Elsevier

Biological Psychiatry

Volume 70, Issue 8, 15 October 2011, Pages 785-793
Biological Psychiatry

Archival Report
The Neural Basis of Drug Stimulus Processing and Craving: An Activation Likelihood Estimation Meta-Analysis

https://doi.org/10.1016/j.biopsych.2011.05.025Get rights and content

Background

The capacity of drug cues to elicit drug-seeking behavior is believed to play a fundamental role in drug dependence; yet the neurofunctional basis of human drug cue-reactivity is not fully understood. We performed a meta-analysis to identify brain regions that are consistently activated by presentation of drug cues. Studies involving treatment-seeking and nontreatment-seeking substance users were contrasted to determine whether there were consistent differences in the neural response to drug cues between these populations. Finally, to assess the neural basis of craving, consistency across studies in brain regions that show correlated activation with craving was assessed.

Methods

Appropriate studies, assessing the effect of drug-related cues or manipulations of drug craving in drug-user populations across the whole brain, were obtained via the PubMed database and literature search. Activation likelihood estimation, a method of quantitative meta-analysis that estimates convergence across experiments by modeling the spatial uncertainty of neuroimaging data, was used to identify consistent regions of activation.

Results

Cue-related activation was observed in the ventral striatum (across both subgroups), amygdala (in the treatment-seeking subgroup and overall), and orbitofrontal cortex (in the nontreatment-seeking subgroup and overall) but not insula cortex. Although a different pattern of frontal and temporal lobe activation between the subgroups was observed, these differences were not significant. Finally, right amygdala and left middle frontal gyrus activity were positively associated with craving.

Conclusions

These results substantiate the key neural substrates underlying reactivity to drug cues and drug craving.

Section snippets

Study Selection Criteria

We imposed criteria for selecting studies from the extant drug cue reactivity literature (over 50 fMRI and PET studies) in an attempt to ensure that selected contrasts were suitable for quantitative meta-analysis and that there was some methodological consistency, despite the variety of approaches employed for cue presentation. A study was selected if it included a contrast of drug cue presentation with a control stimulus or baseline (henceforth control) in a group of drug users. A secondary

Drug and Control Cue Effects

Several regions of significantly convergent findings were observed when coordinates from the drug versus control contrast were analyzed (Figure 1, Table 2): the left amygdala; the bilateral inferior occipital gyrus; the right ventral striatum; and medial regions of the orbitofrontal cortex (OFC), the right inferior frontal gyrus (rIFG), the posterior cingulate, and superior frontal gyrus.

Treatment-Seeking Versus Nontreatment-Seeking Participants

Bilateral amygdala/hippocampus activation was associated with the drug versus control contrast in

Discussion

In the present study, we identified convergence of published neuroimaging results on the processing of drug- or addiction-related cues and craving in populations of drug users with the ALE meta-analysis technique. Consistent with previous studies of Pavlovian conditioning with drug reinforcement, such cues activated the ventral striatum, OFC, and amygdala. Amygdala activity was more consistently observed in studies involving treatment-seeking participants and was also associated with craving,

References (130)

  • S. Caspers et al.

    ALE meta-analysis of action observation and imitation in the human brain

    Neuroimage

    (2010)
  • S.B. Eickhoff et al.

    Assignment of functional activations to probabilistic cytoarchitectonic areas revisited

    Neuroimage

    (2007)
  • S.B. Eickhoff et al.

    A new SPM toolbox for combining probabilistic cytoarchitectonic maps and functional imaging data

    Neuroimage

    (2005)
  • S. Caspers et al.

    The human inferior parietal cortex: Cytoarchitectonic parcellation and interindividual variability

    Neuroimage

    (2006)
  • C. Grefkes et al.

    Human somatosensory area 2: Observer-independent cytoarchitectonic mapping, interindividual variability, and population map

    Neuroimage

    (2001)
  • S. Geyer et al.

    Areas 3a, 3b, and 1 of human primary somatosensory cortex

    Neuroimage

    (1999)
  • S. Geyer et al.

    Areas 3a, 3b, and 1 of human primary somatosensory cortexPart 2. Spatial normalization to standard anatomical space

    Neuroimage

    (2000)
  • P. Voorn et al.

    Putting a spin on the dorsal-ventral divide of the striatum

    Trends Neurosci

    (2004)
  • P. Di Ciano et al.

    Dissociable effects of antagonism of NMDA and AMPA/KA receptors in the nucleus accumbens core and shell on cocaine-seeking behavior

    Neuropsychopharmacology

    (2001)
  • R. Thompson et al.

    Attentional modulation of stimulus representation in human fronto-parietal cortex

    Neuroimage

    (2009)
  • N.D. Volkow et al.

    Cognitive control of drug craving inhibits brain reward regions in cocaine abusers

    Neuroimage

    (2010)
  • J. Peters et al.

    Neural representations of subjective reward value

    Behav Brain Res

    (2010)
  • Y.K. Takahashi et al.

