{"paper_id":"2d1c5aed-3704-46a0-b345-a083caaa2b7c","body_text":"Aberrant dynamic functional and effective connectivity changes of the primary visual cortex in patients with retinal detachment via machine learning | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Aberrant dynamic functional and effective connectivity changes of the primary visual cortex in patients with retinal detachment via machine learning Yu Ji, Yuan-yuan Wang, Qi Cheng, Wen-wen Fu, Ben-liang Shu, Bin Wei, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3808493/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Retinal detachment (RD) is a prevalent and severe eye disease that often leads to vision loss. Previous research has indicated abnormal brain activity in individuals with RD. However, these studies solely focused on localized alterations in brain activity among individuals with RD, and it remains unclear if there are any changes in dynamic functional connectivity (dFC) and dynamic effective connectivity (dEC) in the primary visual cortex (V1) among individuals with RD. Aim: This study utilizes seed-based functional connectivity (FC) analysis and Granger causality analysis (GCA) to examine alterations in dynamic functional and effective connectivity in the V1 among patients with RD. Methods: The study involved 29 patients with RD and 30 healthy controls (HCs) who underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans.Based on the seed regions in the V1, dynamic FC and GCA were conducted between the RD patients and HCs. To examine particular dFC and dEC states as well as associated temporal characteristics, the k-means clustering method was applied.The altered dFC and dEC values were selected as classification features and Support Vector Machine (SVM) classifiers were utilized to differentiate between patients with RD and HCs. Results: Compared to HCs, patients with RD displayed a significantly increased dFC between the right V1 and the temporal lobe, thalamus, frontal lobe, occipital lobe, angular gyrus, and cerebellum.Additionally, patients with RD exhibited significantly increased dFC between the left V1 and the parietal lobe.On the other hand, patients with RD showed a significantly decreased dFC between the left V1 and the cerebellum, amygdala, temporal lobe, and frontal lobe.Using the dynamic GCA algorithm, patients with RD showed a significant increase in dEC outflow from the right V1 to the frontal lobe, the caudate, the parietal lobule, and the angular gyrus.Patients with RD also exhibited a significant increase in dEC inflow to the right V1 from the temporal lobe, thalamus, the occipital lobe, and the parietal lobe.Additionally, patients with RD had significantly increased dEC outflow from the left V1 to the frontal lobe and the parietal lobe.Furthermore, patients with RD displayed a significant increase in dEC inflow to the left V1 from the occipital lobe.In contrast, patients with RD showed a significant decrease in dEC outflow from the left V1 to the occipital lobe. Lastly, patients with RD had significantly decreased dEC inflow to the left V1 from the occipital lobe and the postcentral gyrus[two-tailed, voxel-level p < 0.05, Gaussian random field (GRF) correction, cluster-level p < 0.05].After performing k-means clustering, it was observed that patients with RD predominantly displayed three dFC states and three or four dEC states.Depending on the region of interest (ROI), there are differences in the number of transitions(NT), frequency(F), and mean dwell time(MDT).The SVM model demonstrated accuracies of 0.712, 0.695, 0.525, 0.542, 0.593, and 0.458, along with corresponding areas under the curve (AUC) of 0.729, 0.786, 0.492, 0.561, 0.572, and 0, respectively, in distinguishing between individuals with RD and HCs based on the dFC/dEC values for the different ROI. Conclusion: Individuals with RD exhibited significant disruption in dFC/dEC between the V1 and multiple brain regions. The variability in dFC proved to distinguish individuals with RD from HCs with a high level of accuracy. These findings can contribute to the identification of potential neurological mechanisms underlying visual impairments in individuals with RD. Health sciences/Medical research Health sciences/Neurology Health sciences/Diseases/Eye diseases retinal detachment resting-state functional magnetic resonance imaging dynamic functional connectivity dynamic effective connectivity k-means clustering method Support Vector Machine Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 1. Introduction Retinal detachment (RD) is defined as the separation of the neuroepithelial layer from the pigment epithelial layer in the retina. Failure to promptly address this condition can lead to necrosis of retinal photoreceptor cells and subsequent vision loss, as the detached retina does not receive a blood supply from the choroid. Common clinical symptoms associated with RD include the sudden onset of floaters, flashes of light, the presence of a dark shadow that obscures vision, and vision loss. Several factors contribute to RD, with diabetic retinopathy 1 , high myopia 2 , ocular trauma 3 , post-cataract surgery 4 , and the use of oral quinolone medications 5 being the most prevalent causes. Various diagnostic methods are available to detect RD, including ocular B-ultrasound, optical coherence tomography (OCT), optomap, and mydriatic slit lamp examination of the fundus. However, these methods can only identify local eye lesions and are unable to detect abnormalities in the visual function area of the brain. Previous studies utilizing resting-state functional magnetic resonance imaging (rs-fMRI) have reported abnormal brain activity in regions associated with vision in individuals with RD 6–9 . Nonetheless, it is still unknown whether there are specific abnormalities in the dynamic functional connectivity (dFC) and dynamic effective connectivity (dEC) related to the primary visual cortex (V1) in individuals with RD. In recent years, rs-fMRI has emerged as a valuable noninvasive tool for studying neurological changes in the brain. It has the potential to uncover the underlying neural mechanisms associated with various diseases. One widely used metric in rs-fMRI analysis is functional connectivity (FC), which measures the correlation of blood-oxygen-level-dependent (BOLD) signaling between different brain regions 10 . By examining patterns of FC, researchers can gain insights into how different brain regions communicate and work together. However, FC alone cannot provide information about the causal relationship between brain regions; it merely indicates that two regions are correlated without revealing which region is causing the correlation. This is where Granger causality analysis (GCA) comes into play. GCA is a statistical method that utilizes multiple linear regression to explore the predictive power of past values from one time series on the current values of another time series 11 . In the context of rs-fMRI, GCA can be applied to investigate the causal effects between brain regions, aiding in the identification of information flow directionality by analyzing the temporal dynamics of BOLD signals. Previous studies have integrated FC and GCA methods 12–14 . However, recent research has shown that brain activity exhibits dynamic temporal changes 15 . Therefore, we incorporated sliding window analysis into the aforementioned methods to capture temporal dynamics and examine how brain activity and connectivity patterns change over time in individuals with RD. Additionally, the k-means clustering method, widely used for grouping data based on similarities, was applied to the dFC/dEC values of subjects across different sliding time windows. This facilitated the identification of distinct states or patterns in brain activity during the entire scanning duration. Finally, Support Vector Machine (SVM) is a well-recognized classification method in the field of machine learning 16 . SVM can efficiently process data in high-dimensional space and avoid overfitting, even with limited sample sizes 17 . As a result, SVM has found extensive application in the field of neuroimaging. Moreover, previous researchers have combined k-means clustering and SVM approaches to analyze dynamic interactions among the salience network (SN), central executive network (CEN), and default mode network (DMN) in patients with Alzheimer's disease 18 . In a recent study, abnormal FC and EC alterations were observed in patients with unilateral acute tinnitus and hearing loss. The study revealed abnormalities in FC/EC between the frontostriatal network and various nonauditory regions, as well as their relationship with tinnitus perception 14 . However, no studies to date have identified abnormalities in dFC and dEC in the V1 of patients with RD by integrating k-means clustering and SVM methods. The objective of the study was to examine the changes in dFC and dEC between the V1 and other brain regions in patients with RD. Specifically, we performed a comprehensive analysis of specific connections involving V1 in these patients. Initially, V1 served as the seed region, and a sliding window approach was used to evaluate alterations in dFC and dEC between V1 and all other brain regions. Subsequently, we applied the k-means clustering method to classify the dFC/dEC values obtained for each subject, based on various seed regions, into distinct states. Finally, we employed SVM methods to determine whether abnormal dFC/dEC values could effectively distinguish RD patients from normal controls.This study proposed two hypotheses: ( 1 ) alterations in dFC/dEC values within V1 may shed light on potential neural mechanisms underlying visual function impairment in RD patients; and ( 2 ) as sensitive biomarkers, dFC/dEC levels can distinguish RD patients from healthy individuals. 2. Participants and methods 2.1. Participants The First Affiliated Hospital of Nanchang University's Ethics Committee gave its clearance for this study. Written informed consent was acquired from all participants. The study included 29 patients diagnosed with RD and 30 healthy controls (HCs). The inclusion criteria for RD patients were: ( 1 ) idiopathic RD involving one or both retinal tears, ( 2 ) RD affecting one or both quadrants, and ( 3 ) absence of any eye diseases in both eyes. Patients with recurrent RD, RD caused by high myopia, RD associated with eye trauma, RD caused by diabetes, history of fundus surgery, cardiovascular diseases, mental disorders, and cerebral infarction were excluded. The healthy controls in Nanchang City were randomly selected to match the age, sex, and educational background of the RD patients. The inclusion criteria for the healthy controls were: ( 1 ) absence of eye diseases and major diseases, ( 2 ) visual acuity better than 1.0, and ( 3 ) finishing a number of tests, such as an magnetic resonance imaging(MRI), an OCT, and an ocular B-scan ultrasound. 2.2. fMRI Data Acquisition At the Department of Radiology in the First Affiliated Hospital, Nanchang University, China, rs-fMRI data were gathered using a 3T MR scanner (Siemens, Erlangen, Germany) that had an 8-channel phased-array head coil installed. The data acquisition involved capturing 240 resting-state volumes over an 8-minute period. The parameters used were as follows: field of view of 240 mm x 240 mm, repetition time (TR) of 2,000 ms, echo time of 40 ms, flip angle of 90°, matrix size of 64 x 64, slice thickness of 4 mm, and a 1 mm gap. Each brain volume consisted of thirty axial slices. The following three-dimensional MRI settings were used to obtain each participant's high-resolution T1-weighted images: TR of 1,900 ms, echo time of 2.26 ms, flip angle of 9°, field of view of 240 mm x 240 mm, matrix size of 256 x 256, 176 sagittal slices, and a slice thickness of 1 mm. 2.3. fMRI Data Preprocessing The RESTplus 1.25 rs-fMRI data analysis tools was used to preprocess the data 19 . The preprocessing procedures listed below were used: ( 1 ) The data was categorized into structural and functional images. ( 2 ) The data format was converted from DICOM to NIFTI. ( 3 ) The first ten time points were eliminated to ensure data stability as they captured the unstable signals obtained when the subject entered the MRI scan. ( 4 ) Time layer correction was applied to align the time points of the compartmentalized scanning by the MRI machine. ( 5 ) Head movement correction was implemented, and subjects with head movements exceeding 3 mm and 3°were excluded. ( 6 ) Normalization was performed to standardize the individual space to the Montreal Neurological Institute (MNI) standardized space. ( 7 ) Image smoothing was conducted using a 6 mm (length, width, and height) smoothing kernel to reduce noise differences between neighboring brain regions, resulting in a smoother and more continuous signal and increasing the signal-to-noise ratio for improved sensitivity and reliability of subsequent analyses. ( 8 ) Detrending was performed to eliminate the upward drift in the signal value caused by machinery or external factors. ( 9 ) Regression of interfering covariates was carried out, including the utilization of the Friston-24 parameter model to account for head motion signal 20,21 , global mean signal, white matter signal, and cerebrospinal fluid signal. ( 10 ) Temporal band-pass filtering was applied with a frequency range of 0.01 to 0.08 Hz to reduce noise, remove artifacts, and enhance the signal of interest. 2.4. Seed-based dFC analysis The region of interest (ROI) in this study is the V1 domain of the brain, as shown in Fig. 1 . The MNI coordinates for the V1 region, according to our previous article, are as follows: right V1 (8, -76, 10) and left V1 (-8, -76, 10) 22 . Using the Dynamic Brain Connectome (DynamicBC) toolbox v2.2 23 ,we created a spherical ROI with a radius of 6 mm using the V1 coordinates as the ROI. To analyze the data, we employed the sliding time window method, creating 201 time windows of 30 TR (60s) each, with a step length of 1 TR (2s). Within each window, We determined the correlation coefficients between the bilateral V1 and the average BOLD signal of other voxels in each subject's complete brain.To capture the change of these coefficients over time, we calculated the standard deviation (STD) of the Z-values for each voxel's correlation coefficients. This STD represents the coefficient of variation of dFC. 2.5. Blind Deconvolution Procedure The BOLD signal serves as an indicator for measuring changes in neuronal activity within specific brain regions. It indirectly reflects the level of local neural activity by capturing variations in magnetic field properties around oxygenated and deoxygenated hemoglobin. Hence, the BOLD signal offers an indirect measure of neural activity 24 . Recent studies have indicated that the modulation of the BOLD signal is influenced by cerebrovascular responses and neurovascular coupling 25 . In order to address potential confounding effects presented by the hemodynamic response function (HRF), we employed techniques for Resting-State Hemodynamic Response Function Retrieval and Deconvolution. By using these methods, we were able to deconvolve the observed BOLD signal, which resulted in a more precise calculation of effective connectivity 26 . 