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Decreased Neural Connectivity in the Default Mode Network Among Youth and Young Adults With Chronic Kidney Disease

  • John D. Herrington
    Correspondence
    Address reprint requests to John D. Herrington, PhD, Center for Autism Research, The Children's Hospital of Philadelphia, Roberts Center for Pediatric Research, 5th floor, 2716 South Street, Philadelphia, PA 19146-2305.
    Affiliations
    Center for Autism Research, Children's Hospital of Philadelphia, Philadelphia, PA

    Department of Child Psychiatry and Behavioral Science, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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  • Erum A. Hartung
    Affiliations
    Division of Nephrology, Children's Hospital of Philadelphia, Philadelphia, PA

    Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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  • Nina C. Laney
    Affiliations
    Division of Nephrology, Children's Hospital of Philadelphia, Philadelphia, PA
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  • Stephen R. Hooper
    Affiliations
    Department of Allied Health Sciences, School of Medicine, University of North Carolina School–Chapel Hill, Chapel Hill, NC
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  • Susan L. Furth
    Affiliations
    Division of Nephrology, Children's Hospital of Philadelphia, Philadelphia, PA

    Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA

    Department of Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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      Summary

      An increasing amount of literature has indicated that chronic kidney disease (CKD) is associated with cognitive deficits that increase with worsening disease severity. Although abnormalities in brain structure have been widely documented, few studies to date have examined the functioning of brain areas associated with the specific cognitive domains affected by CKD (namely, attention and executive functions). Furthermore, few studies have examined functional connectivity among CKD youth who are relatively early in the course of the disease. The present study used functional magnetic resonance imaging to examine the resting state connectivity in 67 youth with CKD (mean age, 17 y) and 58 age-matched healthy controls. Using seed-based multiple regression, decreased connectivity was observed within the anterior cingulate portion of the default mode network. In addition, decreased connectivity within the dorsolateral prefrontal cortex, paracingulate gyrus, and frontal pole were correlated significantly with disease severity. These data indicate that connectivity deficits in circuits implementing attentional processes may represent an early marker for cognitive decline in CKD.

