Elsevier

Drug and Alcohol Dependence

Volume 143, 1 October 2014, Pages 206-212
Drug and Alcohol Dependence

Full length article
Visual cortex activation to drug cues: A meta-analysis of functional neuroimaging papers in addiction and substance abuse literature

https://doi.org/10.1016/j.drugalcdep.2014.07.028Get rights and content

Highlights

  • The majority of fMRI drug cue-reactivity studies report effects in visual areas.

  • Drug cue-elicited BOLD activation is found in primary and secondary visual areas.

  • Attentional bias and/or reward processing may relate to drug-cued visual activation.

Abstract

Background

Although the visual cortex does not typically receive much attention in addiction literature, neuroimaging studies often report significant activity in visual areas when drug users are exposed to drug cues. The purpose of this meta-analysis was to investigate the frequency with which occipital cortex activity is observed during drug cue exposure and to determine its spatial distribution.

Methods

A comprehensive literature search was performed of human functional neuroimaging studies of drug cue-reactivity. Fifty-five studies were used to determine the frequency with which clusters of significant visual cortex activity during visual drug cues versus non-drug cues were reported. The spatial distribution of visual cortex activations was determined via activation likelihood estimation (ALE; FDR corrected, p < 0.01) in a subset of these studies (n = 24).

Results

Eighty-six percent of studies that reported fMRI results for drug versus neutral visual cues within a substance-dependent group showed significant drug-elicited activity in the visual cortex. ALE revealed clusters in the left secondary visual cortex (BA 19) and clusters in the primary visual cortex (BA 17) that were consistently activated by drug cues.

Conclusions

These data demonstrate that the visual cortex, often overlooked in our discussions of the neural circuitry of addiction, consistently discriminates drug cues from neutral cues in substance dependent populations. While it remains unclear whether drug cue-elicited activation in occipital cortex is related to the rewarding properties of the drug and/or attentional mechanisms, these data support further exploration.

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.

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