Elsevier

Biological Psychiatry

Volume 62, Issue 10, 15 November 2007, Pages 1191-1194
Biological Psychiatry

Brief Report
A Role for the Human Dorsal Anterior Cingulate Cortex in Fear Expression

https://doi.org/10.1016/j.biopsych.2007.04.032Get rights and content

Background

Rodent studies implicate the prelimbic (PL) region of the medial prefrontal cortex in the expression of conditioned fear. Human studies suggest that the dorsal anterior cingulate cortex (dACC) plays a role similar to PL in mediating or modulating fear responses. This study examined the role of dACC during fear conditioning in healthy humans with magnetic resonance imaging (MRI).

Methods

Novel analyses were conducted on data from two cohorts that had previously undergone scanning to study fear extinction. Structural and functional brain data were acquired with MRI; the functional MRI (fMRI) component employed an event-related design. Skin conductance response (SCR) was the index of conditioned responses.

Results

We found that: 1) cortical thickness within dACC is positively correlated with SCR during conditioning; 2) dACC is activated by a conditioned fear stimulus; and 3) this activation is positively correlated with differential SCR. Moreover, the dACC region implicated in this research corresponds to the target of anterior cingulotomy, an ablative surgical treatment for patients with mood and anxiety disorders.

Conclusions

Convergent structural, functional, and lesion findings from separate groups of subjects suggest that dACC mediates or modulates fear expression in humans. Collectively, these data implicate this territory as a potential target for future anti-anxiety therapies.

Section snippets

Methods and Materials

Subjects were mentally healthy and ranged in age from 19 to 39. Fourteen subjects (8 men, 6 women) participated in the structural magnetic resonance imaging (MRI) component. Thirteen different subjects (7 men, 6 women) participated in the fMRI component. Written informed consent was obtained in accordance with the requirements of the Partners Healthcare System Human Research Committee.

Reported herein are novel analyses of the aforementioned two separate cohorts that underwent a fear

Results

All subjects showed significant increases in SCR to the CS+ relative to the CS−, indicating successful differential conditioning (23, 24). We observed a significant positive correlation between thickness in the dACC region (peak vertex: r = .70, p = .005 [Talairach coordinates −3, 23, 18) and SCR to the CS+ (Figures 1A and 1B). We did not observe a significant correlation that satisfied our statistical threshold (p = .01, two-tailed, uncorrected) between dACC thickness and SCR to the CS− (r =

Discussion

We found that dACC thickness was positively correlated with conditioned fear responses to the CS+, as indexed by SCR. In a separate cohort of subjects, dACC functional activation increased to the CS+ relative to the CS− during fear conditioning, and dACC activity was positively correlated with differential SCR. The convergence of structural and functional correlates of conditioned fear responding in the dACC reported herein is remarkable, considering that these two data sets were obtained from

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