**3. Neurobiological underpinnings**

Research has shown that both mTBI and PTSD are correlated with both structural and functional changes in the brain, as evidenced by advanced neuroimaging. As can

#### **Figure 1.**

*Multiple brain regions have been suggested as vulnerable to mTBI (green), including the dorsolateral prefrontal cortex, the temporal pole, cerebellum, and frontal white matter tracts connecting the amygdala and medial prefrontal cortex. PTSD has been correlated with numerous brain regions as well (red) including the amygdala, hippocampus, dorsolateral and dorsomedial prefrontal cortex, and orbitofrontal cortex. Areas in common to both PTSD and mTBI are displayed in yellow.*

#### *Current Understanding of Biomarkers in Post Traumatic Stress Disorder and Mild Traumatic… DOI: http://dx.doi.org/10.5772/intechopen.102766*

be seen in **Figure 1**, there are many regions of the brain that are known to be particularly susceptible to both mTBI and PTSD.

Within PTSD, structural and functional imaging studies have shown a wide range of brain regions that are affected. These regions include the amygdala, hippocampus, dorsolateral and dorsomedial prefrontal cortex, and the orbitofrontal cortex. As should be apparent, many of these regions have functional implications for the onset and maintenance of PTSD symptomology [39, 40]. When examining brain structure, many studies (including two large meta-analyses) have shown reduced volume in the hippocampus, a brain area that is known to mediate declarative memories [41, 42]. Similarly, reduced volume within the anterior cingulate cortex and insula have also been shown to be related to PTSD onset [43]. When examining the functional neuroimaging data related to PTSD, exposure to stimuli related to an individual's trauma is associated with increased PTSD symptoms in concert with decreased activity within the medial prefrontal cortex and anterior cingulate [44–46]. Additional areas of decreased function during exposure to trauma-related stimuli include the inferior frontal gyrus, parietal cortex, visual association cortex, and hippocampus [44, 47, 48]. In contrast, areas of increased activity relative to controls include the amygdala [49, 50], parahippocampal gyrus [44, 51], and posterior cingulate [44, 45, 51]. Taken together, the existing literature provides strong evidence of dysfunction within a network of brain regions that are highly related to PTSD symptoms including the hippocampus and amygdala, cingulate cortex, and medial prefrontal cortex [52].

When examining the neurological correlates of mTBI, brain regions are most often damaged if the shearing forces that the brain undergoes during an mTBI are of sufficient magnitude to deform neural cells beyond normal tolerance levels [53]. If this deformation is of sufficient force to cause axonal tearing, the effects of the mTBI are likely to consist of longer-lasting neurological sequelae resulting from alterations to functional connectivity or difficulty with neuronal processing of information [54]. In comparison, if such forces are of a lesser magnitude, the neurological, cognitive, and behavioral symptoms are more likely to be short lived. In general, these forces particularly affect the longer white-matter tracts of the brain including the hypothalamic-pituitary–adrenal (HPA) axis, frontal, temporal, and limbic areas [55]. Specifically, these include the dorsolateral prefrontal cortex, the temporal pole, cerebellum, and frontal white matter tracts connecting the amygdala and medial prefrontal cortex [39, 40, 55–67]—all aforementioned areas that are also implicated in PTSD.

Although the role each of these regions play in the formation of cognition is beyond the scope of this chapter, it is apparent that many of these regions are involved in both emotional regulation and executive function, especially those that are affected in both PTSD and mTBI, including the prefrontal cortex and hippocampus [58, 68]. Perhaps not surprisingly, with the large amount of overlap in the neural substrates that are affected by both PTSD and mTBI, there is a fair degree of overlapping symptomology that has a significant impact on optimal methods for both diagnosing and treating PTSD concurrent with mTBI.
