title: Ventromedial prefrontal cortex modulates fatigue after penetrating traumatic brain injury.
abstract: BACKGROUND
  Fatigue is a common and disabling symptom in neurologic disorders including traumatic penetrating brain injury (PBI). Despite fatigue's prevalence and impact on quality of life, its pathophysiology is not understood. Studies on effort perception in healthy subjects, animal behavioral paradigms, and recent evidence in different clinical populations suggest that ventromedial prefrontal cortex could play a significant role in fatigue pathophysiology in neurologic conditions.
  
  
  METHODS
  We enrolled 97 PBI patients and 37 control subjects drawn from the Vietnam Head Injury Study registry. Fatigue was assessed with a self-report questionnaire and a clinician-rated instrument; lesion location and volume were evaluated on CT scans. PBI patients were divided in 3 groups according to lesion location: a nonfrontal lesion group, a ventromedial prefrontal cortex lesion (vmPFC) group, and a dorso/lateral prefrontal cortex (d/lPFC) group. Fatigue scores were compared among the 3 PBI groups and the healthy controls.
  
  
  RESULTS
  Individuals with vmPFC lesions were significantly more fatigued than individuals with d/lPFC lesions, individuals with nonfrontal lesions, and healthy controls, while these 3 latter groups were equally fatigued. VmPFC volume was correlated with fatigue scores, showing that the larger the lesion volume, the higher the fatigue scores.
  
  
  CONCLUSIONS
  We demonstrated that ventromedial prefrontal cortex lesion (vmPFC) plays a critical role in penetrating brain injury-related fatigue, providing a rationale to link fatigue to different vmPFC functions such as effort and reward perception. The identification of the anatomic and cognitive basis of fatigue can contribute to developing pathophysiology-based treatments for this disabling symptom.
authors.affiliation: Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892-1440, USA.
authors.forename: Matteo
authors.initials: M
authors.lastname: Pardini
authors.forename: Frank
authors.initials: F
authors.lastname: Krueger
authors.forename: Vanessa
authors.initials: V
authors.lastname: Raymont
authors.forename: Jordan
authors.initials: J
authors.lastname: Grafman
mesh_terms: D000704:Analysis of Variance; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology; D001930:Brain Injuries / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005221:Fatigue / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005500:Follow-Up Studies; D020197:Head Injuries, Penetrating / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology*; D012042:Registries; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D014057:Tomography, X-Ray Computed; D014728:Veterans; D047829:Vietnam Conflict