title: Decreased resting functional connectivity after traumatic brain injury in the rat.
abstract: Traumatic brain injury (TBI) contributes to about 10% of acquired epilepsy. Even though the mechanisms of post-traumatic epileptogenesis are poorly known, a disruption of neuronal networks predisposing to altered neuronal synchrony remains a viable candidate mechanism. We tested a hypothesis that resting state BOLD-fMRI functional connectivity can reveal network abnormalities in brain regions that are connected to the lesioned cortex, and that these changes associate with functional impairment, particularly epileptogenesis. TBI was induced using lateral fluid-percussion injury in seven adult male Sprague-Dawley rats followed by functional imaging at 9.4T 4 months later. As controls we used six sham-operated animals that underwent all surgical operations but were not injured. Electroencephalogram (EEG)-functional magnetic resonance imaging (fMRI) was performed to measure resting functional connectivity. A week after functional imaging, rats were implanted with bipolar skull electrodes. After recovery, rats underwent pentyleneterazol (PTZ) seizure-susceptibility test under EEG. For image analysis, four pairs of regions of interests were analyzed in each hemisphere: ipsilateral and contralateral frontal and parietal cortex, hippocampus, and thalamus. High-pass and low-pass filters were applied to functional imaging data. Group statistics comparing injured and sham-operated rats and correlations over time between each region were calculated. In the end, rats were perfused for histology. None of the rats had epileptiform discharges during functional imaging. PTZ-test, however revealed increased seizure susceptibility in injured rats as compared to controls. Group statistics revealed decreased connectivity between the ipsilateral and contralateral parietal cortex and between the parietal cortex and hippocampus on the side of injury as compared to sham-operated animals. Injured animals also had abnormal negative connectivity between the ipsilateral and contralateral parietal cortex and other regions. Our data provide the first evidence on abnormal functional connectivity after experimental TBI assessed with resting state BOLD-fMRI.
authors.affiliation: Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut, United States of America; Core Center for Quantitative Neuroscience with Magnetic Resonance, Yale University, New Haven, Connecticut, United States of America.
authors.forename: Asht Mangal
authors.initials: AM
authors.lastname: Mishra
authors.affiliation: Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Bai
authors.affiliation: Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut, United States of America; Core Center for Quantitative Neuroscience with Magnetic Resonance, Yale University, New Haven, Connecticut, United States of America.
authors.forename: Basavaraju G
authors.initials: BG
authors.lastname: Sanganahalli
authors.affiliation: Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut, United States of America; Center for Neuroscience and Regeneration Research, West Haven, Connecticut, United States of America.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Waxman
authors.affiliation: Department of Neurobiology, A. I. Virtanen Institute of Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: Olena
authors.initials: O
authors.lastname: Shatillo
authors.affiliation: Biomedical NMR research group, Biomedical Imaging Unit, University of Eastern Finland, Kuopio, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Grohn
authors.affiliation: Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut, United States of America; Department of Biomedical Engineering, Yale University School of Medicine, New Haven, Connecticut, United States of America; Core Center for Quantitative Neuroscience with Magnetic Resonance, Yale University, New Haven, Connecticut, United States of America.
authors.forename: Fahmeed
authors.initials: F
authors.lastname: Hyder
authors.affiliation: Department of Neurobiology, A. I. Virtanen Institute of Molecular Sciences, University of Eastern Finland, Kuopio, Finland; Department of Neurology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Asla
authors.initials: A
authors.lastname: Pitkänen
authors.affiliation: Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut, United States of America; Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, United States of America; Core Center for Quantitative Neuroscience with Magnetic Resonance, Yale University, New Haven, Connecticut, United States of America.
authors.forename: Hal
authors.initials: H
authors.lastname: Blumenfeld
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology*; D004566:Electrodes; D008279:Magnetic Resonance Imaging; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000503:physiopathology
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