title: Thalamic and extrathalamic mechanisms of consciousness after severe brain injury.
abstract: OBJECTIVE
  What mechanisms underlie the loss and recovery of consciousness after severe brain injury? We sought to establish, in the largest cohort of patients with disorders of consciousness (DOC) to date, the link between gold standard clinical measures of awareness and wakefulness, and specific patterns of local brain pathology-thereby possibly providing a mechanistic framework for patient diagnosis, prognosis, and treatment development.
  
  
  METHODS
  Structural T1-weighted magnetic resonance images were collected, in a continuous sample of 143 severely brain-injured patients with DOC (and 96 volunteers), across 2 tertiary expert centers. Brain atrophy in subcortical regions (bilateral thalamus, basal ganglia, hippocampus, basal forebrain, and brainstem) was assessed across (1) healthy volunteers and patients, (2) clinical entities (eg, vegetative state, minimally conscious state), (3) clinical measures of consciousness (Coma Recovery Scale-Revised), and (4) injury etiology.
  
  
  RESULTS
  Compared to volunteers, patients exhibited significant atrophy across all structures (p < 0.05, corrected). Strikingly, we found almost no significant differences across clinical entities. Nonetheless, the clinical measures of awareness and wakefulness upon which differential diagnosis rely were systematically associated with tissue atrophy within thalamic and basal ganglia nuclei, respectively; the basal forebrain was atrophied in proportion to patients' response to sensory stimulation. In addition, nontraumatic injuries exhibited more extensive thalamic atrophy.
  
  
  CONCLUSIONS
  These findings provide, for the first time, a grounding in pathology for gold standard behavior-based clinical measures of consciousness, and reframe our current models of DOC by stressing the different links tying thalamic mechanisms to willful behavior and extrathalamic mechanisms to behavioral (and electrocortical) arousal.
authors.affiliation: Department of Psychology, University of California, Los Angeles, Los Angeles, CA.
authors.forename: Evan S
authors.initials: ES
authors.lastname: Lutkenhoff
authors.affiliation: Department of Psychology, University of California, Los Angeles, Los Angeles, CA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Chiang
authors.affiliation: Coma Science Group, Cyclotron Research Center and Neurology Department, University and University Hospital of Liège, Liège, Belgium.
authors.forename: Luaba
authors.initials: L
authors.lastname: Tshibanda
authors.affiliation: Division of Neurosurgery, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Kamau
authors.affiliation: Coma Science Group, Cyclotron Research Center and Neurology Department, University and University Hospital of Liège, Liège, Belgium.|Department of Anesthesia and Intensive Care Medicine, Liège University Hospital, Liège, Belgium.
authors.forename: Murielle
authors.initials: M
authors.lastname: Kirsch
authors.affiliation: Division of Neurosurgery, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: John D
authors.initials: JD
authors.lastname: Pickard
authors.affiliation: Coma Science Group, Cyclotron Research Center and Neurology Department, University and University Hospital of Liège, Liège, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Laureys
authors.affiliation: Brain and Mind Institute, University of Western Ontario, London, Ontario, Canada.
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Owen
authors.affiliation: Department of Psychology, University of California, Los Angeles, Los Angeles, CA.|Brain Injury Research Center, Department of Neurosurgery, Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA.
authors.forename: Martin M
authors.initials: MM
authors.lastname: Monti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001284:Atrophy; D001364:Awareness / Q000502:physiology*; D066187:Basal Forebrain / Q000473:pathology / Q000503:physiopathology; D001479:Basal Ganglia / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D001930:Brain Injuries / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D001931:Brain Mapping; D001933:Brain Stem / Q000473:pathology / Q000503:physiopathology; D016022:Case-Control Studies; D003128:Coma / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D003243:Consciousness / Q000502:physiology*; D003244:Consciousness Disorders / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D003430:Cross-Sectional Studies; D005260:Female; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018458:Persistent Vegetative State / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D012720:Severity of Illness Index; D013788:Thalamus / Q000473:pathology / Q000503:physiopathology; D014851:Wakefulness / Q000502:physiology*; D055815:Young Adult