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 ...

Context Understanding the mechanisms underlying nicotine addiction to develop more effective treatment is a public health priority. Research consistently shows that nicotine transiently improves multiple cognitive functions. However, using nicotine replacement to treat nicotine addiction yields generally inconsistent results. Although this dichotomy is well known, the reasons are unclear. Imaging studies showed that nicotine challenges almost always involve the cingulate cortex, suggesting that this locus may be a key region associated with nicotine addiction and its treatment. Objective To identify cingulate functional circuits that are associated with the severity of nicotine addiction and study how nicotine affects them by means of region-specific resting-state functional magnetic resonance imaging. Design Double-blind, placebo-controlled study. Setting Outpatient clinics. Participants Nineteen healthy smokers. Intervention Single-dose (21- or 35-mg) nicotine patch. Main Outcome Measures Correlation of nicotine addiction severity and cingulate resting-state functional connectivity, and effects of short-term nicotine administration on connectivity strength. Results Clearly separated pathways that correlated with nicotine addiction vs nicotine’s action were found. The severity of nicotine addiction was associated with the strength of dorsal anterior cingulate cortex (dACC)–striatal circuits, which were not modified by nicotine patch administration. In contrast, short-term nicotine administration enhanced cingulate-neocortical functional connectivity patterns, which may play a role in nicotine's cognition-enhancing properties. Conclusions Resting-state dACC-striatum functional connectivity may serve as a circuit-level biomarker for nicotine addiction, and the development of new therapeutic agents aiming to enhance the dACC-striatum functional pathways may be effective for nicotine addiction treatment.

Drug addiction is a chronic, relapsing brain disorder characterized by compulsive drug seeking and taking. As a feature commonly associated with drug addiction, impulsivity is a risk factor for and is worsened by cocaine use.¹ In contrast, compulsive drug use is a cardinal feature of the disease. Both impulsivity and compulsivity are associated with abnormal frontostriatal structures in cocaine users (CUs).² In addition, extensive preclinical literature suggests a critical striatal role in cocaine addiction.^3-9 Within striatum, a progressive change from mostly ventral to more dorsal processing domains occurs concurrent with the gradual development of compulsive drug consumption. For example, following chronic cocaine self-administration, the spatial extent and magnitude of neuronal activity as measured by glucose metabolism expands in an orderly fashion from the ventral striatum (VS) to encompass the dorsal striatum (DS).⁴ Cross-sectional human studies also implicate the striatum in cocaine addiction, as evidenced by striatal activation in response to cocaine administration,^10,11 striatal dopamine changes in response to cocaine cues,¹² and striatal morphometric abnormality in CUs^2,13 and their drug-naive siblings.¹⁴