title: Cocaine addiction is associated with abnormal prefrontal function, increased striatal connectivity and sensitivity to monetary incentives, and decreased connectivity outside the human reward circuit.
abstract: Cocaine addiction has been associated with increased sensitivity of the human reward circuit to drug-related stimuli. However, the capacity of non-drug incentives to engage this network is poorly understood. Here, we characterized the functional sensitivity to monetary incentives and the structural integrity of the human reward circuit in abstinent cocaine-dependent (CD) patients and their matched controls. We assessed the BOLD response to monetary gains and losses in 30 CD patients and 30 healthy controls performing a lottery task in a magnetic resonance imaging scanner. We measured brain gray matter volume (GMV) using voxel-based morphometry and white matter microstructure using voxel-based fractional anisotropy (FA). Functional data showed that, after monetary incentives, CD patients exhibited higher activation in the ventral striatum than controls. Furthermore, we observed an inverted BOLD response pattern in the prefrontal cortex, with activity being highest after unexpected high gains and lowest after losses. Patients showed increased GMV in the caudate and the orbitofrontal cortex, increased white matter FA in the orbito-striatal pathway but decreased FA in antero-posterior association bundles. Abnormal activation in the prefrontal cortex correlated with GMV and FA increases in the orbitofrontal cortex. While functional abnormalities in the ventral striatum were inversely correlated with abstinence duration, structural alterations were not. In conclusion, results suggest abnormal incentive processing in CD patients with high salience for rewards and punishments in subcortical structures but diminished prefrontal control after adverse outcomes. They further suggest that hypertrophy and hyper-connectivity within the reward circuit, to the expense of connectivity outside this network, characterize cocaine addiction.
authors.affiliation: Cognition and Brain Plasticity Group (Bellvitge Biomedical Research Institute) IDIBELL, L'Hospitalet de Llobregat, Spain.|Department of Basic Psychology, University of Barcelona, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Vaquero
authors.affiliation: Cognition and Brain Plasticity Group (Bellvitge Biomedical Research Institute) IDIBELL, L'Hospitalet de Llobregat, Spain.
authors.forename: Estela
authors.initials: E
authors.lastname: Cámara
authors.affiliation: School of Medicine, Universitat Autònoma de Barcelona, Spain.
authors.forename: Frederic
authors.initials: F
authors.lastname: Sampedro
authors.affiliation: Addictive Behaviors Unit, Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Sant Pau Biomedical Research Institute (IIB Sant Pau), Spain.|Department of Psychiatry and Legal Medicine, Autonomous University of Barcelona, Spain.|Centro de Investigación Biomédica en Red de Salud Mental CIBERSAM, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Pérez de Los Cobos
authors.affiliation: Addictive Behaviors Unit, Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Sant Pau Biomedical Research Institute (IIB Sant Pau), Spain.|Department of Psychiatry and Legal Medicine, Autonomous University of Barcelona, Spain.
authors.forename: Francesca
authors.initials: F
authors.lastname: Batlle
authors.affiliation: Center for Research and Treatment of addictions (CITA), Spain.
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Fabregas
authors.affiliation: Grup ATRA, Spain.
authors.forename: Joan Artur
authors.initials: JA
authors.lastname: Sales
authors.affiliation: Grup ATRA, Spain.
authors.forename: Mercè
authors.initials: M
authors.lastname: Cervantes
authors.affiliation: Fundació Salut i Comunitat, Spain.|Addiction postgraduate course, School of Psychology, University of Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Ferrer
authors.affiliation: Fundació Salut i Comunitat, Spain.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Lazcano
authors.affiliation: Cognition and Brain Plasticity Group (Bellvitge Biomedical Research Institute) IDIBELL, L'Hospitalet de Llobregat, Spain.|Department of Basic Psychology, University of Barcelona, Spain.|Catalan Institution for Research and Advanced Studies, ICREA, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Rodríguez-Fornells
authors.affiliation: Centro de Investigación Biomédica en Red de Salud Mental CIBERSAM, Spain.|Human Neuropsychopharmacology Group, Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Spain.|Centre d'Investigació de Medicaments, Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, Spain.|Departament de Farmacologia i Terapèutica, Universitat Autònoma de Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Riba
mesh_terms: D001931:Brain Mapping / Q000379:methods; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009042:Motivation / Q000502:physiology*; D009434:Neural Pathways / Q000503:physiopathology*; D017397:Prefrontal Cortex / Q000503:physiopathology*; D012201:Reward; D066328:Ventral Striatum / Q000503:physiopathology*
keywords: cocaine addiction; functional MRI; human; incentive-processing; structural MRI