Prognostication of chronic disorders of consciousness using brain functional networks and clinical characteristics
Abstract
Disorders of consciousness are a heterogeneous mixture of different diseases or injuries. Although some indicators and models have been proposed for prognostication, any single method when used alone carries a high risk of false prediction. This study aimed to develop a multidomain prognostic model that combines resting state functional MRI with three clinical characteristics to predict one year outcomes at the single-subject level. The model discriminated between patients who would later recover consciousness and those who would not with an accuracy of around 88% on three datasets from two medical centers. It was also able to identify the prognostic importance of different predictors, including brain functions and clinical characteristics. To our knowledge, this is the first reported implementation of a multidomain prognostic model based on resting state functional MRI and clinical characteristics in chronic disorders of consciousness, which we suggest is accurate, robust, and interpretable.
Data availability
We have provided anonymised demographic and clinical characteristics of the DOC patients in Appendix 1. We have made the analysis pipeline, including fMRI preprocessing, feature calculation and extraction, regression and classification, and the results visualization publicly available. Also, we have uploaded the fMRI signals in each of region of interest for every DOC patient and healthy control involved in this study. Anyone is welcome to download them from GitHub (https://github.com/realmsong504/pDOC).
Article and author information
Author details
Funding
National Natural Science Foundation of China (81471380)
- Ming Song
National Natural Science Foundation of China (91432302,31620103905)
- Tianzi Jiang
The Science Frontier Program of the Chinese academy of Sciences (QYZDJ-SSW-SMC019)
- Tianzi Jiang
National Key R&D Program of China (2017YFA0105203)
- Tianzi Jiang
Beijing Municipal Science and Technology Commission (Z161100000216139)
- Tianzi Jiang
Beijing Municipal Science and Technology Commission (Z161100000216152)
- Ming Song
Beijing Municipal Science and Technology Commission (Z161100000516165)
- Ying Yang
The Guangdong Pearl River Talents Plan Innovative and Entrepreneurial Team (2016ZT06S220)
- Tianzi Jiang
Youth Innovation Promotion Association of the Chinese Academy of Sciences
- Ming Song
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: The study was approved by the Ethics Committee of the PLA Army General Hospital (protocol no: 2011-097) and the Ethics Committee of the Guangzhou General Hospital of Guangzhou Military Command (protocol no: jz20091287). Informed consent to participate in the study was obtained from the legal surrogates of the patients and from the normal controls.
Copyright
© 2018, Song et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Further reading
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Chemotherapy-induced peripheral neuropathy (CIPN) is a serious therapy-limiting side effect of commonly used anticancer drugs. Previous studies suggest that lipids may play a role in CIPN. Therefore, the present study aimed to identify the particular types of lipids that are regulated as a consequence of paclitaxel administration and may be associated with the occurrence of post-therapeutic neuropathy.
Methods:
High-resolution mass spectrometry lipidomics was applied to quantify d=255 different lipid mediators in the blood of n=31 patients drawn before and after paclitaxel therapy for breast cancer treatment. A variety of supervised statistical and machine-learning methods was applied to identify lipids that were regulated during paclitaxel therapy or differed among patients with and without post-therapeutic neuropathy.
Results:
Twenty-seven lipids were identified that carried relevant information to train machine learning algorithms to identify, in new cases, whether a blood sample was drawn before or after paclitaxel therapy with a median balanced accuracy of up to 90%. One of the top hits, sphinganine-1-phosphate (SA1P), was found to induce calcium transients in sensory neurons via the transient receptor potential vanilloid 1 (TRPV1) channel and sphingosine-1-phosphate receptors.SA1P also showed different blood concentrations between patients with and without neuropathy.
Conclusions:
Present findings suggest a role for sphinganine-1-phosphate in paclitaxel-induced biological changes associated with neuropathic side effects. The identified SA1P, through its receptors, may provide a potential drug target for co-therapy with paclitaxel to reduce one of its major and therapy-limiting side effects.
Funding:
This work was supported by the Deutsche Forschungsgemeinschaft (German Research Foundation, DFG, Grants SFB1039 A09 and Z01) and by the Fraunhofer Foundation Project: Neuropathic Pain as well as the Fraunhofer Cluster of Excellence for Immune-Mediated Diseases (CIMD). This work was also supported by the Leistungszentrum Innovative Therapeutics (TheraNova) funded by the Fraunhofer Society and the Hessian Ministry of Science and Arts. Jörn Lötsch was supported by the Deutsche Forschungsgemeinschaft (DFG LO 612/16-1).
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