A role for the human dorsal anterior cingulate cortex in fear expression.
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.
Milad
Mohammed R
MR
Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129, USA. milad@nmr.mgh.harvard.edu
Quirk
Gregory J
GJ
Pitman
Roger K
RK
Orr
Scott P
SP
Fischl
Bruce
B
Rauch
Scott L
SL
D000328:Adult; D001931:Brain Mapping; D019260:Expressed Emotion / Q000502:physiology*; D005239:Fear; D005260:Female; D005712:Galvanic Skin Response / Q000502:physiology; D006179:Gyrus Cinguli / Q000098:blood supply / Q000502:physiology*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D010100:Oxygen / Q000097:blood; D012044:Regression Analysis
D010100:Oxygen