While the consequences of moderate to severe TBI are well-documented, there has been growing concern about the lingering effects of mild TBI (mTBI) in soldiers who have deployment-related exposure to blasts that are associated with brief loss of consciousness or confusion and manifest chronic symptoms of post-concussive syndrome. These soldiers are often presenting months to years after exposure to the traumatic event and frequently are suffering from behavioral health issues such as post-traumatic stress disorder (PTSD).

The clinical distinction between postconcussive syndrome and PTSD is often very difficult due to the overlapping symptomatology.

Currently there are no definitive biological markers for establishing the clinical diagnoses of mTBI or PTSD, and there is no imaging method for identifying or distinguishing post-concussive syndrome from PTSD. The development of more powerful MRI magnets and new imaging technology, providing improved resolution and novel contrasts to visualize the brain, provides an opportunity for more sensitive investigations into the neuronal substrates of mTBI and PTSD. We have reported preliminary brain imaging findings in mTBI and PTSD using a powerful high field (4 Tesla) MRI system.

MILD TBI

Among the most promising new and experimental imaging techniques for mTBI is diffusion tensor imaging (DTI), an MRI technique that measures the directional variability of random water motion in tissue, quantified as fractional anisotropy (FA).

In studies at the San Francisco VAMC, we have been imaging returning Iraq and Afghanistan veterans with a history of mTBI. Clinical characteristics of this group differ from civilian studies, in that the etiology of the TBI is related to blast exposure in the majority of subjects, and those with TBI from other types of trauma also reported being exposed to blasts.

In addition, more than 80 percent of this group has been diagnosed with PTSD. In preliminary white matter voxelbased DTI analysis of 10 mTBI patients at a group level who are more than two years post injury when compared with age and sex matched civilian controls, we have noted reduced FA values most notably in the internal capsule.

In mild TBI decreased FA suggests reduced structural integrity consistent with loss of tissue architecture such as axonal loss. These findings are consistent with previous DTI reports, although the abnormalities appear to be more extensive. It also raises the question of whether there is a unique pattern of DTI abnormalities related to blast injury, as well as the potential contribution of structural abnormalities from PTSD.

The structural, functional and physiological analysis of PTSD in concurrent studies being conducted at the San Francisco VA suggests that the clinical overlap of mTBI and PTSD may result in a pattern of chronic brain injury that would not have been anticipated by current clinical analysis.

POST-TRAUMATIC STRESS DISORDER

The vast majority of MRI studies of PTSD have focused on the hippocampus, which is known to play a crucial role in the biological response to stress. Several MRI studies found smaller hippocampal volumes in PTSD, though other studies yielded no evidence of structural changes.

MR spectroscopy studies consistently documented abnormal reduced N-acetylaspartate (NAA), a putative marker of neuronal integrity, in the hippocampus in PTSD, implying that the impact of PTSD on hippocampus is not limited to structural alterations. More recently, structural MRI and MR spectroscopy studies found respectively volume loss and reduced NAA in the anterior cingulate cortex in PTSD ACC, indicating that the impact of PTSD is not limited to the hippocampus.

Preliminary results from a 4 Tesla MRI pilot study at the VA in San Francisco, involving a small group of male veterans with (N=13) and without (N=11) PTSD, reveal even more widespread structural alterations in PTSD brains. The figure highlights the regional pattern of systematic gray matter reduction in PTSD, including prefrontal, superior temporal and parietal lobe regions in addition to the medial temporal lobe and the hippocampus. We also used DTI to assess WM integrity of PTSD.

In a study of male veterans (N=19, age=40.0±12.1 years) with PTSD, a trauma exposed control group without PTSD (N=14, age=33.0±13.4 years) and a small trauma-free group (N=5, age=48.2±12.5 years), we found veterans positive for PTSD had reduced FA values in the internal capsule, and angular gyrus. Increased PTSD severity further correlated with decreased FA values of the cingular bundle and internal capsule in PTSD patients.

In conclusion, MRI studies have established that mTBI and PTSD are associated with systematic brain abnormalities. The imaging findings are important to understand the biological correlates of both disorders and could trigger new drug discoveries and novel treatment strategies.

However, prospective imaging studies are warranted to determine if the observed brain abnormalities are a consequence or cause of the clinical manifestations of one or both disorders. ♦