Skip to main content
Download PDF

Altered functional connectivity of resting-state networks and the correlation with clinical characteristics in intermittent exotropia adult patients: a resting-state magnetic resonance imaging study

BMC Ophthalmology volume 24, Article number: 411 (2024) Cite this article

Abstract

Background

The pathogenesis of intermittent exotropia (IXT) remains unclear. The study aims to investigate alterations of resting-state networks (RSNs) in IXT adult patients using resting-state functional magnetic resonance imaging (rs-fMRI) data to explore the potential neural mechanisms.

Methods

Twenty-six IXT adult patients and 22 age-, sex-, handedness-, and education-matched healthy controls (HCs) underwent fMRI scanning and ophthalmological examinations. Brain areas with significant functional connectivity (FC) differences between the IXT and HC groups were selected as regions of interest (ROI) and mean z-scores were calculated to control for individual differences.

Results

Compared with HCs, IXT patients exhibited altered FC in various brain regions within RSNs involved in binocular fusion, stereopsis, ocular movement, emotional processes and social cognition, including the default mode network (DMN), the dorsal attention network (DAN), the visual network (VN), the sensorimotor network (SMN), the executive control network (ECN), the frontoparietal network (FPN) and the auditory network (AN). The degree of exodeviation was positively correlated with FC value of left middle occipital gyrus (MOG) within the VN. Correspondingly, we found a negative correlation between the degree of exodeviation and the FC value of left angular gyrus (AG) within FPN (P < 0.05). The FNC analysis between different RSNs also provides evidence on visual-motor cortical plasticity.

Conclusions

IXT patients showed widespread changes of brain activity within RSNs related to binocular fusion, stereopsis, oculomotor control, emotional processes, and social cognition. These findings extend our current understanding of the neuropathological mechanisms of IXT.

Trial registration

Beginning date of the trial: 2021-09-01. Date of registration:2021-07-18. Trial registration number: ChiCTR 2,100,048,852. Trial registration site: http://www.chictr.org.cn/index.aspx.

Peer Review reports

Background

As the most common subtype of strabismus [1], intermittent exotropia (IXT) manifests as progressive deviation appearance, and leads to impaired binocular fusion and stereoscopic function [2, 3]. The incidence of IXT is about 1% in United States and 3.9% in Asia [4, 5]. IXT can also result in psychosocial problems owing to changes in facial appearance and binocular function impairment [6, 7], and may even increase the risk of affective and anxiety disorders [8].

The underlying mechanisms of IXT are still unclear. Previous studies suggested that anatomical changes of extraocular muscles were the main cause [9,10,11]. Kim et al. found that the ultrastructure of what were described as the “tendon axonal profiles” of IXT patients degenerates over time [10]. Another study found that the medial rectus muscle of IXT patients had a large muscle fiber diameter and small low proportions of PAX7- and PCNA-positive cells relative to the number of muscle fibers per unit area [9]. However, the previously extraocular muscle-related mechanism is incorrect, which could explain the high recurrence rate of 43.9% after surgery [12]. It is increasingly being suggested that the cortical changes may be essential for IXT occurrence and progression. Recent studies found abnormal changes in brain regions related to binocular fusion, stereopsis, and ocular movement in IXT patients [13, 14]. Using functional magnetic resonance imaging (fMRI), He et al. [13] found functional abnormalities in binocular fusion-related regions such as the precuneus (PCUN), stereopsis-related regions including the middle occipital gyrus (MOG), angular gyrus (AG), supramarginal gyrus (SMG) and right inferior parietal lobule, and oculomotor-related regions including the precentral gyrus and postcentral gyrus (PosCG). They also observed abnormal functional connectivity (FC) between primary visual cortex (V1), secondary visual cortex, and oculomotor cortex in IXT patients [15]. In a task-based fMRI study, Li et al. found abnormalities in brain regions involved in binocular fusion such as the MOG, inferior temporal lobule and PCUN in IXT patients [14]. Furthermore, Wang et al. identified a significant reduction in the surface area of the left V1 in IXT patients, and increased surface area and cortical thickness in visual associated cortices including the inferior temporal cortex, orbitofrontal cortex, middle temporal cortex, and inferior frontal cortices [16].

These studies have shed light on the neural mechanisms of IXT, while there is little published data on the brain network of IXT patients. Recent studies reported abnormalities in resting-state networks (RSNs) in patients with strabismus. Kang Yu et al. observed a significant increase in the visual network(VN) and sensorimotor network (SMN) activity in patients with strabismus [17]. Jin reported that individuals with concomitant exotropia had abnormalities in the cerebellar network, SMN, VN, and auditory network (AN) [18]. However, there is wide variation among the different types of strabismus, including the underlying mechanisms. Taken together, the above results cannot explain the etiology of IXT, and the neural pathology remains to be elucidated.

