AB-AB design. On day 1, subjects were fear conditioned to a CS+ (a face) through multiple pairings with a UCS (electric shock) in context A (conditioning context, block A1). Fear responses were extinguished in context B (extinction context, block B1) through multiple CS+ presentations in the absence of the UCS. This procedure was repeated in additional blocks (blocks A2, B2), leading to robust context discrimination. As a control for nonassociative effects, we also used a nonpredictive CS− (a face of opposite gender) that was never paired with the UCS and presented intermixed with the CS+. Contexts were defined by screen color (black in one context, changing between red and orange in the other) and auditory input (two sounds, changing synchronously with the color of the screen in the red–orange context only). These marked physical differences between the two contexts were intended to facilitate context discrimination. On day 2, subjects were tested for CS+-induced recall of fear and extinction memories in both contexts, each context being presented 16 times in alternating order. Recall of fear memory in context A on day 2 was facilitated by additionally presenting one unpaired shock at the beginning of each context A block, thus again firmly associating context A with the UCS. The task was a speeded gender decision task in response to the face stimuli. Gender of faces, conditioning, and extinction contexts and the order of those contexts on day 2 were counterbalanced across subjects. Lightning bolt, Electric shock.

Successful discrimination learning and context-dependent recall. a, SCR. Larger SCRs to the CS+ versus CS− during fear conditioning in context A compared with the extinction context B on day 1 indicate learning of the CS+–UCS contingency (fear memory) in context A and of the CS+−noUCS contingency (extinction memory) in context B on day 1 (left). b, RTs. Slower RTs to the CS+ versus CS− in the conditioning context A compared with the extinction context B on day 2 indicate recall of fear memory in context A and recall of extinction memory in B on day 2 (right). Scale: z scores (unit, SDs). z scores were used instead of raw values (micro-ohms, seconds) to account for interindividual differences. *p < 0.05, one-tailed.

Recall of fear memory. Activations associated with recall of fear memory on day 2. a, Right (R) posterior hippocampus [MNI coordinates (38, −32, −12)]. b, Left (L) amygdala [coordinates (−28, −2, −32)]. Images show group-level estimates for the contrast (CS+ > CS−)_A, modulated by RT, display threshold p ≤ 0.01. Activations superimposed on mean structural image, masked for hippocampus and amygdala. Insets, Group estimates for CS+ > CS− contrasts in both contexts.

Recall of extinction memory. a, Activations associated with context-dependent recall of extinction memory on day 2. Images show contrast (CS+ > CS−)_B > (CS+ > CS−)_A, display threshold p ≤ 0.001, masked for VMPFC and hippocampus. Activations are superimposed on mean structural image. Insets, Group-level estimates for CS+ > CS− contrasts in both contexts. b,CS+-evoked left VMPFC activity is positively correlated with CS+-evoked left anterior hippocampus activity in the extinction context only. Left, Correlation in VMPFC in the extinction context, display threshold p ≤ 0.001, masked by VMPFC activation in a. Right, An extinction context-specific correlation is apparent from the subject-specific estimates for the two CS+ > CS− contrasts (black: conditioning context, r = 0.212, p = 0.207, one-tailed; orange: extinction context, r = 0.715, p = 0.0005, one-tailed). L, Left.