Altered static and dynamic functional connectivity in childhood basic-type intermittent exotropia

This study aimed to investigate static and dynamic functional connectivity alterations between the primary visual cortex, secondary visual cortex, higher visual cortex and oculomotor cortex in children with basic-type intermittent exotropia. A total of 44 children with basic-type intermittent exotropia and 37 healthy controls matched for sex, age and education level were included and underwent resting-state functional MRI. Both sides of Brodmann area (BA) 17, BA18, BA19 and BA8 were chosen as regions of interest. Sliding window method and k-means clustering analysis were employed to investigate static and dynamic functional connectivity as well as temporal metrics based on visual cortices and oculomotor cortices. Differences in functional connectivity and temporal metrics were identified and subsequently correlated with clinical characteristics using Pearson correlation analysis. Diagnostic efficacy of static and dynamic functional connectivity as well as near stereoacuity was assessed using receiver operating characteristic analysis. For static functional connectivity analysis, compared with healthy controls, children with intermittent exotropia showed decreased static functional connectivity between the right higher visual cortex (BA19) and the left oculomotor cortex (BA8), as well as between bilateral oculomotor cortices (BA8). For dynamic functional connectivity analysis, children with intermittent exotropia showed increased dynamic functional connectivity variability between the right secondary visual cortex (BA18) and the left higher visual cortex (BA19), as well as between the left higher visual cortex (BA19) and the right oculomotor cortex (BA8). In addition, the mean dwell time and fraction time in a specific state characterized by negative connectivity between visual cortices and oculomotor cortices were positively correlated with the disease duration. Receiver operating characteristic analyses demonstrated that the combination of static and dynamic functional connectivity exhibited high diagnostic performance for basic-type intermittent exotropia. Children with basic-type intermittent exotropia exhibited aberrant static and dynamic functional connectivity within the bilateral visual-oculomotor cortex pathways, which might be associated with visual perception and eye movement impairments. With the prolongation of disease duration, more time spent in a specific state might be related to aggravated eye movement disorder. The combination of static and dynamic functional connectivity provides a new perspective for exploring the neuropathological mechanisms of basic-type intermittent exotropia and offers a potential neuroimaging biomarker for diagnosis.