Frontal White Matter Hyperintensities Effect on Default Mode Network Connectivity in Acute Mild Traumatic Brain Injury.

Danbin Zhang,Guanghui Bai,Zhihan Yan,Shan Wang,Lijun Bai,Pinghui Zhao,Limei Ye,Pingyi Zhu,Bo Yin

doi:10.3389/fnagi.2021.793491

Abstract

The functional connectivity of the brain depends not only on the structural integrity of the cortex but also on the white matter pathways between cortical areas. White matter hyperintensities (WMH), caused by chronic hypoperfusion in the white matter, play a role in the outcome of traumatic brain injury (TBI) and other neurodegenerative disorders. Herein, we investigate how the location and volume of WMH affect the default-mode network (DMN) connectivity in acute mild TBI (mTBI) patients. Forty-six patients with acute mTBI and 46 matched healthy controls were enrolled in the study. All participants underwent T2-weighted fluid-attenuated inversion recovery magnetic resonance imaging (MRI), resting-state functional MRI (fMRI),and neuropsychological assessments. The volume and location of WMH were recorded. The relationships between the WMH volume and clinical assessments were evaluated using Spearman’s correlation. Patients with higher frontal lobe WMH volume had more severe post-concussion symptoms and poorer information processing speed. Moreover, these patients had significantly lower functional connectivity in the right middle temporal gyrus, left middle frontal gyrus, right superior frontal gyrus, and left anterior cingulate cortex, compared with patients with low frontal lobe WMH volume. Compared to the controls, the patients with high frontal WMH volume exhibited significantly lower functional connectivity in the right inferior temporal gyrus, left anterior cingulate cortex, and right superior frontal gyrus. These findings suggest that frontal lobe WMH volume may modulate the functional connectivity within the DMN. Therefore, the WMH volume in specific regions of the brain, particularly the frontal and parietal lobes, may accelerate the process of aging and cognitive impairment may be a useful biomarker for the diagnosis and prognosis of acute mTBI.

Highlights

Traumatic brain injuries (TBI) is a public health challenge of vast, but insufficiently recognized, proportions, of which70–90% of TBIs are classified as mild traumatic brain injury (Holm et al, 2005)
We explored the negative associations between higher frontal lobe White matter hyperintensities (WMH) volume and functional connectivity of the default-mode network (DMN) to clarify which pathways of connectivity are downregulated when lesions accumulate in mild TBI (mTBI) patients
We speculate that projection fibers, which alter brain activity in vulnerable connected regions, may be directly damaged during the acute phase, resulting in functional disconnection. These factors should be considered when looking for relationships between subcortical structural abnormalities and connectivity. These findings suggest that a higher frontal lobe WMH volume can affect the connectivity of the DMN in patients with mTBI

Summary

Introduction

Traumatic brain injuries (TBI) is a public health challenge of vast, but insufficiently recognized, proportions, of which70–90% of TBIs are classified as mild traumatic brain injury (mTBI) (Holm et al, 2005). Some authors have suggested that mTBI is a process of neuronal plasticity that leads to long-term structural and functional alterations to the brain (Dall’Acqua et al, 2017). These clinical symptoms are not generally associated with visible abnormalities on routine magnetic resonance imaging (MRI) or computed tomography (CT) (Raikes et al, 2018). Advanced techniques such as diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) have been frequently used to assess both the functional and structural connectivity alternations following mTBI (Cubon et al, 2011; Vakhtin et al, 2013; Salat et al, 2017). The mTBI patients have been consistently exhibited with abnormal functional connectivity within the DMN (Mayer et al, 2011; Zhou et al, 2012). The alternated functional connectivity was related to worse neurocognitive performance, which can be served as a biomarker to track disease progression and recovery in mTBI (Zhou et al, 2012)

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