Understanding the interplay between mild traumatic brain injury and cognitive fatigue: models and treatments.

Nearly 2 million traumatic brain injuries occur annually, most of which are mild (mTBI). One debilitating sequela of mTBI is cognitive fatigue: fatigue following cognitive work. Cognitive fatigue has proven difficult to quantify and study, but this is changing, allowing models to be proposed and tested. Here, we review evidence for four models of cognitive fatigue, and relate them to specific treatments following mTBI. The evidence supports two models: cognitive fatigue results from the increased work/effort required for the brain to process information after trauma-induced damage; and cognitive fatigue results from sleep disturbances. While there are no evidence-based treatments for fatigue after mTBI, some pharmacological and nonpharmacological treatments show promise for treating this debilitating problem. Future work may target the role of genetics, neuroinflammation and the microbiome and their role in complex cognitive responses such as fatigue.