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Altered large-scale functional brain networks in neurological Wilson’s disease

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Abstract

Wilson’s disease patients with neurological symptoms have motor symptoms and cognitive deficits, including frontal executive, visuospatial processing, and memory impairments. Although the brain structural abnormalities associated with Wilson’s disease have been documented, it remains largely unknown how Wilson’s disease affects large-scale functional brain networks. In this study, we investigated functional brain networks in Wilson’s disease. Particularly, we analyzed resting state functional magnetic resonance images of 30 Wilson’s disease patients and 26 healthy controls. First, functional brain networks for each participant were extracted using an independent component analysis method. Then, a computationally efficient pattern classification method was developed to identify discriminative brain functional networks associated with Wilson’s disease. Experimental results indicated that Wilson’s disease patients, compared with healthy controls, had altered large-scale functional brain networks, including the dorsal anterior cingulate cortex and basal ganglia network, the middle frontal gyrus, the dorsal striatum, the inferior parietal lobule, the precuneus, the temporal pole, and the posterior lobe of cerebellum. Classification models built upon these networks distinguished between neurological WD patients and HCs with accuracy up to 86.9% (specificity: 86.7%, sensitivity: 89.7%). The classification scores were correlated with the United Wilson’s Disease Rating Scale measures and durations of disease of the patients. These results suggest that Wilson’s disease patients have multiple aberrant brain functional networks, and classification scores derived from these networks are associated with severity of clinical symptoms.

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Funding

This work was supported in part by the National Basic Research Program of China (grant number 2015CB856404), National Natural Science Foundation of China (grant number 61473296), the Clinical Research Key Project of Anhui University of Chinese Medicine (grant number 2014lckf02006), the Anhui Provincial Science and Technology Project (grant number 15011d04009), and NIH grants (EB022573, DA039215, and DA039002).

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  1. Rixing **g and Yongsheng Han contributed equally to this work

Authors and Affiliations

  1. National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Bei**g, China

    Rixing **g

  2. University of Chinese Academy of Sciences, Bei**g, China

    Rixing **g

  3. Institute of Neurology, Anhui University of Chinese Medicine, Hefei, Anhui Province, China

    Yongsheng Han & Yongzhu Han

  4. Department of Biomedical Engineering, School of Bioinformatics, Chongqing University of Posts and Telecommunications, Chongqing, China

    Hewei Cheng

  5. Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China

    Kai Wang

  6. Section of Geriatric Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Daniel Weintraub

  7. Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Yong Fan

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**g, R., Han, Y., Cheng, H. et al. Altered large-scale functional brain networks in neurological Wilson’s disease. Brain Imaging and Behavior 14, 1445–1455 (2020). https://doi.org/10.1007/s11682-019-00066-y

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