Positive Coping Styles Reduction in Elderly End Stage Renal Disease Patients: Mediating Role of White-Matter Mean Diffusivity

Positive Coping Styles Reduction in Elderly End Stage Renal Disease Patients: Mediating Role of White-Matter Mean Diffusivity | 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 Research Article Positive Coping Styles Reduction in Elderly End Stage Renal Disease Patients: Mediating Role of White-Matter Mean Diffusivity Meiling Gu, Yane Zhao, Dongsheng Jin, Yuan Zhong, Huixin Zhang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-924661/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 25 Jan, 2022 Read the published version in Neuroradiology → Version 1 posted You are reading this latest preprint version Abstract End-stage renal disease patients are usually accompanied by abnormalities in white matter microstructure. However. Whether WM changes are different from prior studies and the correlation between the abnormal WM structure and emotion regulation strategies and coping characteristics in elderly ESRD patients remain unclear. Twenty-eight patients and twenty-eight healthy controls (HC) were included in our study. We used Tract-based spatial statistic (TBSS) to investigate the microstructural changes of WM. Emotional Regulation Questionnaire (ERQ) and the Simple Coping Style Questionnaire (SCSQ) were used to measure emotional regulation strategies and coping styles. Our study revealed the damage of WM structure was widespread and there were differences in emotional regulation strategies and coping styles compared elderly ESRD patients with HC. Furthermore, positive coping style and cognitive reappraisal are significantly correlated with changes in WM microstructure. Mediating analysis showed that the mean diffusivity (MD) of the significantly different brain regions played a complete mediating role between group and positive coping style. Taken together, our results may provide a new diagnostic marker to explore the characteristics of WM damage, emotion regulation and coping style in elderly ESRD patients during hemodialysis. Cellular & Molecular Neuroscience Neurology Cognitive Neuroscience The elderly end-stage renal disease emotion regulation strategies positive coping style Tract-based spatial statistics Figures Figure 1 Figure 2 Introduction End-stage renal disease (ESRD) is a syndrome involving multiple organ failure and requires continuous renal replacement therapy. Maintenance hemodialysis can remove the retained metabolites, toxins, water and electrolytes in patients with ESRD, then return the purified blood to the body. However, hemodialysis could not completely remove the medium and macromolecular toxins in patients (Cobo et al., 2018 ). With the aging of population, the development of economic level and the increase of human life expectancy, it is not difficult to predict that the number of elderly patients who maintain hemodialysis will gradually increase. Destruction of white matter (WM) integrity in ESRD patients has been extensively verified (Chou et al., 2013 ; Chou et al., 2019 ; Drew et al., 2017 ; Liu et al., 2020 ; Richerson et al., 2021 ). However, whether WM structural abnormalities in elderly ESRD hemodialysis patients are consistent with prior studies has not been verified. Tract-based spatial statistics (TBSS) method was used in our study to analyze four parameters of WM that is radial diffusivity (RD), axial diffusivity (AD), mean diffusivity (MD) and fractional anisotropy (FA) to further explore the changes of WM microstructure in elderly ESRD hemodialysis patients. Emotional regulation is relatively stable. It is a dynamic process of monitoring and regulating internal emotional processes and external behaviors to adapt to external situations and interpersonal relationships (Gross & Muñoz, 1995 ). The occurrence of emotional dysregulation in ESRD patients may interfere with their behavior, cognitive and social functions and accelerate the disease process. Gross found that cognitive reappraisal and expression suppression were most effective and commonly used emotion regulation strategies (Cotter et al., 2020 ). Expression suppression is more tend to be used by high anxiety people to regulate their emotions (Decker et al., 2008 ). Anxiety, depression and other negative emotions are very common to see in ESRD patients. Are there any differences in emotional regulation strategies in elderly ESRD hemodialysis patients compared with healthy elderly? This forms one of our hypotheses. Existing evidence indicates that WM microstructures are involved in the pathophysiology of the entire spectrum of mood disorders (Yip, 2013). When WM is damaged, both mood and cognition are affected. Changes in FA values within the WM fiber tracts have been observed in patients with schizophrenia, depression, autism, obsessive-compulsive disorder and attention deficit disorders. Li et al. ( 2020 ) found that WM changes are accompanied by emotional disorders (Li et al., 2020 ). So studying WM integrity is the key to understanding the biological basis of emotional disorders. Coping styles are stable across contexts (Bartholomew & Horowitz, 1991 ) and robust in predicting depressive symptoms and mental function (Arnett et al., 2002 ; Rabinowitz & Arnett, 2009 ; Ukueberuwa & Arnett, 2014 ). Coping style can regulate the relationship between brain microstructure integrity and emotion. Individuals' emotional regulation strategies can also affect their psychological harmony through coping style. Proper emotion regulation strategies and coping styles can promote health and thereby limit the adverse effects of prolonged dialysis (Barberis et al., 2017 ). There are growing evidences that emotional and behavioral symptoms are related to the changes in WM microstructure (Greenberg et al., 2021 ; Wier et al., 2019 ). The cognitive reappraisal strategy focuses on the emotion generation process before the emotional response begins. Expression suppression care about inhibits emotional response behavior (Gross & John, 2003 ). Therefore, we hypothesized that emotional regulation strategies and coping styles are associated with the changes in WM microstructure and tried to determine the mediating role of WM. Materials And Methods Study population We collected 32 elderly ESRD maintenance hemodialysis patients in Geriatric Hospital of Nanjing Medical University. Inclusion criteria for the ESRD group are as follows: ① Meeting the diagnostic criteria of the National Kidney Foundation (NKF) K/DOQI grading ESRD; ② The patient should be over 60 years old when starting dialysis. Regular and routine hemodialysis was performed 3 times a week at least 3.5 hours each time, receiving hemodialysis for more than 3 months; All patients underwent biochemical tests to assess renal function before MRI scan and have complete clinical and laboratory data; ③ Right-handed. Healthy controls were recruited inclusion criteria include: ① Age 60 years old and above with normal hearing, vision and mental state; ② No kidney disease and other serious underlying diseases; ③ Right-handed. Exclusion criteria: ① patients with acute renal failure and kidney transplantation. ②Two groups were o taboo of MR scan. ③ mental disorder, substance abuse or any brain injury, such as stroke or tumor. 