    The orbitofrontal cortex and ventral tegmental area are necessary for learning from unexpected outcomes

    Neuron

    (2009)
  • R. Deichmann et al.

    Optimized EPI for fMRI studies of the orbitofrontal cortex

    Neuroimage

    (2003)
  • A. Verdejo-Garcia et al.

    Impulsivity as a vulnerability marker for substance-use disorders: review of findings from high-risk research, problem gamblers and genetic association studies

    Neurosci Biobehav Rev

    (2008)
  • I.P. Pavlov

    Conditioned Reflexes

    (1927)
  • A. Dickinson et al.

    The role of learning in the operation of motivational systems

  • J. Stewart et al.

    Role of conditioned and unconditioned drug effects in self-administration of opiates and stimulants

    Psychol Rev

    (1984)
  • S.V. Glasner et al.

    The role of Pavlovian cues in alcohol seeking in dependent and nondependent rats

    J Stud Alcohol

    (2005)
  • L. Hogarth et al.

    The role of drug expectancy in the control of human drug seeking

    J Exp Psychol Anim Behav Process

    (2007)
  • L. Hogarth et al.

    The associative basis of cue-elicited drug taking in humans

    Psychopharmacology

    (2010)
  • L. Hogarth et al.

    Parallel goal-directed and habitual control of human drug-seeking: implications for dependence vulnerability [published online ahead of print April 18]

    J Exp Psychol Anim Behav Process

    (2011)
  • M.J. Frank

    Dynamic dopamine modulation in the basal ganglia: A neurocomputational account of cognitive deficits in medicated and nonmedicated Parkinsonism

    J Cogn Neurosci

    (2005)
  • W. Schultz et al.

    A neural substrate of prediction and reward

    Science

    (1997)
  • B.G. Hoebel et al.

    Self-injection of amphetamine directly into the brain

    Psychopharmacology (Berl)

    (1983)
  • F.E. Pontieri et al.

    Intravenous cocaine, morphine, and amphetamine preferentially increase extracellular dopamine in the “shell” as compared with the “core” of the rat nucleus accumbens

    Proc Natl Acad Sci U S A

    (1995)
  • H.W. Chase et al.

    Gambling severity predicts midbrain response to near-miss outcomes

    J Neurosci

    (2010)
  • T.D. Steeves et al.

    Increased striatal dopamine release in Parkinsonian patients with pathological gambling: A [11C] raclopride PET study

    Brain

    (2009)
  • M.J. Koepp et al.

    Evidence for striatal dopamine release during a video game

    Nature

    (1998)
  • B.J. Everitt et al.

    Associative processes in addiction and rewardThe role of amygdala-ventral striatal subsystems

    Ann N Y Acad Sci

    (1999)
  • B.J. Everitt et al.

    Neural mechanisms underlying the vulnerability to develop compulsive drug-seeking habits and addiction

    Philos Trans R Soc Lond B Biol Sci

    (2008)
  • B.W. Balleine et al.

    Human and rodent homologies in action control: Corticostriatal determinants of goal-directed and habitual action

    Neuropsychopharmacology

    (2010)
  • B.L. Carter et al.

    Meta-analysis of cue-reactivity in addiction research

    Addiction

    (1999)
  • L. Hogarth et al.

    Human nicotine conditioning requires explicit contingency knowledge: Is addictive behaviour cognitively mediated?

    Psychopharmacology

    (2006)
  • S.J. Robbins et al.

    Designing studies of drug conditioning in humans

    Psychopharmacology

    (1992)
  • S.J. Wilson et al.

    Prefrontal responses to drug cues: A neurocognitive analysis

    Nat Neurosci

    (2004)
  • J.D. Wallis

    Neuronal mechanisms in prefrontal cortex underlying adaptive choice behavior

  • N.H. Naqvi et al.

    Damage to the insula disrupts addiction to cigarette smoking

    Science

    (2007)
  • A.D. Craig

    How do you feel?Interoception: The sense of the physiological condition of the body

    Nat Rev Neurosci

    (2002)
  • A.R. Damasio

    Descartes' Error: Emotion, Reason, and the Human Brain

    (1994)

    • Cited by (250)

    • Neurometabolic profile of the amygdala in smokers assessed with <sup>1</sup>H-magnetic resonance spectroscopy

      2024, NeuroImage

    • An electroencephalographic signature predicts craving for methamphetamine

      2024, Cell Reports Medicine

    • Sex differences in neural responses to stress and drug cues predicts future drug use in individuals with substance use disorder

      2023, Drug and Alcohol Dependence

    • Inhibition, Shifting and Updating: Inter and intra-domain commonalities and differences from an executive functions activation likelihood estimation meta-analysis

      2022, NeuroImage

    • Neural correlates and potential targets for the contribution of orexin to addiction in cortical and subcortical areas

      2022, Neuropeptides

    • The prediction of resilience to alcohol consumption in youths: Insular and subcallosal cingulate myeloarchitecture

      2022, Psychological Medicine
    View all citing articles on Scopus

    Authors HWC and SBE contributed equally to this work.

    View full text
    Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.