Disorganization of anatomical connectivity in obsessive compulsive disorder: A multi-parameter diffusion tensor imaging study in a subpopulation of patients V. Garibotto a,b,1 , P. Scifo b,c,1 , A. Gorini a , Clarke R. Alonso b , S. Brambati a , L. Bellodi a,d , D. Perani a,b,c, ⁎ a Vita-Salute San Raffaele University, Milan, Italy b Nuclear Medicine Unit and Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy c C.E.R.M.A.C., San Raffaele Scientific Institute, Milan, Italy d Department of Clinical Neuroscience, San Raffaele Institute, Milan, Italy abstract article info Article history: Received 24 June 2009 Revised 7 October 2009 Accepted 4 November 2009 Available online 11 November 2009 Keywords: Obsessive compulsive disorder (OCD) White matter Connectivity Diffusion tensor imaging (DTI) Fiber tracts Visuospatial functions Obsessive–compulsive disorder (OCD) is thought to involve large-scale brain systems but the anatomical connectivity via association fibers has not been specifically investigated yet. We evaluated organization and directionality of the major fiber bundles in a subpopulation of OCD, including washers and checkers who presented decision making deficits, by measuring MRI parameters related to water self-diffusion (Fractional Anisotropy, FA) and fiber directionality (Principal Diffusion Direction, PDD) in 15 OCD and 16 control subjects. OCD patients showed significantly lower FA and altered PDD along the corpus callosum, cingulum, superior longitudinal fasciculus, and inferior fronto-occipital fasciculus bilaterally. The track-based analysis of the inferior fronto-occipital fasciculus confirmed a significant bilateral FA reduction. Lower FA values in the inferior fronto-occipital fasciculus, superior longitudinal fasciculus and corpus callosum correlated with symptom severity and neuropsychological performance. This multi-parameter MRI study revealed specific white matter abnormalities in OCD suggesting tract disorganization as main feature, reflected by local changes in fiber directionality. This altered anatomical connectivity might play a specific role in OCD pathophysiology. © 2009 Elsevier Inc. All rights reserved. Introduction Obsessive compulsive disorder (OCD) is a chronically debilitating psychiatric disorder, defined by the presence of recurrent thoughts, intrusive and distressing impulses or images (obsessions), and ritualistic behaviors and mental acts (compulsions), which are typically engaged in order to neutralize the anxiety associated with the obsessive thoughts. OCD is associated with considerable anxiety and socio-occupational dysfunction (American Psychiatric Association, 1994). The worldwide prevalence of this heritable disorder is 2–3% and the mean onset age is usually in the twenties to thirties (Horwath and Weissman, 2000). In the last few decades, a large number of clinical and experimental studies on OCD have focused on the fronto-striatal neural circuits. Converging evidence suggests that the hallmark of OCD is a dysfunction of the neuronal loop running from orbitofrontal and cingulate cortex to the striatum (caudate nucleus and putamen), globus pallidus, thalamus and back to the frontal cortex (Graybiel and Rauch, 2000; Saxena et al., 1998). Neuropsychological studies have shown that OCD patients have deficits in cognitive abilities associated with frontal lobes and fronto-subcortical structures, such as executive function deficits, insufficient cognitive-behavioral flexibility and alteration in decision-making (see Saxena et al., 2001a, for a review). Functional neuroimaging studies employing PET (Kwon et al., 2003; Perani et al., 1995, 2008; Saxena et al., 1999, 2001b) or structural whole-brain mapping techniques, e.g., voxel-based morphometry (Kim et al., 2001; Pujol et al., 2004; Valente et al., 2005) have provided support for this orbitofronto-striatal model. However, both the neuropsychological and neuroimaging findings suggest the additional involvement of regions outside these classically implicated circuits, particularly, the posterior parietal and occipital regions. First of all, the cognitive abnormalities reported by OCD patients cannot be completely ascribed to the orbitofrontal–striatal loop (Menzies et al., 2008a). For example, deficits in decision-making characterize a subgroup of OCD patients (Cavedini et al., 2006; Lawrence et al., 2006), and decision making is not mediated by the orbitofrontal cortex alone, but involves a wider network of brain areas typically associated with working memory and visual attention, including the parietal and occipital cortex (Ernst et al., 2002; Lawrence et al., 2009). The idea that posterior associative cortices play a role in OCD is supported by the observation that OCD patients have deficits in visuospatial performance, correlating with symptoms' Neurobiology of Disease 37 (2010) 468–476 ⁎ Corresponding author. Vita-Salute San Raffaele University, via Olgettina 58, 20132 Milano, Italy. Fax: +39 22641 5202. E-mail address: perani.daniela@hsr.it (D. Perani). 1 These authors contributed equally to this work. Available online on ScienceDirect (www.sciencedirect.com). 0969-9961/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.nbd.2009.11.003 Contents lists available at ScienceDirect Neurobiology of Disease journal homepage: www.elsevier.com/locate/ynbdi