      Keywords

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      REFERENCES

        • US Renal Data System
        USRDS 2011 annual data report: atlas of end-stage renal disease in the Unites States.
        National Institutes of Health, Bethesda, MD2011
        • Gerson AC
        • Butler R
        • Moxey-Mims M
        • et al.
        Neurocognitive outcomes in children with chronic kidney disease: current findings and contemporary endeavors.
        Ment Retard Dev Disabil Res Rev. 2006; 12: 208-215
        • Bugnicourt J-M
        • Godefroy O
        • Chillon J-M
        • Choukroun G
        • Massy ZA
        Cognitive disorders and dementia in CKD: the neglected kidney-brain axis.
        J Am Soc Nephrol. 2013; 24: 353-363
        • Gipson DS
        • Hooper SR
        • Duquette PJ
        • et al.
        Memory and executive functions in pediatric chronic kidney disease.
        Child Neuropsychol J Norm Abnorm Dev Child Adolesc. 2006; 12: 391-405
        • Hooper SR
        • Gerson AC
        • Butler RW
        • et al.
        Neurocognitive functioning of children and adolescents with mild-to-moderate chronic kidney disease.
        Clin J Am Soc Nephrol. 2011; 6: 1824-1830
        • Scholvinck ML
        • Maier A
        • Ye FQ
        • Duyn JH
        • Leopold DA
        Neural basis of global resting-state fMRI activity.
        Proc Natl Acad Sci U S A. 2010; 107: 10238-10243
        • Moodalbail DG
        • Reiser KA
        • Detre JA
        • et al.
        Systematic review of structural and functional neuroimaging findings in children and adults with CKD.
        Clin J Am Soc Nephrol. 2013; 8: 1429-1448
        • Ağildere AM
        • Kurt A
        • Yildirim T
        • Benli S
        • Altinörs N
        MRI of neurologic complications in end-stage renal failure patients on hemodialysis: pictorial review.
        Eur Radiol. 2001; 11: 1063-1069
        • Kurella Tamura M
        • Larive B
        • Unruh ML
        • et al.
        Prevalence and correlates of cognitive impairment in hemodialysis patients: the Frequent Hemodialysis Network trials.
        Clin J Am Soc Nephrol. 2010; 5: 1429-1438
        • Liang X
        • Wen J
        • Ni L
        • et al.
        Altered pattern of spontaneous brain activity in the patients with end-stage renal disease: a resting-state functional MRI study with regional homogeneity analysis.
        PLoS One. 2013; 8: e71507
        • Jahanian H
        • Ni WW
        • Christen T
        • Moseley ME
        • Kurella Tamura M
        • Zaharchuk G
        Spontaneous BOLD signal fluctuations in young healthy subjects and elderly patients with chronic kidney disease.
        PLoS One. 2014; 9: e92539
        • Zhang LJ
        • Wen J
        • Liang X
        • et al.
        Brain default mode network changes after renal transplantation: a diffusion-tensor imaging and resting-state functional MR imaging study.
        Radiology. 2016; 278: 485-495
        • Li H
        • Cao W
        • Zhang X
        • et al.
        BOLD-fMRI reveals the association between renal oxygenation and functional connectivity in the aging brain.
        Neuroimage. 2019; 186: 510-517
        • Wang YF
        • Gu P
        • Zhang J
        • et al.
        Deteriorated functional and structural brain networks and normally appearing functional-structural coupling in diabetic kidney disease: a graph theory-based magnetic resonance imaging study.
        Eur Radiol. 2019; 29: 5577-5589
        • Lu H
        • Gu Z
        • Xing W
        • et al.
        Alterations of default mode functional connectivity in individuals with end-stage renal disease and mild cognitive impairment.
        BMC Nephrol. 2019; 20: 246
        • Wang Y
        • Jiang L
        • Wang X-Y
        • et al.
        Evidence of altered brain network centrality in patients with diabetic nephropathy and retinopathy: an fMRI study using a voxel-wise degree centrality approach.
        Ther Adv Endocrinol Metab. 2019; 102042018819865723
        • Chen HJ
        • Wang YF
        • Wen J
        • Xu Q
        • Lu GM
        • Zhang LJ
        Functional-structural relationship in large-scale brain networks of patients with end stage renal disease after kidney transplantation: a longitudinal study.
        Hum Brain Mapp. 2020; 41: 328-341
        • Shi Y
        • Tong C
        • Zhang M
        • Gao X
        Altered functional connectivity density in the brains of hemodialysis end-stage renal disease patients: an in vivo resting-state functional MRI study.
        PLoS One. 2019; 14e0227123
        • Park BS
        • Kim SE
        • Lee HJ
        • et al.
        Alterations in structural and functional connectivities in patients with end-stage renal disease.
        J Clin Neurol. 2020; 16: 390-400
        • Ma C
        • Gao S
        • Li W
        • Yu L
        • Fu SL
        • Ren YD
        [Study on the changes of spontaneous brain activity in maintenance hemodialysis patients with end-stage renal disease based on three different resting state-functional magnetic resonance low-frequency amplitude algorithms].
        Zhonghua Yi Xue Za Zhi. 2021; 101: 265-270
        • Ni L
        • Wen J
        • Zhang LJ
        • et al.
        Aberrant default-mode functional connectivity in patients with end-stage renal disease: a resting-state functional MR imaging study.
