Prelude to Passion: Limbic Activation by “Unseen” Drug and Sexual Cues

Abstract

BackgroundThe human brain responds to recognizable signals for sex and for rewarding drugs of abuse by activation of limbic reward circuitry. Does the brain respond in similar way to such reward signals even when they are “unseen”, i.e., presented in a way that prevents their conscious recognition? Can the brain response to “unseen” reward cues predict the future affective response to recognizable versions of such cues, revealing a link between affective/motivational processes inside and outside awareness?Methodology/Principal FindingsWe exploited the fast temporal resolution of event-related functional magnetic resonance imaging (fMRI) to test the brain response to “unseen” (backward-masked) cocaine, sexual, aversive and neutral cues of 33 milliseconds duration in male cocaine patients (n = 22). Two days after scanning, the affective valence for visible versions of each cue type was determined using an affective bias (priming) task. We demonstrate, for the first time, limbic brain activation by “unseen” drug and sexual cues of only 33 msec duration. Importantly, increased activity in an large interconnected ventral pallidum/amygdala cluster to the “unseen” cocaine cues strongly predicted future positive affect to visible versions of the same cues in subsequent off-magnet testing, pointing both to the functional significance of the rapid brain response, and to shared brain substrates for appetitive motivation within and outside awareness.Conclusions/SignificanceThese findings represent the first evidence that brain reward circuitry responds to drug and sexual cues presented outside awareness. The results underscore the sensitivity of the brain to “unseen” reward signals and may represent the brain's primordial signature for desire. The limbic brain response to reward cues outside awareness may represent a potential vulnerability in disorders (e.g., the addictions) for whom poorly-controlled appetitive motivation is a central feature.

Acquisition of Responses to a Methamphetamine-Associated Cue in Healthy Humans: Self-Report, Behavioral, and Psychophysiological Measures

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Mobilization of Medial and Lateral Frontal-Striatal Circuits in Cocaine Users and Controls: An Interleaved TMS/BOLD Functional Connectivity Study

“…Cocaine users typically have an attenuated prefrontal cortex response to tasks that require mobilization of both the limbic circuit (eg natural rewards) (Asensio et al, 2010a;Cheetham et al, 2010;Kelley and Berridge, 2002). One of the only things which reliably activates the MPFC in this population appears to be drug cues (Childress et al, 2008;Goldstein et al, 2007;Hester and Garavan, 2009;Prisciandaro et al, 2013).…”

Dopamine Modulates Reward System Activity During Subconscious Processing of Sexual Stimuli

“…Implicit reward processes can be assessed, and are of great informational value as they are unbiased by cognitive incentive, that is, subjective liking or disliking, desires, shame, positive, or negative outcome evaluations, which is especially relevant when presenting stimuli with sexual content. Typically, the reward system already responds to potentially rewarding sex-and drug-related stimuli that are presented outside awareness (Childress et al, 2008;Gillath and Canterberry, 2011). However, it is unknown whether DA modulates implicit motivation for sexual reward, at its earliest onset, outside awareness.…”