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.
Key Words
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References
- New vistas on amygdala networks in conditioned fear.J Neurophysiol. 2004; 92: 1-9
- Neuronal signalling of fear memory.Nat Rev Neurosci. 2004; 5: 844-852
- Extinction learning in humans: Role of the amygdala and vmPFC.Neuron. 2004; 43: 897-905
- Functional MRI of human amygdala activity during Pavlovian fear conditioning: Stimulus processing versus response expression.Behav Neurosci. 2003; 117: 3-10
- Human amygdala activity during the expression of fear responses.Behav Neurosci. 2006; 120: 1187-1195
- The amygdala and individual differences in human fear conditioning.Neuroreport. 1997; 8: 3957-3960
- The effect of medial frontal cortex lesions on respiration, “freezing,” and ultrasonic vocalizations during conditioned emotional responses in rats.Cereb Cortex. 1991; 1: 418-425
- Functions of anterior and posterior cingulate cortex during avoidance learning in rabbits.Prog Brain Res. 1990; 85: 467-482
- Single unit activity in the medial prefrontal cortex during Pavlovian heart rate conditioning: Effects of peripheral autonomic blockade.Neurobiol Learn Mem. 2005; 84: 200-213
- Single neurons in the medial prefrontal cortex of the rat exhibit tonic and phasic coding during trace fear conditioning.Behav Neurosci. 2005; 119: 1496-1510
- Microstimulation reveals opposing influences of prelimbic and infralimbic cortex on the expression of conditioned fear.Learn Mem. 2006; 13: 728-733
- A role for the prefrontal cortex in recall of recent and remote memories.Neuroreport. 2006; 17: 341-344
- Activity in prelimbic cortex is necessary for the expression of learned, but not innate, fears.J Neurosci. 2007; 27: 840-844
- Projections from the lateral nucleus to the basal nucleus of the amygdala: A light and electron microscopic PHA-L study in the rat.J Comp Neurol. 1992; 323: 586-601
- Efferent projections of infralimbic and prelimbic areas of the medial prefrontal cortex in the Japanese monkey, Macaca fuscata.Brain Res. 2001; 888: 83-101
- Lesions of the basal amygdala block expression of conditioned fear but not extinction.J Neurosci. 2005; 25: 9680-9685
- Synaptology of prefrontal cortical projections to the basolateral amygdala: An electron microscopic study in the rat.Neurosci Lett. 1995; 202: 45-48
- Amygdala and hippocampal activity during acquisition and extinction of human fear conditioning.Cogn Affect Behav Neurosci. 2004; 4: 317-325
- Human amygdala activation during conditioned fear acquisition and extinction: A mixed-trial fMRI study.Neuron. 1998; 20: 937-945
- Classical fear conditioning in functional neuroimaging.Curr Opin Neurobiol. 2000; 10: 219-223
- Functional neuroanatomical correlates of electrodermal activity: A positron emission tomographic study.Psychophysiology. 1998; 35: 179-185
- Thickness of ventromedial prefrontal cortex in humans is correlated with extinction memory.Proc Natl Acad Sci U S A. 2005; 102: 10706-10711
- Recall of fear extinction in humans activates the ventromedial prefrontal cortex and hippocampus in concert.Biol Psychiatry. 2007; (Jan 9; Epub ahead of print.)
- Context modulation of memory for fear extinction in humans.Psychophysiology. 2005; 42: 456-464
- Structural and functional dichotomy of human midcingulate cortex.Eur J Neurosci. 2003; 18: 3134-3144
- Volitional control of autonomic arousal: A functional magnetic resonance study.Neuroimage. 2002; 16: 909-919
- Direct electrical stimulation of specific human brain structures and bilateral electrodermal activity.Int J Psychophysiol. 1996; 22: 1-8
- Neuroanatomical correlates of electrodermal skin conductance responses.Psychophysiology. 1994; 31: 427-438
- Neural mechanisms of autonomic, affective, and cognitive integration.J Comp Neurol. 2005; 493: 154-166
- Task-independent functional brain activity correlation with skin conductance changes: An fMRI study.Neuroimage. 2002; 17: 1797-1806
- Neural activity relating to generation and representation of galvanic skin conductance responses: A functional magnetic resonance imaging study.J Neurosci. 2000; 20: 3033-3040
- The role of the human amygdala in the production of conditioned fear responses.Neuroimage. 2005; 26: 1193-1200
- Frontal lobe lesions and electrodermal activity: Effects of significance.Neuropsychologia. 1999; 37: 1227-1241
- Volume reduction in the caudate nucleus following stereotactic placement of lesions in the anterior cingulate cortex in humans: A morphometric magnetic resonance imaging study.J Neurosurg. 2000; 93: 1019-1025
- Neuroimaging and neurocircuitry models pertaining to the neurosurgical treatment of psychiatric disorders.Neurosurg Clin N Am. 2003; 14 (vii–viii): 213-223
- Prospective long-term follow-up of 44 patients who received cingulotomy for treatment-refractory obsessive-compulsive disorder.Am J Psychiatry. 2002; 159: 269-275
- Stereotactic cingulotomy with results of acute stimulation and serial psychological testing.in: Laitinen L.V. Livingston K.E. Surgical Approaches in Psychiatry. MTP, Baltimore, Lancaster, United Kingdom1973: 39-58
- Neurocircuitry models of posttraumatic stress disorder and extinction: Human neuroimaging research—past, present, and future.Biol Psychiatry. 2006; 60: 376-382
- Effects of d-cycloserine on extinction: Translation from preclinical to clinical work.Biol Psychiatry. 2006; 60: 369-375
- Context-dependent human extinction memory is mediated by a ventromedial prefrontal and hippocampal network.J Neurosci. 2006; 26: 9503-9511
- Prefrontal mechanisms in extinction of conditioned fear.Biol Psychiatry. 2006; 60: 337-343
Article info
Publication history
Published online: August 20, 2007
Accepted:
April 24,
2007
Received in revised form:
April 17,
2007
Received:
February 22,
2007
Identification
Copyright
© 2007 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
