title: Aberrant neural signatures of decision-making: Pathological gamblers display cortico-striatal hypersensitivity to extreme gambles.
abstract: Pathological gambling is an addictive disorder characterized by an irresistible urge to gamble despite severe consequences. One of the hallmarks of pathological gambling is maladaptive and highly risky decision-making, which has been linked to dysregulation of reward-related brain regions such as the ventral striatum. However, previous studies have produced contradictory results regarding the implication of this network, revealing either hypo- or hypersensitivity to monetary gains and losses. One possible explanation is that the gambling brain might be misrepresenting the benefits and costs when weighting the potential outcomes, and not the gains and losses per se. To address this issue, we investigated whether pathological gambling is associated with abnormal brain activity during decisions that weight the utility of possible gains against possible losses. Pathological gamblers and healthy human subjects underwent functional magnetic resonance imaging while they accepted or rejected mixed gain/loss gambles with fifty-fifty chances of winning or losing. Contrary to healthy individuals, gamblers showed a U-shaped response profile reflecting hypersensitivity to the most appetitive and most aversive bets in an executive cortico-striatal network including the dorsolateral prefrontal cortex and caudate nucleus. This network is concerned with the evaluation of action-outcome contingencies, monitoring recent actions and anticipating their consequences. The dysregulation of this specific network, especially for extreme bets with large potentials consequences, offers a novel understanding of the neural basis of pathological gambling in terms of deficient associations between gambling actions and their financial impact.
authors.affiliation: Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Kettegaard Alle 30, 2650 Hvidovre, Denmark; Brain and Consciousness group (EHESS/CNRS/ENS), Ecole Normale Supérieure, PSL Research University, 29 rue d'Ulm, 75005 Paris, France. Electronic address: gelskov@gmail.com.
authors.forename: Sofie V
authors.initials: SV
authors.lastname: Gelskov
authors.affiliation: Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Kettegaard Alle 30, 2650 Hvidovre, Denmark; Section for Cognitive Systems, DTU Compute, Technical University of Denmark, Asmussens Alle, Building 322, 2800 Kongens Lyngby, Denmark.
authors.forename: Kristoffer H
authors.initials: KH
authors.lastname: Madsen
authors.affiliation: Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Kettegaard Alle 30, 2650 Hvidovre, Denmark; Center for Decision Neuroscience, Dept. of Marketing, Copenhagen Business School, Solbjerg Plads 3, 2000 Copenhagen, Denmark.
authors.forename: Thomas Z
authors.initials: TZ
authors.lastname: Ramsøy
authors.affiliation: Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Kettegaard Alle 30, 2650 Hvidovre, Denmark; Department of Neurology, Copenhagen University Hospital Bispebjerg, Bispebjerg Bakke 23, 2400 Copenhagen, Denmark.
authors.forename: Hartwig R
authors.initials: HR
authors.lastname: Siebner
mesh_terms: D000328:Adult; D002421:Caudate Nucleus / Q000503:physiopathology*; D003657:Decision Making / Q000502:physiology*; D005715:Gambling / Q000503:physiopathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D017397:Prefrontal Cortex / Q000503:physiopathology*; D055815:Young Adult
keywords: Cortico-striatal hypersensitivity; Decision-making; Loss aversion; Pathological gambling; Reward; fMRI