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.

Modeling Causal Relationship Between Brain Regions Within the Drug-Cue Processing Network in Chronic Cocaine Smokers

“…In cocaine users, it may have indicated reward/motivational processing related to their chronic cocaine use, whereas in controls it may have indicated their effort to learn and retrieve any information relating to the novel cocaine stimuli (Cohn et al, 2010). Our finding of the causal influence of orbital frontal cortex on ventral striatum extends the study by Wilcox et al (2011), which showed an increased restingstate functional connectivity between orbital frontal cortex and ventral striatum in cocaine users compared with controls.…”

“…Also, Wilcox et al (2011) showed an increased restingstate functional connectivity between drug-cue processing regions such as orbital frontal cortex and ventral striatum in cocaine users. Based on these studies, we hypothesized that the cocaine users compared with controls would show a different causal interaction pattern among the ROIs of the drug-cue processing network during cocaine-cue exposure.…”

“…According to Cisler et al (2013), cocaine users had an enhanced functional connectivity of the insular cortex with prefrontal networks compared with controls. Wilcox et al (2011) showed that cocaine users had an increased activation in comparison to controls in dorsolateral prefrontal cortex in response to cocaine cues but not to neutral cues. Also, cocaine users exhibited increased resting-state functional connectivity between cue processing regions such as orbital frontal cortex and ventral striatum.…”

“…A few fMRI studies involving cocaine users have used functional connectivity analysis, which involves correlating activity in spatially remote brain regions (Friston, 1995a), but the results are mixed. Relative to controls, cocaine users have shown enhanced as well as reduced functional connectivity between brain areas during resting state (Cisler et al, 2013;Gu et al, 2010;Wilcox et al, 2011), as well as during an attention and a motor task (Hanlon et al, 2011;Tomasi et al, 2010). According to Cisler et al (2013), cocaine users had an enhanced functional connectivity of the insular cortex with prefrontal networks compared with controls.…”

Psycho-Behavioral Spiral of Disturbances in Prosocial Behavior, Stress Response, and Self-Regulation inSubstance-Related and Addictive Disorders

“…Chronic use of cocaine, opioids or heroin leads to a decrease in the linkage between the amygdala and VMPFC [46,47,48]. On the other hand, the results of several fMRI studies indicate that resting-state overconnectivity between the NAc and VMPFC occurs in pathological gamblers and chronic users of cocaine or heroin [49,50,51]. Moreover, it has been reported that hypoactivity of the NAc-VMPFC pathway is induced by a cocaine cue in chronic cocaine users [50].…”