Identifying neuroimaging biomarkers of major depressive disorder from cortical hemodynamic responses using machine learning approaches

Zhifei Li; Roger S McIntyre; Syeda F Husain; Roger Ho; Bach X Tran; Hien Thu Nguyen; Shuenn-Chiang Soo; Cyrus S Ho; Nanguang Chen

doi:10.1016/j.ebiom.2022.104027

Identifying neuroimaging biomarkers of major depressive disorder from cortical hemodynamic responses using machine learning approaches

EBioMedicine. 2022 May:79:104027. doi: 10.1016/j.ebiom.2022.104027. Epub 2022 Apr 28.

Authors

Zhifei Li¹, Roger S McIntyre², Syeda F Husain³, Roger Ho⁴, Bach X Tran⁵, Hien Thu Nguyen⁶, Shuenn-Chiang Soo⁷, Cyrus S Ho⁸, Nanguang Chen⁹

Affiliations

¹ Institute of Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore; Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore.
² Mood Disorders Psychopharmacology Unit, University Health Network, University of Toronto, Toronto, ON, Canada; Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada.
³ Department of Paediatrics, Yong Loo Lin School of Medicine, NUS, Singapore.
⁴ Institute of Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore; Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address: pcmrhcm@nus.edu.sg.
⁵ Institute for Preventive Medicine and Public Health, Hanoi Medical University, Viet Nam; Bloomberg School of Public Health, Johns Hopkins University, USA.
⁶ Institute for Global Health Innovations, Duy Tan University, Viet Nam; Faculty of Medicine, Duy Tan University, Da Nang, Viet Nam.
⁷ Department of Psychological Medicine, National University Hospital, Singapore.
⁸ Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Psychological Medicine, National University Hospital, Singapore.
⁹ Institute of Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore; Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore; NUS (Suzhou) Research Institute, Suzhou, China.

Abstract

Background: Early diagnosis of major depressive disorder (MDD) could enable timely interventions and effective management which subsequently improve clinical outcomes. However, quantitative and objective assessment tools for the suspected cases who present with depressive symptoms have not been fully established.

Methods: Based on a large-scale dataset (n = 363 subjects) collected with functional near-infrared spectroscopy (fNIRS) measurements during the verbal fluency task (VFT), this study proposed a data representation method for extracting spatiotemporal characteristics of NIRS signals, which emerged as candidate predictors in a two-phase machine learning framework to detect distinctive biomarkers for MDD. Supervised classifiers (e.g., support vector machine (SVM), k-nearest neighbors (KNN)) cooperated with cross-validation were implemented to evaluate the predictive capability of selected features in a training set. Another test set that was not involved in developing the algorithms enabled the independent assessment of the model's generalization.

Findings: For the classification with the optimal fusion features, the SVM classifier achieved the highest accuracy of 75.6% ± 4.7% in the nested cross-validation, and the correct prediction rate of 78.0% with a sensitivity of 75.0% and a specificity of 81.4% in the test set. Moreover, the multiway ANOVA test on clinical and demographic factors confirmed that twenty out of 39 optimal features were significantly correlated with the MDD-distinctive consequence.

Interpretation: The abnormal prefrontal activity of MDD may be quantified as diminished relative intensity and inappropriate activation timing of hemodynamic response, resulting in an objectively measurable biomarker for assessing cognitive deficits and screening MDD at the early stage.

Funding: This study was funded by NUS iHeathtech Other Operating Expenses (R-722-000-004-731).

Keywords: Biomarkers discovery; Depression; Depressive disorder; Feature selection; Functional near-infrared spectroscopy; Supervised learning.

MeSH terms

Biomarkers
Depressive Disorder, Major* / diagnostic imaging
Humans
Machine Learning
Neuroimaging
Neurovascular Coupling*
Support Vector Machine

Substances

Biomarkers