Thickness of ventromedial prefrontal cortex in humans is correlated with extinction memory - PubMed (original) (raw)

Comparative Study

. 2005 Jul 26;102(30):10706-11.

doi: 10.1073/pnas.0502441102. Epub 2005 Jul 15.

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Comparative Study

Thickness of ventromedial prefrontal cortex in humans is correlated with extinction memory

Mohammed R Milad et al. Proc Natl Acad Sci U S A. 2005.

Abstract

The ventromedial prefrontal cortex (vmPFC) has been implicated in fear extinction [Phelps, E. A., Delgado, M. R., Nearing, K. I. & Ledoux, J. E. (2004) Neuron 43, 897-905; Herry, C. & Garcia, R. (2003) Behav. Brain Res. 146, 89-96]. Here, we test the hypothesis that the cortical thickness of vmPFC regions is associated with how well healthy humans retain their extinction memory a day after having been conditioned and then extinguished. Fourteen participants underwent a 2-day fear conditioning and extinction protocol. The conditioned stimuli (CSs) were pictures of virtual lights, and the unconditioned stimulus (US) was an electric shock. On day 1, participants received 5 CS+US pairings (conditioning), followed by 10 CS trials with no US (extinction). On day 2, the CS was presented alone to test for extinction memory. Skin conductance response (SCR) was the behavioral index of conditioning and extinction. Participants underwent MRI scans to obtain structural images, from which cortical thickness was measured. We performed a vertex-based analysis across the entire cortical surface and a region-of-interest analysis of a priori hypothesized territories to measure cortical thickness and map correlations between this measure and SCR. We found significant, direct correlation between thickness of the vmPFC, specifically medial orbitofrontal cortex, and extinction retention. That is, thicker medial orbitofrontal cortex was associated with lower SCR to the conditioned stimulus during extinction recall (i.e., greater extinction memory). These results suggest that the size of the vmPFC might explain individual differences in the ability to modulate fear among humans.

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Figures

Fig. 1.

Fig. 1.

Schematic of the experimental protocol. (Adapted from ref. 24). [Reproduced with permission from Milad et al. (24) (Copyright 2005, Blackwell Publishing).]

Fig. 2.

Fig. 2.

Illustration of psychophysiological data. (A) Mean SCRs collapsed across trials for each experimental phase for the CS+. Hbt, habituation; Cond, conditioning; CX+, conditioning context; CX-, extinction context. (B) Extinction retention index (see text for definition) in each context. CX- corresponding to recall phase and CX+ corresponding to renewal phase. *, P < 0.05.

Fig. 3.

Fig. 3.

Illustration of brain regions of interest and correlational plots between mOFC thickness and extinction retention. (A) Boundaries of ROI: SC, subcallosal cortex; mOFC, medial orbitofrontal cortex; rACC, rostral anterior cingulate cortex; dACC, dorsal anterior cingulate cortex. (B) Regression plots for extinction retention index separately in CX- and CX+ versus cortical thickness in mOFC.

Fig. 4.

Fig. 4.

Regions with positive correlations between cortical thickness and extinction retention in CX- (A) as well as CX+ (B) and regression plots for the correlations between percent extinction retention and cortical thickness in the vmPFC. Threshold is set at P < 0.01 (dark blue) to P < 0.001 (cyan blue). Red areas show incidental negative correlations. Arrow indicates vmPFC region, whereas circle indicates superior parietal correlation.

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