Full length articleVisual cortex activation to drug cues: A meta-analysis of functional neuroimaging papers in addiction and substance abuse literature
Introduction
Drug cue-reactivity – the array of psychological, physiological, and behavioral effects elicited by drug-related stimuli – has been utilized for more than two decades in an attempt to understand drug craving and dependence (Rohsenow et al., 1991, Drummond, 2001, Carter and Tiffany, 1999). As of 2014, there were over 100 functional neuroimaging studies that investigated cue-reactivity in a range of drug using populations. These studies have provided substantial knowledge regarding the neural response to drug cues, revealing a common set of brain regions which are now classically considered a part of the network engaged in response to drug cues and craving. These oft-cited brain regions – up-regulated in the presence of visual drug cues – include the medial prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex, insula, and the striatum (Kühn and Gallinat, 2011, Schacht et al., 2013). These established regions are similarly reported in non-human primate studies of drug self-administration (Porrino et al., 2004), and rodent studies of drug reinstatement (McFarland et al., 2003, Dayas et al., 2007).
In addition to frontal and striatal brain regions, human neuroimaging studies of drug cue-reactivity often observe activation in another fundamental brain region that is given much less emphasis—the visual cortex. Although significant drug cue-elicited activity in the occipital cortex is commonly demonstrated and has been found in previous meta-analyses of drug cue-reactivity (Chase et al., 2011, Engelmann et al., 2012, Schacht et al., 2013), it is rarely reported as a primary finding and has historically not been given very much consideration in the context of addiction. More recently however, numerous investigations have described significant drug cue-elicited activity in visual cortex that directly relates to a host of clinical factors such as cigarette craving during 24-h abstinence but not satiety (McClernon et al., 2009), resisting craving for cigarettes (Brody et al., 2007), as well as measures of self-recognition of problematic cocaine use and desire to change (Prisciandaro et al., 2014). Given these associations, and the fact that visual cortex activity specific to drug cues is compatible with emerging literature regarding the role for primary visual cortex in reward processing (Yalachkov et al., 2010, Shuler and Bear, 2006), we suggest that occipital cortex, including primary visual cortex, activation in response to drug cues deserves much more consideration.
To this end, the primary goal of this proof of concept study was to document and localize the involvement of the visual cortex during functional magnetic resonance imaging (fMRI) studies of drug cue-reactivity. Specifically, the aims were to quantify the frequency with which occipital cortex activity is observed across drug classes and, through activation likelihood estimation (ALE; Turkeltaub et al., 2002, Eickhoff et al., 2012), determine the spatial locations in occipital cortex that are most frequently activated.
Section snippets
Inclusion criteria and identification of articles
We conducted a comprehensive PubMed electronic database search of all English language, addiction-related studies published by August, 2013 that assessed the neural response to drug-related cues using fMRI. Keywords for the imaging component were “imaging”, “MRI”, and “BOLD”. For the addiction component we searched “addict*”, “drug”, “abuse”, as well as individual classes/types of drugs including “nicotine”, “smok*”, “cocaine”, “stimulant”, “methamphetamine”, “alcohol*”, “opiate”, “heroin”,
Visual cortex activity during cue-induced craving: descriptive analyses
Of the 55 studies that used fMRI and whole-brain analyses to examine drug-related visual cues, 50 (91%) reported significant activity in the occipital lobe (primary and secondary visual cortices) during cue exposure. This drug-cued activity in occipital cortex was observed across multiple drug classes (alcohol, cocaine, marijuana, tobacco; Table 1) and there was no significant difference in frequency between the drug classes. Among the 28 studies that reported detailed results from a whole
Discussion
Drug cue-reactivity is one of the most common paradigms employed in human substance abuse literature, largely because drug cue-induced craving is one of the most robust factors that lead to continued use and relapse across substances. Our discussions on treatable-targets for addiction typically focus on the frontal and striatal areas that are activated by drug-related cues. The results of the present investigation however highlight the importance of another often overlooked brain region that is
Role of funding source
Funding for this study was provided by NIDA Grant no. K01 DA027756 (CH) and NIMH Grant no. K01 MH090548 (BC); the NIDA and NIMH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.
Contributors
CH and BC conceived and developed the study. CH, BC, MC, TN, and LD all contributed to the literature searches, data analysis, manuscript composition and illustrations. CH wrote the first draft of the manuscript. All authors have approved the final manuscript.
Conflict of interest statement
All authors declare that they have no conflicts of interest.
Acknowledgment
This study was funded by NIH, Grant nos. K01 DA027756; K01 MH090548.
References (63)
- et al.
Dopaminergic reward signals selectively decrease fMRI activity in primate visual cortex
Neuron
(2013) - et al.
Internal reliability of measures of substance-related cognitive bias
Drug Alcohol Depend.
(2012) - et al.