Independent component analysis (ICA), which is a fully data-driven approach, can achieve blind source separation of fMRI signals and has been widely used for identifying RSNs, given its ability to isolate various brain function networks [19, 20]. Based on previous studies, we hypothesized that IXT patients would exhibit abnormal alterations of RSNs; this hypothesis was tested using ICA method.

Materials and methods

Participants

This cross-sectional study was approved by the Ethics Committee and Institutional Review Board of Capital Medical University, Beijing Tongren Hospital (TRECKY2020-139). Written informed consent was obtained from all participants. Twenty-six IXT patients and twenty-two gender-, age-, and education-matched healthy controls (HCs) were enrolled between May 2020 and August 2021 from the outpatient clinics of the department of Strabismus and Pediatric Ophthalmology in a tertiary medical center. All participants underwent detailed ophthalmological examinations that included best-corrected visual acuity (BCVA), slit lamp examination, synoptophore and Random-dot stereogram. To evaluate the severity of IXT, all patients were assessed for the exodeviation degree using the prism cover test. The inclusion criteria were as follows: (1) IXT diagnose by two ophthalmologists, (2) aged ≥ 18 years, (3) BCVA ≥ 1.0, and (4) the availability of high-quality brain structural and functional imaging data. The exclusion criteria were as follows: (1) strabismus other than IXT, such as constant exotropia accompanied by vertical strabismus, (2) a history of other ocular diseases, (3) previous ocular or brain surgery, (4) serious physical or mental diseases, or brain diseases confirmed by conventional MRI, and (5) significant head motion (> 2 mm maximum displacement in any direction or angular rotation > 2°) during the MRI scan. The demographic and clinical characteristics of the 26 IXT patients and 22 HCs are presented in Table 1.

Table 1 Demographic and clinical characteristics of IXT patients and HCs
Full size table

Image acquisition

All participants underwent MRI examinations performed using a 3.0 T MRI scanner (General Electric Medical Systems, Milwaukee, WI, USA) with an eight-channel phased array coil. They were instructed to rest quietly and relax, without thinking about anything in particular or falling asleep. Earplugs and foam padding were used to decrease scanner noise and head motion.

The following parameters were used for high-resolution T1-weighted imaging: repetition time/echo time (TR/TE), 8.8/3.5ms; field of view (FOV), 240 × 240 mm2; matrix, 256 × 256; slice thickness, 1.0 mm; no gap; flip angle, 13°; and number of slices, 176. The resting-state fMRI data were obtained using an echo planar imaging pulse sequence with the following parameters: TR/TE, 2,000/35ms; FOV, 240 × 240 mm2; matrix, 64 × 64 slice thickness, 3 mm; gap, 1 mm; flip angle, 90°; and number of slices, 180.

Data preprocessing

Data preprocessing was conducted using Gretna software (version 2.0.0; https://www.nitrc.org/projects/gretna/). To allow the signal to stabilize, the first 10 volumes of each subject were removed; this was followed by slice timing, head motion correction, spatial normalization to the Montreal Neurological Institute template (resampling voxel size = 3 × 3 × 3 mm3), and spatial smoothing with a 6 × 6 × 6 mm3 Gaussian kernel.

Independent component analysis (ICA)

ICA was performed using the GIFT toolbox (version 2.0a; https://www.nitrc.org/projects/gift,). The procedure was as follows: (1) data reduction at the individual level, (2) independent component (IC) decomposition using the InfoMax algorithm [21], and (3) standard reconstruction. At present, there is no consensus regarding the optimal number of components. We distinguished 30 ICs and normalized the values using z-scores. In this manner, 30 independent spatial distribution maps and corresponding time series data were obtained. Consistent with previous studies [21, 22], seven RSNs were identified: the VN, SMN, dorsal attention network (DAN), default mode network (DMN), executive control network (ECN), frontoparietal network (FPN), and auditory network (AN).

Statistical analysis

The RSN spatial map for all subjects was subjected to the one-sample t-test to obtain spatial patterns of the seven abovementioned networks in both groups. P-values < 0.001 were considered significant (no voxel-wise correction). Functional network connectivity (FNC) values were compared between the groups using the two-sample t-test. P-values < 0.05 were considered significant (AlphaSim-corrected) and the analysis was limited to voxels within the seven RSNs. Brain areas with significant FC differences between the IXT and HC groups were selected as regions of interest (ROI) and mean z-scores were calculated to control for individual differences. Associations between FC in the RSNs and the degree of exodeviation in IXT patients were analyzed using Pearson correlation; P-values < 0.05 were considered significant. The relevant calculation was then performed using the mean z-scores within the ROI. The analyses were performed using SPSS software (ver. 20.0; SPSS Inc., Chicago, IL, USA).