2.6. Seed-based dEC analysis We applied the same method as the previous dFC analysis to define the ROI, and utilized the DynamicBC toolkit to perform dynamic seed-based GCA. The seed time series was denoted as X, while Y represented the temporal activity of voxels throughout the brain. The \"X to Y\" relationship described how activities in region X influenced activities in region Y, whereas the \"Y to X\" relationship represented the reciprocal influence. For the dynamic analysis, a sliding window approach with a window width of 30TR (60s) and a step length of 1TR (2s) was employed. Each subject's time series was divided into 402 windows, and the directed connection coefficient was calculated between the bilateral V1 region and each window, as well as the average BOLD signal of other voxels throughout the brain. Consequently, a series of sliding window correlation coefficients was obtained for each subject. To capture the temporal variations in these coefficients, we calculated the STD of the Z-values for the directed connection coefficients of each element. This STD represents the coefficient of variation of the directed connection coefficient. 2.7. Statistical analysis The statistical analysis of STD FC and STD EC graphs was conducted in patients with RD and HCs using a two-sample t-test.To account for multiple comparison correction, Gaussian random field (GRF) methods were used with covariates for age and sex included in regression analysis(two-tailed, voxel level p < 0.05, GRF correction, cluster-level p < 0.05). 2.8. Clustering analysis We utilized the k-means clustering algorithm to cluster the dFC/dEC values of the bilateral V1 regions in all subjects through a 30TR sliding window. The similarity between different time windows was assessed using the L1 distance function (Manhattan distance) 27 to ascertain the occurrence state of dFC/dEC. The object was to identify the repeated FC and EC patterns in each window through cluster analysis and determine the optimal clustering coefficient value, K. Lastly, we computed the characteristics of dFC/dEC, including the number of transitions(NT), frequency(F), and mean dwell time(MDT). 2.9. Support vector machine analysis We employed the LIBSVM software package 28 , which is based on Matlab 2017b, to perform SVM classification on individuals with RD and HCs. The main aim of this study was to explore the potential of utilizing dFC/dEC values as diagnostic indicators for RD. The SVM classifier utilized the radial basis kernel function (RBF) as the kernel function and evaluated the performance of different feature subsets through the leave-one-out cross-validation (LOOCV) technique. The analysis flowchart for this study is depicted in Fig. 2 . 2.10.Validation analysis To corroborate our findings regarding the variability of dFC/dEC obtained with sliding windows of 30 TR, we conducted confirmatory analyses utilizing sliding windows of 60 TR and 80 TR lengths. 3. Results 3.1. Demographic characteristics A cohort of 29 RD patients—14 females and 15 males—with a mean age of 53.862 ± 19.093 years were included in this study. In addition, 30 HCs with a mean age of 51.667 ± 13.922 years were present, 15 of whom were male and 15 of whom were female. The RD patients and HCs did not significantly differ in terms of age or gender. Table 1 provides specific demographic information. Table 1 Features of the demographics of and RD patients and HCs Characteristic RD patients HCs P-value Men/women 15/14 15/15 0.895 x Age (years,mean ± STD) 53.862 ± 19.093 51.667 ± 13.922 0.615 t Duration of detachment (days) 15 (7, 30) a N/A N/A IOP (mmHg) 15 (12, 16) a N/A N/A Axial length of eye (mm,mean ± STD) 24.390 ± 1.899 N/A N/A Corneal endothelial cell count (/mm 2 ) 2422(1966,2545) a N/A N/A HAMA score 3 (1, 5) a N/A N/A Abbreviations: x, Data were obtained using Pearson’s chi-square tests;t ,Data were obtained using two-sample t-tests;a ,median(interquartile range);STD,standard deviation;RD, retinal detachment; HCs, healthy controls; IOP, intraocular pressure; HAMA, Hamilton Anxiety Scale; N/A, not applicable 3.2.Typical optomap, B-scan ultrasound, and OCT examinations of RD Figure 3 presents representative images of optomap, B-scan ultrasound, and OCT examinations conducted on patients with RD. The images illustrate key indicators of RD, including: A) the presence of a grayish retinal eminence in the detached region, involving the macular area, with an identifiable hiatal hole situated above it; B) a distinct banded echo that corresponds to the spherical wall echo; and C) detachment of the retinal nerve epithelium. 3.3.Differences in dFC/dEC values between RD and HCs Figure 4 illustrates the brain regions exhibiting significant differences in the dFC/dEC values of bilateral V1 between patients with RD and HCs using a sliding window of size 30TR. Compared to HCs, patients with RD displayed significantly increased dFC between the right V1 and the cerebellum vermis 9, the left superior temporal gyrus (L-STG), the right thalamus (R-THA), the left superior frontal gyrus medial (L-SFGmed), the right middle occipital gyrus (R-MOG), the left middle occipital gyrus (L-MOG), the left angular gyrus (L-ANG), the right middle frontal gyrus (R-MFG), and the right supramarginal gyrus (R-SMG). Additionally, patients with RD exhibited significantly increased dFC between the left V1 and both the left superior parietal gyrus (L-SPG) and the right superior parietal gyrus (R-SPG). On the other hand, patients with RD showed significantly decreased dFC between the left V1 and the right cerebellum crus Ⅰ, the right amygdala (R-AMYG), L-STG, and the right rectus (R-REC).Using the dynamic GCA algorithm, patients with RD showed a significant increase in dEC outflow from the right V1 to the right superior frontal gyrus orbital part (R-SFGorb), the left caudate (L-CAU), the right middle frontal gyrus orbital part (R-MFGorb), the R-MFG, the left middle frontal gyrus (L-MFG), the right inferior parietal lobule (R-IPL), and the right angular gyrus (R-ANG). Patients with RD also exhibited a significant increase in dEC inflow to the right V1 from L-STG, the left middle temporal gyrus (L-MTG), R-THA, the right calcarine (R-CAL), the left cuneus (L-CUN), R-MOG, and R-IPL. Additionally, patients with RD had significantly increased dEC outflow from the left V1 to the left superior frontal gyrus (L-SFG) and R-IPL.Furthermore, patients with RD displayed a significant increase in dEC inflow to the left V1 from the left precuneus (L-PCUN). In contrast, patients with RD showed a significant decrease in dEC outflow from the left V1 to the right precuneus (R-PCUN). Lastly, patients with RD had significantly decreased dEC inflow to the left V1 from R-PCUN and the left postcentral gyrus (L-PoCG) (Figure 4; Table 2;two-tailed, voxel level p < 0.05; GRF correction, cluster-level p < 0.05). Table 2 Significant differences in dFC/dEC values between RD patients and HCs at a sliding window size of 30TR. Seed region Direction Brain region BA Peak t-score MNI coordinates (x, y, z) Cluster size (voxels) dFC R-V1 - Cerebellum-vermis- 9 - 3.794 0,-57,-33 138 L-STG - 4.339 -48 ,0,-9 178 R-THA - 4.169 12,-9,9 91 L-SFGmed 10 3.945 -3,54,6 99 R-MOG - 3.849 -9,-105,6 172 L-MOG 19 4.171 -27,-96,18 104 L-ANG - 5.491 -45,-69,33 375 R-MFG - 3.844 36,6,45 190 R-SMG 2 3.937 51,-30,42 343 L-V1 - R-Cerebellum-Crus-Ⅰ - -4.052 24,-90,-24 184 R-AMYG - -4.047 24,-3,-15 138 L-STG - -5.117 -48,-12,-3 106 R-REC - -4.456 9,30,-18 94 L-SPG - 4.935 -33,-72,54 527 R-SPG - 3.909 33,-66,60 108 dEC R-V1 X to Y R-SFGorb 10 3.452 27,54,-3 83 L-CAU - 3.742 -6,6,3 151 R-MFGorb 10 3.616 36,60,-3 62 R-MFG - 4.260 42,30,30 60 L-MFG - 3.325 -21,45,33 56 R-IPL - 4.110 36,-45,48 65 R-ANG - 3.634 39,-66,48 76 Y to X L-STG - 4.182 -51,-27,3 59 L-MTG 21 3.943 -66,-39,0 43 R-THA - 3.660 18,-15,18 43 R-CAL 31 3.047 6,-69,15 30 L-CUN - 3.217 -3,-69,24 65 R-MOG - 3.593 33,-81,21 46 R-IPL - 3.197 39,-42,48 35 L-V1 X to Y L-SFG - 3.677 -18,54,3 39 R-PCUN - -3.795 12,-66,21 48 R-IPL 40 3.764 42,-51,42 60 Y to X R-PCUN - -3.670 21,-57,24 30 L-PoCG 4 -4.304 -63,-6,24 40 L-PCUN - 3.710 -12,-60,54 36 Abbreviations: dFC,dynamic functional connectivity;dEC, dynamic effective connectivity; HCs, healthy controls; RD, retinal detachment; BA, Brodmann area; MNI, Montreal Neurological Institute;TR,repetition time;R-V1,right primary visual area;L-V1,left primary visual area;X to Y,from seed region to whole brain;Y to X,from whole brain to seed region;L-STG,left superior temporal gyrus;R-THA, right thalamus;L-SFGmed, left superior frontal gyrus medial ; R-MOG, right middle occipital gyrus; L-MOG,left middle occipital gyrus; L-ANG, left angular gyrus ;R-MFG,right middle frontal gyrus;R-SMG,right supramarginal gyrus;R-AMYG,right amygdala;R-REC,right rectus;L-SPG,left superior parietal gyrus;R-SPG,right superior parietal gyrus;R-SFGorb,right superior frontal gyrus orbital part;L-CAU,left caudate;R-MFGorb,right middle frontal gyrus orbital part;L-MFG,left middle frontal gyrus;R-IPL,right inferior parietal lobule;R-ANG, right angular gyrus;L-MTG,left middle temporal gyrus; R-CAL,right calcarine;L-CUN,left cuneus;L-SFG,left superior frontal gyrus;R-PCUN,right precuneus;L-PCUN,left precuneus;L-PoCG,left postcentral gyrus (two-tailed, voxel-level p < 0.05, GRF correction, cluster-level p < 0.05). 3.4. Clustered dFC/dEC states Figure 5 illustrates the utilization of the k-means clustering algorithm to cluster the dFC and dEC values of the bilateral V1 in all subjects within a 30TR sliding window.It was observed that patients diagnosed with RD predominantly exhibited three dFC states and three to four dEC states. Depending on the ROI, there are differences in the NT, F, and MDT.Compared to the HCs,significantly higher frequencies were observed in the RD group at state 4 in the R-V1 to whole-brain dEC clustering results (p = 0.005, t = 2.892).Further details are presented in Table 3. Table 3 The temporal properties of dFC/dEC patterns RD patients and HCs at a sliding window size of 30TR. Seed region Dynamic clustering index P-value t-value dFC R-V1 Number of transitions 0.661 -0.440 Frequency State1 0.908 0.117 State2 0.537 0.622 State3 0.486 -0.701 Mean dwell time State1 0.693 0.396 State2 0.251 1.159 State3 0.632 -0.482 L-V1 Number of transitions 0.907 0.118 Frequency State1 0.935 0.082 State2 0.975 0.031 State3 0.913 -0.109 Mean dwell time State1 0.305 1.035 State2 0.960 -0.051 State3 0.329 -0.985 dEC R-V1(X to Y) Number of transitions 0.292 -1.064 Frequency State1 0.078 -1.797 State2 0.330 -0.983 State3 0.037 -2.133 State4 0.005 # 2.892 # Mean dwell time State1 0.820 -0.228 State2 0.330 -0.983 State3 0.075 -1.814 State4 0.018 2.438 R-V1(Y to X) Number of transitions 0.747 -0.324 Frequency State1 0.313 1.017 State2 0.330 -0.983 State3 0.046 2.036 State4 0.052 -1.982 Mean dwell time State1 0.313 1.017 State2 0.330 -0.983 State3 0.835 0.210 State4 0.036 -2.149 L-V1(X to Y) Number of transitions 0.625 0.491 Frequency State1 0.376 -0.893 State2 0.148 1.466 State3 0.277 -1.097 State4 0.390 -0.867 Mean dwell time State1 0.376 -0.893 State2 0.673 0.424 State3 0.146 -1.474 State4 0.475 -0.719 L-V1(Y to X) Number of transitions 0.204 1.286 Frequency State1 0.197 1.301 State2 0.248 -1.168 State3 0.330 -0.983 Mean dwell time State1 0.237 1.195 State2 0.084 -1.761 State3 0.330 -0.983 Abbreviations: The number of transitions is evaluated using a two-sample t-test(p < 0.05), whereas the frequency and mean dwell time are assessed using the Bonferroni test(p < 0.017);#,Significant value after Bonferroni correction;RD, retinal detachment; HCs, healthy controls;dFC,dynamic functional connectivity;dEC, dynamic effective connectivity;X to Y,from seed region to whole brain;Y to X,from whole brain to seed region. 3.5. SVM classification results Figure 6A illustrates the SVM classification of dFC in the right V1 and the entire brain.The accuracy and area under the curve (AUC) values were determined to be 0.712 and 0.729, respectively.Figure 6B illustrates the SVM classification of dFC in the left V1 and the entire brain.The accuracy and AUC values were determined to be 0.695 and 0.786, respectively.Figure 6C illustrates the SVM classification of dEC from the right V1 to the whole brain.The accuracy and AUC values were determined to be 0.525 and 0.492, respectively.Figure 6D illustrates the SVM classification of dEC from the whole brain to the right V1.The accuracy and AUC values were determined to be 0.542 and 0.561, respectively.Figure 6E illustrates the SVM classification of dEC from the left V1 to the whole brain.The accuracy and AUC values were determined to be 0.593 and 0.572, respectively.Figure 6F illustrates the SVM classification of dEC from the whole brain to the left V1.The accuracy and AUC values were determined to be 0.458 and 0, respectively.The dFC may be helpful in the clinical diagnosis of RD, according to these findings. 3.6.Verification Analyses The analysis, utilizing varying sliding-window lengths of 60 TRs (120s) and 80 TRs (160s), consistently supported our primary finding of altered dFC and dEC (In Supplementary Materials, Figure S1 and S2, Table S1 and S2). 4. Discussion This study is the first, to the best of our knowledge, to investigate the dynamic changes in brain functional activity in patients with RD using a combination of FC and GCA approaches. The seed region chosen for analysis was V1, based on previous research indicating cerebral neurohomogeneity dysfunction in the visual pathway of patients with RD. FC analysis revealed abnormal dFC changes between the V1 seed region and various brain regions including occipital, frontal, rectus gyrus, temporal, amygdala, parietal, angular gyrus, supramarginal gyrus, thalamus, and cerebellum. Furthermore, using the GCA method, we identified abnormal dynamic causal connection changes between the V1 seed region and other brain regions, including occipital, calcarine, cuneus, frontal, postcentral gyrus, temporal, parietal, angular gyrus, caudate, thalamus, and cerebellum. Analysis using k-means clustering revealed that RD patients exhibited three predominant states of dFC and three or four states of dEC. As compared to HCs, individuals with RD exhibited significant variations in the NT, F, and MDT. Our SVM model achieved accuracies of 0.712, 0.695, 0.525, 0.542, 0.593, and 0.458, respectively, with corresponding AUC values of 0.729, 0.786, 0.492, 0.561, 0.572, and 0. An AUC range of 0.7-0.9 indicates high accuracy. Therefore, dFC values can be used as sensitive biomarkers to differentiate between patients with HCs and RDs.These findings could contribute to a better understanding of the underlying neural mechanisms responsible for visual impairment in patients with RD. The occipital lobe is situated posterior to the line connecting the occipital parietal fissure and the anterior occipital notch. The calcarine, on the other hand, is located within the occipital lobe, dividing it into the cuneus gyrus and lingual gyrus. In this study, patients with RD showed increased dFC values in the R-V1 and bilateral MOG. Furthermore, there were increased dEC values from the R-MOG to the R-V1, from the R-CAL to the R-V1, from the L-CUN to the R-V1, from the L-PCUN to the L-V1, as well as a decrease in bidirectional dEC values between the L-V1 and the R-PCUN. Kang et al. 29 reported a decrease in the amplitude of low-frequency fluctuation (ALFF) values in the right occipital lobe in patients with RD. Shao et al. 7 observed decreased functional connection density values in the L-CUN and left occipital lobe among middle-aged patients with RD. Similarly, Huang et al. 6 found decreased regional homogeneity (ReHo) values in the right occipital lobe and bilateral CUN in patients with RD. Our previous study found increased dynamic ALFF values in the left occipital lobe and R-CAL 9 . The occipital lobe plays a primary role in perceiving and processing visual information, making it crucial in complex visual perception processes. The CUN, which collaborates with V1, is a vital component of the occipital lobe responsible for transmitting visual information to extrastriate cortices 30 and also contributing to spatial positioning 31 . In this study, utilizing two analytical methods, we consistently observed higher variability in dFC/dEC in the right V1 and middle occipital gyrus of patients with RD. It is hypothesized that