Electrophysiological correlates of associative learning in smokers: a higher-order conditioning experiment

Abstract

Background: Classical conditioning has been suggested to play an important role in the development, maintenance, and relapse of tobacco smoking. Several studies have shown that initially neutral stimuli that are directly paired with smoking are able to elicit conditioned responses. However, there have been few human studies that demonstrate the contribution of higher-order conditioning to smoking addiction, although it is assumed that higher-order conditioning predominates learning in the outside world. In the present study a higher-order conditioning task was designed in which brain responses of smokers and non-smokers were conditioned by pairing smoking-related and neutral stimuli (CS1smoke and CS1neutral) with two geometrical figures (CS2smoke and CS2neutral). ERPs were recorded to all CSs.

Results: Data showed that the geometrical figure that was paired with smoking stimuli elicited significantly larger P2 and P3 waves than the geometrical figure that was paired with neutral stimuli. During the first half of the experiment this effect was only present in smokers whereas non-smokers displayed no significant differences between both stimuli, indicating that neutral cues paired with motivationally relevant smoking-related stimuli gain more motivational significance even though they were never paired directly with smoking. These conclusions are underscored by self-reported evidence of enhanced second-order conditioning in smokers.

Conclusions: It can be concluded that smokers show associative learning for higher-order smoking-related stimuli. The present study directly shows the contribution of higher-order conditioning to smoking addiction and is the first to reveal its electrophysiological correlates. Although results are preliminary, they may help in understanding the etiology of smoking addiction and its persistence.

Figure 1

Schematic representation of the experimental paradigm.

Figure 2

Smokers' (upper) and non-smokers' ERPs (lower) in response to CS1_smoke and CS1_neutral in Block1 and Block 2. Current Source Density (CSD) maps represent differences in activity between CS1_smoke and CS1_neutral in the 300-800 ms timeframe (P3).

Figure 3

Smokers' (upper) and non-smokers' ERPs (lower) in response to CS2_smoke and CS2_neutral in Block 1 and Block 2. Current Source Density (CSD) maps represent differences in activity between CS2_smoke and CS2_neutral in the 280-500 ms timeframe (P3) and the 200-280 ms timeframe (P2).

Figure 4

Mean P3 amplitudes for smokers and non-smokers per Block and CS1.

Figure 5

Mean P3 amplitude for smokers and non-smokers per Block and CS2.

Figure 6

Mean P2 amplitude for smokers and non-smokers per Block and CS2.

Figure 7

Smokers' and non-smokers' mean self-reported arousal and valence ratings and smokers' mean self-reported craving ratings of the CS2_smoke and CS2_neutral measured with a 10 cm Visual Analogue Scale (VAS). Error bars represent standard deviations.