        Radiology. 2014; 271: 543-552
        • Ma X
        • Jiang G
        • Li S
        • et al.
        Aberrant functional connectome in neurologically asymptomatic patients with end-stage renal disease.
        PLoS One. 2015; 10e0121085
        • Gusnard D
        • Raichle M
        Searching for a baseline: functional imaging and the resting human brain.
        Nat Rev Neurosci. 2001; 2: 685-694
        • Raichle ME
        • MacLeod AM
        • Snyder AZ
        • Powers WJ
        • Gusnard DA
        • Shulman GL
        A default mode of brain function.
        Proc Natl Acad Sci U S A. 2001; 98: 676-682
        • Broyd SJ
        • Demanuele C
        • Debener S
        • Helps SK
        • James CJ
        • Sonuga-Barke EJS
        Default-mode brain dysfunction in mental disorders: a systematic review.
        Neurosci Biobehav Rev. 2009; 33: 279-296
        • Whitfield-Gabrieli S
        • Ford JM
        Default mode network activity and connectivity in psychopathology.
        Annu Rev Clin Psychol. 2012; 8: 49-76
        • Buckner RL
        • Andrews-Hanna JR
        • Schacter DL
        The brain's default network: anatomy, function, and relevance to disease.
        Ann N Y Acad Sci. 2008; 1124: 1-38
        • Smallwood J
        • Brown K
        • Baird B
        • Schooler JW
        Cooperation between the default mode network and the frontal–parietal network in the production of an internal train of thought.
        Brain Res. 2012; 1428: 60-70
        • Mevel K
        • Landeau B
        • Fouquet M
        • et al.
        Age effect on the default mode network, inner thoughts, and cognitive abilities.
        Neurobiol Aging. 2013; 34: 1292-1301
        • Mevel K
        • Chételat G
        • Eustache F
        • Desgranges B
        The default mode network in healthy aging and Alzheimer's disease.
        Int J Alzheimers Dis. 2011; 2011535816
        • Petrella JR
        • Sheldon FC
        • Prince SE
        • Calhoun VD
        • Doraiswamy PM
        Default mode network connectivity in stable vs progressive mild cognitive impairment.
        Neurology. 2011; 76: 511-517
        • Koch W
        • Teipel S
        • Mueller S
        • et al.
        Diagnostic power of default mode network resting state fMRI in the detection of Alzheimer's disease.
        Neurobiol Aging. 2012; 33: 466-478
        • Wu X
        • Li R
        • Fleisher AS
        • et al.
        Altered default mode network connectivity in Alzheimer's disease-a resting functional MRI and Bayesian network study.
        Hum Brain Mapp. 2011; 32: 1868-1881
        • Sun L
        • Cao Q
        • Long X
        • et al.
        Abnormal functional connectivity between the anterior cingulate and the default mode network in drug-naïve boys with attention deficit hyperactivity disorder.
        Psychiatry Res Neuroimaging. 2012; 201: 120-127
        • Liddle EB
        • Hollis C
        • Batty MJ
        • et al.
        Task-related default mode network modulation and inhibitory control in ADHD: effects of motivation and methylphenidate: default mode network modulation in ADHD.
        J Child Psychol Psychiatry. 2011; 52: 761-771
        • Castellanos FX
        • Margulies DS
        • Kelly C
        • et al.
        Cingulate-precuneus interactions: a new locus of dysfunction in adult attention-deficit/hyperactivity disorder.
        Biol Psychiatry. 2008; 63: 332-337
        • Hartung EA
        • Laney N
        • Kim JY
        • et al.
        Design and methods of the NiCK study: neurocognitive assessment and magnetic resonance imaging analysis of children and young adults with chronic kidney disease.
        BMC Nephrol. 2015; 16: 16-66
        • Van Dijk KRA
        • Hedden T
        • Venkataraman A
        • Evans KC
        • Lazar SW
        • Buckner RL
        Intrinsic functional connectivity as a tool for human connectomics: theory, properties, and optimization.
        J Neurophysiol. 2010; 103: 297-321
        • Satterthwaite TD
        • Elliott MA
        • Gerraty RT
        • et al.
        An improved framework for confound regression and filtering for control of motion artifact in the preprocessing of resting-state functional connectivity data.
        Neuroimage. 2013; 64: 240-256
        • Fox MD
        • Snyder AZ
        • Vincent JL
        • Corbetta M
        • Van Essen DC
        • Raichle ME
        The human brain is intrinsically organized into dynamic, anticorrelated functional networks.
        Proc Natl Acad Sci U S A. 2005; 102: 9673-9678
        • Power JD
        • Barnes KA
        • Snyder AZ
        • Schlaggar BL
        • Petersen SE
        Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion.
        Neuroimage. 2012; 59: 2142-2154
        • Van Dijk KRA
        • Sabuncu MR
        • Buckner RL
        The influence of head motion on intrinsic functional connectivity MRI.
        Neuroimage. 2012; 59: 431-438
        • Satterthwaite TD
        • Wolf DH
        • Loughead J
        • et al.
        Impact of in-scanner head motion on multiple measures of functional connectivity: relevance for studies of neurodevelopment in youth.
        Neuroimage. 2012; 60: 623-632
      1. Ward DB. Simultaneous inference for FMRI Data. 2006. Available from: http://afni/nimh.nih.gov/pub/dist/doc/manual/AlphaSim.pdf. Accessed January 1, 2016.

