Article

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

Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129, USA.
Biological Psychiatry (Impact Factor: 10.25). 12/2007; 62(10):1191-4. DOI: 10.1016/j.biopsych.2007.04.032
Source: PubMed

ABSTRACT 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).
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.
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.
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.

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    • "The current neurocircuitry model of fear extinction (Milad and Quirk 2012) implies a dual cortical control of limbic activity with opposing modulatory roles for the two subparts of the PFC: The IL inhibits amygdalar CE fear output via projections to the intercalated cells thereby mediating extinction, while the PL with its excitatory projections to the BLA is directly involved in the expression of learned fear. Although it is difficult to define homologous areas between rodents and humans, the vmPFC, including the subgenual anterior cingulate cortex and the medial orbitofrontal cortex, has been proposed as homologs to the rodent IL (Ongur and Price 2000), while numerous findings support the idea that the dorsal anterior cingulate cortex (dACC) is the human homolog of the rodent PL (Milad et al. 2007a). Although our study confirms the structural basis of vmPFC involvement in extinction learning in humans , we found no significant association between fear acquisition capacity and the thickness of the dACC or any other cortical area. "
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