Altered neural response of the appetitive emotional system in cocaine addiction: an fMRI Study

Abstract

Research on addiction suggests that emotional alterations play an essential role in the development, maintenance, relapse and treatment outcome of substance abuse disorders. Although many neuroimaging studies focussed on the neural response to conditioned stimuli, much less is known about the neural response to natural affective stimuli in this pathological population. Previous research has demonstrated an altered emotional experience and autonomic response to emotional stimuli using the International Affective Picture System (IAPS) in drug abusers. Here we aimed, using functional magnetic resonance imaging (fMRI), to study the alterations in the neural responsitivity to pleasant (erotic), unpleasant and neutral IAPS stimuli in cocaine addiction. Thirty-two cocaine-dependent subjects and 26 matched controls completed an fMRI session during the presentation of a set of IAPS pictures as background, while performing a letter discrimination task. Consistent with previous studies, emotional pictures activated an emotional network including amygdala, medial prefrontal cortex, orbitofrontal cortex and occipito-temporal areas in both groups. However, compared with controls, the cocaine group showed a significant hypoactivation of the dorsal and ventral striatum (including the nucleus accumbens), thalamus, parietal cortex and dorso-medial prefrontal cortex (dmPFC) when processing pleasant pictures. The analysis of pleasant versus unpleasant stimuli suggested that between-group differences in the dmPFC and striatal activation may be attributed to arousal processing rather than valence. These results could reflect the neural basis for the reduced ability of cocaine-dependent subjects to experience pleasure by daily natural reinforcers, suggesting that these alterations in the emotion processing may play an important role in drug dependence, treatment and relapse.

Mobilization of Medial and Lateral Frontal-Striatal Circuits in Cocaine Users and Controls: An Interleaved TMS/BOLD Functional Connectivity Study

“…This was motivated by the knowledge that cocaine users appear to have a very low neural response to natural rewards (Cheetham et al, 2010), which typically engage the limbic system (eg the ventral MPFC, ACC, and striatum) (Asensio et al, 2010a;Kelley and Berridge, 2002). In addition, several resting state functional MRI studies have demonstrated lower baseline resting state functional connectivity with the MPFC in cocaine users Gu et al, 2007;Tomasi et al, 2010), though other studies have demonstrated that cocaine users have higher connectivity in these circuits (Camchong et al, 2011;Hu et al, 2015).…”

“…The executive control loop includes projections from the dorsolateral prefrontal cortex (DLPFC) to the dorsal striatum. Cocaine users typically have an attenuated prefrontal cortex response to tasks that require mobilization of both the limbic circuit (eg natural rewards) (Asensio et al, 2010a;Cheetham et al, 2010;Kelley and Berridge, 2002). One of the only things which reliably activates the MPFC in this population appears to be drug cues (Childress et al, 2008;Goldstein et al, 2007;Hester and Garavan, 2009;Prisciandaro et al, 2013).…”

“…While task-based neuroimaging studies that probe frontalstriatal circuitry involved in arousal to non-drug cues typically reveal 'hypofrontality' among cocaine users (Asensio et al, 2010a), recent resting state neuroimaging studies investigating these limbic circuits have revealed higher resting state functional connectivity in mesolimbic frontal-striatal circuits relative to controls (Camchong et al, 2011;Hu et al, 2015) (Note: lower connectivity between anterior cingulate-striatal circuit has also been observed (Hu et al, 2015)). There are several possible interpretations to the apparent gap in the results of task-based neuroimaging and resting state neuroimaging studies.…”

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

“…As a number of researchers have described [106,149], substance-use disorders are typically accompanied by decreased reward motivation for typical and non-pathological rewards, a phenomenon that has been variously termed ‘motivational toxicity’ [150] and ‘reward-deficiency syndrome’ [151]. For example, Asensio and collegues [152] reported hypoactivation of the dorsal and ventral striatum and the dorsomedial pre-frontal cortex when cocaine addicts viewed pleasant images not linked to substance cues. Gilman and Hommer [153] reported subjective hypoarousal to normative positive images in alcohol-dependent participants.…”

Social cognition in cocaine addiction

“…The prevailing view is that substance-related disorders represent an imbalance between the exaggerated value given to drugs (even after loss of originally strong rewarding effects) and the devalued appeal of a range of natural reinforcers, from food to sex or money (2). Various neuroimaging studies have demonstrated that cocainedependent users show increased activations in the main regions of the brain reward system (striatum, medial prefrontal cortex, and posterior cingulate cortex) in response to drug stimuli, coupled with significantly decreased activations in the same regions in response to sexual stimuli or monetary offers (3)(4)(5). Using an analogy, in the "addicted brain stock market," drug stocks would be continually overrated, and all competitors steadily underrated.…”