Mapping the neurocomputational landscape of obsessive-compulsive disorder (360G-Wellcome-211155_Z_18_Z)

Obsessive-compulsive disorder (OCD) is diagnosed purely based on its symptoms, without regard for underlying neurocognitive causes. This practice entails the likely risk that distinct neural illnesses are diagnosed as a single disorder. The analogy is Parkinsonism, where multiple conditions cause the same symptomatology. This project investigates distinct neurobiological disorders within OCD and determines their neurocognitive phenotypes. In my previous work, I have identified two candidate cognitive phenotypes in OCD, indecisiveness and impaired metacognition. In this fellowship, I will investigate (i) the neural processes underlying these impairments, (ii) the role of neurotransmitter noradrenaline therein, and (iii) determine whether they constitute separable neurocognitive subtypes in OCD. To answer these questions, I will combine simultaneous electroencephalography and functional MRI with pharmacological manipulations, both in healthy volunteers and OCD patients. In addition, I will use large smartphone-based data collection to investigate how indecisiveness and impaired metacognition relate to other cognitive deficits in OCD and to integrate them in a broader landscape of cognitive subtypes in OCD. This project will reveal the neural processes that underlie indecisiveness and metacognitive impairments in OCD. I will determine whether these are separable neural disorders, and whether noradrenaline blockade holds potential as treatment for one of the subtypes.