The motivational determinants of human action, their neural bases and functional impact in adolescents with OCD

Background Establishing the motivational influences on human action is essential for understanding choice and decision-making in health and disease. Here we used tests of value-based decision-making, manipulating both predicted and experienced reward values to assess the motivational control of goal-directed action in adolescents and the functional impact of OCD. Methods After instrumental training on a two action-two outcome probabilistic task, participants underwent Pavlovian conditioning using stimuli predicting either the instrumental outcomes, a third outcome or nothing. We then assessed fMRI during choice tests in which we varied predicted value, using specific and general Pavlovian-instrumental transfer (PIT), and experienced value, using outcome devaluation. Results Both predicted and experienced values influenced the performance of goal-directed actions in healthy adolescent participants, mediated by distinct orbitofrontal (OFC)-striatal circuits involving the lateral-OFC and medial-OFC respectively. To establish their functional significance, we tested a matched cohort of adolescents with obsessive-compulsive disorder (OCD). We found that choice between actions in OCD was insensitive to changes in both predicted and experienced values and that these impairments corresponded to hypoactivity activity in the lateral OFC and hyperactivity in medial OFC during specific PIT and hypoactivity in anterior prefrontal cortex, caudate nucleus and their connectivity in the devaluation test. Discussion We found, therefore, that predicted and experienced values exerted a potent influence on the performance of goal-directed actions in adolescents via distinct orbitofrontal- and prefrontal-striatal circuits. The influence of these motivational processes was severely blunted in OCD resulting in dysregulated action control associated with the intrusion of competing actions.