28 subjects were finally included in both groups. All participants were asked to complete the Emotional Regulation Questionnaire (ERQ) and the Simple Coping Style Questionnaire (SCSQ). ERQ includes two types of emotional regulation strategies that is cognitive reappraisal and expression suppression. SCSQ includes two dimensions: positive coping style and negative coping style. MRI protocol The MR data were acquired at a PHILIPS Ingenia 3.0 T MR imaging system with 16-channel head and neck joint coil. Tell participants keep your eyes closed during the scan but do not fall asleep. Each subject’s T2WI, T2-FLAIR, T1WI and DWI images were sequentially collected and these images were used to diagnose the presence of acute or non-acute lesions in the brain. The single-excitation spin echo plane imaging sequence was used for DTI scanning. FOV = 224 mm × 224 mm, matrix = 112 × 109, TR = 7903 ms, TE = 98 minimum. layer thickness = 2.0 mm, continuous scanning without slice gap and the number of scanning layers is 60. flip angle = 90 o , voxel size = 2 × 2 × 2 mm 3 , 2 mm slice thickness, and the number of diffusion sensitive gradient direction is 24 plus 1 image of B0 without diffusion weighting; B = 0, 800s/mm 2 ; The single scanning time is 7 min 33 s. Image Analysis All DTI images are process by an integration tool called PANDA (Version1.3.1, Published in 2016) (Cui et al., 2013 ). Firstly, data preprocessed start from image format converted that is DICOM image was converted to NIFTI file. Then, the redundant part of the image was cropped and the eddy current/ motion correction was made to eliminate the deformation. Next, the brain extraction was carried out to remove the threshold of non-brain tissue at 0.25 and obtain the brain mask. Next, the DTI tensor is calculated and the related scalar indices of FA, MD, AD and RD are obtained simultaneously. Finally, the diffusion index Space is normalized to 1 mm × 1 mm × 1 mm Montreal Neurological Institute (MNI) 152 Space. TBSS analysis was continued in PANDA and the FA white matter skeleton and average FA image were constructed. The threshold of average FA skeleton was 0.2 by default. GML set up in FSL was used to design the matrix and then each participant’s registered FA, MD, AD and RD images were projected onto the average FA white matter skeleton. Statistical Analysis Demographic, biochemical and psychometric data were analyzed by IBM SPSS Statistics 25.0 for Windows. The differences in age, positive coping style, negative coping style, cognitive reappraisal and expression suppression between ESRD patients and HC was compared by the independent sample T test after the normal test. P < 0.01 (two tail) was considered statistically significant. TBSS Statistics was used to analyze neuroimaging differences between the two groups. First, higher-level design was performed to design matrix and then 5,000 times permutation tests were performed to compare the differences between FA, MD, RD and AD between two groups. Next, threshold free cluster enhancement (TFCE) was used to multiple comparisons and control for FWE. The results with a significant threshold P less than 0.01 were reported. Skeleton regions of the salient areas were labeled by Johns Hopkins University (JHU) White-matter Tractography Atlas. Spearman correlation analysis was used to discover the two groups correlation between mean FA, MD, AD, RD values and cognitive reappraisal, expression suppression positive coping and negative coping (FWE correction) after extract the mean FA, MD, AD, RD values where exist brain regions differences. Finally, we used the SPSS (PROCESS Version 3.3 Model 4) to conduct mediation analysis to test cognitive reappraisal and positive coping at the same time to explore whether the differences between the two groups were affected by the mean RD, AD, MD and FA of different brain regions. The threshold of statistical significance level was set as P < 0.01 (FWE corrected). Results Demographic and Psychometric Data Demographic, biochemical and psychometric results of all subjects are shown in Table 1 . There were no significant differences in gender, age and expression inhibition score between two groups (P > 0.05). The average dialysis time of elderly ESRD hemodialysis patients was 6.7 ± 6.7 years, the mean eGFR was 5.2 ± 2.1 mL/min/ 1.73 m2 and the dialysis efficiency was 1.4 ± 0.2 (kt/v). However, there were significant differences in positive coping, negative coping style and cognitive reappraisal scores between the two groups (P < 0.01). Comparison Four parameters of White Matter Between the Two Groups Figure 1 shows FA decreased in almost all WM areas and MD, AD and RD widespread increased in elderly ESRD hemodialysis patients compared with the HC. FA, AD and RD had only one cluster with great difference at 0.01 significant threshold after FWE correction. The brain areas with significant differences in FWE corrected MD showed 1 cluster and the differences were at the whole brain level when the threshold was set to 0.95. However, two different clusters appeared and these two clusters were large, spanning a total of 20 fiber bundles when the threshold value was set to 0.99. Our findings to enhance the integrity of the study considered the possibility that the length of dialysis time may affect the WM microstructure changes in elderly patients with ESRD. 14 patients in each group after divided the elderly ESRD patients into two groups with 5 years of dialysis as the cut-off point. The group of patients were still matched by gender and age after grouped. No inter-group differences were found in the four parameters of DTI after compared and corrected using the same TBSS process approach. To be specific, FA, MD, RD and AD have no difference between two groups at threshold of 0.01 and 0.05 after FWE correction. This possible due to the small sample size of patients after partitioning. Correlation and Mediation Analysis FA was decreased in almost all WM areas while AD and RD were increased in elderly ESRD hemodialysis patients. we extracted the mean values of discrepant brain regions and exported them to SPSS to assess whether these brain differences in the two types of emotion regulation strategies (expression suppression, cognitive reappraisal) and two coping styles (positive coping, negative coping styles) have effects. Since the two significant regions clusters of MD were large and spanned 20 fiber bundles, we averaged the two significantly different WM regions values and correlated them with the above variables (Table 2). Spearman's analysis showed that the mean FA, MD, RD, AD in the differential brain regions were positively correlated with cognitive reappraisal and positive coping (the significance level was P < 0.01, FWE corrected) and the mean FA, MD, RD, AD in differential brain WM regions were not significantly correlated with expression suppression and negative coping. The mediating model showed that the mean FA, MD, AD and RD of significantly different brain regions had no mediating effect between the group and cognitive reappraisal. Similarly, the mean FA, AD and RD of the differential brain regions did not mediate the relationship between the group and the positive coping styles but the mean MD of the differential brain regions fully mediated the relationship between the group and the positive coping styles (Fig. 2 ). Discussion This study investigated 28 elderly ESRD maintenance hemodialysis patients and 28 HC. According to what we know, our study is the first to use the TBSS method to explore elderly ESRD patients WM microstructural changes and try to determine the relationship between WM abnormalities in emotional regulation and coping styles. Our results showed that FA was significantly reduced and MD, RD and AD were generally increased in almost all WM regions in elderly ESRD maintenance hemodialysis patients compared with HC, indicating that the integrity and density of WM fiber tracts and myelin integrity were damaged. we found that elderly ESRD patients FA value in the whole brain decreased significantly which was slightly different from previous studies. Most previous studies have shown decreased FA in most brain regions in patients with ESRD (Kong et al., 2014 ; Schaier et al., 2021 ; Yin et al., 2018 ) rather