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. 2019 Apr 30;23:101844. doi: 10.1016/j.nicl.2019.101844

Table 2b.

Study findings for all cross-sectional studies included in the review.

Reference Magnet Strength Methodology (software, statistical approach, anatomical-level) Measure of interest Variables controlled for Findings
Early stage (days to 1 year post injury)
Urban et al. (2017), Canada 3 T CIVET (GLM, Vertex-wise) Cortical Thickness None reported Significantly thinner cortex found in TBI group compared to controls in the ldlPFC, right anterior IPL and posterior IPL (Cohen's d = 0.963, 1.152 and 1.002 respectively).
Ryan et al. (2017), AUS 3 T Freesurfer (MANOVA, Network ROI summed for DMN, CEN, SN, MN and MNEN) Volume Age at Scanning and ICV, SES and sex Time between injury and MRI was not significantly related to any measure of global or regional volumes. Volume of DMN, CEN, SN, CCMN and MNEN all significantly differed as a function of group, with significant differences found between severe TBI and all other severity/control groups. vmPFC, PCC, IPL, hippocampus, dlPFC, PPC, TH, vlPFC, ACC, A, STS, TPJ, TP, IPL, iFG-po had reduced volumes in the severe group.
Ryan et al. (2016a), AUS 3 T FreeSurfer (ANCOVA, Network ROI summed for CSN) Volume Age and ICV Significant effect of group on the volume of the total CSN, with smaller CSN for severe injury compared to control, moderate and mild groups. Of the CSN regions, only the severe group differed from controls in vmPFC, nucleus accumbens and ACC.
Ryan et al. (2016b), AUS 3 T Freesurfer (ANCOVA, global-brain and Network ROI summed for SBN) Volume ICV, age and SES Across severity groups and controls, there was no multivariate effect of group on total brain, CC, WM and GM volumes. However, univariate effect of group was found on total WM volume and total SBN volume. SBN (specifically regions of STS, TP, mPFC, OFC, TPJ, cingulate, and insula) was significantly smaller only for severe TBI compared to controls.
Juranek et al. (2012), USA 3 T Freesurfer (ANOVA, ROI) Volume ICV No main effect of TBI/OI group (or gender or hemisphere) on the volume of the amygdala or hippocampus.
Max et al. (2012), USA 1.5 T Freesurfer (MANCOVA, ROI) Volume and Cortical Thickness Age and ICV No effect of group on structural volumes of cerebral GM and WM, cerebellar GM and WM, right and left frontal, right and left temporal, basal ganglia, amygdala, thalamus, corpus callosum and hippocampus.
Wilde et al. (2011), USA 1.5 T Freesurfer (GLM, ROI, Vertex-wise) Volume and Cortical Thickness Volume corrected for ICV, age at testing Smaller volumes were found for bilateral frontal regions, as well as right MFG in the TBI group compared to controls (Cohen's f = 0.42, 0.37 and 0.35 respectively). Reported group effects on cortical thickness across regions of frontal lobe (pTRI, pORB, LOF, MOF, rostral rMFG, FP, SFG) and right temporal lobe (STG, MTG, ITG and FFG).
McCauley et al. (2010), USA 1.5 T Freesurfer (QDEC, vertex-wise) Cortical Thickness Age at testing TBI showed significantly thinner cortex than controls bilaterally for anterior prefrontal (superior, middle, inferior, and medial cortices), temporal lobes and parahippocampal gyri, posterior cingulate, and parietal and precuneus regions.



