Neural Correlates of Working Memory Performance in Veterans with Mild Traumatic Brain Injury

Rationale. Mild traumatic brain injury (mTBI), identified as the “signature” wound of U.S. veterans, is often associated with cognitive complaints, which have been inconsistently linked to working memory (WM) deficits. Moreover, the relationship between WM and brain function in mTBI veterans is understudied. The overarching aim of the study was to examine WM performance and underlying neural mechanisms via fMRI in mTBI veterans.Design. The study aimed to investigate: (1) whether veterans with mTBI demonstrated worse WM performance than veteran controls (VC); (2) whether brain activation in anterior cingulate cortex (ACC) and bilateral dorsolateral prefrontal cortex (DLPFC) during the WM task was higher in veterans with mTBI compared to VC; and (3) whether greater brain activation was associated with better WM performance in veterans with mTBI. Seventy-eight veterans (44 mTBI; 34 VC) completed neuroimaging, a WM task (modified Paced Auditory Serial Addition Test), and neuropsychiatric symptom measures. Hierarchical linear regression models including demographic and psychiatric variables were employed. Results. Veterans with and without mTBI did not differ in WM performance. However, groups differed in ACC activation during correct-incorrect trials (p=.003) after accounting for depression with lower activation in the mTBI group. Within veterans with mTBI, ACC correct-incorrect activation (p=.031) significantly predicted WM, controlling for education, such that higher activation was associated with higher false-alarm rate (worse performance). In VC, ACC activation (p=.030) during correct trials significantly predicted WM, such that higher ACC activation was associated with poorer performance; PTSD symptoms attenuated these associations, however. Conclusions & Implications. Despite similar WM performance, veterans with mTBI exhibited relatively higher ACC activation on incorrect trials than veterans without mTBI. Greater ACC activation was associated with worse WM performance in both groups. Elevated ACC activation was evident only during correct-incorrect trials; thus, the ACC may act as a salience detector signaling increased activation to errors in mTBI. This project enhances our knowledge of WM and brain activation in veterans with mTBI. Findings from this study contribute to our understanding of chronic sequelae following mTBI, which could ultimately be utilized in intervention studies to decrease distress and disability following mTBI in this vulnerable population