title: Imbalance in habitual versus goal directed neural systems during symptom provocation in obsessive-compulsive disorder.
abstract: Intrusive thoughts and compulsive urges to perform stereotyped behaviours are typical symptoms of obsessive-compulsive disorder. Emerging evidence suggests a cognitive bias towards habit formation at the expense of goal-directed performance in obsessive-compulsive disorder. In this study, we test this hypothesis using a novel individualized ecologically valid symptom provocation design: a live provocation functional magnetic resonance imaging paradigm with synchronous video-recording of behavioural avoidance responses. By pairing symptom provocation with online avoidance responses on a trial-by-trial basis, we sought to investigate the neural mechanisms leading to the compulsive avoidance response. In keeping with the model of habit formation in obsessive-compulsive disorder, we hypothesized that this disorder would be associated with lower activity in regions implicated in goal-directed behaviours and higher activity in regions implicated in habitual behaviours. Fifteen patients with obsessive-compulsive disorder and 15 healthy control volunteers participated in this functional magnetic resonance imaging study. Online stimuli were individually tailored to achieve effective symptom provocation at neutral, intermediate and strong intensity levels. During the symptom provocation block, the participant could choose to reject or terminate the provoking stimuli resulting in cessation of the symptom provocation. We thus separately analysed the neural correlates of symptom provocation, the urge to avoid, rejection and relief. Strongly symptom-provoking conditions evoked a dichotomous pattern of deactivation/activation in patients, which was not observed either in control conditions or in healthy subjects: a deactivation of caudate-prefrontal circuits accompanied by hyperactivation of subthalamic nucleus/putaminal regions. This finding suggests a dissociation between regions engaged in goal-directed and habitual behaviours. The putaminal hyperactivity during patients' symptom provocation preceded subsequent deactivation during avoidance and relief events, indicating a pivotal role of putamen in regulation of behaviour and habit formation in obsessive-compulsive disorder. Effective connectivity analysis identified the ventromedial prefrontal cortex/orbitofrontal cortex as the main structure in this circuitry involved in the modulation of compulsivity in obsessive-compulsive disorder. These findings suggest an imbalance in circuitry underlying habitual and goal-directed action control, which may represent a fundamental mechanism underlying compulsivity in obsessive-compulsive disorder. Our results complement current models of symptom generation in obsessive-compulsive disorder and may enable the development of future therapeutic approaches that aim to alleviate this imbalance.
authors.affiliation: 1 Institute for Biomedical Imaging and Life Sciences, Faculty of Medicine, University of Coimbra, Portugal 2 PhD Programme in Experimental Biology and Biomedicine, Centre for Neuroscience and Cell Biology, University of Coimbra, Portugal 3 Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors.forename: Paula
authors.initials: P
authors.lastname: Banca
authors.affiliation: 3 Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors.forename: Valerie
authors.initials: V
authors.lastname: Voon
authors.affiliation: 4 Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: Martin D
authors.initials: MD
authors.lastname: Vestergaard
authors.affiliation: 1 Institute for Biomedical Imaging and Life Sciences, Faculty of Medicine, University of Coimbra, Portugal 5 ICNAS, Brain Imaging Network of Portugal.
authors.forename: Gregor
authors.initials: G
authors.lastname: Philipiak
authors.affiliation: 1 Institute for Biomedical Imaging and Life Sciences, Faculty of Medicine, University of Coimbra, Portugal.
authors.forename: Inês
authors.initials: I
authors.lastname: Almeida
authors.affiliation: 6 Coimbra University Hospital, Portugal.
authors.forename: Fernando
authors.initials: F
authors.lastname: Pocinho
authors.affiliation: 6 Coimbra University Hospital, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Relvas
authors.affiliation: 1 Institute for Biomedical Imaging and Life Sciences, Faculty of Medicine, University of Coimbra, Portugal 5 ICNAS, Brain Imaging Network of Portugal mcbranco@fmed.uc.pt.
authors.forename: Miguel
authors.initials: M
authors.lastname: Castelo-Branco
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001921:Brain / Q000098:blood supply / Q000473:pathology*; D003072:Cognition Disorders / Q000209:etiology*; D005260:Female; D006040:Goals; D006801:Humans; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000150:complications* / Q000473:pathology*; D004856:Postural Balance / Q000502:physiology*; D012678:Sensation Disorders / Q000209:etiology*; D055815:Young Adult
keywords: caudate/putamen; causality; imbalanced circuitry; live symptom provocation; obsessive-compulsive disorder