1. ¹Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
2. ²Department of Clinical Neuropsychology, VU University, Amsterdam, The Netherlands
3. ³Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands

Correspondence: Dr MB de Ruiter, Department of Psychiatry, Amsterdam Institute for Addiction Research, Academic Medical Center, PO Box 75867, 1070 AW Amsterdam, The Netherlands. Tel: +31 205122498; Fax: +31 205122322; E-mail: m.b.deruiter@amc.uva.nl

Received 1 June 2008; Revised 18 August 2008; Accepted 2 September 2008; Published online 1 October 2008.

Abstract

Pathological gambling (PG) is associated with maladaptive perseverative behavior, but the underlying mechanism and neural circuitry is not completely clear. Here, the hypothesis was tested that PG is characterized by response perseveration and abnormalities in reward and/or punishment sensitivity in the ventral frontostriatal circuit. Executive functioning was assessed to verify if these effects are independent of the dorsal frontostriatal circuit. A group of smokers was also included to examine whether impairments in PG generalize to substance use disorders. Response perseveration and reward/punishment sensitivity were measured with a probabilistic reversal-learning task, in which subjects could win and lose money. Executive functioning was measured with a planning task, the Tower of London. Performance and fMRI data were acquired in 19 problem gamblers, 19 smokers, and 19 healthy controls. Problem gamblers showed severe response perseveration, associated with reduced activation of right ventrolateral prefrontal cortex in response to both monetary gain and loss. Results did not fully generalize to smokers. Planning performance and related activation of the dorsal frontostriatal circuit were intact in both problem gamblers and smokers. PG is related to response perseveration and diminished reward and punishment sensitivity as indicated by hypoactivation of the ventrolateral prefrontal cortex when money is gained and lost. Moreover, intact planning abilities and normal dorsal frontostriatal responsiveness indicate that this deficit is not due to impaired executive functioning. Response perseveration and ventral prefrontal hyporesponsiveness to monetary loss may be markers for maladaptive behavior seen in chemical and nonchemical addictions.