## 9 Qualitative Mini Review of Other Studies Regarding the GM Volume Changes in mTBI Patients
### Longitudinal Changes in GM Volume in mTBI Patients  
[PERSON] et al. [27] employed voxel-based morphometry in a cross-sectional sample of 26 patients with mTBI and 12 healthy controls by assessing brain morphometrics at 2 weeks, 1 month, 3 months, 6 months, and 1-year post-injury. Larger GM volume within the ventromedial prefrontal cortex and right fusiform gyrus were correlated with longer duration of time since injury, while the ventromedial prefrontal cortex was positively correlated with neurocognitive performance. Additionally, significantly larger GM volume was reported in more chronic individuals, in contrast with healthy controls [27]. Figure 4: (**A–F**): Brain areas that showed decreased grey matter volume in mTBI patients, as compared to controls. [PERSON] et al. [28] investigated the WM changes in adult survivors of childhood TBIs. Detectable axonal injury or chronic confusion on late conventional MRI was reported. VBM on 12 adults with a history of childhood mild or moderate to severe TBI demonstrated higher mean diffusivity in the right cerebral WM, bilaterally in the forceps major and in the body of the splenium of the corpus callosum, while VBM showed bilaterally reduced WM volumes, mainly along the callosum splenium. No GM volumetric changes were identified in this study [28]. [PERSON] et al. [29] used high-resolution T1-weighted imaging and diffusion tensor imaging (DTI) to evaluate regional changes. Neuropsychological tests and MRIs were performed at approximately 2 and 12.7 months post-injury in 46 TBI patients and 36 matched controls. Significant neuropsychological function improvement was reported from visit 1 to visit 2 and GM and WM changes in all major fiber bundles in the brain including the corpus callosum, cingulum, superior and inferior longitudinal fascicules, uncinate fasciculus and brain stem, thalamus, and bilateral pallidum were observed during imaging. Mild TBI patients also showed small regions of decreased volume in the cingulum, right post-central gyrus, supplementary motor area, right precentral gyrus, and bilateral putamen. In this way, [PERSON] et al. [29] showed that both WM and GM degeneration is a significant contributor to brain volume loss in the post-injury period. GM and WM changes have been also reported by [PERSON] et al. [30] in their study on 48 uncomplicated mTBI patients and 37 orthopedic controls. Using MRI and VBM, significant GM decrease was observed predominantly in the right hemisphere along GM and CSF border in the lateral and medial portions of the sensorimotor cortex extending into the Rolandic operculum, middle frontal gyrus, insula, and temporal pole. In addition, significant WM decrease in the right hemisphere and more specifically the superior fasciculus longitudinalis, arcuate fasciculus, and cortical-pentine tracts, as well as a significant WM increase in the left arcuate fasciculus and left external capsule were reported [30]. [PERSON] et al. [31] calculated regional volume and asymmetry features at the acute and subacute stages of mild to severe traumatic brain injuries in 67 patients and found that there are small structural volume changes in the acute stage that can be strong predictors of unfavorable outcomes. Furthermore, patients with unfavorable outcomes showed increased atrophy [31]. The longitudinal subcortical volumetric changes in mTBI patients have been investigated by [PERSON] et al. [32] in 56 patients and 34 healthy matched controls. A reduction in thalamic and hippocampal volume at 1 month following injury was reported in mTBI patients. The thalamic volume changes persisted for up to 6 months and were correlated with post-concussion symptoms and functional outcomes in mTBI patients [32]. In a prospective cohort study of 25 mTBI patients and 18 matched controls, [PERSON] et al. [33] reported no significant difference in brain volumes between the two groups, but significant decrease in GM volume in mTBI patients between the first visit, which took place at a mean of 63 days, and second visit, at 180 days post-injury.