Cue-Induced Brain Activity Changes and Relapse in Cocaine-Dependent Patients

Abstract

This study used functional magnetic resonance imaging (fMRI) to examine the association between brain activation during exposure to cocaine-related cues and relapse to drug use in cocaine-dependent (CD) patients. We imaged 17 CD subjects during a 2-week in-patient stay. The subjects then entered a 10-week outpatient placebo-controlled, double-blind randomized clinical trial where urine toxicologies were assessed three times weekly to calculate the treatment effectiveness score (TES). Worse TES correlated with BOLD activation in the left precentral, superior temporal, and posterior cingulate cortices (PCC), and right middle temporal and lingual cortices (R40.65; Po0.005). The left PCC activation also distinguished eight nonrelapsers (TES above mean and completed treatment) from nine relapsers. Cocaine-free urines were significantly greater in the nonrelapsers (92%) than in the relapsers (66%), who also remained in treatment for an average of only 3.2 weeks. Self-reports of craving during fMRI did not differ between nonrelapsers and relapsers and did not correlate with TES. Relapse to cocaine abuse was associated with increased activation in the sensory association cortex, the motor cortex, and PCC while viewing images of cocaine-related cues. These results suggest that relapse to cocaine abuse is associated with increased brain activation to cocaine cues in sensory, motor, and cognitive-emotional processing areas. This physiological activation was a better predictor of relapse than subjective reports of craving, and may be a useful target for treatment development.

The Effects of Pharmacological Opioid Blockade on Neural Measures of Drug Cue-Reactivity in Humans

“…fMRI cue-reactivity paradigms represent an ideal platform to probe the involvement of neurobiological pathways subserving the incentive salience system in addiction (Courtney et al, 2016;Ray et al, in press). Given that BOLD measures of drug cue-reactivity have been shown to predict relapse propensity in treatment seeking patients (eg, Beck et al, 2012;Kosten et al, 2006;Schacht et al, 2013b), the investigation of neurochemical systems that alter BOLD measures of cue-reactivity has the potential to improve real-world clinical outcomes in addiction.…”

Altered Neural Cholinergic Receptor Systems in Cocaine-Addicted Subjects

“…Nevertheless, a number of earlier investigators have identified alterations in the MTG in cocaine-addicted populations under a variety of paradigms. Risinger et al (2005) found significant correlations between cocaine-induced anxiety and MTG activation, Paulus et al (2005) reported a correlation between relapse and MTG activation in methamphetamine-dependent subjects, and Kosten et al (2006) noted a relationship between MTG activation during cue-induced craving and treatment outcome. Thus, the MTG may have functions relevant to cocaine addiction distinct from its function in declarative memory.…”

Persistent Alterations in Cognitive Function and Prefrontal Dopamine D2 Receptors Following Extended, but Not Limited, Access to Self-Administered Cocaine

“…Many of these cognitive functions are known to require the prefrontal cortex, and structural and functional imaging studies suggest that indeed, prefrontal cortical function is impaired in addicts (Volkow et al, 1988(Volkow et al, , 1991GoldmanRakic, 1995;Robbins, 1996;Bolla et al, 1998Bolla et al, , 2003Bolla et al, , 2004Liu et al, 1998;Ernst et al, 2002;Matochik et al, 2003;Kosten et al, 2006). It is not clear, however, whether these behavioral and neurobiological deficits precede drug use, and thus potentially contribute to the propensity for addiction, or are a consequence of drug use.…”