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

Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 07/2005; 102(30):10706-11. DOI: 10.1073/pnas.0502441102
Source: PubMed

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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    • "Rodent studies have demonstrated both structural and functional connections between amygdala and mPFC (McDonald et al., 1996; Quirk et al., 2003), and have shown that mPFC lesions (specifically of the infralimbic region; IL) result in impaired extinction retention, while leaving extinction learning intact (Milad & Quirk, 2002; Quirk et al., 2000). Similarly, in humans, recall of extinguished fear memories increases vmPFC reactivity in response to the CS+ (Milad et al., 2007; Phelps et al., 2004), and is positively associated with vmPFC thickness (Milad et al., 2005). Also, on a different emotion regulation task involving cognitive reappraisal of a negative event, the amygdala showed stronger coupling with the dlPFC, OFC, Subgenual ACC, and dmPFC, with the extent of such coupling being positively associated with post-reappraisal attenuation of negative affect (Banks et al., 2007; Ochsner et al., 2002; Urry et al., 2006). "
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    • "To our knowledge there are no studies investigating a potential association between (the rate of) extinction learning (i.e., number of trials until complete extinction) and (the strength of) extinction memory. The prefrontal areas correlating with extinction learning performance in our study strongly overlap with areas that were previously found to correlate with extinction memory (Hartley et al. 2011; Milad et al. 2005). This is consistent with a positive relationship between extinction learning and extinction memory. "
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    • "This idea is consistent with other studies that show that the vmPFC plays a protective role when cognitive appraisals are specifically engaged to regulate emotion (Eippert et al., 2007; Wager et al., 2008). Milad et al. (Milad et al., 2005) Fig. 6. Brain regions activated during rectal distension preceded by uncertain versus certain anticipation. "
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