Cue-Induced Cocaine Craving: Neuroanatomical Specificity for Drug Users and Drug Stimuli

Abstract

Objective: Cocaine-related cues have been hypothesized to perpetuate drug abuse by inducing a craving response that prompts drug-seeking behavior. However, the mechanisms, underlying neuroanatomy, and specificity of this neuroanatomy are not yet fully understood.Method: To address these issues, experienced cocaine users (N=17) and comparison subjects (N=14) underwent functional magnetic resonance imaging while viewing three separate films that portrayed 1 ) individuals smoking crack cocaine, 2) outdoor nature scenes, and 3) explicit sexual content. Candidate craving sites were identified as those that showed significant activation in the cocaine users when viewing the cocaine film. These sites were then required to show significantly greater activation when contrasted with comparison subjects viewing the cocaine film (population specificity) and cocaine users viewing the nature film (content specificity).Results: Brain regions that satisfied these criteria were largely left lateralized and included the frontal lobe (medial and middle frontal gyri, bilateral inferior frontal gyrus), parietal lobe (bilateral inferior parietal lobule), insula, and limbic lobe (anterior and posterior cingulate gyrus). Of the 13 regions identified as putative craving sites, just three (anterior cingulate, right inferior parietal lobule, and the caudate/ lateral dorsal nucleus) showed significantly greater activation during the cocaine film than during the sex film in the cocaine users, which suggests that cocaine cues activated similar neuroanatomical substrates as naturally evocative stimuli in the cocaine users. Finally, contrary to the effects of the cocaine film, cocaine users showed a smaller response than the comparison subjects to the sex film.Conclusions: These data suggest that cocaine craving is not associated with a dedicated and unique neuroanatomical circuitry; instead, unique to the cocaine user is the ability of learned, drug-related cues to produce brain activation comparable to that seen with nondrug evocative stimuli in healthy comparison subjects.

Post-Error Behavior in Active Cocaine Users: Poor Awareness of Errors in the Presence of Intact Performance Adjustments

“…Research suggests that cue-related cocaine craving involves the activation of a network of cortical regions involved in the engagement of attention, and the subsequent ruminations also involve the fronto-parietal network seen in WM rehearsal (Childress et al, 1999;Garavan et al, 2000;Grant et al, 1996;Kilts et al, 2001;Maas et al, 1998). Although speculative, a link between WM demands, cocaine craving and poor error awareness may help explain why cocaine users selfmonitoring, or insight into their own behavior, is particularly poor during craving for the drug (Miller and Gold, 1994).…”

Beyond common resources: the cortical basis for resolving task interference

“…A difficulty exerting high levels of topdown control might also account for clinical symptoms such as ruminative thoughts. For example, studies with cocaine users suggest that cue-induced ruminative thoughts activate a 'WM-like' network of regions (Bonson et al, 2002;Garavan et al, 2000), and impaired performance on a central executive or WM task has been associated with rumination induction in a sample of patients suffering from major depression (Watkins and Brown, 2002). If ruminative thoughts represent the temporary processing of items in WM, the current research suggests that as these WM demands increase it will take a high level of top-down control to inhibit the attention directed towards them, a capacity showing impairment in both of these groups (Bolla et al, 2000;Tekin and Cummings, 2002).…”

Homers regulate drug-induced neuroplasticity: Implications for addiction

“…Importantly, these abnormalities in PFC activity appear to be common across various drug addictions (incl. cocaine, methamphetamine, alcohol, cannabis, heroin and dissociative anesthetics), as well as across such non-drug addictions as gambling, and correlate with self-reports of "craving" and impairments in self-control in addicted individuals [6,[9][10][11][12][13][14][15][16][17].…”

“…[1][2][3][4]. The vast number of clinical neuroimaging studies conducted on addicted individuals reveal striking abnormalities in prefrontal cortex (PFC) activity, relative to control subjects, that include reduced basal metabolic activity, reduced regional activation upon presentation of cues associated with non-drug primary reinforcers and enhanced metabolic activity upon presentation of drug-associated cues [e.g., [5][6][7][8][9]. Importantly, these abnormalities in PFC activity appear to be common across various drug addictions (incl.…”