Age-related change in task-evoked amygdala—prefrontal circuitry: a multiverse approach with an accelerated longitudinal cohort aged 4-22 years

Abstract

There has been considerable interest in the development of the amygdala and its connections with medial prefrontal cortex (mPFC) given the central role of these brain regions in emotional processes. While several studies have suggested that this circuitry exhibits functional changes across the first two decades of life, they have typically employed cross-sectional designs, and findings have been mixed. Additionally, analytic choices may contribute to discrepancies across studies. Here we used an accelerated longitudinal design to examine task-evoked changes in amygdala-mPFC circuitry from 4-22 years of age (N=98; 183 total scans; 1-3 scans per participant). Participants were recruited from the greater Los Angeles area, and completed an event-related emotional face (fear, neutral) task designed to be appropriate for the wide age range. 'Multiverse' analyses examined the robustness of our findings to fMRI analysis choices. 2808 parallel analyses varying in preprocessing and modeling choices found evidence for average age-related decreases in amygdala reactivity to faces. Greater amygdala reactivity at younger ages was attributable to elevated responses during the first few trials relative to later trials. Within-participant changes in amygdala reactivity with age could not be differentiated from between-participant differences, however. Across analysis decision points, we did not find consistent evidence of age-related change in amygdala-mPFC connectivity through generalized psychophysiological interaction (gPPI) or beta-series correlation (BSC) methods. We also did not find evidence for associations between separation anxiety behaviors and amygdala reactivity or amygdala-mPFC connectivity. Within the context of this faces task and age range, age-related changes in amygdala reactivity were more robust to processing pipeline than were task-evoked functional connectivity measures, particularly those using gPPI. These findings highlight both the challenges in estimating developmental change in longitudinal cohorts and the value of multiverse approaches in developmental neuroimaging for assessing robustness of results.

Mediating effect of pubertal stages on the family environment and neurodevelopment: An open-data replication and multiverse analysis of an ABCD Study®

“…It is well understood that measurement error and researcher degrees of freedom contribute to replication ( Loken and Gelman, 2017 ) and generalizability issues ( Flake et al, 2022 ), making multiverse analyses an effective way to meaningfully gauge the robustness of findings. There is increasing evidence from the neuroimaging literature that decision points across an analytic pipeline may impact the conclusions when reproducing or replicating brain-behavior effects ( Bloom et al, 2021 ; Botvinik-Nezer et al, 2020 ; Bowring et al, 2022 ; Bryce et al, 2021 ; Li et al, 2021 ). These issues are confounded in developmental research on environmental stress as a product of overlapping measures and competing theories ( Smith and Pollak, 2020 ).…”

“…Finally, the analyses here focused solely on the tabulated brain imaging data provided by the ABCD consortium and did not focus on alternative operationalizations of brain data. Based on recent analyses demonstrating the impact of decisions within an analytic pipeline ( Bloom et al, 2021 ), between analytic pipelines in neuroimaging ( Li et al, 2021 ) and different brain parcellations on the resulting estimates ( Bryce et al, 2021 ), this multiverse analysis was not well positioned to answer questions regarding how differences in the operationalization of brain variables impacted the mediating models. Future studies focused on replications and multiverse analyses of ABCD data should consider using a combination of data that are tabulated by the consortium and those that test deviations from those methods.…”

“…For instance, Orben et al (2019) evaluated the association between social media use and life satisfaction, reporting inconsistencies that were dependent on how sex was modeled and which analytical method used. Bloom et al (2021) used a multiverse analysis to evaluate the robustness of age-related changes in functional activation and brain connectivity in their longitudinal cohort of 4–22 year-olds. Across their model permutations, they reported age-related associations in functional activation in the amygdala were relatively robust to model permutations but findings for amygdala-medial prefrontal cortex connectivity were inconsistent across model permutations.…”

Does pubertal stage mediate the association between family environment and structure and function of the amygdala-mPFC circuit? A replication study of the longitudinal ABCD cohort

“…In children, responses of the amygdala and mPFC to fearful faces are positively correlated ( Gee et al, 2013b ), whereas adolescents and adults show negative patterns of amygdala-mPFC functional connectivity in response to the same stimuli. This negative pattern of functional connectivity is interpreted as effective top-down control of the amygdala by the mPFC (however, using a multiverse approach Bloom et al, 2021 did not find evidence for age related changes in amygdala-mPFC functional connectivity in response to this task).…”

Associations Between Early-Life Stress Exposure and Internalizing Symptomatology During the COVID-19 Pandemic: Assessing the Role of Neurobehavioral Mediators

“…Finally, variations in neuroimaging preprocessing pipelines and methodological differences can contribute to distinct findings ( 78 ). Future work could examine a mediating effect of frontoamygdala circuitry in stress-psychopathology in a multiverse fashion ( 79 , 80 ) to assess the robustness of findings.…”