Abstract

Delineating common and separable neural alterations in substance use disorders (SUD) is imperative to understand the neurobiological basis of the addictive process and to inform substance‐specific treatment strategies. Given numerous functional MRI (fMRI) studies in different SUDs, a meta‐analysis could provide an opportunity to determine robust shared and substance‐specific alterations. The present study employed a coordinate‐based meta‐analysis covering fMRI studies in individuals with addictive cocaine, cannabis, alcohol, and nicotine use. The primary meta‐analysis demonstrated common alterations in primary dorsal striatal, and frontal circuits engaged in reward/salience processing, habit formation, and executive control across different substances and task‐paradigms. Subsequent sub‐analyses revealed substance‐specific alterations in frontal and limbic regions, with marked frontal and insula‐thalamic alterations in alcohol and nicotine use disorders respectively. Examining task‐specific alterations across substances revealed pronounced frontal alterations during cognitive processes yet stronger striatal alterations during reward‐related processes. Finally, an exploratory meta‐analysis revealed that neurofunctional alterations in striatal and frontal reward processing regions can already be determined with a high probability in studies with subjects with comparably short durations of use. Together the findings emphasize the role of dysregulations in frontostriatal circuits and dissociable contributions of these systems in the domains of reward‐related and cognitive processes which may contribute to substance‐specific behavioral alterations.

Highlights

  • Problematic use of illicit and licit drugs and substance use disorders represent a major challenge for society, in terms of individual suffering and socio-economic costs [1]–[3]

  • The transition from volitional use to problematic and compulsive use is driven by progressive dysregulations in the brain’s motivational and cognitive circuits, the striato-frontal circuits engaged in incentive salience and reward processing, habit formation, and executive control [8]–[10]

  • 3.1 Included study sample characteristics Out of the 99 studies included in the meta-analysis, cocaine studies contributed to 30% (828) of the total foci, while cannabis, alcohol, and nicotine contributed to 23.01% (637), 27.45% (760) and 19.44% (538) respectively of the total foci analyzed, indicating a bias towards a single substance due to an imbalanced data-base

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Summary

Introduction

Problematic use of illicit and licit drugs and substance use disorders represent a major challenge for society, in terms of individual suffering and socio-economic costs [1]–[3]. Based on animal models and human neuroimaging research substance use disorders, addiction as a common pathological endpoint, has been reconceptualized as a chronic relapsing disorder of the brain that is characterized by a preoccupation with drug-seeking and taking, compulsive use, loss of behavioral control, and withdrawal (DSM-V). The transition from volitional use to problematic and compulsive use is driven by progressive dysregulations in the brain’s motivational and cognitive circuits, the striato-frontal circuits engaged in incentive salience and reward processing, habit formation, and executive control [8]–[10]

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