Dataset Information

Abnormal characteristic static and dynamic functional network connectivity in idiopathic normal pressure hydrocephalus.

ABSTRACT:

Aims

Idiopathic Normal pressure hydrocephalus (iNPH) is a neurodegenerative disease characterized by gait disturbance, dementia, and urinary dysfunction. The neural network mechanisms underlying this phenomenon is currently unknown.

Methods

To investigate the resting-state functional connectivity (rs-FC) abnormalities of iNPH-related brain connectivity from static and dynamic perspectives and the correlation of these abnormalities with clinical symptoms before and 3-month after shunt. We investigated both static and dynamic functional network connectivity (sFNC and dFNC, respectively) in 33 iNPH patients and 23 healthy controls (HCs).

Results

The sFNC and dFNC of networks were generally decreased in iNPH patients. The reduction in sFNC within the default mode network (DMN) and between the somatomotor network (SMN) and visual network (VN) were related to symptoms. The temporal properties of dFNC and its temporal variability in state-4 were sensitive to the identification of iNPH and were correlated with symptoms. The temporal variability in the dorsal attention network (DAN) increased, and the average instantaneous FC was altered among networks in iNPH. These features were partially associated with clinical symptoms.

Conclusion

The dFNC may be a more sensitive biomarker for altered network function in iNPH, providing us with extra information on the mechanisms of iNPH.

SUBMITTER: Huang W

PROVIDER: S-EPMC10915979 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Publications

Abnormal characteristic static and dynamic functional network connectivity in idiopathic normal pressure hydrocephalus.

Huang Wenjun W Fang Xuhao X Li Shihong S Mao Renling R Ye Chuntao C Liu Wei W Deng Yao Y Lin Guangwu G

CNS neuroscience & therapeutics 20230322 3

<h4>Aims</h4>Idiopathic Normal pressure hydrocephalus (iNPH) is a neurodegenerative disease characterized by gait disturbance, dementia, and urinary dysfunction. The neural network mechanisms underlying this phenomenon is currently unknown.<h4>Methods</h4>To investigate the resting-state functional connectivity (rs-FC) abnormalities of iNPH-related brain connectivity from static and dynamic perspectives and the correlation of these abnormalities with clinical symptoms before and 3-month after sh ...[more]

PMID: 36949617

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Project description:BackgroundIdiopathic normal pressure hydrocephalus (iNPH) is a ventriculomegaly syndrome characterized by dementia, urinary incontinence, and gait disturbance, which is potentially reversible after ventriculoperitoneal shunting (VPS). Magnetic resonance elastography (MRE) is an evolving imaging technology that noninvasively measures tissue viscoelasticity. We studied iNPH patients using MRE prior to shunting, compared them with normal controls, and analyzed associations between MRE findings and clinical features, as a pilot assessment of MRE in iNPH.MethodsStiffness values were measured on preoperative MRE in 10 iNPH patients scheduled for VPS and compared with those in 20 age- and sex-matched controls. Stiffness results were correlated with clinical iNPH symptoms.ResultsMRE demonstrated significantly increased stiffness in iNPH in cerebrum (P = 0.04), occipital (P = 0.002), and parietal (P = 0.01) regions of interest (ROIs) and significantly decreased stiffness in periventricular ROIs (P < 0.0001). Stiffness was not significantly different in frontal (P = 0.1) and deep gray ROIs (P = 0.4). Univariate analysis showed associations between preoperative iNPH symptoms and abnormally increased stiffness, including urinary incontinence with cerebrum (P = 0.005), frontal (P = 0.04), and cerebellum (P = 0.03) ROIs, and Parkinsonism with occipital ROI (P = 0.04). Postoperative improvement was associated with increased deep gray stiffness (P = 0.01); failure was associated with increased temporal (P = 0.0002) stiffness.ConclusionsBased on the preliminary results of this small, limited analysis, brain stiffness may be altered in iNPH, and these alterations in parenchymal viscoelastic properties may be correlated with clinical symptoms. Increased temporal stiffness may predict surgical failure and potentially suggest an alternative dementing pathology underlying the iNPH-like symptoms. These findings highlight the potential future utility of MRE in iNPH management.

Project description:The glymphatic system has in previous studies been shown as fundamental to clearance of waste metabolites from the brain interstitial space, and is proposed to be instrumental in normal ageing and brain pathology such as Alzheimer's disease and brain trauma. Assessment of glymphatic function using magnetic resonance imaging with intrathecal contrast agent as a cerebrospinal fluid tracer has so far been limited to rodents. We aimed to image cerebrospinal fluid flow characteristics and glymphatic function in humans, and applied the methodology in a prospective study of 15 idiopathic normal pressure hydrocephalus patients (mean age 71.3 ± 8.1 years, three female and 12 male) and eight reference subjects (mean age 41.1 + 13.0 years, six female and two male) with suspected cerebrospinal fluid leakage (seven) and intracranial cyst (one). The imaging protocol included T1-weighted magnetic resonance imaging with equal sequence parameters before and at multiple time points through 24 h after intrathecal injection of the contrast agent gadobutrol at the lumbar level. All study subjects were kept in the supine position between examinations during the first day. Gadobutrol enhancement was measured at all imaging time points from regions of interest placed at predefined locations in brain parenchyma, the subarachnoid and intraventricular space, and inside the sagittal sinus. Parameters demonstrating gadobutrol enhancement and clearance in different locations were compared between idiopathic normal pressure hydrocephalus and reference subjects. A characteristic flow pattern in idiopathic normal hydrocephalus was ventricular reflux of gadobutrol from the subarachnoid space followed by transependymal gadobutrol migration. At the brain surfaces, gadobutrol propagated antegradely along large leptomeningeal arteries in all study subjects, and preceded glymphatic enhancement in adjacent brain tissue, indicating a pivotal role of intracranial pulsations for glymphatic function. In idiopathic normal pressure hydrocephalus, we found delayed enhancement (P < 0.05) and decreased clearance of gadobutrol (P < 0.05) at the Sylvian fissure. Parenchymal (glymphatic) enhancement peaked overnight in both study groups, possibly indicating a crucial role of sleep, and was larger in normal pressure hydrocephalus patients (P < 0.05 at inferior frontal gyrus). We interpret decreased gadobutrol clearance from the subarachnoid space, along with persisting enhancement in brain parenchyma, as signs of reduced glymphatic clearance in idiopathic normal hydrocephalus, and hypothesize that reduced glymphatic function is instrumental for dementia in this disease. The study shows promise for glymphatic magnetic resonance imaging as a method to assess human brain metabolic function and renders a potential for contrast enhanced brain extravascular space imaging.

Dataset Information

Abnormal characteristic static and dynamic functional network connectivity in idiopathic normal pressure hydrocephalus.

Aims

Methods

Results

Conclusion

Publications

Abnormal characteristic static and dynamic functional network connectivity in idiopathic normal pressure hydrocephalus.

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