Synopsis

Keywords: Nerves, Brain, Convergence insufficiency; brain function; functional connectivity; fALFF

Convergence insufficiency (CI) is the most common binocular vision disorder in optometric clinics relevant to the dysfunction of the specific neural circuit, while the neural mechanism is unknown. Using the fractional amplitude of low-frequency fluctuations fALFF and seed-to-voxel analysis, we found increased fALFF in the left cerebellum crus 1 and increased functional connectivity between the left cerebellum crus 1 and the right cerebellum crus 1 in patients with CI than healthy controls, which showed positive correlations with the severity of symptoms. These findings provide evidence of altered brain function features underlying neurobiological mechanisms of patients with CI.

Background

Convergence insufficiency (CI) is the most common binocular vision disorder in optometric clinics in which the eyes have a strong tendency to drift outward with difficulty turning the eyes inward when reading or doing close work1. Patients with CI always exhibit several symptoms such as eye sore, eye hurt, double vision, blurring, and even headaches when occupying near work, especially after reading or computer work, because the two eyes do not converge adequatedly2.To maintain a good binocular single vision, the visual system uses the specific neural circuit to mediate eye movement in near work3. Previous studies reported that the incidence of CI is 42%-43% in patients with acquired brain injure4, suggesting that neural alterations are possibly associated with CI. The precise neural mechanism for this disorder, however, is still unknown. Resting-state functional magnetic resonance imaging (rs-fMRI) provides essential insights to reveal the neural mechanism of various disorders and has been used to investigate many different eye conditions, such as amblyopia and glaucoma5, 6. Thus, this study aimed to examine the underlying intrinsic brain functional abnormalities in patients with CI compared to healthy controls (HCs) using rs-fMRI.

Methods

CI dysfunction was diagnosed by an optometrist using methods described in our previous study7. We recruited 34 patients with CI and 35 HCs in our study.Convergence Insufficiency Symptom Survey (CISS): Before the accommodative and binocular tests, symptoms were examined using the validated CISS 8, 9, which was translated into Chinese based on the Brislin translation model 10.Accommodative and binocular tests: All participants underwent an optometric examination by two optometrists (Y.W and L.X). The accommodative and binocular tests included the following assessments: the direction and magnitude of horizontal and vertical phoria, accommodative convergence/accommodation ratios, positive and negative fusional vergence (PFV/NFV), positive and negative relative accommodation, the near point of convergence (PAN), accommodative facility, vergence facility, and accommodative amplitude. Details about this battery of tests have been described in our previous publication 10. Brain rs-fMRI data were analyzed using the fractional amplitude of low-frequency fluctuations (fALFF) approach. Meanwhile, fALFF value was normalized to the Z-value (zfALFF) in order to reduce individual variances in overall whole-brain fALFF values. Then, a seed-to-voxel whole brain functional connectivity (FC) analysis will be applied based on the results of the voxel-based whole-brain fALFF analysis. Spearman partial correlation analyses were performed to explore the relationships between altered fALFF and FC and clinical symptom severity in all participants, with age and sex as covariates. The significant statistic threshold was set at P<0.05 with corrections for multiple comparisons.

Results

Compared with HCs, patient with CI showed increased fALFF in left cerebellum crus 1 (Figure 1). The seed-based FC analysis showed that left cerebellum crus 1 showed increased FC with right cerebellum crus 1 in patients with CI than HCs (Figure 2). The fALFF and FC values were positively correlated with symptom scores measured by CISS and NPC, and negatively correlated with horizontal phoria at near (PAN) and PFV (Tables 1 and 2).

Discussion

The visual system has a three-level hierarchy in controlling saccadic eye movement in which the cerebellum plays a significant role in maintaining the accuracy of saccades as the second level12, and the lesions in the cerebellar vermis lead to convergence dysfunction13. To a certain extent that fALFF indexes underlying neural activity, our results reveal that the left cerebellum activity and synchronization of metabolic mand from the neurons between bilateral cerebellum were increased in patients with CI. The CISS, NPC, PAN, and PFV measure the severity of CI. The higher CISS score and NPC values but the lower PFV and PAN values, the more severe the symptoms. Thus, the positive correlations between fALFF in the left cerebellum and FC between bilateral cerebellum and CISS scores and NPC and negative correlation with PAN and PFV may suggest that the brain needs more efforts in bilateral cerebellum to maintain good single binocular vision because of more serious exophoria in patients with CI, resulting in more severe visual symptoms.

Conclusion

In conclusion, we found that patients with CI showed increased fALFF in left cerebellum and increased FC between bilateral cerebellum compared with HCs. Moreover, significant correlations between fALFF and FC values and the severity of symptoms measured by CISS, NPC, PAN, and PFV were found. These findings contribute to a better understanding of the underlying neural mechanism of CI.

Acknowledgements

No acknowledgement found.

References

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