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Multivariate Classification of Brain Blood-Oxygen Signal Complexity for the Diagnosis of Children with Tourette Syndrome

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Abstract

Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder characterized by the presence of multiple motor and vocal tics. Because of its varied clinical expressions and lack of reliable diagnostic biomarker, present TS diagnosis still depends on qualitative descriptions of symptoms. Our study aimed to investigate whether the complexity of resting state brain activity can serve as a potential biomarker for TS diagnosis, since it has been used successfully in various neuropsychiatric disorders, including two common TS comorbidities: attention-deficit hyperactivity disorder (ADHD) and obsessive–compulsive disorder (OCD). In the current study, we used both univariate analysis and multivariate searchlight analysis with both linear and non-linear classification methods to explore the group differences in the complexity of resting state brain blood oxygen level-dependent (BOLD) signals between 25 TS boys without comorbidity and 25 sex, age and educational years matched healthy controls (HCs). We also investigated the relation between symptom severity in TS patients (YGTSS scores) and complexity indices derived from different analysis methods. We found: i) univariate analysis revealed reduced complexity in TS patients in the left cerebellum, left superior frontal gyrus, and left medial frontal gyrus; ii) multivariate analysis with non-linear classification method achieved the highest performance (accuracy: 0.94, sensitivity: 0.96, specificity: 0.92, AUC: 0.95) in bilateral supplementary motor areas; iii) significant correlations were found between complexity index derived from multivariate analysis with non-linear classification method and Tic severity (YGTSS scores) in the left cerebellum (r = 0.523, with YGTSS phonic) and in the right supplementary motor area (r = 0.767, with YGTSS motor). Taken together, these results suggested that complexity of resting state BOLD activity is a highly effective index for differentiating TS patients from normal controls. It has a good potential to be a quantitative biomarker for TS diagnosis.

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Data Availability

The datasets used or analyzed during the current study are available from the corresponding author upon reasonable request.

Code Availability

DPABI could be freely available from http://rfmri.org/dpabi. CoSMoMVPA could be freely available from http://www.cosmomvpa.org/. LIBSVM could be freely available from https://github.com/cjlin1/libsvm. Function for MSE calculation could be freely available from https://ww2.mathworks.cn/matlabcentral/fileexchange/62706-multiscale-sample-entropy?s_tid=srchtitle.

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Funding

This work was supported by the Fundamental Research Funds for the Central Universities of China with Project Code: 2019QN81013.

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Authors and Affiliations

  1. Center for Psychological Sciences, Zhejiang University, Hangzhou, 310027, China

    Xiaoyang Xin & Xiaoqing Gao

  2. Eye Center of the 2Nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China

    Yixuan Feng & Ke Yao

  3. Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou, 310009, China

    Yixuan Feng & Ke Yao

  4. Center for Cognition and Brain Disorders and the Affiliated Hospital, Hangzhou Normal University, Hangzhou, 210015, China

    Yufeng Zang

  5. Department of Pediatrics, School of Medicine, the Second Affiliated Hospital, Zhejiang University, Hangzhou, 310058, China

    Yuting Lou

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Contributions

Conception and design: XX and XG; data collection: YF, YZ, YL and KY; data analysis: XG and YF; writing—original draft preparation: XX; funding acquisition: KY and XG; review and editing: YZ, YL, KY and XG. All authors read and approved the final manuscript.

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Correspondence to Ke Yao or Xiaoqing Gao.

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The study was approved by the Local Medical Ethics Committee of the Center for Cognition and Brain Disorders, Hangzhou Normal University, China. The procedures used in this study adhere to the tenets of the Declaration of Helsinki. Informed consent was obtained from all parents.

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Xiaoyang Xin and Yixuan Feng are co-first authors.

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Xin, X., Feng, Y., Zang, Y. et al. Multivariate Classification of Brain Blood-Oxygen Signal Complexity for the Diagnosis of Children with Tourette Syndrome. Mol Neurobiol 59, 1249–1261 (2022). https://doi.org/10.1007/s12035-021-02707-0

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