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      Altered functional connectivity density in the brains of hemodialysis end-stage renal disease patients: An in vivo resting-state functional MRI study

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          Abstract

          Background

          End-stage renal disease (ESRD) patients usually suffer from a high prevalence of central nervous system abnormalities, including cognitive impairment and emotional disorders, which severely influence their quality of life. There have been many neuroimaging research developments in ESRD patients with brain function abnormalities; however, the dysfunction of the salience network (SN) of them has received little attention. The purpose of this study was to investigate the changes of global functional connectivity density (gFCD) in brains of ESRD patients undergoing hemodialysis using resting-state functional magnetic resonance imaging (re-fMRI).

          Methods

          re-fMRI data were collected from 30 ESRD patients undergoing hemodialysis (14 men, 38.33±7.44 years old) and 30 matched healthy controls (13 men, 39.17±5.7 years old). Neuropsychological tests including the Montreal Cognitive Assessment (MoCA) and Beck Depression Inventory (BDI) were used to evaluate the neurocognitive and psychiatric conditions of the subjects. Blood biochemistry tests, including hemoglobin level, serum albumin level, blood urea level, serum phosphate, serum calcium, and parathyroid hormone level, and dialysis-related indicators, including blood pressure fluctuations in dialysis, single-pool Kt/V(spKt/V), and ultrafiltration volume of dialysis were obtained from the ESRD patients. A two-sample t-test was used to examine the group differences in gFCD between ESRD patients and healthy controls after controlling for age, gender and education.

          Results

          Compared with healthy controls, ESRD patients exhibited a significantly increased gFCD in the salience network, including the bilateral insula, and dorsal anterior cingulated cortex (dACC), and there was no significant correlation between gFCD and the structural mean grey matter volume in patients for every cluster in the brain regions showing significant different gFCD between the two groups. Furthermore, there were significant negative correlations between the degree of connectivity in the right insula and spKt/V.

          Conclusion

          Our findings revealed abnormal intrinsic dysconnectivity pattern of salience network-related regions in ESRD patients from the whole brain network perspective. The negative correlation between the right insula and spKt/V suggested that increased fractional removal of urea may reduce the pathological activity in the insula.

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          Most cited references47

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          Interoception: the sense of the physiological condition of the body.

          Converging evidence indicates that primates have a distinct cortical image of homeostatic afferent activity that reflects all aspects of the physiological condition of all tissues of the body. This interoceptive system, associated with autonomic motor control, is distinct from the exteroceptive system (cutaneous mechanoreception and proprioception) that guides somatic motor activity. The primary interoceptive representation in the dorsal posterior insula engenders distinct highly resolved feelings from the body that include pain, temperature, itch, sensual touch, muscular and visceral sensations, vasomotor activity, hunger, thirst, and 'air hunger'. In humans, a meta-representation of the primary interoceptive activity is engendered in the right anterior insula, which seems to provide the basis for the subjective image of the material self as a feeling (sentient) entity, that is, emotional awareness.
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            Validity of the MoCA and MMSE in the detection of MCI and dementia in Parkinson disease.

            Due to the high prevalence of mild cognitive impairment (MCI) and dementia in Parkinson disease (PD), routine cognitive screening is important for the optimal management of patients with PD. The Montreal Cognitive Assessment (MoCA) is more sensitive than the commonly used Mini-Mental State Examination (MMSE) in detecting MCI and dementia in patients without PD, but its validity in PD has not been established. A representative sample of 132 patients with PD at 2 movement disorders centers was administered the MoCA, MMSE, and a neuropsychological battery with operationalized criteria for deficits. MCI and PD dementia (PDD) criteria were applied by an investigator blinded to the MoCA and MMSE results. The discriminant validity of the MoCA and MMSE as screening and diagnostic instruments was ascertained. Approximately one third of the sample met diagnostic criteria for a cognitive disorder (12.9% PDD and 17.4% MCI). Mean (SD) MoCA and MMSE scores were 25.0 (3.8) and 28.1 (2.0). The overall discriminant validity for detection of any cognitive disorder was similar for the MoCA and the MMSE (receiver operating characteristic area under the curve [95% confidence interval]): MoCA (0.79 [0.72, 0.87]) and MMSE (0.76 [0.67, 0.85]), but as a screening instrument the MoCA (optimal cutoff point = 26/27, 64% correctly diagnosed, lack of ceiling effect) was superior to the MMSE (optimal cutoff point = 29/30, 54% correctly diagnosed, presence of ceiling effect). The Montreal Cognitive Assessment, but not the Mini-Mental State Examination, has adequate psychometric properties as a screening instrument for the detection of mild cognitive impairment or dementia in Parkinson disease. However, a positive screen using either instrument requires additional assessment due to suboptimal specificity at the recommended screening cutoff point.
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              Functional connectivity density mapping.