that the whole brain FA. We speculated that this might be caused by factors of end-stage renal disease itself. The increase of MD can indicate the reduction of dendrites and the simplification of brain microstructure (Li et al., 2016 ), MD widespread increase indicates that the water molecules movement in the brain tissues of patients is less restricted. This indicated that diffuse interstitial cerebral edema may exist which is supported by some previous studies (Chen et al., 2007 ; Kong et al., 2014 ). Alexander et al. ( 2007 ) pointed out that AD and RD can provide more detailed indicators of water diffusion direction than MD (Alexander et al., 2007 ), so we included AD and RD in our assessment of WM abnormalities in elderly ESRD hemodialysis patients. The increase of AD was associated with axon injury or nerve filament injury, suggesting gliosis. The increase in RD is related with obstructing myelination or demyelination. The limitation on the diffusion of water molecules along the short axis is reduced when myelin is damaged. Our study results showed that AD and RD were generally increased indicated that axon damage and myelin formation were obstructed in elderly ESRD hemodialysis patients. These results confirm our hypothesis that the WM damage is different in elderly ESRD hemodialysis patient and theirs’ WM injury more widespread. The elderly are more accustomed to adopt cognitive reappraisal with relatively little expression suppression strategy due to they pay more attention to the emotional well-being (Winecoff et al., 2011 ). The elderly ESRD patients were significantly different from HC in cognitive reappraisal in this study. There was no obvious difference in expression suppression which may be related to the cultural specificity of expression suppression (Schimmack et al., 2002 ). Eastern cultural background encourages suppress negative emotion expression (Butler et al., 2007 ; Soto et al., 2011 ). We found significant differences in positive and negative coping style scores between the two groups by compared with elderly ESRD hemodialysis patients with HC. This may be due to the prevalence of negative emotions such as anxiety and depression in ESRD patients during prolonged dialysis (Al-shammari et Al., 2020; Brito et al., 2019 ) resulted in coping styles differences between the two groups. In addition, the use of emotional regulation strategies will affect the style they cope with problem situations. We analyzed the correlation between four DTI parameters and the two emotional regulation strategies and the two coping styles in elderly ESRD hemodialysis patients respectively after extracted the mean FA, MD, RD and AD in the significant different brain regions. The results showed that the significant brain regions mean FA, MD, RD and AD were positively correlated with cognitive reappraisal and positive coping style (significant threshold was 0.01, FWE corrected). There was no significantly different between the four DTI parameters of WM with expression suppression and negative coping style by correction analysis after FWE correction. This suggests that the changes in WM microstructure not only affect the physiological aspects of elderly ESRD patients but also influence some coping style (such as positive coping) and emotional regulation strategies (such as cognitive reappraisal). Finally, the mediating analysis showed that the mean FA, MD, AD and RD of the significant difference brain regions had no mediating effect on the emotional regulation strategies of cognitive reappraisal in elderly ESRD patients and HC. This is inconsistent with our hypothesis. Though we believe that WM matter damage is strongly associated with emotional and cognitive impairment but it may be that emotion regulation strategies involves a more complex aspect as it requires monitoring of the internal and external processes of emotion. FA, AD and RD of the discrepant brain regions did not mediate the positive coping style between elderly ESRD patients and HC but MD played a full mediating role between them. To some extent, this indicates that sufficient attention should be paid to the hydrocephalus in elderly ESRD patients in clinical diagnosis because the changes in WM are involved in the active coping style of individuals. Our current study has several limitations. Firstly, the sample size is small and a larger sample should be recruited in future studies. Second, our patients are only elderly ESRD maintenance hemodialysis patients excluded peritoneal dialysis and non-dialysis elderly ESRD patients, so the results are difficult to be generalized to other elderly ESRD population. In addition, individuals' choice of coping styles and emotion regulation strategies is diverse and our questionnaires involves few coping styles and emotion regulation strategies. Further detailed measurements should be made to comprehensively assess coping styles and emotional regulation strategies in elderly ESRD patients. Conclusion In conclusion, we found that the decrease of FA and the increase of MD, AD and RD were significantly correlated with expression suppression, cognitive reappraisal and positive coping style in elderly ESRD patients through the multi-parameter changes of DTI, ERQ and SCSQ were evaluated. The changes of WM microstructure, especially the increase of MD, played an important role in the positive coping style of elderly ESRD patients. From the perspectives of pathology and psychology, this study revealed that there was a correlation between the changes of WM and coping style in elderly ESRD hemodialysis patients, which not only provided strong evidence for the abnormal theory of WM in elderly ESRD patients but also highlighted the psychological characteristics of emotional regulation strategies and coping style in elderly ESRD patients. Declarations Authors Contributions Yan Chen and Yane Zhao conceived and designed the experiment; Meiling Gu and Dongsheng Jin analyzed the data; Meiling Gu, Dongsheng Jin, Yan Chen and Yane Zhao interpreted the results and wrote the paper; Meiling Gu, Dongsheng Jin, Yuan Zhong, Huixin Zhang, Fupei Tong, Jianze Wu, Yan Chen and Yane Zhao revised the paper. Funding This study was supported by National Natural Science Foundation of China (81871344); Natural Science Foundation of Jiangsu Province (BK20191369); Qing Lan Project of the Higher Educations of Jiangsu Province; Open Research Fund of the Jiangsu Key Laboratory of Mental Health and Cognitive Science(19MHCSKF01). Availability of data and material The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Ethical approval The study was approved by the Ethics Committee of Nanjing Normal University (Ethical code: NNU202106033). Consent to Participate Informed consent was obtained from all individual participants included in the study. Consent to Publish Authors have read and approved the final version of the manuscript. Conflict of interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. References Cobo, G., Lindholm, B., & Stenvinkel, P. (2018). Chronic inflammation in end-stage renal disease and dialysis. Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association - European Renal Association , 33(suppl_3), iii35–iii40. https://doi.org/10.1093/ndt/gfy175 Chou, M. C., Hsieh, T. J., Lin, Y. L., Hsieh, Y. T., Li, W. Z., Chang, J. M. … Liu, G. C. (2013). 