Environmental cues previously paired with drug-related behaviors are potent triggers of drug seeking and relapse. The Pavlovian-to-instrumental transfer (PIT) effect, referring to the invigoration of ongoing goal-seeking behavior by previously reinforced cues, is suggested to model important aspects of drug seeking and relapse. While extensively studied in animals, the neural mechanisms of PIT in addictive humans remain largely unknown. A key component in maintaining goal-directed behaviors are covert desires, urges, and wishes pertinent to obtaining rewards. Using a unique real-time fMRI experimental design, we recently published a study that explored the neural mechanisms underlying the influence Pavlovian cues exert on a reward- associated imagery task in healthy individuals. In this study, participants first learned an instrumental association between motor imagery and monetary reward by receiving monetary rewards for successful activation in motor cortex during a motor imagery task, using a real-time fMRI set-up. Next, conditioned stimuli were associated with either monetary gain or loss using a partial reinforcement Pavlovian learning protocol. Finally, in the transfer test, brain activity was assessed during motor imagery in the presence of the gain and loss related cues, allowing for the assessment of a transfer PIT effect. We reported that cues with motivational salience had an invigorating effect on brain activation in regions involved in value representation and motor imagery. Moreover, we found that during motor imagery, these networks co-activated to higher degree upon the presentation of appetitive vs. aversive cues. The current proposal aims at extending these findings to addictive population by employing two versions of the described experimental design in individuals with different degrees of nicotine dependence. First, we propose to examine the exact same protocol on nicotine-dependent individuals to test the relation between substance dependency and motivational effects on the neural correlates of mental imagery. Second, we wish to study how Pavlovian cues associated with either smoking- related or neutral images affect smoking-related imagery processes in nicotine-dependent individuals. The suggested proposal is thus designed to unravel the neural mechanisms of covert processes preceding actual behavior in human addictive populations, potentially promoting treatment development for addictive behavior and relapse prevention.
The mere presence of cues associated with reward can invigorate goal-directed behavior, an effect known as Pavlovian-to-Instrumental Transfer (PIT). The PIT effect is assumed to play a major role in addiction and drug relapse, by potentiating cue-induced reinstatement of drug- seeking behavior. Here we propose to use a variation of the PIT paradigm designed to examine the effects that motivational cues exert on covert imagery processes in nicotine-dependent humans, by thus elucidating the neural mechanisms mediating cue-induced thoughts pertaining to drug seeking.
| Reddan, Marianne Cumella; Wager, Tor Dessart; Schiller, Daniela (2018) Attenuating Neural Threat Expression with Imagination. Neuron 100:994-1005.e4 |
