Chronology and chronicity of altered resting-state functional connectivity after traumatic brain injury

Open Access
Venkatesan, Umesh Meyyappan
Graduate Program:
Master of Science
Document Type:
Master Thesis
Date of Defense:
February 06, 2014
Committee Members:
  • Frank Gerard Hillary, Thesis Advisor
  • Peter Andrew Arnett, Thesis Advisor
  • Nancy Anne Coulter Dennis, Thesis Advisor
  • Stephen Jeffrey Wilson, Thesis Advisor
  • TBI
  • brain injury
  • neuroimaging
  • functional connectivity
  • resting state
  • default mode
  • neurodegeneration
  • Alzheimer's
While traumatic brain injury (TBI) results in widespread disruption of neural networks, changes in regional resting-state functional connectivity patterns after insult remain unclear. Specifically, little is known about the chronology of emergent connectivity alterations and whether they persist after a critical recovery window. In the current study, resting-state fMRI and seed-voxel correlational analyses were utilized in both cross-sectional and longitudinal designs to probe intrinsic connectivity patterns involving the posterior cingulate cortex (PCC) and hippocampi, regions shown to be important in the default mode network (DMN) and vulnerable to neuropathology. A total of 22 participants in the chronic phase of moderate-severe TBI and 18 healthy controls were included for cross-sectional study. Longitudinal analyses included 13 individuals in the TBI group for whom data approximately three months after injury (subacute) were available. Overall, results indicated dissociable connectivity trajectories of the PCC and hippocampi during recovery from TBI, with PCC alterations characterized by early hypersynchrony with the anterior DMN that is gradually reduced, and hippocampal changes marked by increasing synchrony with proximal cortex and subcortex. The PCC also showed increasing antiphase synchrony with posterior attentional regions, and the hippocampi showed decreasing antiphase synchrony with frontal attentional regions. Antiphase synchrony of the hippocampus and dorsolateral prefrontal cortex at the subacute stage of TBI was positively associated with attentional performance on neuropsychological tests at both the subacute and chronic stages. These findings highlight the heterogeneity of regional-whole brain connectivity changes after TBI, and suggest that residual connectivity alterations exist in the clinically stable phase of TBI. Parallels between the chronicity of the observed effects and findings in other neurologic conditions (e.g., Alzheimer’s disease) are discussed in the context of neurodegenerative potential after TBI.