Assessing the Impact of Post-Traumatic Stress Symptoms on the Resting-State Default Mode Network in a Military Chronic Mild Traumatic Brain Injury Sample.

The relationship between post-traumatic stress disorder (PTSD) and chronic symptoms of mild traumatic brain injury (mTBI) is difficult to discern and poorly understood. An accurate differential diagnosis, assessment, and treatment of mTBI and PTSD are challenging due to significant symptom overlap and the absence of clearly established biomarkers. The objective of this work is to examine how post-traumatic stress influences task-free default mode network in chronic mTBI subjects. Control subjects (N = 44) were compared with chronic mTBI subjects with low (N = 58, PTSD Checklist-Civilian Version [PCL-C] total < 30), medium (N = 124, PCL-C total = 31-49), and high (N = 105, PCL-C total ≥ 60) post-traumatic stress symptoms (PTSS). The results indicate significant differences in Brodmann area 10 for all mTBI subject groups, indicating potential mTBI-related disruptions with regulation of emotions and decision-making. The effects of PTSS were observed in the anterior cingulate and parahippocampus, suggesting possible disruptions pertaining to memory regulation, encoding, and retrieval. The overall results indicate the presence of aberrant connectivity patterns between controls and chronic mTBI subjects with low, medium, and high PTSS. Furthermore, the findings suggest a disruption in attention relating to a network of brain regions involved with emotional regulation and memory coding, rather than a fear-related response. Taken together, the results suggest these regions form a network that could be a target for future research pertaining to PTSD and chronic mTBI. Furthermore, the use of clinical measures, task-based imaging studies, or multimodal imaging could help further elucidate specific neural correlates of PTSS and mTBI.

Assessing Quantitative Changes in Intrinsic Thalamic Networks in Blast and Nonblast Mild Traumatic Brain Injury: Implications for Mechanisms of Injury.

In the global war on terror, the increased use of improvised explosive devices has resulted in increased incidence of blast-related mild traumatic brain injury (mTBI). Diagnosing mTBI is both challenging and controversial due to heterogeneity of injury location, trauma intensity, transient symptoms, and absence of focal biomarkers on standard clinical imaging modalities. The goal of this study is to identify a brain biomarker that is sensitive to mTBI injury. Research suggests the thalamus may be sensitive to changes induced by mTBI. A significant number of connections to and from various brain regions converge at the thalamus. In addition, the thalamus is involved in information processing, integration, and regulation of specific behaviors and mood. In this study, changes in task-free thalamic networks as quantified by graph theory measures in mTBI blast (N = 186), mTBI nonblast (N = 80), and controls (N = 21) were compared. Results show that the blast mTBI group had significant hyper-connectivity compared with the controls and nonblast mTBI group. However, after controlling for post-traumatic stress symptoms (PTSS), the blast mTBI group was not different from the controls, but the nonblast mTBI group showed significant hypo-connectivity. The results suggest that there are differences in the mechanisms of injury related to mTBI as reflected in the architecture of the thalamic networks. However, the effect of PTSS and its relationship to mTBI is difficult to distinguish and warrants more research.

Imaging Cerebral Microhemorrhages in Military Service Members with Chronic Traumatic Brain Injury.

PURPOSE: To detect cerebral microhemorrhages in military service members with chronic traumatic brain injury by using susceptibility-weighted magnetic resonance (MR) imaging. The longitudinal evolution of microhemorrhages was monitored in a subset of patients by using quantitative susceptibility mapping. MATERIALS AND METHODS: The study was approved by the Walter Reed National Military Medical Center institutional review board and is compliant with HIPAA guidelines. All participants underwent two-dimensional conventional gradient-recalled-echo MR imaging and three-dimensional flow-compensated multiecho gradient-recalled-echo MR imaging (processed to generate susceptibility-weighted images and quantitative susceptibility maps), and a subset of patients underwent follow-up imaging. Microhemorrhages were identified by two radiologists independently. Comparisons of microhemorrhage number, size, and magnetic susceptibility derived from quantitative susceptibility maps between baseline and follow-up imaging examinations were performed by using the paired t test. RESULTS: Among the 603 patients, cerebral microhemorrhages were identified in 43 patients, with six excluded for further analysis owing to artifacts. Seventy-seven percent (451 of 585) of the microhemorrhages on susceptibility-weighted images had a more conspicuous appearance than on gradient-recalled-echo images. Thirteen of the 37 patients underwent follow-up imaging examinations. In these patients, a smaller number of microhemorrhages were identified at follow-up imaging compared with baseline on quantitative susceptibility maps (mean ± standard deviation, 9.8 microhemorrhages ± 12.8 vs 13.7 microhemorrhages ± 16.6; P = .019). Quantitative susceptibility mapping-derived quantitative measures of microhemorrhages also decreased over time: -0.85 mm(3) per day ± 1.59 for total volume (P = .039) and -0.10 parts per billion per day ± 0.14 for mean magnetic susceptibility (P = .016). CONCLUSION: The number of microhemorrhages and quantitative susceptibility mapping-derived quantitative measures of microhemorrhages all decreased over time, suggesting that hemosiderin products undergo continued, subtle evolution in the chronic stage.