the detached part of the retina in these patients leads to diminished perception of light stimulation, resulting in weakened visual signals received by the occipital lobe. These elevated dFC/dEC levels suggest that people with RD may have a brain compensatory mechanism to offset vision loss. The frontal lobe serves as the cognitive control center of the brain and plays a crucial role in regulating cognitive function 32 . The basal surface of the frontal lobe is composed of the rectus gyrus and the orbital gyrus. In this study, patients with RD exhibited increased dFC values between R-V1 and L-SFGmed, as well as R-V1 and R-MFG, while decreased dFC values were observed between L-V1 and R-REC. Additionally, the dEC values showed an increase from R-V1 to R-SFGorb, R-V1 to R-MFGorb, R-V1 to R-MFG, R-V1 to L-MFG, and L-V1 to L-SFG. Kang et al. 29 reported a decrease in the ALFF value of the R-MFG in patients with RD, while the ALFF value of the R-SFGorb increased. Shao et al. 7 observed an increase in the functional connection density values of the L-SFG and L-MFG in middle-aged patients with RD. They proposed that the long-term decline in vision in these patients may impair memory function and stimulate frontal lobe function, which could explain the observed increase in the functional connection density values of L-SFG and L-MFG. Similarly, Huang et al. 6 found a decrease in the ReHo value of L-MFG in patients with RD, suggesting cognitive impairment in these individuals. Our previous study revealed an increase in the dynamic ALFF values of the bilateral MFG and the right inferior frontal gyrus (IFG) in patients with RD 9 , which aligns with our current research. Patients who experience RD face challenges in adapting to monocular vision due to the sudden loss of vision. When the affected eye no longer transmits visual information to the corresponding brain area, the frontal lobe compensates by assuming the visual processing function.This compensatory response may be an adaptive mechanism to address the visual function defect caused by vision loss in patients with RD. The parietal lobe, a crucial region in the brain, plays a vital role in spatial visual processing. It is comprised of functional regions such as the angular gyrus, supramarginal gyrus, and postcentral gyrus. This study found significant increases in dFC values between L-V1 and bilateral SPG, R-V1 and L-ANG, as well as R-V1 and R-SMG in RD patients. Additionally, there was a significant increase in dEC values observed from R-V1 to R-IPL, L-V1 to R-IPL, R-V1 to R-ANG, and R-IPL to R-V1. Conversely, a significant decrease in dEC values was found from L-PoCG to L-V1. In a study by Wen et al. 33 , an increase in dALFF value was reported in the SPG of patients with active thyroid-associated ophthalmopathy. This finding was postulated to be associated with delayed visuospatial information processing.Wu et al. 34 discovered a decrease in FC values of the IPL among patients with asthma, potentially influencing attention and executive function. They also found a decrease in cortical thickness values in the L-IPL and R-SPG among high myopia patients, suggesting structural changes impacting associated cognitive and executive functions 35 . In our previous study, we observed a decrease in dynamic ALFF value in the R-SPG among patients with RD. As the SPG plays a role in the transmission and integration of visual information, this finding may contribute to the decline in vision experienced by RD patients 9 . The parietal lobe, positioned adjacent to the occipital lobe, is crucial in the visual pathway by transmitting visual information to the frontal lobe 36,37 . Given the absence of retinal function and the inability to perceive external visual signals, it can be inferred that the brain region responsible for visual function in RD patients with long-term low vision experiences a prolonged lack or reduced level of stimulation. Consequently, to compensate for the reduced function in this brain area, its activity exhibits an increased level. The temporal lobe and the amygdala are two important structures in the brain involved in cognitive and emotional processes. In this study, dFC values demonstrated an increase between the R-V1 and the L-STG, while they decreased between the L-V1 and L-STG, as well as between L-V1 and the R-AMYG in RD patients. Additionally, there was an increase in dEC values observed from L-STG to R-V1 and from the L-MTG to R-V1. Shao et al. 7 observed an increase in the functional connection density of the bilateral inferior temporal gyrus in middle-aged RD patients. This brain region is known to be involved in complex object feature characterization and face perception. The authors postulated that this increased density may represent a compensatory mechanism for the visual decline experienced by middle-aged RD patients. Chen et al. 38 found elevated degree centrality (DC) values in the L-MTG of individuals diagnosed with primary angle-closure glaucoma. The researchers speculated that these patients may experience cognitive difficulties. Wen et al. 39 also discovered diminished FC between the R-ANG and right superior temporal gyrus (R-STG) in individuals diagnosed with thyroid-associated eye disease. The researchers suggested that these patients might experience cognitive changes. In our previous study, we observed an increase in the dynamic ALFF value of the R-MTG in patients with RD. This may potentially indicate a compensatory mechanism for the reduced language comprehension ability 9 . Language and cognition are closely intertwined and play a fundamental role in human communication and thought processes. The MTG plays a pivotal role as a constituent of the DMN, a network implicated in various cognitive processes such as emotion regulation, self-reflection, and memory 40 . Therefore, our speculation revolves around the hypothesis that long-term visual impairment could contribute to a deterioration in patients' ability to perceive external stimuli, potentially resulting in cognitive problems to some degree. However, further investigation is necessary to elucidate the underlying mechanism in detail. The thalamus, caudate nucleus, and cerebellum are three intricate brain structures, each with distinct roles and functions. The thalamus, a key structure in the forebrain, serves a critical function in sensory transduction, particularly in the visual system 41 . Within the thalamus, the lateral geniculate nucleus receives signals from retinal cells 42,43 . The caudate nucleus, located in the striatum of the basal ganglia, actively participates in the corticothalamic circuit and plays important roles in motor and cognitive function 44 . The cerebellum is crucial for functional interaction with the frontal eye fields, contributing to visuomotor coordination, higher-level cognitive functions, and memory processes 45,46 .In our previous research, we found a correlation between high myopia and decreased gray matter volume (GMV) in the R-THA, suggesting a potential contribution of high myopia to thalamic dysfunction 47 . Qi et al. 48 identified heightened FC between bilateral V1 and bilateral caudate in individuals with diabetic retinopathy, suggesting an augmentation of visuomotor function in these patients. Tong et al. 49 also observed increased FC between V1 and specific regions of the cerebellum (left cerebellum crus 1 and left cerebellum 10) in individuals with iridocyclitis, suggesting a compensatory response to vision loss.In our study, significant increases in dFC values were observed between R-V1 and R-THA, as well as between R-V1 and cerebellum-vermis-9, in patients with RD. On the other hand, a decreased dFC value was found between L-V1 and R-cerebellum-crus-I. Additionally, significant increases in dEC values were observed from R-V1 to L-CAU and from R-THA to R-V1. Therefore, we speculate that patients with RD may experience difficulties in visual information transmission, visual-motor coordination, and cognition. In all subjects, we observed the presence of three stable and recurring dFC states, as well as three or four dEC states. Depending on the ROI, there were variations in the NT, F, and MDT. In comparison to the HCs, the RD group exhibited significantly higher frequencies in state 4 of the dEC clustering results from the R-V1 to the whole brain (p = 0.005, t = 2.892). According to these results, people with RD may mostly exhibit state 4 brain activity patterns. MDT, F, and NT are commonly used terms to describe the dynamic temporal characteristics of brain activity, which can be altered in the presence of specific diseases 50 . Furthermore, Li et al. 51 propose that state transitions partially reflect the stability of neural activity, while a previous study has demonstrated that brains affected by cognitive dysfunction exhibit lower stability in neural activity 52 . Therefore, we hypothesize that these temporal characteristics of dEC may serve as potential biomarkers of cognitive impairment in RD patients. Notably,we investigated whether differences in dFC and dEC between individuals with RD and HCs could be utilized as a classifier to differentiate these groups. To address this, we utilized a machine learning approach by employing SVM classifiers based on dFC/dEC values derived from various ROIs.The accuracy of the SVM model to differentiate RD patients and HCs was found to be 0.712, 0.695, 0.525, 0.542, 0.593, and 0.458, respectively. Correspondingly, the AUC were 0.729, 0.786, 0.492, 0.561, 0.572, and 0, respectively.These results suggest that dFC may hold promise as a valuable tool for classifying individuals with RD from the healthy control population. 5. Limitations However, the study has several limitations.Firstly, future research should enlarge the sample size because it is currently too small.Secondly, physiological indicators such as respiratory rate, individual blood oxygen levels, and heart rate were not excluded and could potentially confound spontaneous neuronal activity.Thirdly, the study did not employ multimodal MRI methods to validate the results. 6. Conclusion In this study, we employed seed-based FC analysis, GCA, K-means clustering, SVM, and correlation analysis to examine alterations in dynamic function and effective connectivity in the V1 among patients with RD.This study aims to elucidate the neural mechanisms that underlie a visual impairment in patients with RD and to propose that variability in dFC could serve as a valuable index for clinical diagnosis and assessment. Declarations Data Availability Statement MRI data collection for this project was conducted at Jiangxi Provincial Medical Imaging Clinical Research Center/Clinical Research Center For Medical Imaging In Jiangxi Province (No.20223BCG74001). Ethics Statement The studies involving human participants were reviewed and approved by Declaration of Helsinki and was approved by the medical ethics committee of the First Affiliated Hospital of Nanchang university .The research program was approved by the institutional review board of the First Affiliated Hospital of Nanchang Nanchang university. The participants provided their written informed consent to participate in this study. Author Contributions JY responsible for writing manuscript; WYY is in charge of proofreading and refining the manuscript's wording.CQ FWW SBL WB HQY contributed to data collection, statistical analyses. JY and WYY designed the protocol and contributed to the MRI analysis.JY WYY and WXR designed the study, oversaw all clinical aspects of study conduct, and manuscript preparation. All authors contributed to the article and approved the submitted version. 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Additional Declarations No competing interests reported. Supplementary Files figureS1alldFCdEC60TR.tif figureS2alldFCdEC80TR.tif s1.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-3808493\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Article\",\"associatedPublications\":[],\"authors\":[{\"id\":264062163,\"identity\":\"ac4e81c5-029d-4fbd-940a-c8c8666382bd\",\"order_by\":0,\"name\":\"Yu Ji\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Ophthalmology Department of the First Affiliated Hospital, Jiangxi Medical College, Nanchang 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14:29:18\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-3808493/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-3808493/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":49089645,\"identity\":\"07aa306c-fa50-410f-87b8-157a1dd2043c\",\"added_by\":\"auto\",\"created_at\":\"2024-01-03 01:38:59\",\"extension\":\"png\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":112010,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eThe diagram depicts the distribution of V1 in the brain, with blue representing the right V1 and red representing the left V1.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"1V1.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-3808493/v1/6db71b6b0907fe846fd91f3a.png\"},{\"id\":49091053,\"identity\":\"a955fb35-34ae-46d2-b0a0-e2daf8fb5091\",\"added_by\":\"auto\",\"created_at\":\"2024-01-03 01:46:59\",\"extension\":\"png\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":4372124,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eAnalysis flowchart of this study.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"2flowdiagram.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-3808493/v1/ac8b21d2fe5eea7a748a2b37.png\"},{\"id\":49089646,\"identity\":\"a9557c71-69c6-460c-b1d6-b4b421055f79\",\"added_by\":\"auto\",\"created_at\":\"2024-01-03 01:38:59\",\"extension\":\"png\",\"order_by\":3,\"title\":\"Figure 3\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":1357004,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eThe eye examination results of patients with RD are presented below.A,optomap;B,B-scan ultrasound;C,OCT.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"3RDoptOCTBscans.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-3808493/v1/7e53f4c448cde29c123e37c9.png\"},{\"id\":49091054,\"identity\":\"dec7a8e2-3bc0-4b48-93a4-0b144103a623\",\"added_by\":\"auto\",\"created_at\":\"2024-01-03 01:46:59\",\"extension\":\"png\",\"order_by\":4,\"title\":\"Figure 4\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":11098328,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eBrain regions with significant differences in dFC/dEC values of the bilateral V1 between RD patients and HCs at a sliding window size of 30TR.A,The significant spatial distribution of differences in dFC between the right V1 and other brain regions.B,The significant spatial distribution of differences in dFC between the left V1 and other brain regions.C,The significant spatial distribution of differences in dEC from the right V1 to other brain regions.D,The significant spatial distribution of differences in dEC from other brain regions to the right V1.E,The significant spatial distribution of differences in dEC from the left V1 to other brain regions.F,The significant spatial distribution of differences in dEC from other brain regions to the left V1.Abbreviations: HCs, healthy controls; RD, retinal detachment; dFC, dynamic functional connectivity;dEC,dynamic effective connectivity; R-V1,right primary visual area;L-V1,left primary visual area;L-STG,left superior temporal gyrus;R-THA, right thalamus;L-SFGmed, left superior frontal gyrus medial ; R-MOG, right middle occipital gyrus; L-MOG,left middle occipital gyrus; L-ANG, left angular gyrus ;R-MFG,right middle frontal gyrus;R-SMG,right supramarginal gyrus;R-AMYG,right amygdala;R-REC,right rectus;L-SPG,left superior parietal gyrus;R-SPG,right superior parietal gyrus;R-SFGorb,right superior frontal gyrus orbital part;L-CAU,left caudate;R-MFGorb,right middle frontal gyrus orbital part;L-MFG,left middle frontal gyrus;R-IPL,right inferior parietal lobule;R-ANG, right angular gyrus;L-MTG,left middle temporal gyrus; R-CAL,right calcarine;L-CUN,left cuneus;L-SFG,left superior frontal gyrus;R-PCUN,right precuneus;L-PCUN,left precuneus;L-PoCG,left postcentral gyrus.