title: The application of a mathematical model linking structural and functional connectomes in severe brain injury.
abstract: Following severe injuries that result in disorders of consciousness, recovery can occur over many months or years post-injury. While post-injury synaptogenesis, axonal sprouting and functional reorganization are known to occur, the network-level processes underlying recovery are poorly understood. Here, we test a network-level functional rerouting hypothesis in recovery of patients with disorders of consciousness following severe brain injury. This hypothesis states that the brain recovers from injury by restoring normal functional connections via alternate structural pathways that circumvent impaired white matter connections. The so-called network diffusion model, which relates an individual's structural and functional connectomes by assuming that functional activation diffuses along structural pathways, is used here to capture this functional rerouting. We jointly examined functional and structural connectomes extracted from MRIs of 12 healthy and 16 brain-injured subjects. Connectome properties were quantified via graph theoretic measures and network diffusion model parameters. While a few graph metrics showed groupwise differences, they did not correlate with patients' level of consciousness as measured by the Coma Recovery Scale - Revised. There was, however, a strong and significant partial Pearson's correlation (accounting for age and years post-injury) between level of consciousness and network diffusion model propagation time (r = 0.76, p < 0.05, corrected), i.e. the time functional activation spends traversing the structural network. We concluded that functional rerouting via alternate (and less efficient) pathways leads to increases in network diffusion model propagation time. Simulations of injury and recovery in healthy connectomes confirmed these results. This work establishes the feasibility for using the network diffusion model to capture network-level mechanisms in recovery of consciousness after severe brain injury.
authors.affiliation: Department of Radiology, Weill Cornell Medical College, 1300 York Ave., New York, NY 10065, United States; The Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, 1300 York Ave., New York, NY 10065, United States. Electronic address: amk2012@med.cornell.edu.
authors.forename: A
authors.initials: A
authors.lastname: Kuceyeski
authors.affiliation: Department of Neurology, Weill Cornell Medical College, 1300 York Ave., New York, NY 10065, United States.
authors.forename: S
authors.initials: S
authors.lastname: Shah
authors.affiliation: Department of Radiology, Weill Cornell Medical College, 1300 York Ave., New York, NY 10065, United States; Citigroup Biomedical Imaging Center, 516 East 72nd St., New York, NY 10021, United States.
authors.forename: J P
authors.initials: JP
authors.lastname: Dyke
authors.affiliation: Department of Neurology, Albert Einstein College of Medicine, 1300 Morris Ave., Bronx, NY 10461, United States.
authors.forename: S
authors.initials: S
authors.lastname: Bickel
authors.affiliation: Department of Radiology, Weill Cornell Medical College, 1300 York Ave., New York, NY 10065, United States.
authors.forename: F
authors.initials: F
authors.lastname: Abdelnour
authors.affiliation: Department of Neurology, Weill Cornell Medical College, 1300 York Ave., New York, NY 10065, United States.
authors.forename: N D
authors.initials: ND
authors.lastname: Schiff
authors.affiliation: Department of Radiology, Weill Cornell Medical College, 1300 York Ave., New York, NY 10065, United States; Citigroup Biomedical Imaging Center, 516 East 72nd St., New York, NY 10021, United States.
authors.forename: H U
authors.initials: HU
authors.lastname: Voss
authors.affiliation: Department of Radiology, Weill Cornell Medical College, 1300 York Ave., New York, NY 10065, United States; The Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, 1300 York Ave., New York, NY 10065, United States.
authors.forename: A
authors.initials: A
authors.lastname: Raj
mesh_terms: D000328:Adult; D001930:Brain Injuries / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D001931:Brain Mapping; D063132:Connectome; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000503:physiopathology; D010100:Oxygen / Q000097:blood; D055815:Young Adult
chemical_list: D010100:Oxygen
keywords: Connectomics; Disorders of consciousness; Network analysis; Network diffusion model; Neuroimaging