Brain Structure Correlates of Individual Differences in the Acquisition and Inhibition of Conditioned Fear

Abstract

Research employing aversive conditioning paradigms has elucidated the neurocircuitry involved in acquiring and diminishing fear responses. However, the factors underlying individual differences in fear acquisition and inhibition are not presently well understood. In this study, we explored whether the magnitude of individuals' acquired fear responses and the modulation of these responses via 2 fear reduction methods were correlated with structural differences in brain regions involved in affective processing. Physiological and structural magnetic resonance imaging data were obtained from experiments exploring extinction retention and intentional cognitive regulation. Our results identified 2 regions in which individual variation in brain structure correlated with subjects' fear-related arousal. Confirming previous results, increased thickness in ventromedial prefrontal cortex was correlated with the degree of extinction retention. Additionally, subjects with greater thickness in the posterior insula exhibited larger conditioned responses during acquisition. The data suggest a trend toward a negative correlation between amygdala volume and fear acquisition magnitude. There was no significant correlation between fear reduction via cognitive regulation and thickness in our prefrontal regions of interest. Acquisition and regulation measures were uncorrelated, suggesting that while certain individuals may have a propensity toward increased expression of conditioned fear, these responses can be diminished via both extinction and cognitive regulation.

A unifying model of the role of the infralimbic cortex in extinction and habits

“…This is consistent with the idea that innate differences in these connections may drive the propensity to develop habitual response strategies (de Wit et al 2012). Activity in the subgenual vmPFC has also been shown to be associated with extinction learning in humans and may underlie extinction abnormalities in disease states (Quirk and Beer 2006;Hartley et al 2011;Milad et al 2013). Alhough a majority of these reports have focused on the investigation of fear extinction, given the high overlap between the role of IL in distinct forms of extinction learning in the rodent, it is tempting to speculate that considerable similarity between vmPFC function in fear and reward extinction will exist.…”

Individual differences in learning predict the return of fear

“…Understanding such psychiatric vulnerability and resilience will require a more complete mechanistic model of the cognitive and neural heterogeneity in fear learning and extinction. New insights from structural brain imaging (Hartley, Fischl, & Phelps, 2011) and selective breeding of rats for particular extinction-related phenotypes (Bush, Sotres-Bayon, & LeDoux, 2007) have begun to articulate the neural and behavioral profiles of relevant individual differences. Our hope is that future computational theories of extinction and recovery will integrate and attempt to account for such individual differences in learning.…”

Sensitive Periods in Affective Development: Nonlinear Maturation of Fear Learning

“…Increases in BOLD activation are also observed during extinction recall (Phelps et al, 2004). Both the magnitude of vmPFC BOLD signal as well as the thickness of the cortex in this region have been found to correlate with the degree of extinction retrieval (Hartley et al, 2011;Milad et al, 2005;Milad et al, 2007b). On the basis of these findings, the subgenual vmPFC region has been proposed to be a potential human homologue of the rodent IL region (Hartley and Phelps, 2013;Milad et al, 2007a;Milad and Quirk, 2012), and may diminish fear expression via its projections to the amygdala.…”