Abnormal developmental trends of functional connectivity in young children with infantile esotropia

Abstract

Previous studies have shown that functional networks are present at birth and change dynamically throughout infancy and early childhood. However, the status of functional connectivity is still poorly understood in patients with infantile esotropia (IE). The aim of this study is to investigate the developmental trends of functional connectivity in patients with IE during a critical period of growth and development. A total of 17 patients with IE (9 males and 8 females; mean age: 3.36 ± 2.03 years, age range: 0.67–6.36 years) and 20 healthy subjects matched for age and gender were recruited and underwent resting-state functional magnetic resonance imaging. The whole-brain functional network connectivity was analyzed for the IE group and healthy control group. A general linear model was applied to assess the group-age interaction in terms of the functional connectivity. The discrepancy between the two groups in functional connectivity trajectories was also quantified across age and exhibited by the quadratic parabolic model. There were significant group-age interactions between the visual network and the default mode network, the visual network and the sensorimotor network, the limbic network and the default mode network, and within the limbic network in the functional connectivity. A U-shaped tendency across age, with an “inflection point” ranging from 3.1 to 4.0 years of age was exhibited in the difference between functional connectivity trajectories of the IE patients and normal controls. Abnormality in functional network connectivity could present in IE patients at birth, exhibiting aberrant developmental patterns over time. An abnormal functional network could reduce the ability of the cortex in visual information processing, further reactivating the subcortical visual information processing system, which is probably the pathogenesis of IE. Three to four years after birth is the critical time window for children with IE to establish normal network connections in the brain. Early surgery during this period may be helpful for affected children to have an opportunity to approach the normal development trajectory as early as possible.

Alterations of large‐scale functional network connectivity in patients with infantile esotropia before and after surgery

“…Interestingly, in this study, we demonstrated apparent negative correlations of the age at surgery with longitudinal FC changes in terms of CEN-DMN and V1N-LN, suggesting that the earlier the strabismus surgery is performed, the more benefits the IE patients will obtain in visual processing or emotion regulation, which emphasizes the impor-tance of the timely intervention for IE patients. More importantly, the findings provide robust evidence for our previous hypothesis from cross-sectional studies that corrective surgery for IE patients should be implemented in the early postnatal period to help the affected children to approach the normal developmental trajectories in FC (Guo, Chen, Liu et al, 2022a).…”

“…At baseline, 32 patients with IE and 30 control participants accomplished the resting‐state fMRI scanning and clinical evaluations. Partial data of cross‐sectional analysis have been reported (the original research includes 17 IE patients and 20 healthy controls) (Guo, Chen, Liu et al., 2022a ). The current study recruited additional participants for both IE group and control group and collected new postoperative longitudinal data of IE patients.…”

“…Besides, VN was further divided into medial visual network (V1N) and occipital pole visual network (V2N). Networks were selected as a result of their association with the visual, sensorimotor, and neurocognitive aspects of IE patients (Guo, Chen, Huang et al, 2022a;Guo, Chen, Liu et al, 2022b). For V1N/V2N/SMN, a sphere with 6-mm radius, centered at the global maximum of each network map (Smith et al, 2009), was defined as the seed region (Gao et al, 2013) (Gao & Lin, 2012;Seeley et al, 2007;Vincent et al, 2008), which were located at bilateral intraparietal sulcus, anterior insula, and dorsolateral prefrontal cortex.…”

“…Majority of the studies on resting-state FC, in the context of strabismus, laid importance on V1-based FC analyses, with similar findings of deficient interactions between visual cortex and brain regions pertaining to stereopsis or eye movement Liu et al, 2022;Yan et al, 2019;Zhu et al, 2018). Attaching importance to intra-and internetwork connectivity, instead of regional or global FC, suggests an advance on preceding studies, particularly in view of prominent evidence of disrupted between-network FC in patients with IE (Guo, Chen, Liu et al, 2022a). The VN-SMN internetwork FC is disrupted in IE patients, of which the defects occur in the early postnatal period and persist across the infancy and early childhood, showing a characteristic developmental trajectory with age.…”

“…In addition, controversies concerning the timing of surgery for IE remain difficult to figure out (Mehner et al., 2023 ). Our previous cross‐sectional research has suggested that, compared to healthy subjects, patients with IE have an aberrant developmental trajectory of FC from birth, exhibiting great potential for correction of compromised neurodevelopment during the early postnatal period, thus, the timely surgical interventions may bring satisfactory benefits for improvements in visual function as well as other visual‐related brain functions (Guo, Chen, Liu et al., 2022a ). However, longitudinal studies are necessary for better understanding the effects of surgical intervention on functional recovery of IE during the crucial period of growth and development.…”