Abstract
Elevated drug-cue elicited brain activity is one of the most widely cited, transdiagnostically relevant traits of substance dependent populations. These populations, however, are typically studied in isolation. The goal of this study was to prospectively investigate the spatial topography of drug-cue reactivity in a large set of individuals dependent on either cocaine, alcohol, or nicotine. Functional MRI data was acquired from 156 substance dependent individuals (55 cocaine, 53 alcohol, and 48 nicotine) as they performed a standardized drug-cue exposure task. Clusters of significant activation to drug-cues relative to neutral cues (‘hot spots’) were isolated for each individual. K-means clustering was used to classify the spatial topography of the hotspots in the data set. The percentage of hotspots that would be reached at several distances (2–5 cm) of transcranial magnetic stimulation (TMS) were calculated. One hundred and three participants had at least one cluster of significant frontal cortex activity (66%). K-means revealed 3 distinct clusters within the medial prefrontal cortex (MPFC), left inferior frontal gyrus/insula, right premotor cortex. For the group as a whole (and for alcohol users and nicotine users independently), medial prefrontal cortex (BA 10) was the location of the greatest number of hotspots. The frontal pole was cortical location closest to the largest percentage of hotspots. While there is individual variability in the location of the cue-elicited ‘hot spot’ these data demonstrate that elevated BOLD signal to drug cues in the MPFC may be a transdiagnostic endophenotype of addiction which may also be a fruitful neuromodulation target.
Highlights
Elevated drug-cue elicited brain activity is one of the most widely cited, transdiagnostically relevant traits of current substance dependent populations
We evaluated the percentage of hotspots that would be reached at several distances (2–5 cm) given that the penetration characteristics of repetitive TMS (rTMS) are dependent on coil size
K-means clustering for the full complement of points revealed an optimal solution at 3 clusters which were centered in the medial prefrontal cortex (MPFC)/ACC cortex (Cluster 1: MNI coordinates: 7, 50, 4; 40% of points, Brodmann Areas (BA): 10, 32), left lateral prefrontal cortex (Cluster 2: MNI: −40, 24, 25; 32% of the points, BA: 9,44,45, 46) and right lateral prefrontal cortex (Cluster 3: MNI: 30,18,41; 28% of the points, BA: 8,9) (Fig. 3a)
Summary
Elevated drug-cue elicited brain activity is one of the most widely cited, transdiagnostically relevant traits of current substance dependent populations. Many studies investigating cue-reactivity in either cocaine, nicotine, or alcohol dependent populations have independently demonstrated that drug-cues evoke elevated activity in the medial prefrontal cortex, anterior cingulate, and insula cortex Most of these studies focus on one substance using class, and it is difficult to distinguish which aspects of cue-reactivity are transdiagnostic biomarkers of the addiction process versus those which are specific to alcohol, cocaine, or nicotine dependence. One challenge for retrospective reviews and meta-analyses is that different research institutions often use different drug-cue reactivity paradigms, Hanlon et al Translational Psychiatry (2018)8:186 have different inclusion/exclusion criteria, and do not analyze all of their data using the same analysis pipeline Even when these variables are controlled, there is a lot of individual variability in the brain response to drug-cues and that there may be drug-class specific patterns of cue-reactivity [5]
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