TY - JOUR
T1 - Neural substrates of classically conditioned fear-generalization in humans
T2 - A parametric fMRI study
AU - Lissek, Shmuel
AU - Bradford, Daniel E.
AU - Alvarez, Ruben P.
AU - Burton, Philip
AU - Espensen-Sturges, Tori
AU - Reynolds, Richard C.
AU - Grillon, Christian
PY - 2014/8
Y1 - 2014/8
N2 - Recent research on classical fear-conditioning in the anxiety disorders has identified overgeneralization of conditioned fear as an important conditioning correlate of anxiety pathology. Unfortunately, only one human neuroimaging study of classically conditioned fear generalization has been conducted, and the neural substrates of this clinically germane process remain largely unknown. The current generalization study employs a clinically validated generalization gradient paradigm, modified for the fMRI environment, to identify neural substrates of classically conditioned generalization that may function aberrantly in clinical anxiety. Stimuli include five rings of gradually increasing size with extreme sizes serving as cues of conditioned danger (CS+) and safety (CS-). The three intermediately sized rings serve as generalization stimuli (GSs) and create a continuum-of-size from CS+ to CS-. Results demonstrate 'positive' generalization gradients, reflected by declines in responding as the presented stimulus differentiates from CS+, in bilateral anterior insula, dorsomedial prefrontal cortex, and bilateral inferior parietal lobule. Conversely, 'negative' gradients, reflected by inclines in responding as the presented stimulus differentiates from CS+ were instantiated in bilateral ventral hippocampus, ventromedial prefrontal cortex and precuneus cortex. These results as well as those from connectivity analyses are discussed in relation to a working neurobiology of conditioned generalization centered on the hippocampus.
AB - Recent research on classical fear-conditioning in the anxiety disorders has identified overgeneralization of conditioned fear as an important conditioning correlate of anxiety pathology. Unfortunately, only one human neuroimaging study of classically conditioned fear generalization has been conducted, and the neural substrates of this clinically germane process remain largely unknown. The current generalization study employs a clinically validated generalization gradient paradigm, modified for the fMRI environment, to identify neural substrates of classically conditioned generalization that may function aberrantly in clinical anxiety. Stimuli include five rings of gradually increasing size with extreme sizes serving as cues of conditioned danger (CS+) and safety (CS-). The three intermediately sized rings serve as generalization stimuli (GSs) and create a continuum-of-size from CS+ to CS-. Results demonstrate 'positive' generalization gradients, reflected by declines in responding as the presented stimulus differentiates from CS+, in bilateral anterior insula, dorsomedial prefrontal cortex, and bilateral inferior parietal lobule. Conversely, 'negative' gradients, reflected by inclines in responding as the presented stimulus differentiates from CS+ were instantiated in bilateral ventral hippocampus, ventromedial prefrontal cortex and precuneus cortex. These results as well as those from connectivity analyses are discussed in relation to a working neurobiology of conditioned generalization centered on the hippocampus.
KW - Anxiety
KW - Conditioned generalization
KW - Fear-conditioning
KW - Neurobiology
KW - fMRI
UR - http://www.scopus.com/inward/record.url?scp=84905921226&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84905921226&partnerID=8YFLogxK
U2 - 10.1093/scan/nst096
DO - 10.1093/scan/nst096
M3 - Article
C2 - 23748500
AN - SCOPUS:84905921226
SN - 1749-5016
VL - 9
SP - 1134
EP - 1142
JO - Social Cognitive and Affective Neuroscience
JF - Social Cognitive and Affective Neuroscience
IS - 8
M1 - nst096
ER -