Altered neurovascular coupling in thyroid-associated ophthalmopathy: A combined resting-state fMRI and arterial spin labeling study

Besides the well-documented ophthalmic manifestations, thyroid-associated ophthalmopathy (TAO) is believed to be related to emotional and psychological abnormalities. Given the previous neuroimaging evidence, we hypothesized that TAO patients would have altered neurovascular coupling associated with clinical-psychiatric disturbances. This study was to investigate neurovascular coupling changes in TAO by combining resting-state functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling (ASL) techniques. Amplitude of low-frequency fluctuation (ALFF) was calculated from rs-fMRI, and cerebral blood flow (CBF) was computed from ASL in 37 TAO patients and 21 healthy controls (HCs). Global neurovascular coupling was assessed by across-voxel CBF-ALFF correlation, and regional neurovascular coupling was evaluated by CBF/ALFF ratio. Auxiliary analyses were performed using fractional ALFF (fALFF) and regional homogeneity (ReHo) as rs-fMRI measures. Compared with HCs, TAO patients showed significantly reduced global CBF-ALFF coupling. Moreover, TAO patients exhibited decreased CBF/ALFF ratio in the left lingual gyrus (LG)/fusiform gyrus (FFG), and increased CBF/ALFF ratio in the bilateral precuneus (PCu). In TAOs, CBF/ALFF ratio in the left LG/FFG was positively correlated with visual acuity, while CBF/ALFF ratio in the bilateral PCu was negatively correlated with Montreal Cognitive Assessment score. The auxiliary analyses showed trends of reduced global neurovascular coupling (i.e., CBF-fALFF correlation and CBF-ReHo correlation), as well as significant altered regional neurovascular coupling (i.e., CBF/fALFF ratio and CBF/ReHo ratio) in several brain regions. These findings indicated that TAO patients had altered neurovascular coupling in the visual and higher-order cognitive cortices. The neurovascular decoupling might be a possible neuropathological mechanism of TAO.