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Concussion. 2017 Oct 27;2(4):CNC50. doi: 10.2217/cnc-2017-0003. eCollection 2017 Dec.

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

Wylie GR1,2,3,1,2,3, Flashman LA4,4.

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Kessler Foundation, Rocco Ortenzio Neuroimaging Center, 1199 Pleasant Valley Way, West Orange, NJ 07052, USA.
Department of Physical Medicine & Rehabilitation, New Jersey Medical School, Rutgers University, Newark, NJ 07101, USA.
The Department of Veterans' Affairs, The War Related Illness & Injury Center, New Jersey Healthcare System, East Orange Campus, East Orange, NJ 07018, USA.
Dartmouth Hitchcock Medical Center, Dartmouth College, Geisel School of Medicine, Lebanon, NH 03756, USA.


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.


REVIEW; cognitive fatigue; mild TBI

Conflict of interest statement

Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.

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