title: Functional brain imaging in survivors of critical illness: A prospective feasibility study and exploration of the association between delirium and brain activation patterns.
abstract: OBJECTIVE
  We undertook this pilot prospective cohort investigation to examine the feasibility of functional magnetic resonance imaging (fMRI) assessments in survivors of critical illness and to analyze potential associations between delirium and brain activation patterns observed during a working memory task (N-back) at hospital discharge and 3-month follow-up.
  
  
  METHODS
  At hospital discharge and 3 months later, fMRI assessed subjects' functional activity during an N-back task. Multiple linear regression was used to examine associations between duration of delirium and brain activity, and elastic net regression was used to assess the relationship between brain activation patterns at 3 months and cognitive outcomes at 12 months.
  
  
  RESULTS
  Of 47 patients who underwent fMRI at discharge, 38 (80%) completed the protocol; of 37 who underwent fMRI at 3 months, 34 (91%) completed the protocol. At discharge, the mean (SD) percentage of correct responses on the most challenging version (the N2 version) of the N-back task was 70.4 (23.2; range of 20-100) compared with 76 (23.4; range of 33-100) at 3 months. No association was observed between delirium duration in the hospital and brain region activity in any brain region at discharge or 3 months after adjusting for relevant covariates (P values across all 11 brain regions of interest were >.25).
  
  
  CONCLUSIONS
  Our data support the feasibility of using fMRI in survivors of critical illness at 3-month follow-up but not at discharge. In this small study, delirium was not associated with distinct or abnormal brain activation patterns, although overall performance on a cognitive task of working memory was poorer than observed in other cohorts of individuals with medically related executive dysfunction, mild cognitive impairment, and mild traumatic brain injury.
authors.affiliation: Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN; Center for Health Services Research, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN; Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN; Research Service, Department of Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, TN. Electronic address: james.c.jackson@vanderbilt.edu.
authors.forename: James C
authors.initials: JC
authors.lastname: Jackson
authors.affiliation: Department of Rehabilitation and Aged Care Unit, Hospital Ancelle, Cremona, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Morandi
authors.affiliation: Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN; Center for Health Services Research, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN; Geriatric Research, Education and Clinical Center (GRECC) Service, Department of Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, TN.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Girard
authors.affiliation: Vanderbilt University Institute of Imaging Sciences, Nashville, TN.
authors.forename: Kristen
authors.initials: K
authors.lastname: Merkle
authors.affiliation: Department of Urologic Surgery, Vanderbilt University School of Medicine, Nashville, TN.
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Graves
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, Osaka University, Osaka, Japan.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Thompson
authors.affiliation: Department of Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, TN.
authors.forename: Ayumi K
authors.initials: AK
authors.lastname: Shintani
authors.affiliation: Vanderbilt University Institute of Imaging Sciences, Nashville, TN; Department of Psychology, Vanderbilt University, Nashville, TN; Department of Psychology, Southern Methodist University, Dallas, TX.
authors.forename: Max L
authors.initials: ML
authors.lastname: Gunther
authors.affiliation: Department of Biomedical Engineering, Vanderbilt University School of Engineering, Nashville, TN.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Cannistraci
authors.affiliation: Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN; Department of Biomedical Engineering, Vanderbilt University School of Engineering, Nashville, TN; Department of Radiology and Radiological Sciences, Vanderbilt University School of Medicine, Nashville, TN.
authors.forename: Baxter P
authors.initials: BP
authors.lastname: Rogers
authors.affiliation: Department of Biomedical Engineering, Vanderbilt University School of Engineering, Nashville, TN; Department of Radiology and Radiological Sciences, Vanderbilt University School of Medicine, Nashville, TN.
authors.forename: John C
authors.initials: JC
authors.lastname: Gore
authors.affiliation: Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN; Center for Health Services Research, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN.
authors.forename: Hillary J
authors.initials: HJ
authors.lastname: Warrington
authors.affiliation: Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN; Center for Health Services Research, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN; Geriatric Research, Education and Clinical Center (GRECC) Service, Department of Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, TN.
authors.forename: E Wesley
authors.initials: EW
authors.lastname: Ely
authors.affiliation: Department of Psychology, Brigham Young University, Provo, UT; Department of Medicine, Pulmonary and Critical Care Division, Intermountain Medical Center, Murray UT; Neuroscience Center, Brigham Young University, Provo, UT.
authors.forename: Ramona O
authors.initials: RO
authors.lastname: Hopkins
mesh_terms: D000368:Aged; D001921:Brain / Q000503:physiopathology*; D003072:Cognition Disorders / Q000503:physiopathology*; D015331:Cohort Studies; D016638:Critical Illness; D003693:Delirium / Q000503:physiopathology*; D005240:Feasibility Studies; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D007362:Intensive Care Units; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D008875:Middle Aged; D010351:Patient Discharge; D010808:Physical Examination; D010865:Pilot Projects; D011446:Prospective Studies; D017741:Survivors; D013997:Time Factors
keywords: Cognitive impairment; Delirium; ICU; MRI; Neuroimaging; Sepsis