The Motivational Determinants of Human Action, Their Neural Bases and Functional Impact in Adolescents With Obsessive-Compulsive Disorder

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 healthy adolescents and those with obsessive-compulsive disorder (OCD). METHODS: After instrumental training on a two action-two outcome probabilistic task, adolescents (n = 21) underwent Pavlovian conditioning using distinct stimuli predicting either the instrumental outcomes, a third outcome, or nothing. We then assessed functional magnetic resonance imaging during choice tests in which we varied the predicted value, using specific and general Pavlovian-instrumental transfer, and the experienced value, using outcome devaluation. To establish functional significance, we tested a matched cohort of adolescents with OCD (n = 20). RESULTS: In healthy adolescents, both predicted and experienced values influenced the performance of goaldirected actions, mediated by distinct orbitofrontal-striatal circuits involving the lateral orbitofrontal cortex (OFC) and medial OFC, respectively. However, in adolescents with OCD, choice was insensitive to changes in either predicted or experienced values. These impairments were related to hypoactivity in the lateral OFC and hyperactivity in the medial OFC during specific Pavlovian-instrumental transfer and hypoactivity in the anterior prefrontal cortex, caudate nucleus, and their connectivity in the devaluation test. CONCLUSIONS: We found 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. Furthermore, the influence of these motivational processes was severely blunted in OCD, as was the functional segregation of circuits involving medial and lateral OFC, producing dysregulated action control.