Results

Demographics and clinical characteristics

26 IXT patients (mean age: 28.2 ± 8.1 years; 14 men) and 22 HCs (mean age: 28.8 ± 6.5 years; 10 men) were enrolled in this study. These two groups did not differ significantly in age, sex, handedness, education or the BCVA. Among IXT patients, the mean angle of exodeviation was 73.10 ± 29.68 prism diopters (PD) at near (ranging from 15 to 140) and 69.05 ± 30.77 PD at distance (ranging from 25 to 140), and the median near stereoacuity was 2.20 ± 0.38 log arcsec. In HC group, the median near stereoacuity was 1.97 ± 0.35 log arcsec. The status of binocular function was significantly worser in patients with IXT compared with HC (P = 0.019). Details are provided in Table 1.

Abnormal intranetwork FC analysis

Compared with HCs, IXT patients exhibited a significantly increase in FC of the right anterior cingulate gyrus (ACG) and paracingulate gyrus (PCG) within the DMN, and of the left ACG and PCG within the DAN. In addition, IXT patients showed decreased FC of right calcarine fissure and left middle occipital gyrus (MOG) within the VN (Fig. 1 and 3A); right supplementary motor area (SMA), right precuneus (PCUN) and right postcentral gyrus (PosCG) within the SMN; left PCUN and bilateral mid temporal gyrus (MTG) within the DMN; right superior occipital gyrus (SOG) and right supramarginal gyrus (SMG) within the DAN; right cuneus (CUN) within the ECN; left angular gyrus (AG) within the FPN (Fig. 1 and 3A); and the superior temporal gyrus (STG) within the AN (P<0.05, AlphaSim-corrected) (Table 2; Figs. 1 and 2).

Fig. 1
figure 1

Altered FC value of diverse regions within RSNs between two groups. AlphaSim correction was applied to investigate group differences with ROIs at a threshold of P = 0.05. HC, healthy control; IXT, intermittent exotropia; FC, functional connectivity; ACG, anterior cingulate; PCG, paracingulate gyrus; MOG, middle occipital gyrus; SMA, supplementary motor area; PCUN, precuneus; PosCG, postcentral gyrus; MTG, middle temporal gyrus; SOG, superior occipital gyrus; SMG, supramarginal gyrus; CUN, cuneus; AG, angular gyrus; STG, superior temporal gyrus. RSN, resting-state network; SMN, sensorimotor network; VN, visual network, DAN, dorsal attention network; DMN, default mode network; ECN, executive control network; FPN, frontoparietal network; AN, auditory network

Full size image
Table 2 Altered intranetwork functional connectivity in the IXT patients vs. HCs
Full size table
Fig. 2
figure 2

Altered functional connectivity in brain regions with significant differences for 7 resting-state networks in the IXT group vs. the HC group (two-tailed, p < 0.05, cluster, AlphaSim correction). HC, healthy control; IXT, intermittent exotropia; DMN, default mode network; DAN, dorsal attention network; VN, visual network; SMN, sensorimotor network; ECN, executive control network; FPN, frontoparietal network; AN, auditory network; ACG, anterior cingulate gyrus; PCG, paracingulate gyrus; MOG, middle occipital gyrus; SMA, supplementary motor area; PCUN, precuneus; PosCG, postcentral gyrus; MTG, middle temporal gyrus; SOG, superior occipital gyrus; SMG, supramarginal gyrus; CUN, cuneus; AG, angular gyrus; STG, superior temporal gyrus

Full size image

Correlation between FC of RSNs and clinical characteristics

We found a significant positive correlation between the degree of exodeviation at near and FC value of left MOG within the VN (r = 0.5229, r2 = 0.2734, P = 0.015; Fig. 3B), as well as the degree of exodeviation at distance and FC value of left MOG within VN (r = 0.509, R2 = 0.259, P = 0.018; Fig. 3B). Correspondingly, a significant negative correlation was found between the FC value of left AG within FPN and the degree of exodeviation at near (r = -0.4912, r2 = 0.2413, P = 0.023; Fig. 3B), the FC value of left AG within FPN and the degree of exodeviation at distance (r = -0.4984, r2 = 0.2484, P = 0.0215; Fig. 3B). No associations were found between the FC values in significant altered brain regions and other clinical characteristics.

