White matter microstructure of the neural emotion regulation circuitry in mild traumatic brain injury.

Harm Jan Van Der Horn,Alexander Leemans,Marieke E Timmerman,Namrata R Mangina,Jelmer G Kok,Jacoba M Spikman,Joukje Van Der Naalt,Sandra E Rakers

doi:10.1111/ejn.15199

Abstract

Emotion regulation is related to recovery after mild traumatic brain injury (mTBI). This longitudinal tractography study examined white matter tracts subserving emotion regulation across the spectrum of mTBI, with a focus on persistent symptoms. Four groups were examined: (a) symptomatic (n = 33) and (b) asymptomatic (n = 20) patients with uncomplicated mTBI (i.e., no lesions on computed tomography [CT]), (c) patients with CT‐lesions in the frontal areas (n = 14), and (d) healthy controls (HC) (n = 20). Diffusion and conventional MRI were performed approximately 1‐ and 3‐months post‐injury. Whole‐brain deterministic tractography followed by region of interest analyses was used to identify forceps minor (FM), uncinate fasciculus (UF), and cingulum bundle as tracts of interest. An adjusted version of the ExploreDTI Atlas Based Tractography method was used to obtain reliable tracts for every subject. Mean fractional anisotropy (FA), mean, radial and axial diffusivity (MD, RD, AD), and number of streamlines were studied per tract. Linear mixed models showed lower FA, and higher MD, and RD of the right UF in asymptomatic patients with uncomplicated mTBI relative to symptomatic patients and HC. Diffusion alterations were most pronounced in the group with frontal lesions on CT, particularly in the FM and UF; these effects increased over time. Within the group of patients with uncomplicated mTBI, there were no associations of diffusion measures with the number of symptoms nor with lesions on conventional MRI. In conclusion, mTBI can cause microstructural changes in emotion regulation tracts, however, no explanation was found for the presence of symptoms.

Highlights

Many patients with mild traumatic brain injury develop persistent symptoms, it is still difficult to explain these symptoms for the individual patient (Mayer et al, 2017; van der Horn, Out, et al, 2019; van der Naalt et al, 2017)
This study indicates that microstructural injury to the neural emotion regulation circuitry is not likely to play a role in causing poor recovery after uncomplicated mild traumatic brain injury (mTBI)
Microstructural white matter injury was most pronounced in patients with macroscopic frontal lesions, as detected with Computed tomography (CT)-s cans, and this was most evident in the forceps minor (FM) and right uncinate fasciculus (UF)

Summary

| INTRODUCTION

Many patients with mild traumatic brain injury (mTBI) develop persistent symptoms, it is still difficult to explain these symptoms for the individual patient (Mayer et al, 2017; van der Horn, Out, et al, 2019; van der Naalt et al, 2017). The forceps minor (FM), uncinate fasciculus (UF), and cingulum bundle (CB) are key white matter tracts connecting frontal, limbic, and temporal areas within the emotion regulation circuitry (Ochsner & Gross, 2005; Versace et al, 2015) These tracts have found to be affected in mTBI (Aoki & Inokuchi, 2016; Dodd et al, 2014; Hellstrøm et al, 2017; Mayer et al, 2010; Wallace et al, 2020), and it can be hypothesized that microstructural injury to these tracts contributes to emotion regulation deficits, resulting in persistent symptoms. Because patients with persistent symptoms often undergo conventional MRI (i.e., susceptibility-weighted imaging [SWI] and T2*-gradient echo [GRE]) at the outpatient clinic, we added the presence/absence of lesions on conventional MRI as a variable of interest

| Participants and clinical measures

| RESULTS

Findings

| DISCUSSION