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"4alldFCdEC30TR.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-3808493/v1/707a988b81255c4357cbb0a7.png\"},{\"id\":49089651,\"identity\":\"b29975f6-609b-4c2a-ac5c-3696c6fe3407\",\"added_by\":\"auto\",\"created_at\":\"2024-01-03 01:38:59\",\"extension\":\"png\",\"order_by\":5,\"title\":\"Figure 5\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":9880288,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eThe temporal properties of the dFC/dEC mode of bilateral V1 between the RD and the HCs at sliding window sizes of 30TR.A,the clustering results of dFC in the right V1 and the whole brain.B,the clustering results of dFC in the left V1 and the whole brain.C,the clustering results of dEC from the right V1 to the whole brain.D,the clustering results of dEC from the whole brain to the right V1.E,the clustering results of dEC from the left V1 to the whole brain.F,the clustering results of dEC from the whole brain to the left V1.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"5KmeansdFCdECall.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-3808493/v1/e3f3576af2acf8b27b285851.png\"},{\"id\":49089650,\"identity\":\"671119cc-bfa3-43c5-99ea-b06c0a4b0894\",\"added_by\":\"auto\",\"created_at\":\"2024-01-03 01:38:59\",\"extension\":\"png\",\"order_by\":6,\"title\":\"Figure 6\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":2886925,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eClassification results using SVM based on dFC/dEC values using a sliding window size of 30TR.A,the SVM results of dFC in the right V1 and the whole brain.B,the SVM results of dFC in the left V1 and the whole brain.C,the SVM results of dEC from the right V1 to the whole brain.D,the SVM results of dEC from the whole brain to the right V1.E,the SVM results of dEC from the left V1 to the whole brain.F,the SVM results of dEC from the whole brain to the left V1.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"6allSVM.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-3808493/v1/894ab7200919412c9352d77d.png\"},{\"id\":59018776,\"identity\":\"2e75f9a1-7f1b-4fb1-b0db-45a91eaab1d9\",\"added_by\":\"auto\",\"created_at\":\"2024-06-25 11:17:31\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":37292352,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-3808493/v1/a3dc9380-6a84-4b6b-a215-19fc20fd4522.pdf\"},{\"id\":49089653,\"identity\":\"77069569-0718-4e8d-a293-7068a88f3d3b\",\"added_by\":\"auto\",\"created_at\":\"2024-01-03 01:38:59\",\"extension\":\"tif\",\"order_by\":11,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":3814867,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"figureS1alldFCdEC60TR.tif\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-3808493/v1/08b8ef0adaaaec0556192bc5.tif\"},{\"id\":49091055,\"identity\":\"638b3e3b-6b20-4bbc-ba84-eb0f5129ff35\",\"added_by\":\"auto\",\"created_at\":\"2024-01-03 01:46:59\",\"extension\":\"tif\",\"order_by\":12,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":3564936,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"figureS2alldFCdEC80TR.tif\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-3808493/v1/fdd4857b832581dc63cc83c3.tif\"},{\"id\":49089648,\"identity\":\"ea98fcd6-14d4-4494-95b2-429226818f5d\",\"added_by\":\"auto\",\"created_at\":\"2024-01-03 01:38:59\",\"extension\":\"docx\",\"order_by\":13,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":836105,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"s1.docx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-3808493/v1/b39cfbc91fe4ed9c2fca09f7.docx\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"Aberrant dynamic functional and effective connectivity changes of the primary visual cortex in patients with retinal detachment via machine learning\",\"fulltext\":[{\"header\":\"1. Introduction\",\"content\":\"\\u003cp\\u003eRetinal detachment (RD) is defined as the separation of the neuroepithelial layer from the pigment epithelial layer in the retina. Failure to promptly address this condition can lead to necrosis of retinal photoreceptor cells and subsequent vision loss, as the detached retina does not receive a blood supply from the choroid. Common clinical symptoms associated with RD include the sudden onset of floaters, flashes of light, the presence of a dark shadow that obscures vision, and vision loss. Several factors contribute to RD, with diabetic retinopathy\\u003csup\\u003e1\\u003c/sup\\u003e, high myopia\\u003csup\\u003e2\\u003c/sup\\u003e, ocular trauma\\u003csup\\u003e3\\u003c/sup\\u003e, post-cataract surgery\\u003csup\\u003e4\\u003c/sup\\u003e, and the use of oral quinolone medications\\u003csup\\u003e5\\u003c/sup\\u003e being the most prevalent causes. Various diagnostic methods are available to detect RD, including ocular B-ultrasound, optical coherence tomography (OCT), optomap, and mydriatic slit lamp examination of the fundus. However, these methods can only identify local eye lesions and are unable to detect abnormalities in the visual function area of the brain. Previous studies utilizing resting-state functional magnetic resonance imaging (rs-fMRI) have reported abnormal brain activity in regions associated with vision in individuals with RD\\u003csup\\u003e6\\u0026ndash;9\\u003c/sup\\u003e. Nonetheless, it is still unknown whether there are specific abnormalities in the dynamic functional connectivity (dFC) and dynamic effective connectivity (dEC) related to the primary visual cortex (V1) in individuals with RD.\\u003c/p\\u003e \\u003cp\\u003eIn recent years, rs-fMRI has emerged as a valuable noninvasive tool for studying neurological changes in the brain. It has the potential to uncover the underlying neural mechanisms associated with various diseases. One widely used metric in rs-fMRI analysis is functional connectivity (FC), which measures the correlation of blood-oxygen-level-dependent (BOLD) signaling between different brain regions\\u003csup\\u003e10\\u003c/sup\\u003e. By examining patterns of FC, researchers can gain insights into how different brain regions communicate and work together. However, FC alone cannot provide information about the causal relationship between brain regions; it merely indicates that two regions are correlated without revealing which region is causing the correlation. This is where Granger causality analysis (GCA) comes into play. GCA is a statistical method that utilizes multiple linear regression to explore the predictive power of past values from one time series on the current values of another time series\\u003csup\\u003e11\\u003c/sup\\u003e. In the context of rs-fMRI, GCA can be applied to investigate the causal effects between brain regions, aiding in the identification of information flow directionality by analyzing the temporal dynamics of BOLD signals. Previous studies have integrated FC and GCA methods\\u003csup\\u003e12\\u0026ndash;14\\u003c/sup\\u003e. However, recent research has shown that brain activity exhibits dynamic temporal changes\\u003csup\\u003e15\\u003c/sup\\u003e. Therefore, we incorporated sliding window analysis into the aforementioned methods to capture temporal dynamics and examine how brain activity and connectivity patterns change over time in individuals with RD. Additionally, the k-means clustering method, widely used for grouping data based on similarities, was applied to the dFC/dEC values of subjects across different sliding time windows. This facilitated the identification of distinct states or patterns in brain activity during the entire scanning duration. Finally, Support Vector Machine (SVM) is a well-recognized classification method in the field of machine learning\\u003csup\\u003e16\\u003c/sup\\u003e. SVM can efficiently process data in high-dimensional space and avoid overfitting, even with limited sample sizes\\u003csup\\u003e17\\u003c/sup\\u003e. As a result, SVM has found extensive application in the field of neuroimaging. Moreover, previous researchers have combined k-means clustering and SVM approaches to analyze dynamic interactions among the salience network (SN), central executive network (CEN), and default mode network (DMN) in patients with Alzheimer's disease\\u003csup\\u003e18\\u003c/sup\\u003e. In a recent study, abnormal FC and EC alterations were observed in patients with unilateral acute tinnitus and hearing loss. The study revealed abnormalities in FC/EC between the frontostriatal network and various nonauditory regions, as well as their relationship with tinnitus perception\\u003csup\\u003e14\\u003c/sup\\u003e. However, no studies to date have identified abnormalities in dFC and dEC in the V1 of patients with RD by integrating k-means clustering and SVM methods.\\u003c/p\\u003e \\u003cp\\u003eThe objective of the study was to examine the changes in dFC and dEC between the V1 and other brain regions in patients with RD. Specifically, we performed a comprehensive analysis of specific connections involving V1 in these patients. Initially, V1 served as the seed region, and a sliding window approach was used to evaluate alterations in dFC and dEC between V1 and all other brain regions. Subsequently, we applied the k-means clustering method to classify the dFC/dEC values obtained for each subject, based on various seed regions, into distinct states. Finally, we employed SVM methods to determine whether abnormal dFC/dEC values could effectively distinguish RD patients from normal controls.This study proposed two hypotheses: (\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e) alterations in dFC/dEC values within V1 may shed light on potential neural mechanisms underlying visual function impairment in RD patients; and (\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e) as sensitive biomarkers, dFC/dEC levels can distinguish RD patients from healthy individuals.\\u003c/p\\u003e\"},{\"header\":\"2. Participants and methods\",\"content\":\"\\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003e2.1. Participants\\u003c/h2\\u003e \\u003cp\\u003e The First Affiliated Hospital of Nanchang University's Ethics Committee gave its clearance for this study. Written informed consent was acquired from all participants. The study included 29 patients diagnosed with RD and 30 healthy controls (HCs). The inclusion criteria for RD patients were: (\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e) idiopathic RD involving one or both retinal tears, (\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e) RD affecting one or both quadrants, and (\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e) absence of any eye diseases in both eyes. Patients with recurrent RD, RD caused by high myopia, RD associated with eye trauma, RD caused by diabetes, history of fundus surgery, cardiovascular diseases, mental disorders, and cerebral infarction were excluded. The healthy controls in Nanchang City were randomly selected to match the age, sex, and educational background of the RD patients. The inclusion criteria for the healthy controls were: (\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e) absence of eye diseases and major diseases, (\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e) visual acuity better than 1.0, and (\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e) finishing a number of tests, such as an magnetic resonance imaging(MRI), an OCT, and an ocular B-scan ultrasound.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec4\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003e2.2. fMRI Data Acquisition\\u003c/h2\\u003e \\u003cp\\u003eAt the Department of Radiology in the First Affiliated Hospital, Nanchang University, China, rs-fMRI data were gathered using a 3T MR scanner (Siemens, Erlangen, Germany) that had an 8-channel phased-array head coil installed. The data acquisition involved capturing 240 resting-state volumes over an 8-minute period. The parameters used were as follows: field of view of 240 mm x 240 mm, repetition time (TR) of 2,000 ms, echo time of 40 ms, flip angle of 90\\u0026deg;, matrix size of 64 x 64, slice thickness of 4 mm, and a 1 mm gap. Each brain volume consisted of thirty axial slices. The following three-dimensional MRI settings were used to obtain each participant's high-resolution T1-weighted images: TR of 1,900 ms, echo time of 2.26 ms, flip angle of 9\\u0026deg;, field of view of 240 mm x 240 mm, matrix size of 256 x 256, 176 sagittal slices, and a slice thickness of 1 mm.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec5\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003e2.3. fMRI Data Preprocessing\\u003c/h2\\u003e \\u003cp\\u003eThe RESTplus 1.25 rs-fMRI data analysis tools was used to preprocess the data\\u003csup\\u003e19\\u003c/sup\\u003e. The preprocessing procedures listed below were used: (\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e) The data was categorized into structural and functional images. (\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e) The data format was converted from DICOM to NIFTI. (\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e) The first ten time points were eliminated to ensure data stability as they captured the unstable signals obtained when the subject entered the MRI scan. (\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e) Time layer correction was applied to align the time points of the compartmentalized scanning by the MRI machine. (\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e) Head movement correction was implemented, and subjects with head movements exceeding 3 mm and 3\\u0026deg;were excluded. (\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e) Normalization was performed to standardize the individual space to the Montreal Neurological Institute (MNI) standardized space. (\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e) Image smoothing was conducted using a 6 mm (length, width, and height) smoothing kernel to reduce noise differences between neighboring brain regions, resulting in a smoother and more continuous signal and increasing the signal-to-noise ratio for improved sensitivity and reliability of subsequent analyses. (\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e) Detrending was performed to eliminate the upward drift in the signal value caused by machinery or external factors. (\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e) Regression of interfering covariates was carried out, including the utilization of the Friston-24 parameter model to account for head motion signal\\u003csup\\u003e20,21\\u003c/sup\\u003e, global mean signal, white matter signal, and cerebrospinal fluid signal. (\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e) Temporal band-pass filtering was applied with a frequency range of 0.01 to 0.08 Hz to reduce noise, remove artifacts, and enhance the signal of interest.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec6\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003e2.4. Seed-based dFC analysis\\u003c/h2\\u003e \\u003cp\\u003eThe region of interest (ROI) in this study is the V1 domain of the brain, as shown in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e. The MNI coordinates for the V1 region, according to our previous article, are as follows: right V1 (8, -76, 10) and left V1 (-8, -76, 10)\\u003csup\\u003e22\\u003c/sup\\u003e. Using the Dynamic Brain Connectome (DynamicBC) toolbox v2.2\\u003csup\\u003e23\\u003c/sup\\u003e,we created a spherical ROI with a radius of 6 mm using the V1 coordinates as the ROI. To analyze the data, we employed the sliding time window method, creating 201 time windows of 30 TR (60s) each, with a step length of 1 TR (2s). Within each window, We determined the correlation coefficients between the bilateral V1 and the average BOLD signal of other voxels in each subject's complete brain.To capture the change of these coefficients over time, we calculated the standard deviation (STD) of the Z-values for each voxel's correlation coefficients. This STD represents the coefficient of variation of dFC.