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Sao Paulo medical journal = Revista paulista de medicina , 137(2), 137–147. https://doi.org/10.1590/1516-3180.2018.0272280119 Tables Table 1 Demographics, clinical characteristics and psychometric data of elderly ESRD maintenance hemodialysis patients and HC. Variables HC ESRD P-Value Sex (M/F) 28/14 28/14 -- Age(±SD) 70.0 ± 6.0 71.4 ± 7.2 = 0.421 Dialysis duration (Y) -- 6.7 ± 6.7 -- eGFR (mL/min/1.73m 2 ) -- 5.2 ± 2.1 -- Dialysis efficiency (kt/v) -- 1.4 ± 0.2 -- Positive coping 24.3 ± 6.3 15.8 ± 7.1 < 0.001 Negative coping 9.9 ± 4.1 6.8 ± 2.8 = 0.002 Cognitive reappraisal 32.9 ± 3.5 23.4 ± 6.0 < 0.001 Express inhibition 16.3 ± 5.8 15.6 ± 5.0 = 0.665 Values are represented as mean ± SD. ESRD = end stage renal disease; HC = healthy controls; eGFR = estimated glomerular filtration rate. The P value for age and psychometric tests difference between patients and health chontrols was obtained by independent samples t test. Table 2 The correction coefficient showing corrections between mean FA, MD, AD, RD values of significantly different WM regions and ages, ERQ test, SCSQ tests in elderly ESRD hemodialysis patients and HC. Variables Age Cognitive reappraisal Express inhibition Positive coping Negative coping FA -0.378 0.593** 0.301 0.532** 0.212 MD -0.370 0.570** 0.266 0.548** 0.235 AD -0.357 0.548** 0.277 0.515** 0.139 RD -0.369 0.587** 0.290 0.529** 0.195 ERQ = emotion regulation questionnaire; SCSQ = simplified coping style questionnaire. Cite Share Download PDF Status: Published Journal Publication published 25 Jan, 2022 Read the published version in Neuroradiology → 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. 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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-924661","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":54539107,"identity":"6303ae1c-1d4c-4acd-81d3-b29eb245f090","order_by":0,"name":"Meiling Gu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA40lEQVRIiWNgGAWjYLCChAIJBgb5g40PPhjY2BGpxQCoRYK52XBGQVoykdYYALEEe5s0z4dDjA2EFMtHZCc+eGBgkScf3dhsbGNwgJmB/fDRDfi0GN7I3WwAdFix4Z2DjY9zDO7wMfCkpd3Aq2VG7jYJoJbEjQ2JzcY5Bs+YGSR4zAhp2f4DqqVN2sLgMGMDIS3yErnbQCGWOF8CqIWBGC0GPG83gx22gedgs2GPQVoyGyG/yLfnbvz4o6IucX57+8MHP/7Y2PGzHz6G35YD6Aw2fMrBtjSgM0bBKBgFo2AUoAMAdVxOwKgQkS0AAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-8875-5226","institution":"Nanjing Normal University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Meiling","middleName":"","lastName":"Gu","suffix":""},{"id":54539109,"identity":"b345f9a7-f9fe-4512-90e1-c6e7e3e79e72","order_by":1,"name":"Yane Zhao","email":"","orcid":"https://orcid.org/0000-0003-4797-4120","institution":"Geriatric Hospital of Nanjing Medical University: Jiangsu Province Geriatric Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yane","middleName":"","lastName":"Zhao","suffix":""},{"id":54539110,"identity":"b53411fd-4261-4ff7-b86d-5a816f250115","order_by":2,"name":"Dongsheng Jin","email":"","orcid":"","institution":"Geriatric Hospital of Nanjing Medical University: Jiangsu Province Geriatric Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Dongsheng","middleName":"","lastName":"Jin","suffix":""},{"id":54539114,"identity":"13d7023a-9ed6-45d7-96cb-621c43b871bd","order_by":3,"name":"Yuan Zhong","email":"","orcid":"","institution":"Nanjing Normal University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yuan","middleName":"","lastName":"Zhong","suffix":""},{"id":54539118,"identity":"9f7cd214-2a90-43c6-bdc1-13dce826714c","order_by":4,"name":"Huixin Zhang","email":"","orcid":"","institution":"Geriatric Hospital of Nanjing Medical University: Jiangsu Province Geriatric Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Huixin","middleName":"","lastName":"Zhang","suffix":""},{"id":54539120,"identity":"2569b188-0661-46db-aeca-06138f9348a1","order_by":5,"name":"Fupei Tong","email":"","orcid":"","institution":"Nanjing Normal University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Fupei","middleName":"","lastName":"Tong","suffix":""},{"id":54539123,"identity":"d91f8272-589c-4abc-b4da-4fc33c493b5f","order_by":6,"name":"Jianze Wu","email":"","orcid":"","institution":"Nanjing Normal University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jianze","middleName":"","lastName":"Wu","suffix":""},{"id":54539124,"identity":"b49b24e4-a5a2-4327-a991-8cd44538a649","order_by":7,"name":"Yan Chen","email":"","orcid":"","institution":"Geriatric Hospital of Nanjing Medical University: Jiangsu Province Geriatric Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yan","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2021-09-21 15:28:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-924661/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-924661/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00234-022-02904-1","type":"published","date":"2022-01-26T02:49:45+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":14111615,"identity":"3daada98-1a37-473b-a4b8-3f7acb5aae73","added_by":"auto","created_at":"2021-09-29 14:56:13","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":632248,"visible":true,"origin":"","legend":"Results of RD, AD, MD and FA in elderly ESRD patients (N = 28) compared with HC (N = 28) based on whole-brain comparisons. The standard MNI 152 brain template is the background of the image. The mean FA skeleton for two groups is shown in green and blue voxels represent reduced FA of brain regions in elderly ESRD patients (TFCE for multiple comparisons and control for FWE, P \u003c 0.01). Significant increased MD of brain regions (TFCE for multiple comparisons across space with significant, P \u003c 0.01, FWE corrected) are shown in yellow. Red voxels and violet voxels represent increased AD and RD of brain regions in elderly ESRD patients respectively (TFCE for multiple comparisons and control for FWE, P \u003c 0.01).","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-924661/v1/7c03ddbfc756c97dc22a096e.png"},{"id":14111616,"identity":"de0ddf09-bc30-43ca-9470-3539e4014222","added_by":"auto","created_at":"2021-09-29 14:56:13","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":171124,"visible":true,"origin":"","legend":"Mediating analysis suggested that the mean MD of significant brain regions fully mediated the relationship between the group and positive coping styles. The P value is corrected by FWE. CI: confidence interval.","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-924661/v1/dd774e28e52cfa07f83db4b8.png"},{"id":17652554,"identity":"3b5970d1-efb6-4df1-9c77-aea1a139e4a1","added_by":"auto","created_at":"2022-01-26 02:49:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1188083,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-924661/v1/87d1ad34-3918-4e3c-914b-ccd7c214ebf3.pdf"}],"financialInterests":"","formattedTitle":"Positive Coping Styles Reduction in Elderly End Stage Renal Disease Patients: Mediating Role of White-Matter Mean Diffusivity","fulltext":[{"header":"Introduction","content":"\u003cp\u003eEnd-stage renal disease (ESRD) is a syndrome involving multiple organ failure and requires continuous renal replacement therapy. Maintenance hemodialysis can remove the retained metabolites, toxins, water and electrolytes in patients with ESRD, then return the purified blood to the body. However, hemodialysis could not completely remove the medium and macromolecular toxins in patients (Cobo et al., \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). With the aging of population, the development of economic level and the increase of human life expectancy, it is not difficult to predict that the number of elderly patients who maintain hemodialysis will gradually increase.\u003c/p\u003e \u003cp\u003eDestruction of white matter (WM) integrity in ESRD patients has been extensively verified (Chou et al., \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2013\u003c/span\u003e; Chou et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; Drew et al., \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2017\u003c/span\u003e; Liu et al., \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Richerson et al., \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). However, whether WM structural abnormalities in elderly ESRD hemodialysis patients are consistent with prior studies has not been verified. Tract-based spatial statistics (TBSS) method was used in our study to analyze four parameters of WM that is radial diffusivity (RD), axial diffusivity (AD), mean diffusivity (MD) and fractional anisotropy (FA) to further explore the changes of WM microstructure in elderly ESRD hemodialysis patients.