Fig. 3
figure 3

Independent component analysis and correlations with clinical characteristics in IXT patients. A Decreased functional connectivity in the left middle occipital gyrus (MOG) within visual network (VN) and left angular gyrus (AG) within frontoparietal network (FPN) in IXT patients compared with HCs at a threshold of p < 0.005 (AlphaSim-corrected). B Correlations between degree of exodeviation and FC values in the left MOG with VN and left AG within FPN with p < 0.05 (Pearson correlation). HC, healthy control; IXT, intermittent exotropia; FC, functional connectivity; MOG, middle occipital gyrus; AG, angular gyrus; VN, visual network; FPN, frontoparietal network

Full size image

Functional network connectivity analysis

Compared with HCs, higher functional network connectivity (FNC) coefficients for the DAN IC13-RFPN IC1 and RFPN IC1-SMN IC25 and lower FNC coefficients for the SMN IC25-VN IC11 were seen in IXT patients (Fig. 4).

Fig. 4
figure 4

Functional Network Connectivity (FNC) between different RSNs. The SMN-RFPN, RFPN-DAN and SMN-VN connections were found to be significantly altered between two groups (p < 0.05, voxel, none). RSN, resting state network; VN, visual network, DAN, dorsal attention network; SMN, sensorimotor network; RFPN, right frontoparietal network

Full size image

Discussion

To the best of our knowledge, this is the first study to investigate the intrinsic FC in IXT patients through ICA. Recently, the combination of neuroscience examination and the ophthalmic evaluations have provided useful exploration for further exploring and clarifying the relationship between visual cortex function dysfunction and plasticity, pathogenesis, treatment methods, and prognosis in IXT patients. Though this study, we hope to proceed from the neural mechanism and provide more data and references for the pathogenesis of IXT, and provide guidance for the development of clinical diagnosis and treatment. In this study, compared with HCs, we observed significant alterations of intranetwork FC in the IXT patients within several RSNs including the VN, SMN, DMN, DAN, ECN, FPN and AN, where these networks are involved in binocular fusion, stereopsis, oculomotor and emotional processes and social cognition. Moreover, FNC analysis also revealed significant differences in SMN–VN, DAN–FPN and FPN–SMN connectivity between the two groups.

Abnormal intranetwork FC analysis

Currently, we found decreased FC in right calcarine cortex and left MOG within VN, right PCUN within SMN, left PCUN and bilateral MTG within DMN, right SOG within DAN and right CUN within ECN, which could play a role in dysfunction in various facets of visual perception, including binocular fusion, visuospatial processing, and stereopsis.

Using task-based fMRI, Li et al. demonstrated an increase in bilateral PCUN activity, and suggested that the PCUN plays a role in binocular fusion [14]. The calcarine plays a critical role in the processing of spatial visual information. Wu et al. reported that patients with concomitant exotropia patients showed decreased ALFF values in the calcarine sulcus, and implicated abnormalities herein in visual processing impairments and stereovision [23]. Additionally, within the DMN, bilateral MTG activity was shown to be associated with three-dimensional surface orientation and retinal image velocities [24]. The SOG within DAN is the most important structure in the parietal eye field for visual function, and is also thought to be associated with saccades and in visuo-spatial information processing [25, 26]. Yu et al. suggested that impairment of the right MOG, bilateral calcarine and bilateral CUN may disrupt the integrity of the neural circuitry for vision, resulting in visuospatial impairment [17]. The right CUN within the ECN in IXT patients was shown to be associated with the abnormality of stereopsis and ocular movement [13]. It can be inferred that the CUN is heavily implicated in stereopsis impairment. The MOG within the VN plays an important role in the stereovision function, spatial processing, and so-called “category-selective attention-modulated face/tool processing” [27, 28]. Yan et al. also found that structural abnormalities in the MOG of individuals with concomitant exotropia were related to abnormalities in the dorsal visual pathway [29]. Decreased FC in the left MOG and calcarine (within the VN) may underlie dysfunction of binocular fusion, which is a feature of IXT [15]. It can be deducted that the above altered brain regions within RSNs could prompt the impairment of visuo-spatial processing, binocular fusion and stereopsis function, and may represent the underlying mechanism of IXT. Furthermore, the positive correlation between the FC value of MOG within VN and the degree of exodeviation observed in this study suggests that, to maintain normal binocular fusion and stereopsis during the progression of IXT, the MOG engages in compensatory processes.

