Age-related change in stimulus-elicited amygdala–prefrontal circuitry: a longitudinal multiverse approach

• In Event: Biological embedding of early adversity: new insights on the effects on neurodevelopment and threat processing

Abstract

There has been considerable interest in the developmental course of the amygdala and its connections with medial prefrontal cortex (mPFC) given the central role of both regions in emotion generation, learning, and regulation. While several studies have suggested that this circuitry exhibits developmental changes in function across the first two decades of life (Gee et al., 2013; Silvers et al., 2017), these studies have typically employed cross-sectional designs, and findings on developmental change in amygdala–mPFC circuitry described by the literature have been mixed (Kujawa et al., 2016; Wu et al., 2016; Zhang et al., 2019). Recent work has also highlighted that functional magnetic resonance imaging (fMRI) analytic choices may contribute to such discrepancies across studies (Botvinik-Nezer et al., 2020).
Here, we used an accelerated longitudinal design to examine stimulus-elicited changes in amygdala-mPFC circuitry from 4-22 years of age (N = 98; 183 total scans; 1-3 scans per participant). Participants completed an event-related emotion discrimination task with fearful and neutral faces while undergoing fMRI. We used ‘multiverse’ analyses to examine the robustness of our findings to variations in fMRI preprocessing and modeling choices (Steegen et al., 2016). A preregistered pipeline together with an additional 2800 parallel analyses (each using many distinct preprocessing and modeling choices) found evidence for age-related decreases in amygdala reactivity on average, though such decreases may represent between-participant differences rather than developmental growth. Larger amygdala reactivity at younger ages was likely attributable to elevated amygdala responses to the first few trials relative to later trials. Across our parallel analyses, we did not find consistent evidence of age-related change in amygdala–mPFC connectivity through psychophysiological interaction (gPPI) and beta-series connectivity (BSC) methods. In addition, we did not find evidence for associations between separation anxiety behaviors and amygdala reactivity or amygdala–mPFC connectivity. These findings highlight both the challenges in estimating developmental change in longitudinal cohorts and the value of multiverse approaches for developmental neuroimaging.

Authors

• Paul Alexander Bloom, Columbia University
  Presenting Author

• Michelle VanTieghem, New York University Medical Center
  Non-Presenting Author

• Laurel J. Gabard-Durnam, Northeastern University
  Non-Presenting Author

• Dylan Gee, Yale University
  Non-Presenting Author

• Jessica Flannery, University of North Carolina at Chapel Hill
  Non-Presenting Author

• Christina Caldera, David Geffen School of Medicine
  Non-Presenting Author

• Bonnie Goff, University of California Los Angeles
  Non-Presenting Author

• Eva H Telzer, University of North Carolina at Chapel Hill
  Non-Presenting Author

• Kathryn Humphreys, Vanderbilt University
  Non-Presenting Author

• Dominic Fareri, Adelphi University
  Non-Presenting Author

• Mor Shapiro, Kaiser Permanente
  Non-Presenting Author

• Niall Bolger, Columbia University
  Non-Presenting Author

• Mariam Aly, Columbia University
  Non-Presenting Author

• Nim Tottenham, Columbia University
  Non-Presenting Author