\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec7\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003e2.5. Blind Deconvolution Procedure\\u003c/h2\\u003e \\u003cp\\u003eThe BOLD signal serves as an indicator for measuring changes in neuronal activity within specific brain regions. It indirectly reflects the level of local neural activity by capturing variations in magnetic field properties around oxygenated and deoxygenated hemoglobin. Hence, the BOLD signal offers an indirect measure of neural activity\\u003csup\\u003e24\\u003c/sup\\u003e. Recent studies have indicated that the modulation of the BOLD signal is influenced by cerebrovascular responses and neurovascular coupling\\u003csup\\u003e25\\u003c/sup\\u003e. In order to address potential confounding effects presented by the hemodynamic response function (HRF), we employed techniques for Resting-State Hemodynamic Response Function Retrieval and Deconvolution. By using these methods, we were able to deconvolve the observed BOLD signal, which resulted in a more precise calculation of effective connectivity\\u003csup\\u003e26\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec8\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003e2.6. Seed-based dEC analysis\\u003c/h2\\u003e \\u003cp\\u003eWe applied the same method as the previous dFC analysis to define the ROI, and utilized the DynamicBC toolkit to perform dynamic seed-based GCA. The seed time series was denoted as X, while Y represented the temporal activity of voxels throughout the brain. The \\\"X to Y\\\" relationship described how activities in region X influenced activities in region Y, whereas the \\\"Y to X\\\" relationship represented the reciprocal influence. For the dynamic analysis, a sliding window approach with a window width of 30TR (60s) and a step length of 1TR (2s) was employed. Each subject's time series was divided into 402 windows, and the directed connection coefficient was calculated between the bilateral V1 region and each window, as well as the average BOLD signal of other voxels throughout the brain. Consequently, a series of sliding window correlation coefficients was obtained for each subject. To capture the temporal variations in these coefficients, we calculated the STD of the Z-values for the directed connection coefficients of each element. This STD represents the coefficient of variation of the directed connection coefficient.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec9\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003e2.7. Statistical analysis\\u003c/h2\\u003e \\u003cp\\u003eThe statistical analysis of STD FC and STD EC graphs was conducted in patients with RD and HCs using a two-sample t-test.To account for multiple comparison correction, Gaussian random field (GRF) methods were used with covariates for age and sex included in regression analysis(two-tailed, voxel level p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05, GRF correction, cluster-level p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05).\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec10\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003e2.8. Clustering analysis\\u003c/h2\\u003e \\u003cp\\u003eWe utilized the k-means clustering algorithm to cluster the dFC/dEC values of the bilateral V1 regions in all subjects through a 30TR sliding window. The similarity between different time windows was assessed using the L1 distance function (Manhattan distance)\\u003csup\\u003e27\\u003c/sup\\u003e to ascertain the occurrence state of dFC/dEC. The object was to identify the repeated FC and EC patterns in each window through cluster analysis and determine the optimal clustering coefficient value, K. Lastly, we computed the characteristics of dFC/dEC, including the number of transitions(NT), frequency(F), and mean dwell time(MDT).\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec11\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003e2.9. Support vector machine analysis\\u003c/h2\\u003e \\u003cp\\u003eWe employed the LIBSVM software package\\u003csup\\u003e28\\u003c/sup\\u003e, which is based on Matlab 2017b, to perform SVM classification on individuals with RD and HCs. The main aim of this study was to explore the potential of utilizing dFC/dEC values as diagnostic indicators for RD. The SVM classifier utilized the radial basis kernel function (RBF) as the kernel function and evaluated the performance of different feature subsets through the leave-one-out cross-validation (LOOCV) technique. The analysis flowchart for this study is depicted in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e.\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec12\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003e2.10.Validation analysis\\u003c/h2\\u003e \\u003cp\\u003e To corroborate our findings regarding the variability of dFC/dEC obtained with sliding windows of 30 TR, we conducted confirmatory analyses utilizing sliding windows of 60 TR and 80 TR lengths.\\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"3. Results\",\"content\":\"\\u003cdiv id=\\\"Sec14\\\" class=\\\"Section2\\\"\\u003e\\n \\u003ch2\\u003e3.1. Demographic characteristics\\u003c/h2\\u003e\\n \\u003cp\\u003eA cohort of 29 RD patients\\u0026mdash;14 females and 15 males\\u0026mdash;with a mean age of 53.862\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;19.093 years were included in this study. In addition, 30 HCs with a mean age of 51.667\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;13.922 years were present, 15 of whom were male and 15 of whom were female. The RD patients and HCs did not significantly differ in terms of age or gender. Table \\u003cspan class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e provides specific demographic information.\\u003c/p\\u003e\\n \\u003cdiv class=\\\"gridtable\\\"\\u003e\\n \\u003cdiv class=\\\"colspec\\\" align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/div\\u003e\\n \\u003ctable id=\\\"Tab1\\\" border=\\\"1\\\"\\u003e\\n \\u003ccaption\\u003e\\n \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 1\\u003c/div\\u003e\\n \\u003cdiv class=\\\"CaptionContent\\\"\\u003e\\n \\u003cp\\u003eFeatures of the demographics of and RD patients and HCs\\u003c/p\\u003e\\n \\u003c/div\\u003e\\n \\u003c/caption\\u003e\\n \\u003cthead\\u003e\\n \\u003ctr\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eCharacteristic\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eRD patients\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eHCs\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eP-value\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/thead\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eMen/women\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e15/14\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e15/15\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.895\\u003csup\\u003ex\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eAge (years,mean\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;STD)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e53.862\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;19.093\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e51.667\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;13.922\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0.615\\u003csup\\u003et\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eDuration of detachment (days)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e15 (7, 30)\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eN/A\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eN/A\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eIOP (mmHg)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e15 (12, 16)\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eN/A\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eN/A\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eAxial length of eye (mm,mean\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;STD)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e24.390\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.899\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eN/A\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eN/A\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eCorneal endothelial cell count (/mm\\u003csup\\u003e2\\u003c/sup\\u003e)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e2422(1966,2545)\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eN/A\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eN/A\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eHAMA score\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e3 (1, 5)\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eN/A\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eN/A\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n \\u003ctfoot\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd colspan=\\\"4\\\"\\u003eAbbreviations: x, Data were obtained using Pearson\\u0026rsquo;s chi-square tests;t ,Data were obtained using two-sample t-tests;a ,median(interquartile range);STD,standard deviation;RD, retinal detachment; HCs, healthy controls; IOP, intraocular pressure; HAMA, Hamilton Anxiety Scale; N/A, not applicable\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tfoot\\u003e\\n \\u003c/table\\u003e\\n \\u003c/div\\u003e\\n \\u003cdiv class=\\\"gridtable\\\"\\u003e\\n \\u003cdiv class=\\\"colspec\\\" align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/div\\u003e\\n \\u003cdiv class=\\\"colspec\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e3.2.Typical optomap, B-scan ultrasound, and OCT examinations of RD\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003cp\\u003eFigure 3 presents representative images of optomap, B-scan ultrasound, and OCT examinations conducted on patients with RD. The images illustrate key indicators of RD, including: A) the presence of a grayish retinal eminence in the detached region, involving the macular area, with an identifiable hiatal hole situated above it; B) a distinct banded echo that corresponds to the spherical wall echo; and C) detachment of the retinal nerve epithelium.\\u003c/p\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e3.3.Differences in dFC/dEC values between RD and HCs\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003cp\\u003eFigure 4 illustrates the brain regions exhibiting significant differences in the dFC/dEC values of bilateral V1 between patients with RD and HCs using a sliding window of size 30TR. Compared to HCs, patients with RD displayed significantly increased dFC between the right V1 and the cerebellum vermis 9, the left superior temporal gyrus (L-STG), the right thalamus (R-THA), the left superior frontal gyrus medial (L-SFGmed), the right middle occipital gyrus (R-MOG), the left middle occipital gyrus (L-MOG), the left angular gyrus (L-ANG), the right middle frontal gyrus (R-MFG), and the right supramarginal gyrus (R-SMG). Additionally, patients with RD exhibited significantly increased dFC between the left V1 and both the left superior parietal gyrus (L-SPG) and the right superior parietal gyrus (R-SPG). On the other hand, patients with RD showed significantly decreased dFC between the left V1 and the right cerebellum crus Ⅰ, the right amygdala (R-AMYG), L-STG, and the right rectus (R-REC).Using the dynamic GCA algorithm, patients with RD showed a significant increase in dEC outflow from the right V1 to the right superior frontal gyrus orbital part (R-SFGorb), the left caudate (L-CAU), the right middle frontal gyrus orbital part (R-MFGorb), the R-MFG, the left middle frontal gyrus (L-MFG), the right inferior parietal lobule (R-IPL), and the right angular gyrus (R-ANG). Patients with RD also exhibited a significant increase in dEC inflow to the right V1 from L-STG, the left middle temporal gyrus (L-MTG), R-THA, the right calcarine (R-CAL), the left cuneus (L-CUN), R-MOG, and R-IPL. Additionally, patients with RD had significantly increased dEC outflow from the left V1 to the left superior frontal gyrus (L-SFG) and R-IPL.Furthermore, patients with RD displayed a significant increase in dEC inflow to the left V1 from the left precuneus (L-PCUN). In contrast, patients with RD showed a significant decrease in dEC outflow from the left V1 to the right precuneus (R-PCUN). Lastly, patients with RD had significantly decreased dEC inflow to the left V1 from R-PCUN and the left postcentral gyrus (L-PoCG) (Figure 4; Table 2;two-tailed, voxel level p \\u0026lt; 0.05; GRF correction, cluster-level p \\u0026lt; 0.05).\\u003c/p\\u003e\\n \\u003c/div\\u003e\\n \\u003ctable id=\\\"Tab2\\\" border=\\\"1\\\"\\u003e\\n \\u003ccaption\\u003e\\n \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 2\\u003c/div\\u003e\\n \\u003cdiv class=\\\"CaptionContent\\\"\\u003e\\n \\u003cp\\u003eSignificant differences in dFC/dEC values between RD patients and HCs at a sliding window size of 30TR.\\u003c/p\\u003e\\n \\u003c/div\\u003e\\n \\u003c/caption\\u003e\\n \\u003cthead\\u003e\\n \\u003ctr\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eSeed region\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eDirection\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eBrain region\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eBA\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003ePeak t-score\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eMNI coordinates\\u003c/p\\u003e\\n \\u003cp\\u003e(x, y, z)\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eCluster size (voxels)\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/thead\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd rowspan=\\\"15\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003edFC\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"9\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eR-V1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"9\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eCerebellum-vermis- 9\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e3.794\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e0,-57,-33\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e138\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eL-STG\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e4.339\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-48 ,0,-9\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e178\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eR-THA\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e4.169\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e12,-9,9\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e91\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eL-SFGmed\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e10\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e3.945\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-3,54,6\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e99\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eR-MOG\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e3.849\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-9,-105,6\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e172\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eL-MOG\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e19\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e4.171\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-27,-96,18\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e104\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eL-ANG\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e5.491\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-45,-69,33\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e375\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eR-MFG\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e3.844\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e36,6,45\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e190\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eR-SMG\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e3.937\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e51,-30,42\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e343\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd rowspan=\\\"6\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eL-V1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"6\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eR-Cerebellum-Crus-Ⅰ\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-4.052\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e24,-90,-24\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e184\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eR-AMYG\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-4.047\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e24,-3,-15\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e138\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eL-STG\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-5.117\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-48,-12,-3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e106\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eR-REC\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-4.456\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e9,30,-18\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e94\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eL-SPG\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e4.935\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-33,-72,54\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e527\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eR-SPG\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e3.909\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e33,-66,60\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e108\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd rowspan=\\\"20\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003edEC\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"14\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eR-V1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"7\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eX to Y\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eR-SFGorb\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e10\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e3.452\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e27,54,-3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e83\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eL-CAU\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e3.742\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-6,6,3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e151\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eR-MFGorb\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e10\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e3.616\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e36,60,-3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e62\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eR-MFG\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e4.260\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e42,30,30\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e60\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eL-MFG\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e3.325\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-21,45,33\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e56\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eR-IPL\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e4.110\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e36,-45,48\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e65\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eR-ANG\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e3.634\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e39,-66,48\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e76\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd rowspan=\\\"7\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eY to X\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eL-STG\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e4.182\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-51,-27,3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e59\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eL-MTG\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e21\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e3.943\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-66,-39,0\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e43\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eR-THA\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e3.660\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e18,-15,18\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e43\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eR-CAL\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e31\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e3.047\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e6,-69,15\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e30\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eL-CUN\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e3.217\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-3,-69,24\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e65\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eR-MOG\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e3.593\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e33,-81,21\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e46\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eR-IPL\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e3.197\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e39,-42,48\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e35\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd rowspan=\\\"6\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eL-V1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"3\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eX to Y\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eL-SFG\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e3.677\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-18,54,3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e39\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eR-PCUN\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-3.795\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e12,-66,21\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e48\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eR-IPL\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e40\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e3.764\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e42,-51,42\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e60\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd rowspan=\\\"3\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eY to X\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eR-PCUN\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-3.670\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e21,-57,24\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e30\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eL-PoCG\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-4.304\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-63,-6,24\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e40\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eL-PCUN\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e3.710\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e-12,-60,54\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e36\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n \\u003ctfoot\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd colspan=\\\"8\\\"\\u003eAbbreviations: dFC,dynamic functional connectivity;dEC, dynamic effective connectivity; HCs, healthy controls; RD, retinal detachment; BA, Brodmann area; MNI, Montreal Neurological Institute;TR,repetition time;R-V1,right primary visual area;L-V1,left primary visual area;X to Y,from seed region to whole brain;Y to X,from whole brain to seed region;L-STG,left superior temporal gyrus;R-THA, right thalamus;L-SFGmed, left superior frontal gyrus medial ; R-MOG, right middle occipital gyrus; L-MOG,left middle occipital gyrus; L-ANG, left angular gyrus ;R-MFG,right middle frontal gyrus;R-SMG,right supramarginal gyrus;R-AMYG,right amygdala;R-REC,right rectus;L-SPG,left superior parietal gyrus;R-SPG,right superior parietal gyrus;R-SFGorb,right superior frontal gyrus orbital part;L-CAU,left caudate;R-MFGorb,right middle frontal gyrus orbital part;L-MFG,left middle frontal gyrus;R-IPL,right inferior parietal lobule;R-ANG, right angular gyrus;L-MTG,left middle temporal gyrus; R-CAL,right calcarine;L-CUN,left cuneus;L-SFG,left superior frontal gyrus;R-PCUN,right precuneus;L-PCUN,left precuneus;L-PoCG,left postcentral gyrus (two-tailed, voxel-level p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05, GRF correction, cluster-level p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05).\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tfoot\\u003e\\n \\u003c/table\\u003e\\n \\u003c/div\\u003e\\n \\u003cdiv class=\\\"gridtable\\\"\\u003e\\n \\u003cdiv class=\\\"colspec\\\" align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/div\\u003e\\n \\u003cdiv class=\\\"colspec\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e3.4. Clustered dFC/dEC states\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003cp\\u003eFigure 5 illustrates the utilization of the k-means clustering algorithm to cluster the dFC and dEC values of the bilateral V1 in all subjects within a 30TR sliding window.It was observed that patients diagnosed with RD predominantly exhibited three dFC states and three to four dEC states. Depending on the ROI, there are differences in the NT, F, and MDT.Compared to the HCs,significantly higher frequencies were observed in the RD group at state 4 in the R-V1 to whole-brain dEC clustering results (p = 0.005, t = 2.892).Further details are presented in Table 3.\\u003c/p\\u003e\\n \\u003c/div\\u003e\\n \\u003cdiv class=\\\"colspec\\\" align=\\\"char\\\"\\u003e\\u0026nbsp;\\u003c/div\\u003e\\n \\u003ctable id=\\\"Tab3\\\" border=\\\"1\\\"\\u003e\\n \\u003ccaption\\u003e\\n \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 3\\u003c/div\\u003e\\n \\u003cdiv class=\\\"CaptionContent\\\"\\u003e\\n \\u003cp\\u003eThe temporal properties of dFC/dEC patterns RD patients and HCs at a sliding window size of 30TR.\\u003c/p\\u003e\\n \\u003c/div\\u003e\\n \\u003c/caption\\u003e\\n \\u003cthead\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003cth style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e\\n \\u003cth style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eSeed region\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth style=\\\"height: 35px;\\\" colspan=\\\"2\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eDynamic clustering index\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eP-value\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003cth style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003et-value\\u003c/p\\u003e\\n \\u003c/th\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/thead\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 490px;\\\" rowspan=\\\"14\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003edFC\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 245px;\\\" rowspan=\\\"7\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eR-V1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" colspan=\\\"2\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eNumber of transitions\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.661\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-0.440\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 105px;\\\" rowspan=\\\"3\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eFrequency\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.908\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.117\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.537\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.622\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.486\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-0.701\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 105px;\\\" rowspan=\\\"3\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eMean dwell time\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.693\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.396\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.251\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e1.159\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.632\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-0.482\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 245px;\\\" rowspan=\\\"7\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eL-V1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" colspan=\\\"2\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eNumber of transitions\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.907\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.118\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 105px;\\\" rowspan=\\\"3\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eFrequency\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.935\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.082\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.975\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.031\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.913\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-0.109\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 105px;\\\" rowspan=\\\"3\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eMean dwell time\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.305\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e1.035\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.960\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-0.051\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.329\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-0.985\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 1192px;\\\" rowspan=\\\"34\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003edEC\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 317px;\\\" rowspan=\\\"9\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eR-V1(X to Y)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" colspan=\\\"2\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eNumber of transitions\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.292\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-1.064\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 142px;\\\" rowspan=\\\"4\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eFrequency\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.078\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-1.797\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.330\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-0.983\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.037\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-2.133\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 