title: Frontal networks associated with command following after hemorrhagic stroke.
abstract: OBJECTIVE
  Level of consciousness is frequently assessed by command-following ability in the clinical setting. However, it is unclear what brain circuits are needed to follow commands. We sought to determine what networks differentiate command following from noncommand following patients after hemorrhagic stroke.
  
  
  METHODS
  Structural MRI, resting-state functional MRI, and electroencephalography were performed on 25 awake and unresponsive patients with acute intracerebral and subarachnoid hemorrhage. Structural injury was assessed via volumetric T1-weighted MRI analysis. Functional connectivity differences were analyzed against a template of standard resting-state networks. The default mode network (DMN) and the task-positive network were investigated using seed-based functional connectivity. Networks were interrogated by pairwise coherence of electroencephalograph leads in regions of interest defined by functional MRI.
  
  
  RESULTS
  Functional imaging of unresponsive patients identified significant differences in 6 of 16 standard resting-state networks. Significant voxels were found in premotor cortex, dorsal anterior cingulate gyrus, and supplementary motor area. Direct interrogation of the DMN and task-positive network revealed loss of connectivity between the DMN and the orbitofrontal cortex and new connections between the task-positive network and DMN. Coherence between electrodes corresponding to right executive network and visual networks was also decreased in unresponsive patients.
  
  
  CONCLUSIONS
  Resting-state functional MRI and electroencephalography coherence data support a model in which multiple, chiefly frontal networks are required for command following. Loss of DMN anticorrelation with task-positive network may reflect a loss of inhibitory control of the DMN by motor-executive regions. Frontal networks should thus be a target for future investigations into the mechanism of responsiveness in the intensive care unit environment.
authors.affiliation: From the Department of Neurological Surgery, Columbia University Medical Center, New York (C.B.M., G.P.B., B.E.Y., T.B.N., P.J.K., A.K.C., E.S.C.); Department of Radiology, Weill Cornell Medical College, Cornell University, New York (H.U.V.); and Division of Neurocritical Care, Department of Neurology, Columbia University Medical Center, New York (H.-P.F., J.C.). cbm2104@columbia.edu.
authors.forename: Charles B
authors.initials: CB
authors.lastname: Mikell
authors.affiliation: From the Department of Neurological Surgery, Columbia University Medical Center, New York (C.B.M., G.P.B., B.E.Y., T.B.N., P.J.K., A.K.C., E.S.C.); Department of Radiology, Weill Cornell Medical College, Cornell University, New York (H.U.V.); and Division of Neurocritical Care, Department of Neurology, Columbia University Medical Center, New York (H.-P.F., J.C.).
authors.forename: Garrett P
authors.initials: GP
authors.lastname: Banks
authors.affiliation: From the Department of Neurological Surgery, Columbia University Medical Center, New York (C.B.M., G.P.B., B.E.Y., T.B.N., P.J.K., A.K.C., E.S.C.); Department of Radiology, Weill Cornell Medical College, Cornell University, New York (H.U.V.); and Division of Neurocritical Care, Department of Neurology, Columbia University Medical Center, New York (H.-P.F., J.C.).
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Frey
authors.affiliation: From the Department of Neurological Surgery, Columbia University Medical Center, New York (C.B.M., G.P.B., B.E.Y., T.B.N., P.J.K., A.K.C., E.S.C.); Department of Radiology, Weill Cornell Medical College, Cornell University, New York (H.U.V.); and Division of Neurocritical Care, Department of Neurology, Columbia University Medical Center, New York (H.-P.F., J.C.).
authors.forename: Brett E
authors.initials: BE
authors.lastname: Youngerman
authors.affiliation: From the Department of Neurological Surgery, Columbia University Medical Center, New York (C.B.M., G.P.B., B.E.Y., T.B.N., P.J.K., A.K.C., E.S.C.); Department of Radiology, Weill Cornell Medical College, Cornell University, New York (H.U.V.); and Division of Neurocritical Care, Department of Neurology, Columbia University Medical Center, New York (H.-P.F., J.C.).
authors.forename: Taylor B
authors.initials: TB
authors.lastname: Nelp
authors.affiliation: From the Department of Neurological Surgery, Columbia University Medical Center, New York (C.B.M., G.P.B., B.E.Y., T.B.N., P.J.K., A.K.C., E.S.C.); Department of Radiology, Weill Cornell Medical College, Cornell University, New York (H.U.V.); and Division of Neurocritical Care, Department of Neurology, Columbia University Medical Center, New York (H.-P.F., J.C.).
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Karas
authors.affiliation: From the Department of Neurological Surgery, Columbia University Medical Center, New York (C.B.M., G.P.B., B.E.Y., T.B.N., P.J.K., A.K.C., E.S.C.); Department of Radiology, Weill Cornell Medical College, Cornell University, New York (H.U.V.); and Division of Neurocritical Care, Department of Neurology, Columbia University Medical Center, New York (H.-P.F., J.C.).
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Chan
authors.affiliation: From the Department of Neurological Surgery, Columbia University Medical Center, New York (C.B.M., G.P.B., B.E.Y., T.B.N., P.J.K., A.K.C., E.S.C.); Department of Radiology, Weill Cornell Medical College, Cornell University, New York (H.U.V.); and Division of Neurocritical Care, Department of Neurology, Columbia University Medical Center, New York (H.-P.F., J.C.).
authors.forename: Henning U
authors.initials: HU
authors.lastname: Voss
authors.affiliation: From the Department of Neurological Surgery, Columbia University Medical Center, New York (C.B.M., G.P.B., B.E.Y., T.B.N., P.J.K., A.K.C., E.S.C.); Department of Radiology, Weill Cornell Medical College, Cornell University, New York (H.U.V.); and Division of Neurocritical Care, Department of Neurology, Columbia University Medical Center, New York (H.-P.F., J.C.).
authors.forename: E Sander
authors.initials: ES
authors.lastname: Connolly
authors.affiliation: From the Department of Neurological Surgery, Columbia University Medical Center, New York (C.B.M., G.P.B., B.E.Y., T.B.N., P.J.K., A.K.C., E.S.C.); Department of Radiology, Weill Cornell Medical College, Cornell University, New York (H.U.V.); and Division of Neurocritical Care, Department of Neurology, Columbia University Medical Center, New York (H.-P.F., J.C.).
authors.forename: Jan
authors.initials: J
authors.lastname: Claassen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002543:Cerebral Hemorrhage / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D003244:Consciousness Disorders / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology; D004569:Electroencephalography; D005260:Female; D005625:Frontal Lobe / Q000473:pathology / Q000503:physiopathology*; D059907:Functional Neuroimaging; D006179:Gyrus Cinguli / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000473:pathology / Q000503:physiopathology; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology*; D020521:Stroke / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000473:pathology / Q000503:physiopathology*
keywords: coma; intracerebral hemorrhage; subarachnoid hemorrhage