Decreased FC in the right PosCG within the SMN and left AG within the FPN were observed in our IXT patients in association with eye movement. In our previous study, we observed abnormal FC between the left primary visual cortex(V1) and right PosCG, along with decreased ALFF values in the PosCG of IXT patients, consistent with the present results; which suggested that the PosCG was related to the ocular movements [27]. Moreover, we noted decreased FC in the right PosCG within the SMN. A previous study reported functional connections between many brain regions in SMN and the primary motor cortex(M1) [30]. The development of motor control is related to changes in synaptic strength in the primary motor cortex [31,32,33,34,35]. The decreased FC between PosCG and V1 and M1 seen in IXT patients indicates that ocular movement impairment may disrupt the processing of binocular visual information. The AG is also important for ocular movement; it processes visual information and passes it to the frontal lobe [25]. We observed decreased FC in the left AG within the FPN, which may impair ocular movement control and accelerate the progression of IXT. Long-standing oculomotor abnormalities can disturb the normal pattern of retinal correspondence [36]. We proposed that a decrease in in right PosCG within the SMN and left AG within the FPN may lead to the dysfunction in oculomotor control and coordination, which would in turn exacerbate exodeviation. Furthermore, we also found a negative correlation between the FC of AG within the FPN and the degree of exodeviation. Taken together, the results suggest that FC of the AG within the FPN could serve as a biomarker of the severity of oculomotor cortex impairment in IXT patients.

Besides, decreased FC was observed in the left STG within AN, right SMA within the SMN and right SMG within the DAN. Conversely, the FC value of right ACG and PCG within the DMN and left ACG and PCG within the DAN presented increase in IXT patients. All of these brain regions are involved in cognition, attention and emotion. The top-down attentional control is mediated by the ACG [37], and the SMA is fundamental for the processing of information related to emotions and cognitive functions; a decrease in SMA activity can result in attention deficits [34, 35]. Jonathan et al. found that attention-drawing auditory stimuli can deactivate the visual association cortex [38]. Bilateral STGs within the AN play an important role in the monitoring and reassessment of behavior [39]. Increased activity within the DMN is closely associated with increased sensitivity to both the external environment and self-referential/reflective thought [40]; in particular, increased connectivity in affective regions may reduce connectivity in regions associated with cognitive processing, such as the ACG [41], which may help explain why IXT patients are more vulnerable to depression and anxiety. Additionally, the right SMG is crucial for overcoming egocentricity and developing the ability to recognize emotions [42], and is also associated with mind or empathy [43] and social communication [44]. Therefore, the above brain regions may be related to the impairments in emotional cognition, social communication and attention seen in IXT patients, which can lead to various psychological problems. It can be indirectly proved by a cross-sectional study which found a moderate association between strabismus and a series of mental and psychological problem such as anxiety disorder and schizophrenia [8].

Functional network connectivity analysis

Finally, our FNC analysis showed that the DAN -RFPN, RFPN -SMN and SMN-VN were found significantly altered in IXT patients. Since the FPN is critical in visual-spatial attention and motor function [45], and excessive connection of the SMN-RFPN, RFPN-DAN pathways might represent a compensatory mechanism for visual perception impairments in IXT patients. Moreover, disruption of the VN–SMN pathway may lead to binocular fusion and stereoscopic vision impairments, thus accelerating the progress of IXT. Studying altered interactions between RSNs may provide further insight into visuomotor and cortical plasticity.

Limitations

The current study had several limitations that should be acknowledged. First, we only investigated brain function changes in adult IXT patients, and the results may not apply to their pediatric counterparts. Second, although some changes in some brain regions involved in cognition, attention, and emotion were found, we did not evaluate the psychosocial status of the participants with dedicated scales. Finally, the sample size was not large.

Conclusions

IXT patients exhibited altered FC within several RSNs, including the VN, SMN, DMN, DAN, ECN, FPN and AN, which are associated with visual perception, oculomotor control, and social cognition. Also, our FNC analysis provided evidence of visuomotor and cortical plasticity. These findings improve our understanding of the neuropathological mechanisms of IXT. Moreover, the negative correlation between the FC value of the left AG within the FPN and degree of exodeviation suggested that FC of the AG could serve as a biomarker of the severity of oculomotor cortex impairment in IXT patients. Finally, the positive correlation between the FC value of the MOG within the VN and degree of exodeviation suggested a role for this structure in compensatory processes during the course of IXT.

Availability of data and materials

No datasets were generated or analysed during the current study.

References

  1. McKean-Cowdin R, Cotter SA, Tarczy-Hornoch K, Wen G, Kim J, Borchert M, Varma R. Multi-ethnic Pediatric Eye Disease Study G. Prevalence of amblyopia or strabismus in Asian and non-hispanic white preschool children: multi-ethnic pediatric eye disease study. Ophthalmology. 2013;120(10):2117–24.

