Download Reversal of fear learning in the human brain

Reversal of fear learning in the human brain
Daniela Schiller1,2, Joseph E LeDoux1 and Elizabeth A Phelps1,2
1
Center for Neural Science, 2Psychology, New York University, New York, NY
It is well known that stimuli previously associated with harmful outcomes, such
as the sound of an alarm, are able to elicit a repertoire of protective reactions in
expectation for the harmful stimulus to arrive. This process of fear learning is typically
rapid and resistant to modifications. The persistent nature of fear learning prevents the
need for relearning about danger and can be adaptive in promoting avoidance in the face
of threats. However, if one bad experience were to change our behavior forever it would
be difficult to function in ever-changing environments. Thus, at times, it is also
advantageous to flexibly readjust fear responses. For example, in the movie “The
Terminator 1”, Arnold Schwarzenegger played the human-looking, unstoppable cyborg
that was sent from the future to kill Sarah Connor. However, in “The Terminator 2”, he
was sent again, this time to fight against a shape-shifting cyborg that was sent back from
the future to kill her son. We may remember Sara Connor’s horrified reaction when she
first saw him in “The Terminator 2”. It took her a while to learn that he was her protector
and to shift her fear response to the new terminator.
Laboratory studies of fear learning typically use a procedure called classical
conditioning. In this procedure, an animal is exposed to a meaningless stimulus, such as a
tone, together with a harmful stimulus, such as a mild electric shock. After very few, or
even a single pairing of these stimuli, the presentation of the tone itself is now capable of
eliciting a characteristic pattern of behavioral and physiological stress responses, such as
freezing. In other words, the animal has come to fear the stimulus that was just moments
ago, meaningless. A simple variation of this procedure enables us to study how fear
learning is modified, by reversing the reinforcement contingency between two neutral
stimuli. Investigations of the neural substrates underlying fear learning in animals have
highlighted a brain region called the amygdala in the development of conditioned fear.
However, the mechanisms underlying reversal of fear learning in animals and in humans
are largely unknown. To investigate these mechanisms we have used brain-imaging
techniques while subjects were engaged in a human analogue of the fear learning and
reversal paradigm.
The procedure consisted of the following stages: Acquisition. Subjects were
presented with two visual stimuli (angry faces). One stimulus (face A) co-terminated with
an aversive outcome (wrist shock) on 33% of the trials. The other stimulus was never
paired with the shock (face B). Reversal. This stage was similar to acquisition but the
reinforcement contingency was reversed so that the previously non-reinforced stimulus
co-terminated with the shock. As an index of fear, we used a physiological stress
response, called the skin conductance response.
We found that skin conductance responses were greater to face A than face B
during acquisition, and vice versa during reversal, showing behaviorally that fear learning
occurred and that it was reversed. Brain imaging data pointed out two brain circuits
operating in tandem. One circuitry, consisting of mainly sub-cortical areas including the
amygdala, striatum, midbrain, thalamus, insula and anterior cingulate cortex, showed
greater brain activation to face A than face B during acquisition, and a reversal of this
activation during the reversal stage. Another circuitry, including higher-order areas in the
frontal cortex, the posterior cingulate cortex, the hippocampus, and areas in the parietal
cortex, was exclusively involved in the reversal stage, showing activation to both faces,
the newly reinforced one and the no longer reinforced one.
These results suggest that once fear learning has developed using one brain
circuitry, another circuitry is required to ‘take over’ and modify the initial learning when
environmental circumstances change. This circuitry has a specific role in the maintenance
and updating of currently relevant information, and in the ability to flexibly shift from an
irrelevant response to a newly appropriate one. This ability may be impaired in persons
with fear and anxiety disorders. Thus, understanding the brain mechanisms underlying
reversal of fear learning may shed light on these psychopathologies.
Support: P50 MH058911 to JEL, MH62104 to EAP, CBI-NYU and Fulbright award to
DS