37px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 37px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 37px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.005\\u003csup\\u003e#\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 37px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e2.892\\u003csup\\u003e#\\u003c/sup\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 140px;\\\" rowspan=\\\"4\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eMean dwell time\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.820\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-0.228\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.330\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-0.983\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.075\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-1.814\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.018\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e2.438\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 315px;\\\" rowspan=\\\"9\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eR-V1(Y to X)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" colspan=\\\"2\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eNumber of transitions\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.747\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-0.324\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 140px;\\\" rowspan=\\\"4\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eFrequency\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.313\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e1.017\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.330\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-0.983\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.046\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e2.036\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.052\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-1.982\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 140px;\\\" rowspan=\\\"4\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eMean dwell time\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.313\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e1.017\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.330\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-0.983\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.835\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.210\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.036\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-2.149\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 315px;\\\" rowspan=\\\"9\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eL-V1(X to Y)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" colspan=\\\"2\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eNumber of transitions\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.625\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.491\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 140px;\\\" rowspan=\\\"4\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eFrequency\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.376\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-0.893\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.148\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e1.466\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.277\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-1.097\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.390\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-0.867\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 140px;\\\" rowspan=\\\"4\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eMean dwell time\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.376\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-0.893\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.673\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.424\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.146\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-1.474\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState4\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.475\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-0.719\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 245px;\\\" rowspan=\\\"7\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eL-V1(Y to X)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" colspan=\\\"2\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eNumber of transitions\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.204\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e1.286\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 105px;\\\" rowspan=\\\"3\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eFrequency\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.197\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e1.301\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.248\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-1.168\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.330\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-0.983\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 105px;\\\" rowspan=\\\"3\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eMean dwell time\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.237\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e1.195\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState2\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.084\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-1.761\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr style=\\\"height: 35px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"left\\\"\\u003e\\n \\u003cp\\u003eState3\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e0.330\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"height: 35px;\\\" align=\\\"char\\\"\\u003e\\n \\u003cp\\u003e-0.983\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n \\u003ctfoot\\u003e\\n \\u003ctr style=\\\"height: 40.375px;\\\"\\u003e\\n \\u003ctd style=\\\"height: 40.375px;\\\" colspan=\\\"6\\\"\\u003eAbbreviations: The number of transitions is evaluated using a two-sample t-test(p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05), whereas the frequency and mean dwell time are assessed using the Bonferroni test(p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.017);#,Significant value after Bonferroni correction;RD, retinal detachment; HCs, healthy controls;dFC,dynamic functional connectivity;dEC, dynamic effective connectivity;X to Y,from seed region to whole brain;Y to X,from whole brain to seed region.\\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tfoot\\u003e\\n \\u003c/table\\u003e\\n \\u003c/div\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e3.5. SVM classification results\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003cp\\u003eFigure 6A illustrates the SVM classification of dFC in the right V1 and the entire brain.The accuracy and area under the curve (AUC) values were determined to be 0.712 and 0.729, respectively.Figure 6B illustrates the SVM classification of dFC in the left V1 and the entire brain.The accuracy and AUC values were determined to be 0.695 and 0.786, respectively.Figure 6C illustrates the SVM classification of dEC from the right V1 to the whole brain.The accuracy and AUC values were determined to be 0.525 and 0.492, respectively.Figure 6D illustrates the SVM classification of dEC from the whole brain to the right V1.The accuracy and AUC values were determined to be 0.542 and 0.561, respectively.Figure 6E illustrates the SVM classification of dEC from the left V1 to the whole brain.The accuracy and AUC values were determined to be 0.593 and 0.572, respectively.Figure 6F illustrates the SVM classification of dEC from the whole brain to the left V1.The accuracy and AUC values were determined to be 0.458 and 0, respectively.The dFC may be helpful in the clinical diagnosis of RD, according to these findings.\\u003c/p\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e3.6.Verification Analyses\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003cp\\u003eThe analysis, utilizing varying sliding-window lengths of 60 TRs (120s) and 80 TRs (160s), consistently supported our primary finding of altered dFC and dEC (In Supplementary Materials, Figure S1 and S2, Table S1 and S2).\\u003c/p\\u003e\\n\\u003c/div\\u003e\"},{\"header\":\"4. Discussion\",\"content\":\"\\u003cp\\u003eThis study is the first, to the best of our knowledge, to investigate the dynamic changes in brain functional activity in patients with RD using a combination of FC and GCA approaches. The seed region chosen for analysis was V1, based on previous research indicating cerebral neurohomogeneity dysfunction in the visual pathway of patients with RD. FC analysis revealed abnormal dFC changes between the V1 seed region and various brain regions including occipital, frontal, rectus gyrus, temporal, amygdala, parietal, angular gyrus, supramarginal gyrus, thalamus, and cerebellum. Furthermore, using the GCA method, we identified abnormal dynamic causal connection changes between the V1 seed region and other brain regions, including occipital, calcarine, cuneus, frontal, postcentral gyrus, temporal, parietal, angular gyrus, caudate, thalamus, and cerebellum. Analysis using k-means clustering revealed that RD patients exhibited three predominant states of dFC and three or four states of dEC. As compared to HCs, individuals with RD exhibited significant variations in the NT, F, and MDT. Our SVM model achieved accuracies of 0.712, 0.695, 0.525, 0.542, 0.593, and 0.458, respectively, with corresponding AUC values of 0.729, 0.786, 0.492, 0.561, 0.572, and 0. An AUC range of 0.7-0.9 indicates high accuracy. Therefore, dFC values can be used as sensitive biomarkers to differentiate between patients with HCs and RDs.These findings could contribute to a better understanding of the underlying neural mechanisms responsible for visual impairment in patients with RD.\\u003c/p\\u003e\\n\\u003cp\\u003eThe occipital lobe is situated posterior to the line connecting the occipital parietal fissure and the anterior occipital notch. The calcarine, on the other hand, is located within the occipital lobe, dividing it into the cuneus gyrus and lingual gyrus. In this study, patients with RD showed increased dFC values in the R-V1 and bilateral MOG. Furthermore, there were increased dEC values from the R-MOG to the R-V1, from the R-CAL to the R-V1, from the L-CUN to the R-V1, from the L-PCUN to the L-V1, as well as a decrease in bidirectional dEC values between the L-V1 and the R-PCUN. Kang et al.\\u003csup\\u003e29\\u003c/sup\\u003e reported a decrease in the amplitude of low-frequency fluctuation (ALFF) values in the right occipital lobe in patients with RD. Shao et al.\\u003csup\\u003e7\\u003c/sup\\u003e observed decreased functional connection density values in the L-CUN and left occipital lobe among middle-aged patients with RD. Similarly, Huang et al.\\u003csup\\u003e6\\u003c/sup\\u003e found decreased regional homogeneity (ReHo) values in the right occipital lobe and bilateral CUN in patients with RD. Our previous study found increased dynamic ALFF values in the left occipital lobe and R-CAL\\u003csup\\u003e9\\u003c/sup\\u003e. The occipital lobe plays a primary role in perceiving and processing visual information, making it crucial in complex visual perception processes. The CUN, which collaborates with V1, is a vital component of the occipital lobe responsible for transmitting visual information to extrastriate cortices\\u003csup\\u003e30\\u003c/sup\\u003e and also contributing to spatial positioning\\u003csup\\u003e31\\u003c/sup\\u003e. In this study, utilizing two analytical methods, we consistently observed higher variability in dFC/dEC in the right V1 and middle occipital gyrus of patients with RD. It is hypothesized that the detached part of the retina in these patients leads to diminished perception of light stimulation, resulting in weakened visual signals received by the occipital lobe. These elevated dFC/dEC levels suggest that people with RD may have a brain compensatory mechanism to offset vision loss.\\u003c/p\\u003e\\n\\u003cp\\u003eThe frontal lobe serves as the cognitive control center of the brain and plays a crucial role in regulating cognitive function\\u003csup\\u003e32\\u003c/sup\\u003e. The basal surface of the frontal lobe is composed of the rectus gyrus and the orbital gyrus. In this study, patients with RD exhibited increased dFC values between R-V1 and L-SFGmed, as well as R-V1 and R-MFG, while decreased dFC values were observed between L-V1 and R-REC. Additionally, the dEC values showed an increase from R-V1 to R-SFGorb, R-V1 to R-MFGorb, R-V1 to R-MFG, R-V1 to L-MFG, and L-V1 to L-SFG. Kang et al.\\u003csup\\u003e29\\u003c/sup\\u003e reported a decrease in the ALFF value of the R-MFG in patients with RD, while the ALFF value of the R-SFGorb increased. Shao et al.\\u003csup\\u003e7\\u003c/sup\\u003e observed an increase in the functional connection density values of the L-SFG and L-MFG in middle-aged patients with RD. They proposed that the long-term decline in vision in these patients may impair memory function and stimulate frontal lobe function, which could explain the observed increase in the functional connection density values of L-SFG and L-MFG. Similarly, Huang et al.\\u003csup\\u003e6\\u003c/sup\\u003e found a decrease in the ReHo value of L-MFG in patients with RD, suggesting cognitive impairment in these individuals. Our previous study revealed an increase in the dynamic ALFF values of the bilateral MFG and the right inferior frontal gyrus (IFG) in patients with RD\\u003csup\\u003e9\\u003c/sup\\u003e, which aligns with our current research. Patients who experience RD face challenges in adapting to monocular vision due to the sudden loss of vision. When the affected eye no longer transmits visual information to the corresponding brain area, the frontal lobe compensates by assuming the visual processing function.This compensatory response may be an adaptive mechanism to address the visual function defect caused by vision loss in patients with RD.\\u003c/p\\u003e\\n\\u003cp\\u003eThe parietal lobe, a crucial region in the brain, plays a vital role in spatial visual processing. It is comprised of functional regions such as the angular gyrus, supramarginal gyrus, and postcentral gyrus. This study found significant increases in dFC values between L-V1 and bilateral SPG, R-V1 and L-ANG, as well as R-V1 and R-SMG in RD patients. Additionally, there was a significant increase in dEC values observed from R-V1 to R-IPL, L-V1 to R-IPL, R-V1 to R-ANG, and R-IPL to R-V1. Conversely, a significant decrease in dEC values was found from L-PoCG to L-V1. In a study by Wen et al.\\u003csup\\u003e33\\u003c/sup\\u003e, an increase in dALFF value was reported in the SPG of patients with active thyroid-associated ophthalmopathy. This finding was postulated to be associated with delayed visuospatial information processing.Wu et al.