LeDoux Lab 2006 SfN Abstracts
 
Reversal of fear learning in the human brain

*D. SCHILLER1, J. E. LEDOUX2, E. A. PHELPS1;
1Center for Neural Science & Psychology Department, New York Univ, New York, NY, 2Center for Neural Science, New York Univ, New York, NY.

Fear learning is typically rapid and resistant to modification. This tendency to persist prevents the need for relearning about danger and can be adaptive in promoting avoidance in the face of danger. However, the ability to flexibly readjust behavior is also advantageous, and this ability may be impaired in fear disorders. One way of studying fear modification learning involves reversal of reinforcement contingencies. Animal studies strongly implicate the orbitofrontal cortex in reversal learning. However, the mechanisms underlying fear reversal learning in humans are largely unknown. To investigate these mechanisms we have used whole brain fMRI during a partial reinforcement fear learning and reversal paradigm.
The procedure consisted of the following stages: Acquisition. Subjects were presented with two visual stimuli (angry faces). One stimulus (conditioned stimulus; CS+) co-terminated with an aversive outcome (US, wrist shock) on 33% of the trials. The other stimulus was never paired with the shock (CS-). Reversal. This stage was similar to acquisition but the reinforcement contingency was reversed so that the previously non-reinforced stimulus co-terminated with the US. Galvanic skin responses (GSRs) to the images served as an index of fear.
GSRs were greater to the CS+ than CS- during acquisition, and vice versa during reversal, showing that fear learning occurred and that it reversed. Preliminary fMRI data showed greater activation to the CS+ than CS- during acquisition in the amygdala, striatum, insula, thalamus, and medial prefrontal cortex; these areas reversed their activation during reversal. Interestingly, two areas in the prefrontal cortex (PFC) were selectively activated during reversal and their activation pattern was dissociable. Specifically, during reversal, the superior frontal gyrus showed greater activation to the newly reinforced stimulus (the old CS-), whereas the anterior cingulate cortex showed greater activation to the stimulus that was not reinforced (the old CS+).
Thus, the PFC is activated when changes in environmental conditions occur and different areas of the PFC maintain the previous and current association. This points to a specific role of PFC areas in the maintenance and updating of currently relevant information, and in the ability to flexibly shift from irrelevant responding to a newly appropriate one. This ability may be impaired in persons with fear disorders.
Support Contributed By:P50 MH058911 ( JEL);MH62104 (EAP);CBI-NYU and Fulbright grants (DS

Program No. 370.11/LL1
Poster presentation:
Monday, Oct 16, 2006, 10:00 AM -11:00 AM
Location: Georgia World Congress Center: Halls B3-B5