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We are grateful for funding from the MRC (Programme Grant to DCR), the Wellcome Trust (Senior Fellowship to DCR, studentship for EZ), Wellcome Trust/MRC Strategic grant on Alzheimer's disease, BBSRC/Lilly (Studentship for FT), and the NIHR Biomedical Research Centre at Addenbrooke's Hospital. ""Obsessive-compulsive disorder (OCD) is a heterogeneous psychiatric disorder characterized by clinically significant heptaminol recurrent, intrusive, and disturbing thoughts (obsessions) and by repetitive behaviors that are aimed at reducing anxiety or dread (compulsions) (American Psychiatric Association, 2000?and?American Psychiatric Association, 2013). It is estimated that the lifetime prevalence of OCD is 1�C3% in the general population (Flament et al., 1988?and?Fontenelle and Hasler, 2008), suggesting that each of our social networks may contain family members, friends, or colleagues that live with this often debilitating condition (Ayuso-Mateos, 2006). The rather high burden of OCD and its elusive etiology emphasize the urgent need for additional research into the neurobiological pathways that cause the disorder and the identification of biomarkers for its prediction and prevention (Fineberg et al., 2012). A variety of imaging techniques have allowed researchers to delve deep into the brains of OCD patients to seek out aberrations in the neural circuits that control behavior. The most consistent impairments Ceritinib supplier have been found in cortico-striato-thalamic loops (Brem et al., 2012, Maia et al., 2008, van den Heuvel et al., 2010?and?Walitza et al., 2014a), which connect regions of the neocortex with the striatum and the thalamus to form important feedback loops that regulate neural activity. The cortico-striato-thalamic loops are centrally involved in motor, cognitive, and affective processes, and are assumed to be causally related to OCD symptom generation (Brem et al., 2012?and?van den Heuvel et al., 2010). Structural magnetic resonance imaging Vorinostat datasheet studies have revealed that mainly areas of the medial prefrontal wall �C which contains the anterior cingulate cortex (ACC) and adjacent areas -, orbitofrontal cortex (OFC), striatum, and thalamus are impaired in OCD (Huyser et al., 2009, Menzies et al., 2008, Montigny et al., 2013, Peng et al., 2012?and?Radua et al., 2010). Studies that used diffusion tensor imaging to investigate the integrity of fiber connections have revealed that these prefrontal areas (e.g., ACC and OFC) exhibit altered structural connectivity (Peng et al., 2012?and?Piras et al., 2013). Similar regions have also been identified using functional neuroimaging, mainly during error processing, inhibition, and decision-making tasks, but also during rest (Brem et al., 2012, Harrison et al., 2013?and?Huyser et al., 2009).