title: Thalamo-frontal connectivity mediates top-down cognitive functions in disorders of consciousness.
abstract: OBJECTIVE
  We employed functional MRI (fMRI) to assess whether (1) patients with disorders of consciousness (DOC) retain the ability to willfully engage in top-down processing and (2) what neurophysiologic factors distinguish patients who can demonstrate this ability from patients who cannot.
  
  
  METHODS
  Sixteen volunteers, 8 patients in vegetative state (VS), 16 minimally conscious patients (MCS), and 4 exit from MCS (eMCS) patients were enrolled in a prospective cross-sectional fMRI study. Participants performed a target detection task in which they counted the number of times a (changing) target word was presented amidst a set of distractors.
  
  
  RESULTS
  Three of 8 patients diagnosed as being in a VS exhibited significant activations in response to the task, thereby demonstrating a state of consciousness. Differential activations across tasks were also observed in 6 MCS patients and 1 eMCS patient. A psycho-physiologic interaction analysis revealed that the main factor distinguishing patients who responded to the task from those who did not was a greater connectivity between the anterior section of thalamus and prefrontal cortex.
  
  
  CONCLUSIONS
  In our sample of patients, the dissociation between overt behavior observable in clinical assessments and residual cognitive faculties is prevalent among DOC patients (37%). A substantial number of patients, including some diagnosed with VS, can demonstrate willful engagement in top-down cognition. While neuroimaging data are not the same as observable behavior, this suggests that the mental status of some VS patients exceeds what can be appreciated clinically. Furthermore, thalamo-frontal circuits might be crucial to sustaining top-down functions.
authors.affiliation: From the Department of Psychology (M.M.M., M.R.), University of California Los Angeles; the Department of Neurosurgery (M.M.M.), Brain Injury Research Center (BIRC), Geffen School of Medicine at UCLA, Los Angeles; the Cognition and Brain Sciences Unit (P.F.), Medical Research Council, Cambridge; the Division of Neurosurgery (P.F., E.K., J.D.P.), University of Cambridge, Addenbrooke's Hospital, Cambridge, UK; and the Natural Science Building (A.M.O.), Brain & Mind Institute, The University of Western Ontario, London, Canada. monti@psych.ucla.edu.
authors.forename: Martin M
authors.initials: MM
authors.lastname: Monti
authors.affiliation: From the Department of Psychology (M.M.M., M.R.), University of California Los Angeles; the Department of Neurosurgery (M.M.M.), Brain Injury Research Center (BIRC), Geffen School of Medicine at UCLA, Los Angeles; the Cognition and Brain Sciences Unit (P.F.), Medical Research Council, Cambridge; the Division of Neurosurgery (P.F., E.K., J.D.P.), University of Cambridge, Addenbrooke's Hospital, Cambridge, UK; and the Natural Science Building (A.M.O.), Brain & Mind Institute, The University of Western Ontario, London, Canada.
authors.forename: Matthew
authors.initials: M
authors.lastname: Rosenberg
authors.affiliation: From the Department of Psychology (M.M.M., M.R.), University of California Los Angeles; the Department of Neurosurgery (M.M.M.), Brain Injury Research Center (BIRC), Geffen School of Medicine at UCLA, Los Angeles; the Cognition and Brain Sciences Unit (P.F.), Medical Research Council, Cambridge; the Division of Neurosurgery (P.F., E.K., J.D.P.), University of Cambridge, Addenbrooke's Hospital, Cambridge, UK; and the Natural Science Building (A.M.O.), Brain & Mind Institute, The University of Western Ontario, London, Canada.
authors.forename: Paola
authors.initials: P
authors.lastname: Finoia
authors.affiliation: From the Department of Psychology (M.M.M., M.R.), University of California Los Angeles; the Department of Neurosurgery (M.M.M.), Brain Injury Research Center (BIRC), Geffen School of Medicine at UCLA, Los Angeles; the Cognition and Brain Sciences Unit (P.F.), Medical Research Council, Cambridge; the Division of Neurosurgery (P.F., E.K., J.D.P.), University of Cambridge, Addenbrooke's Hospital, Cambridge, UK; and the Natural Science Building (A.M.O.), Brain & Mind Institute, The University of Western Ontario, London, Canada.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Kamau
authors.affiliation: From the Department of Psychology (M.M.M., M.R.), University of California Los Angeles; the Department of Neurosurgery (M.M.M.), Brain Injury Research Center (BIRC), Geffen School of Medicine at UCLA, Los Angeles; the Cognition and Brain Sciences Unit (P.F.), Medical Research Council, Cambridge; the Division of Neurosurgery (P.F., E.K., J.D.P.), University of Cambridge, Addenbrooke's Hospital, Cambridge, UK; and the Natural Science Building (A.M.O.), Brain & Mind Institute, The University of Western Ontario, London, Canada.
authors.forename: John D
authors.initials: JD
authors.lastname: Pickard
authors.affiliation: From the Department of Psychology (M.M.M., M.R.), University of California Los Angeles; the Department of Neurosurgery (M.M.M.), Brain Injury Research Center (BIRC), Geffen School of Medicine at UCLA, Los Angeles; the Cognition and Brain Sciences Unit (P.F.), Medical Research Council, Cambridge; the Division of Neurosurgery (P.F., E.K., J.D.P.), University of Cambridge, Addenbrooke's Hospital, Cambridge, UK; and the Natural Science Building (A.M.O.), Brain & Mind Institute, The University of Western Ontario, London, Canada.
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Owen
mesh_terms: D000161:Acoustic Stimulation; D000328:Adult; D001921:Brain / Q000503:physiopathology; D016022:Case-Control Studies; D003071:Cognition / Q000502:physiology*; D003244:Consciousness Disorders / Q000503:physiopathology; D003430:Cross-Sectional Studies; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology*; D059907:Functional Neuroimaging; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000503:physiopathology*; D018458:Persistent Vegetative State / Q000503:physiopathology*; D011446:Prospective Studies; D013788:Thalamus / Q000503:physiopathology*; D055815:Young Adult