Neural substrates of resisting craving during cigarette cue exposure
Biol. Psychiatry
(2007) - et al.
The neural basis of drug stimulus processing and craving: an activation likelihood estimation meta-analysis
Biol. Psychiatry
(2011) - et al.
Alcohol attentional bias as a predictor of alcohol abusers’ treatment outcome
Drug Alcohol Depend.
(2002) - et al.
An acute psychosocial stress enhances the neural response to smoking cues
Brain Res.
(2009) - et al.
Distinct patterns of neural activation associated with ethanol seeking: effects of naltrexone
Biol. Psychiatry
(2007) - et al.
Activation likelihood estimation meta-analysis revisited
NeuroImage
(2012) - et al.
Neural substrates of smoking cue reactivity: a meta-analysis of fMRI studies
NeuroImage
(2012) - et al.
Attentional bias in addictive behaviors: a review of its development, causes, and consequences
Drug Alcohol Depend.
(2008)
Selective processing of cannabis cues in regular cannabis users
Drug Alcohol Depend.
Brain reactivity to smoking cues prior to smoking cessation predicts ability to maintain tobacco abstinence
Biol. Psychiatry
Association between CHRNA5 genetic variation at rs16969968 and brain reactivity to smoking images in nicotine dependent women
Drug Alcohol Depend.
Individual differences in smoking-related cue reactivity in smokers: an eye-tracking and fMRI study
Prog. Neuropsychopharmacol. Biol. Psychiatry
A functional magnetic resonance imaging (FMRI) study of cue-induced smoking craving in virtual environments
Appl. Psychophysiol. Biofeedback
Craving correlates with mesolimbic responses to heroin-related cues in short-term abstinence from heroin: an event-related fMRI study
Brain Res.
Acute effects of sublingual buprenorphine on brain responses to heroin-related cues in early-abstinent heroin addicts: an uncontrolled trial
Neuroscience
Persistence of attentional bias toward alcohol-related stimuli in intoxicated social drinkers
Drug Alcohol Depend.
The neural basis of drug craving: an incentive-sensitization theory of addiction
Brain Res. Rev.
Smoking-related cue-induced brain activation in adolescent light smokers
J. Adolesc. Health
Meta-analysis of the functional neuroanatomy of single-word reading: method and validation
NeuroImage
Effects of cue-exposure treatment on neural cue reactivity in alcohol dependence: a randomized trial
Biol. Psychiatry
Development of alcohol-associated cues and cue-induced brain activation in alcoholics
Eur. Psychiatry
Dysfunction of reward processing correlates with alcohol craving in detoxified alcoholics
NeuroImage
Sensory and motor aspects of addiction
Behav. Brain Res.
Neurobiological substrates of cue-elicited craving and anhedonia in recently abstinent opioid-dependent males
Drug Alcohol Depend.
Attentional bias training and cue reactivity in cigarette smokers
Addiction
Alcohol-associated stimuli activate the ventral striatum in abstinent alcoholics
J. Neural Transm.
Meta-analysis of cue-reactivity in addiction research
Addiction
Effects of acute nicotine abstinence on cue-elicited ventral striatum/nucleus accumbens activation in female cigarette smokers: a functional magnetic resonance imaging study
Brain Imag. Behav.
Theories of drug craving, ancient and modern
Addiction
Cited by (68)
Effects of acute exercise on craving and cortical hemodynamics under drug-cue exposure in MA-dependent individuals
2022, Neuroscience LettersCitation Excerpt :At this point there is no approved pharmacological treatments for MA addiction [1]. The success of any other treatment is invariably in jeopardy when abstaining patients experience powerful cravings that are triggered by drug-related cues similar to the cravings for other addictive drugs, such as methamphetamine, nicotine or heroin [2–4]. A growing body of studies have been investigated the effect of acute physical exercise on the control of MA cravings [5–9].
Resting state functional connectivity in alcohol users and co-users of other substances
2022, Psychiatry Research - NeuroimagingThe cue-reactivity paradigm: An ensemble of networks driving attention and cognition when viewing drug and natural reward-related stimuli
2021, Neuroscience and Biobehavioral ReviewsCitation Excerpt :Noteworthy, we observed activity convergence in brain regions linked with visual perceptual processes when considering appetitive (vs. control) cues, suggesting that learned associations between predictive stimuli and rewards modulate top-down attention. As evidenced by prior work, the representation of basic visual features (e.g., local contrast, location, spatial frequency) can be modulated by top-down attention and learned associations between stimuli and reward (Hanlon et al., 2014; Serences, 2008). Pairing visual stimuli with a reward improves stimulus detection (Engelmann et al., 2009; Engelmann and Pessoa, 2007), reduces response times (Nomoto et al., 2010; O’Doherty et al., 2004), and increases accuracy (Seitz et al., 2009).