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  • Author
    Ryan Lowder
  • PI

  • Co-Author

  • Title

    The Relationship Between the Functional Connectivity of the Dorsal Amygdala and Cognitive Control Centers and Cognitive Functioning in Traumatic Brain Injury

  • Program

    CTSI TL1 Summer Program

  • Other Program (if not listed above)

  • Abstract

    Introduction: Traumatic brain injury (TBI) is a significant contributor to mortality and morbidity in the United States. Resting-state magnetic resonance imaging (rsfMRI), from which functional connectivity (FC) values are computed by correlating task-independent blood oxygen level dependent (BOLD) signals within and between anatomically distinct brain regions, has been used to predict recovery and guide interventions following TBI. Given the debilitating cognitive dysfunction many with TBI experience, we evaluated the relationship between seed-to-voxel FCs, with the dorsal amygdala (dAmy), which has been found to modulate cognitive control, as the seed of interest, and cognitive functioning in TBI and healthy controls (HC).

    Methods: Thirty-one individuals with TBI, of which 23 (74.2%) were male, with a mean age of 34.32 ± 14.86 years and a median Glascow Outcome Scale-Extended score of 8 (range = 2-8) participated in this study on average 36.31 ± 17.22 days since injury. Nineteen healthy individuals, of which 11 (57.9%) were male, with a mean age of 36.53 ± 18.97 years, served as controls. fMRIs were collected on 3T Siemens Tim Trio Scanner. Imaging preprocessing and analyses were conducted using CONN version 19b. Seed-to-voxel FC values with the dAmy as the seed of interest were calculated. The FC of voxel clusters greater than 100 that significantly correlated with the dAmy seed were extracted. The Automated Neuropsychological Assessment Metrics (ANAM) was used to assess cognitive function. Independent sample t-tests or Mann-Whitney U tests, as appropriate, and chi-squared tests were used to assess group differences. Pearson correlations (r) were used to examine relationships between extracted FCs and ANAM scores for all subjects.

    Results: Two voxel clusters, located within the left dorsolateral prefrontal cortex (LDLPFC) and dorsal anterior cingulate cortex (dACC), were significantly more connected to the dAmy in individuals with TBI compared to HCs. FC between the dAmy-LDLPFC was significantly correlated with the ANAM total score, with greater FC associated with worse performance on cognitive assessment. FC between the dAmy-dACC had a trending correlation with the ANAM total score.

    Conclusion: The present study found hyperconnectivity between the dAmy and two regions of the brain that are associated with cognitive control, the DLPFC and dACC, following TBI. In all subjects, hyperconnectivity was associated with worse cognitive performance, lending support to the amygdala hijacking hypothesis of cognitive dysfunction, suggesting that heightened modulation by the amygdala on cognitive centers may have a detrimental effect. Further research is needed to clarify these relations and help inform future interventions.

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