No abstract

Cocaine dependence is associated with pronounced elevations of negative affect and deficient regulation of negative emotions. We aimed to investigate the neural substrates of negative emotion regulation in cocaine-dependent individuals (CDI), as compared to non-drug-using controls, using functional magnetic resonance imaging (fMRI) during a re-appraisal task. Seventeen CDI abstinent for at least 15 days and without other psychiatric co-morbidities and 18 intelligence quotient-matched non-drug-using controls participated in the study. Participants performed the re-appraisal task during fMRI scanning: they were exposed to 24 blocks of negative affective or neutral pictures that they should Observe (neutral pictures), Maintain (sustain the emotion elicited by negative pictures) or Suppress (regulate the emotion elicited by negative pictures through previously trained re-appraisal techniques). Task-related activations during two conditions of interest (Maintain>Observe and Suppress>Maintain) were analyzed using the general linear model in SPM8 software. We also performed psychophysiological interaction (PPI) seed-based analyses based on one region from each condition: the dorsolateral prefrontal cortex (dlPFC-Maintain>Observe) and the inferior frontal gyrus (IFG-Suppress>Maintain). Results showed that cocaine users had increased right dlPFC and bilateral temporoparietal junction activations during Maintain>Observe, whereas they showed decreased right IFG, posterior cingulate cortex, insula and fusiform gyrus activations during Suppress>Maintain. PPI analyses showed that cocaine users had increased functional coupling between the dlPFC and emotion-related regions during Maintain>Observe, whereas they showed decreased functional coupling between the right IFG and the amygdala during Suppress>Maintain. These findings indicate that CDI have dysfunctional corticolimbic activation and connectivity during negative emotion experience and re-appraisal.

Reduced ventrolateral PFC activation during shifting may constitute a common neural marker across gambling and cocaine addictions. Additional cocaine-related effects relate to a wider pattern of task-related dysregulation, reflected in signal abnormalities in dorsolateral and dmPFC.

Neural biomarkers for the active detrimental effects of cocaine dependence (CD) are lacking. Direct comparisons of brain connectivity in cocaine-targeted networks between CD and behavioural addictions (i.e. pathological gambling, PG) may be informative. This study therefore contrasted the resting-state functional connectivity networks of 20 individuals with CD, 19 individuals with PG and 21 healthy individuals (controls). Study groups were assessed to rule out psychiatric co-morbidities (except alcohol abuse and nicotine dependence) and current substance use or gambling (except PG). We first examined global connectivity differences in the corticolimbic reward network and then utilized seed-based analyses to characterize the connectivity of regions displaying between-group differences. We examined the relationships between seed-based connectivity and trait impulsivity and cocaine severity. CD compared with PG displayed increased global functional connectivity in a large-scale ventral corticostriatal network involving the orbitofrontal cortex, caudate, thalamus and amygdala. Seed-based analyses showed that CD compared with PG exhibited enhanced connectivity between the orbitofrontal and subgenual cingulate cortices and between caudate and lateral prefrontal cortex, which are involved in representing the value of decision-making feedback. CD and PG compared with controls showed overlapping connectivity changes between the orbitofrontal and dorsomedial prefrontal cortices and between amygdala and insula, which are involved in stimulus-outcome learning. Orbitofrontal-subgenual cingulate cortical connectivity correlated with impulsivity and caudate/amygdala connectivity correlated with cocaine severity. We conclude that CD is linked to enhanced connectivity in a large-scale ventral corticostriatal-amygdala network that is relevant to decision making and likely to reflect an active cocaine detrimental effect.

No abstract

Cocaine dependence-related neuroadaptations in the ventral striatum of the brain network are associated with increased impulsivity and higher rate of cocaine relapse.

Cocaine addiction involves persistent deficits to unlearn previously rewarded response options, potentially due to neuroadaptations in learning-sensitive regions. Cocaine-targeted prefrontal systems have been consistently associated with reinforcement learning and reversal deficits, but more recent interspecies research has raised awareness about the contribution of the cerebellum to cocaine addiction and reversal. We aimed at investigating the link between cocaine use, reversal learning and prefrontal, insula and cerebellar gray matter in cocaine-dependent individuals (CDIs) varying on levels of cocaine exposure in comparison with healthy controls (HCs). Twenty CDIs and 21 HCs performed a probabilistic reversal learning task (PRLT) and were subsequently scanned in a 3-Tesla magnetic resonance imaging scanner. In the PRLT, subjects progressively learn to respond to one predominantly reinforced stimulus, and then must learn to respond according to the opposite, previously irrelevant, stimulus-reward pairing. Performance measures were errors after reversal (reversal cost), and probability of maintaining response after errors. Voxel-based morphometry was conducted to investigate the association between gray matter volume in the regions of interest and cocaine use and PRLT performance. Severity of cocaine use correlated with gray matter volume reduction in the left cerebellum (lobule VIII), while greater reversal cost was correlated with gray matter volume reduction in a partially overlapping cluster (lobules VIIb and VIII). Right insula/inferior frontal gyrus correlated with probability of maintaining response after errors. Severity of cocaine use detrimentally impacted reversal learning and cerebellar gray matter.

These preliminary findings demonstrate that decision-making profiles are associated with cocaine relapse. Moreover, combined decision-making and IQ assessments provide optimal predictive values over stimulant relapse, yielding significant opportunities for clinical translation.