From habits to compulsions: the role of glutamate and serotonin in Obsessive-Compulsive Disorder (360G-Wellcome-204727_Z_16_Z)

This proposal aims to characterize the neural basis of compulsion development. This requires neurobehavioural investigation of the hypothetical transition between habits and compulsions. To achieve this, I will invent a new behavioural paradigm capable of assessing not only habit formation but also habit perseveration. Three specific aims are defined. Firstly, I will characterize the behavioural mechanisms through which both healthy humans and patients with Obsessive-Compulsive Disorder (OCD) arbitrate between intentional and automatic actions after habits have been established by measuring post-training human preferences for habitual versus goal-seeking actions. I will compare the influence of both appetitive and aversive instrumental learning in the shift between purposeful and automatic actions between groups. Secondly, using functional Magnetic Resonance Imaging (fMRI), I will characterise the neural mechanisms underlying the transition from habits to compulsions, by disentangling the neural contributions of the goal-directed and habit systems in their interaction to control behaviour. I will test whether perseveration results from impairment in the goal-directed system, or hyperactive habit circuitry, or perhaps both. Finally, I will use Magnetic Resonance Spectroscopy (MRS) and Positron emission tomography (PET) to measure dynamic changes in glutamate, GABA and serotonin availability to further elucidate the neurochemical abnormalities which may underlie OCD.