    Article  PubMed  Google Scholar 

  2. Firth AY, Davis H, Horwood AM. Binocular visual acuity in intermittent exotropia: role of accommodative convergence. Am J Ophthalmol. 2013;155(4):776–7.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Read JC. Stereo vision and strabismus. Eye (Lond). 2015;29(2):214–24.

    Article  CAS  PubMed  Google Scholar 

  4. Pan CW, Zhu H, Yu JJ, Ding H, Bai J, Chen J, Yu RB, Liu H. Epidemiology of intermittent Exotropia in Preschool Children in China. Optom Vis Sci. 2016;93(1):57–62.

    Article  PubMed  Google Scholar 

  5. Govindan M, Mohney BG, Diehl NN, Burke JP. Incidence and types of childhood exotropia: a population-based study. Ophthalmology. 2005;112(1):104–8.

    Article  PubMed  Google Scholar 

  6. Mao D, Lin J, Chen L, Luo J, Yan J. Health-related quality of life and anxiety associated with childhood intermittent exotropia before and after surgical correction. BMC Ophthalmol. 2021;21(1):270.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Zhao BW, Fu J, Wang JH, Bai HX, Liu PP, Guo YN, Zhang RH, Su H. Quality of life in adult intermittent exotropia and the risk factors. Int J Ophthalmol. 2021;14(3):442–7.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Lee YH, Repka MX, Borlik MF, Velez FG, Perez C, Yu F, et al. Association of Strabismus with Mood Disorders, Schizophrenia, and anxiety disorders among children. JAMA Ophthalmol. 2022;140(4):373–81.

  9. Kim CZ, Lee SJ. Increased myofiber size and reduced satellite cell numbers in medial rectus muscle of patients with intermittent exotropia. Strabismus. 2020;28(4):201–7.

    Article  PubMed  Google Scholar 

  10. Kim SH, Cho YA, Park CH, Uhm CS. The ultrastructural changes of tendon axonal profiles of medial rectus muscles according to duration in patients with intermittent exotropia. Eye (Lond). 2008;22(8):1076–81.

    Article  PubMed  Google Scholar 

  11. Yao J, Wang X, Ren H, Liu G, Lu P. Ultrastructure of medial rectus muscles in patients with intermittent exotropia. Eye (Lond). 2016;30(1):146–51.

    Article  CAS  PubMed  Google Scholar 

  12. Al-Haddad C, Ismail K, Houry R, Al Sayyid S, El Moussawi Z. Recurrence of intermittent exotropia after bilateral lateral rectus recession. Middle East Afr J Ophthalmol. 2020;27(2):123–7.

    Article  PubMed  PubMed Central  Google Scholar 

  13. He X, Hong J, Wang Q, Guo Y, Li T, Qu X, Liu J, Li W, Zhang L, Fu J, Liu Z. Altered spontaneous brain activity patterns and functional connectivity in adults with intermittent Exotropia: a resting-state fMRI study. Front Neurosci. 2021;15:746882.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Li Q, Bai J, Zhang J, Gong Q, Liu L. Assessment of cortical dysfunction in patients with intermittent Exotropia: an fMRI study. PLoS ONE. 2016;11(8):e0160806.

    Article  PubMed  PubMed Central  Google Scholar 

  15. He X, Hong J, Liu Z, Wang Q, Li T, Qu X, Fei N, Li W, Fu J. Decreased functional connectivity of the Primary Visual Cortex and the correlation with clinical features in patients with intermittent Exotropia. Front Neurol. 2021;12:638402.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Wang X, Lu L, Liao M, Wei H, Chen X, Huang X, Liu L, Gong Q. Abnormal cortical morphology in children and adolescents with intermittent exotropia. Front Neurosci. 2022;16:923213.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Yu K, Lin Q, Ge QM, Yu CY, Li QY, Pan YC, Shao Y. Measuring functional connectivity in patients with strabismus using stationary functional magnetic resonance imaging: a resting-state network study. Acta Radiol. 2022;63(1):110–21.

    Article  PubMed  Google Scholar 

  18. Jin H, Chen RB, Zhong YL, Lai PH, Huang X. Effect of impaired stereoscopic vision on Large-Scale Resting-State Functional Network Connectivity in Comitant Exotropia patients. Front Neurosci. 2022;16:833937.

    Article  PubMed  PubMed Central  Google Scholar 

  19. De Luca M, Beckmann CF, De Stefano N, Matthews PM, Smith SM. fMRI resting state networks define distinct modes of long-distance interactions in the human brain. NeuroImage. 2006;29(4):1359–67.