              Brain networks with energy-efficient hubs might support the high cognitive performance of humans and a better understanding of their organization is likely of relevance for studying not only brain development and plasticity but also neuropsychiatric disorders. However, the distribution of hubs in the human brain is largely unknown due to the high computational demands of comprehensive analytical methods. Here we propose a 10(3) times faster method to map the distribution of the local functional connectivity density (lFCD) in the human brain. The robustness of this method was tested in 979 subjects from a large repository of MRI time series collected in resting conditions. Consistently across research sites, a region located in the posterior cingulate/ventral precuneus (BA 23/31) was the area with the highest lFCD, which suggest that this is the most prominent functional hub in the brain. In addition, regions located in the inferior parietal cortex (BA 18) and cuneus (BA 18) had high lFCD. The variability of this pattern across subjects was <36% and within subjects was 12%. The power scaling of the lFCD was consistent across research centers, suggesting that that brain networks have a "scale-free" organization.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: MethodologyRole: Writing – original draft
                Role: Data curation
                Role: Formal analysisRole: Writing – review & editing
                Role: ConceptualizationRole: Supervision
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                31 December 2019
                2019
                : 14
                : 12
                : e0227123
                Affiliations
                [1 ] Department of Nephrology, The Ninth People’s Hospital of Chongqing, Chongqing, China
                [2 ] Department of Medical Imaging, The Ninth People’s Hospital of Chongqing, Chongqing, China
                [3 ] Center for Lab Teaching and Management, Chongqing Medical University, Chongqing, China
                University of Texas at Austin, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0003-1007-1200
                http://orcid.org/0000-0003-2897-9479
                Article
                PONE-D-19-15084
                10.1371/journal.pone.0227123
                6938298
                31891646
                1a247b18-d5e9-4e95-a43b-ba0191808ad7
                © 2019 Shi et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 11 June 2019
                : 12 December 2019
                Page count
                Figures: 2, Tables: 2, Pages: 12
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Medicine and Health Sciences
                Nephrology
                Chronic Kidney Disease
                Medicine and Health Sciences
                Nephrology
                Medical Dialysis
                Research and Analysis Methods
                Imaging Techniques
                Neuroimaging
                Biology and Life Sciences
                Neuroscience
                Neuroimaging
                Biology and Life Sciences
                Psychology
                Emotions
                Social Sciences
                Psychology
                Emotions
                Medicine and Health Sciences
                Health Care
                Patients
                Biology and Life Sciences
                Neuroscience
                Cognitive Science
                Cognitive Neuroscience
                Cognitive Neurology
                Cognitive Impairment
                Biology and Life Sciences
                Neuroscience
                Cognitive Neuroscience
                Cognitive Neurology
                Cognitive Impairment
                Medicine and Health Sciences
                Neurology
                Cognitive Neurology
                Cognitive Impairment
                Physical Sciences
                Chemistry
                Chemical Compounds
                Organic Compounds
                Urea
                Physical Sciences
                Chemistry
                Organic Chemistry
                Organic Compounds
                Urea
                Biology and Life Sciences
                Neuroscience
                Cognitive Science
                Cognitive Neuroscience
                Cognitive Neurology
                Biology and Life Sciences
                Neuroscience
                Cognitive Neuroscience
                Cognitive Neurology
                Medicine and Health Sciences
                Neurology
                Cognitive Neurology
                Custom metadata
                Because the research data contains potentially identifying information, we made a commitment to our patients when we signed the experimental agreement, promising no individual data would be disclosed. Data are available from the Ethics Committee of the Ninth Hospital of Chongqing(contact via +86 2368865180 or jykjb68861781@ 123456163.com ) for researchers who meet the criteria for access to confidential data.

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