Symptom-specific functional and structural connectivity of the fronto-striatal circuitry in obsessive-compulsive disorder

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Obsessive-compulsive disorder (OCD) is a severe psychiatric illness that is characterized by high symptom heterogeneity. Whereas some patients suffer mainly from contamination fears or washing compulsions, others are affected predominantly by obsessive behaviors such as checking compulsions. Recent studies indicated that established therapies are not equally effective in the different psychopathological subgroups. Moreover, there is increasing evidence showing that the different symptom dimensions may be mediated by partially distinct neural systems and may be associated with symptom-specific alterations in functional and structural connectivity within relevant, mainly fronto-striatal, networks.Thus, a more specific characterization of psychopathological subgroups or symptom dimensions in OCD is sensible and important, both from a diagnostic and etiologic perspective, as well as for therapeutic reasons. Multimodal studies investigating specific functional systems (functional connectivity) and subserving white matter fiber tracts (structural connectivity) with regard to symptom-specific alterations have not been performed in OCD so far. Against this background, the proposed project aims at investigating symptom-specific alterations in functional and structural connectivity in patients with OCD. The study will be focusing on patients with predominantly checking compulsions as well as patients with predominantly contamination fears and washing compulsions. These symptom dimensions have been shown to be relatively independent from each other and to be characterized by high construct validity thus allowing for a reliable discrimination of groups. To this aim, the project will employ neurocognitive paradigms examining decision making under uncertainty, reward processing and cognitive control, i.e. processes involving mainly fronto-striatal networks which are known to be altered in the context of the disorder. Structural connectivity will be determined by means of diffusion tensor imaging (DTI). Specific fiber tracts will be examined using tract-based spatial statistics and probabilistic fiber tracking. Postulated alterations in functional connectivity will be studied with ¿Dynamic Causal Modeling¿ (DCM) and will be related to respective white matter alterations using correlational and voxel-based methods. This multimodal procedure should provide specific information about the pathophysiological substrates underlying alterations in functional and structural connectivity in patients with OCD that allow for a neurobiological differentiation between different symptom dimensions or patient subgroups. Perspectively, the identification of symptom-specific neurofunctional alterations may provide the basis for personalized pharmacological and psychotherapeutic treatment strategies.