    Article  PubMed  Google Scholar 

  20. Fox MD, Raichle ME. Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat Rev Neurosci. 2007;8(9):700–11.

    Article  CAS  PubMed  Google Scholar 

  21. Bell AJ, Sejnowski TJ. An information-maximization approach to blind separation and blind deconvolution. Neural Comput. 1995;7(6):1129–59.

    Article  CAS  PubMed  Google Scholar 

  22. Mueller S, Costa A, Keeser D, Pogarell O, Berman A, Coates U, Reiser MF, Riedel M, Moller HJ, Ettinger U, Meindl T. The effects of methylphenidate on whole brain intrinsic functional connectivity. Hum Brain Mapp. 2014;35(11):5379–88.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Wu Q, Guo W, Hu H, Li R, Zhu H, Chen XX, Xu XQ, Liu H, Wu FY. Altered spontaneous brain activity in patients with comitant exotropia before and after surgery: a resting-state fMRI study. Exp Eye Res. 2022;222:109161.

    Article  CAS  PubMed  Google Scholar 

  24. Nguyenkim JD, DeAngelis GC. Disparity-based coding of three-dimensional surface orientation by macaque middle temporal neurons. J Neurosci. 2003;23(18):7117–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Yang X, Zhang J, Lang L, Gong Q, Liu L. Assessment of cortical dysfunction in infantile esotropia using fMRI. Eur J Ophthalmol. 2014;24(3):409–16.

    Article  PubMed  Google Scholar 

  26. Waberski TD, Gobbelé R, Lamberty K, Buchner H, Marshall JC, Fink GR. Timing of visuo-spatial information processing: electrical source imaging related to line bisection judgements. Neuropsychologia. 2008;46(5):1201–10.

    Article  PubMed  Google Scholar 

  27. Zhu PW, Huang X, Ye L, Jiang N, Zhong YL, Yuan Q, Zhou FQ, Shao Y. Altered intrinsic functional connectivity of the primary visual cortex in youth patients with comitant exotropia: a resting state fMRI study. Int J Ophthalmol. 2018;11(4):668–73.

    PubMed  PubMed Central  Google Scholar 

  28. Fortin A, Ptito A, Faubert J, Ptito M. Cortical areas mediating stereopsis in the human brain: a PET study. NeuroReport. 2002;13(6):895–8.

    Article  PubMed  Google Scholar 

  29. Yan X, Lin X, Wang Q, Zhang Y, Chen Y, Song S, Jiang T. Dorsal visual pathway changes in patients with comitant extropia. PLoS ONE. 2010;5(6):e10931.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Biswal B, Yetkin FZ, Haughton VM, Hyde JS. Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn Reson Med. 1995;34(4):537–41.

    Article  CAS  PubMed  Google Scholar 

  31. Ziemann U, Ilić TV, Pauli C, Meintzschel F, Ruge D. Learning modifies subsequent induction of long-term potentiation-like and long-term depression-like plasticity in human motor cortex. J Neurosci. 2004;24(7):1666–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Bütefisch CM, Davis BC, Wise SP, Sawaki L, Kopylev L, Classen J, Cohen LG. Mechanisms of use-dependent plasticity in the human motor cortex. Proc Natl Acad Sci USA. 2000;97(7):3661–5.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Rioult-Pedotti MS, Friedman D, Hess G, Donoghue JP. Strengthening of horizontal cortical connections following skill learning. Nat Neurosci. 1998;1(3):230–4.

    Article  CAS  PubMed  Google Scholar 

  34. Downar J, Crawley AP, Mikulis DJ, Davis KD. A cortical network sensitive to stimulus salience in a neutral behavioral context across multiple sensory modalities. J Neurophysiol. 2002;87(1):615–20.

    Article  PubMed  Google Scholar 

  35. Seeley WW, Menon V, Schatzberg AF, Keller J, Glover GH, Kenna H, Reiss AL, Greicius MD. Dissociable intrinsic connectivity networks for salience processing and executive control. J Neurosci. 2007;27(9):2349–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Serrano-Pedraza I, Manjunath V, Osunkunle O, Clarke MP, Read JC. Visual suppression in intermittent exotropia during binocular alignment. Investig Ophthalmol Vis Sci. 2011;52(5):2352–64.

    Article  Google Scholar 

  37. Marois R, Chun MM, Gore JC. A common parieto-frontal network is recruited under both low visibility and high perceptual interference conditions. J Neurophysiol. 2004;92(5):2985–92.

    Article  PubMed  Google Scholar 

  38. Downar J, Crawley AP, Mikulis DJ, Davis KD. A multimodal cortical network for the detection of changes in the sensory environment. Nat Neurosci. 2000;3(3):277–83.