Chronic stage (1–5 years post injury)
Konigs et al. (2017), Netherlands 3 T SIENAX and FIRST (ANOVA, Global-brain, ROI) Volume Head size Main effect of severity on the volume of total brain WM, but not GM. Mild and Moderate/Severe groups had significantly smaller WM volumes than controls (Cohen's d = −0.74 and − 0.80 respectively). No significant differences were found for the tested subcortical structures.
Drijkoningen et al. (2017), Belgium 3 T Freesurfer (ANOVA, Global-brain, ROI) Volume ICV Total subcortical GM (not total cortical volume) was smaller in the TBI group compared to controls. No significant differences in cortical ROIs, but subcortically, thalamus, putamen, hippocampus and cerebellar cortex were significantly smaller in TBI.
Bigler et al. (2016), Canada & USA 1.5 T Freesurfer (QDEC, vertex-wise) Cortical Thickness Sex, Age No significant effect of group on vertex-wise cortical thickness. Age was significantly related to decreasing cortical thickness, with distribution of age-related changes being similar for TBI and OI.
Drijkoningen et al. (2015), Belgium 3 T SPM8, SUIT toolbox, DARTEL, MRIcron (GLM, Global-brain, Voxel-wise) Volume ICV No significant differences in total ICV. Reduced volume in TBI compared to OI for global infratentorial GM and WM. Cerebellar volume as a percentage of total ICV was significantly lower in TBI. A significant cluster of reduced WM volume in the infratentorial region for TBI compared to OI (but not for GM).
Bigler et al. (2013), USA 1.5 T Freesurfer and VBM (voxel-wise) Volume None reported Smaller CC volumes were found for severe injury compared to controls in anterior, mid-anterior, central, mid-posterior and posterior regions and total CC as well as total brain, total GM, total WM, thalamus, basal ganglia, amygdala and hippocampus. Posterior and anterior CC also showed reductions compared to controls in moderate and mild-complicated injuries. Severe injury group also had greater total ventricular volume and ventricle-to-brain ratio than controls. VBM showed largest significant reductions for severe injury compared to controls in CC, ventral frontal, basal forebrain regions and lateral ventricles.
Dennis et al. (2013), USA 1.5 T Freesurfer (MANOVA, Network ROI summed for DMN, CEN, SN, MN and MNEN) Volume None reported No significant differences in total ICV. Significant reductions in DMN, CEN, SN, MN and MNEN network volumes was found for severe TBI compared to OI and mild-moderate. Severe TBI group had significantly reduced volumes, compared to OIs, in PCC, HF, PPC, TH, I, A and STS.
Bigler et al. (2010), USA 1.5 T Freesurfer and ANALYZE (ANCOVA, ROI) Volume Age at testing TBI had reduced volume compared to controls in amygdala, brain stem, globus pallidus and thalamus, regardless of method (Freesurfer and ANALYZE). Putamen only smaller in TBI group when using ANALYZE method.
Fearing et al. (2008) 1.5 T ANALYZE (MANCOVA and GLM, ROI) Volume Age at Scanning and ICV TBI group showed reduced thalamic GM (but not WM) compared to controls (Cohen's d = 1.050), as well as total midbrain volume (Cohen's d = 1.91) and also its constituent parts, the tectum and tegmentum (d = 0.999 and 1.074 respectively). The pons, medulla and total brainstem did not significantly differ.
Merkley et al. (2008), USA 1.5 T Freesurfer (ANCOVA, ROI) Cortical Thickness Age and gender Significantly reduced cortical thickness in TBI compared to controls was found for lSFG, rpOPER, rFP, bilateral rostral MFG, bilateral caudal MFG, lpreC, bilateral supramarginal, lMTG, bilateral ITG, lFFG, bilateral postC, bilateral SPL, bilateral IPL, and bilateral precuneus regions.
Spanos et al. (2007), USA 1.5 T ANALYZE (GLM, ROI) Volume ICV TBI group showed reduced volumes compared to controls in cerebellar WM and GM (even after removing patients with focal cerebellar lesions. A significant interaction between groups was found, in which a significant positive correlation between DLPFC/cerebellum was found in the TD but not in the TBI group.
Wilde et al. (2007), USA 1.5 T ANALYZE (ANCOVA, ROI) Volume Age and ICV The TBI group showed volumetric reductions in bilateral hippocampus, amygdala and globus pallidus regions (Cohen's d = 2.140, 0.801 & 0.775 respectively) compared to controls, but not putamen and caudate.
Wilde et al. (2006), USA 1.5 T Picture Archival System Software (ANOVA, ROI) Volume None Showed the anterior-commissure volume was significantly smaller in the TBI group compared to controls.
Wilde et al. (2005), USA 1.5 T ANALYZE (MANCOVA, ANCOVA, global brain and regional) Volume Age at testing TBI group showed significantly reduced global brain measures of total brain and GM volumes, as well as increased ventricle to brain ratio, ventricle volume, whole brain, temporal and frontal CSF compared to controls. Regional reductions in the TBI group were found in lateral frontal WM, as well as ventromedial frontal, superior media frontal and temporal GM/WM.



Late chronic stage (9+ years post injury)
Beauchamp et al. (2011b), AUS 1.5 T FSL and ANALYZE (ANCOVA, Global brain and ROI) Volume Age at Scanning and ICV A significant effect of group (TBI vs control) was found for total CSF, GM and WM volumes (Partial η2 = 0.54, 0.41 and 0.17 respectively). Controls had less CSF and greater total GM and left hippocampus volume than all severity groups. Only severe injuries had smaller WM than controls. Right amygdala significantly bigger in controls than mild and moderate injury.
Serra-Grabulosa et al. (2005) 1.5 T ANALYZE (t-test, ROI and global-brain) Volume None reported The TBI group showed significant reductions in global WM (specifically frontal WM) volume and increases in CSF volume. No significant differences were found in total or frontal GM. Significant reductions were found in bilateral hippocampal volume in TBI compared to control.

Note. GLM = general linear model, ICV = Intra-cranial volume, OI=Orthopaedic Injury, QDEC = Query Design Estimate Contrast, ROI = Region of interest, SES = socio-economic status, VBM = voxel-based morphometry.