title: Prelude to passion: limbic activation by "unseen" drug and sexual cues.
abstract: BACKGROUND
  The 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?
  
  
  RESULTS
  We 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
  These 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.
authors.affiliation: Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Anna Rose
authors.initials: AR
authors.lastname: Childress
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Ehrman
authors.forename: Ze
authors.initials: Z
authors.lastname: Wang
authors.forename: Yin
authors.initials: Y
authors.lastname: Li
authors.forename: Nathan
authors.initials: N
authors.lastname: Sciortino
authors.forename: Jonathan
authors.initials: J
authors.lastname: Hakun
authors.forename: William
authors.initials: W
authors.lastname: Jens
authors.forename: Jesse
authors.initials: J
authors.lastname: Suh
authors.forename: John
authors.initials: J
authors.lastname: Listerud
authors.forename: Kathleen
authors.initials: K
authors.lastname: Marquez
authors.forename: Teresa
authors.initials: T
authors.lastname: Franklin
authors.forename: Daniel
authors.initials: D
authors.lastname: Langleben
authors.forename: John
authors.initials: J
authors.lastname: Detre
authors.forename: Charles P
authors.initials: CP
authors.lastname: O'Brien
mesh_terms: D000328:Adult; D003042:Cocaine / Q000008:administration & dosage*; D015331:Cohort Studies; D006801:Humans; D008032:Limbic System / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D012725:Sexual Behavior
chemical_list: D003042:Cocaine