White and gray matter contributions to executive function recovery after traumatic brain injury

Objective: We investigated the association between regional white and gray matter volume loss and performance on executive functions (EFs) in patients with penetrating traumatic brain injury (pTBI). Methods: We studied 164 pTBI patients and 43 healthy controls from the Vietnam Head Injury Study. We acquired CT scans for pTBI patients and divided them according to lesion localization (left and right prefrontal cortex [PFC]). We administered EF tests (Verbal Fluency, Trail Making, Twenty Questions) and used voxel-based lesion symptom mapping (VLSM) and group-based correlational and multiple regression analyses to examine the relative influence of gray and white matter lesions on EF recovery. Results: The VLSM analysis revealed that white and gray white matter lesions were associated with impaired EFs. In the left PFC lesion group, damage to the PFC gray matter, anterior corona radiata, and superior longitudinal fasciculus (SLF) were most correlated with functional recovery. Verbal Fluency, which involves a broad fronto-temporo-parietal network, was best predicted by SLF lesion volume. Trail Making and Twenty Questions, which is associated with more focal left frontal damage, was better predicted by PFC lesions. Conclusions: Our results indicated that whitematter volume loss can be a superior predictor of recovery and a crucial factor driving clinical outcome in functions involving a broad network such as Verbal Fluency. White matter damage may place additional burden on recovery by deteriorating signal transmission between cortical areas within a functional network.