title: Doubt in the Insula: Risk Processing in Obsessive-Compulsive Disorder.
abstract: Extensive cleaning or checking of patients with obsessive-compulsive disorder (OCD) are often interpreted as strategies to avoid harm and as an expression of the widespread belief that OCD patients are more risk-averse. However, despite its clinical significance, the neural basis of risk attitude in OCD is unknown. Here, we investigated neural activity during risk processing using functional magnetic resonance imaging and simultaneously assessed risk attitude using a separate behavioral paradigm in OCD patients with different symptoms versus healthy controls (HCs). We found opposite insula responses to high versus low risk in OCD patients compared to HCs: a positive correlation between insula activity and risk-aversion in patients versus a negative correlation in controls. Although OCD patients overall were not more risk-averse than controls, there were differences between subgroups of OCD patients: patients with doubt/checking symptoms were more risk-averse than other patients. Taken together, OCD patients show a reversed pattern of risk processing by the insula compared to HCs. Moreover, the data suggest that increased activation of the insula signals an abnormal urge to avoid risks in the subpopulation of OCD patients with doubt and checking symptoms. These results indicate a role for the insula in excessive risk-avoidance relevant to OCD.
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of AmsterdamAmsterdam, Netherlands; Brain Imaging Center, Academic Medical Center, University of AmsterdamAmsterdam, Netherlands.
authors.forename: Judy
authors.initials: J
authors.lastname: Luigjes
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of AmsterdamAmsterdam, Netherlands; Brain Imaging Center, Academic Medical Center, University of AmsterdamAmsterdam, Netherlands.
authors.forename: Martijn
authors.initials: M
authors.lastname: Figee
authors.affiliation: Laboratory for Social and Neural Systems Research, Department of Economics, University of Zurich Zurich, Switzerland.
authors.forename: Philippe N
authors.initials: PN
authors.lastname: Tobler
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam Amsterdam, Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: van den Brink
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam Amsterdam, Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: de Kwaasteniet
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of AmsterdamAmsterdam, Netherlands; Brain Imaging Center, Academic Medical Center, University of AmsterdamAmsterdam, Netherlands.
authors.forename: Guido
authors.initials: G
authors.lastname: van Wingen
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of AmsterdamAmsterdam, Netherlands; Netherlands Institute for Neuroscience, The Royal Netherlands Academy of Arts and SciencesAmsterdam, Netherlands.
authors.forename: Damiaan
authors.initials: D
authors.lastname: Denys
keywords: fMRI; insula; obsessive-compulsive disorder; risk avoidance; risk processing