Factors modulating neural reactivity to drug cues in addiction: a survey of human neuroimaging studies

Neurosci Biobehav Rev. 2014 Jan;38:1-16. doi: 10.1016/j.neubiorev.2013.10.013. Epub 2013 Nov 6.


Human neuroimaging studies suggest that neural cue reactivity is strongly associated with indices of drug use, including addiction severity and treatment success. However, little is known about factors that modulate cue reactivity. The goal of this review, in which we survey published fMRI and PET studies on drug cue reactivity in cocaine, alcohol, and tobacco cigarette users, is to highlight major factors that modulate brain reactivity to drug cues. First, we describe cue reactivity paradigms used in neuroimaging research and outline the brain circuits that underlie cue reactivity. We then discuss major factors that have been shown to modulate cue reactivity and review specific evidence as well as outstanding questions related to each factor. Building on previous model-building reviews on the topic, we then outline a simplified model that includes the key modulatory factors and a tentative ranking of their relative impact. We conclude with a discussion of outstanding challenges and future research directions, which can inform future neuroimaging studies as well as the design of treatment and prevention programs.

Keywords: ACC; AMY; AUDIT; Addiction; Addiction severity; Alcohol Use Disorder Identification Test; CER; Craving; Cue reactivity; DA; DLPFC; DLS; DMPFC; DMS; DS; Drug abuse; Drug availability; FG; FG/VC; FTND; Fagerström Test for Nicotine Dependence; Functional magnetic resonance imaging (fMRI); HIPP/PH; IFG; INS; IPC/SPC; ITC; MC; MPFC; Modulation; NAc; OFC; PCC; PET; PFC; PMC; Positron emission tomography (PET); ROI; Regulation; SC; SMA; SN; Sensory modality; Stress; THAL; Treatment status; Treatment success; VLPFC; VMPFC; VS; VTA; Withdrawal; amygdala; anterior cingulate cortex; cerebellum; dopamine; dorsal striatum; dorsolateral prefrontal cortex; dorsolateral striatum; dorsomedial prefrontal cortex; dorsomedial striatum; fMRI; functional magnetic resonance imaging; fusiform gyrus; fusiform gyrus/visual cortex; hippocampus/parahippocampal gyrus; inferior frontal gyrus; inferior temporal cortex; inferior/superior parietal cortex; insula; medial prefrontal cortex; motor cortex; nucleus accumbens; orbitofrontal cortex; pMTG; positron emission tomography; posterior cingulate cortex; posterior middle temporal gyrus; prefrontal cortex; premotor cortex; region of interest; somatosensory cortex; substantia nigra; supplementary motor area; thalamus; ventral striatum; ventral tegmental area; ventrolateral prefrontal cortex; ventromedial prefrontal cortex.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Behavior, Addictive / physiopathology*
  • Behavior, Addictive / therapy
  • Brain / physiopathology*
  • Brain Mapping*
  • Cues*
  • Humans
  • Models, Neurological
  • Substance-Related Disorders / physiopathology*
  • Substance-Related Disorders / therapy