\u003c/p\u003e \u003cp\u003eEmotional regulation is relatively stable. It is a dynamic process of monitoring and regulating internal emotional processes and external behaviors to adapt to external situations and interpersonal relationships (Gross \u0026amp; Mu\u0026ntilde;oz, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e1995\u003c/span\u003e). The occurrence of emotional dysregulation in ESRD patients may interfere with their behavior, cognitive and social functions and accelerate the disease process. Gross found that cognitive reappraisal and expression suppression were most effective and commonly used emotion regulation strategies (Cotter et al., \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). Expression suppression is more tend to be used by high anxiety people to regulate their emotions (Decker et al., \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2008\u003c/span\u003e). Anxiety, depression and other negative emotions are very common to see in ESRD patients. Are there any differences in emotional regulation strategies in elderly ESRD hemodialysis patients compared with healthy elderly? This forms one of our hypotheses.\u003c/p\u003e \u003cp\u003eExisting evidence indicates that WM microstructures are involved in the pathophysiology of the entire spectrum of mood disorders (Yip, 2013). When WM is damaged, both mood and cognition are affected. Changes in FA values within the WM fiber tracts have been observed in patients with schizophrenia, depression, autism, obsessive-compulsive disorder and attention deficit disorders. Li et al. (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2020\u003c/span\u003e) found that WM changes are accompanied by emotional disorders (Li et al., \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). So studying WM integrity is the key to understanding the biological basis of emotional disorders.\u003c/p\u003e \u003cp\u003eCoping styles are stable across contexts (Bartholomew \u0026amp; Horowitz, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e1991\u003c/span\u003e) and robust in predicting depressive symptoms and mental function (Arnett et al., \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2002\u003c/span\u003e; Rabinowitz \u0026amp; Arnett, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2009\u003c/span\u003e; Ukueberuwa \u0026amp; Arnett, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2014\u003c/span\u003e). Coping style can regulate the relationship between brain microstructure integrity and emotion. Individuals' emotional regulation strategies can also affect their psychological harmony through coping style. Proper emotion regulation strategies and coping styles can promote health and thereby limit the adverse effects of prolonged dialysis (Barberis et al., \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). There are growing evidences that emotional and behavioral symptoms are related to the changes in WM microstructure (Greenberg et al., \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Wier et al., \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). The cognitive reappraisal strategy focuses on the emotion generation process before the emotional response begins. Expression suppression care about inhibits emotional response behavior (Gross \u0026amp; John, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2003\u003c/span\u003e). Therefore, we hypothesized that emotional regulation strategies and coping styles are associated with the changes in WM microstructure and tried to determine the mediating role of WM.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003eWe collected 32 elderly ESRD maintenance hemodialysis patients in Geriatric Hospital of Nanjing Medical University. Inclusion criteria for the ESRD group are as follows: ① Meeting the diagnostic criteria of the National Kidney Foundation (NKF) K/DOQI grading ESRD; ② The patient should be over 60 years old when starting dialysis. Regular and routine hemodialysis was performed 3 times a week at least 3.5 hours each time, receiving hemodialysis for more than 3 months; All patients underwent biochemical tests to assess renal function before MRI scan and have complete clinical and laboratory data; ③ Right-handed. Healthy controls were recruited inclusion criteria include: ① Age 60 years old and above with normal hearing, vision and mental state; ② No kidney disease and other serious underlying diseases; ③ Right-handed. Exclusion criteria: ① patients with acute renal failure and kidney transplantation. ②Two groups were o taboo of MR scan. ③ mental disorder, substance abuse or any brain injury, such as stroke or tumor. 28 subjects were finally included in both groups. All participants were asked to complete the Emotional Regulation Questionnaire (ERQ) and the Simple Coping Style Questionnaire (SCSQ). ERQ includes two types of emotional regulation strategies that is cognitive reappraisal and expression suppression. SCSQ includes two dimensions: positive coping style and negative coping style.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eMRI protocol\u003c/h2\u003e \u003cp\u003eThe MR data were acquired at a PHILIPS Ingenia 3.0 T MR imaging system with 16-channel head and neck joint coil. Tell participants keep your eyes closed during the scan but do not fall asleep. Each subject\u0026rsquo;s T2WI, T2-FLAIR, T1WI and DWI images were sequentially collected and these images were used to diagnose the presence of acute or non-acute lesions in the brain. The single-excitation spin echo plane imaging sequence was used for DTI scanning. FOV\u0026thinsp;=\u0026thinsp;224 mm \u0026times; 224 mm, matrix\u0026thinsp;=\u0026thinsp;112 \u0026times; 109, TR\u0026thinsp;=\u0026thinsp;7903 ms, TE\u0026thinsp;=\u0026thinsp;98 minimum. layer thickness\u0026thinsp;=\u0026thinsp;2.0 mm, continuous scanning without slice gap and the number of scanning layers is 60. flip angle\u0026thinsp;=\u0026thinsp;90\u003csup\u003eo\u003c/sup\u003e, voxel size\u0026thinsp;=\u0026thinsp;2 \u0026times; 2 \u0026times; 2 mm\u003csup\u003e3\u003c/sup\u003e, 2 mm slice thickness, and the number of diffusion sensitive gradient direction is 24 plus 1 image of B0 without diffusion weighting; B\u0026thinsp;=\u0026thinsp;0, 800s/mm\u003csup\u003e2\u003c/sup\u003e; The single scanning time is 7 min 33 s.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eImage Analysis\u003c/h2\u003e \u003cp\u003eAll DTI images are process by an integration tool called PANDA (Version1.3.1, Published in 2016) (Cui et al., \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2013\u003c/span\u003e). Firstly, data preprocessed start from image format converted that is DICOM image was converted to NIFTI file. Then, the redundant part of the image was cropped and the eddy current/ motion correction was made to eliminate the deformation. Next, the brain extraction was carried out to remove the threshold of non-brain tissue at 0.25 and obtain the brain mask. Next, the DTI tensor is calculated and the related scalar indices of FA, MD, AD and RD are obtained simultaneously. Finally, the diffusion index Space is normalized to 1 mm \u0026times; 1 mm \u0026times; 1 mm Montreal Neurological Institute (MNI) 152 Space. TBSS analysis was continued in PANDA and the FA white matter skeleton and average FA image were constructed. The threshold of average FA skeleton was 0.2 by default. GML set up in FSL was used to design the matrix and then each participant\u0026rsquo;s registered FA, MD, AD and RD images were projected onto the average FA white matter skeleton.