Aversive learning enhances perceptual and cortical discrimination of indiscriminable odor cues

Abstract

Learning to associate sensory cues with threats is critical for minimizing aversive experience. The ecological benefit of associative learning relies on accurate perception of predictive cues, but how aversive learning enhances perceptual acuity of sensory signals, particularly in humans, is unclear. We combined multivariate functional magnetic resonance imaging with olfactory psychophysics to show that initially indistinguishable odor enantiomers (mirror-image molecules) become discriminable after aversive conditioning, paralleling the spatial divergence of ensemble activity patterns in primary olfactory (piriform) cortex. Our findings indicate that aversive learning induces piriform plasticity with corresponding gains in odor enantiomer discrimination, underscoring the capacity of fear conditioning to update perceptual representation of predictive cues, over and above its well-recognized role in the acquisition of conditioned responses. That completely indiscriminable sensations can be transformed into discriminable percepts further accentuates the potency of associative learning to enhance sensory cue perception and support adaptive behavior.

Fig 1

Experimental paradigm. (A) Chemical structures of the enantiomer pairs. (B) Learning task. Odorants included: a target CS+ (tgCS+) destined for aversive conditioning, its chiral counterpart (chCS+), a non-conditioned control (CS−), and its chiral counterpart (chCS−). A baseline condition comprised odorless air. Stimuli were delivered during pre-conditioning, conditioning, and post-conditioning sessions. During conditioning, tgCS+ presentation co-terminated with electric shock (the US). During post-conditioning, the US was presented with tgCS+ on 4/19 trials to prevent extinction. On each trial participants indicated whether odor was present or absent (marked by *). SCR and respirations were continuously recorded.

Fig. 2

Parallel enhancement of perceptual and neural discrimination after aversive learning. (A) Odor discrimination accuracy was at chance (dashed line) for CS+ and CS− pairs before conditioning, but selectively improved for the CS+ pair after conditioning. Error bars, ± s.e.m. (B) Spatial patterns of fMRI activity in posterior piriform cortex between tgCS+ and chCS+ were highly correlated pre-conditioning, but became more distinct (less correlated) after conditioning, relative to the CS− pair. (C) Learning-induced effects on voxel-wise spatial activity in OFC (left) and anterior piriform cortex (right) indicated that post-conditioning patterns became more correlated (though not significantly) for both CS+ and CS− pairs.

Fig. 3

Spatial maps of posterior piriform activity from one subject. Condition-specific spatial patterns (left two columns) for the CS+ pair (A), but not the CS− pair (B), diverged following conditioning. Difference maps between odorant pairs (right column) highlight the selective differentiation within the CS+ pair at post-conditioning. Each square in the grid represents fMRI signal intensity from a different piriform voxel (n, 86 voxels), arranged in columns from top left to bottom right, in ascending order of signal intensity for tgCS+ in the pre-conditioning phase.

Fig. 4

Effects of aversive olfactory conditioning. (A) SCR significantly increased for tgCS+ at post- vs. pre-conditioning, when compared to CS− stimuli (p = 0.05; Wilcoxon test, two-tailed). (B) During conditioning, tgCS+-evoked activity in amygdala exhibited significant time-dependent response decline, relative to the CS− pair. Activations superimposed on coronal T1-weighted scans (display threshold, p < 0.001). (C) From pre- to post-conditioning, bilateral OFC showed enhanced responses to tgCS+ relative to CS− (axial T1 section; threshold, p < 0.005). (D) Plots of percent signal change for peak activity in left OFC are shown for each condition.