Abstract / Summary
Posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) are prevalent and linked to alterations in limbic–prefrontal circuits. However, prior neuroimaging studies were limited by small samples and often examined these conditions separately. Based on a relatively large sample, we investigated spontaneous brain activity of limbic–prefrontal regions in predominantly veterans with PTSD and TBI using resting-state functional MRI. A total of 507 participants were included in the analyses (PTSD = 80, TBI = 169, healthy controls [HCs] = 258). Spontaneous activity was assessed with fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo) across predefined regions of interest: bilateral amygdala, bilateral hippocampus, and ventromedial prefrontal cortex (vmPFC). Linear mixed-effects models tested group differences while controlling for sex, age, site, and education level. Both PTSD and TBI groups exhibited elevated fALFF in the bilateral amygdala and hippocampus compared with HCs, with no significant differences between PTSD and TBI in these regions. The TBI group, but not PTSD, showed reduced fALFF in the vmPFC relative to HCs. No significant group differences were detected for the ReHo measurements. These findings suggest that PTSD and TBI share heightened spontaneous activity in the bilateral amygdala and hippocampus, while TBI uniquely showed reduced activity in the vmPFC, a key regulatory area. The absence of significant ReHo differences suggests that fALFF may be a more sensitive marker of trauma-related neural alterations than ReHo in veterans. These results may provide neurobiological markers for tailoring personalized treatments for TBI and PTSD.