\\u003csup\\u003e34\\u003c/sup\\u003e discovered a decrease in FC values of the IPL among patients with asthma, potentially influencing attention and executive function. They also found a decrease in cortical thickness values in the L-IPL and R-SPG among high myopia patients, suggesting structural changes impacting associated cognitive and executive functions\\u003csup\\u003e35\\u003c/sup\\u003e. In our previous study, we observed a decrease in dynamic ALFF value in the R-SPG among patients with RD. As the SPG plays a role in the transmission and integration of visual information, this finding may contribute to the decline in vision experienced by RD patients\\u003csup\\u003e9\\u003c/sup\\u003e. The parietal lobe, positioned adjacent to the occipital lobe, is crucial in the visual pathway by transmitting visual information to the frontal lobe\\u003csup\\u003e36,37\\u003c/sup\\u003e. Given the absence of retinal function and the inability to perceive external visual signals, it can be inferred that the brain region responsible for visual function in RD patients with long-term low vision experiences a prolonged lack or reduced level of stimulation. Consequently, to compensate for the reduced function in this brain area, its activity exhibits an increased level.\\u003c/p\\u003e\\n\\u003cp\\u003eThe temporal lobe and the amygdala are two important structures in the brain involved in cognitive and emotional processes. In this study, dFC values demonstrated an increase between the R-V1 and the L-STG, while they decreased between the L-V1 and L-STG, as well as between L-V1 and the R-AMYG in RD patients. Additionally, there was an increase in dEC values observed from L-STG to R-V1 and from the L-MTG to R-V1. Shao et al.\\u003csup\\u003e7\\u003c/sup\\u003e observed an increase in the functional connection density of the bilateral inferior temporal gyrus in middle-aged RD patients. This brain region is known to be involved in complex object feature characterization and face perception. The authors postulated that this increased density may represent a compensatory mechanism for the visual decline experienced by middle-aged RD patients. Chen et al.\\u003csup\\u003e38\\u003c/sup\\u003e found elevated degree centrality (DC) values in the L-MTG of individuals diagnosed with primary angle-closure glaucoma. The researchers speculated that these patients may experience cognitive difficulties. Wen et al.\\u003csup\\u003e39\\u003c/sup\\u003e also discovered diminished FC between the R-ANG and right superior temporal gyrus (R-STG) in individuals diagnosed with thyroid-associated eye disease. The researchers suggested that these patients might experience cognitive changes. In our previous study, we observed an increase in the \\u0026nbsp;dynamic ALFF value of the R-MTG in patients with RD. This may potentially indicate a compensatory mechanism for the reduced language comprehension ability\\u003csup\\u003e9\\u003c/sup\\u003e. Language and cognition are closely intertwined and play a fundamental role in human communication and thought processes. The MTG plays a pivotal role as a constituent of the DMN, a network implicated in various cognitive processes such as emotion regulation, self-reflection, and memory\\u003csup\\u003e40\\u003c/sup\\u003e. Therefore, our speculation revolves around the hypothesis that long-term visual impairment could contribute to a deterioration in patients\\u0026apos; ability to perceive external stimuli, potentially resulting in cognitive problems to some degree. However, further investigation is necessary to elucidate the underlying mechanism in detail.\\u003c/p\\u003e\\n\\u003cp\\u003eThe thalamus, caudate nucleus, and cerebellum are three intricate brain structures, each with distinct roles and functions. The thalamus, a key structure in the forebrain, serves a critical function in sensory transduction, particularly in the visual system\\u003csup\\u003e41\\u003c/sup\\u003e. Within the thalamus, the lateral geniculate nucleus receives signals from retinal cells\\u0026nbsp;\\u003csup\\u003e42,43\\u003c/sup\\u003e. The caudate nucleus, located in the striatum of the basal ganglia, actively participates in the corticothalamic circuit and plays important roles in motor and cognitive function\\u003csup\\u003e44\\u003c/sup\\u003e. The cerebellum is crucial for functional interaction with the frontal eye fields, contributing to visuomotor coordination, higher-level cognitive functions, and memory processes\\u003csup\\u003e45,46\\u003c/sup\\u003e.In our previous research, we found a correlation between high myopia and decreased gray matter volume (GMV) in the R-THA, suggesting a potential contribution of high myopia to thalamic dysfunction\\u003csup\\u003e47\\u003c/sup\\u003e. Qi et al.\\u003csup\\u003e48\\u003c/sup\\u003e identified heightened FC between bilateral V1 and bilateral caudate in individuals with diabetic retinopathy, suggesting an augmentation of visuomotor function in these patients. Tong et al.\\u003csup\\u003e49\\u003c/sup\\u003e also observed increased FC between V1 and specific regions of the cerebellum (left cerebellum crus 1 and left cerebellum 10) in individuals with iridocyclitis, suggesting a compensatory response to vision loss.In our study, significant increases in dFC values were observed between R-V1 and R-THA, as well as between R-V1 and cerebellum-vermis-9, in patients with RD. On the other hand, a decreased dFC value was found between L-V1 and R-cerebellum-crus-I. Additionally, significant increases in dEC values were observed from R-V1 to L-CAU and from R-THA to R-V1. Therefore, we speculate that patients with RD may experience difficulties in visual information transmission, visual-motor coordination, and cognition.\\u003c/p\\u003e\\n\\u003cp\\u003eIn all subjects, we observed the presence of three stable and recurring dFC states, as well as three or four dEC states. Depending on the ROI, there were variations in the NT, F, and MDT. In comparison to the HCs, the RD group exhibited significantly higher frequencies in state 4 of the dEC clustering results from the R-V1 to the whole brain (p = 0.005, t = 2.892). According to these results, people with RD may mostly exhibit state 4 brain activity patterns. MDT, F, and NT are commonly used terms to describe the dynamic temporal characteristics of brain activity, which can be altered in the presence of specific diseases\\u003csup\\u003e50\\u003c/sup\\u003e. Furthermore, Li et al.\\u003csup\\u003e51\\u003c/sup\\u003epropose that state transitions partially reflect the stability of neural activity, while a previous study has demonstrated that brains affected by cognitive dysfunction exhibit lower stability in neural activity\\u003csup\\u003e52\\u003c/sup\\u003e. Therefore, we hypothesize that these temporal characteristics of dEC may serve as potential biomarkers of cognitive impairment in RD patients.\\u003c/p\\u003e\\n\\u003cp\\u003eNotably,we investigated whether differences in dFC and dEC between individuals with RD and HCs could be utilized as a classifier to differentiate these groups. To address this, we utilized a machine learning approach by employing SVM classifiers based on dFC/dEC values derived from various ROIs.The accuracy of the SVM model to differentiate RD patients and HCs was found to be 0.712, 0.695, 0.525, 0.542, 0.593, and 0.458, respectively. Correspondingly, the AUC were 0.729, 0.786, 0.492, 0.561, 0.572, and 0, respectively.These results suggest that dFC may hold promise as a valuable tool for classifying individuals with RD from the healthy control population.\\u003c/p\\u003e\"},{\"header\":\"5. Limitations\",\"content\":\"\\u003cp\\u003eHowever, the study has several limitations.Firstly, future research should enlarge the sample size because it is currently too small.Secondly, physiological indicators such as respiratory rate, individual blood oxygen levels, and heart rate were not excluded and could potentially confound spontaneous neuronal activity.Thirdly, the study did not employ multimodal MRI methods to validate the results.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cbr\\u003e\\u003c/p\\u003e\"},{\"header\":\"6. Conclusion\",\"content\":\"\\u003cp\\u003eIn this study, we employed seed-based FC analysis, GCA, K-means clustering, SVM, and correlation analysis to examine alterations in dynamic function and effective connectivity in the V1 among patients with RD.This study aims to elucidate the neural mechanisms that underlie a visual impairment in patients with RD and to propose that variability in dFC could serve as a valuable index for clinical diagnosis and assessment.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cbr\\u003e\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eData Availability Statement\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eMRI data collection for this project was conducted at Jiangxi Provincial Medical Imaging Clinical Research Center/Clinical Research Center For Medical Imaging In Jiangxi Province (No.20223BCG74001).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eEthics Statement\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe studies involving human participants were reviewed and approved by Declaration of Helsinki and was approved by the medical ethics committee of the \\u0026nbsp;First Affiliated Hospital of Nanchang university .The research program was approved by the institutional review board of the First Affiliated Hospital of Nanchang Nanchang university. The participants provided their written informed consent to participate in this study.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAuthor Contributions\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eJY responsible for writing manuscript; WYY is in charge of proofreading and refining the manuscript\\u0026apos;s wording.CQ FWW SBL WB HQY contributed to data collection, statistical analyses. JY and WYY designed the protocol and contributed to the MRI analysis.JY WYY and WXR designed the study, oversaw all clinical aspects of study conduct, and manuscript preparation. All authors contributed to the article and approved the submitted version.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConflict of Interest\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\u003cli\\u003e\\u003cspan\\u003eMurakami, T. et al. Association between perifoveal hyperfluorescence and serous retinal detachment in diabetic macular edema. Ophthalmology 120, 2596\\u0026ndash;2603 (2013).\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eMattioli, S. et al. Physical exertion (lifting) and retinal detachment among people with myopia. Epidemiology 19, 868\\u0026ndash;871 (2008).\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eShahid, A. et al. 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J Neurosci 35, 9050\\u0026ndash;9063 (2015).\\u003c/span\\u003e\\u003c/li\\u003e\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"retinal detachment, resting-state functional magnetic resonance imaging, dynamic functional connectivity, dynamic effective connectivity, k-means clustering method, Support Vector Machine\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-3808493/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-3808493/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003eBackground: \\u003c/strong\\u003eRetinal detachment (RD) is a prevalent and severe eye disease that often leads to vision loss. Previous research has indicated abnormal brain activity in individuals with RD. However, these studies solely focused on localized alterations in brain activity among individuals with RD, and it remains unclear if there are any changes in dynamic functional connectivity (dFC) and dynamic effective connectivity (dEC) in the primary visual cortex (V1) among individuals with RD.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAim: \\u003c/strong\\u003eThis study utilizes seed-based functional connectivity (FC) analysis and Granger causality analysis (GCA) to examine alterations in dynamic functional and effective connectivity in the V1 among patients with RD.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMethods:\\u003c/strong\\u003e The study involved 29 patients with RD and 30 healthy controls (HCs) who underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans.Based on the seed regions in the V1, dynamic FC and GCA were conducted between the RD patients and HCs. To examine particular dFC and dEC states as well as associated temporal characteristics, the k-means clustering method was applied.The altered dFC and dEC values were selected as classification features and Support Vector Machine (SVM) classifiers were utilized to differentiate between patients with RD and HCs.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eResults: \\u003c/strong\\u003eCompared to HCs, patients with RD displayed a significantly increased dFC between the right V1 and the temporal lobe, thalamus, frontal lobe, occipital lobe, angular gyrus, and cerebellum.Additionally, patients with RD exhibited significantly increased dFC between the left V1 and the parietal lobe.On the other hand, patients with RD showed a significantly decreased dFC between the left V1 and the cerebellum, amygdala, temporal lobe, and frontal lobe.Using the dynamic GCA algorithm, patients with RD showed a significant increase in dEC outflow from the right V1 to the frontal lobe, the caudate, the parietal lobule, and the angular gyrus.Patients with RD also exhibited a significant increase in dEC inflow to the right V1 from the temporal lobe, thalamus, the occipital lobe, and the parietal lobe.Additionally, patients with RD had significantly increased dEC outflow from the left V1 to the frontal lobe and the parietal lobe.Furthermore, patients with RD displayed a significant increase in dEC inflow to the left V1 from the occipital lobe.In contrast, patients with RD showed a significant decrease in dEC outflow from the left V1 to the occipital lobe. Lastly, patients with RD had significantly decreased dEC inflow to the left V1 from the occipital lobe and the postcentral gyrus[two-tailed, voxel-level p \\u0026lt; 0.05, Gaussian random field (GRF) correction, cluster-level p \\u0026lt; 0.05].After performing k-means clustering, it was observed that patients with RD predominantly displayed three dFC states and three or four dEC states.Depending on the region of interest (ROI), there are differences in the number of transitions(NT), frequency(F), and mean dwell time(MDT).The SVM model demonstrated accuracies of 0.712, 0.695, 0.525, 0.542, 0.593, and 0.458, along with corresponding areas under the curve (AUC) of 0.729, 0.786, 0.492, 0.561, 0.572, and 0, respectively, in distinguishing between individuals with RD and HCs based on the dFC/dEC values for the different ROI.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConclusion: \\u003c/strong\\u003eIndividuals with RD exhibited significant disruption in dFC/dEC between the V1 and multiple brain regions. The variability in dFC proved to distinguish individuals with RD from HCs with a high level of accuracy. These findings can contribute to the identification of potential neurological mechanisms underlying visual impairments in individuals with RD.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Aberrant dynamic functional and effective connectivity changes of the primary visual cortex in patients with retinal detachment via machine learning\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2024-01-03 01:38:54\",\"doi\":\"10.21203/rs.3.rs-3808493/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"2c1f5eb6-bc46-4eba-98ee-7e280f76b2fd\",\"owner\":[],\"postedDate\":\"January 3rd, 2024\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[{\"id\":27843378,\"name\":\"Health sciences/Medical research\"},{\"id\":27843379,\"name\":\"Health sciences/Neurology\"},{\"id\":27843380,\"name\":\"Health sciences/Diseases/Eye diseases\"}],\"tags\":[],\"updatedAt\":\"2024-06-25T11:09:04+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2024-01-03 01:38:54\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-3808493\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-3808493\",\"identity\":\"rs-3808493\",\"version\":[\"v1\"]},\"buildId\":\"qtupq5eGEP_6zYnWcrvyt\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}