Research Article: Amygdalar reactivity is associated with prefrontal cortical thickness in a large population-based sample of adolescents

Date Published: May 2, 2019

Publisher: Public Library of Science

Author(s): Matthew D. Albaugh, James. J. Hudziak, Catherine Orr, Philip A. Spechler, Bader Chaarani, Scott Mackey, Claude Lepage, Vladimir Fonov, Pierre Rioux, Alan C. Evans, Tobias Banaschewski, Arun L. W. Bokde, Uli Bromberg, Christian Büchel, Erin Burke Quinlan, Sylvane Desrivières, Herta Flor, Antoine Grigis, Penny Gowland, Andreas Heinz, Bernd Ittermann, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Frauke Nees, Dimitri Papadopoulos Orfanos, Tomáš Paus, Luise Poustka, Sabina Millenet, Juliane H. Fröhner, Michael N. Smolka, Henrik Walter, Robert Whelan, Gunter Schumann, Alexandra S. Potter, Hugh Garavan, Thilo Kellermann.


In structural neuroimaging studies, reduced cerebral cortical thickness in orbital and ventromedial prefrontal regions is frequently interpreted as reflecting an impaired ability to downregulate neuronal activity in the amygdalae. Unfortunately, little research has been conducted in order to test this conjecture. We examine the extent to which amygdalar reactivity is associated with cortical thickness in a population-based sample of adolescents. Data were obtained from the IMAGEN study, which includes 2,223 adolescents. While undergoing functional neuroimaging, participants passively viewed video clips of a face that started from a neutral expression and progressively turned angry, or, instead, turned to a second neutral expression. Left and right amygdala ROIs were used to extract mean BOLD signal change for the angry minus neutral face contrast for all subjects. T1-weighted images were processed through the CIVET pipeline (version 2.1.0). In variable-centered analyses, local cortical thickness was regressed against amygdalar reactivity using first and second-order linear models. In a follow-up person-centered analysis, we defined a “high reactive” group of participants based on mean amygdalar BOLD signal change for the angry minus neutral face contrast. Between-group differences in cortical thickness were examined (“high reactive” versus all other participants). A significant association was revealed between the continuous measure of amygdalar reactivity and bilateral ventromedial prefrontal cortical thickness in a second-order linear model (p < 0.05, corrected). The “high reactive” group, in comparison to all other participants, possessed reduced cortical thickness in bilateral orbital and ventromedial prefrontal cortices, bilateral anterior temporal cortices, left caudal middle temporal gyrus, and the left inferior and middle frontal gyri (p < 0.05, corrected). Results are consistent with non-human primate studies, and provide empirical support for an association between reduced prefrontal cortical thickness and amygdalar reactivity. Future research will likely benefit from investigating the degree to which psychopathology qualifies relations between prefrontal cortical structure and amygdalar reactivity.

Partial Text

Among primates, dense anatomical connections exist between regions of the prefrontal cortex and the amygdalae [1–4]. Given these anatomical connections, it has long been posited that prefrontal regions provide “top-down” modulation of amygdalar functioning [1–4]. In support of this notion, functional magnetic resonance imaging (fMRI) studies of emotion regulation have implicated prefrontal regions in the regulation of amygdalar activity [5–12]. Specifically, across such studies, effective forms of emotion regulation have been associated with increased activation in prefrontal areas, as well as concomitant decreases in amygdalar activation.

In many structural neuroimaging studies, reduced cortical thickness in orbitofrontal and ventromedial prefrontal areas has been interpreted as reflecting an impaired ability to downregulate amygdalar regions. To our knowledge, this is the largest multimodal neuroimaging study to provide support for this widespread speculation. Specifically, using both variable- and person-centered approaches, we revealed an association between high amygdalar reactivity to emotional stimuli and reduced ventromedial prefrontal cortical thickness in a large, population-based sample of adolescents. Further, results from the present study suggest that the relationship between cerebral cortical thickness and amygdalar reactivity is not influenced by sex.




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