Enhanced cue reactivity and fronto-striatal functional connectivity in cocaine use disorders

Abstract

Chronic cocaine use is associated with enhanced cue reactivity to drug stimuli. However, it may also alter functional connectivity (fcMRI) in regions involved in processing drug stimuli. Our aims were to evaluate the neural regions involved in subjective craving and how fcMRI may be altered in chronic cocaine users. Fourteen patients with a confirmed diagnosis of cocaine abuse or dependence (CCA) and 16 gender, age, and education-matched healthy controls (HC) completed a cue reactivity task and a resting state scan while undergoing functional magnetic resonance imaging. CCA showed increased activation compared to HC in left dorsolateral prefrontal and bilateral occipital cortex in response to cocaine cues but not to appetitive control stimuli. Moreover, CCA also showed increased activation within the orbital frontal cortex (OFC) for cocaine cues relative to the appetitive stimuli during a hierarchical regression analysis. A negative association between subjective craving and activity in medial posterior cingulate gyrus (PCC) was also observed for CCA. CCA exhibited increased resting state correlation (positive) between cue-processing seed regions (OFC and ventral striatum), and negative connectivity between cue-processing regions and PCC/precuneus. These alterations in fcMRI may partially explain the neural basis of increased drug cue salience in CCA.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Figures

Figure 1

This figure depicts the regions exhibiting differences in activation between chronic cocaine abuser (CCA) and healthy control (HC) groups during presentation of cocaine cues. Significant clusters included the left dorsolateral prefrontal cortex (DLPFC) and left occipital cortex (OCC). Warm colors indicate greater activation for CCA compared to HC (red: .001 p ≤ .005; yellow: p ≤ .001). Axial (z) slice location is provided according to the Talairach atlas (L= left and R = right). Bar graphs present percent signal change (PSC) values for each cluster (red bars = CCA, blue bars = HC).

Figure 2

This figure presents the regions exhibiting unique variance associated with the cocaine videos in the hierarchical regression analysis for chronic cocaine abuser (CCA; Panel A) and healthy control (HC; Panel B) groups. Cocaine videos elicited activation (warm colors; red: .001 p ≤ .005, yellow: p ≤ .001) within the frontal craving network areas for CCA, including bilateral orbital frontal cortex (OFC) and dorsolateral prefrontal cortex (DLPFC), with minimal deactivation of the default-mode network. In contrast, deactivation (cool colors; blue: .001 < p ≤ .005, cyan: p ≤ .001) of the default-mode network was prominent for HC and included the anterior cingulate gyrus (ACC) and posterior cingulate gyrus (PCC). Axial (z) and sagittal (x) slice locations are provided according to the Talairach atlas (L= left and R = right).

Figure 3

This figure presents regions showing differential functional connectivity for chronic cocaine abusers (CCA; red) and healthy controls (HC; blue) based on seeds in the ventral striatum (VS). Panel A presents increased positive correlations between the left (L) VS and right orbital frontal cortex (OFC) for CCA. Panel B presents regions showing increased anti-correlations with the right (R) VS for CCA, including the middle temporal gyrus (MTG) and precuneus (PRC), which were also observed for several other seeds (see Table 2). Bar graphs indicate mean z-score within these clusters for CCA (red bars) and healthy control (blue bars) groups. Axial (z) and sagittal (x) slice locations are provided according to the Talairach atlas (L= left and R = right).