Single-subject-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mild traumatic brain injury

Ming-Xiong Huang, Sharon Nichols, Dewleen G Baker, Ashley Robb, Annemarie Angeles, Kate A Yurgil, Angela Drake, Michael Levy, Tao Song, Robert McLay, Rebecca J Theilmann, Mithun Diwakar, Victoria B Risbrough, Zhengwei Ji, Charles W Huang, Douglas G Chang, Deborah L Harrington, Laura Muzzatti, Jose M Canive, J Christopher Edgar, Yu-Han Chen, Roland R Lee, Ming-Xiong Huang, Sharon Nichols, Dewleen G Baker, Ashley Robb, Annemarie Angeles, Kate A Yurgil, Angela Drake, Michael Levy, Tao Song, Robert McLay, Rebecca J Theilmann, Mithun Diwakar, Victoria B Risbrough, Zhengwei Ji, Charles W Huang, Douglas G Chang, Deborah L Harrington, Laura Muzzatti, Jose M Canive, J Christopher Edgar, Yu-Han Chen, Roland R Lee

Abstract

Traumatic brain injury (TBI) is a leading cause of sustained impairment in military and civilian populations. However, mild TBI (mTBI) can be difficult to detect using conventional MRI or CT. Injured brain tissues in mTBI patients generate abnormal slow-waves (1-4 Hz) that can be measured and localized by resting-state magnetoencephalography (MEG). In this study, we develop a voxel-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mTBI on a single-subject basis. A normative database of resting-state MEG source magnitude images (1-4 Hz) from 79 healthy control subjects was established for all brain voxels. The high-resolution MEG source magnitude images were obtained by our recent Fast-VESTAL method. In 84 mTBI patients with persistent post-concussive symptoms (36 from blasts, and 48 from non-blast causes), our method detected abnormalities at the positive detection rates of 84.5%, 86.1%, and 83.3% for the combined (blast-induced plus with non-blast causes), blast, and non-blast mTBI groups, respectively. We found that prefrontal, posterior parietal, inferior temporal, hippocampus, and cerebella areas were particularly vulnerable to head trauma. The result also showed that MEG slow-wave generation in prefrontal areas positively correlated with personality change, trouble concentrating, affective lability, and depression symptoms. Discussion is provided regarding the neuronal mechanisms of MEG slow-wave generation due to deafferentation caused by axonal injury and/or blockages/limitations of cholinergic transmission in TBI. This study provides an effective way for using MEG slow-wave source imaging to localize affected areas and supports MEG as a tool for assisting the diagnosis of mTBI.

Keywords: Axonal injury; Blast; Magnetoencephalography; Slow-wave; Traumatic brain injury.

Figures

Fig. 1
Fig. 1
Brain voxels that survived the K–S test for Gaussian distribution in the normative MEG slow-wave database. Top row (yellow) was for 2 mm FWHM, middle row (green) for 3 mm FWHM, and bottom row (blue) for 8 mm FWHM. Left column (transverse plane), middle column (coronal plane), right column (sagittal plane).
Fig. 2
Fig. 2
Zcmax values obtained from MEG source imaging for 1–4 Hz are plotted separately for 1) healthy control, 2) mild blast-induced TBI, and 3) mild non-blast-induced TBI, groups respectively. The embedded plot: the Youden index is plotted as a function of the Zcmax cutoff. The solid and dashed lines in both plots indicate cutoff values of 2.50 and 2.35, respectively.
Fig. 3
Fig. 3
Single-subject-based analysis showing statistically abnormal MEG source-wave sources in representative mTBI cases. Left column (transverse plane), middle column (coronal plane), right column (sagittal plane).
Fig. 4
Fig. 4
Voxel-based maps showing the percent likelihood of abnormal MEG slow-wave generation across the whole brain.
Fig. 5
Fig. 5
MEG slow-wave source magnitude significantly correlated with PCS in blast mTBI group (first 4 panels) and non-blast mTBI group (last panel). FDR corrected p 

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