TY - JOUR
T1 - From fear to safety and back
T2 - Reversal of fear in the human brain
AU - Schiller, Daniela
AU - Levy, Ifat
AU - Niv, Yael
AU - LeDoux, Joseph E.
AU - Phelps, Elizabeth A.
PY - 2008/11/5
Y1 - 2008/11/5
N2 - Fear learning is a rapid and persistent process that promotes defense against threats and reduces the need to relearn about danger. However, it is also important to flexibly readjust fear behavior when circumstances change. Indeed, a failure to adjust to changing conditions may contribute to anxiety disorders. A central, yet neglected aspect of fear modulation is the ability to flexibly shift fear responses from one stimulus to another if a once-threatening stimulus becomes safe or a once-safe stimulus becomes threatening. In these situations, the inhibition of fear and the development of fear reactions co-occur but are directed at different targets, requiring accurate responding under continuous stress. To date, research on fear modulation has focused mainly on the shift from fear to safety by using paradigms such as extinction, resulting in a reduction of fear. The aim of the present study was to track the dynamic shifts from fear to safety and from safety to fear when these transitions occur simultaneously. We used functional neuroimaging in conjunction with a fear-conditioning reversal paradigm. Our results reveal a unique dissociation within the ventromedial prefrontal cortex between a safe stimulus that previously predicted danger and a "naive" safe stimulus. We show that amygdala and striatal responses tracked the fear-predictive stimuli, flexibly flipping their responses from one predictive stimulus to another. Moreover, prediction errors associated with reversal learning correlated with striatal activation. These results elucidate how fear is readjusted to appropriately track environmental changes, and the brain mechanisms underlying the flexible control of fear.
AB - Fear learning is a rapid and persistent process that promotes defense against threats and reduces the need to relearn about danger. However, it is also important to flexibly readjust fear behavior when circumstances change. Indeed, a failure to adjust to changing conditions may contribute to anxiety disorders. A central, yet neglected aspect of fear modulation is the ability to flexibly shift fear responses from one stimulus to another if a once-threatening stimulus becomes safe or a once-safe stimulus becomes threatening. In these situations, the inhibition of fear and the development of fear reactions co-occur but are directed at different targets, requiring accurate responding under continuous stress. To date, research on fear modulation has focused mainly on the shift from fear to safety by using paradigms such as extinction, resulting in a reduction of fear. The aim of the present study was to track the dynamic shifts from fear to safety and from safety to fear when these transitions occur simultaneously. We used functional neuroimaging in conjunction with a fear-conditioning reversal paradigm. Our results reveal a unique dissociation within the ventromedial prefrontal cortex between a safe stimulus that previously predicted danger and a "naive" safe stimulus. We show that amygdala and striatal responses tracked the fear-predictive stimuli, flexibly flipping their responses from one predictive stimulus to another. Moreover, prediction errors associated with reversal learning correlated with striatal activation. These results elucidate how fear is readjusted to appropriately track environmental changes, and the brain mechanisms underlying the flexible control of fear.
KW - Amygdala
KW - Fear conditioning
KW - Prediction error
KW - Reversal
KW - Striatum
KW - vmPFC
UR - http://www.scopus.com/inward/record.url?scp=58149239666&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=58149239666&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.2265-08.2008
DO - 10.1523/JNEUROSCI.2265-08.2008
M3 - Article
C2 - 18987188
AN - SCOPUS:58149239666
SN - 0270-6474
VL - 28
SP - 11517
EP - 11525
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 45
ER -