterations in chronic subjective tinnitus and to characterize the sex-related neural differences in tinnitus patients using arterial spin labeling (ASL) MRI. Methods: Fifty-two tinnitus patients and 51 healthy age- and sex-matched controls were recruited. The SPM8 was used for voxel-wise whole-brain analyses based on Gaussian random field correction. Region-of-interest (ROI) analyses were conducted according to the AAL-90 atlas. The associations between regional CBF and clinical measures, including Tinnitus Handicap Inventory (THI), Tinnitus Evaluation Questionnaire (TEQ), and Visual Analog Scale (VAS), were explored. Subgroup analyses were performed to characterize the sex-specific perfusion patterns. Results: Compared with the controls, the tinnitus patients showed relative hypoperfusion in inferior frontal gyrus, superior temporal gyrus, insula, and opercular regions; while showed relative hyperperfusion in postcentral gyrus, inferior parietal lobule, angular gyrus, supramarginal gyrus, and superior parietal lobule. The CBF in opercular inferior frontal gyrus was positively correlated with tinnitus loudness. In sex-specific analyses, compared with the female patients, the male tinnitus patients showed relative greater hyperperfusion in frontal and precentral cortices; while the female patients showed stronger increases in parietal regions. In healthy controls, males showed greater perfusion in medial prefrontal regions, and females showed stronger activity in sensorimotor and associative cortices. Conclusion: Chronic tinnitus is characterized by widespread CBF alterations in both auditory, cognitive-emotional and attentional networks. Sexually dimorphic perfusion patterns characterize distinct neuropathological mechanisms in tinnitus and support the potential of ASL perfusion imaging for precision medicine strategies in tinnitus.