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eDemographic, biochemical and psychometric data were analyzed by IBM SPSS Statistics 25.0 for Windows. The differences in age, positive coping style, negative coping style, cognitive reappraisal and expression suppression between ESRD patients and HC was compared by the independent sample T test after the normal test. P\u0026thinsp;\u0026lt;\u0026thinsp;0.01 (two tail) was considered statistically significant.\u003c/p\u003e \u003cp\u003eTBSS Statistics was used to analyze neuroimaging differences between the two groups. First, higher-level design was performed to design matrix and then 5,000 times permutation tests were performed to compare the differences between FA, MD, RD and AD between two groups. Next, threshold free cluster enhancement (TFCE) was used to multiple comparisons and control for FWE. The results with a significant threshold P less than 0.01 were reported. Skeleton regions of the salient areas were labeled by Johns Hopkins University (JHU) White-matter Tractography Atlas.\u003c/p\u003e \u003cp\u003eSpearman correlation analysis was used to discover the two groups correlation between mean FA, MD, AD, RD values and cognitive reappraisal, expression suppression positive coping and negative coping (FWE correction) after extract the mean FA, MD, AD, RD values where exist brain regions differences. Finally, we used the SPSS (PROCESS Version 3.3 Model 4) to conduct mediation analysis to test cognitive reappraisal and positive coping at the same time to explore whether the differences between the two groups were affected by the mean RD, AD, MD and FA of different brain regions. The threshold of statistical significance level was set as P\u0026thinsp;\u0026lt;\u0026thinsp;0.01 (FWE corrected).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eDemographic and Psychometric Data\u003c/h2\u003e \u003cp\u003eDemographic, biochemical and psychometric results of all subjects are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. There were no significant differences in gender, age and expression inhibition score between two groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The average dialysis time of elderly ESRD hemodialysis patients was 6.7\u0026thinsp;\u0026plusmn;\u0026thinsp;6.7 years, the mean eGFR was 5.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1 mL/min/ 1.73 m2 and the dialysis efficiency was 1.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2 (kt/v). However, there were significant differences in positive coping, negative coping style and cognitive reappraisal scores between the two groups (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eComparison Four parameters of White Matter Between the Two Groups\u003c/h2\u003e \u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows FA decreased in almost all WM areas and MD, AD and RD widespread increased in elderly ESRD hemodialysis patients compared with the HC. FA, AD and RD had only one cluster with great difference at 0.01 significant threshold after FWE correction. The brain areas with significant differences in FWE corrected MD showed 1 cluster and the differences were at the whole brain level when the threshold was set to 0.95. However, two different clusters appeared and these two clusters were large, spanning a total of 20 fiber bundles when the threshold value was set to 0.99. Our findings to enhance the integrity of the study considered the possibility that the length of dialysis time may affect the WM microstructure changes in elderly patients with ESRD. 14 patients in each group after divided the elderly ESRD patients into two groups with 5 years of dialysis as the cut-off point. The group of patients were still matched by gender and age after grouped. No inter-group differences were found in the four parameters of DTI after compared and corrected using the same TBSS process approach. To be specific, FA, MD, RD and AD have no difference between two groups at threshold of 0.01 and 0.05 after FWE correction. This possible due to the small sample size of patients after partitioning.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eCorrelation and Mediation Analysis\u003c/h2\u003e \u003cp\u003eFA was decreased in almost all WM areas while AD and RD were increased in elderly ESRD hemodialysis patients. we extracted the mean values of discrepant brain regions and exported them to SPSS to assess whether these brain differences in the two types of emotion regulation strategies (expression suppression, cognitive reappraisal) and two coping styles (positive coping, negative coping styles) have effects. Since the two significant regions clusters of MD were large and spanned 20 fiber bundles, we averaged the two significantly different WM regions values and correlated them with the above variables (Table\u0026nbsp;2). Spearman's analysis showed that the mean FA, MD, RD, AD in the differential brain regions were positively correlated with cognitive reappraisal and positive coping (the significance level was P\u0026thinsp;\u0026lt;\u0026thinsp;0.01, FWE corrected) and the mean FA, MD, RD, AD in differential brain WM regions were not significantly correlated with expression suppression and negative coping.\u003c/p\u003e \u003cp\u003eThe mediating model showed that the mean FA, MD, AD and RD of significantly different brain regions had no mediating effect between the group and cognitive reappraisal. Similarly, the mean FA, AD and RD of the differential brain regions did not mediate the relationship between the group and the positive coping styles but the mean MD of the differential brain regions fully mediated the relationship between the group and the positive coping styles (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study investigated 28 elderly ESRD maintenance hemodialysis patients and 28 HC. According to what we know, our study is the first to use the TBSS method to explore elderly ESRD patients WM microstructural changes and try to determine the relationship between WM abnormalities in emotional regulation and coping styles. Our results showed that FA was significantly reduced and MD, RD and AD were generally increased in almost all WM regions in elderly ESRD maintenance hemodialysis patients compared with HC, indicating that the integrity and density of WM fiber tracts and myelin integrity were damaged.\u003c/p\u003e \u003cp\u003ewe found that elderly ESRD patients FA value in the whole brain decreased significantly which was slightly different from previous studies. Most previous studies have shown decreased FA in most brain regions in patients with ESRD (Kong et al., \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2014\u003c/span\u003e; Schaier et al., \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Yin et al., \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2018\u003c/span\u003e) rather that the whole brain FA. We speculated that this might be caused by factors of end-stage renal disease itself. The increase of MD can indicate the reduction of dendrites and the simplification of brain microstructure (Li et al., \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2016\u003c/span\u003e), MD widespread increase indicates that the water molecules movement in the brain tissues of patients is less restricted. This indicated that diffuse interstitial cerebral edema may exist which is supported by some previous studies (Chen et al., \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2007\u003c/span\u003e; Kong et al., \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2014\u003c/span\u003e). Alexander et al. (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2007\u003c/span\u003e) pointed out that AD and RD can provide more detailed indicators of water diffusion direction than MD (Alexander et al., \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2007\u003c/span\u003e), so we included AD and RD in our assessment of WM abnormalities in elderly ESRD hemodialysis patients. The increase of AD was associated with axon injury or nerve filament injury, suggesting gliosis. The increase in RD is related with obstructing myelination or demyelination. The limitation on the diffusion of water molecules along the short axis is reduced when myelin is damaged. Our study results showed that AD and RD were generally increased indicated that axon damage and myelin formation were obstructed in elderly ESRD hemodialysis patients. These results confirm our hypothesis that the WM damage is different in elderly ESRD hemodialysis patient and theirs\u0026rsquo; WM injury more widespread.