    Article  CAS  PubMed  Google Scholar 

  39. Adolphs R. Cognitive neuroscience of human social behaviour. Nat Rev Neurosci. 2003;4(3):165–78.

    Article  CAS  PubMed  Google Scholar 

  40. Zhou Y, Liang M, Tian L, Wang K, Hao Y, Liu H, Liu Z, Jiang T. Functional disintegration in paranoid schizophrenia using resting-state fMRI. Schizophr Res. 2007;97(1–3):194–205.

    Article  PubMed  Google Scholar 

  41. Greicius MD, Flores BH, Menon V, Glover GH, Solvason HB, Kenna H, Reiss AL, Schatzberg AF. Resting-state functional connectivity in major depression: abnormally increased contributions from subgenual cingulate cortex and thalamus. Biol Psychiatry. 2007;62(5):429–37.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Silani G, Lamm C, Ruff CC, Singer T. Right supramarginal gyrus is crucial to overcome emotional egocentricity bias in social judgments. J Neurosci. 2013;33(39):15466–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Esménio S, Soares JM, Oliveira-Silva P, Gonçalves ÓF, Decety J, Coutinho J. Brain circuits involved in understanding our own and other’s internal states in the context of romantic relationships. Soc Neurosci. 2019;14(6):729–38.

    Article  PubMed  Google Scholar 

  44. Wada S, Honma M, Masaoka Y, Yoshida M, Koiwa N, Sugiyama H, Iizuka N, Kubota S, Kokudai Y, Yoshikawa A, Kamijo S, Kamimura S, Ida M, Ono K, Onda H, Izumizaki M. Volume of the right supramarginal gyrus is associated with a maintenance of emotion recognition ability. PLoS ONE. 2021;16(7):e0254623.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Li F, Lu L, Shang S, Hu L, Chen H, Wang P, Zhang H, Chen YC, Yin X. Disrupted functional network connectivity predicts cognitive impairment after acute mild traumatic brain injury. CNS Neurosci Ther. 2020;26(10):1083–91.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors are grateful for the technical support from the radiology department of Beijing Tongren Hospital.

Funding

This work was supported by the National Natural Science Foundation of China (Grant No. 82070998); Capital Research Project of Clinical Diagnosis and Treatment Technology and Translational Application, Beijing Municipal Science & Technology Commission (Z201100005520044); and “Yangfan” clinical technology innovation project, Beijing Municipal Administration of Hospitals (XMLX202103).

Author information

Authors and Affiliations

  1. Beijing Tongren Hospital, Beijing Key Laboratory of Ophthalmology & Visual Sciences, Beijing Tongren Eye Center, Capital Medical University, Dong Jiao Min Xiang Street 1#, Dongcheng District, Beijing, China

    Huixin Li, Jie Hong, Jie Hao, Wei Dai & Jing Fu

  2. Department of Radiology, Beijing Tongren Hospital, Capital Medical University, Dong Jiao Min Xiang Street 1#, Dongcheng District, Beijing, China

    Wei Li & Zhaohui Liu

  3. Department of Quantitative Theory and Methods, Emory University, Atlanta, GA, USA

    Jiawen Liu

Authors
  1. Huixin Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wei Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jie Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jiawen Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jie Hao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wei Dai
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zhaohui Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jing Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization, J.F. and J.H.; methodology, J.F. and J.H.; software, W.L. and Z.L.; validation, J.F., J.H. and H.L.; formal analysis, J.F., J.H. and H.L.; investigation, H.L., J.L., D.W. and W.L.; writing—original draft preparation, H.L. and W.L.; writing—review and editing, J.H, J.H, Z.L. and J.F.; visualization, H.L. and W.L.; supervision, J.H, and J.F.; project administration, Z.L. and J.F.; funding acquisition, J.F. All authors drafted or revised the final manuscript, approved the final version and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding authors

Correspondence to Zhaohui Liu or Jing Fu.

Ethics declarations

Ethics approval and consent to participate

The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee and Institutional Review Board of Capital Medical University, Beijing Tongren Hospital (TRECKY2020-139). Informed consent was obtained from all subjects involved in the study. Written informed consent has been obtained from the participants to publish this paper.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, H., Li, W., Hong, J. et al. Altered functional connectivity of resting-state networks and the correlation with clinical characteristics in intermittent exotropia adult patients: a resting-state magnetic resonance imaging study. BMC Ophthalmol 24, 411 (2024). https://doi.org/10.1186/s12886-024-03672-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12886-024-03672-7

Keywords

BMC Ophthalmology

ISSN: 1471-2415

Contact us