title: Default mode network connectivity in patients with idiopathic normal pressure hydrocephalus.
abstract: OBJECTIVE
  Idiopathic normal pressure hydrocephalus (iNPH) is a neurological disorder characterized by gait disturbance, cognitive impairment, and incontinence. It is unclear whether the pathophysiology of iNPH is associated with alterations in the default mode network (DMN). The authors investigated alterations in the DMN of patients with iNPH and sought to determine whether a relationship exists between the resting-state functional connectivity of the DMN and a patient's clinical symptoms.
  
  
  METHODS
  Resting-state functional MRI (rs-fMRI) was performed in 16 preoperative patients with iNPH and 15 neurologically healthy control subjects of a similar age. Independent component and dual-regression analyses were used to quantify DMN connectivity. The patients' clinical symptoms were rated according to the iNPH grading scale (iNPHGS). Each of their specific clinical symptoms were rated according to the cognitive, gait, and urinary continence domains of iNPHGS, and neurocognitive status was assessed using the Mini-Mental State Examination, Frontal Assessment Battery (FAB), and Trail Making Test Part A. The strength of DMN connectivity was compared between patients and controls, and the correlation between DMN connectivity and iNPHGS was examined using both region of interest (ROI)-based analysis and voxel-based analysis. The correlation between DMN connectivity and each of the specific clinical symptoms, as well as neurocognitive status, was examined using voxel-based analysis.
  
  
  RESULTS
  Both ROI-based and voxel-based analyses revealed reduced DMN connectivity in patients with iNPH. ROI-based analysis showed increased DMN connectivity with worsening clinical symptoms of iNPH. Consistently, voxel-based analyses revealed that DMN connectivity correlated positively with the iNPHGS score, as well as the cognitive and urinary continence domain scores, and negatively with the FAB score. The significant peak in correlation in each case was localized to the precuneus.
  
  
  CONCLUSIONS
  This is the first study to establish alterations in the DMN of patients with iNPH. DMN connectivity may be a useful indicator of the severity of clinical symptoms in patients with iNPH.
authors: Departments of 1 Neurosurgery;
authors: Hui Ming
authors: HM
authors: Khoo
authors: Departments of 1 Neurosurgery;
authors: Haruhiko
authors: H
authors: Kishima
authors: Departments of 1 Neurosurgery;
authors: Naoki
authors: N
authors: Tani
authors: Departments of 1 Neurosurgery;
authors: Satoru
authors: S
authors: Oshino
authors: Departments of 1 Neurosurgery;
authors: Tomoyuki
authors: T
authors: Maruo
authors: Departments of 1 Neurosurgery;|Neuromodulation and Neurosurgery, Center of Medical Innovation and Translational Research;
authors: Koichi
authors: K
authors: Hosomi
authors: Departments of 1 Neurosurgery;
authors: Takufumi
authors: T
authors: Yanagisawa
authors: Psychiatry; and.
authors: Hiroaki
authors: H
authors: Kazui
authors: Radiology; Osaka University Graduate School of Medicine, Suita, Osaka Prefecture;
authors: Yoshiyuki
authors: Y
authors: Watanabe
authors: Department of Ecosocial System Engineering, Graduate School of Medicine and Engineering, University of Yamanashi, Kofu City, Yamanashi Prefecture;
authors: Toshio
authors: T
authors: Shimokawa
authors: Human Brain Research Center, Graduate School of Medicine, Kyoto University;
authors: Toshihiko
authors: T
authors: Aso
authors: Biomedical Statistics and Bioinformatics, Graduate School of Medicine and Faculty of Medicine, Kyoto University, Kyoto, Kyoto Prefecture; and.
authors: Atsushi
authors: A
authors: Kawaguchi
authors: Division of Ultrahigh Field MRI, Institute for Biomedical Sciences, Iwate Medical University, Iwate Prefecture, Japan.
authors: Fumio
authors: F
authors: Yamashita
authors: Departments of 1 Neurosurgery;|Neuromodulation and Neurosurgery, Center of Medical Innovation and Translational Research;
authors: Youichi
authors: Y
authors: Saitoh
authors: Departments of 1 Neurosurgery;
authors: Toshiki
authors: T
authors: Yoshimine
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003072:Cognition Disorders / Q000209:etiology / Q000523:psychology; D018450:Disease Progression; D005260:Female; D020233:Gait Disorders, Neurologic / Q000209:etiology / Q000473:pathology; D006801:Humans; D006850:Hydrocephalus, Normal Pressure / Q000150:complications / Q000473:pathology* / Q000523:psychology; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000473:pathology*; D009483:Neuropsychological Tests; D010296:Parietal Lobe; D014145:Trail Making Test; D014549:Urinary Incontinence / Q000209:etiology
keywords: AD = Alzheimer’s disease; DMN = default mode network; EPI = echo-planar imaging; FAB = Frontal Assessment Battery; FWE = family-wise error; ICA = independent component analysis; MELODIC = Multivariate Exploratory Linear Optimized Decomposition into Independent Components; MMSE = Mini-Mental State Examination; ROI = region of interest; SPM8 = Statistical Parametric Mapping-8; TMT-A = Trail Making Test Part A; default mode network; functional connectivity; iNPH = idiopathic normal pressure hydrocephalus; iNPHGS = iNPH grading scale (c-iNPHGS = cognitive domain, g-iNPHGS = gait domain, and i-iNPHGS = urinary continence domain); idiopathic normal pressure hydrocephalus; resting-state functional MRI; rs-fMRI = resting-state functional MRI