\u003c/p\u003e \u003cp\u003eThe elderly are more accustomed to adopt cognitive reappraisal with relatively little expression suppression strategy due to they pay more attention to the emotional well-being (Winecoff et al., \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2011\u003c/span\u003e). The elderly ESRD patients were significantly different from HC in cognitive reappraisal in this study. There was no obvious difference in expression suppression which may be related to the cultural specificity of expression suppression (Schimmack et al., \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2002\u003c/span\u003e). Eastern cultural background encourages suppress negative emotion expression (Butler et al., \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e2007\u003c/span\u003e; Soto et al., \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e2011\u003c/span\u003e). We found significant differences in positive and negative coping style scores between the two groups by compared with elderly ESRD hemodialysis patients with HC. This may be due to the prevalence of negative emotions such as anxiety and depression in ESRD patients during prolonged dialysis (Al-shammari et Al., 2020; Brito et al., \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2019\u003c/span\u003e) resulted in coping styles differences between the two groups. In addition, the use of emotional regulation strategies will affect the style they cope with problem situations.\u003c/p\u003e \u003cp\u003eWe analyzed the correlation between four DTI parameters and the two emotional regulation strategies and the two coping styles in elderly ESRD hemodialysis patients respectively after extracted the mean FA, MD, RD and AD in the significant different brain regions. The results showed that the significant brain regions mean FA, MD, RD and AD were positively correlated with cognitive reappraisal and positive coping style (significant threshold was 0.01, FWE corrected). There was no significantly different between the four DTI parameters of WM with expression suppression and negative coping style by correction analysis after FWE correction. This suggests that the changes in WM microstructure not only affect the physiological aspects of elderly ESRD patients but also influence some coping style (such as positive coping) and emotional regulation strategies (such as cognitive reappraisal).\u003c/p\u003e \u003cp\u003eFinally, the mediating analysis showed that the mean FA, MD, AD and RD of the significant difference brain regions had no mediating effect on the emotional regulation strategies of cognitive reappraisal in elderly ESRD patients and HC. This is inconsistent with our hypothesis. Though we believe that WM matter damage is strongly associated with emotional and cognitive impairment but it may be that emotion regulation strategies involves a more complex aspect as it requires monitoring of the internal and external processes of emotion. FA, AD and RD of the discrepant brain regions did not mediate the positive coping style between elderly ESRD patients and HC but MD played a full mediating role between them. To some extent, this indicates that sufficient attention should be paid to the hydrocephalus in elderly ESRD patients in clinical diagnosis because the changes in WM are involved in the active coping style of individuals.\u003c/p\u003e \u003cp\u003eOur current study has several limitations. Firstly, the sample size is small and a larger sample should be recruited in future studies. Second, our patients are only elderly ESRD maintenance hemodialysis patients excluded peritoneal dialysis and non-dialysis elderly ESRD patients, so the results are difficult to be generalized to other elderly ESRD population. In addition, individuals' choice of coping styles and emotion regulation strategies is diverse and our questionnaires involves few coping styles and emotion regulation strategies. Further detailed measurements should be made to comprehensively assess coping styles and emotional regulation strategies in elderly ESRD patients.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, we found that the decrease of FA and the increase of MD, AD and RD were significantly correlated with expression suppression, cognitive reappraisal and positive coping style in elderly ESRD patients through the multi-parameter changes of DTI, ERQ and SCSQ were evaluated. The changes of WM microstructure, especially the increase of MD, played an important role in the positive coping style of elderly ESRD patients. From the perspectives of pathology and psychology, this study revealed that there was a correlation between the changes of WM and coping style in elderly ESRD hemodialysis patients, which not only provided strong evidence for the abnormal theory of WM in elderly ESRD patients but also highlighted the psychological characteristics of emotional regulation strategies and coping style in elderly ESRD patients.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthors Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYan Chen and Yane Zhao conceived and designed the experiment; Meiling Gu and Dongsheng Jin analyzed the data; Meiling Gu, Dongsheng Jin, Yan Chen and Yane Zhao interpreted the results and wrote the paper; Meiling Gu, Dongsheng Jin, Yuan Zhong, Huixin Zhang, Fupei Tong, Jianze Wu, Yan Chen and Yane Zhao revised the paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by National Natural Science Foundation of China (81871344); Natural Science Foundation of Jiangsu Province (BK20191369); Qing Lan Project of the Higher Educations of Jiangsu Province; Open Research Fund of the Jiangsu Key Laboratory of Mental Health and Cognitive Science(19MHCSKF01).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Ethics Committee of Nanjing Normal University (Ethical code: NNU202106033).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Publish\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAuthors have read and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCobo, G., Lindholm, B., \u0026amp; Stenvinkel, P. 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A cross-cultural comparison between European Americans and Hong Kong Chinese. \u003cem\u003eEmotion (Washington, D.C.)\u003c/em\u003e, 11(6), 1450\u0026ndash;1455. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1037/a0023340\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAl-Shammari, N., Al-Modahka, A., Al-Ansari, E., Al-Kandari, M., Ibrahim, K. A., Al-Sanea, J. \u0026hellip; Albatineh, A. N. (2020). Prevalence of depression, anxiety, and their associations among end-stage renal disease patients on maintenance hemodialysis: a multi-center population-based study. \u003cem\u003ePsychology, health \u0026amp; medicine\u003c/em\u003e, 1\u0026ndash;9. 