        • MacDonald 3rd, AW
        • JD Cohen
        • Stenger VA
        • Carter CS
        Dissociating the role of the dorsolateral prefrontal and anterior cingulate cortex in cognitive control.
        Science. 2000; 288: 1835-1838
        • Bush G
        • Luu P
        • Posner M
        Cognitive and emotional influences in anterior cingulate cortex [Comment].
        Trends Cogn Sci. 2000; 4: 215-222
        • Pardo J
        • Pardo P
        • Janer K
        • Raichle M
        The anterior cingulate cortex mediates processing selection in the Stroop attentional conflict paradigm.
        Proc Natl Acad Sci U S A. 1990; 87: 256-259
        • Banich MT
        • Milham MP
        • Atchley RA
        • et al.
        Prefrontal regions play a predominant role in imposing an attentional “set”: evidence from fMRI.
        Brain Res Cogn Brain Res. 2000; 10: 1-9
        • Zheng G
        • Wen J
        • Zhang L
        • et al.
        Altered brain functional connectivity in hemodialysis patients with end-stage renal disease: a resting-state functionalMR imaging study.
        Metab Brain Dis. 2014; 29: 777-786
        • Qiu Y
        • Lv X
        • Su H
        • Jiang G
        • Li C
        • Tian J
        Structural and functional brain alterations in end stage renal disease patients on routine hemodialysis: a voxel-based morphometry and resting state functional connectivity study.
        PLoS One. 2014; 9: e98346
        • Sonuga-Barke EJS
        • Castellanos FX
        Spontaneous attentional fluctuations in impaired states and pathological conditions: a neurobiological hypothesis.
        Neurosci Biobehav Rev. 2007; 31: 977-986
        • Tsujimoto S
        • Genovesio A
        • Wise SP
        Frontal pole cortex: encoding ends at the end of the endbrain.
        Trends Cogn Sci. 2011; 15: 169-176
        • Cohen J
        • Braver T
        • O'Reilly R
        A computational approach to prefrontal cortex, cognitive control and schizophrenia: recent developments and current challenges.
        Philos Trans R Soc Lond B Biol Sci. 1996; 351: 1515-1527
        • Fuster J
        The prefrontal cortex.
        5th ed. Academic Press, London, UK1989
        • Owen A
        • Evans A
        • Petrides M
        Evidence for a two-stage model of spatial working memory processing within the lateral frontal cortex: a positron emission tomography study.
        Cereb Cortex. 1996; 6: 31-38
        • Rajkowska G
        • Goldman-Rakic P
        Cytoarchitectonic definition of prefrontal areas in the normal human cortex: II. Variability in locations of areas 9 and 46 and relationship to the Talairach Coordinate System.
        Cereb Cortex. 1995; 5: 323-337
        • Stuss D
        • Levine B
        Adult clinical neuropsychology: lessons from studies of the frontal lobes.
        Annu Rev Psychol. 2002; 53: 401-433
        • Ballesta JJ
        • del Pozo C
        • Castelló-Banyuls J
        • Faura CC
        Selective down-regulation of α4β2 neuronal nicotinic acetylcholine receptors in the brain of uremic rats with cognitive impairment.
        Exp Neurol. 2012; 236: 28-33
        • Ni Z
        • Smogorzewski M
        • Massry SG
        Derangements in acetylcholine metabolism in brain synaptosomes in chronic renal failure.
        Kidney Int. 1993; 44: 630-637
        • Selden NR
        • Gitelman DR
        • Salamon-Murayama N
        • Parrish TB
        • Mesulam MM
        Trajectories of cholinergic pathways within the cerebral hemispheres of the human brain.
        Brain J Neurol. 1998; 121: 2249-2257
        • Sarter M
        • Givens B
        • Bruno JP
        The cognitive neuroscience of sustained attention: where top-down meets bottom-up.
        Brain Res Rev. 2001; 35: 146-160
        • Sarter M
        • Gehring WJ
        • Kozak R
        More attention must be paid: the neurobiology of attentional effort.
        Brain Res Rev. 2006; 51: 145-160
        • Perry E
        • Walker M
        • Grace J
        • Perry R
        Acetylcholine in mind: a neurotransmitter correlate of consciousness?.
        Trends Neurosci. 1999; 22: 273-280
        • Auld DS
        • Kornecook TJ
        • Bastianetto S
        • Quirion R
        Alzheimer's disease and the basal forebrain cholinergic system: relations to β-amyloid peptides, cognition, and treatment strategies.
        Prog Neurobiol. 2002; 68: 209-245