Background and PurposeAlthough previous neuroimaging studies have demonstrated emotion- and psychology-associated brain abnormalities in patients with thyroid-associated ophthalmopathy (TAO), the changes of brain functional connectivity in TAO were seldom focused. We aimed to investigate interregional and intraregional functional interactions in patients with TAO by using resting-state functional MRI (rs-fMRI) with long- and short-range functional connectivity density (FCD) analysis.MethodsThirty patients with TAO and 30 well-matched healthy controls (HCs) were recruited in our study. Long- and short-range FCD values were calculated and compared between the two groups. Correlations between long- and short-range FCD values and clinical indicators were analyzed.ResultsCompared with HCs, patients with showed both increased long- and short-range FCDs in the left middle frontal gyrus (MFG), orbital part of superior frontal gyrus (ORBsup), and dorsolateral part of superior frontal gyrus (SFGdor); meanwhile, both decreased long- and short-range FCDs in bilateral postcentral gyrus (PoCG), left superior parietal gyrus (SPG), and inferior parietal (IPL). In addition, patients with TAO showed increased short-range FCD in the right SFGdor, bilateral medial part of superior frontal gyrus (SFGmed), left orbital part of middle frontal gyrus (ORBmid), and orbital part of inferior frontal gyrus (ORBinf), as well as decreased short-range FCD in the right supplementary motor area (SMA) and the left paracentral lobule (PCL) than HCs. Moreover, the short-range value in the left SFGdor showed a negative correlation with Montreal Cognitive Assessment (MoCA) score (r = −0.501, p = 0.005).ConclusionOur findings complemented the functional neural mechanism of TAO, and provided potential neuroimaging markers for assessing the psychiatric, visual, and emotional disturbances in patients with TAO.

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.