Emotional Modulation of Frontal Alpha Asymmetry - a Novel Biomarker of Mild Traumatic Brain Injury.

Lihua Sun,Keith H. Ogawa,Jari Peräkylä,Venla Kuusinen,Kaisa M. Hartikainen

doi:10.3389/fnhum.2021.699947

Abstract

Objective findings of brain injury or dysfunction are typically lacking in mild traumatic brain injury (MTBI) despite prolonged post-concussion symptoms in some patients. Thus, there is a need for objective biomarkers of MTBI that reflect altered brain physiology underlying subjective symptoms. We have previously reported increased attention to threat-related stimuli in subjects with MTBI, suggesting a physiological vulnerability to depression. Vulnerability to depression has been linked with relatively greater activity of the right than left frontal cortex reflected in inverse pattern in frontal alpha with greater power on the left than right. We investigated whether patients with previous MTBI show this pattern of frontal activity reflected in more negative frontal alpha asymmetry (FAA) scores. Furthermore, in search for potential biomarkers of MTBI, we created a novel index, emotional modulation of FAA (eFAA) and investigated whether it correlates with subjective symptoms. EEG was recorded while subjects with previous MTBI and controls performed a computer-based reaction time task integrating different cognitive executive functions and containing either threat-related or emotionally neutral visual stimuli. Post-concussion symptoms and depression were assessed using the Rivermead Post-Concussion Symptoms Questionnaire (RPQ) and Beck’s depression inventory (BDI). Task-induced FAA was assessed and eFAA calculated by subtracting FAA in the context of neutral stimuli from FAA in the context of emotional stimuli. The MTBI group showed FAA scores reflecting relatively greater right-sided frontal activity compared to healthy controls. eFAA differentiated the symptomatic MTBI from non-symptomatic MTBI group and from healthy controls. eFAA also correlated with RPQ and BDI scores. In conclusion, FAA pattern previously linked with vulnerability to depression, was observed in patients with previous MTBI. Furthermore, eFAA has potential as a biomarker of altered affective brain functions in MTBI.

Highlights

Mild traumatic brain injury (MTBI) is a common neurological injury with a worldwide incidence ranging from 100 to more than 600 per 100 000 people (Cassidy et al, 2004)
Subjects with previous mild traumatic brain injury (MTBI) had frontal alpha asymmetry (FAA) pattern typically seen in individuals vulnerable to depression (Henriques and Davidson, 1991; Gotlib et al, 1998; Thibodeau et al, 2006; Nusslock et al, 2011)
In addition to providing a biomarker for the impact of brain injury on affective brain functions, emotional modulation of FAA (eFAA) suggests an organic basis for the subjectively experienced symptoms. eFAA may be used in future studies to further illuminate neural mechanisms underlying susceptibility to prolonged post-concussion as well as mood-related symptoms after MTBI

Summary

Introduction

Mild traumatic brain injury (MTBI) is a common neurological injury with a worldwide incidence ranging from 100 to more than 600 per 100 000 people (Cassidy et al, 2004). While MTBI is usually associated with full recovery within 1 - 3 months (Belanger et al, 2005; McCrea et al, 2009), there is an estimated 10-20% minority who suffer from prolonged postconcussion symptoms (Ruff, 2005). There is a need for objective biomarkers that reflect altered brain physiology underlying subjective symptoms after MTBI. Prolonged post-concussion symptoms most likely reflect a multifactorial etiology (Ruff, 2005; Silverberg and Iverson, 2011), with psychosocial factors frequently emphasized in adverse outcomes. Post-mortem analysis of brains of four subjects dying within four months of acquiring MTBI showed multiple cell-level pathologies such as astrocytosis, axonal damage, perivascular injury and tauprotein accumulation (Tagge et al, 2018). At the level of higher brain functions, alterations in emotion-attention interaction (Mäki-Marttunen et al, 2015), working memory (Gosselin et al, 2011, 2012) and executive functions (Hartikainen et al, 2010b) have been reported after MTBI

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