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Depression and anxiety among patients undergoing dialysis and kidney transplantation: a cross-sectional study. \u003cem\u003eSao Paulo medical journal = Revista paulista de medicina\u003c/em\u003e, 137(2), 137\u0026ndash;147. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1590/1516-3180.2018.0272280119\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographics, clinical characteristics and psychometric data of elderly ESRD maintenance hemodialysis patients and HC.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eESRD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (M/F)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28/14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28/14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge(\u0026plusmn;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70.0\u0026thinsp;\u0026plusmn;\u0026thinsp;6.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e71.4\u0026thinsp;\u0026plusmn;\u0026thinsp;7.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e=\u0026thinsp;0.421\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDialysis duration (Y)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.7\u0026thinsp;\u0026plusmn;\u0026thinsp;6.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eeGFR (mL/min/1.73m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDialysis efficiency (kt/v)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive coping\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.3\u0026thinsp;\u0026plusmn;\u0026thinsp;6.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.8\u0026thinsp;\u0026plusmn;\u0026thinsp;7.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative coping\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e=\u0026thinsp;0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCognitive reappraisal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.4\u0026thinsp;\u0026plusmn;\u0026thinsp;6.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExpress inhibition\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e=\u0026thinsp;0.665\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eValues are represented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD.\u003c/p\u003e \u003cp\u003eESRD\u0026thinsp;=\u0026thinsp;end stage renal disease; HC\u0026thinsp;=\u0026thinsp;healthy controls; eGFR\u0026thinsp;=\u0026thinsp;estimated glomerular filtration rate.\u003c/p\u003e \u003cp\u003eThe \u003cem\u003eP\u003c/em\u003e value for age and psychometric tests difference between patients and health chontrols was obtained by independent samples t test.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e \u003ccolgroup cols=\"8\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eTable\u0026nbsp;2 The correction coefficient showing corrections between mean FA, MD, AD, RD values of significantly different WM regions and ages, ERQ test, SCSQ tests in elderly ESRD hemodialysis patients and HC.\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVariables\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eCognitive reappraisal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eExpress inhibition\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003ePositive coping\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003e\u003cb\u003eNegative coping\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.378\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.593**\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.301\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.532**\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003e0.212\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.370\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.570**\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.266\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.548**\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003e0.235\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.357\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.548**\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.277\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.515**\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003e0.139\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.369\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.587**\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.290\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.529**\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003e0.195\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003eERQ\u0026thinsp;=\u0026thinsp;emotion regulation questionnaire; SCSQ\u0026thinsp;=\u0026thinsp;simplified coping style questionnaire.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","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":"The elderly, end-stage renal disease, emotion regulation strategies, positive coping style, Tract-based spatial statistics","lastPublishedDoi":"10.21203/rs.3.rs-924661/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-924661/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eEnd-stage renal disease patients are usually accompanied by abnormalities in white matter microstructure. However. Whether WM changes are different from prior studies and the correlation between the abnormal WM structure and emotion regulation strategies and coping characteristics in elderly ESRD patients remain unclear. Twenty-eight patients and twenty-eight healthy controls (HC) were included in our study. We used Tract-based spatial statistic (TBSS) to investigate the microstructural changes of WM. Emotional Regulation Questionnaire (ERQ) and the Simple Coping Style Questionnaire (SCSQ) were used to measure emotional regulation strategies and coping styles. Our study revealed the damage of WM structure was widespread and there were differences in emotional regulation strategies and coping styles compared elderly ESRD patients with HC. Furthermore, positive coping style and cognitive reappraisal are significantly correlated with changes in WM microstructure. Mediating analysis showed that the mean diffusivity (MD) of the significantly different brain regions played a complete mediating role between group and positive coping style. Taken together, our results may provide a new diagnostic marker to explore the characteristics of WM damage, emotion regulation and coping style in elderly ESRD patients during hemodialysis.\u003c/p\u003e","manuscriptTitle":"Positive Coping Styles Reduction in Elderly End Stage Renal Disease Patients: Mediating Role of White-Matter Mean Diffusivity","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-09-29 14:56:12","doi":"10.21203/rs.3.rs-924661/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","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":"aff3f6c0-3f92-4696-93ee-2968fe9fcb14","owner":[],"postedDate":"September 29th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":7519540,"name":"Cellular \u0026 Molecular Neuroscience"},{"id":7519541,"name":"Neurology"},{"id":7519542,"name":"Cognitive Neuroscience"}],"tags":[],"updatedAt":"2022-01-26T02:49:45+00:00","versionOfRecord":{"articleIdentity":"rs-924661","link":"https://doi.org/10.1007/s00234-022-02904-1","journal":{"identity":"neuroradiology","isVorOnly":false,"title":"Neuroradiology"},"publishedOn":"2022-01-26 02:49:45","publishedOnDateReadable":"January 26th, 2022"},"versionCreatedAt":"2021-09-29 14:56:12","video":"","vorDoi":"10.1007/s00234-022-02904-1","vorDoiUrl":"https://doi.org/10.1007/s00234-022-02904-1","workflowStages":[]},"version":"v1","identity":"rs-924661","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-924661","identity":"rs-924661","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}