Neural Correlates of Anxiety Associated with Obsessive-Compulsive Symptom Dimensions in Normal Volunteers David Mataix-Cols, Sarah Cullen, Kezia Lange, Fernando Zelaya, Christopher Andrew, Edson Amaro, Michael J. Brammer, Steven C.R. Williams, Anne Speckens, and Mary L. Phillips Background: The neural correlates of anxiety associated with obsessive-compulsive symptomlike provocation in normal volunteers are unknown. Methods: Ten healthy volunteers participated in four functional magnetic resonance experiments. Subjects were scanned while viewing alternating blocks of emotional (normally aversive, washing-relevant, checking-relevant, or hoarding-relevant pictures) and neutral pictures, and imagining scenarios related to the content of each picture type. Nonparametric brain mapping analyses were used. Results: In response to the provocative pictures in all experiments, increases in subjective anxiety and activation in bilateral ventral prefrontal, limbic, dorsal prefrontal, and visual regions were demonstrated. Anxiety related to different symptom dimensions was associated with differ- ent patterns of activation: provocation of washing-rele- vant anxiety predominantly activated dorsal and ventral prefrontal regions; checking-relevant anxiety predomi- nantly activated dorsal prefrontal regions; and hoarding- relevant anxiety predominantly activated ventral prefron- tal regions and the left amygdala. Conclusions: Our findings support a dimensional model of obsessive-compulsive disorder (OCD) whereby 1) the brain systems implicated in the mediation of anxiety in response to symptom-related material in normal subjects are similar to those identified in OCD patients during symptom provocation, and 2) anxiety associated with differ- ent symptom dimensions is associated with differential pat- terns of activation of these neural systems. Further investi- gation of the neural basis of OCD symptom dimensions is required. Biol Psychiatry 2003;53:482– 493 © 2003 Soci- ety of Biological Psychiatry Key Words: Obsessive-compulsive disorder, symptom dimensions, hoarding, neuroimaging, fMRI, emotion Introduction F unctional neuroimaging studies have substantially in- creased our understanding of the neural mechanisms underlying obsessive-compulsive disorder (OCD). Symptom provocation paradigms have used positron emission tomog- raphy (PET), single photon emission tomography (SPECT), or functional resonance imaging (fMRI) to compare, in a single session, the patterns of brain activation during OCD symptom provocation and control states (Saxena and Rauch 2000). Although findings are discrepant, they strongly associate OCD symptoms with activation of the orbito- frontal cortex, with less consistent involvement of lateral frontal cortex, anterior cingulate gyrus, temporal cortex, striatum, thalamus, amygdala, and insular cortex (Adler et al 2000; Breiter et al 1996; McGuire et al 1994; Rauch et al 1994; Saxena and Rauch 2000). Obsessive-compulsive disorder is heterogeneous, with symptoms that can be summarized in a few consistent, temporally stable, dimensions (Baer 1994; Leckman et al 1997; Mataix-Cols et al 1999a, 2002a; Summerfeldt et al 1999). Despite this phenotypic heterogeneity, most previ- ous neuroimaging studies of OCD have grouped together patients with diverse symptom patterns, although they have included patients with predominantly contamination/ washing or mixed symptoms. To our knowledge, only three functional neuroimaging studies have examined the neural correlates of different symptoms in OCD. In one PET study (Cottraux et al 1996), all patients were predom- inantly checkers, and symptoms were provoked using an individually tailored script-driven paradigm that prompted the urge to check. They found significant increases in orbitofrontal and superior temporal cortex activity, and- ,contrary to most previous findings, lower activity in the basal ganglia compared with control subjects. In another PET study, Rauch et al (1998) found significant correla- From the Division of Psychological Medicine (DM-C, SC, KL, MLP), Departments of Neuroimaging Research (FZ, CA, EA, SCRW), Biostatistics (MJB), and Psychology (AS), GKT School of Medicine and Institute of Psychiatry, London, United Kingdom. Address reprint requests to David Mataix-Cols, Ph.D., Department of Psychological Medicine, GKT School of Medicine and Institute of Psychiatry, 5th Floor Thomas Guy House, Guy’s Hospital, London SE1 9RT United Kingdom. Received March 26, 2002; revised June 12, 2002; accepted June 21, 2002. © 2003 Society of Biological Psychiatry 0006-3223/03/$30.00 doi:10/1016/S0006-3223(03)01504-4